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Immunohistochemical analysis of sentinel lymph nodes from patients with Merkel cell carcinoma.

BACKGROUND: Immunohistochemical analysis of sentinel lymph nodes from patients with breast carcinoma and melanoma has been shown to increase the sensitivity for detecting lymph node metastases. To the authors' knowledge, this technique has not been described in patients with Merkel cell carcinoma. METHODS: Lymphatic mapping and sentinel lymph node biopsy was performed on 26 patients with Merkel cell carcinoma between 1997 and 1999. All sentinel lymph nodes were analyzed with conventional hematoxylin and eosin (H&E) staining and then analyzed with immunohistochemical staining to evaluate whether this additional technique would increase the number of patients found to have lymph node metastasis. RESULTS: The median age of the patients in the current study was 67 years and the median tumor size at the time of presentation was 2 cm. Lymph node metastases were identified in 5 of the 26 patients (19%). Three of these five lymph node positive patients were identified with H&E staining. The remaining two patients were identified only after immunohistochemical analysis. The median follow-up in this group of lymph node positive patients was 14 months, with 2 of the 5 lymph node positive patients developing a recurrence. The median follow-up in the 21 patients who were lymph node negative was 19 months, with only 1 patient having developed a recurrence at the time of last follow-up. CONCLUSIONS: Immunohistochemical analysis of sentinel lymph nodes from patients with Merkel cell carcinoma appears to increase the sensitivity of detecting clinically occult lymph node metastases.

Adult↗

A human monoclonal antibody reacting with Merkel cells: immunofluorescence, immunoperoxidase, and immunoelectron microscopy.

A human monoclonal, mu, kappa, cold agglutinin antibody of the rare specificity Pr h (serum and proper eluates) was used in immunofluorescence and immunoperoxidase techniques and in immunoelectron microscopy on rabbit lip specimens. Pr h antibody strongly reacted with scattered cells in epidermis, which were demonstrated to be Merkel cells by electron microscopy; no nerve fibers were stained. In immunoelectron microscopy (IEM), a strong reaction was seen within the cytoplasm and around the granules. This is the first IEM staining of Merkel cells (MC) so far reported; it demonstrates the expression of a carbohydrate differentiation antigen in MC. The availability of a potent monoclonal antibody reacting with MC but not with neighboring epidermal cells in rabbit lip offers a new tool for the study of several aspects of MC biology, including antigenic properties and kinetics.

Animals↗

Spontaneous regression in Merkel cell (neuroendocrine) carcinoma of the skin.

In two Japanese women, 68 and 88 years old, Merkel cell (neuroendocrine) carcinoma of the face developed. Their tumors regressed after biopsy was performed, a rare occurrence. Histological and electron microscopic examination showed apoptosis, cellular necrosis, and an infiltration composed mainly of lymphocytes in the tumors. These changes may have been related to the mechanism of regression. It is interesting that our two patients were women, as was another patient described with Merkel cell carcinoma regression, in light of the fact that the prognosis of this tumor is sex dependent.

Aged↗

Merkel cell (primary neuroendocrine) carcinoma of the skin with nodal metastasis showing rhabdomyosarcomatous differentiation.

BACKGROUND: We describe a unique case of Merkel cell (primary neuroendocrine) carcinoma of the skin with a lymph node metastasis showing rhabdomyosarcomatous differentiation. Skeletal muscle differentiation has occasionally been described in primary small cell neuroendocrine carcinomas and considered a form of dual differentiation rather than a collision tumor. In the present case, capacity for divergent differentiation appeared late in the course of the tumor, which suggests a clonal origin for both components of the neoplasm. CONCLUSIONS: The coexistence of neural and rhabdomyoblastic types of differentiation, best epitomized by the Triton tumor, has been construed as the product of dual differentiation of cells originated from neural crest-derived ectomesenchyme. Since Merkel cells seem to originate from a pluripotential primitive keratinocyte and not from the neural crest, rhabdomyoblastic differentiation in a metastasis of primary neuroendocrine carcinoma of the skin probably reflects the close proximity between the programs of neural and skeletal muscle differentiation, which would have been sequentially activated in the case we are reporting.

Aged↗

Oral etoposide for Merkel cell carcinoma in patients previously treated with intravenous etoposide.

We describe three patients with advanced Merkel cell carcinoma who were treated with etoposide given orally for recurrent regional lymph node involvement 18 to 30 months after exposure to etoposide given intravenously. Etoposide given orally (100 mg/day) was given for 10 to 14 consecutive days and repeated every 21 to 28 days for a median of three courses (range: two to four). Toxicity was minimal and mainly hematologic. Two patients showed a complete response and one a partial response, all of very rapid onset. All three patients are alive 6, 9, and 42 months from the start of oral treatment. Two remain progression free, and one had a recurrence 1 month after completion of chemotherapy. We suggest that orally administered etoposide, a topoisomerase II inhibitor, has a strong antitumor effect in advanced Merkel cell carcinoma, even in patients previously treated parenterally with the same drug. This action may be explained by the greater dependence of the drug's efficacy on the duration of administration rather than the dose intensity.

Administration, Oral↗

Immunohistochemical distinction between merkel cell carcinoma and small cell carcinoma of the lung.

We assessed the usefulness of several immunohistochemical stains in distinguishing these two neoplasms, including cytokeratin 7, cytokeratin 20 (CK20), neuron-specific enolase, chromogranin, synaptophysin, neurofilaments (NF), thyroid-transcription factor-1 (TTF-1), CD56 antigen, S-100 protein, vimentin, c-erbB-2 oncoprotein, and CD117 antigen. All 13 cases of Merkel cell carcinoma evaluated were positive for CK20, and negative for TTF-1. Twelve of 13 Merkel cell carcinoma cases were positive for NF. Eleven of 13 cases of small cell lung carcinoma were positive for TTF-1. All small cell lung carcinoma cases were negative for NF, and all but one were negative for CK20. In terms of the remaining antigens, there were no differences of significance between the two neoplasms. These findings suggest that a set of three immunohistochemical stains, including CK20, NF, and TTF-1, is useful in affording a distinction between Merkel cell carcinoma and small cell lung carcinoma.

Adult↗

Neuroendocrine carcinoma of the skin (Merkel cell carcinoma): immunocytochemical study of a case.

The immunocytochemical phenotype was evaluated in a case of Merkel cell carcinoma of the skin. Intermediate filaments, i.e. neurofilament, glial fibrillary acid protein, cytokeratins, keratin and panfilament as well as S-100 protein, calcitonin and epithelial membrane antigen were detected by immunoperoxidase methods. Nodular positivity for neurofilament was observed. The remaining intermediate filaments and other markers were negative. Thus the origin of Merkel cell carcinoma appears uncertain and this tumor probably has neuroendocrine activity.

Antibodies, Neoplasm↗

Merkel cell carcinoma with pagetoid spread.

A case of Merkel cell carcinoma showing epidermotropism is presented. The neoplastic cells displayed dotlike immunoreactivity for cytokeratins and strong immunoreactivity for neuron-specific enolase. Although no neuroendocrine granules were found, characteristic paranuclear fibrous bodies were present.

Aged↗

Neuroendocrine skin carcinoma associated with calcitonin production: a Merkel cell carcinoma?

An elderly woman presented with an ulcerating skin carcinoma located over the right parietal area. It healed after local radiotherapy but recurred locally and metastasized to the subcutaneous tissue and one regional lymph node. Neurosecretory granules were demonstrated ultrastructurally, and blood levels of calcitonin were repeatedly elevated. A metastasizing medullary carcinoma of the thyroid was suspected, and a total thyroidectomy was performed; however, no medullary carcinoma or C cell hyperplasia could be identified. Furthermore, the calcitonin levels remained unchanged following thyroidectomy, whereas they decreased twice after the skin tumor or its metastases were ablated. Clinical follow-up for over seven years revealed no other lesion that could have been responsible for the overproduction of calcitonin. The ultrastructural features of this skin carcinoma and its metastases, particularly the neurosecretory granules, were reminiscent of those of the so-called Merkel cell. We conclude that this skin carcinoma might indeed produce calcitonin, that this tumor may be derived from Merkel cells, and that Merkel cells may belong within the APUD system.

Aged↗

Tumor lysis syndrome in a patient with metastatic Merkel cell carcinoma.

A first course of combination chemotherapy for large volume metastatic disease in a patient with Merkel cell carcinoma resulted in a tumor lysis syndrome. After this course a nearly complete response was documented. This case report extends further the chemosensitivity of Merkel cell carcinoma and demonstrates the need for tumor lysis syndrome prophylaxis in patients with bulky disease or fast-growing tumors.

Aged↗

Merkel-cell carcinoma of the pinna.

Merkel-Cell carcinoma is a rare malignant skin tumour. It was first described as 'Trabecular Carcinoma' by Toker in 1972. Since then many reports have appeared in the literature, mainly in the dermatology, pathology and to a lesser extent, in the plastic surgery journals. Surprisingly, the topic is rarely discussed in the otolaryngology literature, though nearly fifty per cent of these tumours arise in the head and neck.

Adenocarcinoma↗

Morphometric characterization of the human neuroendocrine Merkel cells.

In this study, the neuroendocrine Merkel cells (NEMCs) from adult human epidermis are defined morphometrically, using the MOP 20 image analyzer to measure 21 parameters of either the cell as a whole, or particular cellular structures. Maximum diameter (8.09 microns), perimeter (26.51 microns), area (36.87 microns2) and form factor (0.626) for the cell as a whole, and maximum diameter (5.08 microns), perimeter (18.74 microns), area (12.54 microns2) and form factor (0.452) for the nucleus were determined. Also measured were nuclear-cytoplasmic ratio (0.5595), filament thickness (10 nm), and granular numerical density (7.02 granules/micron2). Maximum diameter, area, and form factor of neurosecretory granules were 94.23 nm, 5020.05 nm2, and 0.93, respectively. Length of desmosomes linking NEMCs to keratinocytes was determined (286.9 nm) and compared with that of interkeratinocytic desmosomes (385 nm). In addition, length and diameter of cellular processes (spine-like processes (1.58 micron X 0.26 micron), interstitial processes (1.39 micron X 0.25 micron), and microvilli (0.35 micron X 0.25 micron) were measured after separation and classification according to the particular morphologic characteristics of each.

Adult↗

A study of intermediate filaments (cytokeratin, vimentin, neurofilament) in two cases of Merkel cell tumor.

In two cases of Merkel cell tumor, the study of intermediate filaments, using monoclonal antibodies (vimentin, cytokeratin, neurofilaments), confirmed the double differentiation (neuroendocrine and epithelial) of this tumor as previously observed in histological, electron microscopical and histochemical analyses. Labelling of the tumor cells was positive with monoclonal antibodies against neurofilament proteins and cytokeratin.

Adenocarcinoma↗

Cutaneous neuro-endocrine (Merkel cell) carcinoma.

Two cases of neuro-endocrine (Merkel cell) tumours of the skin are reported. There was evidence of distant relapse in both patients who eventually succumbed to the disease. The wide range of clinical and radiological manifestations of this rare tumour are discussed and the literature reviewed.

Aged↗

Merkel cell carcinoma. Comparison of Mohs micrographic surgery and wide excision in eighty-six patients.

BACKGROUND: Merkel cell carcinoma is an uncommon malignant tumor of the skin that, after standard surgical excision, tends to recur locally and develop regional nodal spread. OBJECTIVE: This study evaluated the use of Mohs micrographic surgery for this aggressive neoplasm. METHODS: A retrospective study of 86 patients with Merkel cell carcinoma established rates of local persistence and the development of regional metastasis after standard surgical excision. Detailed follow-up was available on a subgroup of 13 patients treated with Mohs surgery. RESULTS: Standard surgical excision for local disease was associated with high rates of local persistence (13 of 41 [31.7%]) and regional metastasis (20 of 41 [48.8%]). Mean follow-up was 60 months. Mean follow-up for the group treated with Mohs was 36 months. Only one of 12 (8.3%) Mohs-treated patients with histologically confirmed clearance has had local persistence of disease. This patient underwent a second Mohs excision and has remained disease free for 84 months. Regional metastasis developed in four of 12 cases (33.3%). Regional metastasis developed in none of the four patients treated with radiotherapy after Mohs surgery and in four of eight patients treated with Mohs surgery without postoperative radiotherapy. CONCLUSION: Mohs surgery compares favorably with standard surgical excision. Radiotherapy after Mohs surgery may further reduce persistent metastases in transit and nodal disease.

Adult↗