Case 79
- Wangpan Shi
- Mar 17
- 1 min read
A 80-year-old male with a significant smoking history that showed a large left lower lobe mass. Here is the resection:
What's your diagnosis?
A: Squamous cell carcinoma
B: Adenosquamous cell carcinoma
C: Atypical carcinoid
D: Large cell neuroendocrine carcinoma
Answer
The correct answer is A. The tumor are diffusely positive for P40 and P63 while negative for neuroendocrine markers.
Key Genetic and Epigenetic Features of SCC:
Genomic Alterations:
Comprehensive genomic analysis reveals SCCs with numerous alterations, including an average of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy-number alterations per tumor.
Preferential Pathways Involved:
Oxidative stress pathway: Mutations in NFE2L2, KEAP1, or CUL3.
Squamous differentiation pathway: Involves overexpression/amplification of SOX2 and TP63, mutations in NOTCH1, NOTCH2, ASCL4, and focal deletions in FOXP1.
Frequent Genomic Alterations:
Chromosome amplifications:
3q (SOX2, TP63)
7p (EGFR)
8p (FGFR1)
Chromosome deletions:
9p (CDKN2A)
Common Mutated Genes:
TP53, CDKN2A, PTEN, PIK3CA, KEAP1, KMT2 (MLL2), HLA-A, NFE2L2, NOTCH1, and RB1.
Subtypes and Molecular Profiling:
Gene expression profiling has identified four subtypes of SCC:
Primitive
Classic
Secretory
Basal
Despite these subtypes, there is no correlation between the basal gene expression subtype and the basaloid histological subtype.
Basaloid SCC:
Shared Mutational Landscape: Basaloid SCC shares most of the genetic alterations found in classic SCCs.
Transcriptomic Differences: Compared to non-basaloid SCC, basaloid SCC shows:
Upregulation of genes involved in the cell cycle, embryonic development, mRNA splicing, and chromatin modification.
Downregulation of genes related to squamous differentiation. This is consistent with the aggressive behavior and poor differentiation of basaloid SCC.
Case credit: UCSD pathology
Author: Wangpan Jackson Shi, MD
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