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PubMed1993

The occurrence and fine structure of Merkel cells in the lingual epithelium of the turtle, Clemmys japonica.

Electron microscopic examination of the lingual mucosa of the turtle, Clemmys japonica, revealed the occurrence of Merkel cells that shared many morphological features with Merkel cells in other vertebrates. Merkel cells were located exclusively in the basal portion of the epithelium near the taste buds. We also found occasional Merkel cells devoid of nerve contact. Nerve terminals approaching these non-innervated Merkel cells were occasionally found in the connective tissue just beneath these cells.

Animals↗
PubMed1989

Characterization of Merkel cells and mechanosensory axons of the rat by styryl pyridinium dyes.

The epidermal Merkel cells and their sensory innervation serve tactile sensation in vertebrates. In this study the fluorescent cationic mitochondrial dye, 4-(4-diethylaminostyryl)-N-methylpyridinium iodide (4-Di-2-ASP), which has recently been used as a vital stain for motor and autonomic nerve terminals, was tested for its ability to stain Merkel cells and sensory fibers in the snout of the rat. Brightly-fluorescent structures resembling Merkel cells as well as nerve fibers and their terminations were evident in whole mounts of the vibrissal follicle. Unilateral denervation of the vibrissal follicles soon after birth resulted in a staining pattern remarkably similar to that obtained after labelling of the Merkel cells selectively with the fluorescent marker quinacrine, but all fiber staining was abolished. Likewise, in the separated epidermis of other skin regions, including the hairy and glabrous skin of the nose, the staining pattern revealed by 4-Di-2-ASP was indistinguishable from that obtained by quinacrine fluorescence. These results indicate that certain styryl pyridinium dyes may be used as vital stains for epidermal Merkel cells as well as cutaneous mechanosensory axons.

Animals↗
PubMed1995

Merkel cells in nevus sebaceus. An immunohistochemical study.

Nevus sebaceus, considered to be a hamartoma, is known to develop several secondary hyperplastic and neoplastic proliferations. By the use of immunohistochemical studies, we were able to describe a sometimes very striking increase of Merkel cells in nine of 19 nevi sebacei. Only nevi sebacei that formed follicular germ structures and trichoblastomas showed a Merkel cell hyperplasia. In the hyperplastic epidermis of some cases a slight hyperplasia of singular Merkel cells was observed. In foci with follicular germs and trichoblastomas, however, the Merkel cells were much more abundant and sometimes arranged in clusters. Merkel cell hyperplasia is likely to represent another facet of hamartomatous hyperplasia in nevi sebacei. Our observation that trichoblastomas in nevus sebaceus possess, as a rule, hyperplasia of Merkel cells, might be an additional aid to distinguish these tumors from basal cell carcinomas, which are usually devoid of Merkel cells. Furthermore, our findings are a hint that development of follicular germs and trichoblastomas in nevi sebacei may be promoted by Merkel cells.

Adolescent↗
PubMed1994

Deletion of chromosome arm 1p in a Merkel cell carcinoma (MCC).

A case of neuroendocrine skin carcinoma (Merkel cell carcinoma) with a deletion of the short arm of chromosome 1 (1p) as the sole chromosomal abnormality was examined. The tumor originated in the skin of the left knee of a 67-year-old man. Histopathologic study showed an undifferentiated small cell tumor which expressed neuron-specific enolase, chromogranin, and cytokeratin (CAM 5.2). Cytogenetic analysis of a lymph node metastasis from the groin showed a pseudodiploid cell population with a deletion of the short arm of chromosome 1 as the only abnormality: 46,XY,del(1)(p36.1). In situ hybridization with the D1Z2 probe specific for the terminal band of 1p confirmed the terminal deletion. This is the first case of Merkel cell carcinoma in which only one chromosomal abnormality has been observed. Loss of the terminal portion of 1p suggests that a tumor suppressor gene on 1p plays a role in the pathogenesis of Merkel cell carcinoma.

Carcinoma, Merkel Cell↗
PubMed2005

Characterization of the peri-implant epithelium in hamster palatine mucosa: behavior of Merkel cells and nerve endings.

The purpose of this study was to investigate the relationship between Merkel cells and nerve elements during tissue regeneration after receiving dental implants. Golden hamsters were divided into 3 groups and titanium alloy implants were fixed in their left-side maxilla through the third palatine rug. Animals were sacrificed at 1, 2, 3, 4, 5, 6, and 7 days after the implantation and tissues were characterized at the immunohistochemical and morphological levels. CK 20 and PGP 9.5 antibodies which react with Merkel cells and nerve fibers were used. Immunohistochemically, no CK 20-positive Merkel cells were seen in the peri-implant epithelium throughout the 7 days. However, starting at day 4, PGP 9.5-positive nerve fibers appeared in the connective tissue, and by day 7, nerve fibers had invaded the more superficial layer of the peri-implant epithelium compared to the mucosa removal control group. At the electron microscopic level, the intercellular spaces of the regenerating epithelium in the mucosa removal control group were small. In contrast, intercellular spaces of the peri-implant epithelium tended to be wide and regenerating nerve fibers invaded those intercellular spaces. In both the mucosa removal control group and the implantation group, the basal lamina and connective tissues regenerated completely. However, clear Merkel cells containing neurosecretory granules were not observed. Taken together, our results indicate that Merkel cells in the hamster palatine mucosa do not regenerate in the peri-implant epithelium. However, regenerative nerve fibers seem to play essential roles as part of the defense and sensory systems around the peri-implant epithelium to compensate for the weakened defense mechanism.

Animals↗
PubMed2004

Chondroid syringoma. Cytokeratin 20 immunolocalization of Merkel cells and reappraisal of apocrine folliculo-sebaceous differentiation.

CONTEXT: Chondroid syringoma (CS) is a benign cutaneous adnexal tumor with epithelial and stromal components. Epithelial components derived from folliculo-sebaceous-apocrine germ are evident in apocrine but not in eccrine CS. OBJECTIVES: To further characterize pilosebaceous differentiation and to identify the presence of Merkel cells in the areas of follicular differentiation. DESIGN: Histologic type, folliculo-sebaceous differentiation, character of stroma, and presence or absence of Merkel cells by cytokeratin (CK) 20 immunoreactivity were evaluated in 25 CSs (22 apocrine and 3 eccrine) from the surgical pathology files of Henry Ford Hospital (Detroit, Mich). RESULTS: Most CSs occurred in the head and neck region of patients aged 40 years or older. We found no significant difference in sex, age, or location between apocrine and eccrine types. The stroma varied from myxoid (100%) to chondroid (59%), with various amounts of fat (59%) and ossification identified in 2 cases (9%) of apocrine type, but was homogeneously myxoid in the eccrine type. Follicular and sebaceous differentiation was found in 64% and 32% of apocrine CSs, respectively. Only 2 (14%) apocrine CSs with follicular differentiation were positive for CK20 (a few scattered cells in one case and numerous grouped cells in the other in association with follicular epithelium). No correlation was found between type of stroma and the presence of Merkel cells. Scattered Merkel cells were identified in 83% of normal hair follicles and in 33.3% of normal epidermis. CONCLUSION: A high proportion of apocrine CSs show folliculo-sebaceous differentiation. The presence of Merkel cells in foci of follicular differentiation of CS supports the hypothesis that Merkel cells may be an integral constituent of follicles. To our knowledge, the presence of Merkel cells in CS, particularly in proliferative form, has not been described previously in the literature.

Adenoma, Pleomorphic↗
PubMed2006

Merkel cell carcinoma -- a rarity in the urogenital tract.

BACKGROUND: Merkel cell carcinoma -- a rare, aggressive cancer of the skin integument - is being increasingly diagnosed but represents an absolute rarity in the urogenital tract. CASE REPORT: We report on a 70-year-old man who was referred to us with suspected testicular cancer. The pathology report revealed a metastasized Merkel cell carcinoma. Fulminant disease progression under chemo-therapy (regimen as for small cell lung cancer) resulted in death 5 months later. CONCLUSION: The patient described is considered to be the first to develop testicular metastasis derived from Merkel cell carcinoma. Besides neuroendocrine and epithelial antigen tests, somatostatin receptor scintigraphy is a helpful diagnostic tool. New receptor-associated therapies may allow more effective and less toxic treatment modalities in the mostly elderly or immune deficient patients.

Aged↗
PubMed1994

Selective phototoxic destruction of rat Merkel cells abolishes responses of slowly adapting type I mechanoreceptor units.

1. The fluorescent dye quinacrine which accumulates in Merkel cells in touch domes was administered to rats and the effects of excitation light irradiation on the mechanical responses of slowly adapting (SA) type I units innervating the touch domes were investigated. 2. Histological examination showed that after 10 min of irradiation degeneration was specifically localized to Merkel cells loaded with quinacrine. Nerve terminals associated with Merkel cells remained intact, even after treatment. 3. In SA type I units, responses to standard stimulation (a 100 ms ramp followed by a 2.9 s plateau of 400 microns constant displacement) decreased significantly after irradiation of the domes with quinacrine-excitation light through a 'B' filter ('B' light). With 5 min irradiation, the response decreased to 52 +/- 7% (n = 10, mean +/- S.E.M.) of the pretreated value, to 17 +/- 4% with a 10 min treatment and practically disappeared within 20 min. 4. In SA type I units with non-loaded Merkel cells, the response increased to 119 +/- 8% (n = 13) with 5 min irradiation and was 99 +/- 9% with the 10 min treatment. At around 15 min after the onset of irradiation there was a gradual decrease and within 60 min the response disappeared. 5. When responses were divided into phasic (0-120 ms after the onset of stimulation) and tonic (120-3000 ms) components, 'tonic' responses were more affected than 'phasic' ones in quinacrine-loaded SA type I units. 6. Stimulus-response curves shifted to the right and downwards in SA type I units with quinacrine-loaded Merkel cells after irradiation, but no significant change was seen in SA type I units without quinacrine. 7. Our observations are consistent with the hypothesis that Merkel cells are responsible for mechanoelectric transduction in SA type I units.

Animals↗
PubMed2000

Three-dimensional comparative study of Merkel cell distribution in various body sites of guinea pigs and rats.

The hair cycling pattern differs between humans and mice: for the former it is mosaic, while the latter show a wave pattern. We focused on the presence or absence of synchronization of the hair cycle based on the distribution of Merkel cells. The three-dimensional distribution and number of Merkel cells in the skin at various sites were determined in guinea pigs and rats. Using ethylenediaminetetraacetic acid, various types of hair follicles were obtained from the facial, abdominal, nipple, back, tail, perianal and plantar skin. Epidermal sheets containing numerous hair follicles were immunostained using monoclonal murine antibody CK20 which is generally accepted to be a specific immunocytochemical marker for Merkel cells of various species. Merkel cells were absent in the trunk skin of guinea pigs and rats, in complete contrast to the situation in humans. In vibrissa and other hair follicles within specialized sensitive areas, Merkel cells were found in varying numbers. Some differences in their distribution and number were observed between guinea pigs and rats. The absence of Merkel cells in the hair follicles of the trunk skin of rats and guinea pigs implies that Merkel cells are not essential for the induction and promotion of hair growth but have some different functional significance in hair follicles.

Animals↗
PubMed1984

A quantitative study of the time course of the reduction in Merkel cell number within denervated rat touch domes.

By using the fluorescent dye quinacrine as a marker for the Merkel cells in rat touch domes we have shown that denervation results in a progressive reduction in the number of these cells to a level that remains relatively constant at about 40% of that present at the time of denervation. The time-course of quinacrine fluorescent cell changes after denervation could be described by assuming that (i) there are two populations of quinacrine fluorescent cells, one labile and the other stable, and (ii) the labile population is the one most sensitive to denervation and disappears exponentially with a half-time of ca 10 days. It appeared that this time-course of decay of the labile quinacrine fluorescent cells was the same whether the denervation was performed during the period of postnatal development studied (at 7 and 14 days), when normally Merkel cells are rapidly added to the dome, or later (at 35 and 60 days) when the adult population is virtually established. Correlative electron microscopic studies confirmed that quinacrine fluorescent cell counts reflect fairly accurately the Merkel cell population in denervated domes. These quantitative findings based on the use of quinacrine to visualize the entire Merkel cell population of touch domes show that the normal development and maintenance of these cells are trophically dependent on sensory nerves, although a subpopulation may persist even in long-term denervated domes. In addition, the similarity of the first order rate constant for the decay of quinacrine fluorescent cells after denervation and for the normal generation of quinacrine fluorescent cells suggests that the labile Merkel cell population is one that turns over continuously in the normally innervated touch dome.

Aging↗
PubMed1990

Intraepidermal formation of Merkel cells in xenografts of human fetal skin.

An experimental transplantation model using human fetal skin was applied to approach the question of the embryologic origin of human Merkel cells. Palmar and plantar skin from five fetuses, between 8 and 11 weeks of estimated gestational age (EGA), was xenografted to subcutaneous beds of nude mice. After 4 or 8 weeks of growth, biopsies were taken from these xenografts and examined for the presence of Merkel cells, using immunocytochemistry with antibodies specific for simple epithelial-type cytokeratins and neuron-specific enolase (NSE) as well as using electron microscopy. Skin from the same fetuses at the time of transplantation was screened in the same way. In all fetuses, no (or very scarce) epidermal Merkel cells were detected at the transplantation time, but in all cases abundant epidermal Merkel cells of apparent human origin were found after 4 or 8 weeks in xenograft culture. Dermal nerve fibers, as recognized by neurofilament antibodies, were scarce or essentially absent in the xenografts. These results indicate that Merkel cells regularly develop in epidermis dissected and xenografted in an early fetal stage, although the dissection implies the interruption of the dermal nerves. The results strongly support the notion of the origin of Merkel cells from epidermal precursor cells. The apparent absence of dermal Merkel cells and dermal nerve fibers in the xenografts suggests that the presence of dermal sensory nerve fibers may be required for the dropping off of epidermal Merkel cells into the upper dermis, which occurs in normal fetal development.

Animals↗
PubMed1993

Occurrence of melanosome-containing Merkel cells in mammalian oral mucosa.

The occurrence and fine structure of Merkel cells with melanosomes in the labial epithelium of the dog and cat were studied by electron microscopy. These melanosomes were polarized in the Merkel cell cytoplasm opposite to the major aggregation of dense-cored granules and the closely abutting nerve terminal. None of melanosomes was found in the Golgi complex region where a few immature dense-cored granules were observed. This may suggest that the melanosomes are not produced in the Merkel cell, but are taken from the melanocytes like in keratinocytes. The possible phagocytotic ability of Merkel cells is discussed.

Animals↗
PubMed1998

Pagetoid Merkel cell carcinoma: epidermal origin of the tumor.

We report a case of intraepidermal Merkel cell carcinoma which occurred on the face of a 76-year-old white male. This slow-growing tumor was mostly confined in the epidermis and pilosebaceous apparatus where tumor cells spread in a pagetoid fashion forming tumor cell nests. Histologically it resembled a superficial spreading melanoma. A heavy lymphocytic infiltration was seen beneath the epidermal lesion as is often seen in pagetoid melanomas. Histochemical and ultrastructural features such as the presence of cytokeratin 20, synaptophysin, neuron specific enolase, desmosomes, and dense cored granules confirmed the diagnosis of Merkel cell carcinoma. Occasional mitotic cells and many apoptotic cells were found in the tumor. Dylon positive, amyloid depositions were seen in the lower epidermis and papillary dermis; they were probably derived from apoptotic tumor cells. It was thought that apoptosis limited the speed of growth of this tumor. We believe that this is probably the most convincing case of intraepidermal Merkel cell carcinoma originating from epidermal Merkel cells or its precursors (stem cells).

Aged↗
PubMed1993

A high concentration of Merkel cells in the bulge prior to the attachment of the arrector pili muscle and the formation of the perifollicular nerve plexus in human fetal skin.

The distribution of Merkel cells in human fetal hair follicles was studied using whole mounts of separated epidermis with attached hair follicles. The technique had the advantage of enabling the elucidation of the spatial relationships of Merkel cells with other cells in the skin. In a 16-week-old fetus the hair anlagen had formed one or two epithelial swellings of variable size. In a 17-week-old fetus sebaceous glands and the bulge of the hair follicle were recognizable and immunoreactive. Merkel cells were present in the bulge and surrounding the acrotrichium (intraepidermal follicular canal). In a 20-week-old fetus the sebaceous gland and bulge were well formed and immunoreactive Merkel cells were concentrated in the bulge and infundibulum. In vertical sections of a 20-week-old fetus immunoreactive Merkel cells were also situated in the vicinity of the bulge. Arrector pili muscles were first observable in a 24-week-old fetus being weakly stained with anti-desmin antibody. In a 24-week-old fetus, nerves were also stained within the arrector pili muscles with S-100 protein antibody. In the presumptive arrector pili muscle immunoreactivity for S-100 protein developed before or at the same time as immunoreactivity for desmin. Merkel cells or their products in the bulge may serve as attractants for the growing arrector pili muscle which contain peripheral nerves. Following our report that dermal Merkel cells influence the formation of the dermal nerve plexus, perifollicular Merkel cells near the bulge may also play an inductive and growth-stimulative role for the perifollicular nerve plexus.

Female↗
PubMed1995

Neurochemical markers in human cutaneous Merkel cells. An immunohistochemical investigation.

Merkel cells (MCs) are specialized sensory cells widely distributed in the epithelia of vertebrates. A variable immunohistochemical pattern of neuronal and neurotransmitter markers has been demonstrated in MCs of several species including man. In the present study, we investigated the expression of neurochemical markers in a selected population of human cutaneous MCs by immunofluorescence. The structural neural proteins protein gene product 9.5 and neuron-specific enolase were found to be the most reliable markers for MC identification. Moreover, neurofilament immunoreactivity was shown in a small subset of epidermal MCs. Among the neurotransmitter markers, evidence for expression of calcitonin gene-related peptide, vasoactive intestinal polypeptide, peptide histidine isoleucine amide, neuropeptide Y, neurokinin A, galanin, substance P, somatostatin and phenylethanolamine N-methyltransferase was found. These immunoreactivities were highly variable as far as number of positive cells and staining intensity were concerned. The results indicate that a complex and heterogeneous immunophenotype can be expressed even within a homogeneous population of human MCs.

Adult↗
PubMed1998

Calcium inflow of hamster Merkel cells in response to hyposmotic stimulation indicate a stretch activated ion channel.

The aim of this study was to investigate the existence of the stretch activated ion channels in single Merkel cell using microfluorimetric techniques. Single Merkel cells were dissociated enzymatically from the touch domes in the cheek pouch mucosa of 4-8 week old golden hamsters. They were loaded with calcium (Ca2+) fluorescent indicator fura-2/AM. The increase in intracellular Ca2+ concentration ([Ca2+]i) of a single Merkel cell (quinacrine fluorescent cell) was induced by hyposmotic solution in normal Krebs solution, while it was not induced by Ca2+-free hyposmotic solution in Ca2+-free physiological solution. Gadolinium ion (10 microM) in normal Krebs solution partially blocked the increase in [Ca2+]i of Merkel cells induced by hyposmotic solution. Hence, this study revealed that stretch activated ion channels existed on the Merkel cell membrane.

Animals↗
PubMed2000

Intraepidermal Merkel cell carcinoma with no dermal involvement.

Cutaneous Merkel cell carcinoma (MCC) typically involves the dermis. Less than 10% of MCC have epidermal involvement. Only one MCC confined exclusively to the epidermis has been previously reported but was not recognized until the lesion recurred with typical MCC in the dermis. We present a case of a wholly intraepidermal pagetoid MCC without dermal involvement in a 74-year-old man with a 2.0-cm solitary verrucous papule on the left index finger. The initial biopsy and complete excision specimens showed marked epidermal hyperplasia, focal prominent squamous cell atypia, and MCC with florid pagetoid spread through the epidermis. There was no evidence of tumor within the dermis. The pagetoid MCC tumor cells showed diffuse cytoplasmic staining with antibodies to cytokeratin 20, and negative staining for chromogranin, neurofilament, S-100, vimentin, HMB45, leukocyte common antigen, and CD3. The cell of origin of MCC is still debated. The existence of an entirely intraepidermal variant of MCC would lend support to the view that MCC is a neoplastic expression of Merkel cells in at least some cases. Dermal-based MCC is a high-grade primary cutaneous neoplasm, but MCC confined exclusively to the epidermis may have a better prognosis.

Aged↗
PubMed1980

Ultrastructure of Merkel cells in the hard palate of the squirrel monkey (Saimiri sciureus).

The distribution and ultrastructure of Merkel cells in the hard palate was investigated in the squirrel monkey (Saimiri sciureus) after fixation by vascular perfusion. Merkel cells were clustered at the base of the epithelial rete pegs of the hard palate. They were characterized by concentrations of dense-cored granules and closely associated intraepithelial nerve endings. Numerous spiny processes extending from the Merkel cell were intercalated with adjacent keratinocytes, probably serving to detect and amplify movement of adjacent cells. These spiny processes contained a rigid core of parallel microfilaments which were interrelated with cytoplasmic filament bundles located beneath the cell membrane. Transitional cells containing dense-cored granules and well developed tonofibrils appear to be related to both Merkel cells and keratinocytes. The findings of this study suggest that Merkel cells are highly adapted for detection of movement in adjacent keratinocytes, as well as movement of the epithelium with respect to the underlying connective tissue.

Animals↗