Skin nonmelanocytic tumor
Cite this page: Hale C. Sebaceous adenoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skintumornonmelanocyticsebaceousadenoma.html. Accessed October 20th, 2021.
Definition / general
- Hyperplasia of sebaceous lobules with expasion of germinative basaloid cell layers at periphery
- Unrelated to adenoma sebaceum (facial angiofibromas of tuberous sclerosis)
- Associated with Muir-TorrÈ Syndrome (Histopathology 2010;56:133)
Contributed by Michael Inskip, M.B.Ch.B. and Mark R. Wick, M.D.
- Papule / nodule on face / scalp
Microscopic (histologic) description
- Nodular lobulated growth with dark and light areas corresponding to generative cells (dark) and sebaceous cells (light) with cytoplasmic lipid vacuoles
- Not as organoid as sebaceous hyperplasia
Microscopic (histologic) images
Contributed by Joel Pinczewski, M.D., Ph.D. and Mark R. Wick, M.D.
Images hosted on other servers:
[Differential diagnostics of sebaceous tumors]
Sebaceous tumors are epithelial tumors with a differentiation towards sebaceous adnexal structures of the skin. They imitate the epithelial cells of mature sebaceous glands, sebaceous ducts, immature (embryonic) sebaceous structures or sebaceous glands that are not stimulated by hormones (mantle structures). This article explains the classification of sebaceous tumors on the basis of the normal histology of sebaceous glands. Clinical and histopathological criteria are given for the most important sebaceous tumors. The differential diagnosis of sebaceoma, sebaceous adenoma and various types of sebaceous carcinoma is emphasized. The importance of a specific diagnosis of adnexal tumors is demonstrated by tumor-associated syndromes with involvement of other organs (e.g., Muir-Torre syndrome and Birt-Hogg-Dubé syndrome). Furthermore, conceptional controversies, problems in differential diagnosis and the impact of immunohistochemical staining in the assessment of sebaceous tumors are considered.
Author: Dr Ben Tallon, Dermatologist/Dermatopathologist, Tauranga, New Zealand, 2010.
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Sebaceoma belongs to the group of benignsebaceoustumours.
Histology of sebaceoma
Scanning power of the histology of sebaceoma demonstrates a relatively well-circumscribedtumournodule typically within the deep dermis frequently with attachment to the epidermis. Low power identifies a lobulated tumour, which may demonstrate areas of cyst formation (Figure 1). The tumour is comprised of basaloid cells and a minority of sebaceous cells in addition to small ducts with the crenelated eosinophilic lining seen in sebaceous ducts (Figures 2, 3 and 4). A variable number and distribution of sebocytes is seen, but should remain the minor proportion compared to the basaloid component. Frequent mitoses can be seen in this tumour, though cytological atypia is lacking (Figure 5).
Special stains in sebaceoma
Sebaceous tumours are associated with visceralneoplasms, most commonly gastrointestinal, in the Muir-Torre syndrome [see Lynch syndrome]. Tumours can be shown to demonstrate microsatellite instability, reflecting mutations in mismatch repair genes. Loss of expression of MLH1, MSH2, MSH6 and PMS2 proteins can be seen on readily available immunohistochemical stains and can identify patients at risk of germlineDNA mismatch repair gene mutations.
Histological variants of sebaceoma
This tumour may be seen arising in association with sebaceous naevus (Figures 6 and 7). Note the distinct basal cell carcinoma arising adjacent to the sebaceoma (Figure 6). Figure 7 demonstrates loss of mature follicular structures and dilated eccrine ducts and glands beneath the sebaceoma consistent with pre-existing sebaceous naevus.
Sebaceoma in naevus sebaceous pathology
Differential diagnosis of sebaceoma
Sebaceous adenoma: This tumour is comprised of predominantly sebaceous lobules with a rim of basaloid germinative cells. The sebaceous component forms the majority of the tumour here.
Basal cell carcinoma with sebaceous differentiation: The sheets of basaloid cells will demonstrate areas of palisading and clefting typical of basal cell carcinoma in some areas of the tumour.
Sebocrine adenoma: Less sebaceous cell infiltrate is seen and visible ducts are small and lack the eosinophilic lining. The proliferation has the appearances of a poroma with sebaceous differentiation.
Sebaceous carcinoma: While an increased number of mitoses can be seen in sebaceoma, the presence of cytological atypia, areas of necrosis, deep extension, or adnexal or lymphovascular invasion is suggestive of malignancy.
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- Skin Pathology (2nd edition, 2002). Weedon D
- Pathology of the Skin (3rd edition, 2005). McKee PH, J. Calonje JE, Granter SR
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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.)
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Adenoma pathology sebaceous
Skin nonmelanocytic tumor
Definition / general
- Benign sebaceous neoplasm composed of basaloid cells and mature sebocytes
- Associated with Muir-Torre syndrome (MTS) but can also be an isolated (sporadic) tumor
- Sebaceoma, as a term, is used for tumors with > 50% basaloid cells and sebaceous adenoma is used for tumors with < 50% basaloid cells
- Sebaceous epithelioma, as a term, is confusing and is best not used
- Sebaceous epithelioma could refer to a low grade form of sebaceous carcinoma, a basal cell carcinoma with sebaceous differentiation or sebaceous proliferations of uncertain potential and thus is not a useful term
- Female to male ratio is 4:1
- Wide age range but the majority of patients are in the sixth to ninth decades
- Primarily occurs on the face and scalp
- Occurrence on non head and neck regions should prompt consideration of Muir-Torre syndrome
- Yellow to orange or flesh colored papule, nodule or tumor
- Muir-Torre syndrome (MTS) is considered a phenotypic variant of hereditary nonpolyposis colorectal carcinoma syndrome (HNPCC, Lynch syndrome) and is caused by germline mutations in one allele of the DNA mismatch repair (MMR) genes, most commonly MLH1, MSH2, MSH6 and PMS2
- MTS is associated with sebaceous neoplasia (most commonly sebaceous adenoma), colorectal, GU and other visceral adenocarcinomas
- MSH2 is the gene most commonly mutated in MTS
- If there is concern for MTS (personal or family history of colorectal, GU or breast cancer; or an older patient with numerous sebaceous neoplasms, especially not on the head and neck), further testing for MMR IHC or microsatellite instability can be performed
- IHC cannot differentiate between loss of MLH1 expression caused by a germline mutation versus a somatic hypermethylation - some germline missense mutations may be erroneously interpreted as normal by IHC, because they may result in an antigenically intact but nonfunctional protein
- Microsatellite instability analysis (MSI): performed on formalin fixed tissue, is more sensitive at detecting patients with germline MMR defects than IHC
- Results are either MSI-H (high degree of MSI) or MSI-L (low degree of MSI)
- Germline mutation analysis: blood leukocyte genomic sequencing is preferred to identify germline mutations in the MLH1, MSH2, MSH6 and PMS2 genes - if there are no germline mutations, but the tumor shows MMR deficiency, there may be involvement of other MMR proteins, somatic mutations or hypermethylation of the promoter region
- Sebaceomas can be sporadic, not associated with MTS
- Loss of nuclear staining for MLH1, MSH2, MSH6 or PMS2 suggests microsatellite instability (MSI) and supports a diagnosis of Muir-Torre syndrome
- Mutations in MLH1 and MSH2 have the most severe effect, producing a high frequency MSI phenotype
- When MSH2 is deficient, MSH6 usually is as well, because protein products of MSH2 and MSH6 form a heterodimer MMR recognition factor
- MSH6 is unstable without MSH2 and is quickly degraded
- Once the diagnosis is established, no further treatment is needed
- However, complete excision should be considered if the tumor is only partially biopsied or there is concern for basal cell carcinoma with sebaceous differentiation or sebaceous carcinoma
Contributed by Oriol Corral-Magaña, M.D. and Luis Javier del Pozo, M.D.
Microscopic (histologic) description
- Dermal nodule with variable epidermal involvement consisting of basaloid cells and mature sebocytes
- Greater than 50% of the tumor is made up of basaloid cells
- Variants of sebaceoma have been described with carcinoid-like, reticulated, cribriform, rippled and Verocay body-like features
Microscopic (histologic) images
Contributed by Jerad Gardner, M.D.
Contributed by Jennifer Kaley, M.D.
Ripple pattern sebaceoma
- Basal cell carcinoma with sebaceous differentiation: predominantly shows peripheral palisading and cleft formation with incidental sebaceous differentiation
- BerEP4 staining is positive in basal cell carcinoma and negative in sebaceoma
- Sebaceous adenoma: tumor with < 50% basaloid cells, as opposed to a sebaceoma which has > 50% basaloid cells
- Sebaceous carcinoma: has more nuclear pleomorphism, nucleolar prominence and mitotic activity than sebaceoma, infiltrative growth pattern
- Trichoblastoma with sebaceous differentiation: look for focal hair differentiation and papillary mesenchymal bodies
Board review style question #1
- What is the most common skin tumor associated with Muir-Torre syndrome?
- Basal cell carcinoma
- Sebaceous adenoma
- Sebaceous carcinoma
Board review style question #2
- What is the most common mutation seen in Muir-Torre syndrome?
Sebaceous adenoma is a benign sebaceous neoplasm that occurs on the face and scalp of elderly patients. It appears a small, firm nodule that clinically resembles basal cell carcinoma. Less commonly involved sites include ear, trunk, leg, arm, oral mucosa, and salivary glands. It is a component of the cutaneous lesions seen in Muir-Torre Syndrome.
The tumor has multilobulated appearance and may involve the overlying epidermis (as seen here). The individual lobules attempt to recapitulate the architecture of normal sebaceous glands. At the periphery of the lobules are layers of small germinative cells with basaloid appearance.These cells have small vesicular nuclei and scant cytoplasm. They merge towards the center of the lobules with more mature appearing sebaceous cells containing abundant pale-staining foamy cytoplasm and small hyperchromatic nuclei. At least half of each lobule in sebaceous adenoma consists of mature sebaceous cells. Increased mitotic activity is sometimes seen in sebaceous adenomas and should not be over-interpreted as sebaceous carcinoma.
Image courtesy of: Nephron - Own work, CC BY-SA 3.0, Link
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