Endolymphatic sac tumor misdiagnosed as metastatic renal cell carcinoma: Pitfalls in morphology and immunohistochemistry.

Endolymphatic sac tumor (ELST) is a rare disease that originates from the endolymphatic sac system of the inner ear. Being a low-grade malignant tumor, ELST has a mild morphology and is characterized by a slow but aggressive growth. Most clinicians and pathologists are unfamiliar with this disease. ELST can be misdiagnosed as metastatic renal cancer because of the similarity in morphology and expression of nephrogenic markers such as PAX8. The presented case of a 27-year-old man revealed that observing the characteristic location and confirming the absence of renal neoplasm to rule out the possibility of metastasis are critical for obtaining an accurate final diagnosis.

CD20-negative primary middle ear diffuse large B-cell lymphoma coexpressing MYC and BCL-2 secondary to acute lymphoblastic leukemia: A case report.

RATIONALE: Second diffuse large B-cell lymphoma (DLBCL) after treatment of acute lymphoblastic leukemia (ALL) is uncommon. To our knowledge, primary middle ear DLBCL which presents CD20-negative and coexpression of MYC and BCL-2 has not been reported yet. PATIENT CONCERNS: A 20-year-old Chinese man complained fever and weakness for 2 months. Subsequently bone marrow morphology and flow cytometry immunophenotype suggested ALL. Administrated with 9 cycles of multiagent combined chemotherapy, he felt right ear progressive hearing loss, otalgia, aural fullness. Otoendoscopic examination revealed a pitchy mass obstructing the right external auditory canal. Then the mass resection was performed for biopsy and immunohistochemistry examination. DIAGNOSIS: The mass was diagnosed as DLBCL which was negative for CD20 and double expression of MYC and BCL-2. INTERVENTIONS: Chemotherapy. OUTCOMES: The patient eventually gave up and died of severe infection. LESSONS: Although intensive chemotherapy has markedly improved the survival of ALL, more and more secondary cancers have been reported. In addition, primary middle ear lymphoma is much rare; hence, it is easy to be misdiagnosed. Furthermore, DLBCL with negative CD20 and double expression of MYC and BCL-2 is aggressive, which is characterized by chemotherapy resistance and inferior survival rates. We discuss this case aiming at raising awareness of tumors secondary to ALL and exploring the appropriate treatment options for the rare DLBCL.

Mixed epithelial and stromal tumor of the middle ear: The first case report.

We report a tumor arising in the middle ear of a 65-year-old female patient that was composed of an ovarian-type stroma (OS) and an epithelial component. The tumor consisted of irregular, polypoid masses containing multiple variably sized cystic spaces, which were invariably surrounded by the OS. The cystic spaces were lined by flat, cuboidal, or columnar epithelial cells, in most parts showing mucinous differentiation. The epithelial lining of the cysts strongly expressed cytokeratins AE1-3, CK7, CK8, CK18, CK19, EMA, and S100 protein. The stroma expressed CD34 and smooth muscle actin. No cytological atypia or mitoses were present, and the proliferative activity was less than 1% in both components. The clonality analysis proved the clonal nature of the neoplasm. We believe that this tumor is a new member in the family of neoplasms containing the OS, and therefore we propose the term mixed epithelial and stromal tumor of the middle ear.

Cutaneous Epitheliotropic T-Cell Lymphoma in a Marsh Rice Rat (Oryzomys palustris).

Published reports of spontaneous neoplasia in marsh rice rats (Oryzomys palustris) are sparse. We report here a case of cutaneous epitheliotropic T-cell lymphoma in a 14-mo-old marsh rice rat that involved the ear pinnae, with dissemination to the liver and spleen. Histologically, the thickened ear pinnae showed diffuse infiltration of neoplastic lymphocytes into the epidermis, dermis, and adnexal skin structures, with Pautrier microaggregations present in the epidermis. In addition, neoplastic lymphocytes were observed infiltrating and disrupting the architecture of the liver and spleen. Neoplastic lymphocytes were strongly positive for the T-cell marker CD3 but were negative for the B-cell markers CD19 and CD20. These histologic and immunohistochemical features are consistent with an epitheliotropic T-cell lymphoma, as previously reported in other species, including humans. To our knowledge, this report represents the first published case of spontaneous cutaneous epitheliotropic T-cell lymphoma in a marsh rice rat.

Carcinoid tumor of the middle ear: a case report and review of literature.

Carcinoid tumors of the middle ear are very rare. Here we describe a 37-year-old man with multiple recurrent carcinoid tumor of the right middle ear. The CT demonstrated the recurrent mass that filled the tympanum and mastoid with osteolytic invasion, and the tumor was removed by surgery. The pathological findings showed the tumor cells, without necrosis and mitotic activity, had round, oval, or slightly irregular nuclei and finely-dispersed chromatin, arranged in cords, nests, and glandular structures. They were strongly positive for synaptophysin and CD56, but were negative for S-100 and chromogranin A. Ki-67 proliferation activity was low (<2%). With a review of the literature, the clinical, pathological characteristics and treatment modalities of this rare tumor are discussed.

Endolymphatic sac tumor with von Hippel-Lindau disease: report of a case with atypical pathology of endolymphatic sac tumor.

The authors described a case of a patient with co-existing endolymphatic sac tumor (ELST) and hemangioblastoma in the posterior cranial fossa, which belonged to a subtype of Von Hippel-Lindau (VHL) disease confirmed by the test of VHL-gene. The signs in this 42-year-old female included intermittent headache and dizziness. Imaging revealed a giant mass in the right cerebellopontine angle (CPA) region and another lesion in the left cerebellar hemisphere. The results of biopsy after two operations confirmed the diagnosis respectively. Both of the tumors were resected totally. Nevertheless, we had to confess the misdiagnosis as vascular tumor instead of ELST at the initial diagnosis because of the rarity of ELST associated with atypical histological characteristics. The purposes we reported this case were to describe the atypical pathological feature of ELST and the mutation of germline VHL not mentioned in previously literature, furthermore, to foster understanding of ELSTs with the avoidance of the similar misdiagnosis as far as possible in future.

Sporadic endolymphatic sac tumor--a diagnostic and therapeutic challenge.

Endolymphatic sac tumor (ELST) is a rare low-grade locally aggressive neoplasm of the inner ear that may occur sporadically or in the setting of von Hippel-Lindau syndrome. We herein present a case of sporadic ELST in a 39-year-old man, treated using an interdisciplinary approach (surgery+radiotherapy), with a 10-year follow-up. The patient presented with hearing loss of sudden onset. The treatment of choice for ELST is radical tumor resection, which is associated with a good long-term prognosis. Remission may last for years, but there may be local recurrences, probably as a result of incomplete resection. Adjuvant radiotherapy is an option in case of recurrence and could be discussed after incomplete resection. The purpose of this report is to call attention to ELSTs, which are difficult to diagnose due to their rarity and variety of presentations.

Metastasis germinomas of the external acoustic meatus: in a 19-year-boy: a case report.

BACKGROUND: The external acoustic meatus metastasis of germinomas is a rare event. CASE PRESENTATION: we describe a 19-year-old boy with stuffiness and earplug of the left ear but no other symptoms. The whole body F-18 FDG PET/CT and the brain MRI are performed and demonstrated a germinoma in the pineal gland and vermis cerebellum region and in the right of thalamus. Photomicrograph showing marked infiltration of lymphoplasma cells and macrophages including giant cells. Immunohistochemical analysis results demonstrated the tumor cells are strongly positive for CD117 and PLAP. The final diagnosis was germinoma and all adjuvant therapy was achieved. CONCLUSION: Although the external acoustic meatus metastasis of germinomas is rare, the diagnosis should be taken into serious consideration in order to improve. In addition, F-18 FDG PET/CT was very useful in diagnosis primary disease and excluding distant metastases. To our knowledge, this is the first published report of this type of case.

Immunohistochemical profile of neurotrophins and MIB-1 in jugulotympanic paragangliomas: prognostic value and review of the literature.

Jugulo-tympanic paragangliomas are the most common primary neoplasm of the middle ear, but little is still known about the histological features differentiating the benign and malignant forms. We investigated, with an immunohistochemical procedure, the expression of neurotrophins with their receptors, in fifteen samples of paragangliomas, and MIB-1 in order to consider them as prognostic factors of malignancy. We observed a general positivity for NGF - TrKA - NT4 - TrKC in the cytoplasm, and a strong expression for BDNF in the extracellular space. MIB-1 was moderate in the nucleus of neoplastic cells, weak in the cytoplasm and totally absent in the extracellular space. The comparison between the clinical recurrences and the rate of cytoplasmatic neurotrophins showed strong immunoreactivity in recurrent patients. It should be emphasized that 2 of the 3 recurrences had a wider distribution of the neutrophins, leading to hypothesize the involvement of these substances in the cell proliferation of glomus tumors. Malignant forms of these rare glomus tumors cannot be clearly identified using MIB-1 as a prognostic marker, although we can affirm that neurotrophins and their receptors can be considered as a panel of potential diagnostic markers to monitor the development of such malignancies. Although the small number of patients does not allow definitive conclusions to be made, our findings showed a possible trend towards significance which requires a more powerful study to evaluate this further.

Aggressive low grade middle ear adenocarcinoma with multiple recurrences: a case report.

BACKGROUND: Primary tumours of the middle ear are much less commonly encountered in clinical practice than non neoplastic lesions. Middle ear adenocarcinoma is a very rare, locally invasive neoplasm assumed to arise from the middle ear mucosa. Because the natural course and clinical behavior of this neoplasm are far from established, the sporadic reports of such cases continue to provide basis for better understanding. CASE DESCRIPTION: A case of low grade adenocarcinoma of the middle ear is described in details with regard to its clinical presentation, radiological findings, histopathological, immunohistochemical and ultrastructural findings. The tumour recurred four times.

[Presentation of 2 new cases of cutaneous angiomyolipomas and literature review]. / Angiomiolipomas cutáneos: aportación de dos casos y revisión de la literatura.

We present 2 new cases of cutaneous angiomyolipomas with very similar characteristics, located in the postauricular region of 2 women aged 58 and 52 years. The lesions measured 1.5 cm and 1 cm across and had been present for 5 and 2 years, respectively. Both presented a previously unreported clinical sign: change in size according to the ambient temperature. They had well defined borders and a predominance of smooth muscle and vessels, particularly arteries. In contrast to renal angiomyolipomas, which are often associated with tuberous sclerosis, these angiomyolipomas were negative for melanocytic immunohistochemical markers (human melanoma black-45 antigen and melanoma antigen recognized by T cells 1). The clinical characteristics of the 32 cases published until present are reviewed. The relationship of these tumors with angioleiomyomas and renal angiomyolipomas is discussed.

[Jugulotympanic paraganglioma]. / Paraganglioma giugulo-timpanico.

Jugulo-tympanic paraganglioma is the most commonly recognized neoplasia involving the middle ear, arising from chemopressure receptors. Clinical presentation is variable, with otalgia, dizziness and cranial nerve palsies. This tumor usually occurs in middle aged women and its presentation may be familiar, sporadic, bilateral or multicentric. In the present case the patients presented with otalgia and bradyacusia diagnosed with chronic otitis. A bleeding polypoid lesion in middle ear was seen during surgery. Frozen section of intraoperative specimen showed monomorphic cells organized into nests, without aspects of malignancy, into a highly vascularized stroma. Immunohistochemical analysis revealed two type of cells: chief cells immunostained for chromogranin and synaptophysin and sustentacular cells immunostained for S-100 protein. Clinical presentation of jugulotympanic paraganglioma, when it isn't associated with evidence of hormone secretion, is referred prevalently to bradyacusia, dizziness, and cranial nerve palsies. In event of localized disease, paragangliomas often can be treated by surgical excision, but some cases need radiation therapy.

Middle ear adenoma.

Middle ear adenoma is a benign tumor of the middle ear that can have exocrine (mucinous) and/or neuroendocrine differentiation. Early authors described a separate tumor with predominantly neuroendocrine differentiation as a middle ear carcinoid tumor, but these are now known to be the same tumor. We review the literature of this tumor, including the clinical presentation, gross pathology, histopathology, immunohistochemistry, differential diagnosis, and prognosis.

Fibroblast growth factor receptor expression in aural polyps: predictor of cholesteatoma?

The cytokine, fibroblast growth factor (FGF) and its receptors (FGFR) have a pivotal role in wound repair and have been demonstrated in the perimatrix of active cholesteatoma. Aural polyps are a recognized inflammatory reaction of middle-ear mucosa to cholesteatoma, but may arise in its absence. This study examines 28 archival aural polyp specimens, seeking an increased expression for FGFR1 and FGFR3 in polyps associated with cholesteatoma, when compared with those arising in non-cholesteatomatous, mucosal disease, but produced a null result. There was no difference demonstrated in staining intensity between those polyps associated with cholesteatoma and those without. There was a strong correlation between staining patterns of FGFR1 and FGFR3 (r = 0.4, p <0.03). The expression pattern, of nuclear and perinuclear localization, may support the view that nuclear translocation of growth factors, and their receptors, could be related to the cellular proliferation that is associated with cholesteatoma.

Aspiration cytopathology of middle-ear neuroendocrine carcinoma.

Primary neuroendocrine carcinoma (carcinoid tumor) is among the rarest of middle-ear (ME) neoplasms, with only a rare case of metastatic disease having been reported. Fine-needle aspiration biopsy (FNAB) was performed in a 51-yr-old male with a two-decade history of multiple local recurrences from a right middle-ear neoplasm, with the most recent surgical excision 2 yr ago. He currently presented with an enlarged right parotid gland, and a right infratemporal mass. Aspirate smears showed a monotonous population of cytologically bland cells with a small to moderate amount of pale granular cytoplasm, round to oval nuclei, inconspicuous nucleoli, and finely granular chromatin. Rare, isolated large cells were occasionally seen. Immunohistochemical staining of the cell block made from the aspirated material showed strong cytoplasmic positivity for chromogranin, synaptophysin, neuron-specific enolase (NSE), serotonin, and cytokeratin cocktail, and negative staining for S100 protein. Review of tissue slides from the patient's prior middle-ear tumor showed an identical immunoprofile and morphology, and led to a revision of the original diagnosis of paraganglioma. Middle-ear neuroendocrine carcinoma has a low but definite metastatic potential, which can be diagnosed using FNAB if ancillary immunohistochemical studies are available.

Cytology of endolymphatic sac tumor.

A 77-year-old man presented with decreased mental status and an enhancing partially cystic tumor along the left tentorium on magnetic resonance imaging after mastoidectomy and petrosectomy for an "auditory canal tumor." Smears of the aspirated cyst fluid revealed rare epithelial cell clusters, some with papillary features, foamy macrophages, and blood. The cells were orderly, with fairly bland nuclei and well-defined cell borders. The cell block contained similar epithelium, with cells containing eosinophilic and focally vacuolated cytoplasm, some with pigmented granules resembling hemosiderin. Numerous foam cells were also present. Review of the patient's previous and concurrent resection material showed an endolymphatic sac tumor, a rare neoplasm that arises in the endolymphatic sac in the temporal bone. The previously undescribed cytologic features of this rare neoplasm are discussed.

Middle ear adenoma is an amphicrine tumor: why call it adenoma?

Middle ear adenoma (MEA) is a rare tumor postulated to take origin from the lining epithelium of the middle ear cavity. The authors report on a case of MEA arising in a 53-year old woman suffering from a sensation of fullness in her left ear, otalgia, and light left-sided hearing loss. Histopathologically, the lesion was composed of cuboidal and polygonal cells displaying a trabecular, tubulo-glandular, and solid pattern of growth. Immunohistochemically, neoplastic cells diffusely stained with anti-vimentin antibodies and were focally positive for chromogranin A, neuron-specific enolase, lysozyme, and cytokeratins AE1/AE3. The majority of tumor cells showed weak and diffuse staining with both anti-PP and anti-ACTH antibodies and intense positivity with anti-glucagon and anti Leu-7 antibodies. Ultrastructural investigation revealed both mucinous-glandular and neuroendocrine differentiation. The authors suggest that the appropriate terminology would be adeno-carcinoid or amphicrine tumor of the middle ear rather than "adenoma," a term that does not reflect its dual nature.

Sebaceous carcinoma, trichoblastoma, and sebaceoma with features of trichoblastoma in nevus sebaceus.

A 73-year-old woman had a linear yellowish plaque on the upper part of her right ear since birth. She presented because of the sudden growth of a nodule within the plaque. The plaque was waxy and yellowish, arching around the upper part of the ear. A reddish to yellowish large nodule was seen within the central part of the arc-shaped plaque; in addition, a small pigmented nodule, a small skin-colored nodule, and a few pigmented papules were observed in the anterior half of the arched plaque. Histopathologic examination revealed the large nodule to be sebaceous carcinoma, the small pigmented nodule to be trichoblastoma, the small skin-colored nodule to be sebaceoma with the features of trichoblastoma, a few pigmented papules to be superficial trichoblastomas due to primitive follicular induction, and the linear yellowish plaque to be nevus sebaceus. Although our literature search revealed scanty reports of definite cases of sebaceous carcinoma in nevus sebaceus, the presented case demonstrated the occurrence of sebaceous carcinoma in nevus sebaceus. Malignant neoplasms occurring in nevus sebaceous seem to be extremely rare, but care should be taken when a large nodule suddenly grows in a lesion of nevus sebaceus, especially in older adults. The presented case also suggested a close relation between trichoblastoma and sebaceoma. The cytokeratin staining pattern could not distinguish between sebaceous and follicular neoplasms in our case.