Skin nonmelanocytic tumor

Adnexal tumors

Sebaceous glands

Sebaceous carcinoma


Resident / Fellow Advisory Board: Farres Obeidin, M.D.
Sherehan Zada, M.D.
Bonnie A. Lee, M.D.

Topic Completed: 11 August 2021

Minor changes: 11 August 2021

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

Sherehan Zada, M.D.
Bonnie A. Lee, M.D.
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Cite this page: Zada S, Lee BA. Sebaceous carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skintumornonmelanocyticsebaceouscarcinoma.html. Accessed December 8th, 2021.
Definition / general
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
ICD coding
  • ICD-10: C44.1392 - sebaceous cell carcinoma of skin of eyelid, including canthus
Epidemiology
Sites
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
Diagnosis
Radiology description
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
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 Periocular sebaceous carcinoma

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

Well differentiated

Multivacuolated cells

Multivacuolated cells

Poorly differentiated

Poorly differentiated

Atypical basaloid cells

Atypical basaloid cells

Intraepidermal sebaceous carcinoma

Intraepidermal sebaceous carcinoma


Atypical basaloid cells within the epidermis

Atypical basaloid cells within the epidermis

Poorly differentiated with cystic appearance

Poorly differentiated with cystic appearance

Extensive central (comedo) necrosis

Extensive central (comedo) necrosis

Infiltrative sebaceous carcinoma

Infiltrative sebaceous carcinoma

Infiltrating into skeletal muscle

Infiltrating into skeletal muscle


Androgen receptor

Androgen receptor

Androgen receptor nuclear staining

Androgen receptor nuclear staining

Adipophilin - membranous vesicular staining

Adipophilin - membranous vesicular staining

Adipophilin – granular staining

Adipophilin – granular staining

Positive stains
Negative stains
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
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?

  1. Pagetoid spread is more common in periocular location
  2. Radiation therapy is the first line treatment
  3. Surgical excision is not helpful
  4. 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?

  1. Adipophilin
  2. Androgen receptor
  3. CEA
  4. 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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