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PubMed2000

Merkel cell carcinoma: review of 22 cases with surgical, pathologic, and therapeutic considerations.

BACKGROUND: Merkel cell carcinoma is a primary small blue cell tumor of the skin with a proclivity to metastasize. Surgery and radiation therapy have defined roles in the primary treatment of Merkel cell carcinoma. Systemic chemotherapy can produce good response rates but does not have a primary role in the management of nondisseminated Merkel cell carcinoma patients. METHODS: Twenty-two patients were identified over the last 10 years in a retrospective analysis of tumor registries from the 6 hospitals of the ScrippsHealth facilities. Hospital and clinic charts as well as pathology specimens were reviewed. RESULTS: Eight patients underwent Mohs' surgery with permanent tissue technique. None of these patients had a subsequent local recurrence. Six patients received adjuvant radiation therapy, only one of whom developed a disease recurrence within a radiation port. Systemic chemotherapy was given to seven patients. One patient did not accept further treatment after a punch biopsy. CONCLUSIONS: Merkel cell carcinoma is an aggressive primary neoplasm of the skin, the histologic diagnosis of which can be difficult. Mohs' surgical technique combined with radiation therapy provides excellent local control. Systemic treatment is associated with high response rates, but to the authors' knowledge durable responses are uncommon.

Aged↗
PubMed1984

Malignant Merkel cell neoplasm of the eyelid.

Malignant Merkel cell neoplasms of the eyelid are most commonly found in elderly patients. They occur most frequently on the upper eyelid and are seen as large, nontender , red or violaceous masses with intact overlying skin. Differential diagnosis includes lymphoma and oat cell carcinoma. Conventional light microscopic features are usually distinctive, but tissue should be saved for electron microscopy and immunocytochemical studies, since the presence of dense-core neurosecretory granules and perinuclear microfilaments on electron microscopic examination and positive staining for neuron-specific enolase, are strongly suggestive of malignant Merkel cell neoplasm. Because of the diffuse infiltrative growth pattern and early lymphatic spread of this tumor, treatment requires careful examination of regional lymph nodes and wide surgical excision of the tumor with frozen-section control of margins.

Adenocarcinoma↗
PubMed1994

Merkel cell carcinoma of the head and neck.

Merkel cell carcinoma is a rare cutaneous tumour that typically arises in the head and neck area of elderly patients. The tumour often follows an aggressive course with frequent local recurrences and (regional) metastases, especially when localized above the clavicles. Five patients with a Merkel cell carcinoma of the head and neck, treated in our institute since 1984, are presented, illustrating the need for radical initial treatment consisting of surgery and radiotherapy, and showing how rapidly progressive the disease can be. Four of the five patients were cured of disease by a combination of surgery and radiotherapy.

Aged↗
PubMed1993

The treatment of advanced Merkel cell carcinoma. A multimodality chemotherapy and radiation therapy treatment approach.

BACKGROUND: The optimal management of Merkel cell carcinoma has not been clearly defined. OBJECTIVE: To describe the treatment of eight patients who presented with Merkel cell carcinoma. METHODS: Eight patients with advanced locoregional Merkel cell carcinoma were seen in our institute over a 7-year period. Four patients were successfully treated by induction chemotherapy after excisional biopsy, followed by radiotherapy. Three patients died from widespread metastases and one from neutropenic sepsis induced by chemotherapy. RESULTS: These cases demonstrate the potential lethality and aggressive nature of this rare skin tumor despite its chemosensitive and radioresponsive character. In all four patients who are alive and disease-free, chemotherapy was given first and radiotherapy was given as consolidation. CONCLUSION: We suggest that a multimodality treatment approach--chemotherapy followed by radiotherapy--is indicated in patients with advanced Merkel cell carcinoma.

Adult↗
PubMed1998

Characteristic pattern of chromosomal gains and losses in Merkel cell carcinoma detected by comparative genomic hybridization.

Merkel cell carcinoma or small cell carcinoma of the skin is a rare skin cancer seen in increasing numbers in Queensland, Australia. In its clinical course and histopathology, it resembles small cell lung carcinoma (SCLC). Little is known of the genetic basis of this disease except for a number of cytogenetic studies and three loss of heterozygosity studies. Therefore, comparative genomic hybridization was performed to determine the characteristic DNA gains and losses that occur in this tumor. Comparative genomic hybridization analysis of 34 specimens from 24 patients revealed a pattern of gains and losses that closely resembles that seen in SCLC. Overall frequent loss was seen for chromosomes 3p (46%), 5q (21%), 8p (21%), 10 (33%), 11q (17%), 13q (33%), and 17p (25%). Significant gains were seen for chromosomes 1 (63%), 3q (33%), 5p (38%), 8q (38%), 19 (63%), and X (41%), with smaller numbers having gains for chromosomes 6, 7, 20, and 21. In contrast to SCLC, amplification in Merkel cell carcinoma is a rare event.

Carcinoma, Merkel Cell↗
PubMed2000

Primary neuroendocrine carcinoma ("Merkel cell tumor") of the eyelid: a report of two cases.

BACKGROUND. Merkel cell tumor is an uncommon, aggressive neoplasm of the skin, now regarded as a neuroendocrine carcinoma. Eyelids are among the sites where it can develop, often mimicking a benign process. The purpose of this report is to describe two new cases and to discuss briefly the problems of diagnosis and treatment. METHODS. Two patients with Merkel cell tumor of the eyelids are described. In both cases, the original clinical diagnosis was chalazion. Progressive growth of the lesion identified it as a tumor some 2-7 months after it was first noticed. The patients were treated by surgical excision of the tumor tissue, and only one by a course of local radiotherapy. The visual acuity was measured with Snellen fractions. The dose of local radiotherapy is given in cGy. RESULTS. Histopathological and immunohistochemical studies identified the lesion as a neuroendocrine carcinoma, consistent with Merkel cell tumor. The natural history was marked by aggressive behavior in one case, and by a delayed recurrence in the other, requiring different therapeutic approaches. CONCLUSION. Merkel cell carcinoma of the eyelid is a tumor that ophthalmogists should be aware of, as early diagnosis is a prerequisite for successful treatment. Rapid recurrence of any chalazion in a middle-aged or elderly patient should therefore prompt its histological examination to exclude the possibility of a malignant tumor.

Journal Article↗
PubMed1999

Merkel cells in the human oesophagus.

Merkel cells (MCs) are well recognized in the basal layers of the skin and oral mucosa, but this paper describes for the first time the presence of MCs in the human oesophagus. These cells are not identified in neonatal oesophagus, but are seen singly and in clusters in adult specimens. Application of stereological techniques shows that MCs are more numerous in the mid-oesophageal region. Cells expressing established markers of MCs have also been demonstrated in two out of six primary small cell carcinomas of the oesophagus. Further investigation of the role of MCs in oesophageal innervation and epithelial biology will be of interest.

Adult↗
PubMed2006

Merkel cell cancer of the skin.

Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumor of the elderly with rapidly growing skin nodules found predominantly on sun-exposed areas of the body. The vast majority of patients present with localized disease, while up to 30% have regional lymph node metastases. Despite local excision and the incidence of local recurrence, regional lymph node metastases and distant metastases is high and usually occurs within 2 years of primary diagnosis. The optimal treatment for patients with MCC remains unclear. The best outcome is achieved with multidisciplinary management including surgical excision of primary tumor with adequate margins and post-operative radiotherapy (RT) to control local and regional disease. Patients with regional nodal metastases should be treated with lymph node dissection plus RT. Adjuvant chemotherapy (CT) should be considered as part of the initial management. In case of metastatic disease CT based on regimens used for small-cell lung cancer is the standard treatment of care.

Carcinoma, Merkel Cell↗
PubMedDate not supplied

Lymph node Merkel cell carcinoma with no evidence of cutaneous tumor--report of two cases.

We report two cases of Merkel cell carcinoma within inguinal and axillary lymph nodes, respectively, showing no clinico-pathologic evidence of a primary (extranodal) tumor; one of our patients was alive with no evidence of disease five years and ten months after the surgical excision of the neoplasm with no postoperative chemotherapy. The diagnosis of nodal Merkel cell carcinoma needs to be supported by a careful immunohistochemical study: in fact, cytokeratin- and neurofilament-positive paranuclear "dots", as well as epithelial antigens and neuroendocrine markers may be variably expressed in tumor cells, thus requiring the application of a complete antibody panel. In the presence of a nodal Merkel cell tumor, an exhaustive clinico-radiologic search for a primary tumor must be carried out. After the exclusion of any reasonable starting point of the neoplasm, a provisional diagnosis of "primary" nodal Merkel cell carcinoma may be acceptable; since a primary extracutaneous tumor is expected to follow a less aggressive course than a metastatic one, follow-up data may provide indications as to the truly extracutaneous origin of Merkel cell carcinoma.

Adult↗
PubMed1985

Intermediate filaments in Merkel cell tumors.

A series of ten Merkel cell tumors is described, with special emphasis on intermediate filament expression. The presence of cytoskeletal proteins was studied with a polyclonal antiserum directed against cytokeratin and with monoclonal antibodies against cytokeratin, neurofilament, and vimentin by the immunoperoxidase technique. Cytokeratin was demonstrated in nine of ten tumors. Neurofilament was observed in the two snap-frozen tissues tested and in three of the eight formalin-fixed, paraffin-embedded tissues. No reactivity for vimentin was found. By electron microscopy desmosomes were found to be present in all cases, while tonofilaments were found in only a few cases. neurosecretory granules, although seen in all tumors, were generally present in low numbers. The results of this study indicate that the Merkel cell tumor is a poorly differentiated small cell carcinoma that has the ability to express some neuroendocrine features.

Adenocarcinoma↗
PubMed1979

The specialized junctions between Merkel cell and neurite: an electron microscopic study.

Longitudinal serial sections of one half of the entire sinus hair of a mouse were examined by the electron microscope. Three neurites entering the outer root sheath from the perifollicular blood sinus were encountered. These were separate nerve trunks from those connected with perifollicular tactile nerve endings and exclusively innervated intrafollicular Merkel cells. Two types of specialized junctions were observed at the contact regions between Merkel cell plasma membrane and neurite plasma membrane: (i) desmosome-like structures in which small clear vesicles and/or the large cored vesicles of neurite and thicker membrane (post-synaptic?) of apposed Merkel cell were found ant (ii) synapse-like structures in which Merkel cell granules were concentrated near the plasma membrane and the membrane of the apposed neurite was usually thicker (post-synaptic?). In some of the synapse-like junctions the limiting membrane of Merkel cell granules fused with the Merkel cell plasma membrane and its content seemed to be discharged into the intercellular space. This suggested actual exocytotic secretion of Merkel cell granules. Juxtaposition of 2 types of junctions, i.e. (i) and (ii) above, was also found. This suggested the possibility that the reciprocal synapse would be present between Merkel cells and afferent neurites.

Animals↗
PubMed1992

Species variability in the expression of met- and leu-enkephalin-like immunoreactivity in mammalian Merkel cell dense-core granules. A light- and electron-microscopic immunohistochemical study.

Immunogold staining failed to show met-enkephalin immunoreactivity in the Merkel cell dense-core granules of rats when examined by electron microscopy, but showed gold particle staining in the Merkel cell dense-core granules of mice and nude mice. Merkel cells of hamster, guinea pig, rabbit, cat and dog were also examined using a similar method, and different antisera dilutions. Immunogold particles were consistently found in the dense-core granules of mice and nude mice at all antisera dilutions, but not in the other species, except in the dog, where a very low labelling response was encountered. Merkel cells from skin touch domes or sinus hair follicles, did not exhibit any difference in peptide expression as far as met-enkephalin immunoreactivity was concerned. In addition, all species studied, including mice and nude mice, did not show leu-enkephalin immunoreactivity in their Merkel cell dense-core granules. It is concluded that species variability in peptide expression occurs in the Merkel cell dense-core granules, and may be closely related to the different methodologies used.

Animals↗
PubMed1994

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.

Antibodies, Monoclonal↗
PubMed1992

Merkel cell carcinoma.

A case of Merkel cell carcinoma of the cheek is described, highlighting the clinical behaviour, diagnosis and management of this uncommon tumour.

Aged↗
PubMedDate not supplied

Response of Merkel cells in the palatal rugae to the continuous mechanical stimulation by palatal plate.

The aim of the present study was to investigate the responses of Merkel cells that are numerous in the palatine rugae, due to the continuous mechanical stimulation exerted by the palatal plate. Forty golden hamsters were used in this experiment. The palatal plate was made of adhesive resin and it was set on the palate of the animal. To exert a continuous pressure, a 0.8 mm elevation on the internal surface of the palatal plate was created at the middle portion of the fourth palatine ruga. Thereafter, the number of Merkel cells in the mucosa was calculated by immunohistochemical observation. Morphological changes of Merkel cells were examined by electron microscopy. There was significant difference among the control and any of the treated groups on the number of CK20 positive Merkel cells (p < 0.05) and that numbers were decreased at the sites where continuous mechanical stimulation was exerted. Degeneration of the cytoplasm mitochondria and nerve endings, and a decrease in both the number of neurosecretory granules and cytoplasmic processes were observed. Furthermore, the presence of nuclear chromatin aggregation and fragmentation was recognized. The continuous mechanical stimulation by the palatal plate affected the responses of Merkel cells and nerve endings, thus inducing a decrease in the number of Merkel cells. A portion of these changes was also associated with the expression of apoptosis.

Animals↗
PubMed1993

Neurofilament immunoreactivity in Merkel-cell tumors: a differentiating feature from small-cell carcinoma.

To differentiate Merkel-cell tumor (MCT) from other neuroendocrine (NE) carcinomas, we immunostained (using avidin-biotin-peroxidase method) nine MCT and 37 NE (including 28 small-cell) carcinomas for NE markers (neuron-specific enolase and chromogranin), cytokeratin, neurofilament, vimentin, and a number of other markers. Cytokeratin was positive in 100% of MCT and in 85% of small-cell carcinomas; neurofilament and vimentin were positive in respectively 100% and 22% of MCT and 0% of NE carcinomas. Our data suggest that the coexpression of cytokeratin and neurofilament by an undifferentiated dermal or visceral tumor is of significant help in diagnosing MCT and differentiating it from small-cell carcinomas. The vimentin reactivity is a weak and insignificant discriminant.

Adult↗
PubMed1995

Chemotherapy for Merkel cell carcinoma with carboplatin and etoposide.

Merkel cell carcinoma is a rare malignant tumor of the skin. We treated three patients with Merkel call carcinoma with the combination of carboplatin and etoposide, which have been mostly used in the treatment of small cell lung carcinoma. Two patients experienced partial remission of short duration. The third patient received the combination on an adjuvant basis but relapse occurred briefly. Two of these patients failed to respond to second-line chemotherapy with cisplatin, ifosfamide, and epirubicin. The patient who had the first-line treatment on an adjuvant basis, responded completely with the second-line chemotherapy plus radiotherapy and remains disease-free for 5+months. Merkel cell carcinoma appears to be a sensitive tumor to chemotherapeutic regimens used for small cell lung carcinoma, but the responses are often brief.

Aged↗
PubMed1998

Cytokeratin and neurofilament protein staining in Merkel cell carcinoma of the small cell type and small cell carcinoma of the lung.

Merkel cell carcinoma (MCC) has a small cell variant, indistinguishable in hematoxylin-eosin sections from metastatic small cell carcinoma of the lung (SCCL). To investigate whether intermediate filament expression is helpful in this distinction, 17 MCCs of the small cell type were examined for cytokeratin, as well as neurofilament protein immunostaining, and compared with 59 intermediate-type MCCs and 22 SCCL. With a pan-cytokeratin cocktail (cytokeratin 1-8, 10, 13-16, 19), most (39 of 55) intermediate-type tumors and, more important, 11 of 16 cases of the small cell variant exhibited focal paranuclear staining with dot-like positivity, crescentic positivity, or both. A combined focal (dot-like/crescentic) and diffuse cytoplasmic pan-cytokeratin staining was seen in additional 8 of 55 intermediate and 4 of 16 small cell MCCs. Cytokeratin 20 also evoked focal cytoplasmic staining and occasionally focal and diffuse positivity in the MCCs, irrespective of the subtype. Exclusively diffuse cytokeratin 20 patterns did not occur. Conversely, most SCCL showed a diffuse expression of pancytokeratin, and all cases remained cytokeratin 20 negative. When neurofilament protein was applied, approximately half of the MCCs (25 of 40), including 7 of 11 of the small cell variant, were positive, whereas all SCCL were negative. In conclusion, the cytokeratin and neurofilament protein patterns of small cell MCCs are identical to the pattern of intermediate MCCs but differ from the profile of SCCL, which may help in the differential diagnosis.

Adult↗