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Skin nonmelanocytic tumor

Adnexal tumors

Sebaceous glands

Sebaceous carcinoma

Authors: Sherehan Zada, M.D., Bonnie A. Lee, M.D.

Resident / Fellow Advisory Board: Farres Obeidin, M.D.

Last author update: 11 August 2021

Last staff update: 24 January 2023

Copyright: 2002-2024, PathologyOutlines.com, Inc.

PubMed Search: Sebaceous carcinoma [title] skin review[ptyp]

Table of Contents

Cite this page: Zada S, Lee BA. Sebaceous carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skintumornonmelanocyticsebaceouscarcinoma.html. Accessed December 26th, 2024.

Definition / general

Malignant neoplasm with sebaceous differentiation
Generally classified into periocular and extraocular
Mostly occurs sporadically in elderly patients with an equal gender distribution; periocular locations have a female predominance (Curr Treat Options Oncol 2017;18:47, Onco Targets Ther 2018;11:3713)

Essential features

Periocular versus extraocular
Atypical sebocytes can be well, moderately or poorly differentiated
May rarely occur in association with Muir-Torre syndrome, an autosomal dominant syndrome characterized by a sebaceous neoplasm (adenoma, sebaceoma or carcinoma) and occasionally keratoacanthoma associated with a visceral malignancy (Dermatol Surg 2015;41:1)
Aggressive tumor with 5 year survival rate of 92.7%
Treatment is primarily surgical excision

Terminology

Sebaceous gland carcinoma
Sebaceous cell carcinoma
Meibomian gland carcinoma (J Korean Med Sci 2017;32:1351)

ICD coding

ICD-10: C44.1392 - sebaceous cell carcinoma of skin of eyelid, including canthus

Epidemiology

0.2 - 4.6 % of all malignant cutaneous tumors and the third most common eyelid malignancy (Curr Treat Options Oncol 2017;18:47)
More frequent:
- Patient age > 40
- Asian (periocular) (StatPearls: Sebaceous Gland Carcinoma [Accessed 30 March 2021])

Sites

Most common in periocular area, head and neck but can arise from any sebaceous gland of the skin (StatPearls: Sebaceous Gland Carcinoma [Accessed 30 March 2021])
Periocular (75%) > extraocular (25%) in most studies; however, more recent studies suggest the opposite (Dermatol Surg 2015;41:1, Cancer 2008;113:3372)
Periocular:
- 1.0 - 3.2% of all malignant eyelid tumors
- Upper eyelid > lower eyelid
- Originates from meibomian glands, Zeiss glands, caruncle or skin of eyebrow (Curr Treat Options Oncol 2017;18:47)
Extraocular:
- Occurs on the head and neck mostly, then rarely on the trunk, extremities, genitalia, external auditory meatus
- Very rarely can occur in extracutaneous sites, such as lungs, salivary glands and breast (Dermatol Pract Concept 2012;2:39, J Korean Med Sci 2017;32:1351)
- Can rarely occur in a nevus sebaceus of Jadassohn (J Dermatol 2016;43:175)

Pathophysiology

Unknown

Etiology

Radiation
Immunosuppression
Muir-Torre syndrome: autosomal dominant syndrome with mutation in one or more of the mismatch repair genes (MLH1, MSH2, MSH6 PMS2) and associated microsatellite instability
Production of nitrosamines (food or medication)
Retinoblastoma (Onco Targets Ther 2018;11:3713)

Clinical features

Periocular: presents as a yellow to pink, painless, rapidly enlarging, firm papule, nodule or cystic lesion (Curr Treat Options Oncol 2017;18:47)
Extraocular: presents as yellowish nodule, often with ulceration (StatPearls: Sebaceous Gland Carcinoma [Accessed 30 March 2021])

Diagnosis

Biopsy is essential for the diagnosis (Curr Treat Options Oncol 2017;18:47)

Radiology description

Radiologic studies may help to reveal bone destruction or soft tissue involvement by the tumor (Curr Treat Options Oncol 2017;18:47)

Prognostic factors

5 year relative survival rate: 92.7% (J Am Acad Dermatol 2016;75:1210)
Overall prognosis for localized disease after complete excision is good
Most significant predictor of reduced survival is the presence of metastatic disease at the time of diagnosis
Other factors: multicentricity, pagetoid spread, perineural vascular and lymphatic invasion, poorly differentiated cytology, periocular location, primary site on the ear or lip, tumor size (> 10 mm), black race (Curr Treat Options Oncol 2017;18:47, Dermatol Surg 2015;41:1)
Sebaceous carcinoma may metastasize in 2.4% of the cases; the majority of metastases occur within the first 2 years after initial treatment (Head Neck 2012;34:1765)

Case reports

37 year old woman with Muir-Torre syndrome associated sebaceous carcinoma occurring in the setting of lipedematous scalp (Case Reports Plast Surg Hand Surg 2020;7:124)
55 year old woman presenting with asymptomatic nodular ulcerating lesions on the right side of the vulva (Indian J Dermatol Venereol Leprol 2017;83:221)
59 year old woman with disseminated subcutaneous nodules with history of previously treated sebaceous cell carcinoma (Am J Case Rep 2018;19:1192)
67 year old woman with longstanding history of an ovarian dermoid cyst (Gynecol Oncol Rep 2018;26:37)

Treatment

Wide local excision or Mohs micrographic surgery are the best initial treatment options
Sentinel lymph node biopsy for periorbital sebaceous carcinoma > 10 mm in diameter
Radiation therapy and systemic chemotherapy are only used for patients who are poor surgical candidates or those with recurrent or metastatic disease
Immunohistochemistry to evaluate for microsatellite instability (MSH2, MSH6, MLH1, PMS2) should be offered on sebaceous carcinoma specimens, especially extraocular ones, to screen for Muir-Torre syndrome
Evidence of orbital invasion on imaging necessitates exenteration (Dermatol Surg 2015;41:1)

Clinical images

Contributed by Maria Del Valle Estopinal, M.D.

Periocular sebaceous carcinoma

Images hosted on other servers:

Extraocular sebaceous carcinoma

Muir- Torre syndrome

Gross description

Papule, nodule or cystic lesion

Frozen section description

Lipid and fat staining with frozen sections have been used in the past

Microscopic (histologic) description

Architecture: usually sheets or lobules separated by fibrovascular stroma
- Dermal based tumor with focal connection to the epidermis or follicular epithelium
- Can be rounded nodular aggregates or angulated infiltrative aggregates
- Can appear cystic with central comedo type necrosis
- Less commonly, can have a broad superficial intraepidermal pattern
Cytology: classified as poorly, moderately or well differentiated
- Well differentiated: increased proportion of mature appearing sebocytes (multivacuolated cells) with nuclear indentation relative to basaloid undifferentiated cells
  - Mild pleomorphism, minimal mitoses and necrosis
- Moderately to poorly differentiated: higher proportion of atypical basaloid (undifferentiated) cells with minimal differentiation toward multivacuolated cells
  - Prominent pleomorphism and atypia, frequent mitoses and necrosis
Pagetoid (or intraepidermal sebaceous carcinoma, sebaceous carcinoma in situ) tumor growth is much more commonly observed in periocular than in extraocular locations, where it is rare
Can exhibit squamous metaplasia or focal apocrine differentiation
References: Dermatol Surg 2015;41:1, Curr Treat Options Oncol 2017;18:47, Int J Surg Pathol 2019;27:432, J Korean Med Sci 2017;32:1351

Microscopic (histologic) images

Contributed by Bonnie Lee, M.D. and Maria Del Valle Estopinal, M.D.

Well differentiated

Multivacuolated cells

Poorly differentiated

Atypical basaloid cells

Intraepidermal sebaceous carcinoma

Atypical basaloid cells within the epidermis

Poorly differentiated with cystic appearance

Extensive central (comedo) necrosis

Infiltrative sebaceous carcinoma

Infiltrating into skeletal muscle

Androgen receptor

Androgen receptor nuclear staining

Adipophilin - membranous vesicular staining

Adipophilin – granular staining

Positive stains

Androgen receptor
Adipophilin - membranous vesicular pattern (a granular pattern is considered negative)
Keratin
EMA
LeUM1
Ki67 - increased relative to sebaceous adenoma and sebaceoma
p53 - increased relative to sebaceous adenoma and sebaceoma
BerEP4
References: Onco Targets Ther 2018;11:3713, Curr Opin Ophthalmol 2018;29:445

Negative stains

CEA, S100

Sample pathology report

Skin, right elbow, shave biopsy:
- Well differentiated sebaceous neoplasm with severe nuclear atypia, consistent with sebaceous carcinoma (G1)
- Tumor measures at least 5.5 mm in greatest dimension
- Margins cannot be evaluated in the plane of sections examined
- No definite lymphovascular or perineural invasion identified
- American Joint Committee on Cancer pathologic staging (8th edition): pT1 pNx (Amin: AJJC Cancer Staging Manual, 8th edition, 2017)
Left lower eyelid, wedge excision:
- Recurrent, sebaceous cell carcinoma in situ, moderately differentiated involving the skin of the left lower eyelid
- Tumor size: 0.7 mm
- Lymphovascular space invasion: not identified
- Perineural invasion: not identified
- Mitotic rate: 5 mitoses per square mm
- Surgical margins: nasal, temporal, inferior and deep margins are negative for sebaceous carcinoma
- Microsatellite instability markers for sebaceous carcinoma: positive (retained) nuclear staining for MLH1, PMS2, MSH2 and MSH6
- Pathologic staging: pTIs
- IHC stains: androgen receptor - positive in tumor cells; adipophilin - positive in tumor cells; BerEP4: negative in tumor cells

Differential diagnosis

Basal cell carcinoma with sebaceous differentiation:
- Small basaloid cells with peripheral palisading, surrounded by a fibromyxoid stroma, with focal differentiation toward mature benign appearing multivacuolated sebocytes
- IHC: BerEP4+, EMA-, adipophilin is negative or granular pattern in basaloid cells, AR-
Clear cell squamous cell carcinoma:
- Clear cells are not as multivacuolated as sebocytes
- IHC: AR-, BerEP4-, adipophilin may be negative or granular pattern
Balloon cell melanoma:
- Atypical melanocytes with clear cytoplasm, easily distinguished with melanocytic markers
- IHC: SOX10+ and S100+
Metastatic clear cell carcinoma (renal):
- Cells with more uniform clearing and prominent capillary vessels
- Characteristically positive for CD10+, CAIX + and PAX8, adipophilin is negative or granular rather than vacuolated pattern
Clear cell sarcoma:
- Nested to fascicular architecture with epithelioid to plump spindle cells with vesicular nuclei and macronucleoli separated by thin fibrous septa; scattered multinucleated giant cells and pigment
- IHC: SOX10+ and S100+

Additional references

Mod Pathol 2006;19:S93

Board review style question #1

A 75 year old woman had an excisional biopsy for a rapidly growing mass in her upper eyelid. Histologic details are shown in the image above. Which of the following is true regarding this entity?

Pagetoid spread is more common in periocular location
Radiation therapy is the first line treatment
Surgical excision is not helpful
This tumor is S100 positive

Board review style answer #1

A. Pagetoid spread is more common in periocular location. The pagetoid pattern of sebaceous carcinomas is seen much more in the periocular area. This tumor is characteristically S100 negative. First line treatment is surgical excision. Radiation therapy is helpful in metastatic disease and in poor surgical candidates.

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Reference: Sebaceous carcinoma

Board review style question #2

Which immunostain is negative in sebaceous carcinoma?

Adipophilin
Androgen receptor
CEA
EMA

Board review style answer #2

C. CEA. Sebaceous carcinoma stains positive for EMA, adipophilin, androgen receptor. It is usually negative for CEA.

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Reference: Sebaceous carcinoma

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