Sebaceous carcinoma

SEBACEOUS CARCINOMA

• Rare malignant tumor with sebocytic differentiation

• It consists of two groups

  • aggressive – periocular variant

  • less aggressive – extraocular variant

Periocular sebaceous carcinoma

• more common than the cutaneous extraocular form

• arises in association with the ocular sebaceous glands

• Atleast 5 types of sebaceous adnexae are recognized in the eye

  • Meibomian glands (tarsal glands) – modified sebaceous glands that are associated with tarsal plates of both the upper and lower eyelids and are not associated with hair follicle. These glands contribute to lipids in tear

  • Glands of Zeis – associated with eyelashes at the lid margin

  • Sebaceous glands of caruncle, eyebrows and those of tiny vellous hair of the eyelid

• Most of the tumors arise from meibomian glands and present as slowly non-ulcerated mass

• It is third most common tumor of eyelid

• accounts foe 1% to 5% of malignancies of eyelid

• Age – elderly , but can be seen in young patients also

• Sex – slight female predominance

• poor prognostic factors –

  • involving both upper and lower eyelids

  • multicentric presentation

  • duration of symptoms greater than 6 months

  • distinctly infiltrative architecture

  • Pagetoid involvement of the skin epithelial surface of eyelid

  • lymphovascular and orbital invasion

• Metastasis occurs to regional lymph nodes and organs like lung, liver, brain and bone

• Periocular sebaceous carcinoma is generally less frequently associated with DNA MMR deficiency and Muir-Torre syndrome

• Also associated with radiotherapy and immunodeficiency conditions like HIV and retinoblastoma

Extraocular sebaceous carcinoma

• • Accounts for one quarter of all cases

  • Site – commonly presents in head and neck, but can also occur in thigh, trunk, genitalia, nasal vestibule, breast, nipple, finger, foot, and external auditory canal

  • sex- males are more commonly affected with M:F ratio of 2:1

  • Age – majority in 7th decade (rare in children). but cases associated with Muir-Torre syndrome are of younger age group

  • Grossly – pink to yellow red nodulocystic lesion which grows slowly and can reach upto 8cms in diameter

• It has been associated with 

  • Xeroderma pigmentosa

  • Bowen disease of vulva

  • Immunosuppressed or organ transplant patients

• Other non-cutaneous sites of occurrence are –

  • Hypopharynx

  • Tongue

  • Pulmonary bronchus

  • Lung

  • Submandibular gland

  • Parotid

  • uterine cervix

  • benign cystic teratoma or Dermoid cyst

Pathogenesis 

• Periocular sebaceous carcinoma are associated with HPV infection

• Mutations and nuclear accumulations of TP53 and increased expression of C-erB2 are also associated 

• genetic susceptibility – tumors associated with Muir-Torre syndrome lack the immunoreactivity for MLH1, MSH2, MSH6 and PMS2

Microscopic features 

• Characterized by irregular lobular pattern or less frequently diffuse growth in upper dermis, usually showing foci of continuity with the overlying epidermis

• Lobules are composed of admixture of basophilic germinative sebaceous cells with round or oval nuclei, usually containing several eosinophilic nucleoli and more mature cells with lightly bubbly eosinophilic cytoplasm

• Necrosis is frequently present and can be of comedo type

• Poorly differentiated tumor has cells with more hyperchromatic nuclei and may contain lipid 

• Peripheral palisading is occasionally seen

• keratinization may be seen with associated foreign body giant cell reaction 

• Classified as well, moderately and poorly differentiated carcinomas

  • Well differentiated (Grade I)-

    • Has roughly equal sized cellular lobules 

    • Increased proportion of mature appearing sebocytes (multivacuolated cells) with nuclear indentation relative to basaloid undifferentiated cells

    • mild pleomorphism, minimal mitosis and necrosis

  • Moderately differentiated (Grade II)-

    • Admixture of well defined nests with infiltrative profiles or confluent cell groups

    • higher proportion of atypical basaloid cells (undifferentiated cells) with minimal differentiation towards multivacuolated cells

    • Prominent pleomorphism and atypia

    • Frequent mitosis and necrosis

  • Poorly differentiated (Grade III)

    • highly invasive growth or a medullary sheet like growth pattern

• Pagetoid (Intraepidermal sebaceous carcinoma) growth is much more commonly observed in periocular tissue than extraocular location

• Can exhibit squamous metaplasia or apocrine differentiation

Immunohistochemistry–

• Tumor cells are positive for 

• • Androgen receptor (nuclear receptor)

  • Adipophyllin – membranous vesicular pattern (granular pattern is considered negative)

  • pan keratin

  • EMA

  • Leu M1

  • P53 

  • Ber EP4

  • P40

  • P63

Differential diagnosis

• Basal cell carcinoma – BerEP4 positive but EMA, Adipophyllin and AR negative

• Clear cell squamous cell carcinoma – AR , Ber EP4, Adipophyllin negative. Sebaceous carcinoma is positive for lipid and negative for PAS, Alcian blue or mucicarmine stain for glycogen

• Balloon cell melanoma – SOX10 and S-100 positive

• Sebaceoma – Absence of irregular architecture, pleomorphism, nucleolar prominence, mitotic activity and abnormal mitotic figures