Squamous Cell Carcinoma of the Thymus

Epidemiology and Etiology:

• Middle age usually

Common sites:

• Anterior mediastinum

Gross features:

• Invasion of adjacent structures frequently:
• Lung
• Pericardium
• Major vessels
• solid
• cystic changes or calcium deposits are rare
• differentiating from invasive thymoma
• larger than thymoma typically
• lack of septal or nodular structures typically
• necrosis and hemorrhage foci frequently
• mets
• lymph nodes frequently
• bone
• lung
• liver
• brain

Histologic features:

• nests and cords (hallmark)
• broad zone of fibrohyaline stroma separating tumour cell nests (hallmark)
• clear-cut cytologic atypia
• large, polyhedral cells
• vesicular or hyperchromatic nuclei
• nucleoli readily apparent
• eosinophilic cytoplasm
• keratinization and/or intercellular bridges
• variable mitoses
• intratumoural blood vessel invasion frequently
• foci of necrosis frequently
• May have a lymphoplasmacytic stroma
• Mature lymphocytes admixed with plasma cells
• Differentiation from SCC of other sites:
• Usually no palisading or radial arrangement of cells at the borders of nests

Immunophenotype:

Marker:	Sensitivity:	Specificity:
CD5	frequently	Good (SCCs in other organs are neg), much less common in thymomas
CD117	84%	much less common in thymomas and non-thymic squamous cell carcinomas
FOXN1	70%	Almost all thymomas express, much less common in non-thymic squamous cell carcinomas
CD205	10-60%	Almost all thymomas express, much less common in non-thymic squamous cell carcinomas
MUC1	88%	much less common in thymomas, not helpful for primary site distinction
Neuroendocrine markers (chromogranin, synaptophysin, CD56/NCAM) (focal)	65%
Immature T cell markers (neg) (CD1a, TdT, CD99)		In contrast to thymomas
Keratins
P63	83%
PAX8	75%
Neuroendocrine markers (focal)		Rare in thymomas
Proteasome subunit beta5t (neg)		Almost universal expression in Thymoma B

Molecular features:

• Pattern of gains and losses different from pulmonary squamous cell carcinoma 
• Losses:
• 16q
• 6 (also seen in B3 thymoma)
• 3p
• 17p
• CDKN2A (p16)
• Gains:
• 1q (also seen in B3 thymoma)
• 17q
• 18
• BCL2 commonly
• KIT mutation (up to 11%)
• Dramatic responses to TKI has been reported
• TP53 mutation (20%)
• GTF2I gene mutation (<10%) (21-82% of various thymoma types)
• Rare or absent:
• EGFR, KRAS, NRAS, BRAF, PIK3CA, APC, RET, PTEN mutations
• HER2 amplification

Other features:

•  polymyositis may occur
• no reports of myasthenia gravis or pure red cell aplasia

References:

•  WHO book 2004
• WHO book 2015 (IHC and introduction sections only)