Abstract
Ceruminous glands are modified apocrine glands, situated in the external auditory canal (EAC) that, together with sebaceous glands, produce cerumen. The neoplastic transformation of these structures is exceedingly rare. We encounter two cases of EAC adenocarcinoma with ETV6::NTRK3 fusion. Despite this genetic overlap, the morphology and immunophenotype delineate its clear separation from secretory carcinoma. These cases demonstrate novel primary EAC adenocarcinoma with papillary morphology, which expands the ever-increasing list of ETV6::NTRK3-positive malignancies and which we would like to term ETV6::NTRK3-translocation associated papillary adenocarcinoma. We also advocate the use of molecular techniques in rare tumors of uncertain type or differentiation, to increase understanding and possibilities of reproducible classification of these rare neoplasms. Pathologists and oncologists should recognize this entity, which leads to a direct approach for detecting NTRK fusion for appropriate treatment.
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References
Nagarajan P (2018) Ceruminous neoplasms of the ear. Head Neck Pathol 12(3):350–361
Sandison A (2022) Update from the 5th edition of the World Health Organization classification of head and neck tumours: tumours of the ear. Head Neck Pathol 16(1):76–86
Bruschini L, Ciabotti A, De Vito A et al (2017) Syringocystadenoma papilliferum of the external auditory canal. Am J Case Rep 18:520–524
Laababsi R, Elkrimi Z, Bouzbouz A et al (2020) Hidradenoma papilliferum of the external auditory canal. Case report. Ann Med Surg (Lond) 49:41–43
Bertram CA, Klopfleisch R, Muller K (2019) Complex ceruminous gland adenocarcinoma of the external ear canal in a Guinea pig (Cavia porcellus). J Small Anim Pract 60(7):454
Chiosea SI, Griffith C, Assaad A, Seethala RR (2012) Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands. Histopathology 61(3):387–394
Yosefof E, Boldes T, Dan D, et al. (2023) Salivary gland secretory carcinoma; review of 13 years world-wide experience and meta-analysis. Laryngoscope
Skalova A, Vanecek T, Sima R et al (2010) Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol 34(5):599–608
Taverna C, Pollastri F, Pecci R et al (2021) Papillary-cystic neoplasms of the middle ear are distinct from endolymphatic sac tumours. Histopathology 79(3):306–314
Kinnunen M, Liu X, Niemela E et al (2023) The impact of ETV6-NTRK3 oncogenic gene fusions on molecular and signaling pathway alterations. Cancers (Basel) 15(17):4246
Amin SM, Beattie A, Ling X, Jennings LJ, Guitart J (2016) Primary cutaneous mammary analog secretory carcinoma with ETV6-NTRK3 translocation. Am J Dermatopathol 38(11):842–845
Andreasen S, Skalova A, Agaimy A et al (2017) ETV6 gene rearrangements characterize a morphologically distinct subset of sinonasal low-grade non-intestinal-type adenocarcinoma: a novel translocation-associated carcinoma restricted to the sinonasal tract. Am J Surg Pathol 41(11):1552–1560
Kishikawa S, Hayashi T, Shimizu J et al (2022) Low-grade tracheal adenocarcinoma with ETV6::NTRK3 fusion: unique morphology akin to subsets of sinonasal low-grade non-intestinal-type adenocarcinoma. Virchows Arch 481(5):793–797
Klubickova N, Mosaieby E, Ptakova N et al (2023) High-grade non-intestinal type sinonasal adenocarcinoma with ETV6::NTRK3 fusion, distinct from secretory carcinoma by immunoprofile and morphology. Virchows Arch 483(2):187–195
Ramos J, Mahmud W, Ocampo FA, Alex G, Gattuso P (2020) Primary mammary-analogue secretory carcinoma of the lung: a rare entity with an unusual location. Int J Surg Pathol 28(7):775–781
Rooper LM, Thompson LDR, Gagan J et al (2022) Low-grade non-intestinal-type sinonasal adenocarcinoma: a histologically distinctive but molecularly heterogeneous entity. Mod Pathol 35(9):1160–1167
Seethala RR, Chiosea SI, Liu CZ, Nikiforova M, Nikiforov YE (2017) Clinical and morphologic features of ETV6-NTRK3 translocated papillary thyroid carcinoma in an adult population without radiation exposure. Am J Surg Pathol 41(4):446–457
von der Thusen JH, Dumoulin DW, Maat A et al (2021) ETV6-NTRK3 translocation-associated low-grade mucinous bronchial adenocarcinoma: a novel bronchial salivary gland-type non-small cell lung cancer subtype. Lung Cancer 156:72–75
Ando Y, Morita S, Shimokata T et al (2022) A rapid and durable response to larotrectinib in a patient with NTRK fusion-positive secretory carcinoma originating from the external auditory canal. Int Cancer Conf J 11(4):242–246
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DB, EM, RB, and MA—conception and design of work, acquisition and interpretation of data, and drafting the MS and revising it. All authors have read and approved the final manuscript.
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Part of this work was presented at European Congress of Pathology, Dublin, 2023.
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Bell, D., Maghami, E., Bakkar, R. et al. ETV6::NTRK3-associated papillary adenocarcinoma: let us play it by ear. Virchows Arch (2024). https://doi.org/10.1007/s00428-024-03735-6
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DOI: https://doi.org/10.1007/s00428-024-03735-6