Precancerous diseases and lower lip cancer: classification, histological structure, clinical forms, stage of disease, differential diagnostic, principles and methods of treatment (surgery, radiation, chemotherapy, immune correction, etc.), prevention and prevention of complications. Cancer and sarcomas of the jaws: origin and histological structure, classification, clinical features, differential diagnostic, treatment, complications, prevention. Malignant tumors of the salivary glands: histological structure, clinical forms, differential diagnosis and treatment.
· In your lifetimes, between
· Cancer—“crab”—family of diseases in which tissues grow and spread throughout the body.
· Disease has been around for thousands of years, but prevalence steadily increasing as humans live longer.
Biology of Cancer August 29, 2007
Lecture 1: What is cancer?
Outline:
1. Defining cancer
2. Many diseases
3. Normal vs. abnormal cells
4. Benign vs. malignant tumors
5. How cancers vary
6. Cancer diagnosis/staging
· In your lifetimes, between
· Cancer—“crab”—family of diseases in which tissues grow and spread throughout the body.
· Disease has been around for thousands of years, but prevalence steadily increasing as humans live longer.
Fig. 1-1 Relative frequencies of cancer cases. What does pie chart say?
· Most common cancer: skin cancer
· Also common: prostate, breast, lung, colorectal cancers
Relative frequency of cancer deaths:
· Deadliest cancer is lung cancer, followed by colorectal cancer and breast cancer.
· Skin cancer makes up a small fraction of cancer deaths.
· Pancreatic cancer makes up a small fraction of cancer cases, but is one of the deadliest cancers.
Different regions of the world have different cancer incidences.
To make comparisons between death rates, these are adjusted per 100,000/year
Different cancers have different death rates; death rate trends may change over time.
Fig. 1-2 Describe the trends.
· Death rate due to lung cancer increased between 1930 and 1990, now declining slightly.
Scientists look for factors affecting trends
· Lung cancer increases with increased smoking and passage of time.
Describe the trend in breast cancer death rates.
Describe the trend in stomach cancer death rates.
Biology of Cancer text
Cancer cells have two properties
· Cell proliferate out of control
· Cancer cells spread throughout the body (metastasis)
Cells are the basic units of life.
Levels of organization:
Cells à tissues à organs à organ systems à individual
Initial stages of cancer deal with cells and tissues
Later stages deal with spread of cells via organ systems (circulatory, lymphatic)
Normal growth vs. abnormal growth of tissues
Hypertrophy—increase in cell size i.e. weight trainingàmuscles
Hyperplasia—increase in cell number i.e. callusesàwriting
Dysplasia—disorganized growth
Neoplasia—disorganized growth, increase in # of dividing cells
Fig. 1-4
Normal skin: only basal cells divide; other cells migrate and differentiate
Skin tumor: cell division occurs among more cell types in several layers; lacks needed specialized cells
Benign tumors—grow in a confined area
Malignant tumors—can invade surrounding tissues, enter bloodstream, spread to different parts of the body by metastasis
A cancer is any malignant tumor.
Cancers vary in their site of origin.
Lung vs. liver cancer
Cancers vary in the cell type of origin
Carcinoma vs. sarcoma vs. leukemia
epithelia muscle blood
90% 1% 9% of all human cancers
Leukemia—cancer of circulating blood
Lymphoma—solid tumor containing many blood cells
Table 1-2 Naming tumors
Cancers vary in their survival rates.
Table 1-3; Fig. 1-6
~99% of patients survive 5 yrs with skin cancer
~20% of patients survive 5 yrs with lung cancer
Cancer diagnosis
Remove tissue—biopsy
Pathologist examines for tumor under microscope
Looks for evidence of malignancy
Table 1-4 Microscopic difference benign vs. malignant tumors
Pathologist “grades” the tumor based on differences in size, microscopic appearance and evidence of metastasis
Grade 1: benign tumors à à à grade 4 metastatic tumors
Tumors can also be categorized based on their clinical stage.
In staging, the estimated progression of a person’s cancer is correlated with prospects for successful treatment.
TNM system
T = tumor size
N =lymph node
M = metastasis
(1) How large is the tumor and how far has it invaded into surrounding tissues?
(2) Are lymph nodes positive for cancer cells (have cancer cells spread to regional lymph nodes?
(3) To what extent have cancer cells metastasized to other organs?
Lower combined TNM# –cancer detected early and hasn’t spread
Higher combined TNM#–more difficult to treat successfully
Example: Staging of colon and rectum cancer
|
Classification |
Description |
|
Tis |
Carcinoma in situ |
|
T1 |
Invasion into submucosa layer of colon wall |
|
T2 |
Invasion into submucosa into underlying muscular layer |
|
T3 |
Invasion through muscular layer |
|
T4 |
Invasion into peritoneal cavity and adjacent organs |
|
N0 |
Regional lymph nodes free of tumor |
|
N1 |
1-3 positive nodes |
|
N2 |
4 or more positive nodes |
|
N3 |
Positive nodes oamed vascular trunk |
|
M0 |
No distant metastases |
|
M1 |
Distant metastases present |
Proper staging is critical to proper diagnosis and treatment
|
TNM stage |
Five year survival rate |
Treatment |
|
T1N0M0 |
>90% |
surgery |
|
T4N0M0 |
60-70% |
surgery |
|
T4N1M0 |
40% |
surgery and chemo or radiation |
· Most common cancer: skin cancer
· Also common: prostate, breast, lung, colorectal cancers
Relative frequency of cancer deaths:
· Deadliest cancer is lung cancer, followed by colorectal cancer and breast cancer.
· Skin cancer makes up a small fraction of cancer deaths.
· Pancreatic cancer makes up a small fraction of cancer cases, but is one of the deadliest cancers.
Different regions of the world have different cancer incidences.
To make comparisons between death rates, these are adjusted per 100,000/year
Different cancers have different death rates; death rate trends may change over time.
Fig. 1-2 Describe the trends.
· Death rate due to lung cancer increased between 1930 and 1990, now declining slightly.
Scientists look for factors affecting trends
· Lung cancer increases with increased smoking and passage of time.
Describe the trend in breast cancer death rates.
Describe the trend in stomach cancer death rates.
Biology of Cancer text
The author, Dr. Lewis Kleinsmith, is a professor in cell and molecular biology at the
Cancer cells have two properties
· Cell proliferate out of control
· Cancer cells spread throughout the body (metastasis)
Cells are the basic units of life.
Levels of organization:
Cells à tissues à organs à organ systems à individual
Initial stages of cancer deal with cells and tissues
Later stages deal with spread of cells via organ systems (circulatory, lymphatic)
Normal growth vs. abnormal growth of tissues
Hypertrophy—increase in cell size i.e. weight trainingàmuscles
Hyperplasia—increase in cell number i.e. callusesàwriting
Dysplasia—disorganized growth
Neoplasia—disorganized growth, increase in # of dividing cells
Fig. 1-4
Normal skin: only basal cells divide; other cells migrate and differentiate
Skin tumor: cell division occurs among more cell types in several layers; lacks needed specialized cells
Benign tumors—grow in a confined area
Malignant tumors—can invade surrounding tissues, enter bloodstream, spread to different parts of the body by metastasis
A cancer is any malignant tumor.
Cancers vary in their site of origin.
Lung vs. liver cancer
Cancers vary in the cell type of origin
Carcinoma vs. sarcoma vs. leukemia
epithelia muscle blood
90% 1% 9% of all human cancers
Leukemia—cancer of circulating blood
Lymphoma—solid tumor containing many blood cells
Table 1-2 Naming tumors
Cancers vary in their survival rates.
Table 1-3; Fig. 1-6
~99% of patients survive 5 yrs with skin cancer
~20% of patients survive 5 yrs with lung cancer
Cancer diagnosis
Remove tissue—biopsy
Pathologist examines for tumor under microscope
Looks for evidence of malignancy
Table 1-4 Microscopic difference benign vs. malignant tumors
Pathologist “grades” the tumor based on differences in size, microscopic appearance and evidence of metastasis
Grade 1: benign tumors à à à grade 4 metastatic tumors
Tumors can also be categorized based on their clinical stage.
In staging, the estimated progression of a person’s cancer is correlated with prospects for successful treatment.
TNM system
T = tumor size
N =lymph node
M = metastasis
(1) How large is the tumor and how far has it invaded into surrounding tissues?
(2) Are lymph nodes positive for cancer cells (have cancer cells spread to regional lymph nodes?
(3) To what extent have cancer cells metastasized to other organs?
Lower combined TNM# –cancer detected early and hasn’t spread
Higher combined TNM#–more difficult to treat successfully
Example: Staging of colon and rectum cancer
|
Classification |
Description |
|
Tis |
Carcinoma in situ |
|
T1 |
Invasion into submucosa layer of colon wall |
|
T2 |
Invasion into submucosa into underlying muscular layer |
|
T3 |
Invasion through muscular layer |
|
T4 |
Invasion into peritoneal cavity and adjacent organs |
|
N0 |
Regional lymph nodes free of tumor |
|
N1 |
1-3 positive nodes |
|
N2 |
4 or more positive nodes |
|
N3 |
Positive nodes oamed vascular trunk |
|
M0 |
No distant metastases |
|
M1 |
Distant metastases present |
Proper staging is critical to proper diagnosis and treatment
|
TNM stage |
Five year survival rate |
Treatment |
|
T1N0M0 |
>90% |
surgery |
|
T4N0M0 |
60-70% |
surgery |
|
T4N1M0 |
40% |
surgery and chemo or radiation |
The salivary glands are the site of origin of a wide variety of neoplasms. The histopathology of these tumors is said to be the most complex and diverse of any organ in the body. Salivary gland neoplasms are also relatively uncommon with an estimated annual incidence in the
Benign Neoplasms
Pleomorphic Adenoma
The pleomorphic adenoma or benign mixed tumor is the most common of all salivary gland neoplasms. It comprises about 70% of all parotid tumors, 50% of all submandibular tumors, 45% of minor salivary gland tumors but only 6% of sublingual tumors. The most common location of occurrence is the parotid (85%) followed by the minor salivary glands (10%), in which the palate, upper lip and buccal mucosa are most commonly affected. These tumors are most often diagnosed in the 4th to 6th decades of life and are uncommon in children although they are second only to hemangiomas in this population. They are seen more frequently in women with a female-to-male ratio of 3-4:1.
The typical clinical presentation of a pleomorphic adenoma is a slow-growing, painless and firm mass. In the parotid, 90% occur in the superficial lobe and most commonly are seen in the tail of the gland. Minor salivary gland pleomorphic adenomas most commonly occur on the lateral palate and are covered with normal appearing mucosa. In all locations, they are typically nontender to palpation and tend to be mobile when small but may become fixed with advanced growth. These tumors are nearly always solitary although rare cases of synchronous or metachronous salivary neoplasms have been reported- either involving a second mixed tumor or a distinct lesion, most commonly Warthin’s tumor. Facial nerve paralysis in association with pleomorphic adenomas almost never occurs, even with extremely large tumors.
The gross pathologic appearance of a pleomorphic adenoma is a smooth or lobulated, well-encapsulated tumor that is clearly demarcated from the surrounding normal salivary gland. They are typically solid tumors and may have areas of gelationous myxoid stroma. Cystic degeneration or tumor infarction and necrosis are rarely seen except in large, long-standing lesions. Microscopically, these tumors are composed of varying proportions of gland-like epithelium and mesenchymal stroma. The epithelial cells may display several different patterns of growth—small nests, solid sheets, ductal structures or anastamosing trabeculae. The stroma is just as variable and may be myxoid, chondroid, fibroid or osteoid. Also on microscopic examination, the incomplete encapsulation and transcapsular growth of tumor pseudopods characteristic of pleomorphic adenoma are demonstrated.
Treatment of pleomorphic adenomas is complete surgical excision with a surrounding margin of normal tissue, i.e., superficial parotidectomy with facial nerve preservation, submandibular gland excision or wide local excision for a minor salivary gland. Simple enucleation of these tumors is what is believed to have led to high local recurrence rates in the past and should be avoided. Rupture of the capsule and tumor spillage in the wound is also believed to increase the risk of recurrence, so meticulous dissection is paramount (1,2,3,4).
Warthin’s Tumor
The second most common benign parotid neoplasm is Warthin’s tumor, also known as papillary cystadenoma lymphomatosum. It makes up 6-10% of cases of parotid tumors and has only rarely been described as occurring outside the parotid gland. It is primarily a disease of older white males, often being diagnosed in the 4th to 7th decades of life and occurring with a male-to-female ratio of approximately 5:1. Bilateral or multicentric Warthin’s tumors are seen in 10% of cases. Three percent are associated with other benign or malignant tumors.
Like the pleomorphic adenoma, Warthin’s tumors typically present as a slowly enlarging, painless mass. They tend to be firm or rubbery in texture and may be nodular. A minority of patients may report rapid enlargement of the tumor with associated pain or pressure.
Grossly, a Warthin’s tumor possesses a smooth lobulated surface and a thin but tough capsule. The diagnosis is often obvious just by the appearance of the cut surface of the tumor. Multiple cysts of varying diameter and containing variably viscous fluid are seen. The lining of the cysts appears shaggy and irregular. The lymphoid component makes up the solid areas of the tumor and lymphoid follicles can occasionally be seen. The pathognomonic microscopic features are epithelial cells forming papillary projections into cystic spaces in a background of a lymphoid stroma. The epithelium is a double cell layer with tall columnar cells lining the cystic spaces and cuboidal cells along the basement membrane. The nuclei of the columnar cells is oriented toward the cystic space while the cuboidal cell nuclei is oriented toward the basement membrane.
Treatment of Warthin’s tumors is surgical resection. Enucleation of the tumor may be adequate therapy but superficial parotidectomy with facial nerve preservation is the standard management (1,2,3,4).
Oncocytoma
Oncocytomas are rare tumors that constitute only 2.3% of benign epithelial salivary gland neoplasms. They are most often encountered after the sixth decade of life with a nearly equal male-to-female ratio of occurrence. The majority of these tumors affect the parotid gland (78%), few affect the submandibular gland (9%), none are reported in the sublingual gland and minor salivary gland involvement is most often in the palate, buccal mucosa or tongue.
The clinical presentation of oncocytomas is essentially identical to other benign salivary tumors—a slowly growing, nontender mass, typically in the superficial lobe of the parotid. They are firm, may be multilobulated and mobile on exam. Oncocytomas, along with Warthin’s tumors, have beeoted to demonstrate increased uptake of pertechnetate anion and therefore can be distinguished from some other neoplasms by using technetium-99m pertechnetate scintigraphy.
Gross pathology findings include a homogenous tumor with a smooth surface that may be divided into lobules by fibrous tissue septae. Microscopically, there are sheets, nests or cords of uniform oncocytes. These cells are large with distinct borders and filled with an acidophilic granular cytoplasm. The granularity of the cytoplasm is due to the presence of large numbers of mitochondria that may constitute up to 60% of the cell volume. Special staining procedures such as the phosphotungstic acid hematoxylin stain, Bensley’s aniline-acid fuchsin or Luxol-fast-blue reaction take advantage of this unique characteristic and can help to make the diagnosis of oncocytoma, as can electron microscopy.
Standard treatment of oncocytomas is surgical excision with a margin of normal tissue. There is an exceedingly low rate of recurrence of these tumors if removal is complete. Enucleation or curettage is not appropriate (1,2,3,4).
Monomorphic Adenoma
The term “monomorphic adenoma” refers to a group of rare salivary tumors that includes the basal cell, canalicular, sebaceous, glycogen-rich and clear cell adenoma. Of these, the basal cell adenoma is the most common. It constitutes 1.8% of benign epithelial salivary gland tumors and typically occurs in the 6th decade of life. There are conflicting reports of gender predilection for this tumor but it does seem to occur more frequently among Caucasians than African Americans. The majority of basal cell adenomas occur in the parotid gland where they present as a slowly enlarging firm mass. They are well-encapsulated, smooth tumors on gross inspection and are divided into four subtypes based on their microscopic appearance—solid, trabecular, tubular and membranous.
The presentation of canalicular adenoma peaks in the 7th decade of life and, like the basal cell adenoma, is more common in whites than blacks. There is a female predominance with a female-to-male ratio of occurrence of 1.8-1. This tumor most commonly involves the minor salivary glands of the upper lip (74%) or buccal mucosal (12%). Clinically it presents as a nonpainful submucosal nodule. On gross pathologic examination, canalicular adenomas may or may not possess a capsule and it is not unusual for there to be multifocal growth. Microscopically there are cords of single-layer columnar or cuboidal cells forming duct-like structures in a background of fibrous stroma (1,2,3,4).
The majority of monomorphic adenomas display nonaggressive behavior and are adequately treated with surgical excision.
Myoepithelioma
The rare myoepithelioma accounts for less than one percent of all salivary gland neoplasms. They are seen in the minor salivary glands, primarily palate, parotid glands, and occasionally in the submandibular glands. Like pleomorphic adenomas, these present in the 5th decade of life and are more common in women. Clinical presentation is similar to other benign salivary neoplasms—an asymptomatic, slow-growing mass. They are well-circumscribed tumors with a gross appearance similar to a pleomorphic adenoma but without the myxoid stroma. Three patterns of microscopic appearance have been described. The spindle cell pattern is the most common overall and is typical for parotid myoepitheliomas. The plasmacytoid pattern is less common but the most frequently encountered pattern in palate tumors. The third pattern demonstrates a combination of the spindle and plasmacytoid cells and is uncommon. Myoepitheliomas tend to exhibit benign behavior and complete surgical excision is appropriate therapy (1).
Malignant Neoplasms
Mucoepidermoid Carcinoma
Mucoepidermoid carcinoma is the most common salivary gland malignancy and makes up between 5 and 9% of all salivary gland neoplasms. It develops most commonly in the major salivary glands, most often the parotid (45-70%). The second most common site of occurrence is the palate (18%). This tumor displays a uniform age distribution between the ages of 20 and 70 years, with a slight peak in occurrence in the 5th decade. Although it is rare before age 20, it is the most common salivary gland malignancy in the pediatric and adolescent populations. Mucoepidermoid carcinoma occurs more frequently in women than in men and in Caucasians than in African Americans.
The clinical presentation of a salivary gland malignancy can be very similar to that of a benign lesion. Often the only complaint is the presence of an enlarging but asymptomatic mass. Occasionally patients will report a rapid enlargement of a previously stable mass. Symptoms such as pain, fixation to the surrounding tissues or skin or facial paralysis are uncommon and should increase suspicion for a high-grade tumor. A mucoepidermoid carcinoma occurring in an intraoral minor salivary gland will often be mistaken for a benign or inflammatory process. It is not unusual for them to appear as a bluish or red-purple, soft and smooth growth. Others may present with a papillomatous appearance or as a hard submucosal mass, identical to a torus.
On gross inspection, some mucoepidermoid carcinomas appear well-circumscribed and may be partially encapsulated. Others are poorly defined and infiltrative. The cut surface of the tumor may contain solid areas, cystic areas or both. The cystic spaces contain viscous or mucoid material. Microscopically, these tumors are characterized by the presence of two populations of cells—the mucus cells and the epidermoid cells, the proportion of which helps to define the grade of the tumor. Low-grade mucoepidermoid carcinoma is characterized by prominent cystic structures and mature cellular elements. This tumor contains proportionally more mucus cells, which may form gland-like structures, and fewer epidermoid cells. Intermediate-grade tumors display fewer and smaller cysts and occasional solid islands of epidermoid tumor cells. Although mucus cells are still present, there is an increasing proportion of epidermoid cells and occasional keratin pearl formation. The high-grade carcinomas are hypercellular, solid tumors with noticeable cellular atypia and frequent mitotic figures. These tumors will often be mistaken for a squamous cell carcinoma and the differentiation between the two can be quite difficult. Positive immunohistochemical staining for mucin indicates a high-grade mucoepidermoid carcinoma rather than a squamous cell carcinoma.
Appropriate therapy for mucoepidermoid carcinoma depends primarily upon the stage of disease, but is also influenced by tumor grade and location. Stage I and II disease can often be treated by surgical excision alone—parotidectomy with facial nerve preservation, submandibular gland excision or wide local excision of an involved minor salivary gland. Stage III and IV disease often require more radical excision and may warrant additional intervention such as a neck dissection or postoperative radiation therapy (1,2,3,5).
Adenoid Cystic Carcinoma
Adenoid cystic carcinoma is the second most common salivary gland malignancy overall, but is the most common in the submandibular, sublingual and minor salivary glands. It occurs equally in men and women, peaks in the 5th decade of life and is more common in Caucasians.
Clinical presentation is often an asymptomatic mass, however, this tumor is more likely than others to present with pain or paresthesias. Facial paralysis remains rare, but again, may be seen more frequently with adenoid cystic than with other tumors. Minor salivary gland involvement is characterized by a submucosal mass with or without pain and ulceration.
Gross appearance is typically a well defined but not encapsulated mass that can be seen infiltrating surrounding normal tissue. Despite their name, these are solid tumors that rarely display obvious cystic spaces on the cut surface. Microscopic appearance is described as cribriform, tubular or solid. The cribriform pattern is the most common and most easily recognizable. It is often referred to as the “swiss cheese” pattern. Tumor cells are arranged iests around cylindrical spaces that may contain a mucinous or hyalinized material. Cells that are arranged in layers and form ductal structures characterize the tubular pattern. The solid pattern contains sheets of tumor cells with no intervening spaces.
Current treatment recommendations for adenoid cystic carcinoma include complete surgical resection and postoperative radiation therapy. Because of the propensity for this tumor to demonstrate perineural invasion, sacrifice of the facial nerve may be necessary for tumor eradication. Elective neck dissection is usually not indicated because this tumor rarely involves the cervical lymph nodes. Even with seemingly adequate treatment, local recurrence of adenoid cystic carcinoma is unfortunately not uncommon. Tumor recurrence rates vary in the literature but reportedly can be as high as 42%. Another problem with this tumor is its propensity for distant metastasis, the most common site being the lung. Both local recurrence and distant metastasis can develop many years after initial treatment and multiple recurrences in the same patient have been reported. Although the prognosis for complete cure is poor, the course of disease is often indolent and patients with adenoid cystic carcinoma may survive for many years before eventually succumbing to the disease (1,2,3,5).
Acinic Cell Carcinoma
Acinic cell carcinoma is the second most common parotid malignancy and the second most common pediatric salivary gland malignancy. It is a rare tumor that accounts for about 1% of all salivary neoplasms. This malignancy will typically present in the 5th decade of life and is more common in women and Caucasians. Bilateral parotid disease occurs in approximately 3% of cases.
Clinical presentation is similar to other neoplasms—often an asymptomatic enlarging mass.
Gross appearance demonstrates a mass that is well circumscribed but lacks a true capsule. The cut surface is grayish, friable, and displays solid and cystic areas. Microscopic appearance has been categorized as solid, microcystic, papillary cystic and follicular. Tumor cells are dark staining and have granular or honeycomb cytoplasm. The surrounding stroma often demonstrates a lymphoid infiltrate.
Treatment of acinic cell carcinoma includes surgical excision. Elective neck dissection is not warranted. Postoperative radiation therapy may be helpful in cases of questionable residual disease after surgery. This tumor is generally regarded as a low-grade malignancy. Early survival rates are quite good—82% at 5 years, 68% at 10 years—but this drops off to about 50% by 25 years after treatment. This is due to the fact that this tumor, like adenoid cystic, can recur locally or develop distant metastasis many years after initial treatment (1,2,3,5).
Adenocarcinoma
Adenocarcinomas of the salivary glands are rare but aggressive tumors. They tend to present in patients over 40 years of age and occur with nearly equal frequency in men and women. About half of these tumors present in the parotid glands, the minor salivary glands, particularly the palate, lip and tongue are the next most commonly affected sites.
Clinical presentation again most often involves an enlarging mass. Adenocarcinoma is different from other salivary gland neoplasms in that as many as 25% of patients will complain of pain or facial weakness at presentation.
Gross pathology reveals a firm mass with irregular borders and infiltration into surrounding tissue. It is generally a solid tumor without any cystic spaces. These malignancies can demonstrate a wide range of growth patterns and, for this reason, can be somewhat difficult to classify. However, all adenocarcinomas have in common the formation of glandular structures and they are described as grades I, II or III based upon the degree of cellular differentiation. Grade I lesions have well- formed ductal structures while Grade III lesions have a more solid growth pattern with few glandular characteristics.
Because these are more aggressive tumors, treatment for adenocarcinoma is more aggressive. Complete local excision is the mainstay of therapy. In the parotid this may include facial nerve sacrifice. In the minor salivary glands, a portion of the maxilla or mandible may have to be resected with the tumor. Although the efficacy hasn’t been definitely proven, postoperative radiation therapy does seem to be of some benefit. Lymph node metastasis is not uncommon and in patients with palpable neck disease neck dissection is warranted. Elective neck dissection should probably be reserved for patients with extensive local disease or high-grade lesions. Local recurrence rates vary in the literature but have been cited as high as 51%. Regional metastasis has been reported in 27% and distant metastasis in 26%–most often to the lung and bone. Survival is dependent on the disease stage, which takes into account the extent and location of disease as well as the histologic tumor grade. The overall cure rate at 15 years is 67% for stage I, 35% for stage II and 8% for stage III (1,2,3,5).
Malignant Mixed Tumors
Carcinoma ex-pleomorphic adenoma is the most common of three salivary neoplasms that are broadly referred to as malignant mixed tumors. It occurs when a carcinoma develops from the epithelial component of a preexisting pleomorphic adenoma. The other two tumors in this category, carcinosarcoma and metastasizing mixed tumor, are much less common. In a carcinosarcoma, the metastatic lesions contain both the stromal and epithelial elements. This is different from the carcinoma ex-pleomorphic adenoma in which only the epithelial elements are present in metastasis. The metastasizing mixed tumor refers to an otherwise benign acting pleomorphic adenoma that developes metastatic deposits of tumor.
Carcinoma ex-pleomorphic adenoma accounts for about 3.6% of all salivary neoplasms. It presents in the 6th to 8th decade of life with patients averaging 10 years older than those with pleomorphic adenomas. It occurs most often in the parotid, followed by the submandibular gland and palate. Presentation is usually a painless mass but some patients will report recent rapid enlargement of a long-standing nodule. Pain, fixation to the skin and facial weakness are variably present. The risk of malignant degeneration in a pleomorphic adenoma increases from about 1.5% in the first five years to 9.5% for adenomas present longer than 15 years. Gross pathology of carcinoma ex-pleomorphic adenoma often shows a poorly circumscribed, infiltrative, hard mass. Microscopically malignant appearing cells are present adjacent to a typical appearing pleomorphic adenoma. The malignant portion of the tumor can take the form of any epithelial malignancy except acinic cell. Most commonly this will be in the form of an undifferentiated carcinoma (30%) or adenocarcinoma (25%). This tumor tends to be more aggressive than other salivary malignancies and about 25% of patients will have lymph node metastasis on presentation. Treatment includes radical surgical resection, often in conjunction with neck dissection, and postoperative radiation therapy. Prognosis appears to be related to local extent of disease and the histologic type of the carcinoma component.
Carcinosarcomas, or true malignant mixed tumors, are very rare tumors accounting for only .05% of salivary gland neoplasms. Average age at presentation is about 60 years and men and women appear to be equally affected. The parotid is the most frequent site of occurrence. Microscopically, these tumors have both sarcomatous and carcinomatous elements. In the majority, the sarcoma is the dominating component and chondrosarcoma is the most common cell type. The carcinoma element is usually an undifferentiated or high-grade ductal adenocarcinoma. This is also an aggressive tumor and it is not uncommon for patients to have distant metastasis on presentation. Currently recommended treatment includes radical surgery, neck dissection for palpable nodes and postoperative XRT. Although efficacy has yet to be proven, chemotherapy is likely to have a role in the treatment of this disease given the high rate of distant metastasis (1,2,3,5).
Squamous Cell Carcinoma
Primary squamous cell carcinoma of the salivary glands is quite rare, accounting for about 1.6% of salivary gland neoplasms. In order to make this diagnosis, high-grade mucoepidermoid carcinoma, metastatic squamous cell to the gland or intraglandular nodes and direct extension of a squamous cell carcinoma must first be excluded. There is a 2:1 male-to-female ratio of occurrence and patients are usually over age 60. These tumors present as firm enlarging masses that are not uncommonly fixed to surrounding tissue and associated with pain or facial weakness. The gross and microscopic appearance is similar to squamous cell carcinoma of other primary sites and varies from well-differentiated with keratinization to poorly-differentiated without keratinization. Salivary gland squamous cell carcinoma displays aggressive behavior with rapid growth and early spread to regional lymph nodes. Treatment consists of surgical resection, neck dissection and postoperative radiation (1,2,3,5).
Polymorphous Low-grade Adenocarcinoma
Polymorphous low-grade adenocarcinoma (PLGA) is the second most common malignancy in the minor salivary glands and occurs most frequently in the palate, lip and buccal mucosa. This tumor typically presents in the 7th decade of life and is more common in women (67%). It presents as a painless submucosal swelling that gradually enlarges and may ulcerate and bleed. The microscopic appearance of these tumors is what gives them their name. Any of a variety of growth patterns (solid, tubular, trabecular, glandular, cribriform, cystic) can be seen within the same lesion or among different lesions. PLGA displays a tendency for perinerual and perivascular invasion, however it typically follows an indolent course. Treatment consists of conservative yet complete local excision. Postoperative radiation and neck dissection are probably not necessary. Distant metastasis has not been reported (1,2).
Clear Cell Carcinoma
Clear cell carcinoma has also been called glycogen-rich carcinoma. These are rare tumors that occur most frequently in the minor salivary glands of the palate and the parotid. They occur equally in men and women and typically present in the 6th to 8th decades of life. Microscopically, these tumors display a uniform pattern of round or polygonal cells with peripherally displaced dark nuclei and clear cytoplasm. Tumor cells may grow iests or cords separated by fibrous stroma or solid sheets of cells. Locally infiltrative growth is characteristic. Clear cell carcinomas are classified as low-grade tumors and are treated with complete local excision (1,5).
Epithelial-myoepithelial Carcinoma
Epithelial-myoepithelial carcinoma constitutes less than 1% of salivary gland neoplasms. It occurs in the 6th and 7th decades of life, in women more often than men, and typically in the parotid gland. Some studies have suggested that patients with these tumors are at increased risk for a second primary malignancy—either in the salivary glands or in a separate site (breast and thyroid have been reported). Grossly, these are well-circumscribed, multinodular firm masses with irregular cystic spaces. The microscopic appearance can be highly variable but displays a very typical biphasic character. “Subunits” of tumor growth include a surrounding thickened basement membrane, outer clear myoepithelial cells, and inner cuboidal epithelial cells lining small duct-like structures. Treatment consists of complete surgical resection. Because this tumor is so rare, little is known about whether adjuvant radiotherapy or chemotherapy is beneficial (1).
Undifferentiated Carcinoma
The undifferentiated carcinomas are uncommon but behave aggressively and have a poor prognosis compared to other salivary gland tumors. Lymphoepithelial carcinoma of the salivary glands occurs most commonly in North American and Greenland Eskimos and Asians. Among Eskimos, the parotid gland is most often affected, there is a female predominance and a familial pattern of the disease. Among Asians, the submandibular gland is the most common site and men are affected more often than women. Undifferentiated large-cell carcinoma has a bimodal age distribution with the first peak in the 6th and 7th decades of life and a second peak in the 9th decade. Men are affected more frequently than women and the parotid is the most common site. Undifferentiated small-cell carcinoma occurs most often in the parotid, in patients 50-70 years old, and with a 1.6:1 male-to-female ratio. All of these malignancies have a tendency for local recurrence, regional and distant metastasis. Treatment centers around complete surgical excision, with neck dissection for palpable disease and consideration given to postoperative radiation therapy and possibly chemotherapy (1).
Controversial Issues
Management of the N0 Neck
There is no doubt that treatment of the clinically positive neck, most often with neck dissection and postoperative XRT, is indicated in patients with salivary gland malignancies. However, there still remains no consensus on how the clinically N0 neck should be managed. Clearly, though, this issue should be carefully contemplated because we do know that patients who experience a recurrence of disease in the neck have a low likelihood of salvage. The overall incidence of clinical neck disease in parotid malignancies is 16%. The average 5-year survival for parotid malignancies is 74% wheeck nodes are not involved, this drops to 9% wheeck metastasis are present. Similarly, for the submandibular gland, the incidence of clinically positive nodes is 8%, 5-year survival in patients with a negative neck is 41%, and this drops to 9% when the neck is positive.
Many studies have been done over the years attempting to identify patient or tumor factors that increase the risk for occult neck disease. The outcomes of these studies are somewhat variable but most seem to agree that high-grade lesions and advanced primary tumor stage have an increased incidence of neck metastasis. Other factors that have been found to be significant in some studies are “high-risk” histology (undifferentiated carcinoma, squamous cell carcinoma, adenocarcinoma, high-grade mucoepidermoid carcinoma and salivary duct carcinoma), larger tumor size (>3cm), facial paralysis, patient age over 54 years, extraparotid extension of tumor and perilymphatic invasion.
In addition to deciding when to treat the N0 neck, one must also decide how to treat the N0 neck—with neck dissection or with radiation. The benefit of a neck dissection is that it provides a pathologic stage of neck disease, which helps for predicting prognosis and counseling patients. The disadvantages of a neck dissection include a longer operating time, increased potential complications, and potential functional problems or aesthetic concerns for the patient. If elective neck dissection is chosen, the type of neck dissection should be tailored to address those levels of the neck most at risk for occult disease. Parotid malignancies that develop occult neck metastasis have been shown to most commonly involve the jugular nodes in levels II, III and IV. Submandibular tumors typically involve nodes in level I, II and III. Therefore, selective neck dissection addressing these levels and sparing all normal structures would be the method of choice to surgically manage the N0 neck.
The advantage of primary irradiation of the neck is that it avoids all of the sequelae of surgery. The main disadvantage is the radiation effect upon surrounding normal tissue, which can, like surgery, cause functional problems and cosmetic concerns for the patient. Also of concern, particularly in younger patients, would be the occurrence of radiation induced second malignancies. The argument for treating the N0 neck with primary irradiation is that those factors that increase the likelihood of occult neck metastasis are essentially the same factors that are considered indications for the use of postoperative radiation to the primary tumor. Therefore, if the primary tumor already necessitates adjunctive radiation therapy then it seems reasonable to use radiation to treat the neck as well (6,7,8,9).
Fine-needle Aspiration Biopsy
The efficacy of fine-needle aspiration of salivary gland masses is well established. The accuracy, sensitivity and specificity reported in the literature vary from 84-97%, 54-95% and 86-100% respectively. It has also been established as a safe procedure and one that is well tolerated by patients. Additionally, as surgeons and cytopathologists have become more familiar with the technique, the high false-negative results seen in the past have now been reduced to below 10% in most studies. The only remaining controversy over the use of FNA for salivary neoplasms is whether or not it has any impact on clinical management. Opponents of preoperative FNA claim that regardless of the histology of a major salivary gland neoplasm, surgery will be the treatment and knowing the type of neoplasm does not change the surgical approach. Other reported arguments against FNA include the possibility of altering the tumor histopathology to the point of obscuring final pathologic diagnosis and the frequency of “inadequate” sampling. Proponents of FNA claim that it offers important information regarding the benign or malignant nature of the tumor and that this information is vital for optimal preoperative patient counseling. Knowledge of the type of tumor is also said to allow the surgeon to formulate a more thorough operative plan and avoid intraoperative surprises. Additionally, FNA is highly reliable in differentiating between neoplastic and nonneoplastic lesions. Many patients with nonneoplastic salivary gland lesions can be managed, and should be managed, without surgery. This fact alone contradicts the thinking that any salivary gland mass will be managed with surgery and that FNA will not influence patient management (10,11,12,13).
Tumorigenesis
Two hypotheses have been developed in an attempt to explain and understand the wide variety of histopathology demonstrated by salivary gland neoplasms. These hypotheses, the bicellular and multicellular theories, propose that certain cells that make up the salivary gland unit are responsible not only for normal gland cell turnover and maintenance, but also for the development of different salivary gland tumors.
The bicellular theory was first proposed by Eversole in 1971 and later supported by Regezi and Batsakis in 1977. This hypothesis states that neoplastic development within salivary glands originates from the basal cells seen in the excretory and intercalated ducts. The excretory duct stem cells are believed to give rise to squamous cell carcinoma and mucopeidermoid carcinoma. The intercalated duct stem cells are the origin of pleomorphic adenoma, Warthin’s tumor, oncocytoma, acinic cell carcinoma and adenoid cystic carcinoma. The second hypothesis, the multicellular theory, states that neoplasm development occurs from differentiated cells within the salivary gland unit. In this theory, the striated duct cells give rise to oncocytic tumors, acinar cells give rise to acinic cell carcinoma, excretory duct cells give rise to squamous cell carcinoma and mucoepidermoid carcinoma, and the intercalated duct cells and myopeithelial cells give rise to pleomorphic tumors.
Despite the prevalence of these theories in the otolaryngologic literature and teaching, little if any scientific evidence exists to support their validity. In fact, many physiologic studies have found evidence directly contrary to these hypotheses. Such evidence includes the finding that duct luminal cells, as well as basal cells, are readily capable of replication. Additionally, acinar cells, which are excluded from the histogenetic theories, have clearly been shown to enter the cell cycle. In studies of gland regeneration, two-thirds of acinar cells will replicate and participate in gland recovery while basal cells do not seem to participate in gland regeneration. Finally, several salivary gland neoplasms have been demonstrated to express the S-100 protein by immunohistochemical staining. Iormal salivary gland tissue, this protein is found only in autonomic nerve tissue, not in any secretory or duct cells. This again, argues against the idea that ductal basal cells are the only site of origin of salivary gland tumors (1,14,15).
Cancer patients often present to their physicians in a poor nutritional state. Their nutritional deficits have a significant impact on mortality, morbidity and quality of life. Head and neck cancer patients are no exception. The literature indicates that up to 57% of patients with head and neck cancer present with significant malnutrition (manifest by greater than 10% weight loss from baseline body mass). Alcohol and tobacco use frequently exacerbates this problem. Alcohol provides a large amount of simple carbohydrates without essential vitamins, proteins, and fats. These “empty calories” may actually contribute to cancer growth and further nutritional decay. Tobacco is an appetite suppressant. Moreover, head and neck cancers may cause significant trismus, odynophagia, dysphagia, and aspiration. Large tumors can actually obstruct the aerodigestive system. Treatment options for head and neck cancer include surgery, chemotherapy, and radiation therapy. Each of these interventions have side effects that contribute to malnutrition. Thus, it is especially important that patients with head and neck cancer undergo pretreatment nutritional evaluation, appropriate nutritional supplementation, and continued attention to this detail during and after treatment.
Malnutrition
Malnutrition is generally divided into two types—marasmus and kwashiorkor. The former is characterized by normal serum protein levels and total calorie deprivation from all food sources (starvation). Kwashiorkor is caused by a decrease in protein intake. Serum levels of protein are reduced. Most head and neck cancer patients present with protein-deficiency malnutrition. Thus, diminished nutrient intake, or diminished appropriate nutrient intake is one etiology of cancer malnutrition. As previously discussed, cancers of the head and neck can physically impede the intake of nourishment or cause trismus and odynophagia that limit oral intake. Alcohol and tobacco use, commonly seen in this patient group, add to the problem by providing “empty calories” devoid of essential nutrients, and suppressing appetite. Patients who consume excessive amounts of alcohol have also been shown to have a much decreased intake of fresh fruits and vegetables. A diet low in essential vitamins and minerals has been associated with increased risk of head and neck cancer. The treatment regimens for head and neck cancer often result in side effects that decrease oral intake. Surgical treatment can alter the anatomy such that chewing and swallowing can be temporarily or permanently dysfunctional. Radiation therapy and chemotherapy commonly result in mucositis, dysgeusia, anosmia, xerostomia, nausea, and vomiting. Poor dentition may also contribute by increasing difficulty with mastication. Radiation-induced dental disease can further exacerbate this.
The other factors that can lead to a malnourished state include increased nutritional losses, increased nutritional demand, and tumor-induced metabolic dysfunction. Increased nutritional losses are most commonly seen with vomiting and diarrhea, but can be caused by enterocutaneous fistulae or gastrointestinal malabsorption. Increased nutritional demands result from surgery, radiation, and chemotherapy. Pneumonia, wound infections, and sepsis can further increase nutritional demands. These demands often correspond to the time that oral nutrition is impossible or very limited, i.e. the early postoperative period, or during daily radiation treatments. The nutritional demands during this acute phase result in catabolism of stored glycogen (exhausted during the first 24 hrs) and proteins in the muscles and tissues. Energy stored in fat does not appear to be mobilized to meet the nutritional needs of this phase. After 3 to 7 days the body begins to slowly return to normal metabolism.
Finally, specific tumor-induced anorexia and metabolic dysfunction contribute to malnutrition. Anorexia of cancer is thought to result from alterations ieurotransmitters (possibly serotonin) and possibly from learned food aversions. Alterations in metabolism are profound. Most solid tumors derive their energy from glucose. They are unable to use amino acids or fat to create energy. Tumor factors (thought to include tumor necrosis factor, and interleukins IL-1, and IL-6) result in catabolism of muscle and tissue proteins which are converted to glucose in the liver and used for cell replication by cancer cells. Fat is also catabolized. Elevated levels of plasma free fatty acids are thought to be secondary to hepatic neoketogenesis and are responsible for a relative insulin insensitivity by normal body tissues. This results in a decreased ability for normal tissues to take up amino acids and further fuels gluconeogenesis which feeds the tumor.
Impact of Malnutrition
The impact of malnutrition on patient outcomes is great. Mick, et al. studied a group of patients with stage III/IV head and neck cancer treated with multiple modalities. The strongest independent predictor of survival was pretreatment weight loss. Brookes, et al. showed that head and neck cancer patients have a significant 2-year survival if they are malnourished at presentation (7.5% vs. 57%). Finally, Bertrand, et al and Van Bokhorst-de Van der Shuer showed that 7-10 days of preoperative nutrition resulted in a significant improvement in postoperative quality of life, and led to a 10% decrease in postoperative infectious complications. Patients that have lost 12-20% of their ideal body weight are at increased risk of postoperative sepsis. Malnourished patients have depressed immune systems with a particular decrease in cell-mediated immunity. This is thought to be the reason for the anergy often seen in cancer patients. It is also proposed to be the reason that malnourishment coincides with tumor size and prognosis—that a decrease in the immune system leads to unimpeded tumor growth. Cachectic patients are also frequently unable to tolerate antineoplastic therapies which results in treatment delay and higher costs.
Diagnosis
ecause of the associated risks, it is important to be able to diagnose malnutrition in head and neck cancer patients. Malnutrition has been defined as weight loss greater than 10% of ideal body weight that is associated with loss of muscle. However, there have been multiple systems for assessing malnutrition proposed. A complete history and physical in combination with the 10% “rule” is probably the most commonly used method of evaluating nutritional status. The best muscles to assess for wasting are the quadriceps femoris and the deltoid muscles. Cheilosis, stomatitis, and dry scaling skin can be indicative of vitamin deficiencies. Other parameters include anthropomorphic measurements (tricep skin fold, upper arm diameter), skin testing (for anergy), laboratory values, total lymphocyte count (patients with TLC<1700 have 5X risk of wound infection), and weight as a percentage of baseline weight. Laboratory values include albumin, prealbumin, transferrin, and retinol binding protein. Albumin is often used to evaluate nutritional status, but is handicapped by a long half-life (20 days) whereas the prealbumin, retinol binding protein, and transferring are more indicative of the present nutritional state (half life of 8 days). The creatinine-height index, prognostic nutritional index (PNI), and subjective global assessment (SGA) are all methods of identifying nutritionally deficient patients using one or more of the above parameters. Once high-risk patients are identified, immediate intervention can result in a much improved outcome.
Treatments
Patients with difficulty eating secondary to pain and anorexia can be offered medical treatment. Mucositis is common in patients receiving radiation therapy and chemotherapy. Treatment is generally with topical medications (analgesics, antifungals, coating agents, and antihistamines), and gentle local care. Dental care can address pain of dental origin and frequent sips of water, synthetic saliva, and pilocarpine can address problems of xerostomia. Chemotherapy-related nausea and vomiting have been significantly ameliorated with newer generation antiemetics such as Ondansetron and Granisetron. Patients who suffer from cancer-associated anorexia have shown good response to progestogens such as megestrol. Other agents under investigation include THC, thalidomide, melatonin, and pentoxifylline. The dysgeusia experienced by patients who undergo radiation therapy and chemotherapy usually resolves within a year of treatment. Pain management is important as maximal medical therapy may not be able to completely alleviate the pain associated with these disorders.
Once a patient has been evaluated and his risk of malnutrition identified nutritional counseling should be offered. Patients who appear to be healthy should be counseled in regards to their diet and encouraged to eat a balanced diet with emphasis on high-protein, high-calorie foods. Expectations for future treatments and their influence outrition should be discussed. Interestingly, patients who are counseled to avoid favorite foods during treatment periods seem to return to a normal diet quicker and have fewer food aversions. For patients with mild to moderate malnutrition who tolerate oral feeding, nutritional supplementation should be advised. The most complete nutritional supplementation is found in the commercially available enteral formulas. This can be fairly expensive, and is not necessary in patients who are able to chew and swallow effectively. These patients should be encouraged to eat a balanced diet with an effort to eat high-protein, high calorie foods. They might be counseled to use whole milk instead of fat-free, real mayonnaise instead of dressing, butter, eggs, meats, legumes, ice cream, and “instant breakfast” powders. These changes can significantly increase caloric intake with little change in actual volume. The patient should be invited to stop drinking alcohol and smoking tobacco.
Consulting a dietitian is appropriate whenever one identifies a patient currently malnourished or at risk of malnutrition. Their input is especially helpful when deciding the total caloric needs of a patient and when exploring the options for nutritional supplementation in patients with other medical problems. A dietitian is able to provide nutritional counseling throughout the course of a patient’s cancer treatment and give valuable treatment suggestions for the otolaryngologist—head & neck surgeon.
Patients who are judged at high risk and are unable to eat by mouth should be given enteral feeding. Placement of feeding tubes into the gastrointestinal system effectively bypasses the most common areas of feeding difficulty. Dysphagia, odynophagia, and aspiration are usually not issues once feeding is started through a nasogastric tube, gastrostomy or jejunostomy. The questions of when to initiate tube feeds and what type of tube is appropriate have been addressed by many authors. If the patient is cachectic or unable to satisfy his/her basic caloric needs by oral intake they are a candidate for supplemental tube feeds. Gastrostomy placement before XRT has been shown to prevent weight loss, treatment interruption, and dehydration. In general, a nasogastric feeding tube can be used if expected length of use is less than 30 days. These tubes irritate the nasal mucosa and are not well tolerated. They clog easily and typically require replacement every 10 days. The tip of the tube can be placed in the stomach or the small intestine. If the patient has a history of reflux, or if aspiration is a concern, the tube should be passed into the duodenum. The pyloric sphincter acts as an additional barrier to refluxing feeds. Enteral formula (hypertonic) can be instilled directly through this catheter and given in bolus form. Most authors feel that stomach feeds are more physiologic and are the first choice if aspiration risk is low.
If the patient is likely to require more than 30 days of tube feeds an enterocutaneous feeding tube is indicated. Enterocutaneous feeding tubes can be placed into the stomach or small bowel. They can be performed laporoscopically, open, under fluoroscopy, or endoscopically. When performed endoscopically, the tube can be “pushed” from the oral cavity into the stomach and through an incision in the stomach and skin, or “pulled” through a skin incision into the stomach. Complications are rare with any of the applications, though morbidity is somewhat higher for open procedures. There are case reports of cancer cells seeding the feeding tube site after endoscopic placement. This complication theoretically is avoided by “push,” open, or fluoroscopic procedures.
No matter which type of tube is used, placement of the tip into the stomach is preferred. The stomach acts as a reservoir (allows for bolus feeds) and allows for hypertonic feeds. If the patient has delayed emptying time or other gastric dysfunction (often seen in the critically ill patient) a feeding tube placed into the small bowel may be more appropriate. Other indications for jejunal feeding include proximal fistula or leak, and severe reflux of gastric contents. Jejunal feeding is associated with a decreased rate of pneumonia in critically ill patients. This is thought to be a result of less reflux aspiration. When instilling enteral formula into the small intestine bolus feeds are contraindicated. Instead, a constant rate of up to 180cc/hr is well-tolerated. One study compared nasogastric tube placement with gastrostomy tube placement one day before surgery. Those patients with tonsil or laryngeal SCCA that received a gastrostomy tube spent a significantly shorter time in the hospital (60+% reduction) (Gibson, et al.). Saunders, et al showed that patients tolerated gastrostomy tube placement long-term with high satisfaction levels. Scolapio, et al. followed patients who received a gastrostomy before starting radiation therapy. He reported a significant prevention of weight loss, treatment interruption, and hospitalization for dehydration. Enteral nutrition is well-tolerated and effective. It likely does not matter what tube is used to supply to formula, its effects are the same.
There are a wide variety of enteral formulas available. Most formulas provide 1-2 kcal/ml. In general, enteral feeding formulas can be separated into polymeric, monomeric, and disease-specific formulations. Polymeric contain carbohydrate polymers, complete proteins, and triglycerides. They can be used safely in the vast majority of patients. These formulas can be instilled in the stomach or small intestine. Monomeric formulations are essentially the breakdown products of the polymeric formula. As such, it contains carbohydrates in the form of oligosaccharides or maltodextrin, protein in the form of short peptide chains or free amino acids, and lipids as a mixture of short and long-chain triglycerides. Monomeric formulations are considered more appropriate for patients with poor absorption or other digestion dysfunction. There have beeo studies to clearly confirm the benefit of their use. Disease-specific formulas are made specific to a patient’s disease state. There are formulations for diabetes, renal insufficiency, pulmonary disease, hepatic dysfunction, and immunosuppression. Enteral feeding formulas rich in arginine, glutamine, omega-3 fatty acids, and polyribonucleotides are thought to alter immune function. This has resulted in their increased use for cancer patients. Although a met analysis of relevant studies failed to show any survival benefit in cancer patients, patients on this formula have been shown to have 50% fewer post-op infectious complications. One other important specialized enteral feeding formula is the medium-chain triglyceride formulation which is traditionally used in patients with post-operative chyle leaks (Lipisorb, Mead-Johnson, and Travasorb MCT, Clintec). Although there are formulas to calculate a patient’s daily nutritional needs, metabolic needs are generally 35 kcal/kg/day for maintenance, and 45 kcal/kg/day to support an anabolic state.
Parenteral nutrition is the feeding option of “last resort,” and should be employed only when enteral feeding is not possible or is contraindicated. Total parenteral nutrition (TPN) can be valuable when treating severely malnourished patients who need immediate treatment. This intervention is much more expensive, requires a central line, and is associated with significant complications. The formula is a hypertonic mixture of amino acids, dextrose, fat emulsions, vitamins, trace elements, and electrolytes. Insulin is often added to the formula to treat the hyperglycemia TPN can cause. This allows for automatic titration of the insulin to the amount of formula being administered. TPN requires daily electrolyte monitoring and composition adjustment. Complications include line-related problems, infection and sepsis, and metabolic complications. Patients should always be weaned off TPN before surgery as inadvertent hyper/hypoglycemia can result. Studies show improvement in postoperative morbidity in malnourished patients receiving TPN. Preoperative TPN seemed to provide the most significant improvement. When compared with enteral nutrition, TPN provided no added benefit over enteral feeds. PPN is peripheral parenteral nutrition and is a diluted form of TPN. It is generally used as an adjunct to enteral feeds.
Often, patients are noted to have aspiration or increased dysphagia with certain food consistencies. A growing number of companies now offer a full line of food products adapted to these sorts of needs. Thickened water, juices, and pureed food lines are available if the patient wishes to pursue oral feeding. Long-term enteral nutrition with occasional pleasure eating by mouth is also an option. Patients who undergo surgical or radiation therapies may have long-term nutritional challenges as a result of treatment-related dysphagia and should be evaluated in cooperation with a skilled speech language pathologist.
Alternative Medicine
When discussing nutrition with patients it is important to recognize the role of alternative medical treatments. A growing number of Americans are turning to alternative medicine to either replace or supplement traditional western medicine (estimated at 1/3 of the American population). Much of the alternative or non-western approach is based outritional supplementation. Many of these supplements have been shown to be efficacious and useful. Others have little objective data to base judgments on. It is important to communicate that no treatments currently known to the scientific world can “cure” head and neck cancer outside of the modalities of surgery, radiation, and chemotherapy. Alternative interventions can, however, alleviate symptoms, and increase quality of life for patients with cancer. One study found that 15% of patients with head and neck cancer used alternative medicine. Interestingly, patients were usually well-educated and from high socioeconomic groups. Most patients used alternative medicine in conjunction with mainstream medical treatment. Chinese medicine (acupuncture and herbs), homeopathy, naturopathy, herbal medicine, Ayurvedic medicine, massage, mind-body medicine, chiropractic manipulations, and osteopathic manipulations are all forms of alternative medical practice that might be employed to treat a patient who presents with cancer. Low-dose ginger can be used as an antiemetic (may interfere with anticoagulation and cause hypoglycemia). Of all the alternative interventions, “mind-body intervention” seems to be the most successful. Many studies have shown treatment modalities that concentrate on “mind-body intervention” are effective in helping patients tolerate the side effects of medical therapies. One study comparing patients with melanoma treated with the standard of western medical care with and without mind-body treatments showed decreased recurrence and mortality in the group receiving alternative intervention. Recently, food compounds have been identified that may have an impact on health. Several of these are currently undergoing clinical trials. It is interesting that allopathic medicine is also investigating food nutrients for possible preventional value.
Looking to the Future
Preventing cancer by changing your diet is an emerging field. Some authors have started looking at food-related substances in an effort to identify what foods might offer a protective value against head and neck cancer. Low serum levels of vitamin A or B-carotene have been associated with cancer of the head and neck and cancer of the lung. Schantz, et al. showed an increased risk of head and neck cancer in patients who ate foods deficient in cryptoxanthin, lycopene, and Vitamins C and E. He postulated that these substances might act as free radical scavengers and thus “protect” DNA from mutation. Recently, studies looking at n-3 polyunsaturated fatty acids derived from fish oils have shown some effect in patients who are immunocompromised. This resulted in development of special enteral formulas which contain arginine, dietary nucleotides, and n-3 fatty acids. Studies have shown some improvement in postoperative infection. A meta analysis of these studies, however, showed no added benefit when compared with regular enteral feeds.
Conclusion
Comprehensive care of head and neck cancer patients includes an evaluation of their nutritional status. Once a patient has been identified as suffering from malnutrition they should be assessed for their ability to take food by mouth, and their expected treatment course reviewed. Appropriate supplementation should then be provided. Enteral feeding is very successful in bypassing disease states of the upper aerodigestive system and results in improvement in treatment tolerance, post-treatment morbidity, as well as long-term quality of life and mortality. Alternative medical interventions may also be effective as adjuvant therapies. Scientists with hopes of identifying preventative substances for head and neck cancer may soon find that the best medicine we can take is the food we eat.
1. Introduction
The majority of cases of non-melanoma skin cancer cases that present to the head and neck surgeon’s office will be advanced iature. The previous review in this series detailed the general clinical pathways for treating advanced skin cancers of the head and neck. In this review, we will discuss the specifics of surgical treatment, including a discussion of surgical margins, an introduction to Mohs micrographic surgery, and a detailed outline of surgical approaches for the “difficult to treat” areas of the head and neck.
2. Surgical Margins
The concept of a ‘surgical margin’ is central to the treatment of cutaneous malignancies. The ‘surgical margin’ must be differentiated from the ‘clinical margin’, which refers to the visible edge of the tumor. Indeed, the two are intimately related, as the published recommendations for ‘surgical margins’ for various cutaneous malignancies are defined from the ‘clinical margin’ of the lesion. Importantly, meticulous evaluation and demarcation of the ‘clinical margins’ using magnification has been shown to reduce the rate of positive ‘surgical margins’ .
Published recommendations of empirical surgical margins must be seen as guideline based on the statistical probability of achieving a complete. For BCC, margin of
In regards to the issue of the size of the primary lesion, the greater the lesion diameter, the greater the surgical margin has to be in order to maximize the probability of achieving a complete excision. In a prospective study by Breuninger et al [3], BCC lesions were divided up according to size and the margin required for a 95% 5-year tumor free interval was determined. For tumors less than
The histological subtype of the lesion is also very important when planning surgical excision of a BCC lesion. Hendrix et al [4] conducted retrospective study that compared margins necessary to clear infiltrative BCC vs. nodular BCC after matching patients for tumor location and size, age, gender, type of prior treatment and number of recurrences. The average margin required to completely remove nodular BCC was
The recommended surgical margin for low-risk SCC lesions surgical margins is also
As with BCC, the size of the primary lesion significantly impacts the recommended surgical margin. Brodland et al [5] found that for SCC lesions with a diameter less than
As mentioned above, some of the more rare and aggressive tumors such as DFSP and MCC, margins of 2-3+ cm have been advocated [6-7]. This call for margins is likely borne of frustration in the face of the aggressive and insidious nature of these lesions, but is perhaps misguided in light of alternative strategies, such as intraoperative frozen section control, either through traditional surgical approaches or through Moh’s micrographic surgery.
2.1 Intraoperative Frozen Sections
In corporal lesions, using recommended surgical margins for lesion excision can usually be implemented without difficulty. Indeed, the traditional surgical excision with empiric surgical margins has been shown to achieve acceptable cure rates. However, on the head and neck, adherence to these standards is often impossible without violating aesthetic subunits, functionality, or both. Hence, most head and neck surgeons employ intraoperative frozen sections as a way to ensure negative surgical margins that are intentionally narrowed as the resection edge approaches aesthetic or functional subunits. Furthermore, most of the cases of cutaneous malignancies that present to the head and neck surgeon will be “high risk” lesions by virtue of location, size, histology, or recurrent status, and many have argued that all high-risk tumors should be excised with some form of intraoperative margin control [2]. Hence, a brief discussion of intraoperative margins is warranted.
Intraoperative margin control is a principle is used both by Moh’s micrographic surgeons and non-Moh’s approaches. For non-Moh’s approaches, there is wide variation in the method of sectioning used by pathologists, and this difference in methodology can significantly impact the efficacy of the resection. The serial cross-sectioning (bread-loafing) method of margin analysis is still widely used, but it yields suboptimal results because the margin is only sampled rather than examined in full. A recent study showed that in narrow margin resections (
To get full analysis of the margin of tumor, one must perform some type of “en face” resection of the margin, meaning that the entire peripheral margin must be excised and examined. For standard surgical approaches, this usually implies taking a
Accuracy of intraoperative frozen sections will vary according to institutions and to the lesion being analyzed. The literature shows the accuracy of frozen section to be from 71-99%, which is an alarmingly large range [11]. Some of the studies with low accuracy have been criticized because they were conducted at community hospitals where pathologists trained in dermatopathology were not available [11]. While accuracy may in fact be higher with a trained dermatopathologist reading the slides, the fact is that these specialists are not always available. This highlights the need for the surgeon to become adept in reading their own specimens, just as they are in reading their own radiographic images or other diagnostic studies.
One important principle that should always be followed is good communication between the surgeon and the pathologist with regards to specimen orientation and the definition of a “clear” vs. “close” margin. Proper specimen orientation allows the pathologist to know which side of the specimen the tumor was expected. By sending specimen in quadrants, the pathologist will be able to accurately report to the surgeon which aspect of the tumor site needs additional tissue removal, if any. In regards to the issue of “close” margins, it has been shown that there is tremendous variability between pathologists in this regard, with some calling close anything within a cell’s width away from the inked margin, and others calling close anything within one high powered field (or
2.2 Mohs Micrographic Surgery
Mohs microsurgery was initially formulated by Dr. Frederic Mohs in 1941[13] and now it is recognized as the treatment modality that provides the highest cure rate and maximal tissue conservation. A variety of techniques are successfully utilized to treat majority of malignant skin cancers. These include local excision, cryotherapy, radiation, and curettage and electrodesiccation. However without histopathologic margin evaluation they each lack the ability to define completely and confirm tumor boundaries [14].
Recurrence rate of cutaneous malignancies is determined by two factors; the type of malignancy and its anatomic location. Certain types of tumors can grow unpredictable lengthy finger-like extensions deeply or laterally from the clinically apparent lesion [15]. Tumor can follow nerve tracts, extend along bone and cartilage, or penetrate along embryonic fusion planes. The indications for Moh’s microsurgery includes: 1) recurrent tumor, 2) Tumors with aggressive histology types, 3) Tumors in high-risk locations, 4) Tumors with perineural spread, 5) Tumors with poorly defined clinical margins, 6) Tumors arising in irradiated skin, and 7) Immunosuppressed patients [15]. Besides the most common types of skin cancers (BCC and SCC), other cutaneous neoplasms can be treated successfully with Moh’s microsurgery. As mentioned above, these include DFSP [16], MCC [17], extramammary Paget’s disease [18-19], sebaceous carcinoma [20], verrucous carcinoma [21-122], and microcystic adnexal carcinoma [23-24].
The principles of Mohs micrographic surgery have not changed in the past 50 years, although the fixed–tissue technique is infrequently performed nowadays it was the originally described. The fixed-tissue and fresh-tissue techniques are similar, except that the former involves tissue fixation before excision, thus eliminating the need for anesthesia and creating a blood-free surgical field. The disadvantage is that it caot be completed in one day and immediate reconstruction is not an option. In a fresh tissue technique the frozen section laboratory is located on the premises of the surgery unit and under direct supervision of the micrographic surgeon. The tumor is first debulked. A thin specimen is then removed parallel to the bed of the resection, usually achieved by orienting the scalpel blade 45° to the skin surface towards the lesion. The specimen is then divided in to easily processed portions. Each portion is color coded to denote their exact orientation in the lesion. The frozen sections are cut horizontally from the undersurface of the tissue specimen. This method allows microscopic examination of the entire deep and peripheral surgical margin. The micrographic surgeon evaluates each section, correlates the color dyes with the tissue map, and localizes any residual tumor. The procedures are repeated for each residual tumor area until all margins are clear [14-15].
One of the limitations of Mohs micrographic surgery is that microscopic interpretation of frozen specimen sections can be more difficult than paraffin sections. An inflammatory infiltrate in the specimen may be confused with cancer cells or it may mask the presence of cancer tissue. Furthermore, technical errors with the frozen section process can occur, and these errors have been found to be the most common cause of local recurrences in Mohs micrographic surgery [15]. Another limitation of Mohs surgery is that it can be incredibly time consuming, and the statistical increase in cure rates must be correlated with the resources expended to achieve them. Finally, many head and neck surgeons argue that the tissue sparing aspect of the Moh’s approach is often ultimately negated by the need to excise healthy tissue during reconstruction procedures after the excision is completed. However, despite these detractions, it is clear from the literature that the Moh’s approach to surgical excision of cutaneous malignancies yields excellent clinical results with minimal tissue loss, and for this reason, should be understood by the head and neck surgeon.
3. Reconstruction of Skin Cancer Defects: Difficult Areas
The “reconstructive ladder” (Figure 1) is a useful concept for planning surgical reconstruction of head and neck defects. The principle concept is that reconstructive efforts should start from the safest and least invasive methods of closure while achieving optimal cosmetic outcomes. In general, the progression of reconstructive complexity is as follows: healing by secondary intention, primary closure (including delayed primary closure), skin grafting, local flaps (including use of tissue expansion), and free flaps.
Figure 1. The Reconstructive Ladder
Microvascular Free Tissue Transfer
↑
Distant Flaps
↑
Local Flaps
↑
Tissue Expansion
↑
Skin Grafts
↑
Primary Closure
↑
Healing by Primary Intention
While the “reconstructive ladder” is excellent when planning reconstruction of certain defects on the head and neck (scalp, cheek, forehead), adherence to the “reconstructive ladder” is not always advisable in specific “difficult to treat” anatomical locations. Complications such as ectropion after primary closure of lower lid defects or alar retraction in after skin grafting of nasal ala defects are good examples of how the size of a defect does not dictate the proper reconstructive course. Our goal in this section is to discuss the reconstructive principles and options for these “difficult to treat” areas.
3.1 Nasal Reconstruction
Reconstructive planning for nasal defects involves assessing the extent involvement in three principle anatomic components: the skin/soft tissue, the bone/cartilaginous framework, and the internal lining of the nose.
Skin/soft tissue
Classically, nasal reconstruction has been driven by preservation of nasal aesthetic subunits. These subunits include the nasal tip, the dorsum, the columella, and the paired sidewalls, alar lobules, and soft triangles. Subunits are described as areas where shadows from the contours of the nose fall. Importantly, if a defect occupies more than 50% of an aesthetic subunit, classic teaching is that resection and then reconstruction of the entire subunit will yield superior cosmetic results. However, some authors argue that the use of post-operative dermabrasion obviates the need for adherence to this reconstructive principle [25].
What further distinguishes nasal subunits are their topographic features (convex vs. concave), skin-soft tissue relations (fixed vs. mobile), and the skin quality (color, thickness, texture). Skin over the upper half of the nose and sidewalls is thin and non sebaceous, whereas the skin that is over the tip and ala is thicker and contains sebaceous glands. Nasal skin mobility also varies, with skin over the upper half of the nose being freely movable, whereas over the caudal half the skin is adherent to underlying cartilage and fibrofatty tissues. These tissue differences should be considered when reconstruction is planned.
Healing by secondary intent on the nose is best used on concave surfaces. Thus wounds in the medial canthus region, the nasal alar sulcus, and the nasal alar crease generally have better results than wounds of the nasal tip and dorsum when allowed to heal by secondary scar tissue contracture. The role for primary closure on the nose is limited because of skin immobility. Only small defects of the skin over the nasal dorsum and sidewalls yield satisfactory results after primary closure.
Full-thickness skin grafts (FTSGs) are useful in the reconstruction of superficial defects involving convex surfaces of the nose. This is especially true in the areas of the tip and alar lobules where tissue mobility is limited for the creation of local flaps. As far as donor sites, the tissue from the nasolabial crease is an excellent choice as it matches most closely the thickness, color, and texture of nasal skin. Postauricular skin is well suited for thin grafts. When the defect is deeper than the thickness of an FTSG, it can granulate for 7 to 14 days before scraping the granulation tissue surface and placing a delayed skin graft. Dermabrasion of the area 3 months after grafting will further improve texture match between the graft and its recipient site.
Composite grafts have also been described for selected alar rim defects. A composite skin/cartilage graft can be harvested from either the helical margin or the root of the helix. Because of the tenuous blood supply for these grafts, they are used only for defects less than 1.5cm in size. Further, allowing recipient site wound margins to granulate before grafting may increase the take of these grafts.
Local flaps provide several advantages over skin grafts iasal reconstruction, including superior contour, color, and texture match, decreased scar contracture, and greater graft survival. Some of the most common flaps and their features are discussed below.
Rhomboid: The rhomboid flap is a local flap used for dorsal and sidewall defects where the donor skin is mobile and the size of the defect is less than
Bilobed: The bilobed flap is used for dorsal midline, tip, and supratip defects of up to
Glabellar: This flap is used for defects of the upper 1/3 of the nose. The lax skin of the glabella can be transferred as a rotation, midline transposition, or island flap. When designed appropriately, closure of the donor site can be placed in a natural glabellar frown line with minimal distortion.
Dorsal Nasal: This rotation advancement flap of the dorsal nasal skin is based laterally on the angular vessels and is advanced caudally. Primarily used for nasal tip and midnasal wounds, the dorsal nasal flap requires elevation of the entire nasal dorsal skin with into the glabellar area. The superior aspect of the reconstruction is closed in a V-to-Y fashion, and the remaining skin edges are closed primarily. This flap is reliable because it is based on a fairly wide pedicle, although the resultant deformity can be quite significant.
Melolabial: Melolabial flaps take advantage of the mobile non–hair-bearing skin in the medial cheek area. The superiorly based melolabial flap can be used to repair defects of the lower two thirds of the nose, including the nasal dorsum, nasal alae, and tip. Elevation of the flap should be performed in the midsubcutaneous plane, with careful preservation of the subdermal plexus. The inferiorly based melolabial flap is most useful for wounds of the upper lip, floor of nose, and columella. The medial limb is placed along the nasolabial fold and lateral nasal crease. With both of these approaches, tacking sutures from the flap dermis to the underlying periosteum or temporary external mattress sutures may be used to recreate the nasofacial or alar-facial creases. Further, it should be noted that these are two-stage flaps, requiring a second pedicle takedown procedure. These caveats do not apply to the island melolabial flap, which allows for one-stage reconstruction and does not efface the nasofacial or alar-facial creases.
Paramedian: The paramedian forehead flap is the workhorse flap for subtotal and total nasal reconstruction. It is a true axial flap based on the supratrochlear artery. Preoperative doppler identification of the supratrochlear artery allows for the base to be narrowed to around
Bone/Cartilage Framework
Framework defects, if not repaired, can lead to not only to contour irregularities and contractures of the overlying skin and soft tissues, but also to functional impairment of the nasal airway. Hence, consideration towards framework reconstruction is essential to achieve satisfactory aesthetic and functional results.
The best material for nasal framework reconstruction is autogenous cartilage and bone. Cartilage may be used alone or in a composite graft of skin and cartilage depending on the need. Composite grafts are useful for columellar/alar repair and reconstruction. Grafts may be harvested from the conchal bowl, helical rim, or root of the helix with minimal donor site deformity. Survival of free composite grafts is unpredictable and depends on a recipient site with good blood supply, meticulous hemostasis, and careful immobilization of the graft. In addition, grafts larger than
Reconstruction of the bony nasal framework may be required to recreate the projection and shape of the nasal dorsum and base. Donor sites include calvarial bone (preferred, as membranous bone has decrease reabsorption), rib, iliac crest and inferior turbinate bone. Dorsal grafts are cantilevered to the nasal process of the frontal bone; whereas lateral grafts are fixed to the maxilla. Miniplates or lag screws are usually used for this purpose.
Allografts and homografts should be considered alternatives for situations where autograft material is not available. While a multitude of alloplastic materials have been described, their use is associated with high extrusion rates, foreign body reactions, and susceptibility to infections. Homograft tissues may also be used for nasal skeletal reconstruction, but these demonstrate a high rate of resorption, occasional warping, and a tendency to become mobile over time. Despite these disadvantages, reconstructive surgeons often have to make use of these materials when autogenous materials cannot be harvested.
Internal Lining
Resurfacing of the internal lining is needed to avoid contraction and fibrosis of the nasal airway. The restoration of this thin, vascular lining is best accomplished using similar tissue. When a defect is limited to the alar margin, adjacent nasal lining may be advanced caudally as a bipedicle flap. Other options include skin grafting of the undersurface of the covering flap, a turn-over flap to provide lining, and placement of a second local flap or composite ear cartilage graft that can provide good functional and aesthetic results. If a paramedian forehead flap is used to reconstruct a defect and nasal lining is required, pericranium associated with the distal flap can be used to replace the nasal lining. In cases of a total nasal defect, a fascial forearm flap with a turbinate or mucosal graft can be used.
Prosthetics
Prosthetics represent a reconstructive option that is frequently left out of the classic “reconstructive ladder”. However, new generation prosthetics can be a very attractive alternative to complex and multi-staged reconstruction efforts in selected individuals or in patients with massive defects, such as after total or sub-total rhinectomies. A close working relationships with a maxillofacial prosthodontist for surgical planning and patient management is essential when using prosthetics for head and neck reconstruction, as the use of modern prosthetics often calls for specific surgical manipulations that are needed for implant placement [26-27].
3.2 Lip Reconstruction
The main goals of lip reconstruction are the restoration of oral competence, maintenance of oral opening and restoration of normal anatomic relations. The techniques used to maintain these goals are discussed by region below.
Vermillion Defects
Reconstruction of the vermillion can be performed in a variety of ways. The most preferred method is through primary closure, or if very small, by secondary intention. For larger defects, lip switch procedures give excellent outcomes because of the near perfect match of tissue character and color. For large full thickness defects, the vermillion can be recreated by performing mucosal advancement flaps. Finally, a wide variety of oral mucosal and tongue flaps have been described for vermillion reconstruction.
Lower Lip Defects
Lower lip defects that are <30% of the total width of the lower lip can be closed primarily. For small defects, a simple V-shaped excision with primary closure usually suffices. For more rectangular shaped defects, techniques such as single and double barrel closures (unilateral and bilateral advancement flaps along the labiomental sulcus, respectively) and the stair-step ladder closure are good options.
For lower lip defects >30% of the total width, there are a variety of classic lip flaps that can be used for reconstruction. These include Schuchardt flaps, the Abbe flap, the Estlander flap, the Gilles fan flap, nasolabial/cheek advancement flaps, the Karapandzic flap, and microvascular free flaps. These flaps are described below.
Schuchardt Flap: This is essentially a bilateral advancement flap based on the contours of the labiomental crease, much like the “double barrel” closure described above. The principle difference is that a full-thickness wedge of tissue is removed around the labiomental crease to facilitate greater advancement of tissue for closure. This flap is used primarily for central subtotal defects of the lower lip.
Abbe Flap: The Abbe flap is a lip switch flap that borrows tissue from the opposite lip as a pedicled flap and is used mostly for central lip defects. The height of the flap should equal the height of the defect, where as the width of the flap should be approximately ½ the size of the defect. Blood supply for the Abbe flap is from branches of the labial artery which run circumferentially around the lips in the subcutaneous tissue beneath the vermilion, and they must be preserved by careful dissection in raising the flap. The pedicle is usually divided two to three weeks after the primary surgery.
Estlander Flap: This lip switch flap is similar to the Abbe flap, but is used for more lateral lesions and by design incorporates the oral commissure. The distortion to the commissure from this approach can sometimes necessitate commissuroplasty, usually performed 3 months after the primary surgery.
Gilles “Fan” Flap: This is a rotation advancement flap that is similar to the Estlander flap in that it incorporates the oral commissure into the closure. The principle difference between the two flaps is that the Gilles “fan” flap is based in the nasolabial fold. This allows for closure of defects that extend more medially. The disadvantages to this flap include microstomia, denervation and a rounded commissure.
Nasolabial/Cheek Advancement flaps: Nasolabial/cheek advancement flaps for full thickness lip defects are designed as axial-patterned flaps (based on the angular branch of the facial artery) with their medial border placed in the nasolabial folds. They can be combined with mucosal advancement flaps for reconstruction of the vermillion. Examples of these advancement flaps include the Bernard-von Burrow closure and its modification by Webster.
Karapanzic Flap: The principle advantage of the Karapanzic flap is that it preserves neurovascular structures, yielding near-normal oral sphincter function and oral competence. The flap is raised using the border of the orbicularis oris muscle as its lateral limit. After the skin incision, the subcutaneous tissue and lateral muscle border are bluntly dissected to preserve neurovascular structures. The mucosal component of the flap is next incised and the flap is then transposed. Microstomia is the principal disadvantage of this technique.
Microvascular Free Flaps: In cases of total lower lip defects, some authors have reported successful reconstruction with microvascular free flaps, including the radial forearm-palmaris longus tendon flap [28] and the anterolateral thigh-fascia lata flap [29]. The principle advantage of these flaps over adynamic flaps is that they have the ability to provide some measure of oral function.
Upper lip
Partial thickness defects of the upper lip should be closed while respecting the upper lip aesthetic subunits, which include the central philtrum, and the paired lateral units spanning from the philtral columns to the melolabial folds. As with the nose, entire replacement of a subunit may provide the best cosmetic outcome.
A useful local flap for partial thickness defects of the upper lip is the A to T flap. This technique allows for the lesion to be closed while avoiding crossing the vermillion border. If possible, the vertical scar is placed precisely at the philtral edge. The releasing incision for the A to T flap is made at the vermilion border for camouflage.
Reconstruction of defects in the philtrum are best performed with approaches that emphasize subunit preservation. This is especially true for women, where the defect cannot be camouflaged by facial hair. For partial thickness defects in this area, a full thickness skin graft from auricular skin is a good option [30]. For more extensive defects, an Abbe flap can be used for philtrum reconstruction.
Primary closure can be used for full thickness defects of the upper lip for defects less than 30% of the total width. Care should be taken when aligning the “white roll”, as even slight imperfections in alignment will be noticeable after surgery.
For upper lip defects >30% of the total width, many of the lip flaps described above can be used for reconstruction, with two main differences. First, whenever possible, any flap design for the upper lip should attempt to maintain (or reconstruct) the philtral subunit. Second, because the lower lip, not the upper, is primarily responsible for oral continence, the reconstructive goals for the upper lip are slightly different. Hence, innervated composite flaps (like the Karapanzic or microvascular free flaps) are not necessarily favored over adynamic flaps.
Commissure revisions
Any cross-lip flap that involves tissue transfer around the oral commissure (as in the Estlander and Gilles fan flap) will involve blunting of the commissure. Several methods of revision to address this issue are possible. The most simple method is to create a horizontal incision where the “neo-commissure” is to be located, and then to advance buccal mucosa over the cut edges of this defect. This approach can be complemented with minor modifications, such as removal of a triangle of skin lateral to the blunted commissure or use of pedicled vermillion flaps to make the lip look more natural.
3.3 Eyelid Reconstruction
The goals of eyelid reconstruction are to provide globe protection and to achieve acceptable aesthetic results. Achieving these goals requires a solid understanding of the complex regional anatomy, the upper and lower eyelid complexes, the medial and lateral canthal structures, and the lacrimal apparatus. Further, normative relations between these structures, such as the margin reflex distances and positional relation of medial to lateral canthus, are equally important for avoiding eyelid malposition. While review of these parameters is outside the scope of this chapter, we will cover the reconstructive strategies used for eyelid defects below.
Lower lid
Reconstructive options for anterior lamellar defects not involving the eyelid margin can be closed by secondary intention, primarily, or with local skin flaps. Partial-thickness defects smaller than
The principle strategies for reconstructing full thickness lower eyelid defects include primary closure, lateral cantholysis, Tenzel flaps, free composite grafts, the modified Hughes procedure, and the Mustarde cheek advancement flap. These are discussed below:
Primary Closure: With full thickness lower lid defects, primary closure is an option provided that the defect is limited to 30% of the total lid width (or up to 45% of the lid width in elderly patients with lax skin). An important surgical technique for direct lid closure is to fashion the defect into a pentagon by making perpendicular incisions along the lid margin and then extending a wedge excision below the tarsus. This will facilitate more precise lid margin closure. Full thickness lid defects must be closed in a layered fashion, separately addressing the tarsus, grey line, and overlying skin. Improper alignment or excessive tension can lead to wound dehiscence and eyelid notching.
Lateral Cantholysis: As a general rule, performing cantholysis will yield an additional
Tenzel Flap: This is a semicircular musculocutaneous rotation flap raised from the lateral canthal skin that is then advanced medially and can be used for defects of up to 60% of the lower lid width. Importantly, the semicircular arc must extend above the lateral canthal angle to ensure elevation of the lower eyelid during wound healing. Once the flap is rotated into position and sutured, attachment of the lateral canthus and flap to the lateral orbital rim is performed to achieve lateral support for the graft. For large defects, insertion of autologous cartilage or the use of a strip of periosteum from the lateral orbital rim will provide additional support. The next step is to advance conjunctiva from the inferior fornix to cover the posterior surface of the skin muscle flap, thereby maintaining a lubricating mucosal surface over the globe. Skin closure of the donor site is the final step.
Composite Free Grafts: Free composite grafts are used for posterior lamellar reconstruction and are therefore performed in combination with local musculocutaneous flaps for the anterior lamellar portion of the defect. One of the most widely used composite grafts is the tarsoconjunctival graft. This graft is harvested from the upper eyelid tarsus of the opposing eyelid. A marginal
Modified Hughes Procedure: This is a two-staged tarsoconjunctival bridge flap from the upper eyelid and is suitable for defects greater than 50% of the lower eyelid. In this procedure, the upper lid tarsus and conjunctiva are dissected away from the underlying muscular structures up to the level of the Whitnall ligament. Importantly, as with the tarsoconjunctival free graft, a
Mustarde Cheek Rotation Flap: This advancement rotation flap is useful for sub-total or total lower eyelid defects. Flap design considerations include an adequately high arc above the lateral canthus to ensure good positioning of the lateral canthal angle and to prevent excess flap sagging. It should be noted that this flap does not incorporate orbicularis function, so that lower lid tone must be established through static mechanisms. This flap may also entail separate posterior lamellar reconstruction, such as with a free tarsoconjunctival graft, a nasal septal cartilage graft, or with mucous membrane.
As with lower lid defects, isolated anterior lamellar defects can be treated by secondary intention, primary closure, and local skin flaps. Similarly, for full thickness defects of the upper lid that are 30-50% of the lid width, layered primary closure with upper lateral canthotomy and cantholysis (if needed) can be performed as described above for the lower lid. For larger defects, there are several maneuvers for upper lid reconstruction, including the tenzel flap, the sliding tarsoconjunctival flap, composite free grafts, and the Cutler-Beard bridge flap:
Tenzel flap: This is performed as described above for the lower lid, except that the arc of the semicircular flap is extended inferiorly from the lateral canthal angle.
Sliding Tarsoconjunctival Flap: This composite rotation flap is used for isolated medial or lateral defects. The concept is to borrow a portion of the intact lid for posterior lamellar reconstruction as a pedicled rotation flap. For this procedure, a strip of the intact tarsus is split
Composite Free Grafts: Performed as described above for the lower lid.
Cutler-Beard Flap: This inferior based skin-conjunctival flap is used for defects involving more than 50% of the upper eyelid. A full thickness incision is made through the skin of the lower eyelid 1-
Medial Canthus
Medial canthal reconstruction is fairly straightforward if the defect does not involve the medial canthal tendon or the lacrimal apparatus. Because the medial canthal region is convex, lesion less than
Reconstruction becomes much more complex when the deeper structures are involved. Failure to properly address the medial canthal tendon can result not only in lid laxity, but also in a dysfunctional lacrimal system. For medial canthal tendon repair, the guiding reconstructive principles are an accurate assessment of the extent of lid tension, correct anchorage to the medial periosteum (i.e. the anterior lacrimal crest), and meticulous avoidance of the angular vein and lacrimal sac [32].
Lacrimal Drainage System Reconstruction
If the lacrimal system is disturbed during cancer resection, there are several reconstructive maneuvers that can be considered. First, it should be noted that the superior cannaliculus only marginally contributes to tear drainage and defects do not necessarily require repair. Inferior cannaliculus defects, on the other hand, should be repaired. The most common method is by marsupialization with silicon stenting. The tubing is typically left in place for weeks to months. For extensive lesions, conjunctivorhinostomy via a pedicled composite graft may be warranted, although this will only permit passive draining of the lacrimal system [33]. In cases of persistent post-operative epiphora beyond one year, dacryocystorhinostomy can be performed.
4. Conclusion:
In this review, we discussed the surgical treatment and reconstructive strategies for NMSC of the head and neck. As head and neck surgeons, we should expect that the cases of NMSC that are referred to us will either be advanced iature or will be located in “difficult to treat” areas. We hope that this review will help the surgeon or surgical student to be better prepared for these complex patients as they arrive to our clinics.
