Middle Ear “Adenoma”: a Neuroendocrine Tumor with Predominant L Cell Differentiation

Sylvia, L.; Arkun, Knarik; Tischler, Arthur S.; Qamar, Adnan; Deng, Fang; Perez-Ordoñez, Bayardo; Weinreb, Ilan; Bishop, Justin A.; Wenig, Bruce M.; Mete, Özgür

doi:10.1007/s12022-021-09684-z

Cited by 18 publications

(14 citation statements)

References 31 publications

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“…8). Tumors composed of L cells in the rectum and middle ear have a characteristic pattern of ribbons forming concentric whorls [66][67][68]102] (Figs. 4 and 9).…”

Section: Question 6: What Are the Morphological And Immunohistochemic...mentioning

confidence: 99%

“…All NETs express INSM1, synaptophysin, and chromogranin; the majority express chromogranin A that is the most widely used biomarker, but some express little or none of that form, instead producing chromogranin B and/or chromogranin C. In addition to these general biomarkers of neuroendocrine differentiation, most epithelial NETs express keratins; they are usually identified as epithelial using the AE1/AE3 cocktail, but a more reliable stain is CAM5.2. In addition, NETs can express the specific cytokeratins related to their site of origin; for example, NETs of the lung and upper aerodigestive tract and pancreas consistently express CK7 [102,103]. However, the best biomarkers that distinguish site of origin are the transcription factors and hormones discussed above as well as several other enzymes/proteins such as CEA that is intensely expressed by medullary thyroid carcinoma and prostate-specific acid phosphatase (PSAP) that is expressed by renal and colorectal tumors as well as other pelvic lesions [104].…”

Section: Question 6: What Are the Morphological And Immunohistochemic...mentioning

confidence: 99%

“…Their architecture is variable and includes sheets, glandular configurations, pseudorosettes, trabecula with swirling ribbons, and discohesive single cell infiltration of fibrous stroma. While exceptional cases of mixed middle ear adenoma and neuroendocrine tumors have been reported, a recent study has shown that the neoplastic cells are a homogeneous population that expresses INSM1, synaptophysin, and SATB2 as well as focal CDX2 with occasional weak GATA3; the tumor cells are consistently positive for keratins (AE1/ AE3, CAM5.2) [102]. The majority are composed of L cells that express glucagon, pancreatic polypeptide, and peptide-YY, and like other L cell NETs, chromogranin A positivity is variable; some tumors express serotonin.…”

Section: Question 11: What Are Spinal Middle Ear Neuroendocrine Tumor...mentioning

confidence: 99%

“…9). A MeNET with G3 proliferative features has also been recognized [102]; however, further work is required to determine if grading as G1, G2, and G3 should be implemented as in other NETs.…”

Section: Question 11: What Are Spinal Middle Ear Neuroendocrine Tumor...mentioning

confidence: 99%

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Overview of the 2022 WHO Classification of Neuroendocrine Neoplasms

et al. 2022

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In this review, we detail the changes and the relevant features that are applied to neuroendocrine neoplasms (NENs) in the 2022 WHO Classification of Endocrine and Neuroendocrine Tumors. Using a question-and-answer approach, we discuss the consolidation of the nomenclature that distinguishes neuronal paragangliomas from epithelial neoplasms, which are divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The criteria for these distinctions based on differentiation are outlined. NETs are generally (but not always) graded as G1, G2, and G3 based on proliferation, whereas NECs are by definition high grade; the importance of Ki67 as a tool for classification and grading is emphasized. The clinical relevance of proper classification is explained, and the importance of hormonal function is examined, including eutopic and ectopic hormone production. The tools available to pathologists for accurate classification include the conventional biomarkers of neuroendocrine lineage and differentiation, INSM1, synaptophysin, chromogranins, and somatostatin receptors (SSTRs), but also include transcription factors that can identify the site of origin of a metastatic lesion of unknown primary site, as well as hormones, enzymes, and keratins that play a role in functional and structural correlation. The recognition of highly proliferative, well-differentiated NETs has resulted in the need for biomarkers that can distinguish these G3 NETs from NECs, including stains to determine expression of SSTRs and those that can indicate the unique molecular pathogenetic alterations that underlie the distinction, for example, global loss of RB and aberrant p53 in pancreatic NECs compared with loss of ATRX, DAXX, and menin in pancreatic NETs. Other differential diagnoses are discussed with recommendations for biomarkers that can assist in correct classification, including the distinctions between epithelial and non-epithelial NENs that have allowed reclassification of epithelial NETs in the spine, in the duodenum, and in the middle ear; the first two may be composite tumors with neuronal and glial elements, and as this feature is integral to the duodenal lesion, it is now classified as composite gangliocytoma/neuroma and neuroendocrine tumor (CoGNET). The many other aspects of differential diagnosis are detailed with recommendations for biomarkers that can distinguish NENs from nonneuroendocrine lesions that can mimic their morphology. The concepts of mixed neuroendocrine and non-neuroendocrine (MiNEN) and amphicrine tumors are clarified with information about how to approach such lesions in routine practice. Theranostic biomarkers that assist patient management are reviewed. Given the significant proportion of NENs that are associated with germline mutations that predispose to this disease, we explain the role of the pathologist in identifying precursor lesions and applying molecular immunohistochemistry to guide genetic testing.

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“…8). Tumors composed of L cells in the rectum and middle ear have a characteristic pattern of ribbons forming concentric whorls [66][67][68]102] (Figs. 4 and 9).…”

Section: Question 6: What Are the Morphological And Immunohistochemic...mentioning

confidence: 99%

Section: Question 6: What Are the Morphological And Immunohistochemic...mentioning

confidence: 99%

Section: Question 11: What Are Spinal Middle Ear Neuroendocrine Tumor...mentioning

confidence: 99%

Section: Question 11: What Are Spinal Middle Ear Neuroendocrine Tumor...mentioning

confidence: 99%

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Overview of the 2022 WHO Classification of Neuroendocrine Neoplasms

et al. 2022

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“…They are also called middle ear adenomas, the terminology adenoma is not appropriate, as these tumors can be invasive and even occasionally metastatic. Sylvia L. Asa has shown that these neuroendocrine tumors are usually of low proliferative grade, similar to Grade 1 tumors of the gastroenteropancreatic tract, but they occasionally have Ki67 labeling indices that would allow classification as Grades 2 and 3 neuroendocrine tumors [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

Middle ear neuroendocrine tumor: a case report

Lachkar

Benfadil

Elayoubi

2022

Journal of Surgical Case Reports

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Neuroendocrine tumors are extremely rare in the middle ear. These tumors represent a spectrum of tumors with a diverse range of molecular abnormalities, functionality and anatomical locations. We present a rare case of middle ear neuroendocrine tumor, review the pathology and differential diagnosis of the tumors, and discuss the management and follow-up of patients with these tumors. We suspect that the middle ear neuroendocrine tumor is underdiagnosed and more cases can be detected through education and personal experience. Treatment is surgical resection, and long follow-up is recommended.

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