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Sebaceous Adenoma Workup

  • Author: Dirk M Elston, MD; Chief Editor: William D James, MD  more...
 
Updated: Jan 15, 2016
 

Laboratory Studies

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.
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Imaging Studies

Abdominal CT scanning and MRI assist in detecting an occult internal malignancy, such as kidney and urothelial cancers, in patients with Muir-Torre syndrome.

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Procedures

A biopsy of skin tumors performed for histopathologic examination provides an accurate diagnosis of sebaceous neoplasms, including sebaceous adenomas.[13]

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.[14] Peripheral blood smear, bone marrow examination, and lymph node biopsy may assist in detecting an associated hematologic malignancy in these patients.

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Histologic Findings

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.

Low-power view of a photomicrograph of sebaceous a Low-power view of a photomicrograph of sebaceous adenoma. Note the dome-shaped elevation of the epidermal surface, the sharp circumscription from the adjacent dermal tissue, and the slight central cystic appearance with eosinophilic secretory material. Patients with sebaceous tumors showing more prominent cystic change have been found to have DNA abnormalities that are linked to a higher risk of the development of internal malignancies at a later date.
A medium-power view of the well-differentiated SA A medium-power view of the well-differentiated SA on the forehead of a 64-year-old man, showing proliferation of well-differentiated sebaceous lobules with central, larger, mature sebocytes and peripheral, smaller, less-differentiated, basaloid, germinative cells. Note that the sebaceous lobules are connected to the overlying epidermis and are slightly off-center in this field; a collection of eosinophilic, pink-colored, keratinous material is present in a dilated follicular ostium within the tumor (hematoxylin and eosin, original magnification X75). In contrast to a sebaceous hyperplasia, a sebaceous adenoma such as seen in this microscopic field contains sebaceous lobules with a 2-cell type and not a single-cell type of sebocytes as seen in the former. The neoplasm was completely removed, with no known recurrences to date.
Higher-power view of a photomicrograph of a sebace Higher-power view of a photomicrograph of a sebaceous adenoma. Note the intermingled 2 cell types, ie, well-differentiated pale-staining sebocytes containing vacuolated (bubbly) cytoplasm and smaller, darkly stained, basaloid, less-differentiated matrix cells. An occasional mitotic figure (arrow) was present. The tumor was completely excised, and no recurrence was noted in this patient after 5 years of follow-up (hematoxylin and eosin, original magnification X200).

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).

A close-up, higher-power view of the same sebaceou A close-up, higher-power view of the same sebaceous adenoma. The cytologic details are evident. Notice the predominant, larger sebocytes (arrow) containing pale-staining, bubbly cytoplasm (intracytoplasmic compartmentalization) and a few smaller, basaloid, germinative cells of pilosebaceous structures. The nuclei are vesicular without overt pleomorphism or mitotic activity (hematoxylin and eosin, original magnification X300).

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.

Multiple sebaceous neoplasms on the skin of the ch Multiple sebaceous neoplasms on the skin of the chest and the trunk of a 62-year-old man. The tumors were biopsy-proven sebaceous tumors with varying degrees of sebaceous differentiation. The patient was found to have a well-differentiated adenocarcinoma of the colon by subsequent colonoscopy, CT scan, and MRI examination.

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.[15]   GATA3 is positive in many epithelial tumors.  It may help distinguish sebaceous adenoma from acrospiromas, but not from basal cell carcinoma or sebaceous carcinoma.[16]  

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]

Multiple sebaceous neoplasms on the skin of the ch Multiple sebaceous neoplasms on the skin of the chest and the trunk of a 62-year-old man. The tumors were biopsy-proven sebaceous tumors with varying degrees of sebaceous differentiation. The patient was found to have a well-differentiated adenocarcinoma of the colon by subsequent colonoscopy, CT scan, and MRI examination.

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.

Multiple sebaceous neoplasms on the skin of the ch Multiple sebaceous neoplasms on the skin of the chest and the trunk of a 62-year-old man. The tumors were biopsy-proven sebaceous tumors with varying degrees of sebaceous differentiation. The patient was found to have a well-differentiated adenocarcinoma of the colon by subsequent colonoscopy, CT scan, and MRI examination.

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.[20]

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.[21]

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.[22]

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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Contributor Information and Disclosures
Author

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.

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.

Warren R Heymann, MD Head, Division of Dermatology, Professor, Department of Internal Medicine, Rutgers New Jersey Medical School

Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Grace F Kao, MD Clinical Professor of Dermatopathology, Department of Dermatology, University of Maryland School of Medicine and George Washington University Medical School; Director, Dermatopathology Section, Department of Pathology and Laboratory Medicine, Veterans Affairs Maryland Healthcare System, Baltimore, Maryland

Grace F Kao, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, International Society of Dermatopathology

Disclosure: Nothing to disclose.

Acknowledgements

The author wishes to thank G. William Moore, MD, PhD, and Lawrence A. Brown, MD, for assistance in reviewing and editing the manuscript and for technical support.

References
  1. Mehregan AH, Pinkus H. Life history of organoid nevi. Special reference to nevus sebaceus of Jadassohn. Arch Dermatol. 1965 Jun. 91:574-88. [Medline].

  2. Takayama K, Usui Y, Ito M, Goto H, Takeuchi M. A case of sebaceous adenoma of the eyelid showing excessively rapid growth. Clin Ophthalmol. 2013. 7:667-70. [Medline]. [Full Text].

  3. Ito K, Sato S, Nishijima A, Hiraga K, Hidano A. Melanogenic melanocytes in human sebaceous glands. Experientia. 1976 Apr 15. 32(4):511-2. [Medline].

  4. Ormsby AH, Snow JL, Su WP, Goellner JR. Diagnostic immunohistochemistry of cutaneous metastatic breast carcinoma: a statistical analysis of the utility of gross cystic disease fluid protein-15 and estrogen receptor protein. J Am Acad Dermatol. 1995 May. 32(5 Pt 1):711-6. [Medline].

  5. Swanson PE. Monoclonal antibodies to human milk fat globule proteins. Wick MR, Siegal GP, eds. Monoclonal antibodies in diagnostic immunohistochemistry. New York, NY: Marcel Dekker; 1988. 227-84.

  6. Bayer-Garner IB, Givens V, Smoller B. Immunohistochemical staining for androgen receptors: a sensitive marker of sebaceous differentiation. Am J Dermatopathol. 1999 Oct. 21(5):426-31. [Medline].

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  8. Muir EG, Bell AJ, Barlow KA. Multiple primary carcinomata of the colon, duodenum, and larynx associated with kerato-acanthomata of the face. Br J Surg. 1967 Mar. 54(3):191-5. [Medline].

  9. Torre D. Multiple sebaceous tumors. Arch Dermatol. 1968 Nov. 98(5):549-51. [Medline].

  10. Ollila S, Fitzpatrick R, Sarantaus L, et al. The importance of functional testing in the genetic assessment of Muir-Torre syndrome, a clinical subphenotype of HNPCC. Int J Oncol. 2006 Jan. 28(1):149-53. [Medline].

  11. Rütten A, Burgdorf W, Hugel H, et al. Cystic sebaceous tumors as marker lesions for the Muir-Torre syndrome: a histopathologic and molecular genetic study. Am J Dermatopathol. 1999 Oct. 21(5):405-13. [Medline].

  12. Suspiro A, Fidalgo P, Cravo M, et al. The Muir-Torre syndrome: a rare variant of hereditary nonpolyposis colorectal cancer associated with hMSH2 mutation. Am J Gastroenterol. 1998 Sep. 93(9):1572-4. [Medline].

  13. Marques-da-Costa J, Campos-do-Carmo G, Ormiga P, Ishida C, Cuzzi T, Ramos-E-Silva M. Sebaceous adenoma: clinics, dermatoscopy, and histopathology. Int J Dermatol. 2014 Oct 14. [Medline].

  14. Roberts ME, Riegert-Johnson DL, Thomas BC, Rumilla KM, Thomas CS, Heckman MG, et al. A clinical scoring system to identify patients with sebaceous neoplasms at risk for the Muir-Torre variant of Lynch syndrome. Genet Med. 2014 Sep. 16(9):711-6. [Medline].

  15. Heyl J, Mehregan D. Immunolabeling pattern of cytokeratin 19 expression may distinguish sebaceous tumors from basal cell carcinomas. J Cutan Pathol. 2008 Jan. 35(1):40-5. [Medline].

  16. Mertens RB, de Peralta-Venturina MN, Balzer BL, Frishberg DP. GATA3 Expression in Normal Skin and in Benign and Malignant Epidermal and Cutaneous Adnexal Neoplasms. Am J Dermatopathol. 2015 Dec. 37 (12):885-91. [Medline].

  17. Smith J, Crowe K, McGaughran J, Robertson T. Sebaceous adenoma arising within an ovarian mature cystic teratoma in Muir-Torre syndrome. Ann Diagn Pathol. 2011 Jun 16. [Medline].

  18. Landis MN, Davis CL, Bellus GA, Wolverton SE. Immunosuppression and sebaceous tumors: a confirmed diagnosis of Muir-Torre syndrome unmasked by immunosuppressive therapy. J Am Acad Dermatol. 2011 Nov. 65(5):1054-1058.e1. [Medline].

  19. Marques-da-Costa J, Campos-do-Carmo G, Ormiga P, Ishida C, Cuzzi T, Ramos-e-Silva M. Sebaceous adenoma: clinics, dermatoscopy, and histopathology. Int J Dermatol. 2015 Jun. 54 (6):e200-2. [Medline].

  20. Misago N, Toda S, Narisawa Y. Two histopathologic patterns of well-differentiated extraocular sebaceous carcinoma. J Cutan Pathol. 2011 Oct. 38(10):767-74. [Medline].

  21. Troy JL, Ackerman AB. Sebaceoma. A distinctive benign neoplasm of adnexal epithelium differentiating toward sebaceous cells. Am J Dermatopathol. 1984 Feb. 6(1):7-13. [Medline].

  22. Sachez Yus E, Requena L, Simon P, del Río E. Sebomatricoma: a unifying term that encompasses all benign neoplasms with sebaceous differentiation. Am J Dermatopathol. 1995 Jun. 17(3):213-21. [Medline].

  23. Svec J, Schwarzová L, Janošíková B, Stekrová J, Mandys V, Kment M, et al. Synchronous gastric and sebaceous cancers, a rare manifestation of MLH1-related Muir-Torre syndrome. Int J Clin Exp Pathol. 2014. 7 (8):5196-202. [Medline].

  24. Roberts ME, Riegert-Johnson DL, Thomas BC, Rumilla KM, Thomas CS, Heckman MG, et al. A clinical scoring system to identify patients with sebaceous neoplasms at risk for the Muir-Torre variant of Lynch syndrome. Genet Med. 2014 Sep. 16 (9):711-6. [Medline].

 
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A biopsy-proven sebaceous adenoma on the forehead of a 64-year-old man. The tumor appeared as a dome-shaped, elevated nodule with a circumscribed margin. It measured 8 mm in diameter, with a smooth, shiny, yellow, and speckled appearance. The tumor had a history of slow growth, and the patient had noticed it for more than a year. Note the pearly appearance and the presence of a few capillaries traversing the tumor surface, a feature closely mimicking the clinical appearance of that of a basal cell carcinoma. The total surgical removal of this tumor was uneventful. The patient has not experienced a recurrence.
Low-power view of a photomicrograph of sebaceous adenoma. Note the dome-shaped elevation of the epidermal surface, the sharp circumscription from the adjacent dermal tissue, and the slight central cystic appearance with eosinophilic secretory material. Patients with sebaceous tumors showing more prominent cystic change have been found to have DNA abnormalities that are linked to a higher risk of the development of internal malignancies at a later date.
A medium-power view of the well-differentiated SA on the forehead of a 64-year-old man, showing proliferation of well-differentiated sebaceous lobules with central, larger, mature sebocytes and peripheral, smaller, less-differentiated, basaloid, germinative cells. Note that the sebaceous lobules are connected to the overlying epidermis and are slightly off-center in this field; a collection of eosinophilic, pink-colored, keratinous material is present in a dilated follicular ostium within the tumor (hematoxylin and eosin, original magnification X75). In contrast to a sebaceous hyperplasia, a sebaceous adenoma such as seen in this microscopic field contains sebaceous lobules with a 2-cell type and not a single-cell type of sebocytes as seen in the former. The neoplasm was completely removed, with no known recurrences to date.
Higher-power view of a photomicrograph of a sebaceous adenoma. Note the intermingled 2 cell types, ie, well-differentiated pale-staining sebocytes containing vacuolated (bubbly) cytoplasm and smaller, darkly stained, basaloid, less-differentiated matrix cells. An occasional mitotic figure (arrow) was present. The tumor was completely excised, and no recurrence was noted in this patient after 5 years of follow-up (hematoxylin and eosin, original magnification X200).
A close-up, higher-power view of the same sebaceous adenoma. The cytologic details are evident. Notice the predominant, larger sebocytes (arrow) containing pale-staining, bubbly cytoplasm (intracytoplasmic compartmentalization) and a few smaller, basaloid, germinative cells of pilosebaceous structures. The nuclei are vesicular without overt pleomorphism or mitotic activity (hematoxylin and eosin, original magnification X300).
Multiple sebaceous neoplasms on the skin of the chest and the trunk of a 62-year-old man. The tumors were biopsy-proven sebaceous tumors with varying degrees of sebaceous differentiation. The patient was found to have a well-differentiated adenocarcinoma of the colon by subsequent colonoscopy, CT scan, and MRI examination.
 
 
 
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