'Neuroendocrine' middle ear adenomas: consistent expression of the transcription factor ISL1 further supports their neuroendocrine derivation.
OBJECTIVE
Neuroendocrine middle ear adenoma (MEA) is a rare epithelial neoplasm of uncertain histogenesis that frequently shows neuroendocrine features. To date, <120 cases have been reported. The aims of the current study were to describe our experience with neuroendocrine MEA, to assess the frequency of specific neuroendocrine differentiation, and to test these lesions for transcription factors known to be expressed in a variety of other neuroendocrine tumours.


RESULTS
We investigated six cases of neuroendocrine MEA, and stained them, for the first time, for the transcription factors CDX2, TTF1, PAX8, and ISL1 (islet-1). The patients were four men and two women (mean age, 39 years; range, 27-53 years). Two of four patients with extended follow-up (4.5-22 years) experienced recurrence at 92 months, and at 9 and 22 years, respectively. One case extending into the external ear coexisted with cholesteatoma. Histological examination showed trabecular, solid, acinar, glandular, cribriform, organoid, nested, diffuse non-cohesive plasmacytoid and pseudoalveolar patterns in varying combinations. Immunohistochemistry showed consistent expression of vimentin (4/4), pancytokeratin (6/6), synaptophysin (6/6), CD56 (4/4), and ISL1 (6/6). A CK7 antibody stained scattered cells in two of five cases. The myoepithelial markers and transcription factors TTF1, CDX2 or PAX8 were not expressed in any of the cases.


CONCLUSIONS
Middle ear adenoma is an indolent, locally recurring, but generally non-metastasizing neoplasm with uniform expression of synaptophysin and ISL1, indicating true neuroendocrine differentiation. Because of its highly varied cellular and architectural appearance, MEA should be distinguished from tympanic paraganglioma and a variety of rare benign and malignant lesions at this site.
Institute of Pathology, University Hospital, Erlangen, Germany.
Abbas
A
Agaimy
Michael
M
Lell
Tina
T
Schaller
Bruno
B
Märkl
Joachim
J
Hornung
D000236:Adenoma / Q000473:pathology*; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D004428:Ear Neoplasms / Q000473:pathology*; D004432:Ear, Middle / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000473:pathology*; D014157:Transcription Factors / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1
ISL1; carcinoid tumour; islet-1; middle ear adenoma; neuroendocrine adenoma