Step Serial Sectioning in Head and Neck Squamous Cell Carcinoma of Unknown Primary

Abstract

Importance: Patients with suspected head and neck squamous cell carcinoma of unknown primary (HNSCCUP) may undergo tonsillectomy and tongue base mucosectomy (TBM) to help identify clinicoradiologically occult primary disease. It is hypothesized that when these diagnostic specimens are analyzed, conventional histopathological (CH) techniques risk missing small primary tumors that may be hidden in the tissue blocks.

Objective: To establish the outcomes of a step serial sectioning (SSS) histopathological technique vs CH when analyzing diagnostic tissue specimens from TBM and tonsillectomy performed for HNSCCUP.

Design, setting, and participants: The MOSES prospective multicenter noninterventional cohort study was conducted over a 25-month period from November 2019 at secondary and tertiary care ear, nose, and throat departments in the United Kingdom and included adults with clinicoradiologically occult HNSCCUP who were undergoing TBM.

Intervention: Conventional histopathological techniques performed on TBM and tonsillectomy specimens at participating centers, followed by SSS performed at the central laboratory.

Main outcome: Identification of cancer on central histopathological review of TBM and tonsillectomy specimens.

Results: Tissue from 58 eligible patients was analyzed (median [range] age, 58 [47-82] years; 10 women [17%]), with 20 480 sections cut in the laboratory and 4096 sections directly examined by a pathologist (median [range], 64 [28-135] per patient). The overall identification rate for TBM following SSS according to study protocol was 50.0% (95% CI, 37.5%-62.5%) and by subgroups was 42.9% (95% CI, 21.4%-67.4%) when performed following a negative bilateral tonsillectomy, 46.7% (95% CI, 24.8%-69.9%) at the same time as bilateral tonsillectomy, and 57.1% (95% CI, 36.5%-75.5%) following historic tonsillectomy. Conventional histopathological techniques at central review identified 2 undiagnosed primary tumors and revised the diagnosis of 2 other cases (1 nonmalignant and another down staged). Step serial sectioning identified a single additional tumor: an ipsilateral synchronous tongue base tumor for which a contralateral tumor had been identified on CH. Multifocal disease was seen in 5 (8.6%); all were human papillomavirus-related and in the tongue base.

Conclusions and relevance: In this multicenter cohort study of patients undergoing TBM for HNSCCUP, SSS was associated with added considerable histopathological workload with minimal additional diagnostic benefit. A second opinion for conventional histological techniques may be more beneficial. Synchronous primary disease should be considered when planning diagnostic oropharyngeal surgery for these patients.

Figure 1.. Comparison of the Fidelity of Step Serial Sectioning With Conventional Histology for Palatine Tonsillar Specimens in the MOSES Study

A, Conventional sections from 8 blocks stained with hematoxylin and eosin. B, Step sections taken at 500-μm intervals through the block generates a further 33 sections for examination.

Figure 2.. Right Tongue Base Human Papillomavirus–Associated Squamous Cell Carcinoma Discovered by Serial Step Sections in the MOSES Study

Hematoxylin and eosin (A), p16 immunohistochemistry (B), and high-risk human papillomavirus DNA in situ hybridization (C). The black box highlights patch of positive staining (original magnification ×2.5).