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1.
Am J Dermatopathol ; 43(1): 15-20, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32000217

RESUMO

ABSTRACT: In skin containing hair follicles, specialized epithelial structures known as "touch domes (TDs)" are located where the Merkel cells are clustered. We explored the histogenetic relationship between intraepidermal and dermal Merkel cell carcinomas (MCCs) and investigated which transformed progenitor cells can develop into intraepidermal MCC. We encountered an association between an extremely rare case of dermal and intraepidermal MCC with squamous cell carcinoma, which was examined using standard immunohistochemical methods with various epithelial, neuroendocrine, and TD markers including several immunohistochemical markers. Differential expression levels of CK20 and CD56 were found between intraepidermal and dermal MCCs, indicating molecularly distinct MCC populations. CK15 and CK17, expressed in TDs, were partially expressed in the intraepidermal neuroendocrine component at the tumor periphery in intraepidermal MCC with squamous cell carcinoma. These differences may suggest that the origin of dermal and intraepidermal MCCs is different under pathological conditions. We hypothesize that intraepidermal MCC is derived from tissue-specific stem cells localized within TDs.


Assuntos
Carcinoma de Célula de Merkel/patologia , Carcinoma de Células Escamosas/patologia , Queratinas/análise , Células de Merkel/patologia , Neoplasias Complexas Mistas/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias Cutâneas/patologia , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Célula de Merkel/química , Carcinoma de Células Escamosas/química , Linhagem da Célula , Feminino , Humanos , Imuno-Histoquímica , Células de Merkel/química , Neoplasias Complexas Mistas/química , Células-Tronco Neoplásicas/química , Neoplasias Cutâneas/química
2.
Am J Dermatopathol ; 42(9): 629-640, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32833736

RESUMO

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of unknown origin. We performed a retrospective histologic review of primary cutaneous MCCs diagnosed from 1997 to 2018 in several clinical institutions and literature review to determine the frequency of various unusual morphologic appearances of MCC. Of the 136 primary MCCs identified, intraepidermal carcinoma or epidermotropism was noted in 11/136 (8%) cases. An association with pilar cyst in 1/136 (0.7%) case, with actinic keratosis in 2/136 (1.5%) cases, with either invasive or in situ squamous cell carcinoma (SCC) in 14/136 (10%) cases, with poroma in 1/136 (0.7%), and with basal cell carcinoma in 1/136 (0.7%) case was noted. Trabecular pattern and rosettes were noted in 7/136 (5%) and 3/136 (2%) cases, respectively. There was one case of metastatic MCC in a lymph node with chronic lymphocytic leukemia and one rare case of metastatic MCC and SCC in a lymph node. Although uncommon, differentiation toward other cell lineage can be observed in both primary and metastatic MCCs. The tumor can assume a variety of histologic appearances including association with SCC, basal cell carcinoma, melanocytic neoplasm, and follicular cyst; as well as exhibit glandular, sarcomatous, and mesenchymal differentiation. This diversity of morphologic appearance of MCC reflects the complexity of its underlying pathogenesis.


Assuntos
Carcinoma de Célula de Merkel/patologia , Células de Merkel/patologia , Neoplasias Cutâneas/patologia , Biomarcadores Tumorais/análise , Biópsia , Carcinoma de Célula de Merkel/química , Carcinoma de Célula de Merkel/imunologia , Diferenciação Celular , Diagnóstico Diferencial , Humanos , Hospedeiro Imunocomprometido , Imuno-Histoquímica , Metástase Linfática , Células de Merkel/química , Células de Merkel/imunologia , Polônia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/química , Neoplasias Cutâneas/imunologia , Taiwan , Estados Unidos
3.
Am J Dermatopathol ; 39(11): 803-810, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28027080

RESUMO

This study investigated the nature of carcinoid-like, labyrinthine, rippled, and conventional cell arrangements in sebaceous neoplasms, focusing on vimentin expression and Merkel cell distribution in sebaceous neoplasms relative to these findings in normal sebaceous units and other sebaceous conditions. Immunohistochemistry for vimentin and cytokeratin 20 (CK20) was evaluated in carcinoid-like (n = 2), labyrinthine (n = 4), rippled (n = 3), and conventional (n = 6) sebaceomas; sebaceous mantle hyperplasia (n = 1); steatocystomas (n = 5); fibrofolliculomas (n = 4); sebaceous mantleoma (n = 1); sebaceous gland hyperplasias (n = 4); sebaceous adenomas (n = 4); and sebaceous carcinomas (n = 4) as well as normal skin tissue. The sebaceous mantle and its hamartoma (fibrofolliculoma) showed weak positivity for vimentin in the basal layer of the epithelial component and contained a few CK20-positive Merkel cells within the epithelial component, whereas mature sebaceous lobules were negative for vimentin and did not contain any Merkel cells. All sebaceomas with carcinoid-like or labyrinthine pattern highly expressed vimentin. CK20-positive Merkel cells were distributed with varying numbers in carcinoid-like pattern (2/2) and labyrinthine pattern (3/4) sebaceomas, sebaceous mantle hyperplasia (1/1), steatocystomas (3/5), fibrofolliculomas (3/4), and sebaceous mantleoma (1/1). Vimentin expression and Merkel cell distribution were observed in normal sebaceous mantles and sebaceous mantle-associated lesions, which could be evidence of a sebaceous mantle nature in the limited setting of sebaceous lesions. Furthermore, carcinoid-like/labyrinthine pattern sebaceomas also showed vimentin immunoreactivity and contained Merkel cells. Therefore, carcinoid-like/labyrinthine pattern of cell arrangement in sebaceous neoplasms may represent a morphological phenotype of sebaceous mantles.


Assuntos
Biomarcadores Tumorais/análise , Tumor Carcinoide/química , Carcinoma de Célula de Merkel/química , Imuno-Histoquímica , Células de Merkel/química , Neoplasias das Glândulas Sebáceas/química , Vimentina/análise , Biópsia , Tumor Carcinoide/patologia , Carcinoma de Célula de Merkel/patologia , Humanos , Queratina-20/análise , Células de Merkel/patologia , Valor Preditivo dos Testes , Neoplasias das Glândulas Sebáceas/patologia
4.
Hum Pathol ; 46(3): 443-53, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25623078

RESUMO

Merkel cell carcinoma (MCC) is a neuroendocrine skin malignancy frequently associated with Merkel cell polyomavirus (MCPyV), which is suspected to be oncogenic. In a series of MCC patients, we compared clinical, histopathologic, and prognostic features according to the expression of viral large T antigen (LTA) correlated with viral load. We evaluated the LTA expression by immunohistochemistry using CM2B4 antibody and quantified viral load by real-time polymerase chain reaction. We analyzed formalin-fixed, paraffin-embedded (FFPE) tissue samples (n = 36) and corresponding fresh-frozen biopsies when available (n = 12), of the primary tumor and/or metastasis from 24 patients. MCPyV was detected in 88% and 58% of MCC patients by real-time polymerase chain reaction and immunohistochemistry, respectively. The relevance of viral load measurements was demonstrated by the strong consistency of viral load level between FFPE and corresponding frozen tissues as well as between primary tumor and metastases. From FFPE samples, 2 MCC subgroups were distinguished based on a viral load threshold defined by the positivity of CM2B4 immunostaining. In the LTA-negative subgroup with no or low viral load (nonsignificant), tumor cells showed more anisokaryosis (P = .01), and a solar elastosis around the tumor was more frequently observed (P = .03). LTA-positive MCCs with significant viral load had a lower proliferation index (P = .03) and a longer survival of corresponding patients (P = .008). Depending on MCPyV involvement, 2 MCC subgroups can be distinguished on histopathologic criteria, and the CM2B4 antibody is able to differentiate them reliably. Furthermore, the presence of a significant viral load in tumors is predictive of better prognosis.


Assuntos
Antígenos Transformantes de Poliomavirus/isolamento & purificação , Biomarcadores Tumorais/isolamento & purificação , Carcinoma de Célula de Merkel/patologia , Carcinoma de Célula de Merkel/virologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/virologia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma de Célula de Merkel/química , Carcinoma de Célula de Merkel/epidemiologia , Carcinoma de Célula de Merkel/secundário , Comorbidade , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Células de Merkel/química , Células de Merkel/patologia , Células de Merkel/virologia , Poliomavírus das Células de Merkel/isolamento & purificação , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/epidemiologia , Prognóstico , Neoplasias Cutâneas/química , Neoplasias Cutâneas/epidemiologia , Carga Viral
5.
Ultrastruct Pathol ; 37(1): 62-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21843057

RESUMO

BACKGROUND: Sensory stimuli are conducted by several cutaneous sensory nerves and tactile corpuscles. The latter are specialized sensory organs that represent the starting point of many afferent sensory pathways. To date, our knowledge about the distribution of the sensory innervation in the umbilical skin of females is incomplete. AIM OF THE STUDY: To elucidate the morphology of the cutaneous innervation of the normal female umbilical skin. MATERIALS AND METHODS: Biopsies of normal umbilical skin were obtained from female patients undergoing umbilical hernial repair. The specimens were processed for both immunohistological (antibodies against PGP9.5, pan-neuronal marker, and S-100 protein, marker of Schwann cells) and ultrastructural (transmission electron microscopy) examinations. RESULTS: The authors found abundant genital end-bulb-like structures, numerous epidermal and dermal Merkel cells, Meissner and Ruffini corpuscles, intraepidermal nerve terminals, and multiple free nerve endings surrounding the ducts and acini of the sweat glands. CONCLUSIONS: The umbilical skin of females has abundant sensory innervation similar to that of the glans penis.


Assuntos
Células Receptoras Sensoriais/química , Células Receptoras Sensoriais/ultraestrutura , Pele/inervação , Biomarcadores/análise , Biópsia , Feminino , Hérnia Umbilical/cirurgia , Herniorrafia , Humanos , Imuno-Histoquímica , Mecanorreceptores/química , Mecanorreceptores/ultraestrutura , Células de Merkel/química , Células de Merkel/ultraestrutura , Microscopia Eletrônica de Transmissão , Proteínas S100/análise , Ubiquitina Tiolesterase/análise , Umbigo
6.
Am J Dermatopathol ; 29(3): 249-55, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17519622

RESUMO

We reexamined 11 cases of trichoblastoma, and two cases of trichoblastoma with basal cell carcinoma (BCC)-like foci were found. In these two trichoblastomas with BCC-like foci, the BCC-like foci were often localized in peripheral or deep areas of lesions extending out of the fibrocytic stroma. Immunohistochemistry was performed in five conventional trichoblastomas and in two trichoblastomas with BCC-like foci, using antibodies against CK20 and CK15. No CK20-positive Merkel cells and no expression of CK15 were seen in any neoplastic aggregations of the two trichoblastomas with BCC-like foci. In contrast, increased numbers of Merkel cells and positive staining for CK15 were observed in all five trichoblastomas without BCC-like foci. The five trichoblastomas without BCC-like foci included two trichoblastomas with a popped out or shelled out appearance, which characteristically had a thick fibrous capsule surrounding the fibrotic stroma, demonstrating numerous Merkel cells in the aggregations. Some trichoblastomas may undergo mutations, resulting in the development of foci of BCC and in the loss of the expression of CK15 as well as the disappearance of Merkel cells.


Assuntos
Carcinoma Basocelular/patologia , Doenças do Cabelo/patologia , Folículo Piloso/patologia , Células de Merkel/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma Basocelular/química , Carcinoma Basocelular/cirurgia , Feminino , Doenças do Cabelo/metabolismo , Doenças do Cabelo/cirurgia , Folículo Piloso/química , Humanos , Imuno-Histoquímica , Queratina-15/análise , Masculino , Células de Merkel/química , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/química , Neoplasias Cutâneas/cirurgia
7.
Int J Surg Pathol ; 14(3): 206-11, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16959700

RESUMO

Ninety-eight consecutive surgical biopsies of oral mucosa from 96 patients were evaluated immunohistochemically with an anti-cytokeratin 20 (CK 20) anti-body to evidence Merkel cells (MC). Fifteen cases, showing the highest number of MC, were additionally studied with chromogranin A, S-100 protein, neuro filaments, epithelial membrane antigen, and double immunostaining for CK 20 and Ki67 antibodies to evaluate MC proliferation. Electron microscopy was performed in 2 cases. MC were observed in 58 cases. The highest number of MC was found in the gingival, buccal, and palate mucosa, especially in chronically damaged oral mucosa (lichen and chronic aspecific inflammation) as well as in the mucosa overlying tumors rather than in normal or acute inflammation. MC were not observed in dysplastic or neoplastic epithelium. MC showed evidence of proliferation, as demonstrated by Ki67 positivity, in 3 cases. In conclusion, MC appear to play a role in the reparative processes of oral mucosa.


Assuntos
Células de Merkel/patologia , Mucosa Bucal/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biópsia , Contagem de Células , Proliferação de Células , Criança , Pré-Escolar , Humanos , Imuno-Histoquímica , Queratina-20 , Queratinas/análise , Células de Merkel/química , Células de Merkel/ultraestrutura , Pessoa de Meia-Idade , Mucosa Bucal/química , Mucosa Bucal/ultraestrutura
8.
J Cutan Pathol ; 32(7): 491-5, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16008693

RESUMO

BACKGROUND: Basaloid epidermal proliferations (BEP), morphologically resembling basal cell carcinoma (BCC), have been described overlying dermatofibromas. Distinguishing the two is important because of non-aggressiveness of BEP and local aggressiveness of BCC. The aim of this study is to determine whether CK20 antibody staining for Merkel cells can be used as an adjunct method to differentiate BEP from BCC. METHODS: Ten cases of BEP overlying dermatofibromas were selected. Ten cases of BCC were used as control. The two groups were stained with CK20 antibody. Numerical density of CK20 stained Merkel cells in peri-lesional epidermis, BEP and BCC was determined by examining 300 cells at 400X in two separate areas by three independent pathologists. To determine statistical significance, the results were compared using t-test method. RESULTS: Density of Merkel cells in peri-lesional epidermis was 0.2-0.3%. No merkel cells were detected in the BCC. BEP overlying dermatofibromas showed an obvious increase in CK 20 stained Merkel cells. The difference was statistically significant (P < 0.02) CONCLUSIONS: We report a significant increase in CK20 stained Merkel cells in BEP overlying dermatofibromas as compared to BCC. CK20 antibody staining for Merkel cells can be used as an adjunct method to differentiate BEP overlying dermatofibromas from BCC. Mahmoodi M, Asad H, Salim S, Kantor G, Minimo C. Anti-CK20 staining of Merkel cells helps differentiate basaloid proliferations overlying dermatofibromas from basal cell carcinoma.


Assuntos
Carcinoma Basocelular/diagnóstico , Histiocitoma Fibroso Benigno/diagnóstico , Proteínas de Filamentos Intermediários/análise , Células de Merkel/patologia , Neoplasias Cutâneas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma Basocelular/química , Contagem de Células , Proliferação de Células , Diagnóstico Diferencial , Epiderme/química , Epiderme/patologia , Feminino , Histiocitoma Fibroso Benigno/química , Humanos , Técnicas Imunoenzimáticas , Recém-Nascido , Queratina-20 , Masculino , Células de Merkel/química , Pessoa de Meia-Idade , Neoplasias Cutâneas/química
9.
Arch Pathol Lab Med ; 128(9): 986-90, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15335266

RESUMO

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.


Assuntos
Adenoma Pleomorfo/patologia , Proteínas de Filamentos Intermediários/análise , Células de Merkel/patologia , Neoplasias Cutâneas/patologia , Adenoma Pleomorfo/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Glândulas Apócrinas/citologia , Diferenciação Celular , Glândulas Écrinas/citologia , Feminino , Folículo Piloso/citologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Queratina-20 , Masculino , Células de Merkel/química , Pessoa de Meia-Idade , Glândulas Sebáceas/citologia , Neoplasias Cutâneas/química , Neoplasias das Glândulas Sudoríparas/patologia
10.
Brain Res Mol Brain Res ; 88(1-2): 171-5, 2001 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-11295244

RESUMO

Immunohistochemistry for protein gene product 9.5 was performed on Merkel cells in the palate of wildtype and knockout mice for trkA, trkB or trkC. In wildtype mice, numerous Merkel cells were observed at the top of anterior four rugae. In the posterior four rugae, Merkel cells were fewer and mostly located at the base of rugae. In knockout mice for trkA, trkB and trkC, Merkel cells at the top of rugae mostly disappeared although those at the base of rugae remained unchanged. Therefore, the number of Merkel cells in anterior four rugae decreased. In posterior four rugae, however, the number of Merkel cells in the mutant mice was similar to that for wildtype mice. Immunohistochemistry for S100 also demonstrated that the loss of genes for trkA, trkB and trkC caused the absence of the immunoreactive innervation of Merkel cells. The normal development of Merkel endings at the top of palatal rugae is probably dependent on trkA, trkB and trkC.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Células de Merkel/fisiologia , Receptores de Fator de Crescimento Neural/genética , Animais , Células de Merkel/química , Camundongos , Camundongos Knockout , Palato/inervação , Receptor trkA/genética , Receptor trkB/genética , Receptor trkC/genética , Proteínas S100/análise , Tioléster Hidrolases/análise , Ubiquitina Tiolesterase
11.
Eur J Neurosci ; 12(8): 2694-706, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10971613

RESUMO

During development, a highly differential neurotrophin dependency is reported for various types of nerve endings in the whisker follicle. To what extent these dependencies extend and play a role in adulthood is largely unresolved. We show here, using in situ hybridization and immunohistochemistry that the expression of neurotrophins and trk/p75 receptors persists in adulthood. As suggested by their expression profiles, many classes of cutaneous nerve endings disclose similar ligand-receptor dependencies in adult animals as during development, while other populations appear to switch their dependency. Furthermore, our data suggest that sensory endings that have a high turnover due to mechanical wear and tear, e. g. Merkel cell-neurite complexes at the level of ring sinus show a more complex ligand-receptor expression phenotype than do endings with a less vulnerable location, e.g. the Merkel cell-neurite complexes at the rete ridge collar. Thus, neurotrophin-3 (NT3)/trkA signalling is suggested to be important for a continuous terminal plasticity of Merkel cell-neurite complexes at the level of ring sinus in adulthood. Evidence supporting a role for neurotrophin signalling in maintaining the adult cutaneous innervation also comes from the close correlation between altered ligand-receptor expression(s) and axonal/terminal aberrations in senescence. Thus, an ageing-related decrease in target neurotrophin expression, notably NT3 and NT4, results in a site-specific loss of sensory terminals concomitant with an aberrant growth of regenerating/sprouting axons into new target fields. Ageing of the cutaneous innervation, manifested in degenerative and regenerative events, seems strongly associated with changes in neurotrophic interactions between sensory neurons and target tissues.


Assuntos
Envelhecimento/fisiologia , Degeneração Neural/metabolismo , Fatores de Crescimento Neural/genética , Regeneração Nervosa/fisiologia , Receptores de Fator de Crescimento Neural/genética , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Seio Cavernoso/inervação , Feminino , Imunofluorescência , Regulação da Expressão Gênica no Desenvolvimento , Folículo Piloso/inervação , Hibridização In Situ , Ligantes , Nervo Maxilar/química , Nervo Maxilar/metabolismo , Células de Merkel/química , Células de Merkel/metabolismo , Fatores de Crescimento Neural/metabolismo , Neurotrofina 3/genética , Neurotrofina 3/metabolismo , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Receptor de Fator de Crescimento Neural/análise , Receptor de Fator de Crescimento Neural/genética , Receptor de Fator de Crescimento Neural/metabolismo , Receptor trkA/análise , Receptor trkA/genética , Receptor trkA/metabolismo , Receptor trkB/análise , Receptor trkB/genética , Receptor trkB/metabolismo , Receptor trkC/análise , Receptor trkC/genética , Receptor trkC/metabolismo , Receptores de Fator de Crescimento Neural/análise , Receptores de Fator de Crescimento Neural/metabolismo , Vibrissas/inervação
12.
Arch Oral Biol ; 45(10): 879-87, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10973561

RESUMO

Cytokeratin (CK) 20 is a low molecular-weight intermediate filament reportedly expressed only by benign and malignant gastrointestinal epithelium, urothelium and Merkel cells. The main aims here were to map its expression in normal oral mucosa of humans and other mammals, and to determine whether it was expressed by abnormal human oral epithelium. Salivary and odontogenic epithelium were also analysed. An immunoperoxidase method was used on wax-embedded and cryostat sections. In addition, double-labelling experiments were undertaken to determine the association between CK 20 expression and that of CK 8/18 or S100 protein. Normal human oral mucosa from four sites, together with abdominal skin, was studied in autopsy samples from 32 individuals. CK 20-positive, basally situated, round or angular cells, consistent with Merkel cells, were recorded in 24/32 (75.0%) samples of mandibular gingiva, 25/32 (78.1%) samples of hard palate, 7/32 (21.9%) samples of buccal mucosa, 0/32 samples of lateral border of tongue, and 2/32 (6.3%) samples of abdominal skin. Double-labelling showed that all CK 20-positive Merkel cells also expressed CK 8/18 and S100. The only other cells to express CK 20 were human taste buds. There was no expression by dysplastic or invasive oral epithelium from biopsy samples. Colonic mucosa showed luminal-cell positivity in man, marmoset, ferret, rabbit and guinea-pig, but oral mucosa was universally negative in non-human species. It is concluded that in oral mucosa CK 20 is a specific marker of Merkel cells and taste buds, that Merkel cells are more frequently present in keratinized than non-keratinized oral mucosa, that CK 20-positive Merkel cells are also S100-positive, that there may be interspecies variations in CK 20 polypeptide composition and that, by contrast to urothelium, CK 20 has no value in the diagnosis of oral epithelial dysplasia.


Assuntos
Biomarcadores Tumorais/análise , Proteínas de Filamentos Intermediários/análise , Mucosa Bucal/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/genética , Callithrix , Gatos , Bovinos , Cricetinae , Epitélio/química , Feminino , Furões , Gengiva/química , Cobaias , Humanos , Imuno-Histoquímica , Proteínas de Filamentos Intermediários/genética , Queratina-20 , Queratinas , Macaca mulatta , Masculino , Células de Merkel/química , Mesocricetus , Pessoa de Meia-Idade , Neoplasias Bucais/química , Cistos Odontogênicos/química , Palato Duro/química , Coelhos , Ratos , Proteínas S100/análise , Glândulas Salivares/química , Ovinos , Pele/química , Suínos , Papilas Gustativas/química , Língua/química
13.
Am J Dermatopathol ; 22(4): 311-5, 2000 08.
Artigo em Inglês | MEDLINE | ID: mdl-10949455

RESUMO

Merkel cells are normal constituents of the basal layer of the epidermis and the follicular epithelium. They have been identified in benign neoplasms with follicular germinative differentiation but seem to be absent in basal cell carcinomas (BCCs). Because sclerosing epithelial neoplasms are often sampled by small biopsies, any method that enables distinction among them would be welcome. We used immunohistochemical staining for cytokeratin 20 to assess the presence of Merkel cells in 14 cases of desmoplastic trichoepithelioma (DTE), 12 specimens of syringoma, 11 samples of morpheiform BCC, and 8 specimens of microcystic adnexal carcinoma (MAC). Merkel cells were found in association with all 14 specimens of DTE and in 1 of 11 cases of morpheiform BCC (p < 0.005) but in none of the specimens of syringoma or MAC. Our study supports previous findings that Merkel cells are seen in association with cutaneous neoplasms that are benign and of a follicular germinative origin. Although MAC may differentiate along follicular-sebaceous-apocrine lines, the absence of Merkel cells within it is consistent with its malignancy. The identification of Merkel cells in a sclerosing epithelial neoplasm of the skin points to DTE as the most likely diagnosis.


Assuntos
Carcinoma Basocelular/patologia , Carcinoma de Apêndice Cutâneo/patologia , Células de Merkel/patologia , Neoplasias Cutâneas/patologia , Siringoma/patologia , Biomarcadores Tumorais/análise , Carcinoma Basocelular/química , Carcinoma de Apêndice Cutâneo/química , Feminino , Humanos , Técnicas Imunoenzimáticas , Proteínas de Filamentos Intermediários/análise , Queratina-20 , Masculino , Células de Merkel/química , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Neoplasias Cutâneas/química , Siringoma/química
14.
Am J Dermatopathol ; 21(1): 8-15, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10027518

RESUMO

The morphologic features of trichofolliculoma are variable, reminiscent of the anagen, catagen, and telogen phases of a normal hair follicle in its cycle. We recently described an early, fully developed stage and late stages of trichofolliculoma. Using immunohistochemical examination, we sought to demonstrate hyperplasia of Merkel cells in all three stages of trichofolliculoma. We found this to be the most striking in small lesions of the late stage. The distribution of the Merkel cells in several stages of trichofolliculoma coincided with the known arrangement of normal follicular Merkel cells during the follicular cycle. However, antibodies against neurofilaments failed to detect innervated Merkel cells, in contrast to normal follicular Merkel cells. Antibodies against Ki67 did not reveal proliferative Merkel cells in any of the trichofolliculomas, but for unknown reasons, a distinct cytoplasmic staining of Merkel cell processes sometimes occurred. Nuclear Ki67 was strongly expressed in the nuclei of follicular keratinocytes of the fully developed trichofollicullomas, whereas those at a late stage showed a markedly decreased staining pattern. Our finding of Merkel cells in all trichofolliculomas underlines their classification as hamartomas with follicular differentiation. Hyperplasia of Merkel cells, even in trichofolliculomas at a late stage, as regressing lesions might implicate hitherto unknown regulatory functions of this neuroendocrine cell.


Assuntos
Células de Merkel/patologia , Neoplasia de Células Basais/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Adulto , Pré-Escolar , Feminino , Humanos , Hiperplasia , Imuno-Histoquímica , Proteínas de Filamentos Intermediários/análise , Queratina-20 , Antígeno Ki-67/análise , Masculino , Células de Merkel/química , Pessoa de Meia-Idade , Neoplasia de Células Basais/metabolismo , Pele/química , Neoplasias Cutâneas/metabolismo , Fatores de Tempo
15.
Dermatology ; 196(2): 208-12, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9568409

RESUMO

BACKGROUND: Merkel cells are neuro-endocrine cells present in the basal layer of the human epidermis and the outer root sheath of hair follicles. OBJECTIVE AND METHOD: In order to gain further insight into the as yet ill-defined involvement of Merkel cells in skin diseases, we studied the distribution of these cells in formalin-fixed, paraffin-embedded sections of 165 inflammatory, hyperplastic or tumoral skin lesions of various anatomic locations, with a monoclonal antibody to keratin 20. RESULTS: Lesions with frequently increased Merkel Cell numbers included actinic keratosis, fibrous papules of the face and some conditions with (immature) hair follicle differentiation. CONCLUSION: These results suggest that Merkel cell hyperplasia is unrelated to epidermal proliferation but that it is rather specific to a limited number of skin diseases.


Assuntos
Células de Merkel/citologia , Neoplasias Cutâneas/patologia , Pele/citologia , Pele/patologia , Reações Antígeno-Anticorpo , Contagem de Células , Células Epidérmicas , Epiderme/química , Folículo Piloso/química , Folículo Piloso/citologia , Humanos , Hiperplasia/patologia , Imuno-Histoquímica , Proteínas de Filamentos Intermediários/análise , Proteínas de Filamentos Intermediários/imunologia , Queratina-20 , Células de Merkel/química , Pele/química , Neoplasias Cutâneas/química
16.
J Cutan Pathol ; 24(8): 477-83, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9331893

RESUMO

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.


Assuntos
Carcinoma Basocelular/patologia , Células de Merkel/patologia , Células de Merkel/efeitos da radiação , Radiodermite/patologia , Neoplasias Cutâneas/patologia , Idoso , Biomarcadores Tumorais/análise , Carcinoma Basocelular/química , Cromogranina A , Cromograninas/análise , Feminino , Humanos , Imuno-Histoquímica , Proteínas de Filamentos Intermediários/análise , Queratina-20 , Queratinas/análise , Masculino , Células de Merkel/química , Neoplasias Cutâneas/química
17.
J Cutan Pathol ; 24(1): 14-24, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9027628

RESUMO

The possibility of a neuroendocrine differentiation in basal cell carcinomas (BCCs) has been a matter of debate for many years. In the present immunohistochemical study, applying the cytokeratins 8, 18 and 20 as the most established markers for Merkel cells (MCs), we did not find elevated numbers of MCs in any of 205 BCCs. This speaks against a neuroendocrine line of differentiation in BCCs. In contrast, we found various amounts of MCs in 15 of 36 trichoblastomas, which are the main benign differential diagnosis of BCC. In 4 trichoblastomas abundant MCs were spread over the whole epithelial tumor area. Additionally, the trichoblastomas' overlying epidermis exhibited significantly much higher numbers of MCs than the uninvolved adjacent skin or the epidermis overlying the BCCs. These findings might be an additional aid in the distinction between trichoblastomas and BCCs. Furthermore, concerning the recent discussion about the role of MC in growth and development of follicular germ, our observations are another sign of regulative influences of the MC, also in follicular germ under pathological conditions. Trichoblastomas with high numbers of MCs could be characterized as showing advanced differentiation toward the neuroendocrine component of the hair follicle, i.e., the MCs.


Assuntos
Carcinoma Basocelular/patologia , Células de Merkel/patologia , Neoplasia de Células Basais/patologia , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/química , Epiderme/química , Epiderme/patologia , Humanos , Imuno-Histoquímica , Células de Merkel/química , Neoplasia de Células Basais/química , Neoplasias Cutâneas/química
18.
Exp Brain Res ; 108(3): 357-66, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8801116

RESUMO

An isolated, functioning sinus hair preparation was developed to investigate cytoplasmic Ca2+ concentrations in intact Merkel cells using microfluorimetric techniques. Intracellular Ca2+ levels were monitored by means of photon counters in small groups of Merkel cells loaded with the calcium fluorescent indicators fura-2 or fluo-3. Mechanical stimulation of Merkel cells with fine glass rods resulted in small transient increases in intracellular Ca2+ levels (by about 20%) in the group of Merkel cells around the stimulating probe. A rise in Ca2+ is presumed to be essential for the postulated synaptic transmission to the afferent nerve terminal. Depolarization with a high concentration of potassium chloride (100 mM) caused increases in intracellular Ca2+ concentrations in Merkel cells (by about 70%) only in the presence of extracellular Ca2+, indicating an influx of Ca2+ through voltage-gated channels. The Ca2+ response was abolished neither by (+)-BayK8644 nor omega-conotoxin, suggesting that the Ca2+ channels are different from the classical L- or N-type channels. Extracellular application of ATP (10 microM to 5 mM) caused dose-dependent increases in intracellular Ca2+ levels in Merkel cells of up to sevenfold from the basal level of about 100 nM. Similar responses to ATP were also measured during superfusion with Ca(2+)-free medium, suggesting intracellular stores as the main Ca2+ source. Pre-incubation of Merkel cells with the purinoceptor antagonist suramin (100 microM) for 30 min reduced the Ca2+ responses to ATP by about 50% compared with control conditions. In conclusion, the results have demonstrated that a rise in intracellular Ca2+ in Merkel cells can be evoked by mechanical stimulation, membrane depolarization and chemical stimulation by ATP. These observations strongly suggest a possible contribution of Ca2+ to the normal responsiveness of Merkel cell mechanoreceptors, in turn supporting the hypothesis that Merkel cells are involved in the mechano-electric transduction process in sinus hair type I mechanoreceptors.


Assuntos
Cálcio/análise , Folículo Piloso/citologia , Células de Merkel/química , Células de Merkel/citologia , Trifosfato de Adenosina/farmacologia , Animais , Citoplasma/química , Fura-2 , Folículo Piloso/química , Folículo Piloso/inervação , Ativação do Canal Iônico/fisiologia , Mecanorreceptores/química , Mecanorreceptores/fisiologia , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Células de Merkel/fisiologia , Ratos , Ratos Sprague-Dawley , Vibrissas/química , Vibrissas/citologia , Vibrissas/inervação
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