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PubMed2000

Differential expression of thyroid transcription factor 1 in small cell lung carcinoma and Merkel cell tumor.

The distinction between metastatic small cell lung carcinoma (SCLC) and Merkel cell tumor is difficult by routine histology, prompting the search for specific markers that could separate these neoplasms. Thyroid transcription factor 1 (TFF-1) is a homeodomain containing transcription factor expressed in the normal airway epithelium. The expression of TTF-1 has also been shown in adenocarcinomas and small cell carcinomas of the lung. However, the utility of TTF-1 to differentiate between SCLC and Merkel cell tumor has not yet been investigated. In this study, paraffin sections of 36 SCLCs and 21 Merkel cell tumors were analyzed for the presence of immunoreactive TTF-1 and cytokeratin 20 (CK20), a marker previously demonstrated in Merkel cell tumors. Monoclonal TTF-1 and CK20 antibodies were used with a biotin-streptavidin detection system. Immunostaining for TTF-1 was observed in 97% of SCLCs and in no Merkel cell tumors. Immunoreactivity for CK20 was demonstrated in 76% of Merkel cell tumors and 3% of SCLCs. These data indicate that TTF-1 is a sensitive (97%) and specific (100%) marker for SCLCs and can be used to differentiate SCLCs from Merkel cell tumors.

Carcinoma, Merkel Cell↗
PubMed1999

Sentinel-node guided lymph-node dissection for merkel cell carcinoma.

Merkel cell carcinoma is an aggressive neuroendocrine skin tumour. Treatment is still debatable. Merkel cell carcinoma resembles malignant melanoma in its cutaneous presentation and its embryonic origin; both have unpredictable biological behaviour, early regional lymph node involvement, early distant metastases and a high recurrence rate. In light of these common features, we used pre-operative lymphoscintigraphy, intraoperative lymph-node mapping and sentinel-node biopsy-a well-described technique for the treatment of melanoma-in a 60-year-old man with Merkel cell carcinoma in the right buttock. Following frozen section identification of a metastatic first-order sentinel node, radical right groin dissection was performed. All the other lymph nodes in this basin proved to be disease-free, including the second-order sentinel node and Cloquet node. The patient is now being treated with adjuvant chemotherapy and radiotherapy. This case shows that sentinel-node guided dissection is applicable to Merkel cell carcinoma.

Carcinoma, Merkel Cell↗
PubMed1992

Cytokeratin polypeptide profile of Merkel cells in human fetal and adult skin: difference of expression of cytokeratins in epidermal and dermal Merkel cells.

The origin of Merkel cells is uncertain, although current evidence by immunohistochemical keratin marker studies favors an epidermal derivation. We studied the expression of keratin species in Merkel cells of human fetus and adult using 19 anti-keratin antibodies. Epidermal and dermal Merkel cells contained not only simple epithelium-type but also some stratified epithelium-type keratins. Interestingly, expression of some keratins was different between epidermal and dermal Merkel cells, for example, AN3 (50, 58 kD) and CKB1 (50 kD) recognized epidermal Merkel cells, but not dermal Merkel cells. These results suggest that surrounding keratinocytes influence the expression of cytokeratins in Merkel cells or that dermal Merkel cells undergo a modification from keratin-producing epidermal Merkel cells to a more neural cell type by the association with nerve endings in the upper dermis. On the other hand, certain cytokeratin polypeptides recognizable with Ks19.1 (40 kD), CK5 (45 kD), and CAM5.2 (52.5 kD) were expressed in both epidermal and dermal Merkel cells. The expression of simple epithelium-type keratins in Merkel cells remained even after the epidermal basal cells gradually lost their expression.

Adult↗
PubMed2002

[Merkel cell carcinoma].

Merkel cell carcinoma (cutaneous neuroendocrine carcinoma) is an uncommon, highly malignant, neuroendocrine skin tumour. Typically, the primary is a fast-growing tough dermal nodule that is characterized histologically by uniform round cells with a small cytoplasmic rim. The tumour cells express the cytokeratins 8, 18, 19, 20, neurofilament, synaptophysin, chromogranin, and neuron-specific enolase. A high frequency of local recurrences (25-77%) and lymph-node metastases (50%) are characteristic features of Merkel cell carcinoma. The 5-year survival rate is 30-74%. Merkel cell carcinomas are highly radiosensitive. Thus, besides surgical methods, radiation should be included into the treatment concept in every stage. We present four cases of Merkel cell carcinoma with different courses for a review-like discussion of this disease giving instructions for rapid diagnosis and effective therapy.

Aged↗
PubMed1990

Presumed choroidal metastasis of Merkel cell carcinoma.

Merkel cell carcinoma is a rare skin tumor of neural crest origin and is part of the amine precursor uptake and decarboxylase system. It typically occurs on the face of elderly people. Distant metastasis is almost uniformly fatal. Choroidal metastasis, to our knowledge, has not been described. We report a patient with Merkel cell carcinoma who had a synchronous solid choroidal tumor and a biopsy-proven brain metastasis. Our 56-year-old patient presented with a rapidly growing, violaceous preauricular skin tumor. Computed tomography of the head disclosed incidental brain and choroidal tumors. Light and electron microscopy of biopsy specimens of both the skin and the brain lesions showed Merkel cell carcinoma. Ophthalmoscopy, fluorescein angiography, and A and B echography revealed a solid choroidal mass. The brain and skin tumors responded well to irradiation. A radioactive episcleral plaque was applied subsequently to the choroidal tumor. All tumors regressed, and the patient was doing well 28 months later. To our knowledge this is the first case of presumed choroidal metastasis of Merkel cell carcinoma.

Biopsy↗
PubMed2004

Gene-expression profiling reveals distinct expression patterns for Classic versus Variant Merkel cell phenotypes and new classifier genes to distinguish Merkel cell from small-cell lung carcinoma.

Merkel cell carcinoma (MCC) is a rare aggressive skin tumor which shares histopathological and genetic features with small-cell lung carcinoma (SCLC), both are of neuroendocrine origin. Comparable to SCLC, MCC cell lines are classified into two different biochemical subgroups designated as 'Classic' and 'Variant'. With the aim to identify typical gene-expression signatures associated with these phenotypically different MCC cell lines subgroups and to search for differentially expressed genes between MCC and SCLC, we used cDNA arrays to profile 10 MCC cell lines and four SCLC cell lines. Using significance analysis of microarrays, we defined a set of 76 differentially expressed genes that allowed unequivocal identification of Classic and Variant MCC subgroups. We assume that the differential expression levels of some of these genes reflect, analogous to SCLC, the different biological and clinical properties of Classic and Variant MCC phenotypes. Therefore, they may serve as useful prognostic markers and potential targets for the development of new therapeutic interventions specific for each subgroup. Moreover, our analysis identified 17 powerful classifier genes capable of discriminating MCC from SCLC. Real-time quantitative RT-PCR analysis of these genes on 26 additional MCC and SCLC samples confirmed their diagnostic classification potential, opening opportunities for new investigations into these aggressive cancers.

Biomarkers, Tumor↗
PubMed1992

Merkel cell carcinoma of the labial mucosa. An immunohistochemical and ultrastructural study with a review of the literature on oral Merkel cell carcinomas.

Merkel cell carcinoma is a rare cutaneous neuroendocrine tumor that occurs predominantly in the head and neck region of older patients. An 88-year-old white man had an erythematous, umbilicated tumor on his lower lip, which on histopathologic examination showed solid sheets of infiltrating basaloid round cells with a high mitotic index. Globular, paranuclear immunostaining for low-molecular-weight cytokeratins (Nos. 8, 18, and 19) and neurofilament was observed. On ultrastructural examination, the tumor cells demonstrated paranuclear whorls of intermediate filament aggregates and occasional electron-dense granules. This unique cytokeratin- and neurofilament-staining pattern with coexpression enabled the Merkel cell carcinoma to be differentiated from other small cell malignant tumors that included metastatic neuroendocrine carcinomas from other regions. The follow-up 1 year after surgery and radiation showed that the patient remained disease free. Review of the literature revealed 11 cases of oral Merkel cell carcinomas with a predilection for the labial mucosa of older men. The mode of treatment and the clinical course of these cases are also presented, with an update on therapeutic management of Merkel cell carcinomas.

Aged↗
PubMed2001

Management of Merkel cell carcinoma.

Merkel cell carcinoma is an uncommon cutaneous malignancy. Although it is rare, Merkel cell carcinoma has been described as the most malignant primary skin tumor. It is therefore important that once diagnosed, Merkel cell carcinoma is treated appropriately. The aim of this short review is to provide a summary of the available literature to guide clinicians in the future management of such patients. Inevitably in such a rare disease, there are no randomized trials of therapy. The treatment of individual patients will rely on opinion as much as the 'evidence'.

Carcinoma, Merkel Cell↗
PubMed2004

Complementary role of positron emission tomography in merkel cell carcinoma.

Merkel cell carcinoma is a rare type of neuroendocrine tumor of the skin with approximately 470 documented new cases annually in the United States. These tumors have high metastatic and recurrence rates, making them aggressive and difficult to treat. Diagnostic workup usually includes computed tomography, magnetic resonance imaging, and scintigraphy methods such as octreotide scans. More recently, positron emission tomographic scanning has been used to evaluate Merkel cell carcinomas. A case of Merkel cell carcinoma, in which positron emission tomography imaging with fluorodeoxyglucose played an important role in staging, re-staging, and identifying previously unknown distant metastatic disease, is presented in this article.

Antineoplastic Agents↗
PubMed1995

Penile Merkel cell carcinoma.

Merkel cell carcinoma of the genitalia is very rare and to date has been found only in vulvar mucosa. We describe an aggressive Merkel cell tumor in the frenulum of the penis with lymph node metastases, local recurrence, and eventually widespread dissemination. The primary tumor was associated with discontiguous squamous cell carcinoma in situ. This is the first report of Merkel cell (neuroendocrine) carcinoma in this anatomic site.

Carcinoma, Merkel Cell↗
PubMed1983

Merkel cell carcinoma of the skin: the structure and origin of normal Merkel cells.

A series of 15 Merkel cell tumours of skin is reported. They occur dominantly on the head and neck and on the extremities of elderly women, frequently presenting as a reddish nodule. Three cases were associated with squamous carcinoma at the same site, an association deserving further study. There are two main patterns: the commoner one takes the form of a trabecular carcinoma in the dermis mimicking metastatic carcinoma, including oat-cell carcinoma and neuroblastoma: a dissociated-cell form mimicks malignant lymphoma. The triad of vesicular nuclei with very small nucleoli, abundant mitotic activity and apoptosis is so characteristic as to be virtually pathognomonic in conjunction with structural features. Argyrophilia is common, but Bouin fixation is necessary to demonstrate it regularly. Small round secretory granules (89 +/- 18 nm) with narrow haloes, and an abundance of intermediate size filaments are among the ultrastructural hallmarks. There is a close similarity between better differentiated tumour cells and normal Merkel cells. The neural crest origin of MC is in doubt both on the basis of studies of the development and regeneration of MC and from the study of Merkel cell tumours.

Adenocarcinoma↗
PubMed1993

Merkel cell carcinoma.

Merkel cell carcinoma is a malignant neuroendocrine tumor with features of epithelial differentiation. Biologically aggressive, it may be difficult to diagnose and, particularly in its late stages, even more difficult to treat effectively. This article addresses what is known and what is still controversial about the histogenesis, diagnosis, and management of Merkel cell carcinoma and the structure and function of the Merkel cell from which it is believed to be derived. The incidence, clinical presentation and diagnosis, ultrastructure, immunocytochemistry, treatment, and prognosis of this tumor will be discussed.

Carcinoma, Merkel Cell↗
PubMed2000

Postoperative hyponatremia in a patient with ACTH-producing Merkel cell carcinoma.

Merkel cell carcinoma is characterized by specific neuroendocrine features and the expression of several neuropeptides. We report a case of Merkel cell carcinoma with post-surgical hyponatremia in an 85-year-old Japanese woman. A tumor on the left cheek histopathologically showed the characteristics of Merkel cell carcinoma together with Bowen's disease. Although an increased level of ACTH was found both in the tumor and in the peripheral blood, the postoperative hyponatremia in our patient seems more likely to have been caused by the stress of the operation and indapamide, considering that the ACTH level in the tumor was much lower than those in other ectopic ACTH-producing tumors in previous reports.

Adrenocorticotropic Hormone↗
PubMed2001

Paraneoplastic and metastatic neurologic complications of Merkel cell carcinoma.

Merkel cell carcinoma is a rare primary cutaneous neuroendocrine tumor that is locally aggressive and frequently accompanied by distant metastases. Neurologic complications of Merkel cell carcinoma are rare. We describe a 69-year-old man who presented with Lambert-Eaton myasthenic syndrome and was found to have Merkel cell carcinoma. The paraneoplastic syndrome improved with initial treatment of the malignancy. He subsequently developed a solitary brain metastasis and died of leptomeningeal carcinomatosis.

Aged↗
PubMed1986

On the avian Merkel cells.

Small Merkel cells are described in the hard palate epithelium of the chick. Further, spherical juxtaepithelial Merkel cells and more deeply situated apparently degenerating Merkel corpuscles are also described. The observations are interpreted as a reflection of a sequence of growth and decay of Merkel corpuscles, and seem to support the hypothesis of an epithelial origin of the Merkel cells.

Animals↗
PubMed1992

[The effectiveness of radiotherapy for Merkel cell carcinoma].

Merkel cell carcinoma is a high-grade malignant tumor of the skin that tends to extend locally and metastasize to regional lymph nodes. Surgical resection is the treatment of choice, and the effectiveness of radiotherapy for this disease has not yet been established. We report two cases of biopsy-proven Merkel cell carcinoma effectively treated with radiotherapy. Histopathological examination of the resected specimens after radiotherapy of 50 Gy and 38 Gy, respectively, using 6 approximately 15 MeV electrons showed no malignant cells in either case. No evidence of recurrence or metastasis has been noted in 11 to 21 months after radiotherapy. To our knowledge, no case of Merkel cell carcinoma in which complete cure was obtained by radiotherapy alone has been reported previously. It is considered that preoperative radiotherapy would contribute to the management of this locally invasive but radiosensitive tumor.

Aged↗
PubMed1989

Merkel cell carcinoma.

Merkel cell carcinoma is an unusual primary cutaneous tumor with an aggressive biologic nature. Following surgical treatment, 40% of patients have local recurrences develop, 55% have regional lymph node metastases develop, and 49% have distant metastases develop. We have treated four patients with Merkel cell carcinoma; only one of the four patients was alive and well after 2 years. Two patients died of metastatic disease, one at 11 months following initial treatment and one at 39 months. The fourth patient had a rapid recurrence following initial treatment and is currently in remission following chemotherapy for regional metastases. Recent reports indicate that chemotherapy may be helpful in treating patients with recurrent or metastatic Merkel cell carcinoma.

Age Factors↗
PubMed1983

Immunohistochemical localization of vasoactive intestinal polypeptide (VIP) in Merkel cells of various mammals: evidence for a neuromodulator function of the Merkel cell.

Since met-enkephalin-like substance has been demonstrated only in Merkel cells of some rodents but not of cat, dog, pig, and humans, Merkel cells of these species were analyzed by immunohistochemistry using a variety of different antisera for the occurrence of neuropeptides different from met-enkephalin. In various locations of all species investigated Merkel cells were found to be immunoreactive exclusively to vasoactive intestinal polypeptide (VIP) but not to any of the other antisera used. Thus, in mammalian Merkel cells, neuropeptides occur that are different from met-enkephalin. It is suggested that the Merkel cell-axon complex represents a complex regulatory system involving a presumptive receptor or modulator function whereby the Merkel cell may influence the threshold of the sensory nerve ending via release of a neuropeptide (VIP- or met-enkephalin-like material).

Animals↗