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Dermatologic Manifestations of Sebaceous Carcinoma Workup

  • Author: Wesley Wu, MD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Apr 15, 2016
 

Laboratory Studies

Baseline studies include liver function tests, electrolyte levels, and a complete blood cell count to rule out metastatic disease and to 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.

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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.[62, 63, 64, 65]

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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.[66]

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.[66, 67]

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.[15] 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.[68] 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.[69] 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.[70]

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Procedures

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, 71]

Some authors have recommended fine-needle aspiration for primary and metastatic sebaceous gland carcinoma,[72, 73] but a full-thickness surgical biopsy is mandatory if the results are negative or equivocal.[74]

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.[75]

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Histologic Findings

Histology is the gold 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/squamoid cells.[76] 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.[77]

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.[16] 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.[16] Pleomorphism is not uncommon, and large, bizarre, multinucleated cells may be randomly distributed throughout the lesion.[77] In some cases, well-developed sebocytes can be identified; in a smaller number of cases, sebaceous duct differentiation can be seen.[16] 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.[78] 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.[77]

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[17] 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.[75]

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Contributor Information and Disclosures
Author

Wesley Wu, MD Resident Physician, Department of Dermatology, Baylor College of Medicine

Wesley Wu, MD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery, Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

Mohsin R Mir, MD Director, High Risk Skin Cancer Clinic, Assistant Professor, Mohs Surgery, Laser and Cosmetic Surgery, Department of Dermatology, Baylor College of Medicine

Mohsin R Mir, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

John G Albertini, MD Private Practice, The Skin Surgery Center; Clinical Associate Professor (Volunteer), Department of Plastic and Reconstructive Surgery, Wake Forest University School of Medicine; President-Elect, American College of Mohs Surgery

John G Albertini, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery

Disclosure: Received grant/research funds from Genentech for investigator.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Kelly M Cordoro, MD Assistant Professor of Clinical Dermatology and Pediatrics, Department of Dermatology, University of California, San Francisco School of Medicine

Kelly M Cordoro, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Medical Society of Virginia, Society for Pediatric Dermatology, Women's Dermatologic Society, Association of Professors of Dermatology, National Psoriasis Foundation, Dermatology Foundation

Disclosure: Nothing to disclose.

Acknowledgements

Amy Lynn Basile, DO, MPH Sun Coast Hospital/Largo Medical Center, Largo, Florida

Amy Lynn Basile, DO, MPH is a member of the following medical societies: American Medical Association, American Osteopathic Association, and American Osteopathic College of Dermatology

Disclosure: Nothing to disclose.

James M Spencer, MD Professor of Clinical Dermatology, Mount Sinai School of Medicine, New York; Private Practice, Spencer Dermatology, St Petersburg, Florida

James M Spencer, MD is a member of the following medical societies: American Academy of Cosmetic Surgery, American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, American Dermatological Association, American Medical Association, American Society for Dermatologic Surgery, American Society for Laser Medicine and Surgery, and International Society for Dermatologic Surgery

Disclosure: Graceway Pharmaceutical Honoraria Speaking and teaching; Sanofi Aventis Honoraria Consulting; Medicis Grant/research funds Independent contractor; Peplin Grant/research funds Independent contractor; Leo Pharmicuticals Honoraria Board membership

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