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Neck Node Squamous Cell Metastasis from Unknown Primary and Mutagen Sensitivity: A Case Series.

ABSTRACT: Most of the neck node metastases from cancer of unknown primary (CUP) are squamous cell carcinomas (SCCs). The majority of which are human papillomavirus (HPV)-related, frequently show cystic morphology referring to Waldeyer's ring origin. Here, we report four cases of neck node SCCs metastases from CUP. In our institute, 432 patients with head and neck (HN) SCC underwent pretreatment mutagen sensitivity (MS) assay between 1996 and 2006. Among them, 4 patients ≤50 years of age had metastatic cervical nodes from CUP. The primary treatment was cervical node dissection ± radiotherapy. All patients had elevated (>1.0 chromatid break/cell) MS. One male patient died of progressive neck metastasis within 3 years and the 3 female patients are still alive more than 15 years after initial treatment of HPV+ (two) or cystic (one) SCC. Two female patients developed second and third distant site metachronous primary cancers. HPV+ or cystic HNSCC from CUP with elevated MS indicates good outcome. Distant site metachronous cancers of different histologic origins cannot be explained by field cancerization. The clinical significance of elevated MS in neck node SCC metastasis from CUP requires further investigation.

SUBMITTER: Bukovszky B

PROVIDER: S-EPMC10730097 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature

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Neck Node Squamous Cell Metastasis from Unknown Primary and Mutagen Sensitivity: A Case Series.

Bukovszky Botond B Fodor János J Székely Gábor G Tóth Erika E Major Tibor T Oberna Ferenc F Takácsi-Nagy Zoltán Z Polgár Csaba C

Case reports in oncology 20230101 1

Most of the neck node metastases from cancer of unknown primary (CUP) are squamous cell carcinomas (SCCs). The majority of which are human papillomavirus (HPV)-related, frequently show cystic morphology referring to Waldeyer's ring origin. Here, we report four cases of neck node SCCs metastases from CUP. In our institute, 432 patients with head and neck (HN) SCC underwent pretreatment mutagen sensitivity (MS) assay between 1996 and 2006. Among them, 4 patients ≤50 years of age had metastatic cer ...[more]

PMID: 38116298

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Project description:ImportancePatients 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.ObjectiveTo 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 participantsThe 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.InterventionConventional histopathological techniques performed on TBM and tonsillectomy specimens at participating centers, followed by SSS performed at the central laboratory.Main outcomeIdentification of cancer on central histopathological review of TBM and tonsillectomy specimens.ResultsTissue 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 relevanceIn 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.

Project description:A subset of head and neck squamous cell carcinomas present solely as metastatic disease in the neck and are of unknown primary origin (SCCUP). Most primary tumors will ultimately be identified, usually in the oropharynx. In a minority of cases, the primary site remains elusive. Here, we examine the role of ancillary testing, including mutational signature analysis (MSA), to help identify likely primary sites in such cases. Twenty-two cases of SCCUP in the neck, collected over a 10-year period, were classified by morphology and viral status; including human papillomavirus (HPV) testing by p16 immunohistochemistry (IHC) and RT-qPCR, as well as Epstein-Barr virus (EBV) testing by EBER-ISH. CD5 and c-KIT (CD117) IHC was done to evaluate for possible thymic origin in all virus-negative cases. Whole exome sequencing, followed by MSA, was used to identify UV signature mutations indicative of cutaneous origin. HPV was identified in 12 of 22 tumors (54.5%), favoring an oropharyngeal origin, and closely associated with nonkeratinizing tumor morphology (Fisher's exact test; p = 0.0002). One tumor with indeterminant morphology had discordant HPV and p16 status (p16+/HPV-). All tumors were EBV-negative. Diffuse expression of CD5 and c-KIT was identified in 1 of 10 virus-negative SCCUPs (10%), suggesting a possible ectopic thymic origin rather than a metastasis. A UV mutational signature, indicating cutaneous origin, was identified in 1 of 10 (10%) virus-negative SCCUPs. A cutaneous auricular primary emerged 3 months after treatment in this patient. Primary tumors became clinically apparent in 2 others (1 hypopharynx, 1 hypopharynx/larynx). Thus, after follow-up, 6 tumors remained unclassifiable as to the possible site of origin (27%). Most SCCUPs of the neck in our series were HPV-associated and thus likely of oropharyngeal origin. UV signature mutation analysis and additional IHC for CD5 and c-KIT for possible thymic origin may aid in further classifying virus-negative unknown primaries. Close clinical inspection of hypopharyngeal mucosa may also be helpful, as a subset of primary tumors later emerged at this site.

Dataset Information

Neck Node Squamous Cell Metastasis from Unknown Primary and Mutagen Sensitivity: A Case Series.

Publications

Neck Node Squamous Cell Metastasis from Unknown Primary and Mutagen Sensitivity: A Case Series.

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