Sebaceous Adenoma Workup
- Author: Dirk M Elston, MD; Chief Editor: William D James, MD more...
Appropriate laboratory testing for possible occult internal malignancies, such as gastrointestinal tract, hematologic, or laryngeal carcinomas, is indicated. The following laboratory tests can be of diagnostic value if patients present with cutaneous signs of Muir-Torre syndrome:
Sigmoidoscopy may be performed to screen for colonic polyposis and colonic carcinoma.
Perform endoscopy to check for an occult gastric carcinoma.
Serum carcinoembryonic antigen values are frequently increased in patients with colonic carcinomas.
A complete blood cell count assists in detecting hematologic malignancies.
Bone marrow examination may be needed to further delineate a hematologic malignancy.
Laryngoscopy with biopsy examination of any suspicious lesions can rule out an occult laryngeal carcinoma.
Abdominal CT scanning and MRI assist in detecting an occult internal malignancy, such as kidney and urothelial cancers, in patients with Muir-Torre syndrome.
A biopsy of skin tumors performed for histopathologic examination provides an accurate diagnosis of sebaceous neoplasms, including sebaceous adenomas.
Histopathologic examination of specimens obtained from polypectomy and laryngoscopy of patients with suspected Muir-Torre syndrome confirms the presence or the absence of occult internal malignancy. Peripheral blood smear, bone marrow examination, and lymph node biopsy may assist in detecting an associated hematologic malignancy in these patients.
Controversy surrounds the classification of sebaceous neoplasms. Some authors maintain that all lesions called sebaceous adenoma are, in fact, sebaceous carcinoma. Their arguments are largely based on histologic findings, rather than evidence concerning tumor biology or behavior. Until evidence suggests that these lesions are capable of behaving in a malignant fashion, classifying them separately from sebaceous carcinoma may be preferable. Complete excision of all sebaceous tumors is indicated.
The characteristic microscopic features of classic sebaceous adenoma are described below. The tumor is multilobulated with frequent connection to the surface epidermis, attenuating or replacing it. At low-power view, sebaceous adenoma is sharply demarcated from the surrounding tissue (see first image below), with a proliferation of variously sized sebaceous lobules consisting of central, larger, mature sebaceous cells (sebocytes); peripheral, smaller, undifferentiated, germinative basaloid cells (see second and third images below); and transitional cells.
The sebocytes contain pale-staining, foamy-to-bubbly cytoplasm, and central, crenated, hyperchromatic nuclei. The smaller, germinative cells contain round-to-oval, vesicular nuclei and basophilic cytoplasm (see image below).
The transitional cells show more eosinophilic cytoplasm. The ratio of basaloid and transitional cells to sebocytes varies, but the lesion is traditionally defined as a sebaceous adenoma if 50% or more of the cells are sebocytes. The cellular lobules of sebaceous adenoma sometimes comprise ductal structures with holocrine secretion, which may result in occasional cystic degeneration or formation of intralesional cysts (see image below). Nuclear hyperchromatism, prominent nucleoli, and mitotic activity are rarely observed in sebaceous adenoma lesions.
In both benign and malignant sebaceous proliferations, the characteristic bubbly cytoplasmic profile of the mature sebocyte is maintained. Epithelial membrane antigen (EMA) staining in these tumors is comparable to that seen in non-neoplastic sebaceous epithelium, in that cytoplasmic lipid vesicles are rimmed by EMA reactivity.
To date, specific markers of sebaceous differentiation have not been described. Sebaceous and sweat gland neoplasms do share diagnostically relevant determinants, such as CD15 and BerEP4. However, using an antibody panel directed at EMA, S-100 protein, and carcinoembryonic antigen (CEA) allows differentiation between sebaceous and sweat gland neoplasms in most instances, the former staining positive for EMA, while S-100 protein and CEA decorate sweat gland epithelium.
Cytokine 19 has been found to be useful for separating sebaceous tumors from basal cell carcinomas. GATA3 is positive in many epithelial tumors. It may help distinguish sebaceous adenoma from acrospiromas, but not from basal cell carcinoma or sebaceous carcinoma.
The Muir-Torre variant of sebaceous adenoma tends to show more prominent cystic change, peripheral-disposed basaloid, germinative-type cells, often with mild nuclear pleomorphism, distinct nucleoli, and moderate mitotic activity. Note that patients with Muir-Torre syndrome (see image below) frequently present with sebaceous adenomas with classic histologic features of solitary tumors. No histologic features of sebaceous adenoma can reliably pinpoint an association with Muir-Torre syndrome, but loss of nuclear staining for MLH-1 or MSH-2 is highly suggestive of the syndrome. These tests are performed by the immunoperoxidase method.[17, 18, 19]
Neoplasms with sebaceous differentiation have many and disparate morphologic features because of different degrees of differentiation within the same tumor. Thus, the classification of these tumors can sometimes be difficult and confusing, which has resulted in the use of various histologic diagnostic terms in the literature. The differential features are listed below.
In contrast to sebaceous hyperplasias, sebaceous adenomas contain a mix of 2 cell types (ie, sebocytes and germinative cells). However, sebaceous hyperplasia consists of hyperplastic sebaceous lobules, sebocytes (see image below), and, peripherally, 1 or 2 cell layers of germinative epithelium that sometimes proliferates around dilated follicular ducts.
Sebaceous carcinomas differ from sebaceous adenomas by the presence of dermal aggregates of markedly atypical and poorly differentiated polyhedral tumor cells separated by fibrovascular stroma. The central portion of the cell nests frequently undergoes necrosis, resulting in a comedo pattern on scanning microscopy. The bubbly cytoplasm or intracellular compartmentalized vacuoles in sebaceous carcinoma are not as conspicuous as those seen in sebaceous adenomas.
In sharp contrast to benign sebaceous adenomas, sebaceous carcinomas contain dermal aggregates of markedly atypical, poorly differentiated, polyhedral tumor cells separated by fibrovascular stroma. The presence of tumor cells with sebaceous differentiation requires special histochemical techniques, such as oil red O or Sudan IV stains, on fresh tissue and EMA immunostains in paraffin-embedded tissue to highlight their presence. Sebaceous carcinomas differ from Merkel cell carcinoma (another poorly differentiated skin cancer) in the negative expression of CK20 and neuron-specific enolase (NSE) and positive EMA on immunohistochemical examination.
Sebaceous epitheliomas share many histologic features of sebaceous adenomas, except for the presence of more than 50% of cells of the smaller, germinative, basaloid type.
Some use the term basal cell carcinoma with sebaceous differentiation as a synonym for sebaceous epithelioma because the histologic features of these lesions can be difficult to distinguish; however, the former exhibits more of the histologic criteria of basal cell carcinoma.
Sebaceomas are benign cutaneous adnexal neoplasms with complex histologic differentiating features, including sebaceous epithelioma, trichoepithelioma, and dermal duct tumor.
Sebomatricoma is a term that has been suggested to include all benign tumors with sebaceous differentiation, including sebaceous hyperplasia, sebaceous adenoma, sebaceoma, and sebaceous epithelioma.
MLH-1 and MSH-2 immunostains can be applied to paraffin-embedded sections. Loss of expression suggests microsatellite instability and Muir-Torre syndrome.
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