06. Tumors of soft tissue. Nefro and Neuroblastoma. Mediastinal tumors

TOPIC No.4: Tumors of soft tissue. Nefro and Neuroblastoma. Mediastinal tumors.

Plan:

1.                Tumors of soft tissue:

1.1.           Hemangioma.

1.2.           Lymphangioma.

1.3.           Teratoma.

1.4.           Dermoid cysts.

1.5.           Nevus.

1.6.           Rhabdomyosarcoma.

2.                Nefroblastoma.

3.                Neuroblastoma.

4.                Mediastinal tumors.

 

1. Tumors of soft tissue:

1.1. Hemangioma.

Haemangiomas are proliferations of mature vascular elements. These endothelium-lined vascular spaces are most commonly capillary sized, but larger cavernous spaces also are found, especially in large lesions. Different clinical types of haemangiomas are commonly recognized.

Strawberry haemangiomas may be present at birth but, more typically, develop during the first few weeks of life. They are seen in approximately 3 % of newborn infants, and 80 % are solitary, although multiple haemangiomas also occur. Strawberry haemangiomas range in size from 1 mm to many centimetres. The lesions are well-demarcated, lobular, bright red nodules with a spongy consistency. The surface of the lesion is studded with small capillary tufts, which produce the resemblance to a strawberry.

 

Strawberry haemangiomas seldom require treatment, since the vast majority involute spontaneously by the age of 6 or 7 years. Treatment may be required, however, for lesions situated on the eyelids, nares, or lips, where they may cause functional impairment. Rarely, giant strawberry haemangiomas, particularly those with a cavernous component, may be associated with thrombocytopenia, presumably due to platelet sequestration with the lesion. This phenomenon, known as the Kasabach-Merritt syndrome, may require surgical treatment if other measures fail.

Administration of corticosteroids, which may stimulate gradual involution of lesions is often used as first-line treatment for rapidly growing strawberry haemangiomas. Surgical excision and carbon dioxide laser ablation are often successful, but may produce unacceptable scarring. The efficacy of dye laser treatment is currently being evaluated and promises to be effective.

Cherry haemangiomas are generally smaller than strawberry haemangiomas, and tend to be round and bright red. They begin to appear during childhood, and continue to develop throughout adult life. The tendency to develop cherry haemangiomas appears to be transmitted within families as an autosomal dominant trait. Cherry haemangiomas seldom require treatment other than for cosmetic reasons: they are easily excised with a scalpel or biopsy punch. Occasionally, cherry haemangiomas thrombose, changing in colour from bright red to purplish black. This colour change may alarm patient and physician alike, since the apparent sudden appearance of a black papule raises the spectre of nodular malignant melanoma. Biopsy is indicated in such cases.

Cavernous haemangiomas, like strawberry haemangiomas, may be present at birth and grow rapidly during the first few months of life. They also involute spontaneously. Cavernous haemangiomas are primarily situated beneath the skin, and clinically appear as soft, bluish masses that distend the surrounding features. A typical strawberry haemangioma may form the cutaneous component of a cavernous haemangioma. Both strawberry and cavernous haemangiomas, when multiple, may be the presenting sign of diffuse neonatal haemangiomatosis, in which multiple haemangiomas occur not only in the skin and subcutaneous tissue, but also in the liver and other organs.

 

Port wine stains, unlike haemangiomas, do not represent the proliferation of excessive numbers of vascular elements, but are caused by ectasia of normal numbers of vessels within the skin. The dermal vessels that comprise port wine stains are capillary size or slightly larger. Port wine stains are generally present at birth, and occur in 0.3 %of neonates. Early in life, port wine stains are generally pink or purplish-pink in colour, and macular. With time, the vascular channels become more and more ectatic, imparting a lumpy appearance to the skin. Mature port wine stains are frequently dark purple. Port wine stains are most commonly found on the head and neck, but may also be seen on the trunk, particularly in the pectoral area, and on the extremities, usually the arms. Port wine stains of the orbital region may be associated with unilateral glaucoma.

 

The Sturge-Weber syndrome is characterized by the presence of a port wine stain in the distribution of the first branch of the trigeminal nerve, associated with a similar vascular malformation of the underlying cerebral cortex and meninges. Seizures, mental retardation, and motor cortical deficits are seen in many patients. The Klippel-Trenaunay-Weber syndrome is an association of port wine stain of an extremity or the trunk with arteriovenous malformations and hemihypertrophy.

Treatment for port wine stains was unsatisfactory and produced unacceptable scarring: cryosurgery, carbon dioxide and argon laser surgery, excision and grafting, and tattooing with skin-coloured pigments were all used with variable degrees of success. The development of tuneable dye lasers has revolutionized the treatment of port wine stains, making it possible to remove these lesions partially or completely without excessive scarring.

Pyogenic granuloma is a common vascular lesion that presents as a rapidly-growing papule or nodule which is friable and bleeds easily after minor trauma. Pyogenic granuloma is a misnomer: it is actually an eruptive capillary haemangioma. Treatment with electrofulguration, carbon dioxide laser ablation, or simple excision is usually curative, although lesions may recur. Since the differential diagnosis of a rapidly growing and bleeding nodule also includes nodular malignant melanoma, biopsy should be performed if there is any doubt about the diagnosis.

 

1.2. Lymphangioma.

Introduction

Lymphoma is a generic term used to describe malignant expansion of any of the lymphoid cell series. The nosology of lymphoma is an evolving science with clinical, morphological, and phenotypic studies contributing to the final diagnosis. The historical classification of lymphomas based purely upon morphological appearances under the light microscope has led to confusion and had little prognostic significance, so the Revised Euro-American Lymphoma (REAL) classification is in current use,1 albeit modified by the World Health Organisation (WHO) to include cytogenetic factors.2

Currently, about 15% of lymphomas are regarded as Hodgkin’s disease, defined by the presence of Reed-Sternberg cells on light microscopy, and the remaining 85% as non-Hodgkin’s lymphoma (NHL). NHL may stem from cells that have B-cell or T-cell, including natural killer (NK) cell, lineage. Amongst NHL, B-cell phenotypes account for about 85% of the diagnosed cases, and within Africa, Burkitt lymphoma is the most common B-cell tumour. REAL divides lymphomas into high-, intermediate-, and low-grade tumours, giving prognostic information that is of value. Burkitt lymphoma is regarded as a high-grade tumour and is one of the fastest-growing neoplasms known, with a tumour doubling time of between 24 and 48 hours.3

Aetiology/Pathophysiology

The transformation of cellular behaviour from “normal” to a pattern that we recognise as “malignant” occurs when the genes controlling cellular behaviour are altered in some way. In lymphoid cells, this commonly occurs as a result of chromosomal translocations (e.g., t(8;14) in Burkitt lymphoma, in which a proto-oncogene cmyc is moved from its normal site on chromosome 8 to a site on chromosome 14), chromosomal deletions, or oncogenic viruses.

There is a strong association between the Epstein-Barr virus (EBV) and endemic Burkitt lymphoma; although a causal relationship is not certain, EBV antigen can be detected in up to 90% of children affected by Burkitt lymphoma. Many viruses may, through chronic antigenic stimulation, result in chronic B-cell proliferation, thereby increasing the probability of spontaneous chromosomal aberration. It is possible that the origin of the genomic injuries in endemic Burkitt lymphoma is more complex, involving malaria, EBV, arborviruses,4 and possibly also plant products.5

In only 15% of patients with sporadic Burkitt lymphoma seen outside Central Africa is there an associated EBV infection. Sporadic Burkitt lymphoma also has a different pattern of presentation but is histologically identical to the endemic form. It is likely that sporadic Burkitt lymphoma is a disease different from the African form that shares a similar cellular morphology.

Within each subgroup of NHL, cell size and pattern of growth (nodular or diffuse) reflect the gene products of the altered genome, and these in turn determine the innate aggression of the tumour. Anatomical staging also contributes to treatment decisions. In Africa, the human immunodeficiency virus (HIV) pandemic has greatly altered the epidemiology of lymphoma, resulting in a considerable increase in primary cerebral lymphoma and a substantial increase in the numbers of patients with B-cell NHL.6,7 Burkitt lymphoma is regarded as an acquired immune deficiency syndrome (AIDS)-defining disease in HIV-infected individuals.8 HIV-related Burkitt lymphoma seems to be biologically closer to sporadic Burkitt than to the endemic form and is less responsive to chemotherapy, even for those patients in whom the HIV status allows full chemotherapy doses.3

Clinical Presentation

Patients with lymphoma may present with the following symptoms:

• Lympadenopathy similar to tuberculosis

• Mediastinal mass

• Pleural effusion

• Splenomegaly

• Maxillary mass (Burkitt lymphoma)

• Right iliac fossa mass

• Intussusception

• Bowel obstruction

• Bowel perforation

• Fever, weight loss, night sweats

• Pel-Ebstein fever

Hodgkin’s lymphoma is primarily a disease of lymph nodes, and the clinical presentation largely depends upon which group of nodes is predominantly affected. The classical presentation is of painless lymph node swelling that proceeds to displace structures and may reach massive proportions, causing secondary pressure effects (Figures 104.1–104.3). In NHL, extra-nodal disease is common and is often related to the gastrointestinal (GI) tract or other lymphoid organs, such as the spleen. Lymphoblastic lymphoma, which is difficult to differentiate from a lymphoblastic leukaemia, typically presents with a mediastinal mass or pleural effusion. In Equatorial Africa, the classic picture of Burkitt lymphoma (Figure 104.4) is of a rapidly growing jaw or maxillary tumour in a small child under the age of 5 years. Additional abdominal disease is seen in about half of the patients. Endemic Burkitt lymphoma rarely presents as a right iliac fossa mass that can be confused with an inflammatory lesion, but intestinal involvement can provoke intussusception, intestinal obstruction, and occasionally intestinal perforation, although these symptoms are more common in sporadic cases. However, the pattern of disease presentation varies widely across relatively small geographic areas, suggesting that environmental factors may play a role.9

Figure 104.1: Abdominal radiograph with a mass

 

Figure 104.2: Abdominal computed tomography (CT) scan with a mass

 

Figure 104.3: Abdominal magnetic resonance imaging (MRI) with a mass.

 

Figure 104.4: Burkitt lymphoma

 

Constitutional symptoms of fever, weight loss, and night sweats, known as B symptoms, are associated with extensive extranodal disease and a poorer prognosis, irrespective of the lymphoma subtype.10 B symptoms are more commonly present in patients with HIV-related lymphoma. The well-known Pel-Ebstein fever seen occasionally in patients with Hodgkin’s lymphoma is simply a B symptom with a name.

Investigation and Staging

Appropriate treatment can only follow tissue diagnosis and accurate staging. Because the intranodal pattern of growth still has an important bearing on classification, an entire node should be submitted for examination. Fine needle aspirates and needle biopsies give limited information, but they may suffice in areas where more detailed studies are not available or are irrelevant to management decisions. In children with jaw tumours clinically thought to be Burkitt lymphoma, the diagnosis can often be confirmed by removing one of the free-floating teeth that are characteristic of the lesion. Usually this can be achieved without an operation, as the tooth can be extracted digitally, and the tissue attached to the tooth is adequate for diagnosis.

Cytogenetic studies allow lymphoma to be categorised more precisely, but therapeutic decisions can be made on morphological assessment alone combined with clinical staging. The St. Jude modification of the Ann Arbor Hodgkin’s staging system based on clinical assessment, plain radiology, and ultrasound (Table 104.1) can be applied to NHL.

Burkitt lymphoma should be staged according to the Uganda Cancer Institute staging system. This reflects the high incidence of abdominal disease, even in patients presenting primarily with jaw disease, and recognises the effect of complete surgical resection when this is possible (Table 104.2).

All lymphomas should further be categorised as to the presence or absence of B symptoms. The presence of B symptoms should be signified by an addition of the suffix “B” after the stage shown in Table 104.1. If present, B symptoms would justify an increase in treatment intensity. Serum lactate dehydrogenase (LDH) is a useful marker of tumour activity and can be measured serially to assess response to treatment. Most high-risk lymphomas have initially high levels of LDH; a rapid fall reflects tumour responsiveness and is associated with a more favourable prognosis.11

Treatment

The actual treatment of lymphoma does not usually involve the surgeon, as it is based primarily on chemotherapy with selective use of radiotherapy.

The surgeon may be involved in the diagnosis of lymphoma, particularly in differentiating between tuberculosis nodal enlargement and lymphoma in the HIV-positive child, the definition and resection of localised intraabdominal disease, as well as in the management of complications of either the disease itself or its treatment. High-grade lymphomas, by virtue of their rapid cell proliferation, generally respond well—often dramatically—to chemotherapy. Indeed, the rapidity of cell death after initiating treatment may present the kidney with unmanageable quantities of purines, pyrimidines, phosphate, and other cellular detritus, leading to tumour lysis syndrome. Oncology treatment protocols should include measures, such as prophylactic urate oxidase, hyperhydration, and urine alkalinisation12 to minimise this occurrence.

The outcome for children with Burkitt lymphoma is clearly related to access to effective chemotherapy. This is such a rapidly growing tumour that those in whom there is a delay—either pending histopathology confirmation or pending recovery from laparotomy at which extensive disease precluded total resection—fare worse.13 In addition to systemic chemotherapy, intrathecal methotrexate should be given to reduce the risk of CNS relapse.14

A considerable amount of energy has been expended in attempting to develop a low toxicity, high efficacy regimen for the treatment of Burkitt lymphoma that would be practicable in a resource-limited environment.14 This effort is being cofunded by the International Society for Pediatric Oncology (SIOP). Resource limitations not only impact the actual affordability of treatment drugs but also the availability of supportive care, such as antibiotics, and the ability to manage treatment-related toxicity, particularly bone marrow suppression with, among others, blood component therapy. An ideal regimen should therefore be nontoxic as well as effective, inexpensive, and easy to administer.15 The results of the SIOP studies have been encouraging, and relapse, should it occur, can also be effectively treated within a resource-constrained service.16

Patients with HIV-related lymphomas, excluding cerebral lymphomas, can tolerate effective chemotherapy protocols when treatment is given in conjunction with highly active antiretroviral therapy (HAART).

Surgery

The surgeon may be required to biopsy either a nodal mass, gonad, or mediastinal tumour, although frequently in Africa the diagnosis can be reached with sufficient precision to allow rational treatment following needle biopsy or bone marrow biopsy.

The role of the surgeon in the primary management of children with B-cell lymphoma remains controversial. In endemic areas, localised intraabdominal disease is, unfortunately, not as frequent as it is in sporadic cases occurring outside Equatorial Africa. There is, however, no doubt that on rare occasions abdominal disease is localised, complete resection is beneficial but biopsy only or debulking does not improve survival.17,18 As chemotherapy regimens become more successful and more widely available, pressure on the surgeon is easing.19

In patients who present with an abdominal emergency, such as perforation, obstruction, or intussusception, the decision to operate is easy. The procedure that can be performed is defined by the findings at the time of surgery. Complete resection is ideal if circumstances allow, but the extent of disease may limit this ambition to a bypass procedure or biopsy alone. In patients with residual intraabdominal disease after laparotomy, delay in the administration of chemotherapy should be avoided.17

In patients in whom there is no crisis but an abdominal mass is palpable, the likelihood of complete resection must be judged from clinical assessment and preoperative imaging.

If abdominal disease is associated with extraabdominal lymphoma, then the initial strategy should be chemotherapy.20 If the tumour is judged by the surgeon to be unresectable, the initial treatment should also be chemotherapy.

Staging laparotomy is not required. Even in the absence of sophisticated radiological techniques, it is usually possible to define the extent of disease within the abdomen with ultrasound, and, if necessary, to obtain tissue by using a needle biopsy. In some patients, a diagnostic laparotomy will have been indicated for symptoms at presentation. It is not necessary to remove the spleen or any other organ in order to stage or effectively treat the tumour. In patients with primary bowel lymphoma, chemotherapy can be so effective that the tumour regresses, leaving a hole in the bowel.21

This constitutes a surgical emergency. Surgical management will depend upon the clinical status of the patient as well as the findings at laparotomy. Exsanguinating haemorrhage from the bowel has also been reported in patients while on treatment for intestinal lymphoma. If the bleeding does not respond to conventional resuscitation, operative treatment may be necessary.21

Outcomes

Patients with T-cell and large-cell lymphomas fare worse than those with lymphomas of B-cell lineage.22 Generally, patients with lymphoma and coexistent HIV disease do less well than patients who are not HIV-infected. The advent of HAART may change this perception, as improvement in immune status will allow HIV-infected individuals to tolerate more aggressive chemotherapy with shorter rest periods.10,23

Patients in the developed world have a higher incidence of resectable abdominal disease, and treatment with aggressive chemotherapy, including stem cell rescue, is available. With such aggressive treatment, 5-year survival rates reach 90% for localised disease and 70% for disseminated disease.3

In Africa, outcomes vary according to local geographic and economic factors. The most convincing data come from the Malawi Burkitt Lymphoma Project, which used initial cyclophosphamide monotherapy and later introduced intrathecal methotrexate for CNS prophylaxis. Initially, 63% of those with lesions in the head and neck secured complete remission with monotherapy, but only 33% of those with abdominal or other sites did so.14 More recent studies have shown a 53% event-free survival for stage 3 patients13 and a 71% complete clinical remission in those who relapsed or had primarily resistant tumours.15 These results are encouraging and show that much can be achieved even in the most resource-constrained countries.

 

 

1.3. Teratoma.

Teratomas are tumors comprising more than a single cell type derived from more than one germ layer. A significant degree of confusion has arisen regarding nomenclature for the various subtypes of teratomas. The word itself is derived from the Greek word teraton, meaning monster, and was used initially by Virchow in the first edition of his book on tumors, which was published in 1863. Teratomas range from benign, well-differentiated (mature) cystic lesions to those that are solid and malignant (immature). Besides being mature, with malignant transformation, teratomas also may be monodermal and highly specialized.

 

The term dermoid cyst was coined in the veterinary literature in 1831 by Leblanc when he removed a lesion that resembled skin at the base of a horse’s skull, which he called a kyste dermoid. Both terms, now more than a century old, still are in general use and often are used interchangeably. The earliest implications were that dermoids were composed predominantly of elements similar to skin and its appendages, while teratomas had no such limits. Dermoids now are recognized as often being trigeminal and containing practically any type of tissue. In those who continue to make a distinction, dermoids are tumors that maintain rather orderly arrangements, with well-differentiated ectodermal and mesodermal tissues surrounding endodermal components. Teratomas, specifically solid teratomas, essentially are devoid of organization; thus, the presence of some degree of organization, a high degree of cellular differentiation, and cystic structure differentiates dermoids from teratomas.

Pathophysiology of teratomas. Teratomas are made up of a variety of parenchymal cell types representative of more than a single germ layer, usually all 3. Arising from totipotential cells, these tumors typically are midline or paraxial. The most common location is sacrococcygeal (57%). Because they arise from totipotential cells, they are encountered commonly in the gonads (29%). By far the most common gonadal location is the ovary, although they also occur somewhat less frequently in the testes. Cystic teratomas occasionally occur in sequestered midline embryonic cell rests and can be mediastinal (7%), retroperitoneal (4%), cervical (3%), and intracranial (3%). Cells differentiate along various germ lines, essentially recapitulating any tissue of the body. Examples include hair, teeth, fat, skin, muscle, and endocrine tissue. Mature cystic teratomas can result in significant morbidity. Potential complications vary depending on the site of occurrence.

Association of neoplasia and congenital malformations

The concept that teratogenesis and oncogenesis have shared mechanisms is well documented by numerous examples. Probably, there is simultaneous or sequential cellular and tissue reaction to specific injurious agents. The degree of cytodifferentiation, the metabolic or immunological state of the embryo or fetus, and the length of time of exposure to the agent will determine whether the effect is teratogenic, oncogenic, both, or neither. Many biological, chemical and physical agents known to be teratogenic to the fetus or embryo are carcinogenic postnatally. Alternatively, a teratogenic event during intrauterine life may predispose the fetus to an oncogenic event later in life. This would explaieoplastic transformation occurring in hamartomas, developmental vestiges, heterotopias and dysgenetic tissues. It is postulated that the anomalous tissues harbor latent oncogenes which, under certain environmental conditions, are activated, resulting in malignant transformation of a tumor.

Classification

A formal classification of fetal tumors does not exist. Apart from distinguishing solid from cystic lesions, probably the best classification should be by location. The main compartments of fetal tumors are the head and brain, face and neck, thorax (including the heart), abdomen and retroperitoneum, extremities, genitalia, sacrococcygeal region, and skin.

 

Prenatal diagnosis

The approach for prenatal diagnosis of fetal tumors should be based on three sets of ultrasound signs: general signs, organ-specific signs and tumor-specific signs. The general sonographic features, that should raise the suspicion of an underlying fetal tumor, include:

Ø Absence or disruption of contour, shape, location, sonographic texture or size, of a normal anatomic structure;

Ø Presence of an abnormal structure or abnormal biometry;

Ø Abnormality in fetal movement;

Ø Polyhydramnios; and

Ø Hydrops fetalis.

Polyhydramnios is particularly important, because almost 50% of fetal tumors are accompanied by this finding. The underlying mechanisms include interference with swallowing (such as thyroid goiter or myoblastoma), mechanical obstruction (such as gastrointestinal tumors), excessive production of amniotic fluid (such as sacrococcygeal teratoma), and decreased resorption by lung tissue in lung pathology. Intracranial tumors are also commonly associated with polyhydramnios and the mechanism may be neurogenic lack of swallowing or inappropriate polyuria.

Tumor-specific signs include pathological changes within the tumor mass (calcifications, liquefaction, organ edema, internal bleeding, neovascularization and rapid changes in size and texture). Organ-specific signs are rare, but in some cases they are highly suggestive of the condition (such as cardiomegaly with a huge solid or cystic mass occupying the entire heart, suggesting intrapericardial teratoma).

In some cases, normal and abnormal sonographic findings may mimic fetal tumors. Examples may vary from severe cases of bladder exstrophy (where the protruding bladder mass appears as a solid tumor-like structure), to rare cases of fetal scrotal inguinal hernia (where bowel loops occupy the scrotum, appearing as huge masses).

Prognosis

Apart from intracranial tumors (where the prognosis is generally poor), the prognosis for tumors in other locations is variable and depends on the size of the tumor (with resultant compression of adjacent organs), degree of vascularization (with the risk of causing heart failure and hydrops), and associated polyhydramnios (with the risk of preterm delivery).

SACROCOCCYGEAL TERATOMA

Definition and Epidemiology

 

Sacrococcygeal teratomas are diagnosed commonly in the prenatal period, and complications may occur in utero or during or after birth.

Potential complications in utero include polyhydramnios and tumor hemorrhage, which can lead to anemia and nonimmune hydrops fetalis. If significant atrioventricular shunting occurs within the tumor, hydrops may result from high-output cardiac failure. Development of hydrops is an ominous sign. If it develops after 30 weeks’ gestation, the mortality rate is 25%. If it is recognized, delivery is recommended as soon as lung maturity is documented. Development of hydrops before 30 weeks’ gestation has an abysmal prognosis, with a 93% mortality rate.

Antenatal diagnosis of SCT is very important and increasingly being made with fetal sonography. On ultrasound, SCT may be solid or mixed in echogenicity with interspersed or peripheral cystic components. The imaging of tumors which contain calcification varies in terms of increased echogenicity or echogenicity and shadowing

Sacrococcygeal teratomas are classified according to the degree of exterior component or intrapelvic extension:

Type I tumors are predominantly external, attached to the coccyx, and may have a small presacral component (45.8%). No metastases were associated with this group.

Type II tumors have both an external mass and significant presacral pelvic extension (34%) and have a 6% metastases rate.

Type III tumors are visible externally, but the predominant mass is pelvic and intraabdominal (8.6%). A 20% rate of metastases was found in this group.

Type IV lesions are not visible externally but are entirely presacral (9.6%) and have an 8% metastases rate.

Clinical Presentation. Sacrococcygeal teratomas ( SCT ) are commonly very large ( average 8-10 cm ), well encapsulated and grossly lobulated. These masses possess both cystic and solid components. SCT is nearly always arising from the tip of the coccyx.

Benign teratomas usually produce no functional impairment. The presence of bladder or bowel dysfunction suggest a malignant lesion. Evidence for venous or lymphatic obstruction or lower leg paralysis is found more commonly in malignant tumors. In addition, pressure on a meningomeylocele will often be noticeably transmitted to the anterior fontanel.

15% of patients have associated congenital anomalies: imperforate anus, sacral bone defects, duplication of uterus or vagina, spina bifida, meningomyelocele.

SCT is the most common congenital neoplasm of the fetus with an incidence of 1 in 40,000 births. About 80 per cent occur in girls, but it is more often malignant in boys. A substantial number have been encountered in twins. Most cases are asymptomatic in utero and diagnosed after birth. Fetuses with this malformation are at risk for significant perinatal morbidity and mortality.

Complications.

Postpartum morbidity associated with sacrococcygeal teratomas is attributable to associated congenital anomalies, mass effects of the tumor, recurrence, and intraoperative and postoperative complications. Approximately 10% of sacrococcygeal teratomas are associated with other congenital anomalies, primarily defects of the hindgut and cloacal region, which exceeds the baseline rate of 2.5% expected in the general population.

Tumor mass and associated polyhydramnios frequently caused pre-term labor and delivery; fetal survival depended on lung maturity. Massive hemorrhage into the tumor with secondary fetal exsanguination sometimes occurred spontaneously in utero or was precipitated by labor and delivery. Dystocia, secondary to tumor bulk or tumor rupture, sometimes complicated delivery. Finally, in a few cases, placentomegaly and/or hydrops evolved, which, in turn, precipitated rapid fetal death.

Figure: Giant ruptured sacrococcygeal teratoma

Differential Diagnosis: meningomyelocele , rectal abscess , dermoid cyst , angioma , lipoma, neurogenic tumor, pilonidal cyst.

Figure : Malignant sacrococcygeal teratoma presenting at 3months of age.

Treatmen is primarily surgical, including removal of the coccyx.

In fetuses with tumors larger than 5 cm, cesarean delivery should be considered to prevent dystocia or tumor rupture. Because of the poor prognosis associated with development of hydrops prior to 30 weeks’ gestation, these fetuses may benefit from in utero surgery. In most cases, sacrococcygeal teratomas should be resected electively in the first week of life, since long delays may be associated with a higher rate of malignancy.

Complete excision should be done through a chevron-shaped buttock incision, with careful attention to the preservation of the muscles of the rectal sphincter. The coccyx always should be resected with the tumor, as failure to do so results in a 35-40% recurrence rate. Hemorrhage from the middle sacral vessels and hypogastric arteries is the most common complication.

Malignant = surgical excision + chemotherapy + radiation (metastases to lung, bone, liver).

Prognosis:

Benign – disease free survival is greater than 90%; malignant – significant mortality, although good progress has been made recently in treatment of these tumors.

Time of diagnoses is key:

Ø    < 2 months of age, only 7-10% are malignant

Ø    Age 1 year, 37% malignant

Ø    Age 2 years, 50% malignant

 

1.4. Dermoid cysts.

Congenital dermoid inclusion cysts are superficial and located in proximity to the hyoid bone. They are epithelial-lined cysts with variable skin appendages in a mesodermal stroma. These masses do not move with swallowing or tongue protrusion. On occasion, a dermoid cyst ruptures, resulting in an intense granulomatous inflammatory reaction. In contrast to thyroglossal duct cysts, dermoid cysts rarely become infected.

 

Dermoid cysts are treated with simple excision and do not recur if the entire cyst wall is excised. Excision of a midline cervical cleft is of cosmetic importance only and is treated electively. Excision is done with a series of Z-plasty incisions to prevent a linear contracture that interferes with extension of the head.

1.5. Nevus.

The term naevus refers to a hamartomatous malformation of the skin. Naevi may be principally composed of dermal elements, such as connective tissue naevus, melanocytes (naevocellular naevus), vascular elements, or epidermal elements (epidermal naevi).

Epidermal naevi

Epidermal naevi are verrucous or wart-like and are frequently present at birth although may develop later in childhood or (rarely) in adult life. They may be small, resembling true viral warts, but more typically they form large linear plaques or linear arrays of warty papules. Rarely, large areas of the body surface may be covered by linear or swirling arrays of these lesions. Epidermal naevi are typically asymptomatic, although large linear naevi may become spontaneously inflamed, with the development of pruritus and erythema of the lesions and surrounding skin.

Histologically, epidermal naevi are characterized by acanthosis and hyperkeratosis. Cytological atypism is not seen. They are most commonly removed for cosmetic reasons. Such treatment may involve excision with primary closure, electrodesiccation, carbon dioxide laser ablation, or cryosurgery.

Epidermal naevi are generally of little consequence to the general health of the patient. Very rarely, they may be associated with congenital malformations of underlying osseous and soft tissue structures, particularly when lesions occur on the head and neck. Malignant transformation within epidermal naevi is exceedingly rare, except in the case of a naevus sebaceus.

 

Naevus sebaceus is a type of epidermal naevus that occurs exclusively on the scalp or face. Histologically, naevus sebaceus is characterized by the same type of epidermal proliferation seen in other epidermal naevi, but large mature sebaceus glands and apocrine glands are also present. Before puberty, naevus sebaceus is typically a smooth-surfaced flat plaque with slightly yellowish or yellow-orange colour. When it occurs on the scalp, which is the most common site, the absence of hair within the lesion may bring it to attention. At puberty, the sebaceous element within the naevus begin to hypertrophy and the surface becomes more verrucous. Unlike other epidermal naevi, naevus sebaceus may occasionally undergo malignant transformation, with the formation of basal cell carcinoma within the lesion. Since such transformation occurs in only about 5 %of patients with naevus sebaceus, the common practice of excising these lesions prophylactically is controversial. Benign tumours such as syringocystadenoma papilliferum may also occur within these naevi.

Connective tissue naevi

Connective tissue naevi are generally present at birth. They consist of firm, flesh-coloured papules and plaques and are usually solitary. The hair follicle orifices may be prominent within lesions, giving them the appearance of pig skin. Connective tissue naevi are usually idiopathic and are not associated with any other disease, with the exception of the shagreen patch that occurs in tuberous sclerosis. Histologically, connective tissue naevi are composed of dense aggregations of dermal elements, usually collagen fibres or elastic fibres, or both. Connective tissue naevi are harmless, although they may be excised for cosmetic or functional reasons.

 

1.6. Rhabdomyosarcoma.

Incidence

                Tumors of soft tissue:

1.1.           Hemangioma.

1.2.           Lymphangioma.

1.3.           Teratoma.

1.4.           Dermoid cysts.

1.5.           Nevus.

1.6.           Rhabdomyosarcoma.

2.                Nefroblastoma.

3.                Neuroblastoma.

4.                Mediastinal tumors.

 

1. Tumors of soft tissue:

1.1. Hemangioma.

Haemangiomas are proliferations of mature vascular elements. These endothelium-lined vascular spaces are most commonly capillary sized, but larger cavernous spaces also are found, especially in large lesions. Different clinical types of haemangiomas are commonly recognized.

Strawberry haemangiomas may be present at birth but, more typically, develop during the first few weeks of life. They are seen in approximately 3 % of newborn infants, and 80 % are solitary, although multiple haemangiomas also occur. Strawberry haemangiomas range in size from 1 mm to many centimetres. The lesions are well-demarcated, lobular, bright red nodules with a spongy consistency. The surface of the lesion is studded with small capillary tufts, which produce the resemblance to a strawberry.

 

Strawberry haemangiomas seldom require treatment, since the vast majority involute spontaneously by the age of 6 or 7 years. Treatment may be required, however, for lesions situated on the eyelids, nares, or lips, where they may cause functional impairment. Rarely, giant strawberry haemangiomas, particularly those with a cavernous component, may be associated with thrombocytopenia, presumably due to platelet sequestration with the lesion. This phenomenon, known as the Kasabach-Merritt syndrome, may require surgical treatment if other measures fail.

Administration of corticosteroids, which may stimulate gradual involution of lesions is often used as first-line treatment for rapidly growing strawberry haemangiomas. Surgical excision and carbon dioxide laser ablation are often successful, but may produce unacceptable scarring. The efficacy of dye laser treatment is currently being evaluated and promises to be effective.

Cherry haemangiomas are generally smaller than strawberry haemangiomas, and tend to be round and bright red. They begin to appear during childhood, and continue to develop throughout adult life. The tendency to develop cherry haemangiomas appears to be transmitted within families as an autosomal dominant trait. Cherry haemangiomas seldom require treatment other than for cosmetic reasons: they are easily excised with a scalpel or biopsy punch. Occasionally, cherry haemangiomas thrombose, changing in colour from bright red to purplish black. This colour change may alarm patient and physician alike, since the apparent sudden appearance of a black papule raises the spectre of nodular malignant melanoma. Biopsy is indicated in such cases.

Cavernous haemangiomas, like strawberry haemangiomas, may be present at birth and grow rapidly during the first few months of life. They also involute spontaneously. Cavernous haemangiomas are primarily situated beneath the skin, and clinically appear as soft, bluish masses that distend the surrounding features. A typical strawberry haemangioma may form the cutaneous component of a cavernous haemangioma. Both strawberry and cavernous haemangiomas, when multiple, may be the presenting sign of diffuse neonatal haemangiomatosis, in which multiple haemangiomas occur not only in the skin and subcutaneous tissue, but also in the liver and other organs.

 

Port wine stains, unlike haemangiomas, do not represent the proliferation of excessive numbers of vascular elements, but are caused by ectasia of normal numbers of vessels within the skin. The dermal vessels that comprise port wine stains are capillary size or slightly larger. Port wine stains are generally present at birth, and occur in 0.3 %of neonates. Early in life, port wine stains are generally pink or purplish-pink in colour, and macular. With time, the vascular channels become more and more ectatic, imparting a lumpy appearance to the skin. Mature port wine stains are frequently dark purple. Port wine stains are most commonly found on the head and neck, but may also be seen on the trunk, particularly in the pectoral area, and on the extremities, usually the arms. Port wine stains of the orbital region may be associated with unilateral glaucoma.

 

The Sturge-Weber syndrome is characterized by the presence of a port wine stain in the distribution of the first branch of the trigeminal nerve, associated with a similar vascular malformation of the underlying cerebral cortex and meninges. Seizures, mental retardation, and motor cortical deficits are seen in many patients. The Klippel-Trenaunay-Weber syndrome is an association of port wine stain of an extremity or the trunk with arteriovenous malformations and hemihypertrophy.

Treatment for port wine stains was unsatisfactory and produced unacceptable scarring: cryosurgery, carbon dioxide and argon laser surgery, excision and grafting, and tattooing with skin-coloured pigments were all used with variable degrees of success. The development of tuneable dye lasers has revolutionized the treatment of port wine stains, making it possible to remove these lesions partially or completely without excessive scarring.

Pyogenic granuloma is a common vascular lesion that presents as a rapidly-growing papule or nodule which is friable and bleeds easily after minor trauma. Pyogenic granuloma is a misnomer: it is actually an eruptive capillary haemangioma. Treatment with electrofulguration, carbon dioxide laser ablation, or simple excision is usually curative, although lesions may recur. Since the differential diagnosis of a rapidly growing and bleeding nodule also includes nodular malignant melanoma, biopsy should be performed if there is any doubt about the diagnosis.

 

1.2. Lymphangioma.

Introduction

Lymphoma is a generic term used to describe malignant expansion of any of the lymphoid cell series. The nosology of lymphoma is an evolving science with clinical, morphological, and phenotypic studies contributing to the final diagnosis. The historical classification of lymphomas based purely upon morphological appearances under the light microscope has led to confusion and had little prognostic significance, so the Revised Euro-American Lymphoma (REAL) classification is in current use,1 albeit modified by the World Health Organisation (WHO) to include cytogenetic factors.2

Currently, about 15% of lymphomas are regarded as Hodgkin’s disease, defined by the presence of Reed-Sternberg cells on light microscopy, and the remaining 85% as non-Hodgkin’s lymphoma (NHL). NHL may stem from cells that have B-cell or T-cell, including natural killer (NK) cell, lineage. Amongst NHL, B-cell phenotypes account for about 85% of the diagnosed cases, and within Africa, Burkitt lymphoma is the most common B-cell tumour. REAL divides lymphomas into high-, intermediate-, and low-grade tumours, giving prognostic information that is of value. Burkitt lymphoma is regarded as a high-grade tumour and is one of the fastest-growing neoplasms known, with a tumour doubling time of between 24 and 48 hours.3

Aetiology/Pathophysiology

The transformation of cellular behaviour from “normal” to a pattern that we recognise as “malignant” occurs when the genes controlling cellular behaviour are altered in some way. In lymphoid cells, this commonly occurs as a result of chromosomal translocations (e.g., t(8;14) in Burkitt lymphoma, in which a proto-oncogene cmyc is moved from its normal site on chromosome 8 to a site on chromosome 14), chromosomal deletions, or oncogenic viruses.

There is a strong association between the Epstein-Barr virus (EBV) and endemic Burkitt lymphoma; although a causal relationship is not certain, EBV antigen can be detected in up to 90% of children affected by Burkitt lymphoma. Many viruses may, through chronic antigenic stimulation, result in chronic B-cell proliferation, thereby increasing the probability of spontaneous chromosomal aberration. It is possible that the origin of the genomic injuries in endemic Burkitt lymphoma is more complex, involving malaria, EBV, arborviruses,4 and possibly also plant products.5

In only 15% of patients with sporadic Burkitt lymphoma seen outside Central Africa is there an associated EBV infection. Sporadic Burkitt lymphoma also has a different pattern of presentation but is histologically identical to the endemic form. It is likely that sporadic Burkitt lymphoma is a disease different from the African form that shares a similar cellular morphology.

Within each subgroup of NHL, cell size and pattern of growth (nodular or diffuse) reflect the gene products of the altered genome, and these in turn determine the innate aggression of the tumour. Anatomical staging also contributes to treatment decisions. In Africa, the human immunodeficiency virus (HIV) pandemic has greatly altered the epidemiology of lymphoma, resulting in a considerable increase in primary cerebral lymphoma and a substantial increase in the numbers of patients with B-cell NHL.6,7 Burkitt lymphoma is regarded as an acquired immune deficiency syndrome (AIDS)-defining disease in HIV-infected individuals.8 HIV-related Burkitt lymphoma seems to be biologically closer to sporadic Burkitt than to the endemic form and is less responsive to chemotherapy, even for those patients in whom the HIV status allows full chemotherapy doses.3

Clinical Presentation

Patients with lymphoma may present with the following symptoms:

• Lympadenopathy similar to tuberculosis

• Mediastinal mass

• Pleural effusion

• Splenomegaly

• Maxillary mass (Burkitt lymphoma)

• Right iliac fossa mass

• Intussusception

• Bowel obstruction

• Bowel perforation

• Fever, weight loss, night sweats

• Pel-Ebstein fever

Hodgkin’s lymphoma is primarily a disease of lymph nodes, and the clinical presentation largely depends upon which group of nodes is predominantly affected. The classical presentation is of painless lymph node swelling that proceeds to displace structures and may reach massive proportions, causing secondary pressure effects (Figures 104.1–104.3). In NHL, extra-nodal disease is common and is often related to the gastrointestinal (GI) tract or other lymphoid organs, such as the spleen. Lymphoblastic lymphoma, which is difficult to differentiate from a lymphoblastic leukaemia, typically presents with a mediastinal mass or pleural effusion. In Equatorial Africa, the classic picture of Burkitt lymphoma (Figure 104.4) is of a rapidly growing jaw or maxillary tumour in a small child under the age of 5 years. Additional abdominal disease is seen in about half of the patients. Endemic Burkitt lymphoma rarely presents as a right iliac fossa mass that can be confused with an inflammatory lesion, but intestinal involvement can provoke intussusception, intestinal obstruction, and occasionally intestinal perforation, although these symptoms are more common in sporadic cases. However, the pattern of disease presentation varies widely across relatively small geographic areas, suggesting that environmental factors may play a role.9

Figure 104.1: Abdominal radiograph with a mass

 

Figure 104.2: Abdominal computed tomography (CT) scan with a mass

 

Figure 104.3: Abdominal magnetic resonance imaging (MRI) with a mass.

 

Figure 104.4: Burkitt lymphoma

 

Constitutional symptoms of fever, weight loss, and night sweats, known as B symptoms, are associated with extensive extranodal disease and a poorer prognosis, irrespective of the lymphoma subtype.10 B symptoms are more commonly present in patients with HIV-related lymphoma. The well-known Pel-Ebstein fever seen occasionally in patients with Hodgkin’s lymphoma is simply a B symptom with a name.

Investigation and Staging

Appropriate treatment can only follow tissue diagnosis and accurate staging. Because the intranodal pattern of growth still has an important bearing on classification, an entire node should be submitted for examination. Fine needle aspirates and needle biopsies give limited information, but they may suffice in areas where more detailed studies are not available or are irrelevant to management decisions. In children with jaw tumours clinically thought to be Burkitt lymphoma, the diagnosis can often be confirmed by removing one of the free-floating teeth that are characteristic of the lesion. Usually this can be achieved without an operation, as the tooth can be extracted digitally, and the tissue attached to the tooth is adequate for diagnosis.

Cytogenetic studies allow lymphoma to be categorised more precisely, but therapeutic decisions can be made on morphological assessment alone combined with clinical staging. The St. Jude modification of the Ann Arbor Hodgkin’s staging system based on clinical assessment, plain radiology, and ultrasound (Table 104.1) can be applied to NHL.

Burkitt lymphoma should be staged according to the Uganda Cancer Institute staging system. This reflects the high incidence of abdominal disease, even in patients presenting primarily with jaw disease, and recognises the effect of complete surgical resection when this is possible (Table 104.2).

All lymphomas should further be categorised as to the presence or absence of B symptoms. The presence of B symptoms should be signified by an addition of the suffix “B” after the stage shown in Table 104.1. If present, B symptoms would justify an increase in treatment intensity. Serum lactate dehydrogenase (LDH) is a useful marker of tumour activity and can be measured serially to assess response to treatment. Most high-risk lymphomas have initially high levels of LDH; a rapid fall reflects tumour responsiveness and is associated with a more favourable prognosis.11

Treatment

The actual treatment of lymphoma does not usually involve the surgeon, as it is based primarily on chemotherapy with selective use of radiotherapy.

The surgeon may be involved in the diagnosis of lymphoma, particularly in differentiating between tuberculosis nodal enlargement and lymphoma in the HIV-positive child, the definition and resection of localised intraabdominal disease, as well as in the management of complications of either the disease itself or its treatment. High-grade lymphomas, by virtue of their rapid cell proliferation, generally respond well—often dramatically—to chemotherapy. Indeed, the rapidity of cell death after initiating treatment may present the kidney with unmanageable quantities of purines, pyrimidines, phosphate, and other cellular detritus, leading to tumour lysis syndrome. Oncology treatment protocols should include measures, such as prophylactic urate oxidase, hyperhydration, and urine alkalinisation12 to minimise this occurrence.

The outcome for children with Burkitt lymphoma is clearly related to access to effective chemotherapy. This is such a rapidly growing tumour that those in whom there is a delay—either pending histopathology confirmation or pending recovery from laparotomy at which extensive disease precluded total resection—fare worse.13 In addition to systemic chemotherapy, intrathecal methotrexate should be given to reduce the risk of CNS relapse.14

A considerable amount of energy has been expended in attempting to develop a low toxicity, high efficacy regimen for the treatment of Burkitt lymphoma that would be practicable in a resource-limited environment.14 This effort is being cofunded by the International Society for Pediatric Oncology (SIOP). Resource limitations not only impact the actual affordability of treatment drugs but also the availability of supportive care, such as antibiotics, and the ability to manage treatment-related toxicity, particularly bone marrow suppression with, among others, blood component therapy. An ideal regimen should therefore be nontoxic as well as effective, inexpensive, and easy to administer.15 The results of the SIOP studies have been encouraging, and relapse, should it occur, can also be effectively treated within a resource-constrained service.16

Patients with HIV-related lymphomas, excluding cerebral lymphomas, can tolerate effective chemotherapy protocols when treatment is given in conjunction with highly active antiretroviral therapy (HAART).

Surgery

The surgeon may be required to biopsy either a nodal mass, gonad, or mediastinal tumour, although frequently in Africa the diagnosis can be reached with sufficient precision to allow rational treatment following needle biopsy or bone marrow biopsy.

The role of the surgeon in the primary management of children with B-cell lymphoma remains controversial. In endemic areas, localised intraabdominal disease is, unfortunately, not as frequent as it is in sporadic cases occurring outside Equatorial Africa. There is, however, no doubt that on rare occasions abdominal disease is localised, complete resection is beneficial but biopsy only or debulking does not improve survival.17,18 As chemotherapy regimens become more successful and more widely available, pressure on the surgeon is easing.19

In patients who present with an abdominal emergency, such as perforation, obstruction, or intussusception, the decision to operate is easy. The procedure that can be performed is defined by the findings at the time of surgery. Complete resection is ideal if circumstances allow, but the extent of disease may limit this ambition to a bypass procedure or biopsy alone. In patients with residual intraabdominal disease after laparotomy, delay in the administration of chemotherapy should be avoided.17

In patients in whom there is no crisis but an abdominal mass is palpable, the likelihood of complete resection must be judged from clinical assessment and preoperative imaging.

If abdominal disease is associated with extraabdominal lymphoma, then the initial strategy should be chemotherapy.20 If the tumour is judged by the surgeon to be unresectable, the initial treatment should also be chemotherapy.

Staging laparotomy is not required. Even in the absence of sophisticated radiological techniques, it is usually possible to define the extent of disease within the abdomen with ultrasound, and, if necessary, to obtain tissue by using a needle biopsy. In some patients, a diagnostic laparotomy will have been indicated for symptoms at presentation. It is not necessary to remove the spleen or any other organ in order to stage or effectively treat the tumour. In patients with primary bowel lymphoma, chemotherapy can be so effective that the tumour regresses, leaving a hole in the bowel.21

This constitutes a surgical emergency. Surgical management will depend upon the clinical status of the patient as well as the findings at laparotomy. Exsanguinating haemorrhage from the bowel has also been reported in patients while on treatment for intestinal lymphoma. If the bleeding does not respond to conventional resuscitation, operative treatment may be necessary.21

Outcomes

Patients with T-cell and large-cell lymphomas fare worse than those with lymphomas of B-cell lineage.22 Generally, patients with lymphoma and coexistent HIV disease do less well than patients who are not HIV-infected. The advent of HAART may change this perception, as improvement in immune status will allow HIV-infected individuals to tolerate more aggressive chemotherapy with shorter rest periods.10,23

Patients in the developed world have a higher incidence of resectable abdominal disease, and treatment with aggressive chemotherapy, including stem cell rescue, is available. With such aggressive treatment, 5-year survival rates reach 90% for localised disease and 70% for disseminated disease.3

In Africa, outcomes vary according to local geographic and economic factors. The most convincing data come from the Malawi Burkitt Lymphoma Project, which used initial cyclophosphamide monotherapy and later introduced intrathecal methotrexate for CNS prophylaxis. Initially, 63% of those with lesions in the head and neck secured complete remission with monotherapy, but only 33% of those with abdominal or other sites did so.14 More recent studies have shown a 53% event-free survival for stage 3 patients13 and a 71% complete clinical remission in those who relapsed or had primarily resistant tumours.15 These results are encouraging and show that much can be achieved even in the most resource-constrained countries.

 

 

1.3. Teratoma.

Teratomas are tumors comprising more than a single cell type derived from more than one germ layer. A significant degree of confusion has arisen regarding nomenclature for the various subtypes of teratomas. The word itself is derived from the Greek word teraton, meaning monster, and was used initially by Virchow in the first edition of his book on tumors, which was published in 1863. Teratomas range from benign, well-differentiated (mature) cystic lesions to those that are solid and malignant (immature). Besides being mature, with malignant transformation, teratomas also may be monodermal and highly specialized.

 

The term dermoid cyst was coined in the veterinary literature in 1831 by Leblanc when he removed a lesion that resembled skin at the base of a horse’s skull, which he called a kyste dermoid. Both terms, now more than a century old, still are in general use and often are used interchangeably. The earliest implications were that dermoids were composed predominantly of elements similar to skin and its appendages, while teratomas had no such limits. Dermoids now are recognized as often being trigeminal and containing practically any type of tissue. In those who continue to make a distinction, dermoids are tumors that maintain rather orderly arrangements, with well-differentiated ectodermal and mesodermal tissues surrounding endodermal components. Teratomas, specifically solid teratomas, essentially are devoid of organization; thus, the presence of some degree of organization, a high degree of cellular differentiation, and cystic structure differentiates dermoids from teratomas.

Pathophysiology of teratomas. Teratomas are made up of a variety of parenchymal cell types representative of more than a single germ layer, usually all 3. Arising from totipotential cells, these tumors typically are midline or paraxial. The most common location is sacrococcygeal (57%). Because they arise from totipotential cells, they are encountered commonly in the gonads (29%). By far the most common gonadal location is the ovary, although they also occur somewhat less frequently in the testes. Cystic teratomas occasionally occur in sequestered midline embryonic cell rests and can be mediastinal (7%), retroperitoneal (4%), cervical (3%), and intracranial (3%). Cells differentiate along various germ lines, essentially recapitulating any tissue of the body. Examples include hair, teeth, fat, skin, muscle, and endocrine tissue. Mature cystic teratomas can result in significant morbidity. Potential complications vary depending on the site of occurrence.

Association of neoplasia and congenital malformations

The concept that teratogenesis and oncogenesis have shared mechanisms is well documented by numerous examples. Probably, there is simultaneous or sequential cellular and tissue reaction to specific injurious agents. The degree of cytodifferentiation, the metabolic or immunological state of the embryo or fetus, and the length of time of exposure to the agent will determine whether the effect is teratogenic, oncogenic, both, or neither. Many biological, chemical and physical agents known to be teratogenic to the fetus or embryo are carcinogenic postnatally. Alternatively, a teratogenic event during intrauterine life may predispose the fetus to an oncogenic event later in life. This would explaieoplastic transformation occurring in hamartomas, developmental vestiges, heterotopias and dysgenetic tissues. It is postulated that the anomalous tissues harbor latent oncogenes which, under certain environmental conditions, are activated, resulting in malignant transformation of a tumor.

Classification

A formal classification of fetal tumors does not exist. Apart from distinguishing solid from cystic lesions, probably the best classification should be by location. The main compartments of fetal tumors are the head and brain, face and neck, thorax (including the heart), abdomen and retroperitoneum, extremities, genitalia, sacrococcygeal region, and skin.

 

Prenatal diagnosis

The approach for prenatal diagnosis of fetal tumors should be based on three sets of ultrasound signs: general signs, organ-specific signs and tumor-specific signs. The general sonographic features, that should raise the suspicion of an underlying fetal tumor, include:

Ø Absence or disruption of contour, shape, location, sonographic texture or size, of a normal anatomic structure;

Ø Presence of an abnormal structure or abnormal biometry;

Ø Abnormality in fetal movement;

Ø Polyhydramnios; and

Ø Hydrops fetalis.

Polyhydramnios is particularly important, because almost 50% of fetal tumors are accompanied by this finding. The underlying mechanisms include interference with swallowing (such as thyroid goiter or myoblastoma), mechanical obstruction (such as gastrointestinal tumors), excessive production of amniotic fluid (such as sacrococcygeal teratoma), and decreased resorption by lung tissue in lung pathology. Intracranial tumors are also commonly associated with polyhydramnios and the mechanism may be neurogenic lack of swallowing or inappropriate polyuria.

Tumor-specific signs include pathological changes within the tumor mass (calcifications, liquefaction, organ edema, internal bleeding, neovascularization and rapid changes in size and texture). Organ-specific signs are rare, but in some cases they are highly suggestive of the condition (such as cardiomegaly with a huge solid or cystic mass occupying the entire heart, suggesting intrapericardial teratoma).

In some cases, normal and abnormal sonographic findings may mimic fetal tumors. Examples may vary from severe cases of bladder exstrophy (where the protruding bladder mass appears as a solid tumor-like structure), to rare cases of fetal scrotal inguinal hernia (where bowel loops occupy the scrotum, appearing as huge masses).

Prognosis

Apart from intracranial tumors (where the prognosis is generally poor), the prognosis for tumors in other locations is variable and depends on the size of the tumor (with resultant compression of adjacent organs), degree of vascularization (with the risk of causing heart failure and hydrops), and associated polyhydramnios (with the risk of preterm delivery).

SACROCOCCYGEAL TERATOMA

Definition and Epidemiology

 

Sacrococcygeal teratomas are diagnosed commonly in the prenatal period, and complications may occur in utero or during or after birth.

Potential complications in utero include polyhydramnios and tumor hemorrhage, which can lead to anemia and nonimmune hydrops fetalis. If significant atrioventricular shunting occurs within the tumor, hydrops may result from high-output cardiac failure. Development of hydrops is an ominous sign. If it develops after 30 weeks’ gestation, the mortality rate is 25%. If it is recognized, delivery is recommended as soon as lung maturity is documented. Development of hydrops before 30 weeks’ gestation has an abysmal prognosis, with a 93% mortality rate.

Antenatal diagnosis of SCT is very important and increasingly being made with fetal sonography. On ultrasound, SCT may be solid or mixed in echogenicity with interspersed or peripheral cystic components. The imaging of tumors which contain calcification varies in terms of increased echogenicity or echogenicity and shadowing

Sacrococcygeal teratomas are classified according to the degree of exterior component or intrapelvic extension:

Type I tumors are predominantly external, attached to the coccyx, and may have a small presacral component (45.8%). No metastases were associated with this group.

Type II tumors have both an external mass and significant presacral pelvic extension (34%) and have a 6% metastases rate.

Type III tumors are visible externally, but the predominant mass is pelvic and intraabdominal (8.6%). A 20% rate of metastases was found in this group.

Type IV lesions are not visible externally but are entirely presacral (9.6%) and have an 8% metastases rate.

Clinical Presentation. Sacrococcygeal teratomas ( SCT ) are commonly very large ( average 8-10 cm ), well encapsulated and grossly lobulated. These masses possess both cystic and solid components. SCT is nearly always arising from the tip of the coccyx.

Benign teratomas usually produce no functional impairment. The presence of bladder or bowel dysfunction suggest a malignant lesion. Evidence for venous or lymphatic obstruction or lower leg paralysis is found more commonly in malignant tumors. In addition, pressure on a meningomeylocele will often be noticeably transmitted to the anterior fontanel.

15% of patients have associated congenital anomalies: imperforate anus, sacral bone defects, duplication of uterus or vagina, spina bifida, meningomyelocele.

SCT is the most common congenital neoplasm of the fetus with an incidence of 1 in 40,000 births. About 80 per cent occur in girls, but it is more often malignant in boys. A substantial number have been encountered in twins. Most cases are asymptomatic in utero and diagnosed after birth. Fetuses with this malformation are at risk for significant perinatal morbidity and mortality.

Complications.

Postpartum morbidity associated with sacrococcygeal teratomas is attributable to associated congenital anomalies, mass effects of the tumor, recurrence, and intraoperative and postoperative complications. Approximately 10% of sacrococcygeal teratomas are associated with other congenital anomalies, primarily defects of the hindgut and cloacal region, which exceeds the baseline rate of 2.5% expected in the general population.

Tumor mass and associated polyhydramnios frequently caused pre-term labor and delivery; fetal survival depended on lung maturity. Massive hemorrhage into the tumor with secondary fetal exsanguination sometimes occurred spontaneously in utero or was precipitated by labor and delivery. Dystocia, secondary to tumor bulk or tumor rupture, sometimes complicated delivery. Finally, in a few cases, placentomegaly and/or hydrops evolved, which, in turn, precipitated rapid fetal death.

Figure: Giant ruptured sacrococcygeal teratoma

Differential Diagnosis: meningomyelocele , rectal abscess , dermoid cyst , angioma , lipoma, neurogenic tumor, pilonidal cyst.

Figure : Malignant sacrococcygeal teratoma presenting at 3months of age.

Treatmen is primarily surgical, including removal of the coccyx.

In fetuses with tumors larger than 5 cm, cesarean delivery should be considered to prevent dystocia or tumor rupture. Because of the poor prognosis associated with development of hydrops prior to 30 weeks’ gestation, these fetuses may benefit from in utero surgery. In most cases, sacrococcygeal teratomas should be resected electively in the first week of life, since long delays may be associated with a higher rate of malignancy.

Complete excision should be done through a chevron-shaped buttock incision, with careful attention to the preservation of the muscles of the rectal sphincter. The coccyx always should be resected with the tumor, as failure to do so results in a 35-40% recurrence rate. Hemorrhage from the middle sacral vessels and hypogastric arteries is the most common complication.

Malignant = surgical excision + chemotherapy + radiation (metastases to lung, bone, liver).

Prognosis:

Benign – disease free survival is greater than 90%; malignant – significant mortality, although good progress has been made recently in treatment of these tumors.

Time of diagnoses is key:

Ø    < 2 months of age, only 7-10% are malignant

Ø    Age 1 year, 37% malignant

Ø    Age 2 years, 50% malignant

 

1.4. Dermoid cysts.

Congenital dermoid inclusion cysts are superficial and located in proximity to the hyoid bone. They are epithelial-lined cysts with variable skin appendages in a mesodermal stroma. These masses do not move with swallowing or tongue protrusion. On occasion, a dermoid cyst ruptures, resulting in an intense granulomatous inflammatory reaction. In contrast to thyroglossal duct cysts, dermoid cysts rarely become infected.

 

Dermoid cysts are treated with simple excision and do not recur if the entire cyst wall is excised. Excision of a midline cervical cleft is of cosmetic importance only and is treated electively. Excision is done with a series of Z-plasty incisions to prevent a linear contracture that interferes with extension of the head.

1.5. Nevus.

The term naevus refers to a hamartomatous malformation of the skin. Naevi may be principally composed of dermal elements, such as connective tissue naevus, melanocytes (naevocellular naevus), vascular elements, or epidermal elements (epidermal naevi).

Epidermal naevi

Epidermal naevi are verrucous or wart-like and are frequently present at birth although may develop later in childhood or (rarely) in adult life. They may be small, resembling true viral warts, but more typically they form large linear plaques or linear arrays of warty papules. Rarely, large areas of the body surface may be covered by linear or swirling arrays of these lesions. Epidermal naevi are typically asymptomatic, although large linear naevi may become spontaneously inflamed, with the development of pruritus and erythema of the lesions and surrounding skin.

Histologically, epidermal naevi are characterized by acanthosis and hyperkeratosis. Cytological atypism is not seen. They are most commonly removed for cosmetic reasons. Such treatment may involve excision with primary closure, electrodesiccation, carbon dioxide laser ablation, or cryosurgery.

Epidermal naevi are generally of little consequence to the general health of the patient. Very rarely, they may be associated with congenital malformations of underlying osseous and soft tissue structures, particularly when lesions occur on the head and neck. Malignant transformation within epidermal naevi is exceedingly rare, except in the case of a naevus sebaceus.

 

Naevus sebaceus is a type of epidermal naevus that occurs exclusively on the scalp or face. Histologically, naevus sebaceus is characterized by the same type of epidermal proliferation seen in other epidermal naevi, but large mature sebaceus glands and apocrine glands are also present. Before puberty, naevus sebaceus is typically a smooth-surfaced flat plaque with slightly yellowish or yellow-orange colour. When it occurs on the scalp, which is the most common site, the absence of hair within the lesion may bring it to attention. At puberty, the sebaceous element within the naevus begin to hypertrophy and the surface becomes more verrucous. Unlike other epidermal naevi, naevus sebaceus may occasionally undergo malignant transformation, with the formation of basal cell carcinoma within the lesion. Since such transformation occurs in only about 5 %of patients with naevus sebaceus, the common practice of excising these lesions prophylactically is controversial. Benign tumours such as syringocystadenoma papilliferum may also occur within these naevi.

Connective tissue naevi

Connective tissue naevi are generally present at birth. They consist of firm, flesh-coloured papules and plaques and are usually solitary. The hair follicle orifices may be prominent within lesions, giving them the appearance of pig skin. Connective tissue naevi are usually idiopathic and are not associated with any other disease, with the exception of the shagreen patch that occurs in tuberous sclerosis. Histologically, connective tissue naevi are composed of dense aggregations of dermal elements, usually collagen fibres or elastic fibres, or both. Connective tissue naevi are harmless, although they may be excised for cosmetic or functional reasons.

 

1.6. Rhabdomyosarcoma.

Incidence

Rhabdomyosarcoma is the third most common malignancy of childhood com­prising 5% of childhood malignancies. Four to 7 cases per million population are reported per year. The peak age of incidence is between 3 and 5 years but these tumors have been found ieonates. The male-female ratio is 1:1.4. The head and neck (40%), genitourinary tract (20%), extremities (18%) and trunk (7%) are the most common sites. The retro peritoneum (7%), perineum and other sites (8%) have also been involved. Bladder and vaginal rhabdomyosarcoma usually occur in infants. Extremity rhabdomyosarcomas are most common in adolescents.

 

Clinical Presentation

Clinical presentation varies with organ of origin. Eight}’ percent of patients present with local or regional disease at time of diagnosis. Tumors that develop in the na­sopharynx or auditory canal present with bloody or purulent drainage. If arising from the muscles of head and neck, an asymptomatic firm swelling is apparent. Orbital tumors often cause pain and swelling about the eye with proptosis and diplo­pia. Bloody vaginal discharge or the presence of a red polypoid friable lesion at the introitus are highly suggestive of rhabdomyosarcoma of the vagina. Bladder tumors may mimic an infection with urinary frequency or other difficulties with urination. Prostatic lesions can block the urinary flow necessitating catheterization. Rectal exam is usually diagnostic as the prostatic lesion bulges into the rectum. Lesions of the trunk or extremity present as a firm fixed mass beneath the subcutanteous tissue.

Differentiating these lesions from benigodules or tumors is often impossible without a biopsy. A family history should be taken because of the higher incidence of soft tissue sarcomas found in some families manifesting the Li-Fraumeni syn­drome. The Li-Fraumeni syndrome is a familial clustering of rhabdomyosarcoma, soft tissue tumors in children, adrenocortical adenocarcinoma and early breast can­cer in adults within families found to have a germline mutation of the p53 tumor suppressor gene.

Diagnosis

Ultrasound, CT and MR] can be used to better define the anatomic relation­ships of the primary tumor. Metastatic evaluation includes chest radiographs,

abdominal and chest CT scan, bone scan, skeletal survey, bone marrow aspirate and biopsy.

Diagnosis is made by incisional biopsy with frozen section analysis to be certain that enough representative tissue has been sampled. Fresh tissue should be analyzed for cell surface markers and chromosomes. Special stains can be used to differentiate the small round blue cells of rhabdomyosarcoma from neuroblastoma, lymphoma and Ewing’s sarcoma. Regional lymph nodes should be sampled in children with limb primaries.

Pathology

There are three subtypes of rhabdomyosarcoma: pleomorphic, alveolar and embryonal. The pleomorphic subtype is rarely diagnosed today and consists of sheets of anaplastic cells. It carries a poor prognosis. There are conflicting opinions about the differentiation between alveolar and embryonal rhabdomyosarcoma and the clini­cal significance of establishing the histologic subtype. Newer classification systems propose that any alveolar pattern identified in a tumor would group that tumor in the alveolar subtype. Twenty to 30% of newly diagnosed rhabdomyosarcoma are of the alveolar subtype. The embryonal subtype constitutes two thirds of newly diag­nosed rhabdomyosarcoma. Molecular techniques to differentiate these subtypes are being used more frequently and may clear up some of the confusion in the future.

Classification and Staging

The staging system used for the Intergroup Rhabdomyosarcoma Study (IRS) with the results is outlined in Table 49-1 ■

Treatment

Complete resection of the primary tumor with wide margins can be accom­plished in some cases. In lesions of the head and neck or pelvis this may not be possible and a second look operation following chemotherapy can be performed. Chemotherapy with vincristine, dactinomycin, and cylophosphanide (VAC) has proven efficacy in low-stage tumors. Other drug combinations continue to be evalu­ated to treat patients in the poor prognostic Stages II-IV and include etoposide and ifosfamide. Radiation therapy is recommended for residual disease

Outcomes

The overall prognosis for survival in children with rhabdomyosarcoma is depen­dent upon site of origin. Orbit lesions have the best overall prognosis with a 5-year survival of 94%. The 5-vear survival of other head and neck lesions is considerably less at 50%. Survival at five years for paratesticular, vaginal and limb/trunk lesions is 81%, 67%, and 44%, respectively.

 

2. Nefroblastoma.

Wilms’ tumor or nephroblastoma is the most common childhood abdominal malignancy. In the past 3 decades, the multidisciplinary approach to this tumor has become an example for successful cancer treatment. Currently, survival rates of children affected with this neoplasm approximate 80-90%.

Understanding of the molecular mechanisms that contribute to the development of Wilms’ tumor has greatly expanded over the past years, making Wilms’ tumorigenesis a model for the understanding of the development of other tumors.

Causes. Wilms’ tumor is thought to be caused by alterations of genes responsible for normal genitourinary development. Examples of common congenital anomalies associated with Wilms’ tumor are cryptorchidism, double collecting system, horseshoe kidney, and hypospadias. Environmental exposures, although considered, seem less likely to play a role.

Pathophysiology. The first Wilms’ tumor suppressor gene at chromosome arm 11p13, was identified as a direct result of the study of children with Wilms’ tumor that also had aniridia, genitourinary anomalies, and mental retardation (WAGR syndrome). Karyotypic analysis of these children revealed constitutional deletions within the short arm of one copy of chromosome 11. Subsequently, the 11p13 locus was demonstrated to encompass a number of contiguous genes, including the aniridia gene PAX6 and the Wilms’ tumor suppressor gene WT1, which was cloned in 1990. WT1 encodes a transcription factor critical to normal kidney and gonadal development.

The characterization of this novel tumor suppressor gene has provided insight into the mechanisms underlying normal kidney development and Wilms’ tumorigenesis. The WT1 gene has now been shown to be the specific target of mutations and deletion events in a subset of sporadic Wilms’ tumors, as well as in the germline of some children with genetic predisposition to this cancer.

A second Wilms’ tumor predisposing gene has been identified (but is not yet cloned) telomeric of WT1, at 11p15. This locus has been proposed based on studies of patients with both Wilms’ tumor and Beckwith-Wiedemann syndrome (BWS), another congenital Wilms’ tumor predisposition syndrome linked to chromosome arm 11p15. BWS is an overgrowth syndrome characterized by visceromegaly, macroglossia, and hyperinsulinemic hypoglycemia. In addition, patients with BWS are predisposed to several embryonal neoplasms including Wilms’ tumor. Thus far, a few candidate loci for Wilms’ tumor and BWS have been proposed. These include the insulinlike growth factor II gene (IGFII), H19 (an untranslated RNA) and p57kip2.

Frequency. Wilms’ tumor affects approximately 10 children per one million before the age of 15 years. In 5-10% of cases, both kidneys are affected either at the same time (synchronous bilateral Wilms’ tumor) or one after the other (metachronous bilateral Wilms’ tumor).

Age. The median age at diagnosis is approximately 3.5 years. The median age is highest for unilateral unicentric cases (36.1 mo) and lowest for synchronous bilateral Wilms’ tumor (25.5 mo).

Sex. Among patients with unilateral Wilms’ tumor, the male-to-female ratio was 0.92:1.00. For patients with bilateral disease, the male-to-female ratio was 0.60:1.00.

Race. Wilms’ tumor is relatively more common in blacks than in whites and is less common in East Asians.

Clinical

History. The most common presentation is an asymptomatic abdominal mass discovered by the parent or physician. Occasionally the child presents with haematuria, but symptoms are ofteon-specific: abdominal fullness, abdominal pain, gastrointestinal upset, fever, weight loss, malaise, and anaemia. Hypertension is sometimes detectable.

A small number of patients who have hemorrhaged into their tumor may present with signs of hypotension, anemia, and fever. Rarely, patients with advanced-stage disease may present with respiratory symptoms related to the presence of lung metastases.

Physical. Examination often reveals a palpable abdominal mass. Pay special attention to features of those syndromes (WAGR and BWS) associated with Wilms’ tumor, ie, aniridia, genitourinary malformations, and signs of overgrowth. Rarely, a left varicocele arises as a result of tumor occlusion of the left renal vein.

Figure  A 4-year-old girl presenting with a 6-month history of abdominal mass. At operation, a 6.5-kg left Wilms’ tumour was excised.

Examination of the abdominal mass should be performed carefully. Concern has been raised that palpating a mass too vigorously could lead to rupture of a large tumor into the peritoneal cavity.

Lab Studies

Ø     Complete blood cell count

Ø     Chemistry profile including kidney function tests and routine electrolytes with calcium

Ø     Urinalysis

Ø     Coagulation studies

Cytogenetics studies

Ø     An 11p13 deletion as in the WAGR syndrome (Wilms’, aniridia, genitourinary abnormalities, mental retardation)

Ø     A duplication of the paternal allele 11p15 as in BWS

Ø     Mutational analysis of the WT1 gene in cases where Denys-Drash syndrome (intersexual disorders, nephropathy, Wilms’ tumor) is suspected

Imaging Studies

Renal ultrasonography – With dynamic imaging of the renal vein and interior vena cava

CT scanning. Abdominal CT scanning helps determine the tumor’s origin, lymph node involvement, bilateral kidney involvement, and invasion into major vessels (eg, inferior vena cava or liver metastases). If findings on chest CT scanning are positive while chest radiographic findings are negative, diagnostic biopsy of the lesions noted on the chest CT scan is recommended.

Chest radiography (4-field) – Detects lung metastases (Patients with lung lesions on chest radiography receive whole lung radiotherapy.)

Procedures.

Histopathologic confirmation of disease is essential. Consequently, in North America, patients with suspected Wilms’ tumor undergo nephrectomy immediately. During this procedure, the contralateral kidney is explored to ensure that the disease is indeed unilateral, and lymph node biopsies are obtained for staging purposes. Lymph node dissection is not indicated. In contrast to immediate surgery, most European centers make a presumptive diagnosis of Wilms’ tumor based on findings on imaging studies alone. The SIOP centers prefer to administer prenephrectomy chemotherapy. In North America, immediate nephrectomy is not performed in bilateral disease at presentation, when sparing of renal tissue becomes important. Transcutaneous biopsy is not indicated and may in fact complicate treatment.

Patients with negative findings on chest radiography and positive findings on CT scanning of the lungs require tissue diagnosis of the lung nodule(s) because several conditions such as histoplasmosis, atelectasis, pseudotumor, intrapulmonary lymph node, and pneumonia can mimic pulmonary metastases.

Histologic Findings. The classic histologic pattern is composed of epithelial, blastemal, and stromal elements (triphasic). Approximately 90% of all renal tumors have the so-called favorable histology (FH). Three to 7% of Wilms’ tumors are characterized by anaplastic changes, a feature that, if present diffusely throughout the tumor, predicts for poor outcome. Wilms’ tumors with anaplastic changes are called unfavorable histology Wilms’ tumors. Finally, 2 tumor types previously included in the unfavorable histology Wilms’ tumor category are in fact clearly separate malignant entities. This includes clear cell sarcoma of the kidney (CCSK) and rhabdoid tumor of the kidney (RTK).

Medical Care: The usual approach in most patients is nephrectomy followed by chemotherapy with or without postoperative radiotherapy. Table 1 summarizes the current approach to patients with Wilms’ tumor according to the fifth National Wilms’ Tumor Study Group (NWTSG) study report (NWTS-5).

 

Table 8.1

Current Approach to Wilms’ Tumor by Stage and Histology

*Current radiotherapy dosage is approximately 1080 cGy for the abdomen and 1200 cGy for the lung. Only patients with stage IV with lung metastases receive whole lung radiotherapy.

 

Further Inpatient Care.

Diet. No special diet is recommended.

Activity. No precautions on activity are advised, although the patient and parents should be aware that after therapy the patient only has one kidney. Activities such as boxing and hockey that carry an inherent risk of kidney injury should be avoid.

Up to a third of patients with Wilms’ tumor can present with hypertension. The blood pressure usually normalizes after nephrectomy but occasionally requires longer therapeutic intervention.

Five to 10% of patients present at diagnosis with acquired von Willebrand disease. If present, excessive bleeding during surgery should be expected and prenephrectomy therapy instituted. Whenever possible, the use of blood derivatives should be avoided because of the potential for transmission of viral infections. Instead, an initial trial of desmopressin (DDAVP), a drug that promotes the release of vWF from storage sites and has been shown effective in most patients with type I von Willebrand disease and in some type II cases, is recommended. If administered, fluid and electrolyte balance should be monitored carefully. If DDAVP is ineffective, cryoprecipitate or a specific vWF concentrate should be administered.

Further Outpatient Care:

·                     The patient must be seen at the follow-up clinic after completing all therapy. The purpose of follow-up care is to check for recurrence and also late effects of therapy. Table 2 outlines the types and frequency of radiographic studies during the follow-up period according to the NWTSG.

Table 8.2

Imaging Studies Recommended for Follow-Up of Children with Wilms’ Tumor Free of Metastasis at Diagnosis*

*Subsequent imaging studies should be performed as clinically indicated.

 

Patient Education. The parent and patient must know that long-term follow-up care is essential because of the late effects of treatment.

Complications. The primary treatment, nephrectomy, may damage kidney function. However, additional treatment modalities may cause damage to several organs such as the heart, lungs, liver, bones, and gonads. In addition, both chemotherapeutic agents and radiation therapy can induce second malignant neoplasms.

Renal function. Children with Wilms’ tumor are at risk for impaired renal function primarily related to the nephrectomy performed as part of treatment. In selected patients, ie, those who receive radiation therapy, the function of the remaining kidney can be further endangered. The development of compensatory postnephrectomy hypertrophy of the remaining kidney has been well documented in patients with Wilms’ tumor. NWTSG data suggest that most patients with unilateral Wilms’ tumor do not develop serious long-term renal complications. By contrast, renal function can be impaired for those with bilateral disease. The most common cause for renal failure in patients with bilateral Wilms’ tumor is bilateral nephrectomy. Treatment-related injury (eg, radiation-induced damage, surgical complications) of the remaining kidney is the second leading cause of renal insufficiency.

Cardiac function. Congestive heart failure is a well-known complication following the administration of anthracyclines. Therefore, patients with Wilms’ tumor who receive anthracyclines, most commonly doxorubicin, should be monitored for cardiac dysfunction.

Pulmonary function. Because radiation therapy can affect pulmonary function, patients with Wilms’ tumor metastatic to the lung who are treated with bilateral pulmonary irradiation require pulmonary function monitoring. The total lung capacity (TLC) and vital capacity (VC) of patients receiving bilateral irradiation can be expected to decrease by 50-70% of predicted.

Hepatic function. The liver of patients treated for Wilms’ tumor may be damaged by several cytotoxic agents, including dactinomycin, and irradiation.

Some patients with Wilms’ tumor have been reported to develop hepatic veno-occlusive disease (VOD). This is primarily a clinical diagnosis characterized by hepatomegaly or right upper quadrant pain, jaundice, ascites, and unexplained weight gain. The syndrome occurs both in patients with Wilms’ tumor undergoing upfront nephrectomy as well as in those receiving combination chemotherapy prior to surgery.

Using the currently accepted radiotherapy techniques, radiation-induced hepatitis is rare in survivors of Wilms’ tumor.

Gonadal function. Women who received whole abdominal irradiation in childhood can develop ovarian failure. Male patients are at risk for testicular failure after the administration of radiation therapy (whole abdomen) or certain chemotherapeutic agents, most notably alkylating agents.

Prognosis. Approximately 80-90% of diagnosed children survive with current multimodality therapy. Patients with FH tumors have at least an 80% overall survival rate at 4 years after initial diagnosis, even in patients with stage IV disease.

Synchronous bilateral cases have a 70-80% survival rate, while those with metachronous tumors have a 45-50% survival rate. The prognosis for patients who relapse is not good, with only 30-40% expected to survive after retrieval therapy.

 

3. Neuroblastoma.

Background and Etiology

Neuroblastoma is a tumor derived from neuroblasts. Neuroblasts are derived from neural crest cells and migrate during fetal development to form the autonomic nervous system. There are two paths of migration:

1. along developing nerves to form the sympathetic plexuses, where they form ganglion cells and

2. to the adrenal gland to form the medulla.

Tumors of the neuroblasts can be either malignant or benign. The tumors are named ganglioneuromas, ganglioneuroblastoma and neuroblastoma depending on the degree of malignant potential with ganglioneuromas being completely benign and neuroblastoma being malignant with the ganglioneuroblastoma as an interme­diate tumor.

Neuroblastoma is the most common extracranial solid tumor in children accounting for 8-10% of all childhood cancers. This tumor occurs in approximately 1 in 7000-18,000 live births. There are about 550 new cases each year in the United States. There is no ethnic prevalence. There is a slight male predominance with a ratio of 1.2:1 (male to female). The median age at diagnosis is 22 months, and 97% of neuroblastomas are diagnosed in children less than ten years of age. The inci­dence is biphasic with a peak at less than one year of age and a second peak at 2-4 years. Prenatal or postnatal exposure to drugs, chemicals or radiation has not been unequivocally demonstrated to increase the incidence of neuroblastoma.

Although most cases of neuroblastoma are thought to be sporadic, there is a subset of patients that exhibit a predisposition to develop disease in an autosomal dominant pattern. About 22% of neuroblastomas are thought to be the result of a germinal mutation. The hereditary form of the disease has an earlier mean age at diagnosis (9 months versus 22 months) and has a higher incidence of bilaterality and multifocal tumors (20%). Neuroblastoma is thought to follow a two-mutation hypothesis of tumorogenesis.

Pathology

Neuroblastomas arise from the primitive pluripotential sympathetic cells that are derived from neural crest cell and normally differentiate to form tissues of the sympathetic nervous system. All fetuses have neuroblastic nodules between 17-20 weeks gestational age. Most regress before birth or shortly thereafter. Neuroblas­toma in situ is frequently found in infants three months or younger dying from

other causes. Therefore the cells that form neuroblastoma mav be fetal remnants that fail to regress.

Neuroblastomas belong to a group of tumors classified as the “small round blue cell” tumors. Others in this category include Ewing’s sarcoma, non-Hodgkin’s lym­phoma, primitive neuroectodermal tumors (PNETs) and undifferentiated soft tis­sue sarcomas such as rhabdomyosarcoma. Neuroblastomas am be differentiated from other tumors in this category by using immunohistochemistry. These tumors are positive for the marker neuron specific enolase. Neuroblastoma cells have neuritic processes called neuropil. Homer-Wright pseudorosettes are formed by neuroblasts surrounding areas of eosinophilic neuropil. Ganglioneuromas, the benign variety of this tumor, are composed of mature ganglion cells, neuropil and Schwann cells. Ganglioneuroblastomas are a heterogeneous group of tumors with varying degrees of mature ganglion cells. These cells may be focal or diffuse with the diffuse variety associated with less aggressive behavior. These tumors show dense neurosecretory granules as well as microfilaments on electron microscopy (EM).

There have been attempts to determine prognosis based on histologic criteria. The Shimada classification compares patient age and

1. the presence or absence of Schwann cell stroma, 1. degree of differentiation and

3. mitosis-karyorrhexis index (MKI) to differentiate tumors into favorable or unfavorable prognosis.

The Joshi classification considers the presence of calcifications and mitotic rate. A low mitotic rate (< 10 per high power field) and the presence of calcifications predicts a favorable outcome (grade 1). Grade 3 tumors have neither feature and are associated with a poor prognosis.

Several cellular and molecular characteristics have prognostic significance in patients with neuroblastoma. Tumor cells produce varying amounts of DNA. The measurement of this is called the DNA index. For normal cells, the DNA content is diploid and the DNA index is 1. Some neuroblastomas have a high DNA content and are called hyperdiploid (DNA index >1). In younger children, tumors that are hyperdiploid are more likely to have a lower stage of tumor and be responsive to cyclophosphamide and doxirubicin. Hyperdiploid tumors in older children do not have the same favorable outcome. The most consistent specific genetic abnormality identified in children with neuroblastoma is a deletion of the short arm of chromo­some 1 (lp). This most likely represents a deletion of a tumor suppressor gene.

Neuroblastomas may also show n-myc amplification. This region of amplifica­tion is located on the distal short arm of chromosome 2 and contains the N-mvc protoconcogene. Amplification of n-myc occurs in 25% of patients with neuroblas­toma and is associated with advanced stage of disease, rapid tumor progression, and poor prognosis. Molecular studies have demonstrated a correlation between the lp deletion and n-myc amplification. An important pathway iormal differentiation of neuroblasts involves a differentiation factor called nerve growth factor (NGF) and its receptor (trk A). Most neuroblastoma cell lines are not responsive to NGF. Tumors that have high trk A are associated with a good biological response to therapy and a favorable prognosis. Trk A expression is inversely correlated with n-myc am­plification.

Clinical Presentation

Tumors arise anywhere there are sympathetic nerves from the brain to the pelvis. Most primary tumors occur in the abdomen (65%) (Fig. 39-1)- The frequency of adrenal tumors is slightly higher (40%) in children compared to infants (25%). Infants have more thoracic and cervical primary tumors. The clinical presentation depends on the location of the primary. Often the symptoms are few and general. The patients often appear ill and fail to thrive. Those with cervical tumors (Fig. 39-2) present with a mass in the neck or with Horner’s syndrome (meiosis, anhydrosis and ptosis). Those with thoracic primaries are diagnosed after a mass is found on a rou­tine chest radiograph. The parents often find abdominal tumors when they are bathing the child. Abdominal tumors are more irregular than Wilms’ tumors and more often cross the midline. Pelvic tumors may result in obstructive symptoms (urethral or colonic). Rarely they compress or infiltrate the iliac veins and/or arteries and present with lower extremity edema. Tumors that extend intraspinal in any of these loca­tions may present with neurologic symptoms.

Two specific syndromes sometimes occur in patients with neuroblastoma. Opsoclonus-myoclonus is a constellation of symptoms including polymyoclonia, cerebellar ataxia with gait disturbance, and opsoclonus (“dancing eyes”). More that 50% of children with this syndrome have primary tumors located in the thorax. Although this syndrome is often associated with a favorable outcome, the symptoms may or may not resolve after tumor removal. Rarely, patients with neuroblastoma present with profuse watery diarrhea if the tumor secretes vasoactive intestinal pep­tide (VIP). The diarrhea resolves once the tumor is removed.

“Blue berry” nodules

 

Example of raccoon eyes.

Ninety to ninety-five percent of tumors are biologically active secreting vanillymandelic acid (VMA) or homovanellic acid (HVA) or other catecholamine metabolites. HVA represents degradation products of the dopamine pathway. More differentiated tumors produce norepinephrine and epinephrine that give rise to VMA. The VMA: HVA ratio has some prognostic implication with levels > 1 indicating tumors with a more favorable prognosis. Ten percent of neuroblastomas secrete ace­tylcholine and not catecholamines; these tumors tend to be more malignant.

There are two main patterns of metastatic spread in patients with neuroblas­toma. The first is lymphatic spread. Thirty-five percent of children with apparently localized disease have lymph node metastasis at the time of presentation. Spread of tumor to lymph nodes outside the cavity of the primary tumor is considered dis­seminated disease but these patients may have a better outlook than those with other forms of disseminated disease. The other form of metastatic spread is hematogenous. The most common sites of metastasis are bone marrow, bone, liver and skin. Only rarely does neuroblastoma metastasize to lung or brain and these are usually manifestations of end-stage disease.

Table : Presenting complaints with neuroblastoma.

Staging

Patients with neuroblastoma are staged based on the extent of primary disease and the presence or absence of metastases. Completeness of surgical resection is also factored into the staging system. There have been two main staging systems in the past but recently a new international staging system has been devised which com­bines the previous systems (Table 39-1)-

 

Left adrenal neuroblastoma of large size and with marked calcification demonstrates medial aortic displacement and inferior displacement of the left kidney.

 

Diagnosis

The diagnosis of neuroblastoma is based on the clinical signs and symptoms discussed previously. Once there is suspicion that a child has a neuroblastoma con­firmatory testing is done. The child’s urine is sent for HVA and VMA. The primary tumor is usually assessed with computed tomography (CT) scan which helps deter­mine the extent of disease, invasion into surrounding structures, and lymph node involvement. In children with a primary abdominal tumor, involvement of the liver with tumor can also be assessed. For patients who present with neurologic symp­toms, magnetic resonance imaging (MRI) can be helpful to define involvement of the spinal canal or cord. Metaiodobenzylguanidine (MIBG) is a compound resem­bling norepinephrine that binds to norepinephrine sites and is stored ieural crest cells. When this substance is labeled with ^l23I or ¹³¹I it can define the tumor or identify metastases even in those few patients with normal catecholamine levels. To assess for metastases, a bone scan and a plain chest radiograph are obtained. Com­puted tomography of the chest is only warranted if there are suspicious findings on a chest radiograph. Bone marrow aspirates are done from bilateral iliac crests as are trephine (core) bone marrow biopsies.

The diagnosis of neuroblastoma is confirmed by:

1. Biopsy with unequivocal diagnosis of neuroblastoma by light microscopy or

2. Bone marrow biopsy or aspirate with unequivocal tumor cells and increased serum or urine catecholamines.

Because of the heavy dependency of treatment plans on tumor biology, there is a strong rationale for sampling tumor in most cases.

Large white arrows indicate cervical neuroblastoma well shown by mag­netic resonance imaging.

 

Treatment

Treatmenc for patients with neuroblastoma involves a combination of surgery, radiation and chemotherapy. The goal of the initial surgical intervention in patients with neuroblastoma is to establish a diagnosis, provide tissue for biological studies (1-5 grams of tissue), stage the tumor surgically and excise completely those tumors where this is feasible. Complete excision should only be undertaken when there is not a concern for undue morbidity to vital organs or the patient. Sacrifice of major organs such as the kidnev or spleen should be avoided, especially in children less than one year of age. If there are known distant metastases then the most accessible tissue is obtained for diagnosis and biological studies.

For thoracic tumors, a posterior-lateral thoracotomy is generally used. Attach­ments to the sympathetic chain and intercostal nerves are often found but en bloc excision of the chest wall is not required. Dumbbell shaped tumors that enter the neural foramina are generally treated initially with chemotherapy These tumors were historically treated with radiation and laminectomy but had a higher rate of spinal column sequelae than those treated with chemotherapy.

For abdominal tumors, a generous transverse incision is usually employed. Liga­tion of feeding vessels is attempted early but care must be taken as larger tumors can rotate the aorta and distort the celiac, superior mesenteric and renal vessels. Lymph node sampling is performed regardless of the gross appearance of the nodes as inspection only has been shown to be in error 2 5% of the time. For sampling, non­contiguous nodes above and below the tumor are sampled. For those tumors in the abdomen and pelvis, contralateral lvmph nodes are important. For infants less than one year of age, liver biopsy may be indicated if stage 4S (Table 39-1) disease is suspected.

For those patients who have incomplete resection initially, a delayed attempt at resection of residual tumor is undertaken at the end of induction chemotherapy (12-24 weeks after diagnosis). Surgery is not indicated for those patients who have progressive disease at this time. If there has been some response, the goal is complete resection of residual disease. The efficacy of eradication of the primary tumor at this time is not proven, but survivors have had complete resection more often thaonsurvivors. For patients with stage 4 and 4S, there is a 30% relapse rate if there is complete excision of the primary tumor and a greater than 90% rate in those with­out excision of the primary tumor.

Complications of surgical intervention include atelectasis, infection, ileus, and complications specific to the resection of the primary tumor. Overall the complica­tion rate is low, estimated at 5-25%. Patients with localized tumors have lower rates of complication. Complications occur most frequently in infants after attempted excision of large tumors.

Chemotherapy is usually multiagent therapy. The most frequently used drugs include cyclophosphamide, cisplatin, doxirubicin and epipodophyllotoxins (teniposide-V’M-26 and etoposide-VP-16). In general, drugs are combined so that the noncell cycle specific agents are given followed by the cell cycle specific agents.

Neuroblastoma is considered a radiosensitive tumor but the role of radiation therapy in patients with this tumor is now minimal due to the newer chemotherapy agents. Presently radiation therapy s used for regional lymph node metastasis if com­plete response is not achieved with chemotherapy, for infants with 4S disease who have respirator}’ distress from hepatomegaly secondary to tumor involvement, and in those patients who require total body irradiation for bone marrow transplantation.

Bone marrow transplantation is currently considered an investigational therapy for Stage 3 and 4 patients. Autologous bone marrow is given to the patients with or without purging to remove the neuroblastoma cells. Long-term results survival rates approach 40%. In these patients, recurrence most commonly occurs at the primary site of the tumor or in the bone or bone marrow.

Outcomes

When considered alone, the two most important clinical variables for predicting outcome ieuroblastoma patients are the disease stage and the patient age at diag­nosis. Disease tree survival of all patients with stages 1, 2, or 4S is 75-90%. Infants less than one year of age with stage 3 and 4 have cure rates of 80-90% and 60-75%, respectively. Those children older than one year of age with stage 3 and 4 disease have 3-year survivals of 50% and 15%, respectively.

Presently, trials are underway to randomize patients into low, intermediate and high risk groups based on age, stage, histology and biologic markers as discussed in previous sections. The therapies would then be streamlined based on the risk group in an attempt to minimize morbidity from therapy while maximizing survival. Low risk patients may get no or minimal chemotherapy, intermediate risk patients would get moderately aggressive chemotherapy with or without a consideration for radia­tion therapy. High-risk patients, in whom survival has not improved in the past three decades, would get chemotherapy, radiation therapy followed by bone marrow transplantation.

1. Grosfeld JL. Neuroblastoma. In: O’Neill Jr. JA et al. eds. Pediatric Surgery, 5^th Edition. St. Louis: Mosby 1998; 405-419.

2. Shimada H et al. Identification of subsets of neuroblastoma by combined histo­pathologic and N-myc analysis. J Natl Cancer Inst 1995; 87:1470.

3. Haase GM. Head and neck neuroblastomas. Semin Pediatr Surg 1994; 3:194.

4. Black CT. Neuroblastoma. In: Andrassy RJ ed. Pediatric Surgical Oncology. Phila­delphia: W.B. Saunders Company 1998; 175-211.

 

4. Mediastinal tumors.

The classic anatomic description divides the mediastinum, represented by the substernal central thoracic space bounded laterally by the parietal pleura, into four compartments: superior, anterior, middle and posterior. The superior mediastinum lies between the thoracic inlet superiorly and the level of the fourth thoracic verte­brae inferiorly, and contains the thymus, lymphatics and vascular structures. The anterior mediastinum is the space below the superior compartment, bounded by the pericardium and diaphragm. The middle mediastinum contains the pericardium, heart, origins of the great vessels, trachea, main-stem bronchi and lymphatics. The posterior mediastinum is bounded by the great vessels anteriorly and the vertebral bodies posteriorly. The normal structures in this space include the esophagus, sym­pathetic ganglia, thoracic duct, vessels and lymphatics. Understanding of the ana­tomical subdivisions of the mediastinum and the relative frequency of specific pathology in these subdivisions aids in the differential diagnosis (Table 45-1)-

Etiology and Embryology

In addition to classification by location, mediastinal masses can also be catego­rized as developmental, neoplastic, or inflammatory. It is presumed that incomplete separation and tubulization of the esophagus and trachea after the proliferative phase, which normally occurs by the fifth week of gestation, results in foregut duplication. Additionally, these duplication cysts can communicate with the spinal canal, and are referred to as neuroenteric cysts. The thymus develops as paired primordium from the ventral third pharyngeal pouch and descends to an area anterior to the aortic arch during the seventh week of gestation. Incomplete descent or obliteration of its tract may result in a cystic or ectopic thymus in the neck. In the middle mediastinum, bronchogenic cysts develop from abnormal budding of the tracheal diverticulum or ventral portion of the foregut. Pericardial cysts occur from the fail­ure of disconnected lacunae in the mesenchyme to coalesce to form the pericardial sac.

The most commoeoplasm of the anterior mediastinum in children is lym­phoma, accounting for up to 45% of pediatric mediastinal masses. Germ cell tu­mors (25%), mesenchymal tumors (15%), and thymic tumors (17%) comprise the remainder. Most of these tumors are malignant. Neurogenic lesions, which com­prise approximately 20% of mediastinal tumors, are usually located in the posterior mediastinum.

Acute infection of the mediastinum is most often seen following esophageal per­foration, cardiac operations, or penetrating chest trauma. Many developmental con­ditions of the mediastinum (i.e., thymic cysts, enteric cysts, bronchogenic cysts, and cystic hygroma) are at increased risk for acquired infection.

Clinical Presentation

Most mediastinal masses are asymptomatic, often discovered incidentally on chest radiographs taken for other indications. However, clinical symptoms are frequently the result of mass effects oormal structures within a particular compartment. Large masses in the anterior and middle mediastinum are particularly significant for their potential influence on respiratory tract symptoms, including airway obstruc­tion. Symptoms may range from noisy, stridorous breathing in infants to cough, chest pain, dyspnea, and orthopnea in older children. Cardiac compression may result in cyanosis, syncope, and dysrhythmias. Great vessel compression can lead to superior vena cava syndrome, characterized by venous engorgement along with head and neck swelling. By contrast, posterior mediastinal masses can be quite large and yet asymptomatic. However, posterior mediastinal masses, especially those that enter neural foramina, can cause symptoms of spinal cord compression.

Certain pathology presents with specific symptoms. Hodgkins lymphomas may have concomitant cervical or supraclavicular nodes as well as fever, night sweats and

weight loss (‘B’ symptoms) in one-third of patients. Neuroblastoma in the upper mediastinum involving the stellate ganglion produces Horner’s syndrome, charac­terized by ptosis, miosis, and anhydrosis. Although rare, a pediatric patient with thymic neoplasia may present with myasthenia gravis or hypoplastic anemia.

Diagnosis

Two-view chest radiographs often confirm the presence of mediastinal masses. Ultrasound study can differentiate the cystic nature of the mass, but contrast-enhanced computed tomography (CT) provides far more information about the mass and its relationship to the surrounding mediastinal structures. Magnetic resonance imag­ing (MRI) is helpful to define spinal involvement or vascular lesions. However, the sedation required for adequate MRI study in pediatric patients may compromise the airway in patients with large anterior mediastinal masses. An esophagogram or echocardiogram also provides additional information to further define mediastinal masses.

Ultrasound or CT-guided percutaneous needle biopsy of solid mediastinal mass can be performed to establish tissue diagnosis. Complications such as pneumotho­rax, bleeding, perforation, or tumor seeding occur infrequently. Tissue diagnosis may also be obtained from sites alternative to the tumor itself, such as lymph node or bone marrow. Incisional or excisional biopsies of the tumor are performed using thoracoscopy, mediastinoscopy or mini-thoracotomy. However, the goal of the pre­operative work-up is to help define the optimal surgical approach for resection, and open direct tissue biopsy of masses is rarely indicated in pediatric patients.

Tumor markers such as serum 3-human chorionic gonadotropin (p-HCG) or a-fetoprotein may help in the diagnosis and follow-up of malignant mediastinal tumors. Since more than 90% of patients with neuroblastoma produce high levels of catecholamines, quantification of the corresponding by-products (vanillylmandelic acid, homovanillic acid) in urine over a 24-hour period can confirm the diagnosis.

Anterior and Superior Mediastinum

The common tumors in order of decreasing frequency are lymphomas, terato­mas, germ cell tumors, lymphangioma (cystic hygromas), and thymic tumors. Malignant lymphomas present most frequently in older children, and sometimes, diagnosis can be sought from nonmediastinal areas such as bone marrow and nodal tissues. Among Non-Hodgkin lymphomas, the lymphoblastic subtype is most likely to present in the mediastinum. This is a diffuse, fast-growing tumor of T cell and pre-B cell origin.

Teratomas are the second most common tumors of the anterior mediastinum. They are derived from multiple germ cell layers and can have both cystic and solid components. Teratomas frequently have calcifications, and only 25% of teratomas are malignant in pediatric patients. p-HCG and a-fetoprotein can also help to dif­ferentiate various germ cell tumors and are especially important postoperatively as an early marker of recurrence. Seminomatous germ cell tumors are responsive to radiation therapy and should be distinguished from other types.

Lymphangiomas in the mediastinum frequently present as a mediastinal exten­sion of a cervical lesion. Thev demonstrate extensive endothelial-lined buds within tissue planes and complete resection is required to avoid recurrence. Large

lymphangiomas may be treated with slcerosing injections (i.e., OK-432, a mono­clonal antibody produced by Streptococcus pyogenes) but the value and efficacy of this therapy is not established.

Thymic cysts are usually asymptomatic but can become infected. Large lesions produce symptoms due to mass effect. Thymolipoma is benign, but along with thymic cysts, resection is indicated for proper diagnosis and prevention of complica­tions. Thymomas originating in the thymic epithelium are usually aggressive, but account for less than 1% of mediastinal tumors. Thvmomas associated with myas-thenia gravis may produce autoantibodies to acetylcholine receptors which leads to progressive muscle weakness. Resection produces some improvement in symptoms for 30-50% of these children.

Middle Mediastinum

Pericardial cysts are benign, fluid-containing cysts lined with mesothelium. They are usually asymptomatic and CT imaging can provide accurate diagnosis. When the diagnosis is uncertain or the cysts become too large, thoracotomy or thoraco-scopic resection or evacuation of the cysts should be performed. Pericardial effusion may, on rare occasions, represent underlying pathology such as cardiac hemangioma or rhabdomyoma. Bronchogenic cysts develop from abnormal budding of the tra­cheal diverticulum or ventral portion of the foregut. These mucus filled cysts are lined with bronchial epithelium and are frequently located at paraesophageal, paratracheal, or perihilar regions. Excision is performed electively to avoid the com­plications of infection, hemorrhage, or problems due to mass effects. Complete resection via thoracotomy or video-assisted thorocoscopy is the preferred treatment of bronchogenic cysts; recurrence and malignancy are extremely rare.

Posterior Mediastinum

The posterior mediastinum is the common site of benign and malignant neuro­genic tumors. Sixty percent are malignant, most ofteeuroblastoma or ganglioneuroblastoma, and thirty percent are benign tumors such as ganglioneuroma, neurofibroma or schwannoma. The remaining 10% represent miscellaneous mesen­chymal tumors or granulomas. Enteric duplication cysts may occur in this location, are lined by esophageal or gastric epithelium, and occasionally communicate with a viscus lumen. Most are asymptomatic and benign. Treatment is usually complete resection, but stripping of the mucosal lining of a foregut duplication may be adequate for long tubular duplications. Neuroenteric cysts are foregut duplications that also have connections to the spinal canal. They often present as an intraspinal mass. MRI or CT with myelogram should be considered when a posterior mediastinal mass is associated with vertebral anomalies. Total excision is recommended with simultaneous laminectomv as necessarv.

Treatment

For cysts, regardless of symptoms, removal should be seriously considered to prevent future complications of infection, bleeding or compression on adjacent nor­mal structures. For similar reasons, benign mediastinal tumors should also be resected. Ganglioneuromas and neurofibromas often remain encapsulated and can be easily removed. The role of surgery regarding malignant tumors spans the spectrum from

diagnostic procedures to complete resection or debulking of the tumor mass to relieve complications. Patients with Non-Hodgkins lymphoma and bulky anterior medias­tinal involvement may require surgical intervention for respiratory symptoms, pleu­ral effusion or superior vena cava syndrome. Neuroblastomas, when found in early stages (I or II), are considered for complete primary resection. Seminomatous tumors are treated with chemotherapy and radiation, while germ cell tumors of other origin are treated with resection or debulking followed by chemotherapy.

In general, the surgical approach to mediastinal masses depends on location, size and pathology. Thoracoscopy can be useful for resection or biopsy in approachable lesions, such as foregut duplications (enteric cysts and duplications, bronchogenic cysts, neurenteric cysts) and simple solid masses. Large anterior mediastinal masses are best approached through a median sternotomy.

Outcome

Prognosis depends on the underlying pathology. Patients with benign cysts and tumors have excellent outcomes with complete recovery. Recent protocols for Hodgkins disease have improved the overall 5-year survival, which is now approaching 90%. Although, the youngest patients have the best prognosis, overall prognosis for neuroblastoma remains poor.