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PubMed2006

Expression profiles associated with aggressive behavior in Merkel cell carcinoma.

Primary neuroendocrine carcinoma of the skin, or Merkel cell carcinoma, is the most aggressive cutaneous neoplasm. In spite of its similarities to small cell carcinomas from other locations, Merkel cell carcinoma shows many peculiarities probably related to its epidermal origin and the etiologic role of UV radiation. We have immunohistochemically investigated 43 markers on a tissue microarray in which 31 surgically resected Merkel cell carcinomas were represented. Of these, 15 patients remained free of disease after removal, whereas 16 developed metastases. Immunoreactivity was scored according to staining intensity and the percentage of positive cells. We found statistically significant correlations between metastatic tumor spread and overexpression of matrix metalloproteinase (MMP) 7, MMP10/2, tissue inhibitor of metalloproteinase 3, vascular endothelial growth factor (VEGF), P38, stromal NF-kappaB, and synaptophysin. Also detected were statistically significant correlations between the expression levels of MMP7 and VEGF, MMP7 and P21, MMP7 and P38, MMP10/2 and VEGF, P38 and synaptophysin, P38 and P53, and P21 and stromal NF-kappaB. These findings may be helpful in predicting the clinical course of Merkel cell carcinoma and are potentially useful for the development of targeted therapies.

Biomarkers, Tumor↗
PubMed1997

[Merkel cell tumor or neuroendocrine skin carcinoma].

Merkel cell carcinoma is a rare malignant tumor of the skin with predominance in older patients; 78.6% of patients are older than 59 years. Female and male patients are equally involved in the age group below 60 years. After 60 years, Merkel cell carcinomas are more often observed in female patients. The tumor is most often located in the head and neck region (50.8%) or the extremities (33.7%). The average size is 29 mm at presentation. Clinically, only a presumptive diagnosis of Merkel cell carcinoma can be established. The definite diagnosis is made by histological, especially immunohistological methods (detection of intermediate filaments and neuroendocrine markers). The therapy of choice is local excision. Secondary therapy may be a combination of operation and radiation or chemotherapy. Since this combination may reduce the risk of recurrences it should be applied for patients with poor prognostic features. Especially in young patients, additional lymphadenectomy should be discussed. Clinical control is necessary. Distant metastases should be treated by chemotherapy. Bad prognostic features are: lymph node metastasis, size larger than 2 cm, male sex.

Adolescent↗
PubMed1997

Functional evidence for calcium-induced calcium release in isolated rat vibrissal Merkel cell mechanoreceptors.

1. Single unit recordings were made from Merkel cell (sinus hair type I; St I) and sinus hair type II (St II) mechanoreceptors in isolated rat vibrissae. Responses were determined as the number of spikes evoked by controlled mechanical displacement of the hair shaft for 5 s every 30 s. 2. Superfusion of caffeine (10 mM) increased the responses of Merkel cell receptors by 50-180% of control (mean +/- S.E.M., 64 +/- 12.6%, n = 6, P < 0.001). Similar concentrations of caffeine inhibited St II receptor responses by 20-60% (mean +/- S.E.M., 35 +/- 8%, n = 5, P < 0.01). In both receptor types, caffeine induced a low-frequency increase in spontaneous firing. 3. When Merkel cell receptor responses were completely blocked by superfusion of high Mg2+-containing solution (to competitively block Ca2+ influx) caffeine had no effect when added after complete inhibition, but when added during partial inhibition of responses, the Mg2+-induced inhibition was transiently reversed or halted. This suggests that Ca2+ influx was a prerequisite for the action of caffeine. 4. Ryanodine (1 microM) increased the responses of Merkel cell receptors to mechanical stimulation by 7-60% (mean +/- S.E.M., 32 +/- 10.9 %, n = 5, P < 0.05) but had no effect on St II receptor responses. 5. The Ca2+-induced Ca2+ release (CICR) inhibitor procaine inhibited St I receptor responses in a concentration-dependent manner. Near-maximal inhibition was attained with 100 microM procaine. In four St I units, mean responses were depressed to 25% of control values. When both procaine (100 microM) and caffeine (10 mM) were introduced together, no net effect was seen. The responses of St II receptors were little affected by up to 100 microM procaine superfusion. 6. It is concluded that the mechano-electrical transduction process in St I receptors (but not St II) includes a CICR pathway. Taken with previous findings on the role of Merkel cells, it is likely that CICR is occurring in the Merkel cells.

Animals↗
PubMed1983

The morphology and distribution of Merkel cells in primate gingival mucosa.

The morphology and distribution of Merkel cells in primate gingival mucosa have been studied by correlated light and electron microscopic techniques. The gingival mucosa is composed of a stratified squamous epithelium with a dense underlying connective tissue stroma. The epithelium inter-digitates with the underlying connective tissue forming long interconnected rete ridges. Merkel cells and their associated axons are abundant in gingival mucosa where they are located, either individually or in clusters, at the base of epithelial rete ridges. These cells have an identical morphology to Merkel cells described by others in the hard palate, hairy skin, glabrous skin and eyelid. While individual Merkel cells are found throughout the gingival mucosa, Merkel cell clusters are most numerous in the mandibular lingual gingival mucosa. When correlating this finding with data from other investigators, it appears that Merkel cell clusters are located preferentially in the masticatory mucosa in intimate contact with the tongue and thus may function as an important source of somatosensory feedback providing valuable information regarding the position of the tongue in the oral cavity.

Animals↗
PubMed2005

B-cell specific activation protein encoded by the PAX-5 gene is commonly expressed in merkel cell carcinoma and small cell carcinomas.

PAX-5 is a B cell specific transcription factor crucial for B cell ontogeny and has been detected in most of human B-cell lymphomas. In mouse, PAX-5 is also highly expressed in the central nervous system under tight temporal and spatial controls during embryogenesis. In humans, however, detection of PAX-5 in cells other than B lymphocytes has rarely been reported. We have encountered cases of Merkel cell carcinoma expressing PAX-5 during our routine evaluation of lymphoma. Because Merkel cell carcinoma is a small blue round cell tumor constantly in the differential diagnosis of lymphoma, we expanded our study in an effort to determine if PAX-5 is significantly expressed in neuroendocrine tumors. Based on our immunohistochemistry results using a monoclonal anti-PAX5 antibody with paraffin-embedded tissue sections, we report herein that PAX-5 was detected in 29 of 31 (93.5%) of Merkel cell carcinoma and 22 of 30 (73.3%) of small cell carcinoma, but in none of 17 cases of carcinoid tumor. Furthermore, the staining intensity of PAX-5 in Merkel cell carcinoma was frequently comparable with that in most B-cell lymphomas. We conclude that expression of PAX-5 is not confined to the B cell lineage and is frequently associated with neuroendocrine carcinomas.

B-Lymphocytes↗
PubMed2000

Merkel cell carcinoma of the auricle.

Merkel cell carcinoma is a rare, although increasingly recognized, malignant tumor of the skin. The most common site of occurrence is the head and neck (50%). Only five cases of this tumor on the auricle have been reported previously. We present a further such case. The incidence, clinical features, diagnosis, prognosis, and treatment of the Merkel cell carcinoma are discussed.

Aged↗
PubMed2002

Oropharyngeal metastasis of a Merkel cell carcinoma of the skin.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin characterized by frequent local and regional recurrence, a high incidence of distant metastases and therefore a high mortality. Here, we report a case of an oropharyngeal metastasis of a Merkel cell carcinoma of the skin localized at the left base of the tongue causing dysphagia and the sensation of globus pharyngeus. The unusual metastatic site is presented, and diagnosis and treatment are discussed.

Aged↗
PubMedDate not supplied

[Cervicofacial neuroendocrine Merkel cell carcinoma: radiotherapy].

The Authors report a case of Merkel cell carcinoma of the cervicofacial district, particular due to its clinical and evolutive characteristics. The Merkel cell carcinoma was first identified by Toker in 1972 and is also known as a primary neuroendocrine the or trabecular carcinoma of the skin. The Merkel cell carcinoma is a rare aggressive skin cancer most frequently localized in the cervicofacial district. Although in earlier reports on the clinical history of these tumors primary emphasis was placed on their local aggressive behaviour, it has recently become evident that these neoplasms have a marked propensity for early dissemination. Distant metastases are often responsible for disease-related mortality. Merkel cell carcinoma have classically been managed with surgery alone or surgery followed by radiation therapy. Treatment of Merkel cell carcinoma with radiation therapy alone has usually been reserved for advanced unresectable tumors.

Adenocarcinoma↗
PubMed2004

Merkel cell carcinoma in a malignant pleural effusion: case report.

BACKGROUND: Merkel cell (neuroendocrine) carcinoma is a small round blue cell malignant neoplasm that primarily presents in the skin. The diagnosis of Merkel cell carcinoma in a pleural fluid is challenging because of the morphological similarity to many other malignant neoplasms. Immunohistochemical stains can be essential to establish the diagnosis of Merkel cell carcinoma. CASE PRESENTATION: A 77 year-old woman presented with a mass in her right buttock thought clinically to be a boil or sebaceous cyst. Upon histopathologic review including immunohistochemical analysis, a diagnosis of Merkel cell carcinoma was rendered. Wide-excision and sentinel lymph node biopsy revealed negative margins and no evidence of metastasis. Ten months later she complained of bone pain and a bone scan revealed multiple lesions. An abdominal CT scan revealed a T4 vertebral mass and local radiotherapy was administered. Two months later the patient presented with shortness of breath. A chest radiograph showed an effusion and thoracentesis was performed. The fluid was confirmed to contain metastatic Merkel cell carcinoma by cytology and immunohistochemical analysis. CONCLUSIONS: Merkel cell carcinoma is an aggressive neoplasm that can, despite careful surgical management, occasionally present as a malignant pleural effusion in a relatively short time period. Immunohistochemical analysis can aid in confirming this rare outcome.

Journal Article↗
PubMed2005

Merkel cell carcinoma: improved outcome with adjuvant radiotherapy.

BACKGROUND: Merkel cell carcinoma is an aggressive primary cutaneous neuroendocrine carcinoma. Patients remain at high risk of locoregional and distant relapse despite treatment. Most studies support the incorporation of locoregional adjuvant radiotherapy in reducing the risk of relapse. METHODS: Between 1980 and 2002, 86 patients diagnosed with Merkel cell carcinoma were treated with curative intent at Westmead Hospital, Sydney. Multivariate analysis was performed using Cox regression analysis. Disease-free survival and overall survival was calculated using Kaplan-Meier survival curves. RESULTS: Median age at diagnosis was 75 years (range 46-89 years) in 49 men and 37 women. Median duration of follow up was 31 months (range 6-153 months). Fifty-one (59%) patients presented with a primary lesion, 19 (22%) with a primary lesion and clinical nodal disease and 16 (19%) with lymph node metastases from an unknown primary. A total of 47 of 86 (55%) relapsed with regional nodal relapse, the commonest site of first relapse. Local relapse was similar for patients undergoing surgery (5/37; 14%) compared with surgery and adjuvant radiotherapy (3/25; 12%). Nodal relapse occurred in 14 of 36 (37%) treated with surgery compared with 7 of 38 (18%) patients treated with surgery and adjuvant radiotherapy. Patients treated with surgery and adjuvant radiotherapy experienced a better median disease free survival compared to those undergoing surgery alone (10.5 months vs 4 months; P < 0.01). The 5-year overall and disease-free survival rate for the entire study population was 47% and 25%, respectively. Twenty-six patients (30%) died as a result of Merkel cell carcinoma. CONCLUSION: Merkel cell carcinoma is an aggressive skin cancer. The addition of adjuvant radiotherapy markedly improves regional control rates and should be considered best practice.

Aged↗
PubMed1996

Chloroquine specifically impairs Merkel cell mechanoreceptor function in isolated rat sinus hairs.

The function of Merkel cells in mechanotransduction has remained controversial Single unit recordings were made from Merkel cell receptors (sinus hair type I, St I) and another slowly adapting mechanoreceptor (sinus hair type II, St II) in isolated rat sinus hairs by applying controlled mechanical displacements to the hair shaft. Chloroquine (50-300 microM) caused a concentration dependent inhibition of Merkel cell receptor responses to mechanical stimulation. In contrast, both stimulated and spontaneous spike activity of St II receptors was increased by the same concentrations of chloroquine. Ultrastructural examination of chloroquine treated sinus hairs revealed swollen Merkel cells with multiple vacuoles and randomly distributed granules while other neural and surrounding structures showed no striking morphological changes. These results suggest that the Merkel cell plays a mechanotransducer role in Merkel cell receptors.

Animals↗
PubMed1997

Merkel cell carcinoma: an aggressive malignancy.

Merkel cell carcinoma is a rare and aggressive malignant tumor of the skin. We retrospectively reviewed five patients treated from January 1987 to December 1995. The mean age was 75 years (range, 65-85). There were three primary lesions of the head and neck and two of the extremities. Three were stage II and two were stage III. All primary tumors underwent wide excision with clear margins. Four patients recurred, with a mean time to recurrence of 10 months (range, 2-17). All tumors were positive for immunohistochemical stains (cytokeratin and neuron-specific enolase). Only the two patients who did not have radiotherapy to the primary site had a local recurrence. There was regional recurrence in two of the three patients who had adjuvant radiotherapy to regional lymph nodes. One patient who had a wide excision of the primary lesion, prophylactic lymph node dissection (15 of 34 lymph nodes were positive), and adjuvant chemotherapy is alive and disease free at 23 months. Three patients have died with disease, and two are alive and disease free. Merkel cell carcinoma should be treated aggressively with wide excision of the primary lesion (3-cm margins), and prophylactic lymphadenectomy followed by irradiation to the primary site. If lymph node involvement is detected, then irradiation to the lymph node region must be performed. The role of chemotherapy in this disease is not well defined.

Aged↗
PubMed1994

Merkel cell distribution in human hair follicles of the fetal and adult scalp.

The distribution of Merkel cells in fetal and adult terminal hair follicles of human scalp was studied immunohistochemically using cytokeratin (CK) 20 as a specific Merkel cell marker. In hair follicles of adult scalp, abundant Merkel cells were found enriched in two belt-like clusters, one in the deep infundibulum and one in the isthmus region. No Merkel cells were found in the deep follicular portions including the bulb, or in the dermis. In early fetal hair follicles (bulbous peg stage), Merkel cells were only detected in the basal layer of the developing infundibulum but not in deeper follicular areas. In later stages, Merkel cells were also present in the isthmus and bulge. No Merkel cells were seen in the dermis around developing hair follicles. Nerve growth factor receptor was not only present in nerves but was found to be widely distributed within fetal skin. In adult skin, this receptor was localized to the basal cell layers of the outer root sheath of the bulb and the suprabulbar area, but was not detectable in the areas containing Merkel cells. The present study localizing Merkel cells within the permanent hair follicle structures close to their possible stem cells suggests that they have paracrine functions.

Adult↗
PubMed2006

Changes in the number of Merkel cells with the hair cycle in hair discs on rat back skin.

BACKGROUND: Hair discs are known to contain a large number of Merkel cells and are ideal for investigating Merkel cell biology. Hair follicles, which are important elements of hair discs, undergo unique cyclical morphological and biological changes. OBJECTIVES: To define the relationships between the number and the morphology of Merkel cells within the hair disc in association with the hair cycle on rat back skin. METHODS: Merkel cells in hair discs were observed three-dimensionally using immunohistochemistry. Epidermal sheets were incubated with monoclonal murine antibody to CK20. As a result, Merkel cells in hair discs were clearly demonstrated as whole shapes and were counted under a light microscope. RESULTS: Merkel cells in hair discs increased during the early to middle phase of anagen and decreased during the middle phase of anagen to catagen and telogen in perinatal and postnatal rat back skin. We observed the morphological variation of Merkel cells in hair discs of rat back skin, and consequently divided them into two subtypes at the light microscopic level: the oval type and the dendritic type. The number of oval-type Merkel cells was not markedly affected by the hair cycle. In contrast, the number of dendritic-type Merkel cells markedly changed with the hair cycle. CONCLUSIONS: This difference of the hair cycle dependency between oval and dendritic-type Merkel cells suggests some functional differences, such as a secretory function, related to the hair cycle.

Aging↗
PubMed1981

Fine structure of Merkel cells in lampreys.

The structure of Merkel cells occurring in the epidermis of adult and larval stages of Lampetra spp. is described; it is comparable to that reported from the gnathostome classes. The cells bear microvilli, grouped on the distal and proximal aspects, and are associated with sparsely branching and varicose nerve fibres. One branch of the neurite bears a spur-like process which indents the proximal side of the Merkel cell. Most of the specific Merkel granules are situated in the vicinity of this neurite projection; the cell membrane adjacent to the tip of the spur process bears structures resembling presynaptic densities. Occasionally, desmosome-like junctions are found between the neurite and the Merkel cell.

Animals↗
PubMedDate not supplied

Localization of Merkel cells at hairless and hairy human skin sites using keratin 18.

Merkel cells are neurosecretory cells of the skin with epithelial features such as desmosomes and expression of keratins 8, 18, 19, and 20. Merkel cells are scarcely distributed in adult human skin. Although they are present in hair follicles, their density is higher at hairless anatomic sites such as palms and soles. These cells are often innervated by sensory nerve fibers and are thought to be specialized mechanosensory skin receptor cells. However, their precise origin and function are not clearly established. The aim of this study was to localize Merkel cells in human hairless and hairy skin by immunohistochemistry with antibodies Ks18.174 and Ks19.1 directed against keratins 18 and 19, respectively. In glabrous skin of palm and sole, Merkel cells have been localized at the bottom of the rete ridges, in the epidermal basal layer. To study Merkel cell distribution at hairy anatomic sites, we have chosen breast skin, a tissue containing small hair follicles typical of those covering most of the body's surface. Merkel cells were present in the interfollicular epidermis. In hair follicles, they have been identified in the isthmus region.

Adult↗
PubMed1999

Merkel cell carcinoma: a distinct lesion of the eyelid.

Merkel cell carcinoma (trabecular cell carcinoma) is a rare, distinct, primitive, neuroendocrine malignancy of the skin, usually affecting elderly patients. It develops from Merkel cells and nearly one out of every 10 Merkel cell carcinomas occurs in the eyelids and periocular region. The tumor manifests itself clinically as a bulging lesion near the lid margin, painless, reddish colored with teleangiectatic blood vessels on the surface. Histologically, the tumor can mimic malignant lymphoma, undifferentiated melanoma, sebaceous carcinoma or cutaneous metastases of pulmonary microcytoma. Immunohistochemical studies with antibodies to neuron-specific enolase, cytokeratins and neurosecretory granules are necessary to differentiate these tumors. One third of all Merkel cell carcinomas result in death. In the present paper, we present data on the clinical features, treatment and long-term follow-up of three patients.

Journal Article↗
PubMed1999

Ampullary somatostatinoma in a patient with Merkel cell carcinoma.

A 59-yr-old white man with Merkel cell carcinoma of his right leg status post extensive skin resection and chemotherapy had dilated hepatic and common bile ducts on a routine follow-up abdominal CT scan. A 1.9-cm ampullary mass was appreciated on endoscopy. Histology showed psammoma bodies and positive immunoperoxidase staining consistent with a somatostatinoma. Merkel cell tumors and somatostatinomas are extremely rare neuroendocrine tumors derived from neural crest cells. Associations have been found between somatostatinomas and other islet cell tumors with multiple endocrine neoplasia syndromes, but no reported association has been published between islet cell tumors and Merkel cell tumors. This patient represents the first documented case of Merkel cell carcinoma and somatostatinoma in a single patient. Such an occurrence may represent a previously undescribed neuroendocrine tumor syndrome, and this possibility should be considered when either tumor is diagnosed.

Carcinoma, Merkel Cell↗