Osteogenic tumular new formations of jaws (fibrous osteodysplasia, parathyreoid osteodysplasia: etiology, pathogeny, histological structure, clinic, differential diagnostics, treatment, complication.
Osteogenic tumular new formations of jaws (illness Peget”s, eosynophilum granuloma): etiology, pathogeny, histological structure, clinic, differential diagnostics, treatment, complication.
Bening tumors and cysts of salivary glands: classification and origin, histological structure, clinic, differential diagnostics, principles and methods of treatment.
Osseous Diseases and Systemic Diseases Affecting Bone
Primary Hyperparathyroidism
CLINICAL PRESENTATION AND PATHOGENESIS
Primary hyperparathyroidism is caused by hypersecretion of parathyroid hormone (PTH), most commonly by the subset of four hyperplastic glands, less commonly by a parathyroid adenoma, or very rarely by a true carcinoma. Most cases today are identified by hypercalcemia (.10.5 mg/dL [2.6 mmol/L], after correction for serum albumin) on routine multipanel serum testing. Less than 5% of cases are recognized by the presence of an osteolytic defect with giant cells, a condition referred to as a brown tumor. Some cases are suspected by the presence of renal “stones” (nephrocalcinosis). However, only 5% of people with nephrocalcinosis have primary hyperparathyroidism. Primary hyperparathyroidism is more common in women and in those older than 50 years. Most gland hyperplasias are of unknown cause, but some are related to the multiple endocrine neoplasia syndrome of familial inheritance types I and IIa (MEN I and MEN IIa). Because most cases are due to an idiopathic hyperplasia of each gland, a neck mass is usually not palpable. In addition, most cases are asymptomatic. However, as serum calcium levels increase, symptoms may occur that are related to the hypercalcemia per se or to the disease’s effects on bone and on the urinary tract. The pathogenesis of hypercalcemia is the oversecretion of active PTH. This polypeptide hormone increases serum calcium levels by the following three mechanisms (in order of decreasing effect): (1) increasing osteoclastic bone resorption; (2) reducing renal excretion of calcium; and (3) increasing calcium absorption in the small intestines. The resultant abnormal laboratory test results are, therefore, hypercalcemia, a compensatory hypophosphatemia, and an alkaline phosphatase level that is usually normal but can be elevated in widespread lytic disease.
Hypercalcemia.Related Signs and Symptoms
The symptoms most commonly associated with hypercalcemia include thirst, nausea, and vomiting. In addition, constipation, weight loss, anemia, and peptic ulcer disease, as well as hypertension, may develop. If the hypercalcemia is severe (>15 mg/dL [3.75 mmol/L]) or long.lasting, depression and psychosis may result. Higher serum calcium levels also are associated with fatigability, muscle weakness, and paresthesias.
Primary Hyperparathyroidism
CLINICAL PRESENTATION AND PATHOGENESIS
Primary hyperparathyroidism is caused by hypersecretion of parathyroid hormone (PTH), most commonly by the subset of four hyperplastic glands, less commonly by a parathyroid adenoma, or very rarely by a true carcinoma. Most cases today are identified by hypercalcemia (.10.5 mg/dL [2.6 mmol/L], after correction for serum albumin) on routine multipanel serum testing. Less than 5% of cases are recognized by the presence of an osteolytic defect with giant cells, a condition referred to as a brown tumor. Some cases are suspected by the presence of renal “stones” (nephrocalcinosis). However, only 5% of people with nephrocalcinosis have primary hyperparathyroidism. Primary hyperparathyroidism is more common in women and in those older than 50 years. Most gland hyperplasias are of unknown cause, but some are related to the multiple endocrine neoplasia syndrome of familial inheritance types I and IIa (MEN I and MEN IIa). Because most cases are due to an idiopathic hyperplasia of each gland, a neck mass is usually not palpable. In addition, most cases are asymptomatic. However, as serum calcium levels increase, symptoms may occur that are related to the hypercalcemia per se or to the disease’s effects on bone and on the urinary tract. The pathogenesis of hypercalcemia is the oversecretion of active PTH. This polypeptide hormone increases serum calcium levels by the following three mechanisms (in order of decreasing effect): (1) increasing osteoclastic bone resorption; (2) reducing renal excretion of calcium; and (3) increasing calcium absorption in the small intestines. The resultant abnormal laboratory test results are, therefore, hypercalcemia, a compensatory hypophosphatemia, and an alkaline phosphatase level that is usually normal but can be elevated in widespread lytic disease.
Hypercalcemia.Related Signs and Symptoms
The symptoms most commonly associated with hypercalcemia include thirst, nausea, and vomiting. In addition, constipation, weight loss, anemia, and peptic ulcer disease, as well as hypertension, may
develop. If the hypercalcemia is severe (>15 mg/dL [3.75 mmol/L]) or long.lasting, depression and psychosis may result. Higher serum calcium levels also are associated with fatigability, muscle
weakness, and paresthesias.
TREATMENT
Medical treatment for primary hyperparathyroidism is indicated only in those in whom surgery is contraindicated and in those with mild hypercalcemia (< 11 mg/dL [2.75 mmol/L], albumin corrected) who show no evidence of organ dysfunction. Treatment consists of increased fluids, exercise, avoidance of prolonged inactivity, and avoidance of thiazide diuretics, because these drugs decrease calcium excretion and raise serum calcium levels. For postmenopausal patients, estrogen hormone therapy also may be considered. Most patients with primary hyperparathyroidism require surgery. Today, this surgery involves removal of at least three of the four glands and, in some cases, a subtotal resection of the fourth. The success of surgery is closely related to the experience level of the surgeon. If the disease has been isolated to a specific adenoma or carcinoma, excision of only that particular tumor is the rule. However, it should be noted that most pathologists report a diagnosis of “adenoma” for all parathyroid glands removed because of primary hyperparathyroidism. This does not mean that the glands were adenomatous, that is, that they were enlarged and would continue to grow if not removed. Instead, the use of the term is based on historical precedent, in which “adenoma” refers to any pathologic gland. In fact, primary hyperparathyroidism represents a more complex systemic disease of which hypersecretion of the parathyroid glands is a central component. After surgery, most patients are expected to become hypocalcemic within 12 to 24 hours. This course should be checked with determination of serum calcium and serum albumin levels as well as eliciting a positive Chvostek sign. This assessment is required because a rapid fall in serum calcium to subnormal levels may produce a hypocalcemic tetany. A positive Chvostek sign is facial muscle twitching elicited by tapping a facial nerve component. It is also prudent to recall that early tetany may be manifested as carpopedal spasm and that hypocalcemic tetany is associated with reduced ionized calcium levels. Therefore, hyperproteinemia or respiratory alkalosis (hyperventilation) in particular may precipitate a tetanic episode by driving ionized calcium to a bound form. Some patients require large amounts of calcium, vitamin D3 (cholecalciferol), and increased dietary magnesium in the first 1 week to 1 month following surgery while the residual parathyroid gland responds to the hypocalcemia with its own hyperplasia. Efforts should be made to keep serum calcium levels above 8.0 mg/dL (2 mmol/L).
PROGNOSIS
The prognosis after surgery is very good as the remaining parathyroid gland adapts to the increased demands placed on it. Supplemental calcium, vitamin D, or magnesium is rarely needed after the first few months. The disease may recur, often many years after surgery. Most of these recurrences are hyperplasias of glands not excised at surgery. Such recurrences have been reduced by the current approach of removing three and sometimes three and one half of the four native glands.
Cherubism
CLINICAL PRESENTATION AND PATHOGENESIS
Cherubism is an autosomal.dominant genetic defect that affects bone remodeling in the specific anatomically confined limits of the embryologic mandible and sometimes of the mandible and maxilla. Cherubism does not occur in any other bone and will not cross a bony suture to an adjacent bone. Cherubism first begins to manifest itself by the age of 2.5 years and is fully expressed by the age of 5 years. It affects males slightly more than females because of a 100% genetic penetrance in males and only a 50% to 70% genetic penetrance in females. Its relatively rapid progression between the ages of 2.5 and 5 years is often associated with regional lymphadenopathy and, if the maxilla is involved, nasal obstruction with resultant mouth breathing. Nasal obstruction is caused by enlargement of the middle concha. Because the genetic defect is expressed on the embryologic maxilla or mandible only, the other conchae—the inferior concha, which is an independent bone, and the superior concha, which is part of the ethmoid bone—are not involved. The rapid evolution of the disease often creates significant concern in the parents, particularly if the defect is a mutation and no direct family members or ancestors are known to possess the condition. Spontaneous mutations, called “sporadic occurrences,” are more common in cherubism than in most other inherited diseases and account for up to 40% of cases. Cherubism has three levels of expression. Type I forms only in the bilateral rami of the mandible, sparing the condyle and extending only to the third molar region. This form may be so subtle that it escapes clinical detection until radiographs are taken years later. It is probable that most of the reported cases of so.called bilateral giant cell lesions of the mandible actually represent this type of cherubism, often called a forme fruste or incomplete expression of the disease. Type II forms only in the mandible and also spares the condyle, but it extends to at least the mental foramen bilaterally and may extend to involve the entire mandible.Type III is the form that prompted the name “cherubism.” This form involves the mandible to an advanced degree as compared to type II and also includes the maxilla. The involvement of the maxilla’s contribution to the orbital floor and orbital rim displaces the globes upward, causing a scleral show. This feature, combined with the expansion of the maxilla, gives a child with cherubism the chubby.faced appearance and the “upward.to.heaven”.looking eyes of a cherub. The maxillary involvement includes the alveolar bone and palate but does not extend beyond the maxillary sutures. Therefore, the adjacent palatine bones, vomer, zygomas, and nasal bones are completely normal. The child will, therefore, present with some degree of expanded facies and the possibility of nasal obstruction, lymphadenopathy, dry mouth, drooling, and rarely, pain. Clinically, there may be missing teeth, multiple diastemas, and misplaced teeth. Radiographically, the involved bones show a dramatic multilocular radiolucency with thin and expanded cortices, including the inferior border. The condyle and condylar neck appear normal. Unerupted and displaced teeth are common. Radiographically and clinically, cases show symmetric involvement. Cases that do not show symmetry (ie, unilateral involvement) may not be true cherubism but similar giant cell lesions that are variable components of other diseases such as Noonan syndrome or Jaffe.Campanacci syndrome.
DIFFERENTIAL DIAGNOSIS
Cherubism, like most fibro.osseous diseases, requires a clinical and radiographic diagnosis rather than a histopathologic diagnosis. It must, therefore, be distinguished from other bilateral multilocular radiolucent lesions of the jaws in young children. Other entities that may mimic this presentation are primary hyperparathyroidism, Langerhans cell histiocytosis, and multiple odontogenic keratocysts, perhaps as part of the basal cell nevus syndrome. In addition, Noonan syndrome and Jaffe.Campanacci syndrome may be considered, particularly if a fibrovascular giant cell lesion is confirmed by a biopsy. The specific clinical and radiographic features that permit a diagnosis of cherubism are symmetric presentation, radiographic evidence of multilocular contiguous lesions, sparing of the condyle, lack of involvement of adjacent bones, middle concha enlargement (variable) in the maxilla, and emergence and expression of the disease between the ages of 2 and 5 years.
HISTOPATHOLOGY
The lesions of cherubism consist of a vascular fibrous stroma, extravasated erythrocytes, and scattered multinucleated giant cells. An increase in the amount of fibrous tissue and a corresponding decrease in the number of giant cells is probably associated with regressing lesions. An eosinophilic perivascular cuffing of collagen is considered characteristic of cherubism; however, this feature is frequently absent. Clinical and radiographic correlation is necessary, as the histologic features strongly resemble those seen in central giant cell tumors and the lesions of hyperparathyroidism.
TREATMENT AND PROGNOSIS
As with any genetic disease, cherubism currently is not curable. However, the natural course of cherubism is one of gradual enlargement that continues until the onset of puberty. After puberty, a gradual involution begins and is often complete by age 18 to 20 years, and almost never lasting beyond age 30 years. The result is a nearly complete reversal of the facial expansion, which is usually very well accepted by the individual. Radiographs show only partial bony regeneration as residual radiolucent areas persist. There also may be unerupted and displaced teeth. This eruption disturbance, which occurs throughout the childhood years, may cause the patient to be partially edentulous. The general clinical approach is to avoid surgery altogether and allow natural involution to take place or defer surgeries until after puberty. If reduction of the expanded bone (osseous contouring) is required because of pain or psychologic needs, it is done with the knowledge that the operated bone will re.expand at the same or a higher rate of expansion as before surgery. There is some concern that osseous contouring may accelerate the rate of expansion, but the limited experience with surgery on these patients does not support this concern. There is also no evidence that surgical intervention will stimulate malignant transformation. If osseous contouring is required, especially on a young patient, the surgeon must be aware of the vascular nature of the bone and proceed with the same intraoperative hemorrhage control procedures as would be used in treating a central giant cell tumor (ie, an elevated head position, hypotensive anesthesia, an accessible supply of hemostatic packs, and a preparation of autologous blood or “designated donor” blood available for transfusion). On occasion, the nasal obstruction can become severe, leading to airway concerns or to significant mouth breathing and an open.bite deformity. In such cases, removal of the middle concha and turbinates is a reasonable and beneficial procedure.
Fibrous Dysplasia
CLINICAL PRESENTATION AND PATHOGENESIS Fibrous dysplasia is a disease of bone maturation and remodeling in which the normal medullary bone and cortices are replaced by a disorganized fibrous woven bone. The resultant fibro.osseous bone is more elastic and structurally weaker than the original bone. It is caused by the deletion of a bone maturation protein during embryogenesis. There is no evidence to suggest a hereditary influence. Fibrous dysplasia is conceptualized into three types. Each type usually presents as an asymptomatic, slowly expanding portion of one or more bones. The condition develops in children and teenagers primarily, with few if any cases beginning after the age of 25 years. Monostotic fibrous dysplasia, which involves a single focus in one bone, accounts for about 75% of fibrous dysplasia cases. In the jaws, this may be seen most frequently in the body of the mandible or in the premolar.molar regions of the maxilla. Today it is understood that all types of fibrous dysplasia result from a defect in bone maturation that begins in the embryo. At certain times in the histodifferentiation phase of the embryo, a genetic mutation or deletion occurs in the gene that encodes for an intracytoplasmic transducer protein required for bone maturation. Consequently, all the daughter cells of this original aberrant cell will lack this signal transducer, and therefore a certain population of cells in the individual will be able to produce only fibrous dysplastic bone rather than mature bone. If the genetic defect occurs early in embryonic development, a large number of daughter cells will be affected, some of which may not yet have migrated to their eventual skeletal site. When such early term.altered cells migrate into several skeletal sites, they produce polyostotic fibrous dysplasia. If the genetic defect occurs in an even earlier phase of embryonic development, the original cell may produce daughter cells of divergent differentiation —that is, some that will migrate into bone primordia, some into skin primordia, and some into endocrine gland primordia—and thus produce either the McCune.Albright syndrome or the Jaffe.Lichtenstein type of polyostotic fibrous dysplasia. The time at which these genetic alterations occur is thought to be before the sixth week of fetal life. When the embryo is in its sixth week of development, most histodifferentiation and cell migration have already occurred. If the same genetic defect occurs around this time, the daughter cells will be localized to one region and thus may produce the craniofacial type of fibrous dysplasia, which involves several contiguous bones in a broad area. If the genetic defect occurs slightly later, the daughter cells will be even more localized and will thus produce monostotic fibrous dysplasia. Polyostotic fibrous dysplasia involves two or more noncontiguous bones. This form is less common than monostotic fibrous dysplasia and may involve the skull, jaws, or a facial bone together with ribs, long bones, or the pelvis. Two syndromes involving polyostotic fibrous dysplasia have been isolated. McCune.Albright syndrome encompasses polyostotic fibrous dysplasia with cutaneous melanotic pigmentations called cafe.au.lait macules and endocrine abnormalities. The most common of the endocrine abnormalities is precocious puberty. In fact, the youngest childbirth on record occurred when a 5.year.old Peruvian girl with McCune.Albright syndrome gave birth. Other endocrinopathies that may be part of this syndrome are hyperthyroidism, acromegaly, and hyperprolactinemia. Jaffe.Lichtenstein syndrome, less well.known than McCune.Albright syndrome, describes polyostotic fibrous dysplasia with cutaneous melanotic pigmentations in the absence of endocrine abnormalities. Craniofacial fibrous dysplasia involves two or more bones of the jaw.midface.skull complex in continuity. This type of fibrous dysplasia is seen relatively often in dental and oral and maxillofacial practices. It is frequently underestimated and thought to be a monostotic fibrous dysplasia of the maxilla, yet it often includes the zygoma, sphenoid, temporal bone, nasal concha, and clivus.
Fig. Fibrous dysplasia of apper jaw.
RADIOGRAPHIC PRESENTATION
Nearly all cases of fibrous dysplasia will show a diffuse, hazy trabecular pattern that has been called the ground.glass appearance. However, some reports have described this pattern as radiolucent while others have described it as mottled pagetoid. These radiographic descriptions are suspect today because these reports emerged when the diagnosis and biologic behavior of fibrous dysplasia were not well.known and CT scans were not available. Since then, more strict clinical and radiographic criteria have been developed so that fibrous dysplasia is better defined. Today, most radiographic and CT scan pictures of fibrous dysplasia show a homogeneous, finely trabecular bone pattern replacing the medullary bone and both cortices and often the lamina dura as well. Its shape is fusiform and its margins are indistinct, showing a gradual blend into normal bone. It shows greater buccal than lingual expansion and does not displace the inferior alveolar canal.
Rtg. Fibrous dysplasia of apper jaw.
Rtg. Fibrous dysplasia of lower jaw.
DIFFERENTIAL DIAGNOSIS
The single most important differential diagnosis for fibrous dysplasia is to distinguish it from an ossifying fibroma. Other entities that may resemble fibrous dysplasia include chronic sclerosing osteomyelitis, Paget disease, and sometimes osteosarcoma. The features distinguishing fibrous dysplasia from ossifying fibroma are listed. Fibrous dysplasia arises and is established by the age of 20 years. Although some ossifying fibromas also develop in youth, most begin at an older age. Radiographs and/or CT scans of axial views show an ossifying fibroma to be spherical to egg shaped, heterogeneous, and well demarcated from normal bone. Also shown are an expanded or a thinned residual uninvolved cortex and displacement of the inferior alveolar canal. The radiographs and scans support the concept advanced by Worth that an ossifying fibroma is a disease within bone while fibrous dysplasia is a disease of bone.
Chronic diffuse sclerosing osteomyelitis resembles fibrous dysplasia in its diffuse and poorly demarcated radiographic appearance. It too may occur in teenagers and preteens, but it is more common in adults. However, unlike fibrous dysplasia, chronic diffuse sclerosing osteomyelitis is usually severely and constantly painful; there is frequently a history of endodontic therapy, an abscessed tooth, or some other infection; and appropriate cultures may yield Actinomyces species and Eikenella corrodens. Paget disease can be distinguished from fibrous dysplasia by its onset in individuals older than 40 years and its increased alkaline phosphatase levels. Osteosarcoma may be difficult to distinguish from fibrous dysplasia radiographically and certainly must be ruled out by histopathologic studies if the diagnosis is not clear. In general, osteosarcomas do not remodel but rather resorb a cortex and expand outward from a destroyed cortex.
HISTOPATHOLOGY
In fibrous dysplasia, normal bone is replaced by a generally loose, cellular fibrous tissue composed of haphazardly arranged, variably shaped trabeculae of woven bone, which typically lack osteoblastic rimming but often contaiumerous osteocytes. The osseous component thus may appear to arise directly from the fibrous stroma. The lesion has no definable borders, and the osseous trabeculae blend into the normal surrounding bone. Aggregates of multinucleated giant cells may be present. Over time, fibrous dysplasia of the jaws may show maturation, which is characterized by formation of lamellar bone and parallel arrangement of the trabeculae. Histologic features alone, however, are unreliable for diagnosis; therefore, clinical and radiographic correlation is imperative.
TREATMENT AND PROGNOSIS
The preferred approach to maxillofacial monostotic fibrous dysplasia and craniofacial fibrous dysplasia is no treatment. Most children adapt well to the facial expansion and do not desire osseous contouring surgery. If osseous contouring surgery is desired, it is ideal to defer it until adulthood (ages 18 to 21 years). Like cherubism, fibrous dysplasia shows less growth and its activity is reduced as adulthood approaches, although occasional late expansions and regrowth have occurred in adulthood. Regrowth is most commonly seen when surgeries are performed on patients younger than 21 years. If, because of symptoms or psychologic needs, surgery is required during this time period, it is important to remember that fibrous dysplasia undergoes episodic growth, unlike cherubism, which undergoes a slow and steady growth. Although the surgery itself does not stimulate regrowth, the earlier in life a surgery is performed, the more likely it is that a natural episode of growth will occur postsurgically. Therefore,surgery should be avoided during a period of active expansion even though that is often the time that pain or peer pressure forces its consideration. In such cases, the active phase should remit for a period of 3 months before osseous contouring is performed. Resection is not usually indicated, even for severe craniofacial fibrous dysplasia, unless neural compression threatens vision or hearing. In such cases, local resection only around the area of the nerve compression or around the involved foramen is ofteecessary. Monostotic fibrous dysplasia or a focus of polyostotic fibrous dysplasia of the skull does lend itself to a local en.bloc resection. The defect is usually reconstructed with a split calvarial graft from an adjacent area. However, resection is not indicated in monostotic fibrous dysplasia of the jaws. The structural weakness of fibrous dysplasia does not functionally impair the jaws to a great extent. Therefore, jaw resection with subsequent bony reconstruction is not justified unless it is an unusual situation in which the patient’s function and appearance are significantly altered and osseous contouring is not an option. Radiotherapy is contraindicated in the treatment of fibrous dysplasias. Numerous cases of radiation sarcomas arising from radiotherapy have been documented. The time from radiation to sarcoma ranges from 10 to 35 years, with a mean at about 20 years. To date, repeated biopsies and surgeries have not been shown to be a stimulus for malignant transformation. However, about 0.8% of long standing, usually polyostotic fibrous dysplasias spontaneously transform into sarcomas.
Paget Disease
CLINICAL PRESENTATION AND PATHOGENESIS Paget disease is a condition of excessive bone resorption followed by disorganized repair. Its etiology is unknown, but several theories have been advanced, of which a slow virus theory has received the greatest support. It is not, however, a metabolic abnormality of bone as previously thought. The pathogenesis begins with overactive osteoclasis of bone. The bone responds by osteoblastic differentiation in which these osteoblasts lay down haphazard bone in many different directions. An increase in vascularity to cope with the demands of so much new bone formation develops. As the disease continues, the abundant osteoid becomes increasingly mineralized, resulting after many years in a dense, sclerotic, end.stage bone that has reduced cellularity and vascularity. Most symptoms occur during the early and intermediate phases of Paget disease, when bone activity and vascularity are at their peak. Patients classically complain of deep bone pain as an early symptom. The pagetoid bone is structurally weak, leading to bowed tibias, kyphosis, or frequent fractures of long bones, depending on the bones involved. Paget disease usually occurs in individuals older than 50 years (3% of the population older than 50 years is said to have at least one isolated lesion of Paget disease), although rare cases of juvenile Paget disease exist. Men are affected more frequently than women by a 3:2 margin. The bones most commonly affected are the spine, femurs, skull, pelvis, sternum, and jaws. The maxilla is affected twice as frequently as the mandible. Together, cases affecting the maxilla and/or mandible account for about 17% of all cases. The patient with jaw involvement will present with expansion and deep bone pain. The affected area will often feel warm with visibly enlarged veins or a bluish hue because of the increased vascularity. The teeth will have diastemas and lingual inclinations because of dental compensations in response to the slow expansion. A denture wearer may present with the classic complaint of a denture that has become too small and may even have had several appliances made to keep pace with the expansion . Analogously, some of Paget’s original reports described skull enlargement that necessitated ever.increasing hat sizes. Patients with jaw involvement may also complain of constant lip and associated soft tissue pain reminiscent of a neuralgia. With skull involvement, headache is the most common complaint, but neuralgiform facial pain and other neurologic complaints such as vertigo, facial paralysis, visual disturbances, and hearing loss are also reported. Such neurologic complaints are believed to be caused by pagetic bone expansion and subsequent compression around the foramina at the base of the skull or within the skull. Although pagetically weakened long bones may fracture pathologically, the jaws usually do not because of the reduced compressive forces placed on them. When such fractures heal, they heal with pagetic bone.
Fig. Paget disease
RADIOGRAPHIC APPEARANCE
Pagetic bone appears as a mottled mixture of radiopacities and radiolucencies. The ratio of these elements depends on the duration of the disease. The radiographic pattern has been termed the “cotton wool” appearance because it is characterized by a fluffed, radiodense, cloud.like aggregation In the jaws, this bone may cause root resorption as well as tooth displacement. Teeth may exhibit hypercementosis or the loss of the lamina dura.
DIFFERENTIAL DIAGNOSIS
A radiopaque, painful expansion of the jaws in an adult may be suggestive of osteomyelitis, particularly chronic diffuse sclerosing osteomyelitis. Osteosarcoma is another consideration. Fibrous dysplasia may resemble Paget disease radiographically but would have been present from early life. An ossifying fibroma, particularly one that is large and mature with densely formed bone, may also resemble Paget disease radiographically and is more consistent with the age of onset. Long.standing secondary hyperparathyroidism will also produce expansile bone with a mottled radiopaque.radiolucent pattern and may be painful as well. Radiopacities of florid cemento.osseous dysplasias also mimic the “cotton wool” appearance of Paget disease and may be painful from secondary infection.
DIAGNOSTIC WORK.UP
The hallmark of diagnosis for a suspected case of Paget disease is a markedly elevated serum alkaline phosphatase level. Serum calcium and phosphate values are normal unless the patient has been recently immobilized, in which case hypercalcemia will develop. Biopsy is usually not necessary unless the alkaline phosphatase levels are near normal and radiographs are equivocal. If a biopsy is performed, the most diagnostic area is the lesion’s center at the point of greatest expansion. A brisk, oozing type of bleeding will occur during biopsy because of the rich vascularity Hemorrhage can be controlled by pressure and local hemostatic agents.
HISTOPATHOLOGY
Active Paget disease is characterized by repeated destruction and repair of bone with no functional organization. First is osteoclastic resorption within the haversian canals and a fibrovascular proliferation within the marrow. Subsequently, osteoblasts lay dowew bone. This process continues in random fashion. The osteoclasts are unusually large and contaiumerous nuclei, sometimes more than 100.The repeated destruction and repair creates a pattern of irregular cemental lines that mimics a mosaic. This finding is characteristic but not pathognomonic. The stroma is fibrous and contains a rich supply of dilated capillaries. This marked vascularity is of surgical significance because there may be profuse bleeding during operative procedures. Healing of this type of pagetic bone is usually uncomplicated, but the healed bone nonetheless remains pagetic bone. Paget disease may “burn out” in certain areas, in
which case there may be considerable sclerosis of bone, fibrosis, and diminished vascularity. Such areas may exhibit slow healing and complications.
TREATMENT AND PROGNOSIS
Mild cases require no treatment. Paget disease is currently incurable, but the pain and deformity can be controlled with treatment. Current therapy, which is aimed at inhibiting osteoclastic bone resorption and, therefore, breaking the cycle of bone resorption.distorted repair, focuses on the anti.osteoclastic actions of calcitonin or the bisphosphonates. Synthetic salmon calcitonin (Calcimar, Aventis) is given in doses ranging from 50 to 100 IU subcutaneously daily or three times weekly over a period of months or even years. Alternatively, nasal salmon calcitonin (Miocalcin, Sandoz) may be used at 200 IU/spray once daily. A 200.mg oral dose of disodium etidronate may be given twice daily; the dosage should be modified to 5 mg/kg daily for underweight individuals. However, it is important to note that this drug is usually given for 3. to 6.month periods and then interrupted before another course is given because prolonged use of etidronate will adversely affect bone mineralization in the rest of the skeleton. Pamidronate (Aredia, Novartis) is another drug effective in Paget disease, but it must be given intravenously in 500 mL of normal saline at a dosage of 30 mg over 4 hours. Response to this therapy lasts for 3 to 6 months, then the dosage must be repeated. Therapy with any of these three drugs results in a reduction in pain and bony expansion. Serum alkaline phosphatase levels as well as urinary hydroxyproline levels fall in response to this therapy, enabling patients to live near.normal and often active lifestyles. However, some patients with long. standing disease develop renal failure or nephrocalcinosis caused by hypercalcemia. Others undergo spontaneous malignant transformation into osteosarcoma. The incidence of this is heavily debated and mostly overstated. However, it is in the range of 2% to 5% of cases. Radiation in Paget disease is contraindicated because it has been proven to incite malignant transformation. FOLLOW.UP Follow.up for patients with Paget disease is usually on a semi.annual or annual basis if the condition is stable. Radiographs and serum alkaline phosphatase levels are evaluated. Signs that may herald a sarcomatous transformation are rapid clinical expansion, surface ulceration, necrosis, development of new radiolucent areas, and an increase over previous alkaline phosphatase levels.
BIOLOGIC BEHAVIOR AND TREATMENT
Osteopetrosis is frustrating for the clinician and the individual. Unlike in other diseases involving exposed nonviable bone, debridement is not the focus of therapy in osteopetrosis. In fact, the strategy is to avoid bony surgery and to limit the degree of surgery as much as possible. The involvement of the entire skeleton does not allow the surgeon to debride to “healthy bone,” and bone grafts are not available from any site. Therefore, almost all surgeries in which bone is debrided and a soft tissue closure is obtained result in re.exposure of a greater amount of bone and further risk of fracture. In a similar sense, tooth removal should be avoided if possible. Therefore, frequent dental visits with prophylaxis and prompt restorative and endodontic care are recommended. A removed tooth often initiates the development of persistently exposed bone and low.grade infection. The clinician is relegated to mostly nonsurgical management even when fractures occur. The exposed one is cultured and then best treated with the limited intervention of smoothing rough or sharp bony edges, chlorhexidine gluconate oral rinses, and frequent irrigations to reduce numbers of the microorganisms. During periods of secondary infection, culture.directed antibiotics are recommended. Hyperbaric oxygen, which produces angiogenesis in osteoradionecrosis, has been suggested for the treatment of osteopetrosis. However, its use is of limited value because osteopetrosis, unlike osteoradionecrosis, does not produce the necessary oxygen gradient loss in soft tissues. It therefore should be reserved for use as an adjunct to antibiotics and wound irrigations in episodes of secondary infection. Should a patient with osteopetrosis require surgery under general anesthesia, the intubation should be either a fiberoptic.assisted or an awake nasal intubation. Use of a laryngoscope, which extends the neck, risks paralysis from spinal cord compression because of the high risk of cervical spine subluxation and fracture.
Salivary Gland Neoplasms
While the clinical presentation of a salivary gland neoplasm is usually an asymptomatic mass that may occasionally be ulcerated or cause pain, the histologic presentation is far more complex. The tumor spectrum is vast, and yet repetitive features may be seen in a variety of neoplasms with differing biologic behavior. Developing salivary glands arise from the stomodeum as ectodermal buds that proliferate as cords into the underlying mesenchyme. The ends thicken to form terminal bulbs. These undergo branching, followed by continued advancement into the mesenchyme. This process repeats itself, all the while maintaining continuity with the oral epithelium. This branching process gives rise to the lobular architecture of the gland. The terminal tubular elements differentiate into acinar cells, and between the acinar cells and basal lamina myoepithelial cells form. These are strap.shaped and stellate cells, which may appear as clear cells prior to the development of myofilaments. Intercalated and smaller striated ducts also differentiate from this area. The original cords and their branches become the excretory ducts.
The histogenesis of salivary gland tumors has been controversial. Some suggest acinar cells, since these have been shown to have a regenerative capacity. Others however, propose a stem or reserve cell in the salivary duct system. The complexity of salivary gland tumors is due in part to the fact that in most instances more than one cell type is involved. These may be acinar, luminal, myoepithelial, basal, or squamous. Adding to this diversity, extracellular secretory products are a striking component of many tumors. These products include basal lamina, collagen fibers, elastic fibers, and glycosaminoglycans. It is believed that these substances are probably secreted by the neoplastic myoepithelial cells. Salivary gland tumors may involve major or minor glands. The largest number of cases are found within the parotid. While most types of tumors may be found in both sites, relative frequency can vary. Thus approximately 80% of parotid tumors are benign. In minor salivary glands, however, the benign.malignant ratio is closer to 1:1, while in the sublingual gland, an uncommon site for neoplasms, the majority are malignant. The pleomorphic adenoma is the most common tumor both in major and in minor salivary glands. Warthin tumors, basal cell adenomas, oncocytomas, acinic cell carcinomas, and sebaceous tumors have a strong predilection for the major glands, but the polymorphous low.grade adenocarcinoma has a marked predilection for the minor glands. While most intraoral salivary gland tumors favor the palate, the canalicular adenoma favors the upper lip. Tumors occurring within salivary glands are predominantly of epithelial origin. However, it should be appreciated that nonepithelial neoplasms also may arise within the gland that are not actually of salivary gland or ductal origin. Most of these are found in the parotid gland. Among the more common benign tumors is the hemangioma, which is the most frequently occurring tumor in the parotid gland in children. Lipomas and neurogenic tumors also may be seen. Hodgkin and non. Hodgkin lymphomas and, most infrequently, soft tissue sarcomas may develop. Metastatic tumors such as renal cell carcinoma and melanoma may also occur.
Pleomorphic Adenoma
CLINICAL PRESENTATION
The pleomorphic adenoma is the prototypical benign yet true neoplasm; that is, it will continue to grow—or regrow if not completely removed—but it is incapable of metastasis. It occurs at different statistical incidences in all salivary glands. Eighty percent of tumors that occur in the parotid gland are benign: of these, 75% are pleomorphic adenomas and 5% are Warthin tumors (papillary cystadenoma lymphomatosum). Pleomorphic adenomas, and salivary gland tumors in general, are not commonly found in the submandibular and sublingual glands. Nevertheless, they account for about 20% to 30% of all tumors in these glands. Oral pleomorphic adenomas are somewhat common, accounting for about 45% of all oral minor salivary gland tumors.Then they arise in the oral mucosa, the site of predilection is the mucosa over the posterior hard palate and anterior soft palate; otherwise, pleomorphic adenomas can occur in any location where minor salivary glands exist. Consequently, the two most common clinical presentations are a painlessfirm mass in the superficial lobe of the parotid gland and a painless firm mass in the posterior palatal mucosa. Eighty percent of all pleomorphic adenomas in the parotid gland develop in the superficial lobe, which constitutes 80% of the parotid gland. It presents as a freely movable, firm mass. Peculiarly and rarely, these can fluctuate in size or be painful. Pleomorphic adenomas do not induce facial nerve paresis. Any facial nerve weakness not attributable to previous surgery should be considered a malignancy until proven otherwise. When a pleomorphic adenoma arises from the deep lobe of the parotid gland, it usually goes unrecognized for a number of years until its size creates symptoms of dysphagia or gagging. These present orally as a bulge arising from the tonsillar fossa area. When a pleomorphic adenoma presents in the mucosa of the hard palate.soft palate junction, it will be a firm, painless mass with intact overlying mucosa. If the mucosa is ulcerated and the ulceration is not attributable to trauma or a biopsy, the mass should be considered a malignancy. In the palatal mucosa, the mass will seem to be fixed to the palate. Since the pleomorphic adenoma cannot invade bone, this is not caused by bony invasion but rather by the inelasticity of the palatal mucosa, which becomes distended by the tumor mass and may eventuate in a cupped.out resorption of bone. In other oral mucosal sites, the pleomorphic adenoma presents as a freely movable, circumscribed mass. Pleomorphic adenomas can arise at any age but are somewhat more common between the ages of 30 and 50 years and are slightly more common in women.
Fig. Pleomorphic adenoma
DIFFERENTIAL DIAGNOSIS
The differential diagnosis of a firm mass in the parotid gland must include a Warthin tumor (papillary cystadenoma lymphomatosum), which is particularly likely in men, and basal cell adenoma, which preferentially develops in the parotid gland. In addition, malignant salivary gland tumors that must be considered include mucoepidermoid, adenoid cystic, and acinic cell carcinomas. Nonsalivary gland neoplasms that are known to occur in the parotid gland—ie, hemangiomas, lymphangiomas, lipomas, and lymphomas within parotid lymph nodes—may also present in a similar fashion. The clinician must also be aware that skiodules such as sebaceous cysts can form a subcutaneous mass in the area that may give an impression of being located in the parotid gland. The differential diagnosis of a firm mass in the palatal mucosa with intact overlying epithelium is primarily a subset of other salivary gland neoplasms. In order of statistical likelihood, they are adenoid cystic, mucoepidermoid, and polymorphous low.grade adenocarcinomas. Another benign tumor that requires some consideration is the canalicular adenoma. In addition, several nonsalivary gland tumors may present with a similar appearance, such as non.Hodgkin lymphoma and neurofibroma.
DIAGNOSTIC WORK.UP AND TREATMENT
For a mass in the parotid gland, a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan is valuable to confirm its location in the parotid, specifically in the superficial lobe. This should be followed by a superficial parotidectomy, which represents both the diagnostic biopsy and the definitive treatment (see pages 567 to 569). In such a presentation, an incisional parotid biopsy would be contraindicated because seeding of tumor cells throughout the biopsy site is a concern. For a mass in the palatal mucosa, a CT scan, particularly coronal views, also is recommended to determine its extent and the degree of any resorption of the palate. A deep incisional biopsy of the mass is recommended in its center to establish a firm permanent.section diagnosis prior to planning definitive surgery. This is different from the parotid gland approach, in which biopsy and definitive surgery are one and the same, because an oral incisional biopsy can be accomplished without seeding tumor cells. If a pleomorphic adenoma is confirmed, it is excised with 1.cm clinical margins at its periphery and includes the overlying surface epithelium and the periosteum of the palate. Excision or scraping of the palatal bone is not required because the periosteum is an effective anatomic barrier and pleomorphic adenomas do not elaborate osteoclast.activating factor to invade bone. If the tumor extends to the area of the soft palate, the excision includes the fascia over the soft palate musculature. The muscles of the soft palate need not be excised unless frozen sections indicate tumor at this margin. For pleomorphic adenomas in other mucosal sites, a peripheral excision with 1.cm margins is recommended. This will include overlying mucosa but should not include overlying skin if the mass is located in the lip or buccal mucosa. In these instances, the muscle fascia of the orbicularis oris or buccinator is an effective anatomic barrier. In any site, enucleation, or a “shelling out” of a pleomorphic adenoma, is contraindicated. The pseudocapsule of a pleomorphic adenoma will certainly give the clinical impression of a complete removal of an “encapsulated nodule or mass” with these approaches, but the extracapsular tumor projections left behind may lead not only to recurrence but to multicentric recurrences caused by the remaining tumor projections and foci within the tissue at the circumference of the resections.
HISTOPATHOLOGY
From a therapeutic standpoint, the most significant histologic features relate to the capsule of the tumor. While not all pleomorphic adenomas, particularly those affecting minor salivary glands, will have a well.developed capsule, these are well.demarcated masses. Unfortunately, this characteristic, coupled with the fact that these tumors are clinically freely moveable, particularly when palpated in such areas as the lip, belies the fact that tumor cells are found within the capsule and as extensions through and beyond it. Thus a “conservative” enucleation would almost ensure residual tumor cells and set the patient up for multifocal recurrences. Grossly, these tumors have a smooth, sometimes bosselated surface. The cut surface is typically white and resembles a cut potato. Bluish areas representing cartilage.like material may be seen, and a gelatinous component may be present. Older tumors often show cyst formation. The microscopic picture is typically diverse. Essentially, there is a proliferation of both ductal epithelium and a myoepithelial component. This gives rise to cellular, epithelial areas as well as mesenchymal.like tissue that usually has a myxochondroid appearance. The relative quantities of these two types can vary considerably. In general, the minor salivary gland tumors are more cellular than those of the major glands. The cellular portion of the tumor may form a variety of patterns such as islands, sheets, ribbons, or ductal configurations. Squamous cells and keratin pearls may be present. Occasionally, there may be cribriform areas, suggesting the pattern of adenoid cystic carcinoma. However, such areas usually compose only a small portion of the tumor, and the infiltrative nature of the carcinoma is not evident. Aggregates of oncocytic cells may be seen, but this can occur in a variety of salivary gland tumors. Plasmacytoid (hyaline) cells may also be seen. Both of these have been identified as myoepithelial cells. In some tumors, one or both of these cell types constitute practically the entire lesion. If the ductal and glandular component constitutes less than 5% of the tumor, these would be classified as myoepitheliomas. Basal lamina produced by myoepithelial cells appears to be responsible for the eosinophilic hyalinized material that can form a striking component of many tumors . The myoepithelium also deposits the basophilic, mucoid material, which then separates the cells so that the tissue appears myxoid. Degeneration of cells with vacuolation produces the chondroid pattern. Crystalline material may sometimes be seen. Malignant degeneration is possible within pleomorphic adenomas, and the incidence increases with tumor duration and size. Histologic features suggestive of malignant transformation include extensive hyalinization, cellular atypism, necrosis, calcification, and invasion.
PROGNOSIS
Excision with controlled frozen sections and clear intraoral margins and excision via superficial parotidectomy are associated with a cure rate of more than 95%. Incomplete removals uniformly result in tumor recurrence. Clinically, recurrence is first manifested about 4 to 6 years postoperatively and is often unknown to the original surgeon, which has given false credence to enucleation procedures. Pleomorphic adenomas are benign tumors with a well.documented transformation to malignancy (carcinoma ex pleomorphic adenoma). It is estimated that up to 25% of untreated pleomorphic adenomas undergo malignant transformation, a process that is size. and time.related. Therefore, early definitive treatment is strongly recommended. Although malignant transformation requires histopathologic confirmation, clinical clues of such transformation may be readily apparent. They include ulceration, fluctuance, pain, neural deficits, or a change from a single circumscribed mass to a lobulated mass .
Surgeries of the Parotid Gland
Introduction
Parotid surgery for all conditions comprises six definitive basic procedures: (1) fine needle aspirations for diagnostic cytology; (2) incisional parotid biopsy; (3) superficial parotidectomy; (4) total parotidectomy with nerve preservation; (5) total parotidectomy with nerve transsection and nerve grafting; and (6) excision of the deep lobe of the parotid gland. Each is discussed with reference to its indications and surgical technique.
Fine Needle Aspiration for Diagnostic Cytology
INDICATIONS Fine needle aspirations (FNAs) are indicated in the treatment of solitary parotid masses suspected to represent a tumor. The purpose of an FNA cytology is to gain a diagnosis prior to definitive parotid surgery without risking the seeding of tumor cells by performing an incisional parotid biopsy. Because of the limited number of cells obtained, it is often impossible to gain a definitive diagnosis. However, the clinician is well served if the pathologist can distinguish the specimen as either benign or malignant. This presurgical knowledge, along with a CT or MRI scan, allows the surgeon to plan the necessary type of parotid surgery (ie, superficial parotidectomy versus total parotidectomy with nerve preservation versus total parotidectomy with nerve transsection and grafting, etc). This also allows the surgeon to better advise the patient and elicit more definitive informed consent.
PROCEDURE
The FNA technique for a parotid mass is identical to an FNA for cervical lymph nodes. The skin is prepared with a surgical scrub and draped. It is anesthetized with local anesthesia. With the parotid mass stabilized between two fingers, a 21.gauge or smaller needle attached to a 10.mL syringe is inserted. The clinician should be able to discern the needle entering the tumor mass by an increase in resistance as it enters it. To confirm the needle’s presence in the mass, it is toggled back and forth by the fingers used to stabilize it. If the needle is within the mass, the syringe will move with it. The syringe plunger is drawn back forcibly to dislodge cells into the needle lumen. Negative pressure should be maintained as the needle is withdrawn. The cells within the needle lumen are forcibly expressed onto a dry glass slide and quickly smeared as thin as possible with the needle itself. The specimen slide is then immediately placed into the fixative (it is best to use 95% alcohol, although formalin will also suffice). This process should take less than 10 seconds.
Incisional Parotid Biopsy
INDICATIONS
Incisional parotid biopsies are indicated when it is necessary to confirm or rule out autoimmune or systemic diseases that involve salivary gland tissue. They are particularly indicated to confirm Sjogren syndrome, benign lymphoepithelial lesions, sarcoidosis, sialosis, and lymphoma in the parotid gland. They are contraindicated in firm, circumscribed masses in the parotid or knoweoplasms.
PROCEDURE
Incisional parotid biopsy may be accomplished as an office procedure under local anesthesia. An incision is placed at the inferior margin of the pinna beneath the earlobe for cosmetic reasons. A 1.5.cm incision is made through skin and subcutaneous tissue to expose and identify the thicker white parotid.masseteric fascia. This fascia and the thin parotid capsule, which are usually fused together, are incised to expose a small portion of the parotid. The gray lobulations of the parotid confirm the location, which is distinguishable from yellow subcutaneous fat. Several lobules are then taken and placed in formalin (parotid tissue, which will sink, can again be distinguished from fat, which will float, once the container has been shaken). The parotid.masseteric fascia is closed, as are the subcutaneous and skin layers; no drain is required. Sialoceles do not result as a complication of this procedure because no major ducts are transsected. Facial nerve injury is also not a complication of this procedure because this surgical site is in an area where the facial nerve is much deeper (
Superficial Parotidectomy
INDICATIONS
A superficial parotidectomy is indicated in cases of benign tumors in the superficial lobe and some low.grade malignant tumors (if frozen sections document clear margins). It is also indicated in selected cases of symptomatic sialosis, Sjogren syndrome, HIV parotitis, lymphoepithelial cysts, and parotid injuries with refractory sialocele or salivary.cutaneous fistulae.
PROCEDURE
The standard superficial parotidectomy, called the “central approach,” is accomplished with a continuous incision that begins in the preauricular area and continues around the earlobe and gently curves to parallel the angle and posterior body of the mandible about 2 to
Total Parotidectomy with Nerve Preservation
INDICATIONS
A total parotidectomy with nerve preservation is indicated in cases of benign and low. grade malignant tumors that encroach upon or extend into the deep lobe .
PROCEDURE
The surgery is identical to the standard or modified superficial parotidectomy except that access to the deep lobe is gained between the upper and lower divisions of the facial nerve. In this approach, each division, including the buccal branch, must be dissected completely. The upper division, along with the buccal branch, is retracted superiorly, and the lower division is retracted inferiorly. A portion or, in some cases, all of the deep lobe may be removed through this access .
Total Parotidectomy with Nerve Transsection and Nerve Grafting
INDICATIONS
A total parotidectomy with nerve transsection and nerve grafting is indicated in cases of malignant tumors of the superficial lobe that require aggressive resection and diffuse benign tumors that involve both lobes.
PROCEDURE
This surgery is identical to the standard or modified superficial parotidectomy except that access to the deep lobe is gained through transsection of all five branches of the facial nerve and a nerve graft is accomplished after the tumor is removed. As each branch of the facial nerve is transsected, each end is tagged and allowed to retract. The mandible is dislocated forward and each portion of the facial nerve ends is retracted to excise a deep lobe tumor extension. At the same time, a 6. to 8.cm length of the greater auricular nerve is harvested and separated into five fascicles. Each fascicle is grafted to the proximal and distal ends of the transsected nerve, usually via an epineurial closure with 8.0 nylon suture on a BV130.5 needle with the aid of a microscope. Direct re.anastomosis may be accomplished, but nerve retraction will place tension on the anastomosis and may compromise nerve regeneration.
Excision of the Deep Lobe of the Parotid Gland
INDICATIONS
Excision of the deep lobe of the parotid gland is indicated in cases of benign or low.grade malignant tumors located in and limited to the deep lobe of the parotid gland .
PROCEDURE
Access to the deep lobe of the parotid gland is blocked by the mandible and the superficial lobe. An access approach developed for parapharyngeal space tumors (Attia approach) also provides access to the deep lobe of the parotid gland. The incision resembles a posteriorly extended Risdon approach to the mandible. A preauricular or superficial parotidectomy incision is not needed. As the mandible is approached, the masseter attachments and the lateral periosteum are not reflected, except just anterior to the mental foramen and just above the lingual aspect, in anticipation of osteotomies in each area. The ramus access is gained by incising the periosteum at the posterior ramus border and reflecting the upper fibers of the masseter anteriorly. Reconstruction plates of 2.4 or
