Pleomorphic Carcinoma

(Subset of Sarcomatoid Carcinoma)

Epidemiology and Etiology:

• Smokers mostly

Common sites:

• Upper lobes > lower lobes

Gross features:

• Frequent pleural invasion and chest wall invasion
• Peripheral often
• Well-circumscribed usually
• Necrosis and/or cavitation often
• > 5cm usually

Histologic features:

• Poorly differentiated NSCLC (Squamous, adeno, or undifferentiated)
• At least 10% spindle and/or giant cells (may consist entirely of these)
• Definitive diagnosis may only be made on resection
• Admixed with adenoCA (most), squamous (~20%), or undifferentiated NSCLC (up to 40%)
• Giant tumour cells:
• Abundant, often eosinophilic, sometimes granular cytoplasm
• Eosinophilic globules maybe
• Nuclei large, irregular, multilobated or multiple, with coarse or vesicular chromatin and prominent nucleoli
• Neutrophil emperipolesis common
• Necrosis common
• Vascular invasion common

Immunophenotype:

Marker:	Sensitivity:	Specificity:
Vimentin (pleomorphic, spindle, or giant cell components)
Fascin (pleomorphic, spindle, or giant cell components)
Cytokeratins	Variable
Napsin A	Variable
TTF-1	Variable
P63	Variable
Desmocollin 3	Variable

Molecular features:

• TP53 mutations
• KRAS mutations (up to 38%)
• EGFR mutations (up to 25%)
• Pleomorphic carcinomas with adenoCA component should be tested for EGFR and ALK
• Gains:
• Chromosomal regions (see list in WHO)
• MET has been reported
• FGFR2 has been reported

Other features:

• Poor prognosis, even in early stage
• Aggressive
• Distant mets commonly, including unusual locations

References:

• Travis et al. (eds.) WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart, 4^th ed. (2015)