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PubMed2006

Sentinel lymph node biopsy for evaluation and treatment of patients with Merkel cell carcinoma: The Dana-Farber experience and meta-analysis of the literature.

OBJECTIVE: To determine the diagnostic accuracy and usefulness of sentinel lymph node biopsy (SLNB) and computed tomographic scans in the initial evaluation and treatment of patients with Merkel cell carcinoma (MCC). DESIGN: Single-institution case series and literature-based case-level meta-analysis. SETTING: Academic cutaneous oncology clinic.Patients Sixty-one adults with biopsy-proven MCC (30 who had undergone SLNB) plus 92 cases from the literature of patients who had undergone SLNB. MAIN OUTCOME MEASURES: Relapse-free survival. RESULTS: In 122 patients with no nodal disease found by physical examination, SLNB findings revealed nodal involvement in 39 cases (32%). At 3 years, the recurrence rate for those with a positive SLNB was 3 times (60%) higher than for those with a negative SLNB (20%; P = .03). Patients with a positive SLNB who received adjuvant nodal therapy had a relapse-free survival rate of 51% at 3 years (n = 26) compared with 0% for patients who did not receive nodal therapy (n = 3; P < .01). In contrast, among patients with a negative SLNB there was no significant difference in 3-year relapse-free survival rates for those who did (90%; n = 24) or did not (70%; n = 19; P = .26) receive adjuvant nodal therapy. Using SLNB plus clinical follow-up as a gold standard, computed tomographic scans had low sensitivity (20%) for detecting MCC that had spread to the lymph node basin and low specificity for distant disease (only 4 of 21 "positive" scans were confirmed during 6 months of follow-up). CONCLUSIONS: Sentinel lymph node biopsy detects MCC spread in one third of patients whose tumors would have otherwise been clinically and radiologically understaged and who may not have received treatment to the involved node bed. There was a significant benefit of adjuvant nodal therapy, but only when the SLNB was positive. Thus, SLNB is important for both prognosis and therapy and should be performed routinely for patients with MCC. In contrast, computed tomographic scans have poor sensitivity in detecting nodal disease as well as poor specificity in detecting distant disease.

Adult↗
PubMed1988

Neuroendocrine (Merkel cell) carcinoma of the skin. Its natural history, diagnosis, and treatment.

Over 400 cases of neuroendocrine (Merkel cell) carcinoma of the skin (NCS) have been reported. This tumor continues to pose problems in diagnosis and effective treatment for physicians unfamiliar with its biological characteristics. Reported here are five additional cases of NCS and the literature for this rare neoplasm is comprehensively reviewed. An early and accurate diagnosis is made possible by combining clinical presentation with results of histologic study, immunoperoxidase staining for neuron-specific enolase (NSE), epithelial membrane antigen (EMA), cytokeratins, and electron microscopy. NCS is an aggressive tumor. Depending on the length of follow-up, up to 40% of tumors locally recur, 55% develop regional nodal metastases, and 36% undergo distant metastasis. Survival is sex, but not age, dependent, with an overall 2-year survival rate of 72% (males 58% vs. females 79%). No standard procedure for initial and/or follow-up treatment for NCS exists. The authors recommend that NCS be treated, whenever possible, using the same rationale as applied for the treatment of squamous cell carcinoma of the skin.

Adenocarcinoma↗
PubMed2003

High-risk Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group Study--TROG 96:07.

PURPOSE: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy was prospectively assessed in a group of patients with high-risk Merkel cell carcinoma (MCC) of the skin. PATIENTS AND METHODS: Patients were eligible if they had disease localized to the primary site and nodes, and were required to have at least one of the following high risk features: recurrence after initial therapy, involved nodes, primary tumor size greater than 1 cm, gross residual disease after surgery, or occult primary with nodes. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks and synchronous carboplatin (area under the curve, 4.5) and intravenous etoposide 80 mg/m2 days 1 to 3 was given in weeks 1, 4, 7, and 10. The median age of the group was 67 (range, 43-86) years, and there were 39 males and 14 females. Involved nodes (stage II) were present in 33 cases (62%). The sites involved were head and neck (22 patients), occult primary (13 patients), upper limb (eight patients), lower limb (eight patients), and trunk (two patients). RESULTS: Fifty-three patients were entered between 1996 and 2001. The median potential follow-up was 48 months. There were no treatment related deaths. The 3-year overall survival, locoregional control, and distant control were 76%, 75%, and 76%, respectively. Tumor site and the presence of nodes were factors that were predictive for local control and survival. Multivariate analysis indicated that the major factor influencing survival was the presence of nodes; however, this was not a significant factor in locoregional control. CONCLUSION: High levels of locoregional control and survival have been achieved with the addition of chemotherapy to radiation treatment for high-risk MCC of the skin. The role of chemoradiotherapy for high-risk MCC warrants further investigation.

Adult↗
PubMed2001

Analysis of toxicity of Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group study.

PURPOSE: The acute and late toxicities of synchronous carboplatin, etoposide, and radiation therapy were prospectively assessed in a group of patients with high-risk Merkel cell carcinoma of the skin. PATIENTS AND METHODS: Forty patients from six different centers throughout Australia were entered into a Phase II study under the auspices of the Trans-Tasman Radiation Oncology Group. The trial was activated in 1996 and continues to accrue. Patients are eligible if they have disease localized to the primary site and nodes and are required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, gross residual disease after surgery, or occult primary with nodes. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (area under curve [AUC] 4.5) and etoposide (80 mg/M(2) i.v.) were given on days 1-3 during weeks 1, 4, 7, and 10. The median age of the group was 67 years (43-78). RESULTS: The median duration of follow-up was 22 months (2-45). There were no treatment-related deaths. Grade 3 or 4 skin toxicity occurred in 63% of patients (95% CI 48, 78). The most serious acute effect was on neutrophils with Grade 3 or 4 (neutrophils < 1 x 10(9)/L), occurring in 60% (95% CI 45, 75) of cases. Complications from neutropenia (fever and sepsis) occurred in 16 patients (40% of cases). The median time for neutropenic complications was 27 days (9-35), and 10/16 (62%) cases of neutropenic fever occurred after the second cycle of chemotherapy. The probability of Grade 3 or 4 late effects on platelets (<50 x 10(9)/L) and hemoglobin (<8 g/dl) was 10% (95% CI 1, 20) and 6% (95% CI 2, 15), respectively. Of the 40 patients, 35 were able to complete 4 cycles of chemotherapy. There were no factors predictive for neutropenic toxicity at a p value < 0.05. CONCLUSIONS: The protocol has acceptable toxicity, and the treatment has been deliverable in a multi-institutional trial setting. Neutropenia is likely to occur with synchronous carboplatin/etoposide and radiation in this population of patients. The risk of a febrile neutropenia was greatest at the time of the second cycle of chemotherapy, when there was moist desquamation of skin or mucosal membranes that provided a portal for infection. This should be considered in the design of subsequent protocols with chemoradiotherapy.

Adult↗
PubMed1992

Response of metastatic adenoid cystic carcinoma and Merkel cell tumor to high-dose melphalan with autologous bone marrow transplantation.

Two patients with metastatic spread of unusual tumors responded to treatment with high-dose Melphalan and autologous bone marrow transplant. One patient had adenoid cystic carcinoma of a minor salivary gland and the other had Merkel cell tumor of the scalp. Both patients had undergone prior surgery and radiotherapy, but later relapsed with distant metastases. Both patients had progression of their disease despite conventional and salvage chemotherapy. Treatment with high-dose Melphalan and autologous bone marrow transplant resulted in partial responses for both patients. High-dose Melphalan should be considered for therapy earlier in the course of patients with these unusual cancers.

Adult↗
PubMed2005

A case report of Merkel cell carcinoma on chronic lymphocytic leukemia: differential diagnosis of coexisting lymphadenopathy and indications for early aggressive treatment.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a monoclonal disorder, characterized by a progressive proliferation of functionally incompetent B lymphocytes. There is increased evidence of association between CLL and skin cancers, including the uncommon Merkel cell carcinoma (MCC). CASE PRESENTATION: A case report of an 84-year old male, who presented with an aggressively recurrent form of MCC on the lower lip, on the background of an 8-year history of untreated CLL. During the recurrences of MCC, coexisting regional lymphadenopathy, posed a problem in the differential diagnosis and treatment of lymph node involvement. Histopathology and immunoistochemistry showed that submandibular lymphadenopathy coexisting with the second recurrence of MCC, was due to B-cell small lymphocytic lymphoma. The subsequent and more aggressive recurrence of the skin tumor had involved the superficial and deep cervical lymph nodes. Surgical excision followed by involved field radiation therapy has been proven effective for both malignancies. CONCLUSION: MCC has a high incidence of regional lymphadenopathy at presentation (12-45%) and even when it arises on the background of chronic leukemia, lymphadenopathy at presentation should be managed agressively with elective lymph node dissection. We overview the postulated correlation between Merkel tumor and CCL, the differential diagnosis of regional lymphadenopathy during the recurrences of the skin tumor and the strategies of treatment.

Aged, 80 and over↗
PubMed2007

The Wnt-signaling pathway is not implicated in tumorigenesis of Merkel cell carcinoma.

BACKGROUND: The Wnt-signaling pathway, involving beta-catenin, apc, and axin, plays a critical role in numerous developmental events. Alterations in the Wnt-signaling pathway have been detected in a wide variety of neoplasms. However, similar aberrations have not been described in Merkel cell carcinoma (MCC). The aim of this study was to determine the status of the Wnt-signaling pathway in MCC. METHODS: Twelve cases of MCC were tested for the expression of beta-catenin and mutational status of CTNNB1 (gene for beta-catenin), APC, AXIN1, and AXIN2. Genomic DNA extracted from paraffin blocks was subjected to a polymerase chain reaction/single-strand conformation polymorphism analysis and sequencing. RESULTS: Nuclear accumulation of beta-catenin was observed in only one case (8.3%), as determined by immunochemistry. No mutations were found in CTNNB1, APC, and AXIN2 in all cases, although silent mutations in AXIN1 were detected in three cases. CONCLUSIONS: We conclude that the Wnt-signaling pathway does not play an important role in tumorigenesis in MCC.

Aged↗
PubMed2002

Anti-Hu antibodies in Merkel cell carcinoma.

Anti-Hu antibody is an antineuronal autoantibody found in a subset of patients with paraneoplastic neurological disease. The antibody was first associated with small cell carcinoma of the lung and is most often used as a marker for this neoplasm in patients presenting with suspected paraneoplastic syndromes. Here we report a patient with a multifaceted neurological disorder in the setting of Merkel cell carcinoma. The patient's serum contained antibodies against the Hu antigen, and the expression of the Hu antigen was demonstrated in the patient's tumor.

Aged↗
PubMed2002

CD117 (KIT receptor) expression in Merkel cell carcinoma.

The KIT receptor tyrosine kinase (CD117 antigen) is found in a variety of normal tissue cell types and in several malignant tumors, including acute myeloid leukemia. We recently encountered two tumors initially suspected as acute myeloid leukemia cutis and expressing CD117 that showed punctate positivity for cytokeratin 20 diagnostic for Merkel cell carcinoma. We evaluated 20 additional cases of MCC and found that 21 of 22 tumors (95%) expressed CD117. Intensity of CD117 expression did not appear to correlate with aggressive behavior. While the function of the KIT receptor in MCC is not known, its pathogenic role in other malignant neoplasms suggests the possibility of a similar role in MCC.

Aged↗
PubMed1981

Merkel cell receptors: structure and transducer function.

An electron microscopic and electrophysiological investigation was made of Merkel cell-neurite complexes in the sinus hair follicles of the cat. These mechanoreceptors respond with very precise phase locking to heavy-frequency vibratory stimuli as well as to static hair displacements. The mechanoelectric transduction process is faster than that known for any other somatic mechanoreceptor. These data show that the nerve endings themselves and not the Merkel cells are the mechanoelectric transducer elements in these receptors.

Action Potentials↗
PubMed1993

Immunohistochemical and immunoelectron microscopic demonstration of chromogranin A in formalin-fixed tissue of Merkel cell carcinoma.

BACKGROUND: Chromogranin A (CGA) is the major protein of neurosecretory granules (NSG) of cells of the diffuse neuroendocrine system, and the amount of CGA corresponds to the number of NSGs. OBJECTIVE: Because formalin fixation may destroy NSGs, a study was performed to examine the presence of CGA in Merkel cell carcinoma (MCC) to determine whether CGA depends on the presence of intact NSGs. METHODS: Formalin-fixed, paraffin-embedded tissue of 15 MCCs was investigated by immunohistochemistry and immunoelectron microscopy for the presence of CGA and NSGs. RESULTS: CGA was demonstrated in 12 of 15 MCCs by immunochemistry and in 6 of 10 MCCs by immunoelectron microscopy although intact NSGs could not be discerned in all cases. CONCLUSION: CGA remains demonstrable even when no morphologically intact NSGs are present, which suggests that CGA is not exclusively responsible for the electron density of NSGs.

Adult↗
PubMed2001

Cutaneous neuroendocrine (Merkel cell) carcinoma occurred after resection of malignant melanoma.

An elderly man presented with a brown border nodule of the left upper lip that appeared to be clinically consistent with metastatic melanoma; he had previously undergone two surgical removals of melanoma in the right temporal region. Routine histologic examination was not sufficient for diagnosis, but Merkel cell carcinoma was diagnosed by immunohistochemical studies Neuroendocrine carcinoma of viscera was excluded. Because this case could not be differentiated from amelanotic melanoma and malignant lymphoma based on histologic appearances, immunohistochemical staining was helpful for diagnosis and differentiation.

Aged↗
PubMedDate not supplied

Rapid growth of cutaneous neuroendocrine (Merkel cell) carcinoma during treatment of refractory cardiac allograft rejection with OKT3 monoclonal antibody.

OKT3 monoclonal antibody has proved to be a potent immunosuppressive agent in treating refractory heart allograft rejections. Recently, however, an increased incidence of lymphoproliferative disorders after OKT3 therapy has been found. This short report describes the rapid growth of a cutaneous neuroendocrine (Merkel Cell) carcinoma, a rare tumor of the dermis promoted by OKT3 administration. Because OKT3 therapy seems to be associated with an increased incidence of neoplasms, frequent patient follow-up is essential.

Carcinoma, Merkel Cell↗
PubMed1986

Trabecular (Merkel cell) carcinoma of the skin. Treatment of primary, recurrent, and metastatic disease.

Four new patients with trabecular (Merkel cell) carcinoma of the skin are described, and an additional 76 patients from the literature are reviewed. The mean age of the combined group of patients was 68; 84% were 60 years or older. Primary tumors appeared most frequently on the head and neck (44%), leg (28%), arm (16%), or buttock (9%). No primary tumor appeared on the trunk. The rate of local recurrence was 36%, regional metastatic disease, 53%; distant metastases, 28%; and death due to metastatic tumor (minimally), 25%. It appears that trabecular carcinoma of the skin is more aggressive and lethal than previously thought. The authors recommend that patients with this tumor undergo wide resection of the primary site and, in healthy patients, prophylactic regional node dissection. Both radiation therapy and chemotherapy are effective in palliating unresectable disease.

Adenocarcinoma↗
PubMedDate not supplied

Neuroendocrine (Merkel-cell) carcinoma of the skin. Fine needle aspiration cytology and clinicopathologic study of a case.

Neuroendocrine (Merkel-cell) carcinoma of the skin, a neoplasm usually found in elderly individuals, is often locally aggressive and has the potential to metastasize to lymph nodes and cause death. Microscopically the neoplasm is a small-cell carcinoma that involves primarily the dermis. We report a case of such a neoplasm in a 61-year-old female, stressing the possible contribution of fine needle aspiration cytology in the recognition of this neoplasm and its differentiation from other small-cell neoplasms that may involve the skin.

Biopsy, Needle↗
PubMedDate not supplied

Neuroendocrine (Merkel-cell) carcinoma of the skin. Cytology, intermediate filament typing and ultrastructure of tumor cells in fine needle aspirates.

The light and transmission electron microscopic findings and the intermediate filament typing of tumor cells from fine needle aspirates of primary, recurrent and metastatic neuroendocrine (Merkel-cell) carcinoma of the skin are described. The tumor cells in the smears coexpressed keratins and neurofilaments and were characterized by "intermediate filament buttons," i.e., buttonlike fragments of cytoplasm of tumor cells, which could be observed either by staining with intermediate filament-specific antibodies using immunofluorescence or by their appearance in hematoxylin-and-eosin-stained smears. These features may help in the differential diagnosis of fine needle aspirates of neuroendocrine carcinomas of the skin.

Adenocarcinoma↗