Are You Confident of the Diagnosis?
What you should be alert for in the history
The diagnosis of sebaceous adenoma is predominantly based on the characteristic pathologic features. Sebaceous adenoma is a rare, benign tumor of sebaceous glands. Approximately 70% of lesions develop on the head and face, with the nose and cheek most commonly affected; 30% of lesions occur on the neck, trunk and extremities. Sebaceous ademomas may rarely develop in salivary glands (parotid and submanidular glands) and on the oral mucosa. Both solitary and multiple lesions have been described. They are usually slow growing, although rapid growth has been described.
The mean age of affected patients is 60 years. Lesions occur in both men and women. A series of patients reported by the AFIP described a male predominance, atlhough that may have represented a selection bias.
Recognition of this tumor is critical as it can be associated with Muir-Torre Syndrome (MTS). Sebaceous adenoma is the most common sebaceous lesion associated with this syndrome. Lesions that develop in patients with MTS more commonly occur on the trunk and extremities. Other cutaneous lesions seen in MTS include sebaceous epithelioma, sebaceous carcinoma and keratoacanthoma, the latter often with sebaceous features.
Characteristic findings on physical examination
On physical examination, lesions are yellow, tan, pink or skin-colored papules. They are typically less than 5mm in diameter although larger lesions (several centimeters) have been reported. Bleeding, ulceration and pain can occur. They are often clinically mistaken for basal cell carcinoma.
Expected results of diagnostic studies
Histologically, sebaceous adenomas are multilobulated, well-circumscribed intradermal tumors. They can be contiguous with or replace the epidermis. Lobules are composed of mature sebocytes (vacuolated cytoplasm, crenated and scalloped nucleus) centrally, surrounded by germinative basaloid cells at the periphery (Figure 1, Figure 2, Figure 3).
The germinative cells are characteristically more than two layers thick and compose less than half of the tumor cell volume. This is an important feature as it distinguishes the lesion from sebaceoma, in which the germinative component represents more than half the tumor cell volume. A fibrous pseudo-capsule usually surrounds the tumor. Cytologic atypia and mitoses are not typically present.
Immunohistochemical stains are available to look for loss of mismatch repair proteins in paraffin embedded tissue: MSH-2, MLH-1, MSH-6. Loss of expression of these proteins is associated with MTS. Initial studies examined expression of MLH-1 and MSH-2. More recently, loss of MSH-6 has also been demonstrated in patients with MTS. The positive predictive value for a diagnosis of MTS when combining these three markers ranges from 55% to 100%.
The histologic differential diagnosis includes basal cell carcinoma with sebaceous differentiation, sebaceoma and sebaceous hyperplasia. Basal cell carcinoma with sebaceous differentiation is fundamentally a basal cell carincoma that has foci of mature sebocytes within tumor lobules. The presence of peripheral palisading of a predominantly basaloid tumor with retraction artifact separating the tumor lobule from the adjacent stroma and a loose mucinous stroma are clues to a basal cell carcinoma.
CK 19 positivity has been reported as a helpful tool in differentiating basal cell carcinoma from sebaceous tumors. Strong CK 19 positivity supports a diagnosis of basal cell carcinoma. Sebaceoma is distinguished from sebaceous adenoma by the presence of germinative cells that constitute more than half of the tumor volume. Sebaceous hyperplasia is characterized by an increased number of mature sebaceous lobules that surround a hair follicle. The germinative component is less than two layers thick, in contrast to a sebaceous adenoma, which is more than two layers in thickness.
Who is at Risk for Developing this Disease?
Sebaceous adenoma is often sporadic but may be a marker for Muir-Torre syndrome (MTS), particularly when lesions are multiple and located on the trunk and extremities. MTS is an autosomal dominant defect in DNA mismatch repair associated with multiple sebaceous tumors, keratoacanthomas and internal malignancy. It demonstrates a slight male predominance (male:female ratio 3:2). The median age at presentation of the first malignancy is 53 years.
What is the Cause of the Disease?
The cause for sporadic disease is unknown. Cases associated with Muir-Torre syndrome are due to a defect in DNA mismatch repair proteins. The best studied genes are MSH-2 on chromosome 2, which is most common, and MLH-1 on chromosome 3. Other implicated genes include MSH-6 and MLH-3. These proteins function to repair mismatches in DNA. Mutations lead to microsatellite instability and tumors. Microsatellitle instablity is also seen in hereditary nonpolyposis colorectal cancer, and MTS may be a variant of those disorders.
Systemic Implications and Complications
Patients with Muir-Torre syndrome are at risk for visceral malignancy. Of the visceral malignancies, colorectal carcinoma is most common. Genitourinary, breast, upper gatrointestinal, laryngeal, and hematologic malignancies have also been reported. Although the visceral neoplams in MTS may have a less aggressive course compared with sporadic counterparts, 60% of patients with MTS develop metastatic disease. Half of all patients have two or more internal malignancies; 56% of cutaneous lesions are diagnosed after the internal malignancy; 22% of cutaneous lesions occur before the internal malignancy; and 6% are concomitant.
Sebaceous adenomas are benign, yet most lesions are completely removed by local, conservative excision.
Other reported therapies include topical photodynamic therapy for solitary lesions, athough this was not very effective. Oral isotretinoin has been reported to stabilize the number of new lesions in patients with MTS. The dosages used in the reported cases range from 0.85mg/kg/day to 0.2mg/kg/day. Treatment duration has also been variable, from months to years, with the longest reported time on isotretinoin being 4 years. Oral isotretinoin has also been used in combination with interferon alpha-2a and isotretinoin gel. The latter is not available in the United States.
Optimal Therapeutic Approach for this Disease
Optimal therapy of the cutaneous lesion is conservative excision.
Evaluation for possibiltiy of MTS is important and can be done with immunohistochemical stains and patient history. Patients with MTS should undergo close cancer surveillance and assesment of family members.
Genetic tesing on peripheral blood is also available to confirm microsatellite instability.
Close follow-up in patients with MTS is critical to evaluate for visceral malignancies, particularly colorectal and genitourinary. Current recommendations include annual dermatologic examinations, cervical Pap smears, urinary cytology, chest radiography, colonoscopy (every 3 to 5 years, starting at age 25 to 30), mammography, endometrial biopsy (every 3 to 5 years, starting at age 50), upper gastrointestinal (GI) endoscopy (in families with reported gastric cancer) and serum carcinoembryonic antigen (CEA) concentration.
Unusual Clinical Scenarios to Consider in Patient Management
There are several reports of sebaceous adenoma and MTS in patients with AIDS. Multiple sebaceous adenomas and sebaceous carcinoma were reported in a patient with chronic progressive multiple sclerosis, although she did not meet criteria for MTS.
What is the Evidence?
Rulon, DR, Helwig, EB. “Cutaneous sebaceous neoplasms”. Cancer. vol. 33. 1974. pp. 82-102. (Historically seminal review article examining clinical and pathologic features of 95 sebaceous tumors diagnosed at the AFIP).
Eisen, DB, Michael, DJ. “Sebaceous lesions and their associated syndromes: part I”. J Am Acad Dermatol. vol. 61. 2009. pp. 549-60. (Review article focusing on the clinical and histologic characteristics of MTS, Lynch syndrome and linear nevus sebaceus syndrome.)
Zare-Mahmoodabadi, R, Salehinejad, J, Saghafi, S, Ghazi, N, Mahmoudi, P, Harraji, A. “Sebaceous adenoma of the submandibular gland: a case report”. J Oral Sci. vol. 51. 2009. pp. 641-4. (Single case reporting a sebaceous adenoma in the submandibular gland of 38-year-old woman.)
Heyl, J, Mehregan, D. “Immunolabeling pattern of cytokeratin 19 expression may distinguish sebaceous tumors from basal cell carcinomas”. J Cutan Pathol. vol. 35. 2008. pp. 40-5. (CK 19 positivity favors a diagnosis of basal cell carcinoma over other sebaceous tumors. Basal cell carcinoma showed strong positivity in 64% of cases examined and focal positivity in 14% of cases. Focal but not strong positivity was seen in 20% of sebaceous adenomas, 50% of sebaceous epitheliomas and 17% of sebaceous carcinomas.)
Abbas, O, Mahalingam, M. “Cutaneous sebaceous neoplasms as markers of Muir-Torre syndrome: a diagnostic algorithm”. J Cutan Pathol. vol. 36. 2009. pp. 613-9. (The authors review the significance and role of immunohistochemical stains for microsatellite instablility in the diagnosis of MTS and propose an algorithm for histopathologic diagnosis of possible MTS in sebaceous tumors of the skin.)
Akhtar, S, Oza, KK, Roulier, RG. “Multiple sebaceous adenomas and extraocular sebaceous carcinoma in a patient with multiple sclerosis: case report and review of literature”. J Cutan Med Surg. vol. 5. 2001. pp. 490-5. (This is a report of a 44-year-old woman with chronic progressive multiple sclerosis who developed multiple sebaceous adenomas and sebaceous carcinoma on the scalp. She had no history of internal malignancy, although she did have a strong family history of visceral malignancy including colon, uterine, bladder, and kidney. The authors state that she did not meet criteria for MTS, although genetic testing on tissue or peripheral blood was not performed.)
Frantz, S, Greiner, A, Schoen, C, Langmann, P, Klinker, H. “A sebaceous tumor in a patient with acquired immunodeficiency syndrome”. Eur J Med Res. vol. 7. 2002. pp. 135-7. (This is a report of a rapidly enlarging sebaceous adenoma in a patient with AIDS.)
Kim, SK, Lee, JY, Kim, YC. “Treatment of sebaceous adenoma with topical photodynamic therapy”. Arch Dermatol. vol. 146. 2010. pp. 1186-8. (Two patients with sebaceous adenomas are treated wtih PDT threapy. Both lesions were on the face. One patient had failed prior treatment with laser. Both patients had only partial response to PDT.)
Ponti, G, Ponz de Leon, M. “Muir-Torre syndrome”. Lancet Oncol. vol. 6. 2005. pp. 980-7. (This review article describes the epidemiology, clinical features and molecular biology of Muir Torre syndrome. It explores the relationship of MTS to Lynch syndrome and details the management and appropriate follow-up of persons with MTS.)
Graefe, T, Wollina, U, Schulz, H, Burgdorf, W. “Muir-Torre syndrome—treatment with isotretinoin and interferon alpha-2a can prevent tumour development”. Dermatology. vol. 200. 2000. pp. 331-3. (A 57-year-old man with MTS was treated with a combination of topical isotretinoin gel, oral isotretinoin and interferon alpha-2a, which resulted in a marked decrease in the incidence of new cutaneous tumors.)
Spielvogel, RL, DeVillez, RL, Roberts, LC. “Oral isotretinoin therapy for familial Muir-Torre syndrome”. J Am Acad Dermatol. vol. 12. 1985. pp. 475-80. (Oral isotretinoin is reported to slow down the onset of new cutaneous tumors in two patients with MTS.)
Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved.
No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM.