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PubMed1997

Merkel cell carcinoma with partial spontaneous regression: an immunohistochemical, ultrastructural, and TUNEL labeling study.

We report a case of Merkel cell carcinoma that partially regressed after biopsy. A 76-year-old woman presented with an 1 month history of a rapidly enlarging nodule on her left cheek. After biopsy, the nodule reduced to almost half the size and was excised 1 month later. The excised specimen showed a dense cluster of lymphocytes and fibrosis around the tumor nests. In addition, lymphocytes showed apposition with tumor cells. An immunohistologically dense, even infiltration of CD4+ and CD8+ cells was found around the tumor nests, and more CD8+ cells than CD4+ cells were seen in the tumor nests. By electron microscopy (EM), apoptosis of tumor cells and lymphocytes was observed. Many apoptotic cells were also detected by in situ nick end-labeling (TUNEL) of DNA-breaks, especially in the marginal area of tumor nests surrounded by dense lymphocytic infiltrates. It seems likely that T-cell immunity, which induces apoptosis of tumor cells, may have been involved in tumor regression.

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PubMed1993

Merkel cell carcinoma of the vulva.

We present the clinical, histopathologic, and ultrastructural features of a primary vulvar Merkel cell carcinoma. This tumor appears to have a more aggressive behavior than those at other anatomic sites. A review of reported cases is presented. Preoperative evaluation and the role of surgery, radiotherapy, and chemotherapy in the management of these tumors are discussed.

Carcinoma, Merkel Cell↗
PubMed1993

[Merkel cell carcinoma of the skin. Two clinical cases].

In this study are described two clinical cases of Merkel cell tumor treated in the first half of 1991. The MCC is a rare primary skin tumor with an aggressive biologic nature. The elective therapy of primary sites is surgical management with lymphadenectomy although this kind of treatment is debated. Local recurrence high incidence requires a frequent and careful follow-up with possibility of second surgical treatment in the cases without metastasis and a radiochemotherapy in the patients affected by systemic recurrences.

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PubMed2003

Merkel cell carcinoma after chronic lymphocytic leukemia: case report and literature review.

Increasing evidence supports an association of Merkel cell carcinoma (MCC) with immunodeficiency and neoplasia, and the management and outcome of these patients requires study. This report describes a 72-year-old man with newly diagnosed chronic lymphocytic leukemia (CLL) who developed MCC of his right upper extremity and died of bone marrow metastases at 8 months. In the five previously reported cases of MCC after CLL, a shorter time interval between the diagnosis of CLL and the onset of MCC was associated with a better prognosis. In contrast, in this case the near simultaneous onset of CLL and MCC was followed by a rapid, lethal outcome.

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PubMed2005

A second field metachronous Merkel cell carcinoma of the lip and the palatine tonsil confirmed by microarray-based comparative genomic hybridisation.

Merkel cell carcinoma was diagnosed in a 79-year-old Caucasian woman. The tumour was localised to the upper lip and was in stage T2. After successful cryosurgery and a 7-year tumour-free period, a new tumour developed in her palatine tonsil. Histologically and immunohistochemically, this resembled the tumour in the lip. The regional lymph nodes were devoid of metastasis. The paraffin-embedded material of the two tumours and the unaffected lymphatic tissue were analysed with DNA microarrays for comparative genomic hybridisation to assess the genetic relationship of the tumours. In both tumours, regions on 2p and 10p were commonly over-represented, while 41 regions on chromosomes 1-4, 6, 8-9, 11 and 14-22 were commonly under-represented. Chromosomes 1, 3, 4, 16-18 and X were most frequently involved in the DNA losses. In gene copy numbers in the two tumours, 31 chromosome locations were found to be differently affected. The partly similar and partly different molecular patterns indicated a genetic relationship between the tumours and excluded the possibility that the tonsillar tumour was a metastasis. The findings suggest that a genetically altered field was the reason for the development of the tonsillar cancer; thus, it can be regarded pathogenetically as a second field tumour.

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PubMed1997

Polymorphism of Merkel cells in the rodent palatine mucosa: immunohistochemical and ultrastructural studies.

Our pervious electron microscopic studies indicated that Merkel cells (MCs) in the gerbil palatine mucosa were polymorphic, possibly reflecting different function. In order to verify and extend this evidence, the shape of and the innervation to MCs in the palatine mucosa of six different species of rodents including the Mongolian gerbil and the rat were examined by immunohistochemistry and transmission electron microscopy. Immunohistochemistry using anti-cytokeratin 20 (CK20) antibody revealed that in the gerbil palatine mucosa, approximately half of MCs were dendritic. Confocal laser scanning microscopy after double labeling with anti-cytokeratin and anti-PGP 9.5 or anti-Na+/K(+)-ATPase beta 1 subunit antibodies indicated that most of the dendritic MCs (DMCs) in these mucosae were free of innervation. Electron microscopy showed that all species of rodents examined contained abundant dendritic MCs as well as roundish (oval to round) MCs (RMCs) with typical innervation. Secretory granules of the RMCs were usually concentrated at the synaptic site, whereas those of the DMCs tended to accumulate in the tips of the cytoplasmic processes and in the cytoplasm facing the basal lamina. Some MCs showed features intermediate between those of the RMC and DMC. These results indicate that MCs in rodent palatine mucosae are consistently polymorphic, and that DMCs may represent a distinctive subset with specific, presumably including endocrine and paracrine, functions different from those of RMCs.

Aging↗
PubMed2003

Merkel cell carcinoma developing after antithymocyte globulin and cyclosporine therapy for aplastic anemia.

We report a patient who developed Merkel cell carcinoma (MCC) after treatment with antithymocyte globulin and cyclosporine for aplastic anemia. The clinical course was progressive and poor prognosis. Although MCC is relatively rare in second cancers arising after immunosuppressive therapy, patients should be closely monitored for the development of this complication as well as other second malignancies.

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PubMed2006

[Merkel cell carcinoma of the skin: two case reports located at the hand, with a review of litterature].

The Merkel cell carcinoma of the skin are rare neuroendocrine tumours, with a dermal location. Their severity and metastatic potential are higher than cutaneous melanomas'. Two cases are reported at the hand. A review of literature displays the pejorative prognosis of these tumours. Hand surgeons must be aware of them, in order to fasten the diagnosis and include the patient among a multidisciplinary medical team.

Adult↗
PubMed2002

Merkel cell carcinoma and multiple cutaneous squamous cell carcinomas in a patient with pityriasis rubra pilaris.

A 79-year-old female was diagnosed with Merkel cell carcinoma (MCC) and multiple cutaneous squamous cell carcinomas (SCC) occurring on a background of pityriasis rubra pilaris. At the time of initial diagnosis and treatment for upper limb MCC, axillary nodal metastases were clinically evident. In the ensuing months, she developed multiple rapidly progressing SCC and eventually a left arm soft tissue deposit of metastatic MCC. Treatment involved multiple courses of fractionated radiotherapy. The salient clinical features and supporting evidence for this case are presented.

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PubMed1991

Slowly adapting cutaneous mechanoreceptor afferent units associated with Merkel cells in frogs and effects of direct currents.

In the bullfrog, two types of slowly adapting (SA) cutaneous mechanoreceptor afferent units have been identified physiologically: irregularly discharging frog type I (Ft I) units in both warty and nonwarty skin, and regularly discharging frog type II (Ft II) units in the nonwarty skin. In the present study, mechanosensitive spots of Ft I units were located around the skin warts in the warty skin. The quinacrine technique (Crowe and Whitear, 1978) revealed that quinacrine-accumulating Merkel cells were present around the skin warts and near the orifice of skin glands that also surrounded the skin warts. Thus, a significant correlation was found between the location of Merkel cells and the receptive fields (RFs) of Ft I units in the warty skin. Direct current (DC) stimulation was applied for 1 sec to the skin inside and outside the mechanical RFs of the two types of SA units. RFs for DC stimulation were located on those for mechanical stimulation in both types of SA units. The current threshold required to produce a single spike was lower in cathodal than in anodal pulses in both types of SA units. Greater current intensity elicited an increased number of spikes, but the effective polarity of currents was anodal for Ft I units and cathodal for Ft II units. The optimal current intensity for producing prolonged discharges ranged from +60 to +100 microA in Ft I units and - from -50 to -80 microA in Ft II units. The sequence of impulses evoked was irregular in Ft I units and regular in Ft II units, as seen in mechanical responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Prognostic significance of p27Kip1, p45Skp2 and Ki67 expression profiles in Merkel cell carcinoma, extracutaneous small cell carcinoma, and cutaneous squamous cell carcinoma.

AIMS: To compare the immunohistochemical expression of prognostic markers p27(Kip1), p45(Skp2) and Ki67 in Merkel cell carcinoma (primary neuroendocrine carcinoma of the skin, MCC), small cell neuroendocrine carcinoma of lung and urinary bladder (SNC), and cutaneous squamous cell carcinoma (SCC). METHODS AND RESULTS: Immunohistochemistry was performed using antibodies directed against p27(Kip1), p45(Skp2) and Ki67 on 72 tumour cases: 24 MCC, 25 SCC, and 23 SNC (15 from the lung and eight from the urinary bladder). Percentages of positive cells were determined for each marker and statistically analysed. Expression profiles on MCC and SCC were significantly different for all three markers. MCC and SNC exhibited significant similarities in their p27(Kip1) and p45(Skp2) expression profiles. In contrast, MCC and SNC differed significantly in their Ki67 proliferation indices, which were much higher in SNC. Additionally, MCC cases showed an association between increased proliferation indices and the appearance of local recurrence(s) and/or metastases. CONCLUSION: The immunohistochemical profile of MCC differs from that of SCC, in spite of their common oncogenesis and the supposed metaplastic origin of MCC, and resembles that of SNC, except for Ki67 levels, which were higher in the latter (characterized by greater biological aggressiveness). High levels of Ki67 also appear to be a prognostic factor in MCC.

Analysis of Variance↗
PubMed1991

Merkel cell carcinoma. Improved locoregional control with postoperative radiation therapy.

Between April 1981 and May 1990, 11 patients with Merkel cell carcinoma were treated with radiation therapy in Tucson, Arizona. The length of follow-up time from the time of irradiation ranged from 6 to 64 months. Locoregional control was maintained in seven of eight patients treated with surgery and postoperative radiation therapy for primary or recurrent cancer. The other three patients had bulky metastatic disease at the time of referral. Palliation was achieved in all three patients with radiation therapy. Hyperthermia also appeared to be beneficial in the one patient in which it was used, and chemotherapy achieved responses in two of four patients. These results, combined with a review of the literature, suggest that the administration of radiation therapy postoperatively to both the surgical bed and the draining lymph nodes improves locoregional control and may result in long-term disease-free survival when administered after the initial surgical resection.

Carcinoma, Merkel Cell↗
PubMed2005

Merkel cell carcinoma: changing incidence trends.

BACKGROUND: The objective of this study was to define the incidence trends of Merkel cell carcinoma (MCC), a rare and aggressive cutaneous malignancy. MATERIALS AND METHODS: All cases of MCC of the skin between 1986 and 2001 were identified using the surveillance, epidemiology, and end results (SEER) program. Overall age-adjusted, gender-specific, age-specific, stage-specific, and regional incidence rates were calculated. All rates are per 100,000 and age-adjusted to the 2000 US standard population. Estimated annual percent change (EAPC) was calculated using a linear least squares model. RESULTS: A total of 1,124 cases of MCC were identified in the SEER registries. The rate of MCC increased from 0.15 cases per 100,000 in 1986 to 0.44 cases per 100,000 in 2001. The EAPC for the time period was 8.08%. This was statistically significant (95% CI: 6.29, 9.90, P-value < 0.05). Age-specific incidence (5-year age groups) were highest in the elderly, 4.28 per 100,000 in the 85+ age group. CONCLUSIONS: MCC incidence rates have increased threefold over the 1986-2001 period. Rates are highest in the elderly population. Further etiologic studies and identification of high-risk populations are warranted.

Adult↗
PubMed1997

Merkel cell carcinoma: report of ten cases with emphasis on clinical course, treatment, and in vitro drug sensitivity.

BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon primary neuroendocrine skin tumor most often seen in the elderly. The clinical course varies. Treatment is controversial and few data on drug sensitivity are available. OBJECTIVE: We evaluated the clinical course and treatment of 10 MCC patients and determined MCC chemosensitivity. METHODS: Clinical records as well as laboratory and histopathologic data from 10 patients with MCC treated in our department were examined. Chemosensitivity to various chemotherapeutic agents and interferons of MCC cells from four patients was determined in a soft agar clonogenic assay. RESULTS: MCC behaved as an aggressive tumor with early and frequent local relapses (4 of 10 patients at a 2.2-month average), regional (4 of 10 patients at 2.5 months), and distant metastases (5 of 10 patients 9.6 months after excision of the primary tumor). In all but one patient, regional metastases preceded distant ones. Metastatic spread was associated with an average survival of 21 months from the initial diagnosis. Long-term survival (53+ and 65+ months) was observed in two women. Wide excision of the primary tumor, alone or combined with adjuvant chemotherapy and radiotherapy, was the most effective treatment. In advanced disease, chemotherapy and radiotherapy were not able to induce long-term remission. In vitro assays for MCC drug sensitivity revealed cisplatin, doxorubicin, and vindesine to be the most active. CONCLUSION: MCC has a poor prognosis in advanced stages; therefore the primary tumor should be aggressively treated. The in vitro clonogenic assay may help to identify the chemosensitivity profile of MCC and to optimize chemotherapy protocols.

Adult↗
PubMed1989

Merkel cell carcinoma: management of primary, recurrent and metastatic disease. A clinicopathological study of 17 patients.

The clinicopathology of Merkel cell carcinoma (MC) has been evaluated in 17 patients, and its outcome and clinical management in 14 of these. The histopathologic diagnosis was confirmed by electronmicroscopy and/or immunohistopathology. The location of the primary lesions demonstrated a predilection for the skin of the face and the extremities. The primary treatment usually consisted of a wide excision only. Four out of five patients with MC of the face suffered from local and/or nodal relapses, in contrast to only one out of seven patients with primary lesion on the extremities. The three patients treated for local recurrences and/or regional node metastases were alive and disease-free 22-72 months after recurrences. Three patients developed distant metastases. Two of these died within 4 months after initial diagnosis. One patient completely responded to chemotherapy. The high frequency of local recurrences would justify an excision with generous margins, except when the tumour is close to a vital structure. Radiotherapy could in these cases obviate the necessity for extensive operations. If the primary lesion is located on an extremity, regional lymphadenectomy seems only to be necessary whenever nodal involvement is suspected. Node dissection is also recommended for suspected nodes in the face or on the neck, but the guidelines for elective node dissections in these sites are not obvious since the results of salvage therapy were excellent and the location of relapses unpredictable.

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PubMed2002

Lumbosacral metastatic extradural Merkel cell carcinoma causing nerve root compression--case report.

A 63-year-old man presented with a rare metastatic Merkel cell carcinoma (MCC) involving the lumbosacral spine and causing nerve root compression. Magnetic resonance (MR) imaging revealed an extradural soft tissue mass at the L5-S1 levels. The tumor was subtotally removed and chemotherapy was administered, but he died of multiple metastases from the primary epigastric tumor. Lumbosacral metastatic epidural tumor can manifest as lumbar disc disease symptoms, but MR imaging can non-invasively and rapidly reveal the presence of spinal epidural tumor and any extension to the spinal canal. Extradural MCC metastasis in the lumbosacral area should be considered in the differential diagnosis of radicular symptoms caused by disc herniation.

Abdominal Neoplasms↗
PubMed2005

Adjuvant locoregional radiotherapy as best practice in patients with Merkel cell carcinoma of the head and neck.

BACKGROUND: Australians have the highest rate of skin cancer in the world. Merkel cell carcinoma (MCC) is the most aggressive skin cancer reported, with a high propensity for relapse. The purpose of this study was to report the patterns of recurrence after initial treatment, the outcomes, and any predictors for survival. METHODS: We identified 37 patients who were diagnosed with MCC of the head and neck between 1980 and 2002. In this retrospective analysis, multivariate analysis was performed by use of Cox regression analysis. Disease-free survival (DFS) and overall survival (OS) were calculated with Kaplan-Meier survival curves. RESULTS: The median age at diagnosis was 75 years (range, 46-89 years), with 24 men and 13 women. The median duration of follow-up was 26 months (range, 7-104 months). Twenty-nine patients (78%) initially were seen with a primary lesion, and eight (22%) had a primary lesion and clinical nodal disease. A total of 24 (65%) of 37 patients had a relapse, with regional relapse the most common site of the first relapse (12 of 37). The rates of local relapse were similar for patients undergoing local surgery (three of 17; 18%) or surgery and adjuvant radiotherapy (two of 19; 11%). Nodal relapse developed in seven (50%) of 14 patients not receiving regional treatment compared with six (26%) of 23 patients receiving regional treatment of some type. Patients treated with surgery and adjuvant radiotherapy experienced a significantly longer median DFS than did those undergoing surgery alone (23 months vs 6 months; p < .01). The 3-year OS and DFS rates for the entire study population were 66% and 25%, respectively. CONCLUSION: MCC is an aggressive skin cancer. There is a sufficient body of evidence, including this study, to consider the addition of adjuvant locoregional radiotherapy as best practice in markedly improving freedom from relapse.

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PubMed1986

Ultrastructural, lectin histochemical and immunohistological observations on Merkel cell tumors.

The clinicopathological and ultrastructural findings of 10 cases of Merkel cell tumor (MCT) are presented. Three patients died rapidly due to tumor dissemination. The tumor cells in eight out of the 10 cases were positive for neuron-specific enolase, however, all were negative for the ten polypeptide hormones examined, as well as for the argentaffin and argyrophil reactions. One of the patients had suffered from chronic lymphocytic leukaemia. Particularly in this case, but also in the others, the differentiation of MCT from a malignant lymphoma necessitated immuno-histological, lectin histochemical and ultrastructural studies. The focal peanut agglutinin positivity of the tumor cells in 6 out of the 10 MCTs seems to be a characteristic feature of these cells.

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