Case 84

A 67-year-old male with presentation of a a neck mass.

What's the diagnosis?
A: metastatic hepatocellular carcinoma
B: keratinizing squamous cell carcinoma
C: non-keratinizing squamous cell carcinoma
D: Poorly differentiated adenocarcinoma

Answer

The correct answer is B. This is a case of keratinizing squamous cell carcinoma.

5–10% of head and neck cancers present as cancer of unknown primary (CUP).
With recent diagnostic advances, the primary site is identified in >90% of these cases, most commonly in the oropharynx.
A neck mass is the initial symptom in 44% of patients with oropharyngeal HPV-associated squamous cell carcinoma (SCC).
In EBV-endemic areas, the nasopharynx is a common site of primary tumor.
In metastatic cutaneous head and neck SCC, about 25% of patients have an unknown index lesion.
The percentage of true CUP (where no primary is found even after thorough evaluation) is <3% of suspected CUP cases.
HPV and EBV are proven carcinogenic factors and play a significant etiological role in CUP.
UV radiation signature mutations (e.g., C>T substitutions at dipyrimidine sites, including CC>TT) indicate sun-induced DNA damage.
Presence of UV signature mutations in CUP suggests a cutaneous (skin) primary, seen in:
- Metastatic cutaneous SCC
- Polyomavirus-negative Merkel cell carcinoma
Polymorphous adenocarcinomas, especially the cribriform subtype with PRKD1/2/3 gene rearrangements, are associated with a higher risk of nodal metastasis.

Case credit: UCSD pathology

Author: Wangpan Jackson Shi, MD

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