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PubMed2004

Recurrent DNA copy number changes revealed by comparative genomic hybridization in primary Merkel cell carcinomas.

Comparative genomic hybridization (CGH) was used to search for gains, high-level amplifications and losses of DNA sequences along all chromosome arms in 19 primary Merkel cell carcinomas (MCC). Extensive genetic aberrations, with a mean value of 5.5+/-1.1 changes per tumor were detected in 13 out of the 19 samples analyzed. Our CGH results reveal several new and other previously known chromosomal regions that are involved in the pathogenesis of MCC. The majority of the alterations were gains of whole chromosomes or whole chromosome arms. Compared to losses, the frequency of DNA copy number gains was two-fold. DNA sequence copy number gains were most common in chromosomes 6 (42%), 1 (37%), and 5 (32%). The most frequent minimal common regions of gains were 6pterqter (42%), 1q11q31 (32%), and 5p (32%). No recurrent high-level amplifications were observed. High-level amplifications of small chromosomal regions were found in four samples out of the 19 tumors analyzed (21%). Amplifications affected 1q22q24 (5%), 4p (5%), and 5p (5%). Losses most frequently affected chromosomes 13 (21%) and 4 (16%). Minimal common regions with the most frequent losses were 13q13q31 (21%), 4q (16%), and 16q (11%). No significant statistical correlation between genomic aberrations and clinicopathological factors was revealed, despite the fact that there was an obvious tendency towards it. Primary MCC expressing DNA alterations were predominantly distinguished in large tumors, and risk of metastatic dissemination was three-fold compared to tumors with no DNA alterations.

Aged↗
PubMed1982

Small-cell neuroepithelial tumor of skin: a Merkel-cell neoplasm?

Two patients with small-cell undifferentiated neuroepithelial tumors of skin are reported. The histologic and ultrastructural features of this neoplasm are presented. Characteristic membrane-bound, dense-core neurosecretory granules were seen in the cytoplasm of the tumor cells in both cases. The literature is reviewed in regard to the clinical behavior of these lesions and their possible cell of origin. Dermatologists should be aware of these tumors because they may require electron microscopy for accurate diagnosis. The tumors should be treated aggressively to minimize the chance of local recurrence and nodal or visceral metastases.

Aged↗
PubMed1985

Small cell carcinoma of the skin "non-Merkel cell type".

An 81-year-old Japanese woman developed small cell carcinoma of the skin, which was different from trabecular carcinoma or neuroendocrine carcinoma of the skin. The tumor was composed of spindle-shaped or fusiform cells with scanty cytoplasm and numerous mitoses. The tumor cells were arranged in a streaming pattern and not in anastomosing trabecular fashion at all. No granules were detected by Grimelius' stain either. Immunoperoxidase staining for neuron specific enolase (NSE) did not reveal any activity. Ultrastructural study showed scanty organelles in the cytoplasm which contained a few round mitochondria, rough endoplasmic reticulum, and free polysomes. Occasionally, filamentous bundles, desmosomes, and intracytoplasmic canaliculi were recognized in the cytoplasm, but neurosecretory granules were not found throughout the cytoplasm. Electron microscopic features suggest that this tumor originated from the embryonal stratum germinativum. The present tumor can be distinguished from trabecular carcinoma or neuroendocrine carcinoma of the skin, and may be regarded as "small cell carcinoma" of the skin.

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PubMed1991

[Merkel cell carcinoma: an endocrine differentiated tumor in the head-neck area].

Merkel's cell carcinomas are rare tumours of the skin, frequently on the head and neck. Electron microscopical and immunohistological techniques are employed for differentiation from other skin malignancies. With two cases the clinical picture, the typical histology and the therapy are elucidated. To detect pathognomic antigen expression, antibodies against Neuron-specific-enolase (NSE) as a marker for endocrine activity and cytokeratin to prove the epithelial character of cells were used (Abb. 4 a,b). The best treatment of Merkel's cell carcinoma is surgical resection, including the regional lymph nodes. Consecutive radiotherapy is strongly recommended.

Aged↗
PubMed1986

[Merkel cell carcinoma with metastasis to the bone marrow].

The information concerning the concept of Merkel cell-neuron as a mechanoreceptor is revised. We are presenting an autopsy case in which a Merkel cell carcinoma infiltrated bone marrow and provoked its hypoplasia. An analysis of the literature let us see that the behavior of this neoplasia can be quiescent, but also could be very aggressive, with development of distant metastasis to lymph node, skin, liver, brain, bone and lung. These tumors can give origin to a paraneoplasic syndrome.

Adenofibroma↗
PubMed2005

Reliability of sentinel lymph node biopsy for regional staging of head and neck Merkel cell carcinoma.

OBJECTIVE: To determine (1) the reliability of sentinel lymph node (SLN) biopsy and (2) the need for cytokeratin 20 (CK-20) immunostaining in the staging of head and neck Merkel cell carcinoma (MCC). DESIGN: Retrospective cohort study (median follow-up of 34.5 months). SETTING: Tertiary care center. PATIENTS: Ten patients with head and neck MCC who underwent regional staging with SLN biopsy (SLNB) and CK-20 immunostaining. INTERVENTIONS: Sentinel lymph nodes were identified using preoperative lymphoscintigraphy, intraoperative gamma probe, and isosulfan blue dye. The SLNs were evaluated with hematoxylin-eosin and CK-20 immunostaining. Patients with negative SLNB results were followed up clinically. MAIN OUTCOME MEASURES: Percentage of positive SLNs, regional recurrence in the setting of a negative finding from SLNB, and percentage of positive SLNs requiring CK-20 immunostaining for diagnosis of micrometastatic MCC. RESULTS: At least 1 SLN was identified in every patient. Of 24 nodes, 19 (79%) were from the neck region and 5 (21%) were from the parotid basin. Two of the 24 SLNs, in 2 (20%) of 10 patients, were positive for metastatic disease. Both positive SLNs appeared negative on hematoxylin-eosin-stained sections, but small foci of micrometastatic MCC were identified with CK-20 immunostaining. No cranial nerve complications occurred. Regional failure in the setting of a negative finding on SLNB was observed in 1 (12%) of 8 patients. CONCLUSIONS: Biopsy of SLNs represents a safe and reliable technique for regional staging of MCC of the head and neck. It provides pathologists with a limited number of SLNs for focused analysis, which is imperative because hematoxylin-eosin immunostaining is often insufficient for identifying micrometastatic MCC. The use of anti-CK-20 antibody allows accurate identification of micrometastatic MCC.

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PubMed1997

[Merkel cell carcinoma. A rare differential keratoacanthoma diagnosis].

A 90 year old woman presented with a rapidly growing nodular tumor at the tip of the nose. Clinically, keratoakanthoma was tentatively diagnosed. Histological examination, however, revealed Merkel cell carcinoma. This case supports the necessity of a surgical excision with a subsequent histological examination even when the clinical aspect is suggestive for keratoacanthoma.

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PubMed1990

Presence of Merkel cells in sun-exposed and not sun-exposed skin: a quantitative study.

Merkel cells (MCs), the neuroendocrine cells of the skin cannot be identified with certainty using conventional light microscopic staining methods. Using immunoperoxidase microscopy with antibodies specific for cytokeratin 18, which has been established as a marker protein of MCs, we have evaluated the numbers of MCs per mm2 skin in normal and sun-damaged upper arm skin. The sun-exposed skin contained twice as many MCs as the not sun exposed skin. Further quantification of MC density at various body sites (trunk, leg) showed a rather variable but often unexpectedly high MC density. The possible role of MC in development of actinic elastosis is discussed.

Adolescent↗
PubMed1990

Immunocytochemical labelling of Merkel cells of human oral mucosa by means of antibodies to protein gene product 9.5.

Merkel cell (MC) are one of the non-keratinocyte cell populations that reside in oral epithelium. Protein gene product 9.5 (PGP 9.5) is a protein specifically present in the cytoplasm of neurons and neuroendocrine cells. It is demonstrated by immunofluorescence and immunoperoxidase that MC of oral human mucosa express PGP 9.5-like immunoreactivity. This finding is in agreement with the hypothesis that oral MC are paraneurons or neuroendocrine cells. The use of anti-PGP 9.5 serum may be of value for future studies of MC in normal and pathological oral tissues.

Antibodies↗
PubMedDate not supplied

Merkel cell carcinoma.

A rare, primary, malignant carcinoma of the skin exists of which the Merkel cell has been implicated as the cell of origin. Until recently, reports of this cancer were sparse. A review of the literature is presented along with a case report in which the primary tumor occurred on the lower leg.

Aged↗
PubMed2001

Merkel cell carcinoma can be distinguished from metastatic small cell carcinoma using antibodies to cytokeratin 20 and thyroid transcription factor 1.

AIM: To investigate whether immunohistochemical staining for cytokeratin 20 (CK20) and thyroid transcription factor 1 (TTF-1) is useful in distinguishing Merkel cell carcinomas (MCCs) from metastatic small cell carcinomas (SCCs). METHODS: Eleven cases of MCC and 10 of lung SCC were stained for CK20 and TTF-1. RESULTS: Ten of 11 MCCs stained with the antibody to CK20. None was positive for TTF-1. No SCC stained with anti-CK20 and all stained strongly with anti-TTF-1. CONCLUSIONS: The use of both anti-CK20 and anti-TTF-1 can reliably distinguish between MCC and metastatic SCC, thus avoiding the need for a detailed clinical investigation of patients with MCC in whom metastatic SCC must be excluded.

Biomarkers, Tumor↗
PubMed1996

Expression of bcl-2 and p53 in Merkel cell carcinoma. An immunohistochemical study.

Bcl-2 is a protooncogene thought to play a role in oncogenesis by inhibiting programmed cell death. It may interact with p53, a tumor-suppressor gene which induces apoptosis in certain circumstances. We have studied these gene products by immunohistochemistry in 15 cases of Merkel cell carcinoma, a tumor characterised by prominent apoptosis. Five cases showed moderate/strong staining for p53, with moderate/strong bcl-2 staining in 10 patients. In seven cases abundance of p53 and bcl-2 expression was mutually exclusive. Two patients died within 1 year of diagnosis and six had nodal recurrences. Gene expression and survival appear unrelated. The role of Bcl-2 and p53 in tumorigenesis is complicated and may be inter-related with other genes known to be involved in programmed cell death.

Aged↗
PubMedDate not supplied

Merkel cell carcinoma of the skin. Treatment of primary, recurrent, and metastatic disease: review of clinical cases.

The clinical features of 10 cases with the adjunct of a literature review of primary neuroendocrine carcinoma of the skin (Merkel cell tumor) are reported. This cancer arises in the dermis and subcutaneous tissue of elderly individuals. Natural history is characterized by local recurrences (40%), regional lymph-nodes metastases (50%), and distant metastases (60%). Surgery is the elective treatment of primary and locoregional disease and subsequent radiotherapy prevents local recurrences and prolong disease-free survival in literature reports. Chemotherapy and radiotherary resulted in only a short-term palliative response in the metastatic setting.

Adult↗
PubMed2001

A study of apoptosis in Merkel cell carcinoma: an immunohistochemical, ultrastructural, DNA ladder, and TUNEL labeling study.

We performed immunohistochemical, ultrastructural, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL), and DNA ladder studies of apoptosis in nine cases of Merkel cell carcinoma (MCC). None of the cases showed spontaneous regression as has been reported in several MCCs. Neuron-specific enolase was demonstrated by immunohistochemistry (8/8 MCCs), and staining for cytokeratin 20 was positive (2/8 MCCs). Ultrastructural examination revealed many cytoplasmic dense-cored granules, desmosome-like structures, and intermediate filaments. The granules were seen along the plasma membrane or around perinuclear centrioles. We found various stages of development of apoptotic bodies. Apoptosis resulted in vacuolization and fragmentation of nuclei and phagocytosed bodies in tumor cells. Apoptotic cells were also detected by TUNEL, DNA ladder, and immunostaining using the antibody against Fas (Apo- 1/CD95) antigen. It seems that a high apoptotic rate is a common finding in MCC, although spontaneous regression is an exceedingly rare event. It is thus unlikely that apoptosis alone would explain spontaneous regression.

Aged↗
PubMed1986

Variability of expression and arrangement of cytokeratin and neurofilaments in cutaneous neuroendocrine carcinomas (Merkel cell tumors): immunocytochemical and biochemical analysis of twelve cases.

Twelve specimens of cutaneous neuroendocrine carcinomas (Merkel cell tumors) available as fresh tissue were analyzed for intermediate filament (IF) expression by immunocytochemical and biochemical methods. In immunofluorescence microscopy, most cases were positive for both simple-epithelium-type cytokeratins and the neurofilament L- and M-polypeptides. Several different IF staining patterns ranging from presence of plaque-like structures (fibrous bodies) only to nearly exclusive expression of delicate cytokeratin fibrils could be distinguished. In immunoelectron microscopy the labeling for both cytokeratin and neurofilament polypeptides seemed evenly distributed among the IFs of the fibrous bodies. In primary culture, tumor cells maintained the coexpression of both IF types. Desmoplakin-positive true desmosomes were found in 5 specimens. Biochemically, cytokeratins nos. 8, 18 and, variably, 19, as well as IT protein and, in many specimens, the neurofilament L-protein and a putative neurofilament M-protein were detected. Only traces of the neurofilament H-polypeptide were found. Our results show that a coexpression of cytokeratin IFs and neurofilaments in variable patterns is a characteristic feature of cutaneous neoendocrine carcinomas; occasionally, however, neurofilaments may be very scarce. The biological, histogenetic and diagnostic implications are discussed.

Adult↗
PubMed1990

Primary neuroendocrine (Merkel cell) carcinoma presenting in the calvarium: case report.

A case of a primary neuroendocrine carcinoma arising in the calvarium and involving the bone, dura, and underlying brain is presented. The histopathology and immunohistochemical staining characteristics of tumor were consistent with those of Merkel cell tumor. The natural history and histopathology of this tumor are discussed, along with the possible explanation for the origin of this tumor in the calvarium.

Aged↗
PubMed2001

A Merkel cell carcinoma of the skin.

A 79-year old female caucasian patient presented in January 91 with a nodular lesion of the right cheek that had appeared rapidly. The histologic specimen was in favour of a primary neuroendocrine skin tumor, Merkel cell carcinoma-. In March 91, a relapsing nodule had grown up and adenopathies were found on the right parotid and sub-mandibular spaces. An aggressive polychemotherapy was performed for 6 cycles and a complete remission was obtained. In November 91 the sub-mandibular lymph node had reappeared. A complete staging was again performed. After 3 cycles of chemotherapy, a regional radiotherapy completed the treatment. With a follow-up of more than 8 years the patient stays in complete remission in April 2000.

Aged↗