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Merkel cell tumor of the thigh.

This case of a Merkel cell carcinoma is unusual due to the occurrence of the tumor on the thigh; most Merkel cell tumors have been found on the sun-exposed region of the head and neck. Histologically, the nodule was composed of sheets of uniform, poorly differentiated cells with a high nuclear to cytoplasmic ratio. Electron microscopy revealed perinuclear filaments, scattered dense core granules, and complex, interdigitating processes within cytoplasmic membranes. Treatment consisted of surgical excision of the tumor with a wide margin.

Aged↗

Primary nodal neuroendocrine (Merkel cell) tumor in a patient with HIV infection.

Lymphadenopathy in the human immunodeficiency virus (HIV) can be of diverse etiology, ranging from infection to cancer. A neoplasm of epithelial origin manifested as inguinal lymphadenopathy without a primary lesion is rare. We report a case of Merkel cell tumor confined only to a lymph node in a patient with the acquired immunodeficiency syndrome (AIDS). We believe this is the first report of primary nodal Merkel cell tumor in a patient with HIV. Because Merkel cell tumor is a rare skin neoplasm with features suggestive of high malignant potential, it is important to distinguish a primary nodal Merkel cell tumor from malignant metastatic processes on the one hand and relatively benign causes of adenopathy on the other.

Acquired Immunodeficiency Syndrome↗

Distribution of Merkel cells in acute UVB erythema.

Merkel cells (MC) were identified immunohistochemically using antibodies specific for cytokeratin (CK) 20 within human epidermis 12 to 72 h after exposure to UVB (4 MED). 12 h after exposure all MC were normally localized within the epidermal basal layer. However, 24 h after exposure 4% of the MC were detected suprabasally, the remaining 96% still being situated in the basal layer. Surprisingly, at 48 h and 72 h more than 50% had lost contact with the basal membrane. The MC of hair follicles did not show any obvious changes. These results argue, in the context of acute epidermal UV damage, for an abnormal turnover in dermatitis.

Acute Disease↗

The intermediate filament proteins of rabbit normal epidermal Merkel cells are cytokeratins.

Four hundred Merkel cells (MC) have been studied by double-label immunofluorescence using: (1) a monoclonal antibody which has been previously demonstrated to react with MC and (2) antisera and monoclonal antibodies against the 5 types of intermediate filaments. It was demonstrated that MC did not react with vimentin, desmin, glial acidic fibrillary protein, or neurofilament antisera. A strong staining of MC was observed with 2 antisera and 2 monoclonal antibodies against keratin. The cytokeratin polypeptide pattern of MC is probably similar to that of simple epithelia. These findings attest to the epithelial nature of MC.

Animals↗

The Merkel cell in oral human mucosa.

A study of the mucosal Merkel cells from 10 patients showed that the cell contained an intranuclear rodlet, clear cell qualities, fine desmosomes, characteristic membrane-bound Merkel granules, and cellular "horns" and had a close relationship to terminal axons. The Merkel cell is an intraepithelial cell with features of neurons and of amine-storage cells.

Axons↗

MRI of merkel cell carcinoma: histologic correlation and review of the literature.

OBJECTIVE: The objective of this study was to determine the MRI characteristics of Merkel cell carcinoma, with an emphasis on histologic correlation. MATERIALS AND METHODS: The demographic information about 15 patients from our institution and their MRI examinations were retrospectively reviewed by three musculoskeletal radiologists by consensus for lesion location and intrinsic characteristics. The study group was composed of three women and 12 men who ranged in age from 48 to 87 years, with a mean age of 75 years. Histology results of resected specimens were reviewed in all cases and were correlated with imaging. RESULTS: MRI showed skin thickening, subcutaneous reticular stranding (n = 9, 60%); multiple anatomically aligned subcutaneous soft-tissue masses, representing lymphatic tumor nodules (n = 5, 33%); lymph node enlargement with fine, compressed, retained fatty tissue (n = 5, 33%); nodal necrosis (n = 1); and perifascial and intramuscular metastases (n = 2). Histology confirmed the lymphatic nature of the soft-tissue Merkel cell tumors. CONCLUSION: Patients with Merkel cell tumors may present at imaging with subcutaneous lymphatic reticular stranding, multiple subcutaneous masses, and lymph node metastases. Often there is massive lymph node enlargement with fine, compressed, retained fatty tissue.

Aged↗

Merkel cells express desmosomal proteins and cytokeratins.

Indirect immunofluorescence experiments performed on various mammalian tissues rich in Merkel cells show that these cells contain keratin intermediate filaments and desmosomal proteins, which demonstrates their epithelial nature. Although they share desmosomes with neighbouring keratinocytes, Merkel cells differ from them, since they contain keratin polypeptides usually found in simple epithelia. In that respect, Merkel cells resemble fetal keratinocytes.

Animals↗

Merkel cell carcinoma of the scrotum.

We report a rare case of Merkel cell carcinoma arising from the scrotal skin of an 84-year-old man. The tumor was treated by wide, local excision and radiation. The man died due to extensive metastatic disease 16 months after his surgery. The natural history, histology, and pathogenesis of Merkel cell carcinoma are discussed briefly.

Aged↗

[Merkel cell carcinoma of the skin in a patient with myasthenia gravis].

Merkel cell carcinoma is a rare, aggressive neuroendocrine tumor of the skin commonly seen in the elderly on the head, neck and extremities, with a predisposition for local regional and distant spreading. A case of Merkel cell carcinoma occurred in a woman treated with immunosuppressive therapy for myasthenia gravis, is described and the possibility of a link between the immunosuppressive and/or oncogenic therapy and this tumor is suggested.

Aged↗

Lectin and proteoglycan histochemistry of Merkel cell carcinomas.

Changes in carbohydrate residue expression and in proteoglycan distribution occur during different stages of tumor development and progression. However, few data concerning carbohydrate residue analysis as performed by lectin histochemistry and proteoglycan distribution of Merkel cell carcinoma, a rare malignant tumor of the skin, have been reported. Hence, lectin- and proteoglycan immunohistochemistry was performed on paraffin wax material of 9 cases of Merkel cell carcinomas characterized by cytokeratin and neurofilament immunohistochemistry. The lectin binding pattern of tumor cells varied between lectins with different sugar binding specificities, while within a given nominal sugar specificity intensities were remarkably similar between tumors from different patients. The most intensive reaction was observed using Con A (mannose/glucose-specific) followed by LCA with the same specificity and the N-Acetyl glucosamine-specific lectins (WGA, UDA, CMA), while no fucose binding sites were detected (UEA-I). In addition, N-Acetyl galactosamine residues were only occasionally detected. The lectin binding pattern of Merkel cell carcinoma cells indicated that predominantly N-linked glycans and not O-linked glycans, typical for mucins of most epithelia, were present. Hence these tumor cells were relatively undifferentiated and resembled stem cells more closely than differentiated epithelia. The tumor stroma was especially evaluated in this study and showed a lectin reaction, which was intermediate between the tumor cells and extra-tumoral stroma. For example, the reactions of N-Acetyl galactosamine-specific lectins were intensive in the extra-tumoral stroma but nearly negative in tumor cells, while the lectin reaction of the intra-tumoral stroma was similar to the cellular reaction. These results indicated an influence of tumor cells on the stromal constituents. Antibodies against chondroitin type glycosaminoglycans reacted with the tumor stroma and the pericellular substance around the tumor cells most intensely in - and around the major tumor septae which, in general, were well vascularized. The most intensive immunoreactivity was detected using the chondroitin-6-sulfate antibody. The cellular and membrane-associated reaction for heparan sulfate was less intensive in comparison to epidermal cells. In conclusion the pattern of lectin-binding sites, the high chondroitin(sulfate) specific reactivity and the relatively low intensity of heparan sulfate immunohistochemistry indicate a low degree of differentiation and high malignity of the tumors, which is consistent with the clinical behavior of Merkel cell carcinomas.

Biomarkers, Tumor↗

The use of VP16 and cisplatin in the treatment of Merkel cell carcinoma.

A 70-year-old male with regionally recurrent Merkel cell cancer obtained a complete remission with three cycles of VP16 and cisplatin. His response was consolidated with local radiation therapy. Two additional patients have been reported to have responded to the same combination. Chemotherapy consisting of either cyclophosphamide, vincristine, and doxorubicin or VP16 and cisplatin should be considered in locally recurrent Merkel cell cancer.

Aged↗

Expression of alpha subunit of guanine nucleotide-binding protein Go in Merkel cell carcinoma.

The alpha subunit of guanine nucleotide-binding protein Go (Go alpha), which was initially isolated from bovine brain, interacts with muscarinic cholinergic receptors and regulates neuronal calcium channels. Go alpha is known to be localized in neural tissues, some endocrine cells, and neuroendocrine tumors. We have immunohistochemically investigated the expression of Go alpha in 4 cases of Merkel cell carcinoma using the method of microwave treatment. In all cases of Merkel cell carcinoma, Go alpha was consistently detected on the plasma membrane and cytoplasm of the tumor cells. Nerve fibers in the skin were also positive for Go alpha, but other epidermal or dermal components such as keratinocytes, melanocytes, fibroblasts, or lymphoid cells were negative. Tumor cells of squamous cell carcinoma, cutaneous lymphoma, sweat gland carcinoma, and malignant melanoma were negative for Go alpha. The present study indicates that Go alpha may be a useful immunohistochemical marker of Merkel cell carcinoma.

Aged↗

Intracranial spread of Merkel cell carcinoma through intact skull.

We report an unusual case of Merkel cell carcinoma presenting as a frontal scalp mass with apparent invasion into underlying brain parenchyma through grossly intact calvaria. Despite wide local excision, craniectomy, intracranial tumor resection, and postoperative adjuvant irradiation, widespread systemic metastases resistant to chemotherapy developed, and the patient died 9 months after surgery. This case report confirms that Merkel cell carcinoma of the head and neck, already known to be an aggressive tumor, has the capacity for rapid intracranial extension. We propose that in this case, the mechanism of intracranial metastasis was via communicating veins rather than through bone destruction or systemic metastasis. Appropriate preoperative imaging should be carried out to define the extent of this tumor when it is adjacent to the skull. We found contrast-enhanced magnetic resonance imaging to be superior to computed tomography for defining soft tissue extent and marrow space involvement within underlying bone.

Bone Marrow Neoplasms↗

Keratin expression in Merkel cells of fetal rat skin.

The cytokeratin expression of Merkel cells in fetal rat skin was studied by light- and electron microscopy. Employing a pre-embedding staining method, 2 monoclonal anti-keratin antibodies (RCK-102, MA-902) were shown to stain Merkel cells specifically. Neighbouring keratinocytes were unstained. The staining reaction seems to be based on the expression of 52.5 kD cytokeratin.

Animals↗

Merkel cell carcinoma: CT findings in 12 patients.

OBJECTIVE: The purpose of this report is to determine CT imaging findings in patients with Merkel cell carcinoma. MATERIALS AND METHODS: Fifty-three CT scans in 12 patients with biopsy-proven Merkel cell carcinoma were retrospectively reviewed with regard to size, location, and attenuation of primary skin lesions and visceral and lymph node metastases. Findings that were present in 12 patients form the basis of this report. RESULTS: Primary skin lesions were manifested on CT scans in four patients as cutaneous nodules that were hyper- or isodense in relation to muscle. Sites of metastases included regional lymph nodes (n = 6), distant lymph nodes (n = 11), the liver (n = 3), and subcutaneous fat (n = 4). We also found metastases in the mediastinum, the peritoneum, the adrenal gland, and the lung. Usually nodal and subcutaneous metastases were slightly hyperdense. Subcutaneous linear stranding was associated with the lesions. CONCLUSION: CT is useful in the staging of Merkel cell carcinoma.

Aged↗

Merkel cell carcinoma in organ-transplant recipients: report of two cases with unusual histological features and literature review.

BACKGROUND: Non-melanoma skin cancers are the commonest malignancies after organ transplantation and are often associated with human papillomavirus (HPV). Merkel cell carcinoma is an uncommon neuroendocrine skin tumor, of which 67 cases have been reported up till now, usually briefly, in organ transplant patients. METHODS: Among a cohort of 2340 organ-transplant recipients, two patients (one renal, one heart) developed cutaneous Merkel cell carcinomas 5 and 12 years of post graft, respectively. These were studied histologically and immunohistochemically, as well as virologically for the presence of HPV. A thorough literature review of all reported cases of Merkel cell carcinoma following solid organ transplantation was performed. RESULTS: Despite a typical immunophenotype, the tumors showed unusual histological features: both were epidermotropic, and one was intermingled with a bowenoid squamous cell carcinoma. Search for HPV by immunohistochemistry and PCR proved negative in both cases. CONCLUSION: In the setting of organ transplantation, Merkel cell carcinoma is much rarer than other non melanoma skin cancers but may show unusual histologic features. HPV do not seem to be involved in its pathogenesis.

Aged↗

Merkel cell distribution in the epidermis as determined by quinacrine fluorescence.

The Merkel cell distribution in the basal epidermis of amphibian and mammalian skin was visualized in whole mounts by means of quinacrine fluorescence. In most cases only the isolated epidermis was viewed following dermal-epidermal separation. Tadpole tentacles contained numerous quinacrine fluorescent cells (QFC) 25-40 microns apart. Groups of 2-4 QFC were found around the gland openings in frog epidermis but not in salamander epidermis where the QFC were irregularly scattered 40-100 microns apart. In the rat, ring-like clusters of a few to 200 or more QFC were distributed across the basal epidermis of trunk skin (at touch domes or Haarscheiben), eyelid, ear, nose, and whisker pad. The ridged (glabrous) skin of the nose and footpad contained numerous QFC that appeared to follow the contours of the epidermal ridges. The isolated external root sheath of rat vibrissae contained an upper cylindrical cuff of several hundred QFC; enzymatic dissociation of these sheaths produced individually isolated as well as small clusters of fluorescent and non-fluorescent cells. Electron-microscopic examination of several of these cells confirmed that the fluorescent ones are Merkel cells, identified by the presence of characteristic dense-cored granules; in contrast, the non-fluorescent cells lack this ultrastructural feature.

Ambystoma↗