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PubMed1990

Primary cutaneous neuroendocrine carcinoma (Merkel cell tumor). An adnexal epithelial neoplasm.

We report 18 cases of primary cutaneous neuroendocrine carcinoma (CNEC, Merkel cell tumor) that occurred mainly in the sun-exposed skin of elderly patients as dermal and subcutaneous masses of generally monomorphic cells with foci of pronounced pleomorphism. All 18 cases showed immunoreactivity for neuron-specific enolase (NSE), whereas 16 of them showed immunoreactivity for another neuroendocrine marker, protein gene product 9.5 (PGP 9.5). Positivity for PGP 9.5 was more intense and more sharply localized to tumor cells than the staining for NSE. Immunoreactivity for keratins detected by AE1/AE3 and CAM 5.2 monoclonal antibodies was found in 16 and 15 cases, respectively, with prominent paranuclear globular staining. One case stained positively for S-100 protein; all were negative for leukocyte common antigen (LCA). Typical ultrastructural features of neuroendocrine differentiation were noted in all of 14 tumors examined. Morphological and immunohistochemical similarities between these neoplasms and pulmonary small-cell anaplastic carcinoma, now thought to be of bronchial basal cell origin, suggest that CNEC are also derived from epithelium. In addition, their dermal location suggests that this epithelium is likely to be adnexal rather than epidermal.

Adnexal Diseases↗
PubMed1987

Recurrent and metastatic cutaneous neuroendocrine (Merkel cell) carcinoma mimicking angiosarcoma.

An elderly man presented with bright red-to-purple confluent nodules and plaques of the scalp that appeared clinically consistent with angiosarcoma. He had undergone surgical removal of a similar lesion from his left temple seven months before this presentation. Although routine histologic examination was not sufficient for diagnosis, Merkel cell carcinoma was diagnosed by immunohistochemical studies and electron microscopy. In addition, oat cell carcinoma of the lung was excluded with a computed tomographic scan of his chest. With chemotherapy, the recurrent and metastatic lesions of Merkel cell carcinoma completely resolved, rapidly recurred, and resolved a second time with chemotherapy. Eight months following the fourth course of chemotherapy, the patient again developed widespread cutaneous lesions. He committed suicide within one month of this last recurrence. An autopsy revealed no primary tumor other than of the skin.

Aged↗
PubMed1994

Neurologic complications of Merkel cell carcinoma.

We describe a 61-year-old man with a multiple neurologic complication of Merkel cell carcinoma, a rare skin cancer. An enhancing brain mass, and cytologically proven leptomeningeal disease produced a succession of symptoms including seizures, bilateral radiculopathies, myoclonus, a cauda equina syndrome and altered mental status. Aggressive treatment prolonged his survival marginally.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Staining of Merkel cells of pig snout epidermis using the uranaffin reaction. Morphometric analysis of neuroendocrine granules.

The uranaffin reaction (UR) specifically stains neurosecretory (NS) granules of the neuroendocrine system when performed at pH 3.9 and at a 4% concentration of uranyl acetate. Merkel-cell NS granules stained using the UR were found to have a different appearance than granules observed after routine processing. We therefore compared the average values obtained with both methods, examining the maximum diameter, area, form factor, and numerical density of such NS granules. The maximum diameter and area of NS granules were significantly greater (P less than 0.001) in samples stained using a conventional technique (CT) (93.30 nm, 6,411 nm2) that in those stained with the UR (63.95 nm, 2,148 nm2). The form factor of conventionally stained NS granules (0.9) was significantly greater (P less than 0.001) than that of granules stained with the UR (0.7). No significant difference in numerical density was found for the two techniques (CT: 8.11 +/- 2.51; UR: 6.14 +/- 2.38). It was found that the UR is a useful cytochemical marker for NS granules of Merkel cells, and that the ultrastructural morphology and intracellular arrangement of NS granules stained with the UR are different from those revealed using CT.

Animals↗
PubMed1998

Merkel cell carcinoma, Bowen's disease and chronic occupational arsenic poisoning.

We diagnosed a unique case of Merkel cell carcinoma (MCC) coexisting with Bowen's disease on the sole of the foot of a 72-year-old man who had worked for about 4 years in a factory handling inorganic arsenic. He had a past history of arsenical keratosis and multiple Bowen's disease. The tumour first appeared as a reddish macule and then showed marked growth over the next month. The tumour was excised and the specimen was examined histopathologically. The tumour consisted of two components: a group of atypical cells representing Bowen's disease in the epidermis and another group of atypical cells with a trabecular pattern characteristic of MCC in the dermis. Neither group of cells showed transitional findings, and the tumour elements were divided by a clear basement membrane. The tumour cells in the dermis were positive for neurone-specific enolase, and on electron microscopy had dense core granules in the cytoplasm. Inorganic arsenic can cause various cutaneous neoplasms, but to our knowledge, this is the first report of a case of MCC associated with Bowen's disease.

Aged↗
PubMed2005

Merkel cell carcinoma: a clinicopathological study of 11 cases.

OBJECTIVE: To report our 12-year experience with Merkel cell carcinomas (MCCs) from a clinical and pathological point of view. SUBJECTS AND SETTING: Eleven MCCs were diagnosed at our institution between 1991 and 2002. METHODS: A retrospective clinical, histopathological and immunohistochemical study was performed. Age, gender, location, size, stage, treatment and follow-up data were collected. Histopathological pattern and immunohistochemical study with CAM 5.2, cytokeratin 20 (CK20), CK7, Ber EP4, neurofilaments, synaptophysin, chromogranin, S100 protein, p53 protein, CD117, leucocyte common antigen (LCA) and Ki-67 were accomplished. RESULTS: Six females and five males with a mean age of 82 years were identified. Tumours were located on the face (n = 6), extremities (n = 3) and trunk (n = 1). At diagnosis, one patient was in stage Ia, six in stage Ib, three in stage II and one in stage III. All but one patient experienced wide surgical excision of the tumour. Additional treatment consisted of lymph node dissection in two patients, radiotherapy in four patients and systemic chemotherapy in one patient. Local recurrence developed in five patients. Three patients died because of MCC after 14 months of follow-up. Intermediate-size round cell proliferation was found in all cases. Additional small-size cell pattern and trabecular pattern were observed in seven and six cases, respectively. Eccrine and squamous cell differentiation were found in three cases. A dot-like paranuclear pattern was observed in all cases with CAM 5.2 and neurofilaments, and in 89% of cases with CK20. Seventy-five per cent of cases reacted with Ber EP4, chromogranin and synaptophysin, 70% with p53, 22% with S100 protein, 55% with CD117 and none with LCA. Ki-67 was found in 75% of tumoral cells on average. Fifty per cent of MCCs reacted with CK7 and showed eccrine differentiation areas. CONCLUSIONS: MCC is an aggressive neuroendocrine tumour of the elderly. Wide surgical excision is the recommended treatment. Lymph node dissection, adjuvant radiotherapy and chemotherapy decrease regional recurrences but have not been demonstrated to increase survival. Immunohistochemically, MCC is an epithelial tumour with neuroendocrine features.

Aged↗
PubMed1998

[Merkel cell carcinoma of the auricle].

A case of a 80-year-old woman suffering from Merkel cell carcinoma of the auricle with regional cervical lymph nodes metastases has been described. Surgical treatment (tumour and regional lymph nodes dissection) was applied at first. Metastasis to one lymph node was established in postoperative histological examination. Chemotherapy (farmorubicin, cyclophosphamide, vincristine) in 3 cycles was applied within 2 months. In spite of the above, 4 months after tumour excision, metastatic lymph node manifested in the neck. Combined treatment, radical neck dissection and radiotherapy was applied then.

Aged↗
PubMed1998

Merkel cell carcinoma of the eyelid: histological and immunohistochemical features with special respect to differential diagnosis.

BACKGROUND: Merkel cell carcinomas (MCC) not infrequently involve the periorbital region and the eyelids. Clinically, they are relatively characteristic but often unsuspected. Histologically, MCC are often misdiagnosed as lymphoma, melanoma, or metastatic small cell carcinoma of the lung (SCCL). METHODS: We present clinical, histological, and immunohistochemical data on six eyelid cases (all females; age 63-102 years; one with concomitant CLL) from our files of 77 MCC with special respect to differential diagnosis. For comparison, 22 SCCL were analyzed. Immunohistochemistry was done with antibodies against pan-cytokeratin (pan-CK), cytokeratin-20 (CK-20), neurofilament protein (NF), neuron-specific enolase (NSE), chromogranin (CHR), and S100 protein (S100). RESULTS: Morphologically, five of six MCC were prototypic, one was of the small cell variant. Immunohistochemically, dot-like positivities for pan-CK and CK-20 were seen in all six MCC, and for NF in five tumors. None of the 22 SCCL stained positively for CK-20 or NF but 21/22 cases were positive for pan-CK. Only 1/21 SCCL showed dot-like patterns for pan-CK; 20/21 reacted diffusely. All MCC and 13/22 SCCL displayed CHR-positive cells. All MCC and all SCCL were positive for NSE and negative for S100. CONCLUSIONS: Dot-like positivities for CK-20 or NF are important to prove MCC and to exclude SCCL in clinically and morphologically doubtful cases. Dot-like positivities for pan-CK favor MCC, but do not always exclude SCCL. NSE and CHR are of no value for the differential diagnosis of MCC and SCCL. Melanoma and lymphoma are ruled out by negativity for S100 and pan-CK, respectively.

Aged↗
PubMedDate not supplied

Merkel cell carcinoma of the cheek with metastases to the parotid gland: a report of two cases.

Merkel cell carcinoma (MCC) is a rare tumor of neuroendocrine origin. It is a highly invasive and aggressive neoplasia, that frequently presents regional and distant metatases. Therefore, there is high mortality associated with it. This report presents two male patients, one sixty three years and the other eighty eight years of age, with MCC of the cheek and invasive metastatic lesions to the head and neck areas. One of the patients died of associated distant metastatic disease and the other patient died of comorbid conditions present at time of tumor excision.

Aged↗
PubMed1988

Cytogenetic studies in primary and metastatic neuroendocrine Merkel cell carcinoma.

Direct preparations of five primary and metastatic neuroendocrine Merkel cell carcinomas of the skin were analyzed using a G-banding technique. A recurrent structural abnormality was a rearranged chromosome #1 with involvement of p and q arms. In two cases this rearrangement appeared as a unique structural cytogenetic change. Evidence for clonal origin and karyotypic stability of this tumor was suggested by the occurrence of the same karyotypic changes in two metachronous metastases and in primary and metastatic tumor specimens of two different patients. The bands involved in rearrangements could be of significance in the molecular process of the neoplastic transformation of Merkel tumor because genes relevant to the differentiation of neural crest-derived tissue have been mapped in those regions.

Adenocarcinoma↗
PubMed1989

Cutaneous neuroendocrine (Merkel cell) carcinoma: an immunophenotypic, clinicopathologic, and flow cytometric study.

Twenty-one cases of cutaneous neuroendocrine (Merkel cell) carcinoma (CNEC) were examined by the ABC-immunoperoxidase method with a panel of antibodies to 5 intermediate filaments, 6 neuroendocrine-associated antigens, 6 peptide hormones, as well as melanoma-associated cytoplasmic antigen (HMB-45) and leukocyte common antigen. All tumors showed strong cytokeratin staining in characteristic dense, inclusion-like, cytoplasmic globules and in a reticular peripheral cytoplasmic pattern. Cytoplasmic coexpression of inclusions of neurofilament antigen was observed in 9/21 cases. Staining for one or more neuroendocrine markers in formalin-fixed tissue (bombesin, 7/20; chromogranin, 11/21; synaptophysin, 6/21) was weak and focal but present in 17/21 cases. In 3 cases, sections of unfixed, snap-frozen tumor were compared with formalin-fixed tissue, and these showed strong, diffuse staining for multiple neuroendocrine antigens. Immunostaining for peptide hormones was not observed, with the exception of weak, focal staining for insulin (1 case), calcitonin (1 case) and somatostatin (2 cases). In 13 cases DNA indices and S-phase fractions (SPF) were determined by flow cytometry on nuclear suspensions from paraffin blocks. DNA histograms in 12 of 13 cases had normal range DNA content (diploid) and elevated S-phase fractions (mean 15%, range 8 to 22%). Mean SPF was not significantly different in the group of patients who developed recurrent and/or metastatic disease (15.6%, N = 10) compared with patients without recurrence (15.8%, N = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2001

Indium-111 octreotide scintigraphy of Merkel cell carcinomas and their metastases.

BACKGROUND: Somatostatin receptor scintigraphy (SRS) may be of interest for staging Merkel Cell Carcinoma (MCC). This study was undertaken to evaluate the sensitivity and specificity of SRS and to determine its role compared to conventional investigations. PATIENTS AND METHODS: From 1993 to December 2000, 20 patients (10 females and 10 males, aged from 38 to 88, mean 66 years) were included prospectively. At the time of SRS: 12 patients had been diagnosed as having stage I disease, 6 stage II and 4 stage III. Two patients had two SRS studies during the course of their disease. SRS was performed with Indium-111 pentetreotide (Octreoscan), a radiolabelled somatostatin analogue. Patients were treated according to the clinical stage. A regular follow-up was scheduled every three months. RESULTS: SRS depicted stage I and II MCC tumour sites with an overall sensitivity of 78% (95% confidence interval (CI): 40%-97%) and a specificity of 96% (81%-100%). The histopathological diagnosis was used as the gold standard. Sites visualised by SRS were compared to those detected with conventional modalities and to follow-up data for all stages: SRS visualised four out of five primary tumour sites, six out of eight lymph node sites, no skin metastases (14 sites in 2 patients), two out of three thoracic metastases and zero out of two hepatic metastases. SRS did not influence treatment decision-making in any of the cases. CONCLUSIONS: Although SRS seems highly specific in MCC and could be of help in difficult cases, it cannot be recommended for routine evaluation.

Adult↗
PubMedDate not supplied

[Merkel cell tumor].

The authors review 274 cases of Merkel's cells tumor reported in literature and present one case they personally observed. This kind of neoplasm develops itself inside the derma without involving the epidermidis and shows an aggressive biological behaviour. The authors describe its anatomopathologic characteristics and underline the importance of the immunohistochemistry particularly for a differential diagnosis with respect to lymphoma, amelanotic melanoma and the scarcely differentiated metastatic carcinoma. Undoubtedly the surgical treatment is to be preferred. It consists of the removal of the primitive lesion together with a preventive regional lymphadenectomy. Radio and chemotherapy still don't play a standard role, their results are anyway encouraging even if not well defined up to now. These therapies are used in several ways: together with surgery in case of local relapses or metastasis or as sole treatment. In consideration of the small number of available data, we can finally state that Merkel's cells tumor must be further studied in order to come to a certain definition of this neoplasm from a histogenetic and anatomopathologic point of view and, above all, to find out a treatment able to reduce the high mortality rate that still today characterizes the prognosis.

Carcinoma, Merkel Cell↗
PubMed1997

Merkel cell hyperplasia in chronic radiation-damaged skin: its possible relationship to fibroepithelioma of Pinkus.

Moderate hyperplasia of Merkel cells (MC) in chronic sun-damaged skin and hypertrophic actinic keratoses is well known. In the present study we investigated the number of MC in 24 samples of chronic radiation dermatitis and 19 cases of fibroepithelioma of Pinkus (FP), which is known to arise preferably in radiation-damaged skin. Using antibodies against the low molecular weight cytokeratins 8, 18, and 20 and chromogranin A to visualize MC, we found hyperplasia of MC in chronic radiation dermatitis. Additionally, in all FPs we could detect many MC, especially in areas with a pronounced fenestrated pattern. Recently, regulative functions of MC on the growth of follicular epithelium under various conditions were discussed. Thus, MC hyperplasia suggests a causal role also in the development of FP. In this context, hyperplasia of MC in chronic radiation dermatitis could explain the frequent occurrence of FP due to radiation exposure. As we recently found MC also in trichoblastomas but not in basal-cell carcinomas, the MC in FP may indicate its relationship to the benign trichoblastoma rather than to the basal-cell carcinoma. It is possible that regulative influences of the MC are important for the clinically rather benign course of FP.

Aged↗
PubMed1997

Merkel cell carcinoma: analysis of clinical, histologic, and immunohistologic features of 132 cases with relation to survival.

BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon malignancy of the skin and has a high rate of recurrence and metastasis. There have been few large studies of the biologic behavior of MCC. OBJECTIVE: Our purpose was to determine whether there were clinical or histologic features of MCC that predict its biologic behavior. METHODS: We reviewed 132 cases of MCC. Clinical and histologic features were correlated with follow-up information to determine whether any of these were associated with prognosis. RESULTS: Clinical information was available on 126 patients; 57 were alive, 1 was alive with tumor, 28 died of tumor, 27 died from other causes, and 14 were lost to follow-up. MCC on the buttock/thigh area or trunk had the worst prognosis, and those on the distal extremities had the best prognosis; however, the difference was not statistically significant. Sex and age were not significant factors. Small cell size, high mitotic rate, and large tumor size were associated with a low survival rate. When cell size was excluded, male sex and depth of invasion were associated with a worse survival, although these were not statistically significant. CONCLUSION: Cell size, mitotic rate, and tumor size are significant factors in relation to the biologic behavior of MCC.

Adolescent↗
PubMed1986

Cytogenetic study of a Merkel cell carcinoma.

Banded karyotypes from two metastatic sites of a Merkel cell carcinoma were analyzed. The results indicate very close similarity between the two specimens including an overall tendency to triploidy and the same five marker chromosomes. One of the markers represented by two copies in most of the karyotyped cells was 1q-.

Aneuploidy↗
PubMed1987

[Eyelid localization of a Merkel cell tumor (trabecular carcinoma)].

The authors present four cases of Merkel cells tumor of the eyelid. These cases conform to the standard clinical and histological criteria specified in the dermatological literature. Immuno-histochemical studies have been performed (specific neuron enolase, cytokeratin KL 1). Il the last case an ultrastructural study has made evident the characteristic neurosecretory granulations and intermediate filaments. Various hypothesis concerning the origin of this tumor are discussed in light of anatomical evidence.

Adenocarcinoma↗