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Neuroendocrine Neoplasms of the Larynx: A Clinicopathologic Analysis of 27 Neuroendocrine Tumors and Neuroendocrine Carcinomas

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Abstract

Laryngeal neuroendocrine neoplasms (NENs) are rare and heterogeneous, encompassing well-differentiated neuroendocrine tumors (NETs; grade 1, 2, and 3), neuroendocrine carcinomas (NECs, small cell and large cell types), and mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN). We aimed to study the clinicopathologic spectrum of these neoplasms. A retrospective review of all primary laryngeal NENs diagnosed from 2005 to 2017 was undertaken. Mitotic index was divided into < 2, ≥ 2–10, and > 10 mitoses/2 mm2, with a Ki-67 labelling index of < 2%, ≥ 2–20%, and > 20% for the NET grade 1, 2 and 3 categories, respectively. A total of 27 patients were included. The median age at presentation was 60 years; the male-to-female ratio was 8:1. Supraglottis (n = 22) was the most frequently affected subsite. There were 9 NETs grade 2 (G2), and 18 NECs cases. There were no NET grade 1 or 3 cases in our cohort. Among the NETs G2, the morphology was epithelioid (2), plasmacytoid (3), clear (2), oncocytic (1), and rhabdoid (1). Unique ‘glomeruloid structures’ (n = 5), calcification (n = 3), lymphoid aggregates (n = 5), intranuclear inclusions (n = 2), hyaline globules (n = 3), and Leisegang rings (n = 2) were identified. NECs comprised 16 small cell neuroendocrine carcinoma and 2 large cell neuroendocrine carcinoma. On immunohistochemistry, tumor cells expressed AE1/AE3 (86%), synaptophysin (100%), chromogranin (100%), INSM1 (100%), calcitonin (33.3%). In the NEC group, p53 aberrant expression (87.5%), Retinoblastoma (Rb) loss (88.2%), and diffuse p16 immunoreactivity (66.7%) were additionally observed. Lymph-node metastasis was detected in 62.5% and 85.7%, while distant metastasis in 55.6% and 76.9%, respectively in NET G2 and NEC. Laryngeal NENs are aggressive neoplasms with a high rate of nodal and distant metastasis. Awareness of the wide pathologic spectrum of laryngeal NENs and appropriate use of IHC is needed to render an accurate diagnosis. Ki67 assessment is strongly recommended for laryngeal NEN prognostication

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Acknowledgements

We sincerely thank Dr Jay Mehta, Center of Oncopathology, Mumbai, for his generous support in IHC standardization, and Shirsat laboratory, ACTREC, Ms. Priti Shenoy and Ms. Neelam for their technical assistance during the study.

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Authors and Affiliations

  1. Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India

    Munita Bal, Aishwarya Sharma, Swapnil Ulhas Rane, Neha Mittal & Asawari Patil

  2. Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India

    Devendra Chaukar

  3. Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India

    Kumar Prabhash

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  1. Munita Bal
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [AS], and [MB]. The first draft of the manuscript was written by [MB] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Munita Bal.

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All procedures performed in the study were in accordance with the ethical standards of the Institutional Ethics Committee.

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Not required as per institutional ethics committee’s policy for retrospective case series. The authors declare that all information is anonymized and the submission does not include images that may identify any patient.

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Bal, M., Sharma, A., Rane, S.U. et al. Neuroendocrine Neoplasms of the Larynx: A Clinicopathologic Analysis of 27 Neuroendocrine Tumors and Neuroendocrine Carcinomas. Head and Neck Pathol 16, 375–387 (2022). https://doi.org/10.1007/s12105-021-01367-9

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