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.

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.

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.

Recurrent adult myofibromatosis. A case report.

Myofibromatosis generally is regarded as a fibrous proliferative disease of neonates and children that, even when multicentric, has an excellent prognosis and a propensity for spontaneous involution. Reported is a case of solitary, locally recurrent myofibromatosis in the ear canal of an adult patient. It was initially thought to be a leiomyoma. The diagnosis of myofibromatosis was made on the basis of its histologic appearance and corroborated by immunohistochemical stains. Clinicians and pathologists should be aware that myofibromatosis may occur in adults in unusual locations, with a potential for local recurrence. Furthermore, its histologic appearance may mimic that of other mesenchymal neoplasms.

Leiomyosarcoma of the middle ear and temporal bone.

Leiomyosarcoma is a malignant tumor of smooth muscle origin. It is rarely encountered in the head and neck area. A patient with leiomyosarcoma of the middle ear and the temporal bone with unusual bone destruction is presented. To our knowledge it is the first report of a middle ear and temporal bone leiomyosarcoma.

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.

Ovine squamous cell carcinoma: immunocharacterisation of neoplastic cells and peritumoural cellular infiltrate.

An immunohistochemical characterisation of neoplastic cells and peritumoural cellular infiltrate of ovine squamous cell carcinomas (OSCC) in different stages of growth was carried out using a commercially-available panel of seven antibodies, and formalin-fixed and paraffin-embedded tissue samples. Neoplastic cells reacted with the anti-keratin monoclonal antibody RCK-102 and with an anti-keratin polyclonal antibody, whereas they were unreactive with the anti-keratin monoclonal antibody NCL-5D3. The tumour cells were unreactive with the anti-vimentin polyclonal antibody. Increased numbers of CD3+ T-lymphocytes, IgG-containing plasma cells and lysozyme+ macrophages were associated with precancerous lesions (actinic keratosis) and with early OSCC. These results show that early lesions of OSCC induce an in situ cellular and humoral immune response. In advanced OSCC, the number of CD3+ T-lymphocytes and macrophages in the peri- and intratumoural cellular infiltrate remained high, whereas a significant decrease of IgG-containing plasma cells was found compared with early OSCC. This finding suggests an in situ decrease in the humoral immune response in advanced OSCC.

Amelanotic melanocytic tumors of the pinna in six F344 rats.

Spontaneous amelanotic melanocytic tumors of the pinna were found in six females of 960 male and 960 female albino (F344/DuCrj) rats which had been used in three different 24-month chronic toxicity studies. The age when the pinnal tumors were detected ranged from 37 to 59 weeks. The tumors were located unilaterally in the pinna and observed as subcutaneous spherical to irregular, solid white masses measuring 7 to 25 mm in diameter. The pinnal tumors were histologically classified into spindle cell and pleomorphic cell types. The spindle cell type was observed in four rats and composed of fusiform cells arranged in interlacing bundles. The pleomorphic cell type was observed in the remaining two rats and composed of pleomorphic large cells arranged in sheets. One tumor of the latter type metastasized to the submaxillary lymph node and lung. Melanin pigments were not demonstrated in any of the tumors. In immunohistochemistry, nuclei and cytoplasm of tumor cells in all the tumors were slightly positive for S-100 protein. Ultrastructurally, tumor cells contained a considerable number of premelanosomes in the cytoplasm. Desmosomes were occasionally observed between the cell membranes of the adjacent tumor cells. No distinct basal lamina was seen around tumor cells.

Frozen section diagnosis in a jugulo-tympanic paraganglioma.

The light microscopy and immunohistochemical findings of a jugulo-tympanic paraganglioma occurring in a 29-year-old man are reported. Diagnostic difficulties from frozen sections are stressed and selected literature is briefly commented upon.

Malignant melanoma of the ear.

This paper reports on 16 cases of primary malignant melanoma of the external ear and the patients were followed up for two to 116 months. Fourteen patients had surgical excision with wide margins as initial treatment, whilst two had an amputation performed. Eleven patients had no recurrences, two died of other diseases, and four died of malignant melanoma. The five patients who developed recurrences received further surgery and two also radiotherapy. Seven of the cases were histologically of the nodular type, six were superficial spreading, two were in situ melanoma, and one was a lentigo maligna. The thickness ranged from 0.15 to 11.5 mm. Classification according to Clark et al. (1969) revaled that as many as nine cases were Clark level IV or more. Immunostaining with PCNA yielded strong positivity in all cases, however, statistical analysis did not reveal any differences that could be correlated to the prognosis. Estimation of the vascularization at the base of the tumours by means of immunostaining with CD31 did not reveal any significant differences either. We concluded that in our material the thickness of the tumour is of greater prognostic value than the estimation of proliferation by PCNA and vascularization by CD31. The value of PCNA and CD31 as possible prognostic parameters needs to be evaluated in a larger series. It is emphasized that malignant melanoma of the external ear is a highly malignant tumour, and that four of our 16 patients died of their disease, three of them within a year after diagnosis. Malignant melanoma of the external ear is readily inspected and thereby an early diagnosis should be possible.

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.

[Amphicrine adenoma of the middle ear. Histological, immunohistochemical and ultrastructural study of a case]. / Adénome amphicrine de l'oreille moyenne. Etude histologique, immunohistochimique et ultrastructurale d'un cas.

Middle ear adenoma is a rare benign tumor that exhibits a pleomorphic histological pattern, with solid, cribriform, tubular and trabecular features, which often lead to a diagnosis of a malignant tumor. We report a case of middle ear adenoma, displaying the typical amphicrine biphasic cell growth, better visualized by immunohistochemical and ultrastructural studies. These tumors are composed of two cell types, endocrine B cells containing neurosecretory granules and labelled with anti-keratin, anti-vimentin and anti-neuron specific enolase antibodies, and exocrine A cells containing mucous granules and immunoreactive with anti-keratin and anti-epithelial membrane antigen antibodies. These immunohistochemical and/or ultrastructural characteristics may be helpful to confirm the diagnosis of middle ear adenoma which should be treated by local excision without additional therapy. The essential identity of middle ear adenoma and so called carcinoid tumors of the middle ear is highlighted. We propose to name these tumors middle ear amphicrine adenoma which better reflects their benign and biphasic nature.

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.

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.

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.

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.