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Merkel cell carcinoma: in vitro and in vivo characteristics of a new cell line.

BACKGROUND: Few studies exist that describe Merkel cell carcinoma (MCC) growth characteristics in vitro, in vivo, or both. OBJECTIVE: Our purpose was to evaluate the pathologic features of MCC implanted into athymic mice and to determine cytogenetic abnormalities in the established cell line. METHODS: Tumor tissues from a patient with MCC were grown in culture. Cultured cells were karyotyped and inoculated subcutaneously into athymic mice. Nude mouse tumors were re-implanted into other athymic mice. Tissues from the primary skin tumor and the nude mouse tumor were processed for light and electron microscopy and immunocytochemistry. RESULTS: The cell line showed a doubling time of 64.8 hours. Xenografts of 4 x 10(6) cells produced tumors in athymic mice with a doubling time of 16.1 days. The nude mouse tumors showed pathologic features similar to those of the primary skin tumor. Cytogenetic studies showed a t(1;17) (p36;q21) translocation in 100% of the cells. CONCLUSION: MCC implanted into athymic mice retained the pathologic features of the primary skin tumor and behaved aggressively. The t(1;17) (p36;q21) translocation may be a marker of an aggressive phenotype.

Animals↗

Merkel cell carcinoma in a patient with autoimmune hepatitis.

Merkel cell carcinoma (MCC) has been shown to have a higher incidence in many etiologically distinct immunosuppressed populations. We report a case of aggressive MCC diagnosed in a man with autoimmune hepatitis who was treated with immunosuppressive therapy for more than 30 years.

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NT3 expressed in skin causes enhancement of SA1 sensory neurons that leads to postnatal enhancement of Merkel cells.

To determine the role of NT3 in the postnatal maturation of Merkel cell (MC) sensory neurite complexes (touch domes), we examined the development of their neural and end-organ components in wild-type and transgenic mice that overexpress NT3 (NT3-OE). Touch domes are sensory complexes of the skin that contain specialized MCs innervated by slowly adapting type 1 (SA1) neurons. Touch domes are dependent on NT3 and, though formed in newborn mice that lack NT3, are severely depleted during postnatal maturation. Mice that overexpress NT3 in the skin have larger touch domes characterized by enhanced neural innervation and MC number. In this study, we asked how this NT3-mediated enhancement occurs, whether through stimulatory effects of NT3 on the SA1 neuron, or the MC, or both. The innervation density and number of MCs associated with each touch dome were measured in wild-type and transgenic animals at postnatal times. In newborn NT3-OE mice, touch dome innervation was enhanced. Surprisingly, however, the number of MCs was lower in newborn NT3-OE animals than in wild-type littermates, and equivalent numbers were not reached until postnatal day 8 (PN8). Not until the PN12 and PN16 time points did MCs increase in NT3-OE mice. To examine the neural dependence of MCs in NT3-OE mice, touch domes were chronically denervated by resecting dorsal cutaneous nerves. Both wild-type and NT3-OE animals showed similar depletion in the number of MCs associated with touch domes. These data indicate that NT3 is not a survival factor for MCs and that the NT3-mediated enhancement of MC number is indirect and neurally dependent.

Animals↗

Merkel cell tumor.

A case of a rapidly growing Merkel cell tumor occurring on the lower extremity in an 83-year-old woman is reported. A brief review of the clinical characteristics of this tumor as well as its immunohistochemical and ultrastructural features are presented.

Age Factors↗

Merkel cell carcinoma of the eyelid.

A case of Merkel cell carcinoma of the eyelid of an 85-year-old woman is presented. We define the essential morphological features of this much-debated neuroendocrine cutaneous tumor and its clinical and morphobiological peculiarities, with particular reference to its location in the palpebral region.

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Merkel cell carcinoma. Histopathology, immunohistochemistry, and cytogenetic analysis.

BACKGROUND: Merkel cell carcinoma (MCC) is a cutaneous neoplasm, histopathologically difficult to differentiate from other small blue cell neoplasms. Immunohistochemical and ultrastructural analyses are usually helpful in differentiating these neoplasms. Recently, cytogenetic analysis has emerged as a potential tool in the diagnosis of solid neoplasms, including MCC. OBJECTIVE: To describe the immunohistochemical and cytogenetic features of a case of primary MCC and to review the cytogenetics literature on MCC. METHODS: Formalin-fixed tissue was processed routinely and labeled with a battery of antibodies. Metaphase cells from fresh tissue were prepared by Giemsa banding. RESULTS: Histopathologically, there were irregular aggregates of pyknotic cells with little cytoplasm. Immunohistochemically, the neoplastic cells stained positive for neurofilament, cytokeratin, neuron-specific enolase, and epithelial membrane antigen. Leucocyte common antigen, S-100, 013, and chromogranin were negative. Karyotyping of neoplastic cells showed loss of chromosome Y (-Y). CONCLUSIONS: Coexpression of cytokeratin and neurofilament is characteristic of MCC and allows it to be differentiated from similar neoplasms. The significance of Y chromosome loss is unclear. Further cytogenetic analyses are warranted to identify genetic mutations significant to the pathogenesis of MCC.

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[Merkel cell tumor: a case report and literature review].

Merkel cell tumor (MCT) is extremely rare, being discovered so far about 400 cases in literature. It is classified among neuroendocrine tumors. We report a case of MCT in the subclavicular region in a 93 years old woman. We confirm the efficacy of radiotherapy associated with octreotide, which these tumours express specific receptors for.

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[Merkel cell carcinoma of the skin. 2 clinical cases].

Merkel cell carcinoma of the skin is a tumor generally found in elderly people. This neoplasm involves primarily the dermis; it is locally aggressive often metastatizing to the lymph nodes and, sometimes, diffusely in the body. It must be considered in the diagnostic approach of the cutaneous neoplastic nodules. The clinical, histologic and ultrastructural features of two cases are presented and compared with previously reported examples.

Aged↗

Merkel cell carcinoma (endocrine carcinoma of the skin) of the head and neck.

Merkel cell carcinoma, also known as endocrine carcinoma of the skin, is a recently recognized and particularly aggressive form of skin cancer that exhibits histologic features similar to those of endocrine malignant neoplasms arising from other tissues. Forty-one patients with Merkel cell carcinoma arising from the cutaneous surfaces of the head and neck were seen at the University of Texas M. D. Anderson Hospital, Houston, between 1966 and 1983. Regional lymph node metastasis occur early and frequently, with a 79% overall incidence observed during the course of the disease. Treatment should consist of a wide resection of the primary tumor. A regional lymphadenectomy, when feasible, is successful in controlling nodal metastases. Postoperative radiation is recommended as an important adjuvant.

Adult↗

Immunohistochemical expressions of mGluR5, P2Y2 receptor, PLC-beta1, and IP3R-I and -II in Merkel cells in rat sinus hair follicles.

We previously found that Merkel cells (MCs) of the rat and monkey show a strong immunoreaction of the alpha-subunit of Gq protein. The Galphaq-subunit isoform activates isozymes of phospholipase C-beta (PLC-beta), which produces inositol-(1,4,5)-triphosphate (IP3) which mobilizes intracellular Ca(++) from calcium stores via IP3 receptors. Glutamate and adenosine triphosphate (ATP), which are candidates for neurotransmitters in Merkel endings, are known to couple to Galphaq. Although MCs showed positive immunoreactions of metabotropic glutamate receptor 5 (mGluR5) in our preliminary study, these cells were not reactive to all antibodies to PLC-beta isozymes. We, therefore, reinvestigated immunohistochemical affinities to MCs of antibodies to PLC-beta isozymes and mGluRs using frozen sections of rat sinus hair follicles that were briefly postfixed in formaldehyde. We also studied the immunohistochemical expressions of P2Y receptors for ATP and IP3 receptor subtypes using similar sections. Merkel cells showed positive immunoreactions of PLC-beta1 and mGluR5. It was also found that MCs show positive immunoreactions of P2Y2, IP3R-I, and IP3R-II receptors. These results suggest that the Galphaq isoform in MCs couples to both the P2Y2 receptor and mGluR5 and regulates the intracellular Ca(++) concentration via the PLC-beta-IP3 cascade.

Adenosine Triphosphate↗

Merkel cell carcinoma and melanoma: etiological similarities and differences.

Merkel cell carcinoma (MCC) of the skin and cutaneous malignant melanoma can now be compared epidemiologically through the use of population-based data not previously available for MCC. The results may provide new clues to etiology. In this study, United States data covered by the Surveillance, Epidemiology, and End Results (SEER) Program were from nine areas of the United States (approximately 10% of the population). In 1986-1994, 425 cases of MCC were registered. The annual age-adjusted incidence per 100,000 of MCC was 0.23 for whites and 0.01 for blacks; among whites, the ratio of melanoma to MCC was approximately 65 to 1. Only 5% of MCC occurred before age 50, unlike the lifelong risk of nodular and superficial spreading melanoma. Regional incidence rates of both cancers increased similarly with increasing sun exposure as measured by the UVB solar index. The most sun-exposed anatomical site, the face, was the location of 36% of MCC but only 14% of melanoma. Both cancers increased in frequency and aggressiveness after immunosuppression and organ transplantation (36 cases from the Cincinnati Transplant Tumor registry and 12 from published case reports) and after B-cell neoplasia (5 cases in this study; 13 from case series in the literature). The SEER data contained reports of six patients with both types of cancer; 5 melanomas before the diagnosis of MCC and 1 after diagnosis. MCC and melanoma are similarly related to sun exposure and immunosuppression, but they differ markedly from one another in their distributions by age, race, and anatomical site, especially the face.

Age Factors↗

[Merkel cell carcinoma -- a case report with regard to the current treatment concepts].

A 54-year-old female patient was admitted due to a slow growing, painless resistance on the dorsum of the left hand. The intraoperative aspect of the tumor showed a yellow to white doughy tissue mass infiltrating the metacarpal musculature and bone. After immunohistopathological staining, the diagnosis of a Merkel cell carcinoma was confirmed. A high frequency of local recurrences (25 to 77 %) and lymph node metastases (50 %) are characteristic features of Merkel cell carcinoma. In 30 % of the cases, the disease has a fatal outcome. In primary Merkel cell tumors, surgical excision is the basic therapy, although this carcinoma is highly radiosensitive. Thus, besides surgical treatment, radiation should be included into the treatment concept. In the presented case, after radical excision of the tumor and sentinel-lymphnode biopsy, the patient has been free of local recurrence and metastases for 13 months.

Carcinoma, Merkel Cell↗

[Primary neuroendocrine carcinoma of the skin (Merkel cell tumor)].

Primary neuroendocrine carcinoma of the skin (Merkel cell tumor), a rare malignancy originating from the skin, has only been established in the recent years. It has a main predilection on the skin in the head and neck region with an obvious tendency of local recurrence and early metastasis. Histopathologically, it resembles the neuroendocrine carcinoma from other sites of the body in morphology, immunohistochemistry and ultrastructure. Diagnosis of this tumor is quite difficult. Based upon two of our cases as verified by electron microscopy and/or immunohistochemistry, the clinical and pathological features of this tumor are described and the literature reviewed.

Adult↗

Merkel cell (trabecular) carcinoma of skin treated by radiotherapy.

Merkel cell tumour is a recently described aggressive primary neoplasm of the skin. It is commonly seen in the elderly, on the head and neck or extremities. Surgical excision is the recommended treatment, but local recurrence or dissemination is not an uncommon consequence of this form of therapy. Radiotherapy is usually used as a palliative treatment for metastatic disease. We present two patients, in one an extensive primary was controlled by superficial X-ray, in the other, lymph node metastases were controlled with radiotherapy after excision of the primary.

Aged↗

Merkel cell carcinoma: a clinical, histopathologic, and immunohistochemical review.

Merkel cell carcinoma is a rare aggressive neoplasm, with about 400 cases diagnosed in the United States each year. Among the cutaneous-derived neoplasms, it is the most deadliest, with a higher mortality rate than melanoma. Although the classic clinical presentation as a rapidly growing papule in a sun-exposed site of an elderly patient is not specific, certain histopathologic and ancillary pathologic features allow for its discrimination in most cases. Herein, we review the etiology, pathogenesis, clinical, and pathologic attributes as well as the staging treatment and prognosis of this important public health menace.

Carcinoma, Merkel Cell↗

Spontaneous regression of Merkel cell carcinoma of the skin.

We report a 65-year-old man who presented with a Merkel cell carcinoma on his right ear, a small satellite nodule and regional lymph node metastases. No treatment was given because of his generally poor state of health. Spontaneous regression of all the lesions was observed within a month. Merkel cell carcinoma is a potentially aggressive tumour. Only four cases of spontaneous regression have been reported previously.

Aged↗

Merkel cell carcinoma of skin: diagnosis and management strategies.

Merkel cell carcinoma (MCC) of the skin is a rare form of cutaneous malignancy of neuroendocrine origin with a propensity to affect predominately elderly patients in sun-exposed areas. The tumour has an extremely aggressive growth pattern with the potential to seed into the dermal lymphatics at an early stage as well as spread to nodes and distant sites. Successful outcomes can be achieved with early diagnosis and a multidisciplinary approach to management. Patients with MCC should be carefully staged to exclude distant metastatic disease. Treatment should be approached with both the primary site and the lymph nodes in mind. The primary site should be excised with clear margins, followed by postoperative radiotherapy to the primary site and affected nodes. Addition of chemotherapy to patients perceived to be at high-risk of distant recurrence (e.g. those with involved nodes) has been considered, but evidence supporting this approach is relatively scant. This treatment strategy needs to be approached with caution in the elderly because of the risk of myelosuppression. An aggressive treatment approach is warranted at the first attempt to treat MCC as treatment for recurrent disease is less likely to be successful.

Aged↗

Merkel cell carcinoma. Prognosis and management.

Seventy patients with Merkel cell carcinoma were treated at Memorial Sloan-kettering Cancer Center between 1969 and 1989. The overall estimated 5-year survival rate was 64%. Factors predictive of improved survival included head and neck site and negative lymph nodes at presentation. Local recurrence was seen in 18 patients (26%) and did not correlate with patient-, tumor-, or treatment-related variables. Nine patients with local recurrence (50%) were free of disease following aggressive reoperation. Regional nodes were involved at some point during the course of the disease in forty-six patients (66%). Regional lymph node involvement was apparent within 2 years of diagnosis in 40 (87%) of 46 patients in whom it occurred. Systemic disease was nearly uniformly preceded by the appearance of nodal metastases and was uniformly fatal regardless of subsequent therapy. This suggests an orderly "cascade" pattern of spread for this tumor, in which elective regional lymph node dissection may be justified. Our recommendations for treatment include a wide excision of the primary tumor and either elective or early therapeutic regional node dissection. The role of adjuvant radiotherapy or chemotherapy remains unproven.

Carcinoma, Merkel Cell↗