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PubMed1989

Merkel cell hyperplasia in hypertrophic varieties of actinic keratoses.

Hyperplasia and dysplasia of the epidermal neuroendocrine cells (i.e., Merkel cells, MC) have been suggested in lesional skin of actinic keratosis and chronic radiation dermatitis. Because several histological types of actinic keratosis exist, we investigated the occurrence of such MC hyperplasia according to each of the histological patterns. Using an immunoperoxidase technique and the cytokeratin monoclonal antibody CAM 5.2, we counted 0.02 CAM 5.2 + cells (i.e., MC)/mm epidermis in normal-appearing perilesional skin; 0.05 MC/mm epidermis in nonhypertrophic actinic keratoses and 4.09 MC/mm epidermis in hypertrophic actinic keratoses. This number was as high as 14.40 MC/mm epidermis when hypertrophic actinic keratoses showed club-like epithelial proliferations. In contrast to normal epidermis, where MC were found isolated within the basal cell layer, MC clustered in these club-like epithelial proliferations as they did in the normal parakeratotic zone of the rabbit lip epithelium. The significance of this selective MC hyperplasia is discussed.

Animals↗
PubMed1986

Merkel cell (small cell) carcinoma of the skin: immunohistochemical and ultrastructural demonstration of distinctive perinuclear cytokeratin aggregates and a possible association with B cell neoplasms.

Three cases of Merkel cell (small cell) carcinoma of the skin are presented with immunohistochemistry for epithelial and neuroendocrine antigens. All three cases showed distinctive punctate perinuclear cytoplasmic positivity for cytokeratin which corresponded to aggregates of intermediate filaments, seen ultrastructurally in two cases. Epithelial membrane antigen was also identified in two cases. Only one case showed cytoplasmic positivity for neuron specific enolase, and immunostaining for a battery of polypeptide hormones was negative. The demonstration of cytokeratin perinuclear inclusions provides a distinctive immunohistochemical feature to aid in their diagnosis. Two of the three patients had chronic lymphocytic leukaemia years before the diagnosis of Merkel cell carcinoma. The possible association of lymphoproliferative disorders, particularly B cell tumours, and Merkel cell carcinoma is discussed.

Aged↗
PubMedDate not supplied

Merkel cell carcinoma of the auricle.

Merkel cell carcinoma is a rare malignant tumor of the skin. The face and extremities are the most common locations. We present a case of Merkel cell carcinoma of the auricle in a 93-year-old man subsequently treated with surgery and radiotherapy. The clinical features, prognosis, and treatment of the Merkel cell carcinoma are discussed.

Aged, 80 and over↗
PubMed1998

Mixed Merkel cell carcinoma and squamous cell carcinoma of the skin.

Four mixed Merkel cell and squamous cell carcinomas of the skin are described. The patients ranged in age from 74 to 90 years and demonstrated or had a history of previous ultraviolet or infrared damage to the skin, manifested by basal cell carcinoma, squamous cell carcinoma, actinic keratoses, solar elastosis, and erythema ab igne. Light microscopic examination of all 4 cases revealed invasive neoplasms consisting of 2 distinct but admixed cell types. The predominant cell type was consistent with Merkel cell carcinoma and was characterized by scant cytoplasm, a small dark polygonal nucleus with granular chromatin, a high mitotic rate, and cytokeratin 20 positivity. In each case, the Merkel cell component merged with a cytokeratin 20 negative squamous component characterized by abundant eosinophilic cytoplasm, intercellular bridges, and keratinization with focal squamous pearl formation. Immunohistochemical staining patterns were consistent with the usual pattern for that cell type; transitional cells were not demonstrated. The intimate admixture of the 2 antigenically different neoplastic cell types, and common etiologic role of ultraviolet and possibly infrared damage, lend support to the theory that some Merkel cell carcinomas and squamous cell carcinomas may arise from a pluripotent epidermal stem cell.

Aged↗
PubMed2001

The nerve-dependency of Merkel cell proliferation in cultured human fetal glabrous skin.

Merkel cells are thought to function as slowly adapting mechanoreceptors and are known as targets for sensory nerves. However, the nerve-dependency of Merkel cells remains controversial. In this respect, some investigators have found interregional differences between hairy and glabrous skin and others have shown intraregional differences within denervated rat touch domes. Differences between species have also been reported. This study was performed to determine whether Merkel cells proliferate in vitro in the absence of the systemic factors, blood vessels and the intact nerves in human skin. Suspension organ culture was performed using fetal digits to investigate their in vitro proliferation. Merkel cells and cutaneous nerves were identified using antibodies to cytokeratin 20 and protein gene product 9.5 (PGP 9.5), respectively. Fetal digits of 56-82 day gestational age were cultured in serum free medium in a high O2 (45%) environment. Tissues were harvested before starting culture (D0) and 1, 4, 7, 14, 28 d after culture. Merkel cells were observed in the volar pads and dorsal nail matrices at D0. After 28 d of suspension organ culture, digits looked healthy structurally and the number of Merkel cells had increased. However, PGP 9.5-immunoreactive nerves were markedly diminished after 1 day of culture and almost disappeared after 4 days. Merkel cell proliferation in vitro suggested that Merkel cell development is probably nerve-independent in human fetal glabrous skin.

Cell Division↗
PubMed1996

Merkel cells in mouse skin: intermediate filament pattern, localization, and hair cycle-dependent density.

The distribution and antigen expression of Merkel cells in mouse skin is as yet ill defined. Since the mouse offers an excellent model for studying the origin and functions of Merkel cells, the Merkel cell distribution as well as the expression of intermediate filament proteins and neuronal markers was characterized in C57 BL/6 mouse skin by immunohistochemistry and electron microscopy. Merkel cells in whisker pads, back, and foot pad skin as identified by staining for neuron-specific enolase-an established neuroendocrine marker--expressed cytokeratins (CK) 8,18, and 20 (i.e., simple-epithelial CKs), but not CKs 4 and 13. Sequential double staining for neuron-specific enolase and CK 20 showed consistent co-expression in Merkel cells, establishing CK 20 as a specific immunocytochemical marker for mouse Merkel cells. The Merkel cells also were immunoreactive for synaptophysin but not for neurofilament proteins, peripherin, S-100 protein, and neural cell adhesion molecule. Using CK 8, 18, and 20 as markers, we detected many Merkel cells in the outer roots sheath of vibrissae hair follicles and in foot pad skin. However, only few Merkel cells were found in back skin. These were restricted to small clusters, localized basally within the Haarscheiben epidermis of tylotrich hair follicles, and formed close contacts to prominent nerve fiber terminals as shown by electron microscopy. In striking contrast to human skin, Merkel cells were never found in the epithelium of pelage hair follicles. Even more strikingly, the density of Haarscheiben-associated Merkel cells changed substantially during the highly synchronized, depilation-induced C 57 BL/6 hair cycle, with a minimum in back skin with all hair follicles in telogen or catagen, and a maximum in back skin with all hair follicles in anagen IV-VI. These observations on the Merkel cell hair cycle-dependent distribution in murine skin point to important differences in Merkel cell functions between humans and mice, and raise intriguing questions as to the role of Merkel cells in hair biology.

Animals↗
PubMed1987

The development of the Merkel cells in the tentacles of Xenopus laevis larvae.

The Merkel cells in the larval tentacles of Xenopus laevis were examined by TEM. Different forms of Merkel cells were found, depending on the age of the larvae or the location in the tentacles. These forms have the appearance of intermediate states between Merkel cells and superficial epidermal cells; thus an epidermal origin for the Merkel cells seems more likely than an immigration from the neural crest. The forms differ in (1) their location in the epidermis, (2) their shape, (3) the number and extension of their desmosomes, (4) the content and distribution of dense-core granules, and (5) the outgrowth of their finger-like processes. Also the relation to a nerve ending is different. By marking Merkel cells with quinacrine, fluorescence spots were observed between the superficial and basal epidermal cells or, in the very tip, within the superficial epidermal cells. These latter spots represent immature Merkel cells, as confirmed by TEM. This indicates a development of Merkel cells from superficial epidermal cells and migration towards the basal layer. Dermal Merkel cells were never observed.

Animals↗
PubMed1984

Lectin-binding properties of the Merkel cell and other root sheath cells in perinatal rat vibrissae.

Surface carbohydrates on the Merkel cell of the outer root sheath (ORS) were investigated in 1- to 4-day-old rat vibrissae by use of rhodamine isothiocyanate (RITC)-conjugated lectins. The red fluorescence of RITC provided a convenient assay for lectin binding to the Merkel cell, which is itself identified by its green fluorescence following selective uptake of the dye quinacrine. In monolayers or suspensions of freshly dissociated ORS cells, the Merkel cell showed high affinity for the alpha-fucose-specific lectin, Ulex europeus agglutinin I (UEA-I), thus revealing a novel feature for a basally located cell. Other high-affinity lectins included concanavalin A (Con A), wheat germ agglutinin (WGA), soybean agglutinin (SBA), and Ricinus communis agglutinin I (RCA-I). In contrast, Dolichos biflorus (DBA), Bandeiraea simplicifolia I and II (BS-I and BS-II), and peanut agglutinin (PNA) virtually excluded the Merkel cell, though PNA-binding sites were unmasked after neuraminidase treatment. Other dispersed ORS cells had varying lectin affinities, and generally binding was inhibited by a competing haptenic sugar. The pattern of lectin binding seen in cryostat and paraffin sections of the vibrissa suggested that the Merkel cells share surface properties with their neighboring basal and/or spinous cells; however, unshared properties are likely to exist since ingrowing mechanosensory nerves recognize the Merkel cells, and not other epidermal cells, as their targets.

Animals↗
PubMed1993

Merkel cells in human fetal eccrine glands.

The presence of human Merkel cells in the eccrine ridges and eccrine germs was studied, using antibodies to simple epithelial keratins, in separated epidermal sheets with attached eccrine ducts. The localization of Merkel cells could be analysed three-dimensionally in the wet, whole-mount of the stained sheets. In the plantar skin of a 12-week-old human fetus, immunoreactive (ir-) Merkel cells were randomly located in the flattened epidermis. In the plantar skin of a 15-week-old human fetus, there was early development of eccrine germs, and Merkel cells were concentrated in eccrine gland ridges. In the plantar skin of a 20-week-old human fetus, eccrine germs were well formed and ir-Merkel cells were located within the developing eccrine ridges and ducts. In the plantar skin of adults, the eccrine concentration of Merkel cells was markedly reduced. Concentration of Merkel cells on the eccrine structures was also observed in the scalp skin of human fetuses. This tendency continued into adult life, although there was a marked reduction in the total number of Merkel cells. These findings suggest that epidermal Merkel cells move down into the eccrine ducts as eccrine germs extend into the mesenchyme. Alternatively, they may develop de novo from the keratinocytes of the eccrine duct. In view of the expression of nerve growth factor receptor in fetal Merkel cells, it is postulated that these eccrine gland Merkel cells play a role in the formation of the periglandular nerve plexus.

Adult↗
PubMed1994

Immunohistochemical demonstration of the expression of neurofilament proteins in Merkel cells.

The presence of immunoreactive neurofilament proteins has previously been reported in Merkel cell carcinomas but not in normal human epidermal and dermal Merkel cells. We have studied the immunoreactivity of epidermal Merkel cells for neurofilament triplet proteins (68 KD, 70 KD, 160 KD, 200 KD), using epidermal sheets prepared from the plantar skin of human adults, which enabled us to survey large numbers of Merkel cells. Neurofilament protein 200 KD-positive cells were readily identified, while neurofilament protein 68 KD-, 70 KD- and 160 KD-positive cells were largely absent. 200 KD-positive cells in the epidermis were confirmed to represent Merkel cells by a sequential immunoenzyme labeling for the simple epithelial type cytokeratin (No. 8). 200 KD-positive cells were 5.9% of the total number of epidermal Merkel cells. Despite a heterogeneous expression of neurofilament protein subspecies between the normal and transformed Merkel cells, the presence of neurofilament proteins in epidermal Merkel cells may link them to Merkel cell carcinomas.

Adult↗
PubMed1987

Immunohistochemical demonstration of simple epithelia-type keratin intermediate filament in a case of Merkel cell carcinoma.

A case of Merkel cell carcinoma that developed on the right cheek of a 77-year-old woman is reported. The diagnosis was ultrastructurally made by demonstrating dense-core granules in the cytoplasm of the tumor cells. Immunohistochemically, the tumor cells were shown to possess simple epithelia-type keratin intermediate filaments, but no neurofilaments. This finding was in accordance with that obtained on normal Merkel cells. No bioactive peptides examined could be detected in the tumor cells. Typing of intermediate filaments in tumor cells may be one of the important markers, along with the ultrastructural findings, in diagnosing Merkel cell carcinoma.

Adenocarcinoma↗
PubMed2006

Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an unusual primary neuroendocrine carcinoma of the skin. MCC is a fatal disease, and patients have a poor chance of survival. Moreover, MCC lacks distinguishing clinical features, and thus by the time the diagnosis is made, the tumour usually have metastasized. MCC mainly affects sun-exposed areas of elderly persons. Half of the tumours are located in the head and neck region. METHODS: MCC was first described in 1972. Since then, most of the cases reported, have been in small series of patients. Most of the reports concern single cases or epidemiological studies. The present study reviews the world literature on MCC. The purpose of this article is to shed light on this unknown neuroendocrine carcinoma and provide the latest information on prognostic markers and treatment options. RESULTS: The epidemiological studies have revealed that large tumour size, male sex, truncal site, nodal/distant disease at presentation, and duration of disease before presentation, are poor prognostic factors. The recommended initial treatment is extensive local excision. Adjuvant radiation therapy has recently been shown to improve survival. Thus far, no chemotherapy protocol have achieved the same objective. CONCLUSION: Although rare, the fatality of this malignancy makes is important to understand the etiology and pathophysiology. During the last few years, the research on MCC has produced prognostic markers, which can be translated into clinical patient care.

Journal Article↗
PubMed1985

[Merkel-cell tumor].

A Merkel cell tumor of the preauricular region in a seventy-seven years old woman is described. Histological, electronmicroscopic and tissular hormonal studies, were made. From the pathological point of view, a nodular and trabecular pattern of oval or elongated cells with poor basophilic cytoplasma is characteristic. Large nuclei with irregular, oval prominent nucleoli are also present. Electron microscopy shows oval and polygonal cells of irregular nuclei with one or multiple prominent nucleoli. In the cytoplasm of these cells, microfilaments and dense core granules with clear halo are found. The tissular hormonal determinations were normal. Two years after the surgical treatment, the patient remains asymptomatic.

Adenocarcinoma↗
PubMed1999

Merkel cell tumour: case reports and review.

Merkel cell carcinoma, a small-cell undifferentiated/neuroendocrine carcinoma, is a highly invasive primary malignant neoplasm of the skin that may arise from Merkel cells or an epithelial precursor cell. One tenth of all cases affect the eyelids and periocular region, typically in the elderly population. The presentation is generally as a painless erythematous nodule with telangiectatic blood vessels and often intact overlying skin. The rarity of Merkel cell carcinoma of the eyelid can lead to delay in diagnosis and treatment of this tumour. In the present paper, the authors illustrate the aggressive nature of Merkel cell carcinoma, and the importance of early and wide surgical treatment and close follow-up. They discuss the role of rapid paraffin histology compared to frozen section. METHODS: Three cases are described, discussing the clinical presentation, diagnosis and treatment, with a review of the pathology. RESULTS: All three patients were female, presenting with rapidly growing upper eyelid tumours 20 mm in size; one case had paraffin sections suggesting incomplete clearance when frozen section had appeared clear; exenteration was required. The other two cases had lymph node involvement at one and two months post wide local excision. All patients remain alive at follow-up of 6, 4.6, and 2 years, respectively. DISCUSSION: The cases illustrate the aggressive nature of the tumour, the unusual tarsal involvement and the typical pathology. Sampling errors associated with limited frozen section control of excision may be avoidable by the use of rapid paraffin histology. The highly invasive nature of this tumour requires close follow-up following resection.

Journal Article↗
PubMed1995

Merkel cell carcinoma. Diagnosis and treatment.

BACKGROUND: Merkel cell carcinoma is an uncommon malignancy of the skin that often portends a poor prognosis. Since its first description by Toker in 1972, a plethora of case reports and articles regarding the etiopathogenesis and treatment have been published spanning multiple medical and surgical disciplines. Much confusion still exists regarding the diagnosis and treatment of this ominous tumor. OBJECT: Through extensive review of the medical, surgical, and pathological literature, to collate the observations of multiple investigators and summarize these findings. METHODS: Articles from journals of multiple subspecialties were carefully reviewed with particular emphasis placed on epidemiology, prognosis, histology, immunohistochemistry, electron microscopy, tumor origin, treatment, and work-up of Merkel cell carcinoma. RESULTS: Merkel cell carcinoma is an aggressive malignant neoplasm. Local recurrence develops in 26-44% of patients despite therapy. Up to three-fourths of patients eventually develop regional nodal metastases with distant metastases occurring in one-third of all patients. Reported overall 5-year survival rates range from 30% to 64%. CONCLUSION: Treatment recommendations unfortunately are based more on anecdotal than scientific data because of the rarity of the tumor and its recognized high risk. Most authors recommend wide local excision of the primary lesion and regional lymph node resection if lymph nodes are palpable followed by x-irradiation of both the postsurgical bed and lymph node basin. The role of elective lymph node resection in the absence of clinically positive nodes remains controversial.

Carcinoma, Merkel Cell↗
PubMed2005

Human Merkel cells--aspects of cell biology, distribution and functions.

Human Merkel cells were first described by Friedrich S. Merkel in 1875 and named "Tastzellen" (touch cells) assuming a sensory touch function within the skin. Only ultrastructural research revealed their characteristics such as dense-core granules, plasma membrane spines and dendrites as well as a loosely arranged cytoskeleton. Biochemical analysis identified the expression of very specific cytokeratins (most notably CK 20) allowing the immunohistochemical detection of Merkel cells. In humans, they occur within the basal epidermis, being concentrated in eccrine glandular ridges of glabrous skin and in Haarscheiben of hairy skin, within belt-like clusters of hair follicles, and in certain mucosal tissues. Within the human skin, the dense-core granules contain heterogeneously distributed neuropeptides, some of which might work as neurotransmitters through which Merkel cells and their associated nerves exert their classical function as slowly adapting mechanoreceptors type I. This is the case in the Haarscheiben, small sensory organs containing keratinocytes with a special program of differentiation that includes the expression of CK 17 and Ber-EP4. Other peptides may act as growth factors and thus might participate in growth, differentiation and homeostasis of cutaneous structures. It is not yet clear whether the Merkel cell carcinomas, aggressive skin carcinomas, indeed arise from Merkel cells. We summarize and discuss data on the distribution, function and heterogeneity of human Merkel cells in normal and diseased skin.

Adult↗
PubMed1987

Pathway of granule formation in Merkel cells: an ultrastructural study.

Merkel cells (MC) are characterized by dense core granules morphologically similar to secretory granules of endocrine cells, as well as the presence in their cytoplasm of organelles involved in polypeptide synthesis. The aim of this study was to follow the pathway of granule formation in MC. Four compartments, the cis and trans Golgi cisternae, the condensing granules in the Golgi stacks, the bristle-coated granules, and the noncoated granules, are observed by transmission electron microscopy in MC. This suggests that: (1) the organelles usually involved in the formation of secretory polypeptides are present in the cytoplasm of MC; (2) the pathway of Merkel cell granule (MCG) formation appears to be similar to that of secretory endocrine or exocrine cells; and (3) MC might be involved in a secretory process.

Animals↗