Aggressive papillary tumor of endolymphatic sac: case report of a rare neoplasia

Laboratorial ISSN: 1676-2444 jbpml@sbpc.org.br,adagmar.andriolo@g mail.com Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial Brasil Cambruzzi, Eduardo; Pêgas, Karla Lais; Almeida, Leandro P.; Perondi, Gerson Evandro; Dini, Leandro I. Aggressive papillary tumor of endolymphatic sac: case report of a rare neoplasia Jornal Brasileiro de Patologia e Medicina Laboratorial, vol. 52, núm. 1, febrero, 2016, pp. 31-34 Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial Rio de Janeiro, Brasil


introDuCtion
Aggressive papillary tumor of the endolymphatic sac is an uncommon process arising in temporal bone/endolymphatic sac that is characterized by an aggressive local behavior without metastasizing potential (1)(2)(3) .It has also been reported as an aggressive papillary middle-ear tumor, endolymphatic sac tumor (ELST), aggressive papillary tumor of temporal bone, low-grade adenocarcinoma of endolymphatic sac origin, among others (1)(2)(3)(4)(5) .ELST occurs in both genders with a similar distribution, affecting patients with a median age of 42 years.A similar number of ELST involves the right and left side, and bilateral tumors are extremely rare lesions.The most frequent clinical complaints are unilateral hearing loss and vertigo (1)(2)(3)(4)(5) .

Convincing
anatomic, morphological and immunohistochemical data support the origin of ELST in the epithelium of the inner ear.Most lesions arise in the petrous portion of temporal bone, but the tumor is also described in the areas of the jugular bulb, mastoid, posterior cranial fossa, and middle ear, without unequivocal radiologic evidence of endolymphatic sac involvement (2)(3)(4)(5)(6)(7) .Herein, the authors report an example of large recurrent ELST arising in the temporal bone, and discuss clinical and pathologic aspects of this rare tumor.

CaSE rEPort
A 38-year-old female patient was taken to the neurology service with clinical complaint of right facial paralysis in the last two months.On physical/neurological examination, right fifth through eighth cranial nerve paralysis was identified.Ophthalmic examination exhibited a normal optic nerve papilla.The other organs and systems showed no clinical alterations, as there was no previous history of relevant disease.Computed tomography (CT) imaging revealed a large, hypodense, expansive lytic lesion involving right temporal bone and middle ear (Figure 1).CT/magnetic resonance (RM) imaging of the chest and abdomen did not identify significant alterations.The patient underwent resection of the lesion.The pathologic specimen was composed of some irregular gray fragments of tissue, the largest measuring 1.5 cm in the largest dimension.At microscopy, a neoplastic process was identified exhibiting monomorphic epithelial columnar cells with clear/eosinophilic cytoplasm, round to oval nuclei, and mild atypias, arranged in a papillary pattern (Figure 2).No mitotic figures or necrosis were noted.The lesion exhibited positive immunoexpression for pancytokeratins, epithelial membrane antigen, and vimentin; and negative stains for synaptophysin, glial fibrillary acid protein, enolase neuron-specific, thyroglobulin, transthyretin, chromogranin, thyroid transcription factor 1 (TTF-1), transacting T-cell specific transcription factor GATA-3, intestinal transcription factor CDX-2, villin, napsin-A, and desmin.The diagnosis of ELST was then established.Six years after initial therapy, CT identified a large mass on the right temporal bone, compatible with lesion recurrence (Figure 3).

DiSCuSSion
ELST is a rare invasive tumor of the temporal bone/ middle ear that is described in patients aged 4 years to 85 years (1,5,6,(8)(9)(10) .In general, the affected patients complain of audiological symptoms, vertigo, cerebellar disorders, and facial nerve paralysis.Rare cases are related to a tumor mass that fills the tympanic cavity.A long-standing symptom history and indolent clinical course are typical of ELST (1,3,5,6,(8)(9)(10) .Bilateral ELST are very rare, and these cases are commonly associated with von Hippel-Lindau syndrome (VHLS).This syndrome is a rare, genetically based, autosomal dominant disorder that affects around 1:39,000 people, and until 20% of ELST cases are related to VHLS.The gene associated with VHLS is mapped on chromosome 3p25-p26, and pheochromocytomas, paragangliomas, pancreatic neuroendocrine tumors, pancreatic islet tumors, clear cell renal cell carcinoma, and central nervous system hemangioblastomas, are important manifestations of this disease (2,3,7,(11)(12)(13) .In the inner ear, the membranous labyrinth, which is a closed system with a sac, the endolymphatic sac, is lined by a simple epithelium except in the endolymphatic sac, where the cells are columnar and probably associated to

FigurE 2 − Aggressive papillary tumor of endolymphatic sac. A) a neoplastic process exhibiting papillary structures lined by a single layer of epithelial cells, 100×; B) monomorphic columnar cells with clear cytoplasm, ovoid central nuclei, and mild atypias covering papillary structures with numerous capillaries, 200×
endolymph absorption.The endolymphatic sac, lying in the subdural space of the underlying brain, and the choroid plexus have neuroectodermal origin (6,7,10,14,15) .ELST are usually reddish brown gritty tumors, exhibiting soft tissue density on radiological scans.The characteristic invasive aspect of the tumor can be identified on computed tomography, and the petrous temporal bone, mastoid process, or even the cerebellum, are frequently compromised (1-3, 6, 8, 9, 14) .Advanced tumors can extend into cranial fossa or to skull base near jugular foramen.Reported tumor sizes in the international literature ranged from 7.5 cm to 0.5 cm (1-3, 6, 8, 9, 14) .At microscopy, the process shows a complex interdigitating papillary pattern with variablesized fibrovascular septa, which are covered by a simple layer of low, cuboidal to columnar epithelial cells.In some cases, the neoplastic cells are disposed in cords and/or trabeculae (2-4, 7, 9, 12, 16) .An acinar pattern or microcysts are rarely found.Fibrotic response varies from minimal to desmoplastic reactions.Extensive infiltration of bone and soft tissue, cholesterol clefts, and hemorrhagic areas are common findings (2-4, 7, 9, 12, 16) .Tumoral cells can demonstrate an eosinophilic, clear, or vacuolated cytoplasm, with indistinct cell borders and centrally placed oval nuclei with granular chromatin.A low mitotic index is the rule (6,8,9,12,14,17) .ELST shows positive immunoexpression for cytokeratin, vimentin, and epithelial membrane antigen; and negative expression for thyroglobulin, transthyretin, synaptophysin, chromogranin, desmin, and actin.Some tumors can show positive expression for glial fibrillary acid protein (GFAP), S100, and neuron-specific enolase (NSE).Cytokeratin 7 (CK7), cytokeratin 20 (CK20), napsin-a, CDX-2, villin, GATA-3, and mammaglobin antibodies can be used to exclude metastatic lesions from colon, lung and breast (2,3,7,10,13,18) .The Table shows some cases of ELST found in the international literature that are comparable to the reported case.

FigurE 1 −
FigurE 1 − Aggressive papillary tumor of endolymphatic sac: CT showing an expansile lytic lesion arising in the right temporal bone (A and B) CT: computed tomography.

FigurE 3 −
FigurE 3 − Aggressive papillary tumor of endolymphatic sac.Six years after surgical resection, CT scans revealed tumor recurrence CT: computed tomography.

taBLE −
Similar cases of aggressive papillary tumor of endolymphatic sac reported in the literature F: female; M: male.