Ultrastructural studies of perichromatin granules with special references to Merkel cell carcinoma.

Since it has been convincingly demonstrated that Merkel cell polyomavirus (MCPyV), a new type of virus, isolated in 2008, induces some of Merkel cell carcinoma (MCC), we searched MCPyV in specimens taken from MCC patients by electron microscopy. The purpose of this communication is to report the presence of perichromatin granules (PCGs), which can be misinterpreted as virus-like particles (VLP). Tissues from several cutaneous tumors including MCC were examined by electron microscopy (EM). EM revealed intranuclear and spherical electron-dense particles with halo, approximately 55 nm in diameter suggesting possible VLP. However, granular structures were detected in MCPyV DNA positive and also negative MCC. Moreover, the same structures were detected in the tumor cells of SCC associated with MCC, those of malignant melanoma (MM), schwannoma, and also in the lesional melanocyte, fibroblast, apoptotic cell and mitotic cell. Since MCPyV DNA could not be detected in collision MCC with SCC, MM and schwannoma, this observation could mean that the granular structures we dealt with in this report represent PCGs, but not VLP and show an absence of viral particles in MCC.

Homo- and heterotypic cell-cell contacts in Merkel cells and Merkel cell carcinomas: heterogeneity and indications for cadherin switching.

AIMS: Merkel cell carcinomas (MCCs) are rare but aggressive tumours associated recently with Merkel cell polyomavirus (MCV). As development and progression of several types of carcinomas can be promoted by changes in cell adhesion proteins, the aim of this study was to examine homo- and heterotypic cell contacts of Merkel cells and MCCs. METHODS AND RESULTS: Merkel cells of healthy glabrous epidermis and 52 MCCs were analysed by double-label immunostaining, immunofluorescence and confocal microscopy. Merkel cells were connected to keratinocytes by E- and P-cadherin, desmoglein 2 and desmocollin 2. In contrast, the vast majority of MCCs (90%) contained N-cadherin, but only 67% and 65% contained E- and P-cadherin, respectively. Interestingly, P-cadherin was absent significantly more frequently in lymph node metastases than in primary tumours and by trend in more advanced clinical stages. Moreover, major subsets of MCCs synthesized desmoglein 2 and, surprisingly, tight junction proteins. No significant differences were observed upon stratification for MCV DNA, detected in 84% of tumours by real-time polymerase chain reaction. CONCLUSIONS: Assuming that MCCs originate from Merkel cells, our data indicate a switch from E- and P-cadherin to N-cadherin during tumorigenesis. Whether the unexpected heterogeneity of junctional proteins can be exploited for prognostic and therapeutic purposes will need to be examined.

Multicentric cutaneous neuroendocrine (Merkel cell) carcinoma in a dog.

Multicentric cutaneous neuroendocrine (Merkel cell) carcinoma was diagnosed in a 5-year-old castrated male Keeshond dog with multiple firm nodular cutaneous masses. The neoplastic tissue locally effaced the periadnexal and deep dermis and consisted of densely cellular confluent clusters of round to polygonal cells supported by a delicate fibrovascular stroma. The cells were moderately immunoreactive with chromogranin A, synaptophysin, and cytokeratin. Ultrastructurally, the cells had characteristic membrane-bound dense-core neuroendocrine granules approximately 120 nm in diameter and randomly dispersed throughout the cytoplasm. Effacement of dermal structures and multicentric distribution suggested low-grade malignant phenotype. These findings contrast with the typical benign behavior of canine cutaneous neuroendocrine tumors.

Spontaneous regression of recurrent and metastatic Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a malignant neuroendocrine tumor with a high rate of recurrence and metastasis. Despite its high degree of malignancy, spontaneous regression has been documented. We report an 87-year-old woman who presented with recurrent MCC on her left cheek and regional lymph node metastasis. Although she received no treatment due to her poor condition, the recurrent metastatic lesion regressed spontaneously within 2 months.

Merkel cells, normal and neoplastic: an update.

Merkel cells (MC) occur in the basal epidermal layer, hair follicles, and oral mucosa, as complexes with sensory axons. The axons transduce slowly adapting type I mechanoreception, and MC modulate their sensitivity. MC also determine and maintain the 3-dimensional epidermal structure. They have neuroendocrine granules, rigid spinous processes, and desmosomal junctions with each other and with keratinocytes. Rare MC are dermaWl. Current evidence supports a basal cell origin. Merkel cell carcinomas (MCC) occur mostly in sun-exposed skin in old age. Trabecular, intermediate, or small cell in pattern, MCC have neuroendocrine granules, intercellular junctions, rigid spinous processes, and a paranuclear collection of intermediate filaments staining for cytokeratin 20. Most MCC behave indolently, but those with the small cell pattern, and some with the intermediate pattern, are aggressive and rapidly fatal.

Clinicopathological and immunohistochemical analysis of 20 cases of Merkel cell carcinoma in search of prognostic markers.

AIMS: To evaluate the clinicopathological and immunohistochemical characteristics of Merkel cell carcinoma (MCC) in an attempt to find new, potentially significant, prognostic markers. METHODS AND RESULTS: Clinical data and follow-up, histopathological features (pattern, cell size, thickness, mitoses, vascular invasion, lymphocytic infiltration) and immunohistochemical detection [CK20, thyroid transcription factor (TTF-1), chromogranin A, synaptophysin, p53, Ki67, Fli-1, CD99, c-Kit] were evaluated in 20 cases of MCC. Fli-1 and CD99 were detected in 90% and 55% of cases, respectively. Tumour size>30 mm, stage II, 'absent' lymphocytic infiltration, and the presence of>50% of Ki67+ tumour cells, were found to be prognostic indicators of disease-free interval (DFI), but only 'absent' lymphocytic infiltration constituted an independent prognostic factor of DFI after multivariate analysis. For overall survival, the same variables, together with local recurrence and lymph node involvement, had prognostic significance, with only local recurrence as an independent prognostic factor after multivariate analysis. CONCLUSIONS: Absence of lymphocytic infiltration and Ki67 immunoreactivity in more than 50% of tumour cells should be evaluated in conjunction with other well-known prognostic markers in MCC. Furthermore, recognizing that Fli-1 and CD99 expression is commonly found in MCC by immunohistochemistry may avoid misinterpretation in the differential diagnosis of MCC with other small round cell tumours.

[Merkel cell carcinoma]. / Le carcinome de Merkel.

Merkel cell carcinoma is a neuroendocrine tumor of the skin, originating from neuroendocrine cells. A case report of Merkel cell carcinoma, discovered in a 77-Year-old woman, was diagnosed and confirmed on a biopsy. Diagnostic and therapeutic orientations of this unusual but malignant tumor are described.

Merkel cell carcinoma of the parotid gland associated with Warthin tumour: report of two cases.

AIMS: Two cases of Merkel cell carcinoma occurring simultaneously and in close association with a Warthin tumour of the parotid gland are reported. METHODS AND RESULTS: The patients were a 65-year-old man and a 70-year-old man, respectively. The Merkel cell carcinoma component was immunoreactive for chromogranin and keratin 20 and contained neuroendocrine-type granules at the ultrastructural level. CONCLUSIONS: The histogenesis of this heretofore undescribed combination is discussed.

Clinicopathologic and electron microscopic study of cutaneous neuroendocrine (Merkel cell) carcinoma in a cat with comparisons to human and canine tumors.

Malignant neuroendocrine carcinoma of the skin (Merkel cell tumor) was diagnosed in an 18-year-old spayed female Maine Coon Cat. The diagnosis was made on the basis of morphologic and electron microscopic findings. The cat was euthanatized 321 days after surgical excision of the tumor. The tumor's malignancy contrasted with the benign nature of Merkel cell tumors reported in dogs and was consistent with the malignancy of Merkel cell tumors reported in humans.

Cytomorphologic features of Merkel cell carcinoma in fine needle aspiration biopsies. A study of two atypical cases.

OBJECTIVE: To report atypical cytomorphologic features in fine needle aspiration biopsies (FNABs) from two cases of Merkel cell carcinoma (MCC), a primary neuroendocrine neoplasm of skin. STUDY DESIGN: Retrospective review of FNABs with histologic correlation from six patients with MCC and a report of findings from two whose smears showed atypical features. RESULTS: Typically the aspirates produce highly cellular smears of loosely clustered and individual, relatively monomorphic, small tumor cells with round to oval, regularly contoured nuclei. In two of our cases, the tumor cell nuclei exhibited a spectrum of pleomorphism ranging from moderately complex nuclear membranes with cleaves, indentations and protrusions in one case to large, markedly bizarre, convoluted nuclei and multinucleate tumor cells in the extreme case. Both cases were primary neoplasms, and the diagnosis was based on clinical, histologic and immunohistochemical data. Additionally, electron microscopy was performed on the tumor with bizarre nuclei and demonstrated rare, dense core neurosecretory granules and paranuclear bundles of intermediate filaments.

Tumor neuroectodermal primitivo periférico o una variante de él? / Primitive neuroectodermal tumor or a variant?

Se presentan cuatro casos de tumor de Merkel en pacientes añosos, con evolución entre tres meses y un año. La inmunomarcación e histopatología fueron similares en todos. Dos estaban localizados en zonas expuestas al sol, y dos en áreas ocultas. Todos tenían situación subcutánea o corion mucoso, ninguno en relación con epitelios suprayacentes, dato que reforzaría nuestra sospecha de su origen en restos embrionarios de tejido neuroblástico. Todos evolucionaron mal, no obstante una terapéutica adecuada. El último se encuentra con metástasis ganglionares y viscerales

Tumor neuroectodermal primitivo periférico o una variante de él? / Primitive neuroectodermal tumor or a variant?

Se presentan cuatro casos de tumor de Merkel en pacientes añosos, con evolución entre tres meses y un año. La inmunomarcación e histopatología fueron similares en todos. Dos estaban localizados en zonas expuestas al sol, y dos en áreas ocultas. Todos tenían situación subcutánea o corion mucoso, ninguno en relación con epitelios suprayacentes, dato que reforzaría nuestra sospecha de su origen en restos embrionarios de tejido neuroblástico. Todos evolucionaron mal, no obstante una terapéutica adecuada. El último se encuentra con metástasis ganglionares y viscerales (AU)

Ovarian small cell tumors: an electron microscopic review.

Small cell tumors of the ovary are uncommon but represent an important group to recognize in the differential diagnosis of primary and metastatic ovarian neoplasms. In some cases the correct diagnosis cannot be confidently made on the basis of clinical setting, routine light microscopy, and immunohistochemistry, and electron microscopy may be supportive or definitive in establishing cell type. The cell type is often important in choosing optimal therapy and in predicting prognosis. The authors performed electron microscopy on a moderate number of ovarian small cell tumors and here describe and illustrate the diagnostic features of representative examples of various types. The ultrastructural features of the metastatic tumors, such as embryonal rhabdomyosarcoma, neuroblastoma, and melanoma, are identical to those of their respective primary tumors, are well known, and usually pose no problem in diagnosis. On the other hand, the ultrastructural features of some primary ovarian small cell tumors may present a more difficult differential diagnosis, because they have features that are subtle and/or in common. Exemplary of tumors in this category are diffuse adult granulosa cell tumor, endometrial stromal sarcoma, and small cell carcinomas of the hypercalcemic and pulmonary (oat cell) types. Distinguishing among them may be difficult but is possible, and electron microscopy may be a valuable supplement to the diagnostic information obtained from the clinical presentation, light microscopy, immunohistochemistry and, in some tumors, cytometric analysis of these neoplasms.

Merkel cell carcinoma of palatal mucosa in a young adult: immunohistochemical and ultrastructural features.

The first case report of a merkel cell carcinoma arising from the palatal mucosa in a young adult is presented. The histopathological similarities of this tumour in skin and oral mucosa are also discussed. The patient was a 14-year-old female with a non-symptomatic painful swelling in the left molar region of the maxilla. Under the diagnosis of a malignant tumour, a partial maxillary resection was performed, but there was a recurrence, and finally the patient died of cerebral metastasis. The tumor was composed mainly of uniform small cells. Immunohistologically, a large number of the cells were reactive to neuron specific enolase (NSE) and cytokeratin CK19, and some of the cells were positive to CK8, CK13, CK20, PGP9.5 and CEA focally and slightly. Pseudo-rosette formation and squamous differentiation were frequently detected. The ultrastructure of the tumour cells showed abundant Golgi bodies associated with neurosecretory granules. We conclude that it is the first case of a Merkel cell tumour arising from palatal mucosa and invading underlying bone with reactive hyperplasia. These findings closely resemble those of the same tumour occurring in the skin

Merkel cell carcinoma diagnosed by fine-needle aspiration.

Merkel cell carcinoma is a relatively rare neoplasm of the skin. The present study describes three cases of Merkel cell carcinoma diagnosed by fine-needle aspiration cytology and reviews their histologic, cytologic, and ultrastructural features. The advantages of using fine-needle aspiration to diagnose Merkel cell carcinoma (and other cutaneous neoplasms) are emphasized.

Merkel cell carcinoma with a desmoplastic portion.

Merkel cell carcinoma of the skin usually has a trabecular, intermediate-cell or small-cell pattern of differentiation. We report the case of a 66-year-old man who developed a progressive multinodular plaque that showed a prominent desmoplastic component on preliminary biopsy. Immunohistochemical and ultrastructural studies and the final surgical specimen confirmed that the tumor was a Merkel cell carcinoma. The presence of desmoplasia may mask the diagnosis of Merkel cell carcinoma.

Malignant melanoma with clinical and histologic features of Merkel cell carcinoma.

We describe a patient with malignant melanoma that resembled a Merkel cell carcinoma both clinically and histologically. Immunohistochemical studies showed focally positive staining with S-100 protein and strongly positive staining with HMB-45. Ultrastructural study confirmed the diagnosis by demonstrating premelanosomes and melanosomes. Although the tumor appeared to be clinically unimpressive, it was a deep melanoma with a Breslow level of 3.8 mm that necessitated aggressive treatment. Small cell melanoma must be considered in the differential diagnosis of small cell tumors, which also includes lymphoma, eccrine carcinoma, squamous cell carcinoma, and Merkel cell carcinoma. The diagnosis of amelanotic melanoma, including the small cell variant, may require electron microscopic studies.