Middle ear neuroendocrine tumour/Middle Ear Adenoma (old term)
Histopathology:
– Surface mucosa appears unremarkable.
– Mainly solid nests and trabecular growth patterns in a background of loose fibrous stroma, with pseudo-infiltrative looking pattern (carcinoid like look).
– The single area shows a large glandular pattern.
– Neoplastic cells show monotonous round to ovoid nuclei with coarsely granular chromatin pattern and abundant granular pale eosinophilic cytoplasm (neuroendocrine like featuress)
– Mitoses, necrosis, and significant cytologic atypia are not seen.
– Zallballen pattern and destructive patterns are also not seen.
Practical points of Pathoclinics:
- Middle ear neuroendocrine tumour/Middle Ear Adenoma is an uncommon benign tumor with a dual neuroendocrine and mucin-secreting differentiation.
- Middle ear neuroendocrine tumour/Middle Ear Adenomasare small size (less than 1 cm) slow-growing tumors, often filling the middle ear cavity and affecting the ossicular chain. Extension outside the middle ear is uncommon.
- Microscopically, middle ear neuroendocrine tumour/middle Ear Adenomas are unencapsulated and infiltrative tumors but without tissue destruction. Middle ear neuroendocrine tumour/Middle Ear Adenomas have multiple different growth patterns: glandular and tubular patterns, pseudorosettes and cribriform structures, pseudopapillary degenerative-type changes, sold sheets, nests, ribbons and variable size organoid elongated trabeculae, cords, and single-cell patterns in a fibrous and collagenised stroma. Abrupt transitions between various patterns are common. Glandular patterns often show two cell layers with inner, luminal, flattened eosinophilic cells and outer basal, cuboidal-columnar cells with finely granular cytoplasm. Glands may show intraglandular secretion.
- Tumor cells are usually cuboidal to columnar type with a round to oval nuclei, finely granular salt and pepper nuclear chromatin, and a moderate amount of eosinophilic granular cytoplasm. In some cases, plasmacytoid and spindled cells are also found. Cytologic atypia is of low grade in most cases. Necrosis, significant atypia, and prominent nucleoli are usually not present. Peri-neural and lympho-vascular invasion are not seen.
- Associated cholesteatoma is a common finding.
- Immunohistochemistry helps to confirm the diagnosis. Middle ear neuroendocrine tumour/Middle Ear Adenomas are positive for keratin (strong and diffuse). Inner glandular cells are positive for CK7, while outer basal cells react strongly with neuroendocrine markers including INSM1. Middle adenoma also shows expression of ISL-1 (transcription factor expressed in pancreatic islet cells), pancreatic polypeptide, serotonin, glucagon, and SATB2. CK20 and TTF1 are negative.
- Middle ear neuroendocrine tumour/Middle Ear Adenomas have a very low proliferation rate but rates up to 20% have been reported. Increased proliferation rate has been associated with local recurrence and metastasis.
- The important differential is adenocarcinoma, due to the presence of an infiltrative looking pattern of glandular, tubular, cribriform, and back-to-back arrangement of glands. But careful observation and recognition of fibrotic and collagenized stroma separates it from desmoplastic stroma of adenocarcinoma. Tumor cells of adenocarcinomas more often show moderate to marked pleomorphism with mitoses and necrosis.
- Paraganglioma is another close differential,as both show delicate granular salt-pepper chromatin patterns and neuroendocrine markers. Paraganglioma often shows a nesting/trabecular pattern with surrounding vascularized loose stroma (Zellballen pattern) and, more often a basophilic granular cytoplasm. Reticulin stain highlights the zellballen architecture. Highlighting sustentacular cells with S100 protein along with negativity for cytokeratin are helpful feature for confirming a paraganglioma. Expression of ISL-1, pancreatic polypeptide, serotonin, glucagon, and SATB2 are helpful to distinguish middle ear neuroendocrine tumour/middle Ear Adenoma from paraganglioma.
- Ceruminous gland adenoma is a tumor of external auditory canal. It has an Inner luminal cells with decapitation secretions and outer basaloid cell. It is negative for neuroendocrine markers.
- Complete surgical resection, including the ossicles is usually received in multiple pieces for pathologic evaluation. The possibility of recurrences is likely in cases with incompletely excised tumors, but without risk of metastasis.
References and further reading:
- Asa SL, Arkun K, Tischler AS, Qamar A, Deng FM, Perez-Ordonez B, Weinreb I, Bishop JA, Wenig BM, Mete O. Middle Ear “Adenoma”: a Neuroendocrine Tumor with Predominant L Cell Differentiation. Endocr Pathol. 2021 Dec;32(4):433-441. doi: 10.1007/s12022-021-09684-z. Epub 2021 May 27. PMID: 34041698.
- Katabi N. Neuroendocrine Neoplasms of the Ear. Head Neck Pathol. 2018 Sep;12(3):362-366. doi: 10.1007/s12105-018-0924-4. Epub 2018 Aug 1. PMID: 30069842; PMCID: PMC6081292.
- Sandison A. Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumours of the Ear. Head Neck Pathol. 2022 Mar;16(1):76-86. doi: 10.1007/s12105-022-01450-9. Epub 2022 Apr 9. PMID: 35397067; PMCID: PMC9018943.
