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PubMed2006

Merkel cell carcinoma (primary cutaneous neuroendocrine carcinoma): an overview on management.

Merkel cell carcinoma is an uncommon but aggressive primary cutaneous neuroendocrine (small cell) carcinoma. There is ongoing debate regarding the optimal treatment of this disease. The early literature comprised small institutional studies with inherent weaknesses. Recent data have emerged from larger studies, including those from Australian institutions, that adds support to a multimodality approach as best practice. Despite this, the outcome for patients with unfavourable disease remains poor and in most series 25-30% of patients die as a direct result of Merkel cell carcinoma. The head and neck is the commonest site for presentation (50-60%) and wide excision (2-3 cm) of the primary lesion is usually recommended, although achieving this is often difficult within functional and cosmetic constraints. All clinically node-negative patients should be considered candidates for elective nodal treatment and those with clinical nodal disease should undergo nodal dissection and adjuvant radiotherapy. Recent evidence suggests that patients treated with surgery and adjuvant locoregional radiotherapy experience a better disease-free survival compared with those undergoing surgery alone. The role of platinum-based chemotherapy is evolving. The aim of this article is to discuss relevant issues in the management of a patient with Merkel cell carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Merkel cell carcinoma in situ.

BACKGROUND: Merkel cell carcinoma (MCC) is a dermal small blue-cell tumor that occurs in the elderly on the sun damaged head and neck. Epidermal involvement is unusual and MCC limited to the epidermis is very rare. CASE REPORT: A slightly tender pink hyperkeratotic papule was noted on the dorsal right hand of a 76-year-old man with a history of multiple skin cancers. An intraepidermal proliferation of small blue cells distributed in nests and single units at all levels of the epidermis was found within a solar keratosis and adjacent to an area of squamous cell carcinoma in situ. Cytokeratin 20 and neuron specific enolase highlighted these cells and failed to reveal dermal involvement. There was no residue on re-excision. CONCLUSION: We report the third case of MCC in situ. These lesions have only been reported in association with squamous neoplasms on the extremities.

Aged↗
PubMed1997

Merkel cell carcinoma of the pinna.

Merkel cell carcinoma is an increasingly recognized tumour of the skin. The commonest presentation is the head and neck region. Only three cases of this rare tumour have been reported on the pinna. A further such case is presented here.

Aged↗
PubMed1991

Metastatic Merkel cell carcinoma to the eye.

Merkel cell carcinoma is an infrequent but highly aggressive cutaneous neoplasm. Previous reports of ocular involvement have included primary eyelid carcinomas, eyelid and orbital metastases, and a clinically diagnosed choroidal metastasis. The authors report the histopathologic documentation of a metastatic lesion to the ciliary body, confirming the intraocular metastatic potential of this tumor.

Aged↗
PubMed2005

Anti-cytokeratin 20 staining of Merkel cells helps differentiate basaloid proliferations overlying dermatofibromas from basal cell carcinoma.

BACKGROUND: Basaloid epidermal proliferations (BEP), morphologically resembling basal cell carcinoma (BCC), have been described overlying dermatofibromas. Distinguishing the two is important because of non-aggressiveness of BEP and local aggressiveness of BCC. The aim of this study is to determine whether CK20 antibody staining for Merkel cells can be used as an adjunct method to differentiate BEP from BCC. METHODS: Ten cases of BEP overlying dermatofibromas were selected. Ten cases of BCC were used as control. The two groups were stained with CK20 antibody. Numerical density of CK20 stained Merkel cells in peri-lesional epidermis, BEP and BCC was determined by examining 300 cells at 400X in two separate areas by three independent pathologists. To determine statistical significance, the results were compared using t-test method. RESULTS: Density of Merkel cells in peri-lesional epidermis was 0.2-0.3%. No merkel cells were detected in the BCC. BEP overlying dermatofibromas showed an obvious increase in CK 20 stained Merkel cells. The difference was statistically significant (P < 0.02) CONCLUSIONS: We report a significant increase in CK20 stained Merkel cells in BEP overlying dermatofibromas as compared to BCC. CK20 antibody staining for Merkel cells can be used as an adjunct method to differentiate BEP overlying dermatofibromas from BCC. Mahmoodi M, Asad H, Salim S, Kantor G, Minimo C. Anti-CK20 staining of Merkel cells helps differentiate basaloid proliferations overlying dermatofibromas from basal cell carcinoma.

Adult↗
PubMed1996

Isolated hyperthermic limb perfusion chemotherapy in Merkel cell tumour: a case report.

Merkel cell carcinoma of the skin is a rare malignant tumour first described in 1972 by Toker. The optimal management of this disease has not been clearly defined, especially that of advanced locoregional disease. Surgery, radiotherapy and chemotherapy have been advocated separately or in combination, with less-than-optimal results. Localized high-dose chemotherapy has never been tried, although it would seem to be the logical step forward.

Aged↗
PubMed2002

Merkel cell carcinoma and HIV infection.

Merkel cell carcinoma (MCC) is a rare skin cancer that occurs more frequently after organ transplantation or B-cell malignancy, conditions of suppressed or disordered immunity. To assess further whether immune suppression increases MCC risk, we studied its occurrence in a cohort of 309365 individuals with acquired immunodeficiency syndrome (AIDS) by using linked AIDS and cancer registries. We identified six cases of MCC, corresponding to a relative risk of 13.4 (95% CI 4.9-29.1) compared with the general population. These results suggest that immune suppression induced by the human immunodeficiency virus increases MCC risk.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Mohs' micrographic surgery for Merkel cell carcinomas of the eyelid.

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumour that may affect the eyelid. There is no consensus on the optimal treatment for eyelid MCC, and management remains controversial. Here we present our experience in a case of eyelid MCC treated by Mohs' micrographic surgery. Although this treatment has been advocated for general skin MCCs, there is very little experience with this technique in relation to eyelid MCCs. We suggest that Mohs' micrographic surgery may be an appropriate method of treating MCCs of the eyelid.

Aged↗
PubMed1999

Farnesylthiosalicylic acid inhibits the growth of human Merkel cell carcinoma in SCID mice.

Merkel cell carcinoma (MCC) is a neuroendocrine malignancy showing poor response to a variety of therapeutic strategies. We evaluated the antitumor activity of S-trans, trans-farnesylthiosalicylic acid (FTS), a new inhibitor of Ras signal transduction, in a newly established SCID mouse xenotransplantation model for human MCC (seven animals per group). FTS injected intraperitoneally at 5 mg/kg per day for 2 weeks up-regulated the tumor suppressor p53 and induced tumor cell apoptosis in established MCCs growing subcutaneously in SCID mice. These effects led to a statistically significant inhibition of MCC growth (P<0.002). The mean tumor weights following FTS or control treatment were 0.32+/-0.15 g and 1.08+/-0.29 g, respectively. There was no evidence of FTS related toxicity at the effective dose used. Our findings stress the notion that FTS may qualify as a novel and rational treatment approach for MCC and possibly for other tumors that rely on tyrosine kinase signaling.

Aged↗
PubMed1993

[Merkel cell carcinoma].

Eight patients with Merkel cell carcinoma are reported to document their response to surgery and/or radiotherapy. Four patients who initially underwent surgery without postoperative radiation therapy all had local recurrence. Two patients were treated with postoperative radiation therapy and two were treated with radiation therapy without excision of the tumour. None of these four patients had local recurrence. Five patients developed regional recurrence. Recurrence was seen in one patient in the irradiated field. Metastatic disease was not seen in any case. These results combined with a review of the literature suggest that radiation therapy postoperatively to both the surgical bed and the draining lymph nodes may improve local regional tumour control.

Aged↗
PubMed1996

Comparative genomic hybridization (CGH) discloses chromosomal and subchromosomal copy number changes in Merkel cell carcinomas.

We analyzed three Merkel cell carcinomas (MCC), applying comparative genomic hybridization (CGH) with DNA from paraffin-embedded and cultured tumor material as the probes. By this method, numerous changes in chromosome copy numbers were observed in each tumor investigated. Recurrent gains of chromosomes 1, 6, 18q and 20 were detected in two tumors. A third tumor showed complex chromosomal copy number changes, including gain of chromosome 8 and 9. These gains, as well as gain of chromosome 1 in the first two tumors, were confirmed by fluorescence in situ hybridization to paraffin tissue sections. Our results support the view that important genes for MCC development may be located on chromosomes 1, 6, 18q and 20.

Aged↗
PubMed2005

Merkel cell carcinoma of the auricle.

Merkel cell carcinoma (MCC) is an uncommon cutaneous neoplasm which arises in adults with a peak incidence in the sixth and seventh decades. MCC most often arises in the head and neck area and extremities. Among head and neck primary sites, auricular MCC has proven to be rare and only 20 cases have been reported in the literature. Auricular MCC follows the same aggressive course as has been documented for MCC arising elsewhere: the tumor has a propensity for recurring locally and metastasizing to regional lymph nodes and distant sites. Location of MCC in the auricular regions does not appear to confer any survival advantage compared with MCC arising elsewhere. The mainstay of treatment is surgery, with attempts at complete surgical excision being of paramount importance. What role regional node dissection, radiation therapy and chemotherapy may play in the standard treatment of auricular MCC remains to be clearly established.

Adolescent↗
PubMedDate not supplied

[Merkel cell carcinoma: diagnostic and treatment].

Merkel cell carcinoma (MCC) is an uncommon neuro-endocrine tumor of the sun-exposed skin predominantly observed in white patients in the sixth decade of the life. In electron microscopy MCC characteristically contains dense core secretory granules. This tumor expresses both epithelial (keratins of low molecular weight of the simple epithelial type, epithelial membrane antigen) and neuro-endocrine markers (neuron-specific enolase, chromogranin A). The analysis of available literature indicates that MCC has a propensity for involvement of regional lymphatics (12% of patients at the date of initial diagnosis and 50 to 66% afterwards) and for metastases to distant sites (20 to 52%). The prognosis of metastatic disease is poor. The overall survival from the diagnosis of metastases is 6 months. The optimal treatment of locoregional stages should include excision and post-operative radiation. The role of chemotherapy in this tumor is unclear but recent data suggest a high chemosensitivity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Deletion mapping on the short arm of chromosome 1 in Merkel cell carcinoma.

Twenty-two Merkel cell carcinoma (MCC) biopsies and six cell lines from 24 patients were examined for loss of heterozygosity (LOH) at 11 loci on 1p and one on 1q, to determine LOH regions on chromosome 1p. Sixteen (73%) tumors had LOH for at least one locus; 14 demonstrated LOH at more than one locus, and 7 (29%) samples had more than one region of loss, with 4 of these having loss at all informative loci on 1p. Three common regions of loss (SRO) were defined by LOH in multiple tumors. Eight samples demonstrated LOH between D1S214 and D1S160 (1p36), seven between D1S234 and D1S186 (1p35), and 11 for the region centromeric of D1S211 and D1S220 (1p32-1p33). Seven samples (29%) demonstrated more than one region of loss. LOH on 1p occurs frequently in MCC and more than one tumor suppressor gene on 1p is likely to play a role in the development of this tumor type.

Allelic Imbalance↗
PubMed1997

Early aggressive treatment for Merkel cell carcinoma improves outcome.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of dermal origin. Treatment recommendations are limited owing to a paucity of retrospective data and an absence of prospective data. The objective of this study was to determine current therapeutic trends and their impact upon outcome. METHODS: A retrospective study (1983 to 1996) was performed with patients from the Department of Defense and our University-affiliated hospitals. RESULTS: Thirty-five patients were evaluated with a mean follow-up of 31 months. Overall, 1- and 2-year survival rates were 80% and 50%, respectively. Patients undergoing wide local excision, prophylactic lymph node dissection, and adjuvant radiotherapy had significantly decreased locoregional and distant recurrence rates and improved survival when compared with their counterparts. Adjuvant chemotherapy did not diminish recurrence rates nor improve survival. Both locoregional and distant recurrence significantly decreased survival. CONCLUSIONS: These data suggest that early aggressive treatment for MCC improves both tumor control and survival, whereas the early use of chemotherapy does not improve outcome.

Adult↗
PubMed1996

Merkel cell tumor in a woman with chronic lymphocytic leukemia.

We describe a 69-year-old woman with basal cell carcinoma, and chronic lymphocytic leukemia who developed Merkel cell tumor. This latter malignancy first appeared as enlarged lymph nodes in the axilla and elbow regions and responded initially to radiotherapy. Later, the patient developed obstructive jaundice which was due to pancreatic metastases of the Merkel cell tumor, documented by post-mortem examination. To our knowledge, this is the first description of a Merkel cell tumor causing obstructive jaundice, in a patient with chronic lymphocytic leukemia.

Aged↗
PubMed2003

Merkel cell carcinoma--current therapeutic options.

Merkel cell carcinoma (MCC) is a rare, highly malignant skin tumour of neuroendocrine origin that occurs predominantly in elderly people in sun-exposed areas. It exhibits high levels of radiosensitivity and chemosensitivity both in vivo and in vitro. A variety of adverse prognostic factors have been identified which allow more aggressive therapy to be delivered to patients who are at higher risk of recurrence. The most powerful prognostic factor is the presence of nodal secondaries. Local disease should be excised, but there is some controversy over how wide the margins should be. Wide resection margins are not required provided postoperative radiotherapy is used. In the event of inoperable disease, patient refusal of surgery or frailty, radiotherapy can be used as the sole treatment modality, with a high likelihood of achieving local control. Patients with involved nodes have a higher risk of distant disease. Traditionally, involved nodes have been managed with resection but, currently, there are protocols exploring the use of synchronous chemoradiotherapy as definitive treatment. Although adjuvant chemotherapy has been used in this setting to reduce the risk of distant metastases, its role still remains under investigation. The presence of distant disease carries a grave outlook with responses to chemotherapy occurring frequently, albeit of short duration.

Antineoplastic Agents↗
PubMed2026

High tumor mutational burden and PIK3CA mutations correlate with poor Merkel cell carcinoma-specific survival.

Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma of the skin characterized by poor prognosis. This study aimed to explore the relationship between genetic alterations, tumor mutational burden (TMB), and MCC-specific survival (MCC-SS) in patients who underwent genomic profiling of tumors with OncoPanel. Univariate and multivariable analysis were used to assess the impact of genetic alterations on MCC-SS. Of the 188 identified patients, 164 were included in the analysis. The cohort had a mean age of 72.4 years (SD = 11.03), including 61.6% male. The median TMB was 5.32 (IQR = 3.04-25.53). Kaplan-Meier curves by high versus low TMB were significantly different (log-rank test, P = 0.017). PIK3CA (adjusted P = 0.003), SETBP1 (adjusted P = 0.002), KDR (adjusted P = 0.028), and RET (adjusted P = 0.033) were selected for multivariable analysis. In the multivariable regressions, only PIK3CA (HR = 2.07 [95% CI, 1.10-3.88]; P = 0.024) remained significant. PIK3CA remained significant across prespecified sensitivity analyses. In this study, high TMB and PIK3CA alterations were associated with poor MCC-SS. Identifying a higher-risk subgroup may inform risk stratification and motivate further evaluation of PI3K pathway targeting in future studies.

Humans↗