Metastasizing middle ear carcinoid: an unusual case report, with focus on ultrastructural and immunohistochemical findings.

BACKGROUND: There are only 4 unequivocal cases of metastasizing middle ear carcinoid previously reported. OBJECTIVE: To present a case of metastasizing middle ear carcinoid, to review previously reported cases, and to discuss the clinical nature of this tumor, which is similar to "orthotopic" carcinoids bearing definite metastatic potential. STUDY DESIGN: Case report. PATIENT, INTERVENTION, RESULTS: We present a 72-year-old woman who developed ipsilateral parotid gland and cervical lymph node metastases 8 and 11 months after surgical removal of a primary middle ear lesion. She subsequently required 2 revision procedures and radiotherapy for local recurrences. Her case was complicated by nonsurgically induced permanent facial nerve paralysis, the cause of which remains obscure. At the end of the 8-year follow-up, the patient was alive with locally, recurrent tumor eroding the cranial base and invading the posterior intracranial fossa but with no signs of metastases. MAIN OUTCOME MEASURES: Light microscopy and immunohistochemical analysis. CONCLUSION: Considering the reported high rate of recurrence and their consequent metastases, a middle ear carcinoid should be classified as a neuroendocrine low-grade carcinoma.

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.

[Extracranial meningioma: morphological and histogenetical aspects and relations with perineurioma].

The clinicomorphological, immunohistochemical, and ultrastructural characteristics of 11 cases of extracranial meningioma versus 79 soft tissue perineuriomas were studied. There were significant similarities (cell morphology, immunoprofile, ultrastructural features of perineurial differentiation) of both entities. Considering the point of view that arachnoid and perineurial cells are anatomically, embryologically, and functionally related, it is most possible that extracranial meningiomas may be derived from perineurial cells (or their progenitor cell) rather than from displaced arachnoid cells.

Carcinoid tumor of the middle ear.

The patient was a 32 year-old man who was first seen in 2003 for 2 years hearing loss. On otoscopic examination, a whitish mass could be observed through the intact tympanic membrane. High resolution computed tomography showed a tumor like lesion in the middle ear with no evidence of bone destruction. A tympanomastoidectomy was performed. Light microscopy showed fragments of cellular tissue in which both glandular and trabecular growth pattern could be identified Immunohistochemical examinations showed positive staining of the tumor cells for cytokeratin and chromogranin. The diagnosis of carcinoid tumor should be considered in all cases of adenomatous neoplasms of the middle ear and mastoid. Conservative surgical excision is the treatment of choice, and local recurrence following complete excision is uncommon.

Spindle cell carcinoma of the external auditory meatus with intracranial extension: histological, immunohistochemical and electron microscopic evaluation.

We present a case of squamous spindle cell carcinoma of the external auditory meatus in a 38-year-old man. The tumour was extended to the inner ear, the temporal bone, the middle cranial fossa and the meningo-cerebral tissue. The surgical intervention of temporo-occipital craniotomy removed most of the neoplasia. At pathologic examination, the tumour showed an undifferentiated spindle cell pattern. Immunohistochemistry with a large antibody panel found a weak positivity only to EMA. The diagnosis was made when the electron microscopy showed rare junctional structures and tonofilaments.

Primary cultures of human vestibular schwannoma: selective growth of schwannoma cells.

OBJECTIVE: To establish primary vestibular schwannoma (VS) cultures that selectively favor the growth of schwannoma cells. BACKGROUND: The lack of a suitable in vitro model of human VS cells has directly limited the progress of research on tumorigenesis and therapy. The problems of establishing pure VS culture include control of fibroblast proliferation. Current efforts to extend VS cell life span using viral oncogenes, by conferring the ability to proliferate in vitro, will yield cells intrinsically different from in vivo VS tumors. Much more desirable is the ability to culture VS cells without cellular transformation. METHODS: Tumor specimens from 17 patients were processed for cell culture and grown at 37 degrees C with 5% CO2 and 100% humidity. Key modifications limiting fibroblast proliferation included using selective medium without L-valine, supplemented by Nu-Serum for at least a week; the use of cytosine arabinoside to kill contaminating fibroblasts; and using the Dulbecco modified medium, supplemented with brain-derived neurotrophic factor and 10% fetal calf serum after the initial serum-free period. RESULTS: Twelve of 17 VS were successfully cultured. The presence of schwannoma cells and the absence of fibroblasts were confirmed immunohistochemically using S100 and CD90 markers, respectively. Scanning and transmission electron microscopy demonstrated typical spindle-shaped cells and the presence of "fibrous long-spacing collagen." CONCLUSION: We describe a method for obtaining short-term, essentially fibroblast-free, primary VS cultures. Such pure VS cultures, retaining in vivo characteristics, are extremely useful as an in vitro model to study the pathobiology of schwannoma cells.

Experimental microcomputed tomography study of the 3D microangioarchitecture of tumors.

Differences between soft X-ray imaging and microcomputed tomography (micro-CT) in the microangiographic depiction of small vessels in tumors were compared to evaluate the tumors' 3D microangioarchitecture and the progress of growth-related neovascularization. VX2 carcinomas transplanted to the auricles of 24 rabbits randomly assigned to three groups were examined after 1, 3, and 7 days. Eight rabbits without transplants were the controls. Barium sulfate was injected into the auricular artery, and conventional soft X-ray images and micro-CT microangiograms of auricle specimens were studied. Micro-CT detected vessels with diameters of less than 50 microm, and imaging from several angles clearly showed the network of tumor vessels. Moreover, micro-CT confirmed the 3D process of growth-related neovascularization. There were no significant differences between the present findings and those of our previously published microscopic study. Micro-CT should prove useful for evaluating the 3D microarchitecture of tumors and for clear imaging of tumor angiogenesis.

Surface structures of aural polyps: a scanning electron microscopic study.

Surfaces of aural polyps collected from 30 patients were examined by scanning electron microscopy. In the polyps not associated with cholesteatoma, the epithelial lining showed individually variable metaplasia towards cuboidal 'cobblestone'-type and squamous epithelium covered with microvilli of various shapes and sizes. Squamous epithelium was present on the surface of all polyps with underlying cholesteatoma, with superficial cells possessing elongated microvilli, microplicae of different sizes, grooves and pits. Such surface structures reflect different stages of the keratinization process that seems to be characteristic for the epithelial lining of polyps with underlying cholesteatoma. Incomplete epithelium accompanied by granulation tissue was found in several polyps; in two cholesteatoma-associated polyps plate-like cholesterol crystals were observed.

Middle ear adenomatous tumor with a predominant neuroendocrine component.

A primary adenomatous tumor of the middle ear was examined by light microscopy, ultrastructural and immunohistochemical techniques. In support of its extensive neuroendocrine differentiation, was the diffuse detection of neuron-specific enolase (NSE) and positive immunoreaction with antibodies to chromogranin and synaptophysin. The great majority of tumor cells contained neurosecretory granules and intraluminal mucin production could be focally detected. These characteristics confirm the diagnosis of a middle ear adenomatous tumor (MEAT) of a biphasic nature and with a prominent neuroendocrine component.

Acoustic neuromas and meningiomas. Histopathological aspect: a post mortem study on temporal bones.

The histopathological changes in the temporal bones of three deceased donors individuals, two with concomitant acoustic tumors and one with concomitant petroclival meningioma have been studied. The differences between neuromas and meningiomas are examined. The different clinical relevance and the different therapeutic guidelines are discussed.

Ultrastructure of the vestibular dark cell area in patients with acoustic neurinoma.

The human vestibular dark cell (DC) areas of the utricle and ampulla of the lateral semicircular canal were investigated ultrastructurally in 7 patients with acoustic neurinoma. Two types of DCs mainly constituted the epithelial cells of the DC area. One type of DC had basolateral infoldings that were closely interwoven with the melanocyte processes, and the pinocytotic vesicles were frequently found within the basolateral infoldings and the melanocyte processes. The other type of DC had basolateral infolsings stacked upon each other. The former type of DC was more frequently found than the latter type in the DC area adjacent to the sensory epithelium and in the mid portion of the DC area. However, the latter type of DC was more predominant in the DC area distant from the sensory epithelium. These findings suggest that the activity of DCs is modulated by the melanocytes and that the former type of DC has a more active role in ion and/or fluid transport than the latter type of DC. Thus, the DC area near the sensory epithelium might be more actively engaged in the production and regulation of vestibular endolymph than that distant from the sensory epithelium.

Laminin promotes differentiation, adhesion and proliferation of cell cultures derived from human acoustic nerve schwannoma.

The influence of laminin on cell cultures derived from unilateral acoustic nerve schwannomas was investigated. Cell cultures were initiated from 12 schwannomas, removed via the enlarged middle cranial fossa approach. Tumor tissue was dispersed by collagenase treatment and cells seeded in uncoated or laminin-coated culture dishes. Confluent cultures were immunocytochemically characterized with antibodies against S-100, CD 68, factor VIII-related antigen and type IV collagen. Cell adhesion in response to different doses of laminin was evaluated with an electronic cell counter. The effect of laminin on cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxy-uridine (BRDU) into cellular DNA. Cells cultured on laminin as substrate appeared more differentiated with long, fusiform, cytoplasmic processes. Cultured cells stained positive for S-100, not for factor VIII-related antigen or CD 68. Only cells cultured on laminin deposited a dense extracellular network of type IV collagen. When laminin was added to the culture medium, cell attachment and proliferation was stimulated in a dose dependent manner. Maximal stimulation of both was observed with a laminin concentration of 50 micrograms/ml, which induced a nearly 2-fold increase in cell attachment and an approximately 66% increase in DNA content. Since laminin is a major component of the extracellular matrix in schwannomas, the possibility exists that laminin is also mitogenic for human neoplastic Schwann cells in situ.

[Primary adenoid cystic carcinoma of the skin. Histologic and ultrastructural study of two cases localized in the external auditory canal]. / Les carcinomes adénoïdes kystiques cutanés primitifs. Etude histologique et ultrastructurale de deux cas localisés au conduit auditif externe.

Primary cutaneous adenoid cystic carcinoma is a rare tumor, even if its frequency has often be underestimated, its localization in the external auditory meatus being generally considered separately. The results of the histological and ultrastructural study of two cases of adenoid cystic carcinoma, arising in the external auditory meatus, are presented, confirming the essential morphological similarity of adenoid cystic carcinoma of the skin and salivary glands. In these two cases, the ultrastructural study revealed two types of unique intra luminal inclusions, composed respectively of parallel straight tubular arrays and paracrystalline quadrangular structures, probably corresponding to a peculiar organization of secretion products or cellular debris. The review of 126 published cases of adenoid cystic carcinoma of the skin, including 89 cases developed in the auditory canal, shows that 78% of the cases were located in areas containing numerous apocrine glands, supporting an apocrine gland origin for this tumor. Contrasting with the low (8%) metastatic potential of cutaneous adenoid cystic carcinomas of other locations, adenoid cystic carcinoma of the auditory meatus present a 30% metastatic risk, similar to those or adenoid cystic carcinoma of salivary glands.

Well-differentiated endocrine tumours of the middle ear and of the hindgut have immunocytochemical and ultrastructural features in common.

The immunocytochemical analysis of two cases of well-differentiated endocrine tumours (carcinoids) of the middle ear revealed predominant cell populations producing pancreatic polypeptide (PP)-related peptides, glucagon-related peptides, and serotonin (the latter only in one case). In consecutive sections PP- and glucagon-related immunoreactivities mainly colocalized in the same tumour cells. Ultrastructurally tumour cells were characterized by medium-sized to large granules of moderate to high density, on which PP and glicentin were localized by the immunogold technique. No amphicrine cells were found. These features are consistent with those of similar tumours in the rectal mucosa that are mainly composed of L cells coexpressing both PP-related and glucagon-related peptides. Additional tumour antigens of hindgut type detected immunohistochemically were prostatic acid phosphatase and CAR-5 mucin. Expression of the CAR-5 antigen was also found in samples of normal middle ear mucosa, in which endocrine cells have not been identified. In case 1 peritumoral mucosal invaginations showed a proliferation of endocrine cells identical immunophenotypically to tumour cells, possibly representing a precursor lesion. It is concluded that well-differentiated endocrine tumours of the middle ear are a distinct pathological entity characterized by multiple hormone production, typically involving three classes of hormones (pancreatic polypeptide-related peptides, glucagon-related peptides, and serotonin) of the hindgut endocrine system.

[Pilomatrixoma of the auricle. Differential diagnosis with carcinoma pilomatrixoma]. / Pilomatrixoma de pabellón auricular. Diagnóstico diferencial con el carcinoma pilomatrixial.

A 34 year-old man, with a two centimeter diameter quickly growing nodule on the auricular pavillion is presented. After mass excision the histologic diagnosis of pilomatrixoma was made. Pilomatrixoma is a rare benign tumor arising on the hair matrix. The differential diagnosis include pilomatrix carcinoma, a locally and recurrent aggressive tumor capable to make pulmonary metastasis. A review of the literature is included, with emphasis on the clinical and histopathological aspects and the therapeutic attitude.

Paramyxovirus-like inclusions in an intradermal nevus from a healthy woman.

A healthy 52-year-old woman had an intradermal nevus removed from the right preauricular region. Histopathologic examination disclosed intranuclear and intracytoplasmic inclusions in many of the nevus cells. A basal-cell carcinoma, an additional intradermal nevus, and a fibrous papule of the nose were also excised, however, none of these lesions showed histologically similar inclusions within the lesions. Electron microscopic studies showed inclusions that were similar to those observed in cases of subacute sclerosing panencephalitis. Immunoperoxidase and polymerase chain reaction studies for the measles virus were performed, with negative results. The patient remains in good health 2 years after excision of the skin lesions.

[Cystic adenoidal carcinoma of the external ear]. / Carcinoma adenoide quístico de conducto auditivo externo.

Tumors of the ceruminous glands can affect the auricula and periauricular skin and should be included in the differential diagnosis of lesions of these regions. Correct management of these tumors depends on precise histopathologic classification and diagnosis of their extension. We report a case of cystic adenoid carcinoma of the external auditory canal. Signs and symptoms, histopathology, and treatment of these lesions as reported in the literature are reviewed.

Primary poorly differentiated adenocarcinoma of the middle ear.

Adenocarcinoma of the middle ear is seldom encountered in clinical practice. In the past 20 years, nearly 20 cases of primary adenocarcinoma of the middle ear have been reported, and most cases of these tumors have been described without histologic presentation. To our knowledge, only one case of adenocarcinoma originating in the postoperative middle ear has been reported. We describe a case of primary poorly differentiated adenocarcinoma in the middle ear which was surgically treated for chronic otitis media 50 years ago. Planning diagnostic and therapeutic procedures in connection with middle ear tumors is also discussed.

[Adenocarcinoma of the ceruminous glands: report of three cases]. / Adenocarcinoma de glándulas ceruminosas: presentación de tres casos.

We report three cases of ceruminoma seen in our department over a 1-year period and review the neoplasms of the ceruminous glands. According to the Welti classification, our three cases were ceruminous adenocarcinomas. Based on existing literature, ceruminous adenocarcinoma is the least frequent neoplasm of the ceruminous glands.