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Immunohistochemical Expression of Choline Acetyltransferase and Catecholamine-Synthesizing Enzymes in Head-and-Neck and Thoracoabdominal Paragangliomas and Pheochromocytomas

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Abstract

Paragangliomas (PGLs) are neural-crest-derived, non-epithelial neuroendocrine tumors distributed along the parasympathetic and sympathetic nerves. Head-and-neck PGLs (HNPGLs) have been recognized as nonchromaffin, nonfunctional, parasympathetic tumors. By contrast, thoracoabdominal paragangliomas and pheochromocytomas (PPGLs) are chromaffin, functional, sympathetic tumors. Although HNPGLs and PPGLs have the same histological structure, the zellballen pattern, composed of chief and sustentacular cells surrounded by abundant capillaries, the pathobiological differences between these types of PGLs remain unclarified. To determine the phenotypic features of these PGLs, we performed an immunohistochemical study using specific antibodies against choline acetyltransferase (ChAT), an enzyme involved in acetylcholine synthesis, and enzymes for the catecholamine-synthesis, tyrosine hydroxylase (TH), and dopamine beta-hydroxylase (DBH), in 34 HNPGLs from 31 patients, 12 thoracoabdominal PGLs from 12 patients, and 26 pheochromocytomas from 22 patients. The expression of ChAT, TH, and DBH was 100%, 23%, and 10% in the HNPGLs; 12%, 100%, and 100% in the pheochromocytomas; and 25%, 67%, and 100% in the thoracoabdominal PGLs, respectively. These results designate HNPGLs as acetylcholine-producing parasympathetic tumors, in contrast to PPGLs being catecholamine-producing tumors. The other most frequently used neuroendocrine markers are synaptophysin and chromogranin A expressed 100% and 80%, respectively, and synaptophysin was superior to chromogranin A in HNPGLs. This is the first report of HNPGLs being acetylcholine-producing tumors. Immunohistochemistry of ChAT could be greatly useful for pathologic diagnosis of HNPGL. Whether measurement of acetylcholine levels in the blood or urine could be a tumor marker of HNPGLs should be investigated soon.

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Acknowledgements

The authors thank to Azuma M, MT. CIAC, Department of Diagnostic Pathology, National Hospital Organization Hakodate Hospital, Hakodate, Japan, for the technical support in immunohistochemistry.

Funding

This study was supported in part by a Grant-in-Aid from the Japan Agency for Medical Research and Development (AMED) under Grant Number 20ek0109352h0003.

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Authors and Affiliations

  1. Department of Clinical Research, Department of Diagnostic Pathology, National Hospital Organization Hakodate Hospital, Hakodate, Japan

    Noriko Kimura

  2. Department of Head & Neck Surgery, Iwate Medical University School of Medicine, Morioka, Japan

    Kiyoto Shiga

  3. Department of Otolaryngology-Head and Neck Surgery, Nagasaki University Graduate School of Bio-Medical Sciences, Nagasaki, Japan

    Ken-ichi Kaneko

  4. Department of Endocrinology and Metabolism, Hamamatsu Medical School, Hama-Matsu-Kita Hospital, Hamamatsu, Japan

    Yutaka Oki

  5. Division of Diabetes, Metabolism and Endocrinology, Showa University Fujigaoka Hospital, Yokohama, Japan

    Chiho Sugisawa

  6. Endocrinology and Diabetes Center, Yokohama Rosai Hospital, Yokohama, Japan

    Jun Saito

  7. Department of Gastroenterology, Osaka General Medical Center, Osaka, Japan

    Seiich Tawara

  8. Department of Endocrinology and Metabolism, Toyama Prefectural Central Hospital, Toyama, Japan

    Hiroshi Akahori

  9. Medical Oncology, KKR Sapporo Medical Center, Sapporo, Japan

    Susumu Sogabe

  10. Kyoto University Graduate School of Medicine, Faculty of Medicine, Department of Diabetes, Endocrinology and Nutrition, Metabolism and Endocrinology, Division of Internal Medicine, Kishiwada City Hospital, Kishiwada, Japan

    Takafumi Yamashita

  11. Division of Sports Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

    Kazuhiro Takekoshi

  12. Department of Endocrinology, Metabolism, and Hypertension, National Hospital Organization, Kyoto Medical Center, and Endocrine Center, Ijinkai Takeda General Hospital Kyoto, Japan

    Mitsuhide Naruse

  13. Division of Metabolism and Endocrinology, Department of Internal Medicine, St. Marianna University School of Medicine Yokohama City Seibu Hospital, Yokohama, Japan

    Takayuki Katabami

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  1. Noriko Kimura
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Contributions

NK and KS designed the study. KS, KK, YO, CS, JS, ST, HA, SS, TY, TK, and MN collected materials and clinical data. KT analyzed gene mutations. NK analyzed pathologic data and interpretation, and wrote the first draft of the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Noriko Kimura.

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Institutional Review Board Statement

The paraffin sections used in this study were obtained from archival materials. Institutional Ethical Board in National Hospital Organization Hakodate Hospital approved the research, #R3-0730001.

Informed Consent Statement

Informed consent for the research was obtained from all patients at each institute.

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The authors declare no competing interests.

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Kimura, N., Shiga, K., Kaneko, Ki. et al. Immunohistochemical Expression of Choline Acetyltransferase and Catecholamine-Synthesizing Enzymes in Head-and-Neck and Thoracoabdominal Paragangliomas and Pheochromocytomas. Endocr Pathol 32, 442–451 (2021). https://doi.org/10.1007/s12022-021-09694-x

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