Dermatologic Manifestations of Sebaceous Carcinoma Workup

Updated: Mar 22, 2019
  • Author: Wesley Wu, MD; Chief Editor: Dirk M Elston, MD  more...
  • Print

Approach Considerations

If a sebaceous carcinoma is initially suspected, a biopsy should be performed. After histopathologic diagnosis of a sebaceous carcinoma, various risk factors should be reviewed, including pagetoid spread, multicentricity, size, growth pattern, lymphovascular and perineural spread, and involvement of one or both eyelids. If high-risk features are present, multidisciplinary consultation is recommended as well as consideration of staging.

Moreover, Muir-Torre syndrome should be suspected in all sebaceous carcinomas, and this can be evaluated by family history of early visceral malignancies and immunohistochemistry staining of biopsy specimens for loss-of-mismatch-repair genes. If either of these two is positive, it should be suggested that the patient consider geneticist consultation. Regardless, all patients with sebaceous carcinoma should undergo age-appropriate cancer screening. [68]


Laboratory Studies

To rule out metastatic disease, baseline studies including liver function tests, electrolyte levels, and a complete blood cell count may be considered and may help establish a baseline for future care. Normal results of these tests also help to rule out any tumors associated with Muir-Torre syndrome.

More detailed studies can be directed by these findings.


Imaging Studies

No formal guidelines exist regarding the role of imaging in further evaluating sebaceous carcinoma. Chest radiography may be performed to rule out metastatic disease and to establish a baseline for future care. Isolated reports recommend the use of computed tomography (CT) scanning, magnetic resonance imaging (MRI), or positron emission tomography (PET) scannning for patients with clinically or histologically aggressive features, frank regional lymphadenopathy, or a positive sentinel lymph node biopsy. [69, 70, 71, 72] Suspicion for lymph node and orbital involvement may warrant orbital CT scanning or MRI; ultrasonography of the parotid, submandibular, and cervical nodes; and fine-needle aspiration biopsy of frank lymph nodes. [73]


Other Tests

A systemic evaluation includes a complete medical and family history and a physical examination, including a detailed ophthalmologic examination, palpation of the lymph nodes, a thorough skin examination, and a review of systems.

A scoring system developed by Roberts et al may be useful in identifying patients with sebaceous neoplasms at risk for Muir-Torre syndrome, weighing in age at diagnosis, number of sebaceous neoplasms, and personal or family history of Lynch syndrome–related cancer. [74]

Deletion or mutation of mismatch repair genes MLH1, MSH2, MSH6, PMS2, and EPCAM may be tested on tumors via immunohistochemistry, similar to sebaceous adenoma. However, their sensitivity in sebaceous carcinoma has been reported to be less than that of other sebaceous neoplasms. [74, 75]

Evaluation for Muir-Torre syndrome includes a preliminary rectal examination, colonoscopy or barium enema, and a first-morning urine for cytologic analysis. Colorectal carcinoma is the most common visceral malignancy in Muir-Torre syndrome. [16] Most of these malignancies occur proximal to the splenic flexure, and, thus, digital examination and flexible sigmoidoscopy would be inadequate to aid in the diagnosis. The urine cytologic analysis is used to screen for genitourinary malignancy.

An autosomal recessive subtype of Muir-Torre syndrome, accounting for up to 35% of tumors in syndromic patients, has been described. [76] In Muir-Torre syndrome type II, biallelic inactivation of MYH, a base excision repair gene, leads to later-onset development of internal malignancy and gastrointestinal polyposis. [77] Unlike the predominant form of Muir-Torre syndrome, genetic analysis in this second subtype does not show microsatellite instability and would require referral to a geneticist for further workup and surveillance.

Noninvasively, meibography may be helpful in differentiating chalazion from sebaceous carcinoma and mapping the latter. The carcinoma has been shown to have higher reflectivity over an irregular and marginated lesion around the nodule, especially when pagetoid spread is present. [78]



Successful diagnosis results from clinic suspicion and performing an adequate biopsy.

A full-thickness eyelid biopsy is generally recommended in cases in which a papular or nodular primary tumor is evident. [11, 79]

Some authors have recommended fine-needle aspiration for primary and metastatic sebaceous gland carcinoma, [80, 81] but a full-thickness surgical biopsy is mandatory if the results are negative or equivocal. [82]

Approximately 50% of patients have clinically inapparent extension of tumor cells in the surrounding epidermis, termed pagetoid spread. This may extend considerable distances beyond the main body of the tumor. Conjunctival map biopsies are recommended to delineate the presence and extent of pagetoid spread. [83]


Histologic Findings

Histology is the criterion standard for diagnosis of sebaceous carcinoma. Sebaceous gland carcinoma demonstrates disordered invasion of the dermis by lobules of poorly defined sebaceous cells (see image below) or basaloid and squamoid growth patterns. [84] Lobules may form sheets of basaloid tumor cells, but no peripheral palisading or clefting is present. The lesions have atypical mitosis, asymmetry, poor circumscription, and infiltrative borders. Necrosis in lobule centers may be prominent. [85] Four patterns may be recognized: lobular, comedocarcinoma, papillary, and mixed. [32]

Irregular lobules and sheets of atypical sebaceous Irregular lobules and sheets of atypical sebaceous cells (20x magnification).

Sebocytes tend to have multivacuolated clear cytoplasm, causing the nucleus to be scalloped from the lipid invasion. [17] In many cases, moderate-to-severe atypia can be found, as well as a high nuclear/cytoplasm ratio and a perinuclear halo, identified in all 30 cases presented by Izumi et al. [17] Pleomorphism is not uncommon, and large, bizarre, multinucleated cells may be randomly distributed throughout the lesion. [85] In some cases, well-developed sebocytes can be identified; in a smaller number of cases, sebaceous duct differentiation can be seen. [17]

Sebaceous carcinoma can be stained positively with oil red-O or Sudan black, which are specific for cytoplasmic fat, but epithelial membrane antigen (EMA) immunoperoxidase staining may be a better supplemental stain for confirming sebaceous differentiation. [86] Adipophilin, a monoclonal antibody against an intracellular lipid droplet surface protein, was found to have a greater ability to highlight cytoplasmic lipid vesicles than Oil Red O, and a sensitivity of 82-100%, depending on the differentiation of the sebaceous carcinoma. A membranous vesicular staining pattern of adipophilin is the most specific for sebaceous neoplasms and was shown to be negative in 100% of basal cell and squamous cell carcinomas in 43 control cases. [85] An annular staining of adipophilin in immature sebaceous cells contrasts with a more granular staining pattern in basal cell and squamous cell carcinomas. [87] In addition, cytokeratin, Ber-EP4, cyclooxygenase 2, peroxisome proliferator-activated receptor gamma, and androgen-receptor stains are positive. Sebaceous carcinomas also express more proliferation markers like p53 and Ki-67, but reduced antiapoptotic markers such as bcl-2 and p21. Sebaceous carcinomas do not express carcinoembryonic antigen, S100 protein, or gross cystic disease fluid protein. [87, 88]

In evaluating for Muir-Torre Syndrome, microsatellite mismatch repair gene instability is evaluated. Germline mutations include MSH2 (>90%), MLH-1 (< 10%), MSH-6, and PMS-2. [89] Cystic histopathologic changes have also been associated with Muir-Torre Syndrome. [90]

Sebaceous gland carcinoma may also exhibit clinically inapparent extension beyond the obvious tumor within the adjacent epithelia. Cells seen in the adjacent epithelia, often appearing to be separate from the main tumor, are known as pagetoid spread. Intraepithelial cells exhibit nuclei that are larger than neighboring keratinocytes. This typically occurs within the conjunctivae, but it can also occur in the adjacent skin or the cornea. This phenomenon is seen in approximately 40-80% of reported series. [11] The significance of these pagetoid cells is unclear, with some authors reporting a worse prognosis when present [18] and others reporting no significant difference in outcome when present. Given the possibility that these cells represent tumor infiltration rather than premalignant or reactive cells, a conjunctival map biopsy to delineate the presence and the extent of pagetoid spread seems warranted. [83]