Definition/General
Introduction:
Sebaceous carcinoma is a rare aggressive adnexal carcinoma with sebaceous differentiation
It constitutes <1% of all skin cancers
It shows high potential for metastasis and local recurrence
It demonstrates predilection for periocular region (75% of cases)
It has association with Muir-Torre syndrome (MSH/MLH mutations).
Origin:
Arises from sebaceous glands of skin
Most commonly from meibomian glands of eyelids
Can originate from Zeis glands (eyelash follicles)
May arise from caruncular sebaceous glands
Extraocular cases arise from facial and scalp sebaceous glands
Shows malignant transformation of sebaceous epithelium.
Classification:
WHO classifies as sebaceous neoplasm
Ocular sebaceous carcinoma (75% of cases)
Extraocular sebaceous carcinoma (25%)
Well-differentiated sebaceous carcinoma
Poorly differentiated sebaceous carcinoma
Muir-Torre associated sebaceous carcinoma
Sporadic sebaceous carcinoma.
Epidemiology:
Peak incidence in 6th-7th decades
Female predominance (2:1) for ocular lesions
Equal gender distribution for extraocular lesions
Risk factors include advanced age
Muir-Torre syndrome
Radiation exposure
Indian population shows similar epidemiology but lower overall incidence.
Clinical Features
Presentation:
Slowly enlarging eyelid nodule (most common)
Yellow to pink papule or nodule
Chalazion-like appearance
Unilateral upper eyelid involvement typical
May present as chronic blepharoconjunctivitis
Loss of eyelashes (madarosis) may occur.
Symptoms:
Painless eyelid swelling (most common)
Recurrent chalazion
Loss of eyelashes
Chronic irritation
Yellowish discharge
Patients often report non-healing eyelid lesion
Advanced cases may cause visual obstruction.
Risk Factors:
Age >60 years
Muir-Torre syndrome (MSH2, MLH1, MSH6 mutations)
Previous radiation therapy
Immunosuppression
Family history of colorectal cancer
Personal history of sebaceous neoplasms
Asian ethnicity (higher incidence).
Screening:
Ophthalmologic examination for eyelid lesions
Biopsy of suspicious eyelid lesions
Genetic counseling for Muir-Torre syndrome
Colonoscopy screening (associated GI malignancies)
Family history assessment.
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Gross Description
Appearance:
Yellow to pink nodular lesion
Firm consistency
Size typically 0.5-3 cm
May show central depression or ulceration
Chalazion-like appearance
Cut surface shows yellow-white lobulated tissue.
Characteristics:
Well-circumscribed to infiltrative margins
Lobulated architecture
May show cystic areas
Yellowish color due to lipid content
Firm to rubbery consistency
Cut surface appears multilobulated.
Size Location:
Size ranges from 0.5-5 cm (median 1.5 cm)
Upper eyelid most common (60%)
Lower eyelid (30%)
Inner canthus (10%)
Extraocular: face, scalp, trunk
Parotid gland (rare).
Multifocality:
Pagetoid spread along conjunctiva (characteristic)
Multicentric growth
Skip lesions in conjunctiva
Regional lymph node metastases (15-25%)
Distant metastases (10-15%).
Microscopic Description
Histological Features:
Lobules of sebaceous cells with varying differentiation
Foamy cytoplasm with lipid vacuoles
Indented nuclei
Pleomorphic cells with mitotic activity
Basaloid cells at periphery
Pagetoid spread along surface epithelium.
Cellular Characteristics:
Sebaceous cells with foamy cytoplasm
Multiple lipid vacuoles
Small indented nuclei
Basaloid reserve cells
Pleomorphic nuclei in malignant areas
Prominent nucleoli
Mitotic figures present.
Architectural Patterns:
Lobular growth pattern
Infiltrative margins
Connection to surface epithelium
Pagetoid spread characteristic
Comedonecrosis may be present
Desmoplastic stromal response.
Grading Criteria:
Well-differentiated: Prominent sebaceous differentiation
Moderately differentiated: Mixed sebaceous and basaloid cells
Poorly differentiated: Predominantly basaloid with minimal sebaceous features
Mitotic rate variable
Pagetoid spread indicates aggressive behavior.
Immunohistochemistry
Positive Markers:
Adipophilin (85-95% positive)
EMA (90-95%)
CK7 (80-90%)
Androgen receptor (70-80%)
p53 (overexpression in 60%)
Ki-67 (variable)
Oil Red O (fresh tissue).
Negative Markers:
CK20 (usually negative)
CEA (negative)
S-100 (negative)
Melanoma markers (negative)
TTF-1 (negative)
CDX2 (negative).
Diagnostic Utility:
Adipophilin most specific marker
EMA highlights pagetoid spread
Oil Red O demonstrates lipid content
Essential for poorly differentiated cases
Useful for differential diagnosis
Androgen receptor supports sebaceous differentiation.
Molecular Subtypes:
MSH2/MLH1 mutations (Muir-Torre syndrome)
MSH6 mutations (rare)
TP53 mutations (60-70%)
KRAS mutations (20-30%)
PIK3CA mutations (15-20%)
Microsatellite instability (Muir-Torre cases).
Molecular/Genetic
Genetic Mutations:
TP53 mutations (60-70%)
MSH2 mutations (Muir-Torre syndrome)
MLH1 mutations (Muir-Torre syndrome)
KRAS mutations (20-30%)
PIK3CA mutations (15-20%)
RB1 mutations (subset)
CDKN2A deletions.
Molecular Markers:
p53 protein accumulation
MSH2/MLH1 protein loss (Muir-Torre)
Microsatellite instability
KRAS activation
PIK3CA activation
Rb protein loss
Cyclin D1 overexpression.
Prognostic Significance:
Muir-Torre syndrome indicates germline mutation
TP53 mutations associated with aggressive behavior
Pagetoid spread indicates poor prognosis
MSH2/MLH1 loss predicts associated malignancies
Location affects prognosis (ocular worse).
Therapeutic Targets:
Anti-EGFR therapy (cetuximab)
mTOR inhibitors (everolimus)
PI3K inhibitors
Immunotherapy (MSI-high tumors)
Targeted therapy based on molecular profile
Hormonal therapy (androgen receptor positive).
Differential Diagnosis
Similar Entities:
Basal cell carcinoma (with sebaceous differentiation)
Squamous cell carcinoma (poorly differentiated)
Sebaceous adenoma (benign)
Chalazion (reactive)
Metastatic adenocarcinoma
Pagetoid squamous cell carcinoma.
Distinguishing Features:
Sebaceous carcinoma: Adipophilin positive
Sebaceous carcinoma: Foamy cytoplasm
BCC: Peripheral palisading
SCC: Keratinization
Sebaceous adenoma: Benign cytology
Chalazion: Granulomatous inflammation.
Diagnostic Challenges:
Distinguishing sebaceous adenoma from carcinoma
Poorly differentiated sebaceous carcinoma
Pagetoid spread vs primary conjunctival lesion
Recurrent chalazion vs carcinoma
Small biopsy specimens
Oil Red O staining essential.
Rare Variants:
Signet ring sebaceous carcinoma
Spindle cell sebaceous carcinoma
Clear cell sebaceous carcinoma
Mucinous sebaceous carcinoma
Sebaceous carcinoma with neuroendocrine differentiation
Combined sebaceous-squamous carcinoma.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[Eyelid/skin] excision from [site], measuring [X x Y x Z] cm
Diagnosis
Sebaceous Carcinoma
Differentiation
Differentiation: [well/moderately/poorly] differentiated
Microscopic Features
Shows lobules of sebaceous cells with foamy cytoplasm and [degree of] pleomorphism
Size and Depth
Tumor size: [X] cm; Depth of invasion: [X] mm
Margins
Margins: [involved/uninvolved], closest margin [X] mm
Pagetoid Spread
Pagetoid spread: [present/absent/not assessable]
Lymphovascular Invasion
Lymphovascular invasion: [present/absent/not identified]
Immunohistochemistry
Adipophilin: [positive/negative]; EMA: [positive/negative]; [other markers]: [results]
MSI Status
MSH2/MLH1: [retained/lost/not performed] - consider Muir-Torre syndrome if lost
Final Diagnosis
Sebaceous Carcinoma, [differentiation], [size] cm