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PubMed1988

Immunocytochemical analysis of calcitonin gene-related peptide and vasoactive intestinal polypeptide in Merkel cells and cutaneous free nerve endings of cats.

Calcitonin gene-related peptide (CGRP)- and vasoactive intestinal polypeptide (VIP)-immunoreactivity were observed to coexist in Merkel cells of cats. No differences in peptide content were found between Merkel cells located in epithelia of the hard palate, in hairy and glabrous skin of the upper lip, and in vibrissae follicles. CGRP- and VIP-immunoreactive nerve fibres were also found near CGRP/VIP-immunoreactive Merkel cells. In the vibrissae follicles some CGRP- and VIP-immunoreactive nerve terminals end abutting on the glassy membrane. Other CGRP-immunoreactive nerve fibres penetrate the epithelium of the skin and end within it. Electron microscopy of vibrissae follicles revealed that Merkel cell neurites are not immunostained and that immunostained nerve fibres form unmyelinated bundles before ending freely. Thus, CGRP- and VIP-immunoreactive nerve fibres in cat skin do not end as Merkel cell neurites but as different kinds of free nerve endings.

Animals↗
PubMed1996

Merkel cell carcinoma of the skin.

Primary neuroendocrine carcinoma of the skin or Merkel cell carcinoma is an aggressive primary neoplasm. It is commonly seen in the elderly, on the head, neck and extremities, where it can mimic a benign or less malignant skin tumour. Pathological examination shows a generally dense growth of small dark cells, with immunohistochemical evidence of neuroendocrine differentiation. The microscopic appearance is very similar to metastatic oat cell carcinoma from the lung and this must be excluded by clinical means and appropriate imaging studies. In this study we present 13 new cases of Merkel cell carcinoma (the largest published series in the UK) and summarize 214 cases from the literature in which the survival data are given. In our series, 5 of 13 patients died from spread of the Merkel cell carcinoma. From this and other studies, it appears that early diagnosis and wide local excision may be the only way to prolong survival. No other adjuvant therapy has proved effective.

Aged↗
PubMed2000

Magnetic resonance imaging appearance of metastatic Merkel cell carcinoma to the sacrum and epidural space.

Merkel cell carcinoma (MCC) is a rare malignant tumor of the skin and often is diagnosed histologically as lymphoma, melanoma and even metastatic small cell carcinoma of the lung (SCCL). Classified as a neuroendocrine tumor, clinically it originates in the head and neck region and may present with metastatic disease at the time of presentation [1]. Osseous involvement in the past has been described to involve regional facial bones only. We present the first reported MRI findings of distant osseous metastasis from a Merkel cell carcinoma to the lumbosacral spine with associated soft tissue and epidural involvement. Appropriate treatment and patient survival depend on prompt diagnostic imaging for establishment of metastatic disease. Previous reports have advocated CT for diagnosis and staging of distant metastases [2,3]. When spinal involvement is suspected, MRI may be a more suitable modality for assessment of the epidural space and appropriate staging and follow-up in such cases.

Aged↗
PubMedDate not supplied

Merkel cell carcinoma of the skin with leptomeningeal metastases.

Merkel cell carcinoma is a rare skin tumor that is thought to arise from epithelial cells that have undergone neuroendocrine differentiation. It usually presents in older adults and has a slight male predominance. The most frequent site of occurrence is in the head and neck. It is an aggressive disease that has a high rate of local-regional and distant recurrence. Optimal treatment is controversial but generally consists of surgery and adjuvant radiotherapy. The role of chemotherapy is less defined. This report documents the first known case of Merkel cell carcinoma with perineural spread to the central nervous system with leptomeningeal dissemination. Whether this represents a more aggressive variant is unknown. Regardless, this pattern of spread is likely a rare event.

Carcinoma, Merkel Cell↗
PubMed1989

Merkel cell tumor of the eyelid: a review and report of an unusual case.

We describe a case of a Merkel cell tumor of the eyelid that manifested as a recurrent chalazion. This tumor had the classic characteristics of a Merkel cell neoplasm by light microscopy. Electron microscopy showed dense-core neurosecretory granules and perinuclear microfilaments consistent with the diagnosis. Because a Merkel cell tumor may manifest as a chalazion, pathologic evaluation of all atypical chalazia is essential. Merkel cell tumors are malignant, and they must be treated aggressively to minimize recurrence or metastasis.

Aged↗
PubMed2004

Treatment of merkel cell carcinoma.

PURPOSE: The purpose of this study was to evaluate the treatment of Merkel cell carcinoma. MATERIALS AND METHODS: We reviewed 85 cases of Merkel cell carcinoma. There were 68 males and 17 females. The majority of cases involved head and neck sites (48%), followed by the extremities (38%) and trunk (14%). Sixty-seven percent of the patients had stage I disease that was localized to the skin of origin at presentation. Twenty-five percent and 8% were stage II (nodal metastasis) and stage III (distant metastasis), respectively. Surgical intervention included local or wide local excision +/- nodal dissection (68%), radical resection +/- nodal dissection (22%), and amputation (4%). Five patients (6%) underwent biopsy only because of metastatic disease or unresectability at presentation. Fifty-one percent received adjuvant therapy consisting of external beam radiation therapy and/or combination chemotherapy. RESULTS: With an average follow-up time of 39.5 months, 12% had persistent disease and 40% had recurrent disease. The median time to recurrence was 8 months with a mean of 10.6 months. Although the addition of adjuvant therapy did not affect survival, the recurrence rate was 32.5% for surgery +/- adjuvant radiation therapy +/- chemotherapy as compared with 52.7% for surgery-only patients. Although the 40.7% recurrence rate for patients receiving surgery and adjuvant radiation therapy was approximately the same as for patients receiving surgery and adjuvant chemotherapy (40%), the effect of systemic chemotherapy on recurrence is less clear as a result of the small number of patients who received such therapy. Although tumor size and site of presentation were not observed to be statistically significant in overall survival, significant differences were observed based on sex and tumor stage. For females, the median survival time was 96 months (mean, 94.5 months) compared with 63 months (mean, 76.8 months) for males. This difference was significant (P < 0.01). Patients presenting with low-stage (stage I) disease had a significant (P < 0.01) survival benefit when compared with high-stage individuals (stages II and III). The 5-year actuarial survival rates were 68% and 42%, respectively. CONCLUSION: In this retrospective study, surgery remains the primary modality for Merkel cell carcinoma, and adjuvant radiation therapy +/- systemic chemotherapy reduces local recurrence. Female patients and those who present with early-stage disease appear to have a better prognosis.

Aged↗
PubMed1989

Chromogranin A in the mammalian Merkel cell: cellular and subcellular distribution.

Chromogranin-A (CGA), which accounts for more than half the soluble matrix protein in secretory granules of various neuroendocrine cells, has a wide spectrum of potential biological roles and is considered an important marker of the diffuse neuroendocrine system (DNES). Light and electron microscopic immunohistochemistry of mammalian skin revealed that Merkel cells are exclusively CGA-immunoreactive (ir) and that the immunoreaction is localized in the secretory granules. This finding supports the classification of the Merkel cell as a member of the DNES. The CGA immunoreactivity was restricted to Merkel cells of pigs and humans. In human embryonic skin, CGA was expressed in Merkel cells as early as week 11 of gestation. The antisera differed in their ability to stain Merkel cells in different species and developmental stages, reflecting a variable chemical coding for CGA. CGA probably represents a precursor for smaller regulatory peptides or acts as a messenger on its own on various target tissues, suggesting a neurosecretory function of the Merkel cell.

Age Factors↗
PubMed1997

p53 abnormalities are rare events in neuroendocrine (Merkel cell) carcinoma of the skin. An immunohistochemical and SSCP analysis.

The aim of the present study was to assess a possible role of the tumour suppressor gene p53 in neuroendocrine (Merkel cell) carcinoma of the skin with regard to tumour development and tumour progression. p53 was investigated in a series of routinely processed Merkel cell carcinomas, with application of four different p53 antibodies (CM-1, PAb1801, DO7, and PAb240) to 25 carcinomas and screening for p53 mutations of exons 4-8 by single-strand conformation polymorphism (SSCP) analysis in 9 cases. All 25 tumours in the present series showed the characteristic microscopic and immunohistochemical features of Merkel cell carcinoma of the skin. In 5 of the 25 Merkel cell carcinomas investigated 5-10% of tumour cell nuclei showed a positive p53 reaction with at least one anti-p53 antibody. A few scattered p53 positive nuclei were found in an additional 9 cases. The remaining 11 cases completely lacked p53 immunostaining. SSCP analysis of exons 4-8 revealed no significant alterations in the mobility shift of the single strand DNAs in the five cases with 5-10% p53-immunoreactive tumour nuclei or in five cases lacking p53 accumulation significant. Our results suggest that alterations of the p53 gene play only a minor part in the development or progression of Merkel cell carcinoma of the skin.

Aged↗
PubMed2002

Development and rapid dissemination of Merkel-cell carcinomatosis following therapy with fludarabine and rituximab for relapsing follicular lymphoma.

This report deals with an unusual case of a patient with follicular small cleaved lymphocytic lymphoma who developed Merkel-cell carcinoma soon after receiving chemoimmunotherapy with a fludarabine-containing regimen and rituximab. The presentation of the Merkel-cell carcinoma in this patient was atypical because of the absence of dermal involvement and the very rapid clinical progression. In the light of recent reports which suggest a possible link between the immunocompromised state and the development of Merkel-cell carcinoma, the atypical presentation seen in this patient may indeed imply a possible link between the therapy given and the development of Merkel-cell carcinoma. To the best of our knowledge, this is the first documentation of Merkel-cell carcinoma appearing in a patient soon after treatment with fludarabine and/or rituximab.

Antibodies, Monoclonal↗
PubMed2001

Merkel cell carcinoma of the head and neck: effect of surgical excision and radiation on recurrence and survival.

BACKGROUND: Merkel cell carcinoma is a rare malignant neoplasm of the skin that most often arises in the head and neck region. Despite the innocuous appearance of the primary lesion, Merkel cell carcinoma often has an aggressive clinical course with frequent locoregional recurrences and distant metastases. We evaluated the association of the width of surgical margins and the use of postoperative radiation therapy with locoregional control and survival rates. METHODS: The medical records of 66 patients with head and neck Merkel cell carcinoma seen between 1945 and 1995 were retrospectively reviewed. The Fisher exact test was used to compare outcomes. Kaplan-Meier survival curves were constructed. RESULTS: Eighteen patients for whom there was adequate information were divided into the following groups according to the width of their surgical margins: smaller than 1 cm, 1 to 2 cm, and larger than 2 cm. No statistical difference in locoregional control or survival was found among these groups owing to the small patient population. In contrast, a comparison of the patients who did (n = 26) and did not (n = 34) receive postoperative radiation therapy revealed a significant difference in local (3 [12%] vs 15 [44%], respectively; P<.01) and regional (7 [27%] vs 29 [85%], respectively; P<.01) recurrence rates. There was, however, no significant difference in the disease-specific survival between these groups (P = .30). Distant disease developed in 36% of all patients regardless of therapy. CONCLUSIONS: Any effect of the width of surgical margins on outcome was not detectable in the small number of patients analyzed. The use of postoperative radiation therapy was associated with a significant improvement in locoregional control. There was no detectable influence of the type of initial therapy on the rates of distant metastases or on survival. Future therapeutic innovations should be directed toward controlling the development of distant metastases in patients with Merkel cell carcinoma.

Adult↗
PubMed1998

123I-MIBG SPECT of Merkel cell carcinoma.

131I-MIBG may be useful in the detection of neuroendocrine tumours. Merkel cell carcinoma is a neuroendocrine tumour of the skin. We evaluated a patient with Merkel cell carcinoma using 123I-MIBG single photon emission computed tomography (SPECT) which demonstrated tumour accumulation of the radiotracer in the right eyelid. This result suggests that 123I-MIBG SPECT may be useful in the evaluation of Merkel cell carcinoma.

3-Iodobenzylguanidine↗
PubMed1992

Somatostatin analogue scintigraphy. A simple and sensitive method for the in vivo visualization of Merkel cell tumors and their metastases.

BACKGROUND: Trabecular carcinomas of the skin, or Merkel cell tumors, are aggressive neoplasms that tend to occur in sun-exposed skin. These tumors frequently metastasize and, despite therapy, the number of disease-related deaths is high. Ultrastructurally and immunocytochemically, the majority of these tumors have neuroendocrine characteristics. Recently, we described the in vivo visualization of various neuroendocrine tumors after injection of a radiolabeled somatostatin analogue (octreotide). In this study, we report the results of scintigraphy with radioactive-labeled somatostatin analogues in five patients with Merkel cell tumors. OBSERVATIONS: In all four patients in whom tumor was detected using computed tomographic scanning and ultrasound, the tumor sites were also demonstrated on octreotide scintigrams. In one patient, a tumor with a diameter that was smaller than 0.5 cm could not be detected with octreotide scintigraphy, computed tomography, or ultrasound. Using octreotide scintigraphy we found presumed tumor spots in two patients that were not evident when other techniques were used. CONCLUSIONS: Octreotide scintigraphy has an equal or even greater sensitivity than computed tomography and ultrasound for detecting Merkel cell tumors and their metastases. Establishing the spread of the disease in this way may ensure an optimal choice of treatment in patients with this type of tumor.

Aged↗
PubMed1998

Merkel cells in hyperplastic and neoplastic lesions of the skin. An immunohistochemical study using an antibody to keratin 20.

BACKGROUND: Merkel cells are neuro-endocrine cells present in the basal layer of the human epidermis and the outer root sheath of hair follicles. OBJECTIVE AND METHOD: In order to gain further insight into the as yet ill-defined involvement of Merkel cells in skin diseases, we studied the distribution of these cells in formalin-fixed, paraffin-embedded sections of 165 inflammatory, hyperplastic or tumoral skin lesions of various anatomic locations, with a monoclonal antibody to keratin 20. RESULTS: Lesions with frequently increased Merkel Cell numbers included actinic keratosis, fibrous papules of the face and some conditions with (immature) hair follicle differentiation. CONCLUSION: These results suggest that Merkel cell hyperplasia is unrelated to epidermal proliferation but that it is rather specific to a limited number of skin diseases.

Antigen-Antibody Reactions↗
PubMed1986

Merkel cell carcinoma: combined surgery and radiation therapy.

Merkel cell carcinoma, first reported as "trabecular carcinoma" by Toker in 1972, is a dangerous, often fatal primary skin tumor. The current authors report eight patients, only one of whom is considered to have a totally successful clinical outcome. Two patients died and one was preterminal with widespread disease in 10 to 20 months. Two others had recurrence or metastases within a year, and two patients died early of intercurrent disease after first developing regional lymph node involvement. Review of 139 patients reported in the literature indicates local recurrence in 30 per cent, regional lymph node metastases in 50 per cent, and death from neoplasm in 18 per of the cases. All patients in the present series received radiation therapy with encouraging response. The tumor was quite radiosensitive, and in only one instance was there recurrence within an irradiated field. Wide surgical excision with prompt postoperative irradiation to the local site and regional lymphatics is the therapy of choice in early lesions. Regional lymphadenectomy is recommended whenever nodal involvement is suspected. Currently, an aggressive combined surgical and radio-therapeutic approach to this dangerous neoplasm appears warranted, although further data may show that early and routine use of radiotherapy in Merkel cell carcinoma could obviate the necessity for extensive operative procedures.

Adenocarcinoma↗
PubMed1994

CD44 expression in Merkel cell carcinoma may correlate with risk of metastasis.

We retrospectively studied 25 cases of cutaneous primary, locally recurrent or metastatic Merkel cell carcinoma to see if expression of the cell surface marker CD44 correlated with metastatic potential. In 3 of 6 cases in which metastasis was documented, CD44 was found on membranes of tumor cells. Three cutaneous lesions associated with local metastasis did not express CD44. Three primary tumors expressed CD44 but had not disseminated at the time of this report; follow-up after excision of the primary lesion in these cases was less than 6 months. None of the primary or locally recurrent Merkel cell carcinomas followed longer than 6 months (14 of 19 cases) expressed CD44. We conclude that expression of CD44 in Merkel cell carcinoma may eventually be of some value in the assessment of prognosis of cutaneous Merkel cell carcinoma.

Aged↗
PubMed1984

Dermal Merkel cells in the nevus of Ota and leopard syndrome.

We observed dermal Merkel cells around vellus hair follicles in one patient with nevus of Ota and one with leopard syndrome. These Merkel cells were in contact with Schwann cells and nerve endings in the dermis. The question of whether or not Merkel cells exist normally in adult dermis remains unanswered. However, their presence in these abnormal conditions suggests that normally they do occur in the dermis but go undetected because their numbers are so few or they are in a form not readily identifiable by currently available methods.

Abnormalities, Multiple↗
PubMed1996

Merkel cell carcinoma of the eyelid.

PURPOSE: To demonstrate the clinical variability and histologic characteristics of Merkel cell carcinoma of the eyelid. METHODS: We investigated two cases of Merkel cell carcinoma of the eyelid in a 67-year-old man and an 83-year-old woman, respectively. Both lesions were initially misdiagnosed as benign tumors on clinical examination. RESULTS: After the correct diagnosis was made, both lesions were treated with wide resection aided by frozen sections, and reconstructive surgery. CONCLUSIONS: Merkel cell carcinoma is an aggressive tumor with variable clinical manifestation. Radical surgical therapy and close follow-up are indicated.

Aged↗
PubMed1989

Merkel cell carcinoma of the vulva: a case report.

The clinical and pathologic findings of Merkel cell carcinoma of the vulva were reported. The light microscopic findings of sheets of small, uniform cells were consistent with a diagnosis of neuroendocrine tumor. The electron microscopic characteristics revealed membrane-bound secretory granules, confirmed the diagnosis of Merkel cell carcinoma. Regional lymphnode metastases were present at the time of initial surgery and the adjunctive radiotherapy was also given. This case was unusual because Merkel cell carcinoma was usually found on the face, extremities and buttocks.

Adult↗