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PubMed2000

Regeneration of cutaneous innervation in a human hand allograft.

On Sept 23, 1998, a human hand allograft was done in our hospital. We followed up the patients for 24 months to assess the skin structure by immunohistology. Most cutaneous structures (including dermal nerves with their Schwann cells and perineurial fibroblasts) were present immediately after surgery and remained detectable throughout the study; from day 464 onwards, axons became detectable within dermal nerves, and their density increased progressively with time. Merkel cells reappeared in the epidermis 12 months after the operation. The regeneration of cutaneous innervation paralleled the recovery of cutaneous sensitivity.

Antigens, CD34↗
PubMed1984

[Neuroendocrine carcinoma of the skin. Morphology and differential diagnosis based on 2 clinical cases].

Two cases of neuroendocrine carcinomas of the skin were examined by light microscopic and electron microscopic methods. In both patients the disease showed an unusual course characterized by the occurrence of numerous and wide-spread skin nodules. Light microscopically, we found a uniform tumor tissue with trabecular, nest- or cord-like arrangement of cancer cells. At electron microscopic investigation, neurosecretory granules (dense-cored vesicles) were detected. These organelles had a diameter between 90 and 220 nm. Furthermore, small bundles of intermediate filaments and a well-developed Golgi system as well as numerous vesicular structures were recognized. Specialized cell junctions were lacking, tumor cell complexes were often enveloped by a basal lamina-like structure. The light microscopic and electron microscopic observations are in accordance with other reports. The relationship of neuroendocrine skin carcinomas to Merkel cells is discussed. However, we suggest an origin of these carcinomas from multipotent epithelial stem cells. The multicentric development in our cases, the tumor localization, and recent electron microscopic findings in basal cell carcinomas lend the basis for speculations on relations between neuroendocrine carcinomas and basal cell carcinomas of the skin. Lastly, the morphologic differential diagnosis of neuroendocrine carcinomas is presented. Special attention is called to the distinction from melanomas, lymphomas and other neuroendocrine tumors. In spite of the fact that neuroendocrine carcinomas of the skin are well defined and considered to be a clinico-pathologic entity there are some open questions concerning the tumor biology and histogenesis.

Adenocarcinoma↗
PubMed1996

Keratin 19 as a biochemical marker of skin stem cells in vivo and in vitro: keratin 19 expressing cells are differentially localized in function of anatomic sites, and their number varies with donor age and culture stage.

This study was undertaken to evaluate keratin 19 (K19) as a biochemical marker for skin stem cells in order to address some long standing questions concerning these cells in the field of cutaneous biology. We first used the well-established mouse model enabling us to identify skin stem cells as [3H]thymidine-label-retaining cells. A site directed antibody was raised against a synthetic peptide of K19. It reacted specifically with a 40 kDa protein (K19) on immunoblotting. It labelled the bulge area of the outer root sheath on mouse skin by immunohistochemistry. Double-labelling revealed that K19-positive-cells were also [3H]thymidine-label-retaining cells, suggesting that K19 is a marker for skin stem cells of hair follicles. K19-expression was then used to investigate the variation in mouse and human skin stem cells as a function of body site, donor age and culture time. K19 was expressed in the hair follicle and absent from the interfollicular epidermis at hairy sites (except for some K18 coexpressing Merkel cells). In contrast, at glabrous sites, K19-positive-cells were in deep epidermal rete ridges. K19 expressing cells also contained high levels of alpha 3 beta 1 integrin. The proportion of K19-positive-cells was greater in newborn than older foreskins. This correlated with keratinocyte culture lifespan variation with donor age. Moreover, it could explain clinical observations that children heal faster than adults. In conclusion, K19 expression in skin provides an additional tool to allow further characterization of skin stem cells under normal and pathological conditions in situ and in vitro.

3T3 Cells↗
PubMedDate not supplied

Neuroendocrine carcinomas of the skin: light microscopic, ultrastructural, and immunohistochemical analysis.

Three primary skin carcinomas were analyzed by light microscopy, immunohistochemistry, and electron microscopy. In all cases, local recurrences, regional lymph node metastases, distant metastases, or all three developed. One patient had elevated serum calcitonin levels that did not decrease after thyroidectomy but did return to normal after removal of the skin tumor recurrences, its metastases, or both. The tumor cells were arranged in solid clusters; a trabecular arrangement was occasionally seen. In 2 cases the cells were of intermediate size and showed vesicular central nuclei and pale, moderately abundant cytoplasm. In the remaining case the cells were distinctly smaller and either round or fusiform. Mitoses were more abundant in the latter case than in the former two. By immunohistochemistry, calcitonin- and somatostatin-containing cells were demonstrated in all cases and ACTH in one. By electron microscopy, the cases consisting of intermediate-size cells displayed moderately abundant neurosecretory-type granules irregularly dispersed throughout the cytoplasm. The case consisting of smaller cells displayed fewer and smaller granules that tended to concentrate in slender cytoplasmic processes. We conclude that these tumors constitute parts of the broadening spectrum of neuroendocrine skin carcinomas that may derive from Merkel cells.

Aged↗
PubMed1996

Malignant rhabdoid tumor in adults--heterogenous tumors with a unique morphological phenotype.

Five cases of malignant rhabdoid tumors in adult patients are described. The tumors were characterized by sheets of poorly cohesive cells with distinctive hyaline cytoplasmic inclusions and eccentrically placed large vesicular nuclei with prominent nucleoli. A variety of lineage differentiation was shown by immunohistochemistry and electron microscopy, the lesions representing leiomyosarcoma, gastric carcinoma, epithelioid sarcoma, Merkel cell carcinoma and desmoplastic small round cell tumor. Previously reported cases of rhabdoid tumors in adults support the contention that such tumors, although of distinctive morphologic phenotype, are of heterogenous lineage differentiation, and do not represent a distinct clinicopathologic entity.

Adult↗
PubMed2001

Cytokeratin 20 immunoreactivity in renal oncocytomas.

Cytokeratins (CKs) are a group of 20 antigenically distinct intermediate filaments, generally confined to epithelia and their neoplasms. Immunostaining for CKs, in particular coordinate staining for CK7 and CK20, has become a useful tool in diagnostic pathology. Although studies defining CK distribution in neoplasms identify 0--7.7% of renal cell carcinomas (RCCs) positive for CK20, none has described the incidence of CK20 immunopositivity in renal oncocytomas (ROs). Distinction between RCC and RO may be difficult but this distinction is clinically significant, prompting us to establish the incidence of CK20 positivity in RO. We selected fifteen surgical cases of RO from our archives and studied their immunoreactivity for CKs including CK7 and CK20; 12/15 (80%) were positive for CK20, with variation in the number of cells staining. There was also variation in the distribution of CKs within the cells, including diffuse cytoplasmic, perinuclear, and a punctate or dot-like pattern. Such punctate staining corresponds to cytoplasmic balls of intermediate filaments and has been described with CAM 5.2 in RO and CK20 in Merkel cell carcinomas. Our findings suggest that CK20 immunohistochemistry is a useful tool for distinguishing RCCs from ROs. (J Histochem Cytochem 49:919-920, 2001)

Adenoma, Oxyphilic↗
PubMed1994

Distribution patterns of the paraneuronal endocrine cells in the skin, gills and the airways of fishes as determined by immunohistochemical and histological methods.

The neuro-endocrine cells of fish skin and respiratory surfaces, and their bioactive secretion as far as is known, are reviewed, and compared with similar elements in tetrapods, particularly amphibians. In the skin of teleost fish, immunohistochemistry has shown that Merkel cells react for serotonin, neuron-specific enolase and enkephalins. The pharmacology is not established in dipnoans or lampreys. In some teleosts, neuromasts react for substance P and leu-enkephalins; substance P is also reported from some ampullary organs (electroreceptors). Taste buds of teleosts may react for enkephalin and substance P. Basal cells of taste buds react for serotonin and neuron-specific enolase. Some unicellular skin glands of teleosts express bioactive compounds, including serotonin and some peptides; this ectopic expression is paralleled in amphibian skin glands. The dipnoan Protopterus has innervated pulmonary neuro-endocrine cells in the pneumatic duct region with dense-cored vesicles. In Polypterus and Amia the lungs have serotonin-positive neuro-endocrine cells that are apparently not innervated. In fish gills, a closed type of neuro-endocrine cell reacts for serotonin, an open type for enkephalins and some calcium-binding proteins (calbindin, calmodulin and S-100 protein). The functions of neuro-endocrine cells in fishes await investigation, but it is assumed they are regulatory.

Animals↗
PubMed2006

Management of malignant and benign eyelid lesions.

PURPOSE OF REVIEW: The management of benign and malignant eyelid neoplasms has been extensively examined. This paper offers an overview of the most common eyelid lesions and their management based on a review of the relevant bibliography. RECENT FINDINGS: Recent studies have focused on the results of nonsurgical approaches for benign and premalignant lesions that are routinely surgically excised. In the malignant group, a consensus has been reached over the preferred method of tumor excision for basal cell carcinoma: Mohs surgery or complete surgical excision with frozen-section control of the margins offers the lowest tumor-recurrence rate. Important acquisitions have been made on squamous cells for which sentinel node biopsy may reveal early metastatic cancer. Intraepithelial tumor growth is a peculiar feature of sebaceous gland carcinoma that seems to indicate an increased risk for orbital invasion. Recent reports regarding the rare tumor, Merkel cell carcinoma, recommend a wide surgical excision with 5 mm margins; this may reduce the incidence of lymph-node metastasis, haematogenous spread and local recurrences. SUMMARY: Although treatment of the most common benign and malignant tumours affecting the eyelids has not radically changed over the years, recent reports have significantly improved the standard of care for affected patients.

Eyelid Neoplasms↗
PubMed1991

[Mouse monoclonal antibody (FKH1) detecting human melanoma-associated antigens: production, partial characterization and immunohistochemical analysis].

A mouse monoclonal antibody, FKH1, was produced to detect cytoplasmic melanoma-associated antigen. FKH1 was raised using cultured human melanoma cell line KHm-6 as immunogen. Reactivity of this antibody was assessed by immunohistochemical techniques. Positive reactions were seen against 5 human melanoma cell lines and cultured human epidermal melanocyte. It stained cytoplasm of melanoma cells in a diffuse and granular pattern with indirect immunofluorescence. Immunoelectron microscopy showed diffuse distribution of immuno-reactant in the cytoplasm of KHm-1 cells excluding melanosomes and other subcellular organelles. In immunoblotting, FKH1 bound with proteins having molecular weight of 71 kd and 55 kd extracted from KHm-6 cells. Reactivity against frozen and alcohol-fixed paraffin-embedded melanocytic tumors was also tested with indirect immunofluorescence or ABC (avidin biotin peroxidase complex) techniques. All cases of frozen sections from benign and malignant melanocytic tumors including 2 cases of amelanotic melanoma showed positive staining with FKH1. In fixed tissues, reactivity was 16/19 (84.2%) in malignant melanoma and 30/44 (68.2%) in other melanocytic tumors. FKH1 did not react against normal melanocytes, C-type nevus cell, intradermal nevus pigmentosus with neuroid structure and neurofibroma. It was demonstrated that FKH1 recognized proliferative melanocytes originated from melanoblast or melanoblastic nevoblast. FKH1 failed to stain normal human peripheral nerves and nonmelanocytic tumors except APUDoma and malignant Merkel cell tumor. In halo nevus, nevus cells were clearly distinguished from intermingling inflammatory cell infiltrate. It was suggested that FKH1 is a useful monoclonal antibody in diagnosing human malignant melanoma, particularly in evaluating tumor thickness of Breslow more precisely.

Animals↗
PubMed2002

Radiotherapy of skin tumors.

The incidence of cancers of the skin is increasing, as is life expectancy among most of the population. Besides surgery, all skin cancers can be treated with radiotherapy, with excellent results. Unfortunately, both less training and less equipment are available than earlier, which means that dermatologists also have less experience in this field. We would like to propose radiotherapy for medium-sized or larger lesions, especially on the face in elderly people. Good indications are keratoacanthomas, extensive actinic keratoses, Bowen's disease including erythroplasia of Queyrat, basal cell and squamous cell carcinomas, but also lentigo maligna and lentigo maligna melanomas. These tumors can be treated in a curative way. Excellent results of palliative X-ray therapy are achieved in Kaposi's sarcoma and in lymphomas, and also in Merkel cell tumors. After 100 years of treatment of skin cancers by radiotherapy, dermatologists should not forget that if appropriate principles are followed and precautions are taken, X-ray treatment is still a safe and effective method.

Dose Fractionation, Radiation↗
PubMed1994

Effects of water-borne cadmium on the skin of the common carp (Cyprinus carpio).

The skin of carp, Cyprinus carpio, was studied at the ultrastructural level after exposure of the fish to low and high concentrations of cadmium in the water (22 and 560 micrograms/L, respectively) for different periods. The effects of the low concentration of cadmium were similar to those of the high concentration, although they appeared later. The basal lamina and the skin surface became highly undulating. Chloride cells appeared between the pavement cells. Necrotic pavement cells were seen from the first day on, while apoptotic pavement cells appeared after several days. Filament cells contained many electron-transparent and electron-dense secretory vesicles. Mitotic cells were commonly seen, mainly in cells adjacent to club cells or close to the epidermal surface. Mucous cells differentiated close to the skin surface. They became elongated and synthesized highly electron-dense mucosomes. The epidermis became infiltrated by many leucocytes. As the experiment progressed, many leucocytes degenerated, and their remnants were found within macrophages and club cells. Fibroblasts displayed intense synthesis and, in fish from the low cadmium concentration, deposited a dense network of collagen fibers in the dermis. Melanosomes were located in the extensions of melanocytes. In these cells aggregation of melanosomes and apoptotic processes were common. Several of these changes were observed earlier under the impact of stressors other than cadmium. Some changes, such as the appearance of tumorlike bodies at the skin surface, the appearance of Merkel cells throughout the epidermis, and the coupling of leucocytes, may be specific for cadmium.

Animals↗
PubMed2003

Immunohistochemical detection of the human herpes virus 8 (HHV8) latent nuclear antigen-1 in Kaposi's sarcoma.

AIMS: The molecular genetics of the human herpes virus 8 (HHV8) has now been characterised and the virus appears to be important in the pathogenesis of Kaposi's sarcoma (KS). This study attempts to determine the rate of HHV8 infection in KS in an Australian cohort. METHODS: Routine streptavidin-biotin-peroxidase immunostaining with diaminobenzidine was performed on paraffin-embedded archival tissues of 37 KS cases using a murine monoclonal antibody directed against the C-terminus of the latent nuclear antigen-1 molecule of HHV8 (clone 13B10; Novocastra) at 1:50 dilution. RESULTS: Positive HHV8 nuclear staining was detected in the nuclei of the spindle cells and endothelial cells of the vascular channels in about 78% (29/37) of all cases. HHV8 staining was absent in the non-neoplastic vessels in the adjacent tissue (P=0.0001, chi(2)=44.46; chi(2)-test with continuity correction) and the negative control cases of Merkel cell carcinoma (P=0.02, chi(2)=5.07; chi(2)-test with continuity correction). HHV8 staining was detected in 80% (8/10 cases) of the patch stage, 88% (7/8 cases) of the plaque stage and 74% (14/19 cases) of the late stage. No significant difference was found between HHV8 positivity and HIV status, age, gender, tumour recurrence, multiplicity or site of the lesions. CONCLUSIONS: The latent nuclear antigen-1 of HHV8 can be detected by immunohistochemistry in the majority of human KS lesions, raising the possibility of its future potential use as an adjunct for the diagnosis of KS in problematic cases.

Antibodies, Monoclonal↗
PubMed1977

Electron microscopy of cutaneous nerves and receptors.

Recent ultrastructural observations on the connective tissue sheaths of nerves, Schwann cell-axonal relations, and nerve terminals and receptors are reviewed. It seems likely that endoneurial collagen is formed by perineurial cells during development and postnatally. New observations on "collagen pockets" are presented. Attention is drawn to freeze-fracture studies of peripheral nerve, particularly in relation to junctional complexes associated with compact myelin, and further application of the technique is considered. Current views on Merkel cells, encapsulated endings, and free nerve terminals are discussed.

Animals↗
PubMed1985

Canine neuroendocrine carcinoma. A tumor resembling histiocytoma.

The clinical and light- and electron microscopic features of 20 cases of canine neuroendocrine carcinoma, initially classified as atypical histiocytomas, are reported. The locally expansile well-circumscribed dermal tumor nodules were composed of solid masses of cells with high mitotic index and multinucleation, arranged in a trabecular pattern with prominent fibrovascular connective tissue stroma rich in reticulin fibers that outlined compact cell nests. Ultrastructural studies revealed evenly dispersed chromatin, focally indented nuclei and abundant cytoplasm with perinuclear filaments, membrane-bound dense core granules, and prominent interdigitating plasma membrane projections with primitive intercellular junctions. Clinical and pathological comparisons between canine neuroendocrine carcinoma, canine histiocytomas, and human Merkel cell neoplasms are discussed.

Age Factors↗
PubMed2001

Cytokeratins as markers of follicular differentiation: an immunohistochemical study of trichoblastoma and basal cell carcinoma.

Trichoblastoma(s) (TB) are benign neoplasms of follicular differentiation frequently found in nevus sebaceus. Many morphologic features are shared with nodular basal cell carcinoma(s) (BCC), sometimes rendering the differential diagnosis difficult. Because both neoplasms can simulate components of mature hair follicles histologically, we attempted to corroborate this by immunohistochemical examination of cytokeratins and hair keratins differentially expressed in the hair follicle. Trichoblastoma(s) and BCC showed homogenous expression of CK14 and CK17. The innermost cells of the tumor nodules in all TB and in 72% of BCC were positive for CK6hf. Using a specific CK15 antibody, 38% of TB showed a focal labeling and all BCC remained negative; 70% of TB and 22% of BCC expressed CK19. CK8 was expressed by numerous Merkel cells present in all TB but in none of the BCC examined. All type I and II hair keratins tested, (especially hHa1, hHa5, and hHa8) remained negative in all tumors examined. Trichoblastoma(s) and BCC show consistent expression of CK6hf, CK14, and CK17; variable expression of CK15 and CK19; and absence of hair keratins. This indicates a differentiation toward the outer root sheath epithelium or the companion layer and not toward the inner root sheath, matrix, or cortex.

Biomarkers, Tumor↗
PubMed2006

Primary cutaneous signet ring cell carcinoma expressing cytokeratin 20 immunoreactivity.

Primary cutaneous signet ring cell carcinoma (PCSRCC) is a very unusual but distinctive clinicopathologic entity that can simulate metastatic adenocarcinomas. It is defined as a diffuse malignant epithelial neoplasia localized in the dermis and subcutis without epidermal involvement, showing variable amounts of signet ring cells, without evidence of visceral adenocarcinoma. We present 2 cases of PCSRCC, which involved eyelids and axilla respectively. Despite thorough systemic workup, primary sources could not be demonstrated in either case. The tumor cells are positive for gross cystic disease fluid protein 15 in addition to a variety of glandular markers. Furthermore, both cases were immunostained with cytokeratin 20 (CK20). In conclusion, we report 2 cases of PCSRCC expressing CK20 immunoreactivity. CK20-positive primary cutaneous tumors should include PCSRCC in addition to Merkel cell carcinoma.

Aged↗
PubMed2002

Caruncle tumor as the first sign of metastatic lung carcinoma.

PURPOSE: Report of a neuroendocrine carcinoma of the caruncle as the first sign of a metastatic lung carcinoma. DESIGN: Interventional case report. METHODS: Excision of a rapidly growing caruncular tumor in a 76-year-old woman with a history of breast cancer. RESULTS: Pathology revealed a large cell neuroendocrine carcinoma, consistent with metastatic lung carcinoma. Computerized tomography of chest, abdomen, and a bone scan disclosed signs of malignancy in the lungs, liver, and bones, originally considered as metastatic breast cancer. However, this diagnosis was excluded on the basis of histopathological findings and clonality analysis. A primary neuroendocrine (Merkel cell) carcinoma was ruled out on morphologic and immunohistochemical grounds. CONCLUSION: We present a unique case of a metastatic large cell neuroendocrine carcinoma of the caruncle.

Aged↗
PubMed1991

Molecular diversity of cytokeratins: significance for cell and tumor differentiation.

Normal and transformed epithelial cells are characterized by the expression of a distinct class of intermediate filaments (IFs), the cytokeratin (CK) filaments. Their constituents, the CKs, comprise a complex multigene family of related proteins which can be subdivided into two sequence types (I and II). In the various epithelial cell types (excluding trichocytes), 19 different CK polypeptides (CKs 1-19) have been distinguished until recently. An additional cytoskeletal polypeptide of Mr 46,000 has been detected, by gel electrophoresis and by immunocytochemistry, in certain types of epithelia including gastric foveolar epithelium, small and large intestinal epithelium, urothelium, and epidermal Merkel cells. On the basis of its biochemical properties and considerable sequence homologies with several type I CKs, this new cytoskeletal protein is suggested to be included in the catalogue of human CKs as CK 20. The various CK polypeptides, as detected by gel electrophoretic and/or immunocytochemical analysis, are expressed in different epithelia and carcinomas in various combinations in a differentiation-dependent manner. Moreover, co-expressions of CKs with other IF classes (vimentin, neurofilaments, glial filaments) are also characteristic of certain epithelial differentiation lineages. Both non-neoplastic epithelial alterations as well as malignant transformation may result in similar modifications of the IF expression profiles although there is a considerable tendency of conservativity. In several instances, a reduced degree of differentiation is paralleled by an increased complexity of the IF protein pattern. CK (and IF) typing can be successfully used in the tracing of developmental lineages as well as in the histological differential diagnosis of primary and metastatic carcinomas. Certain CK polypeptides (CKs 5, 6, 14, 16, 17) identify squamous cell carcinomas including poorly differentiated ones, while other CKs, including CK 20, are typical of primary and metastatic urothelium-derived carcinomas. Among simple-epithelial tumors, CK analysis is of potential diagnostic value in the distinction of mesotheliomas from adenocarcinomas, the discrimination of different carcinomas within the gastrointestinal tract, and the distinction of certain gastrointestinal carcinomas from other adenocarcinoma types including breast and lung carcinomas. Among the individual CKs, CKs 5, 7, 13, 14, 19, and 20 appear to be particularly useful for diagnostic purposes. An important task in the future will be the development of additional monospecific CK-antibodies, particularly such which work on routine paraffin sections.

Cell Differentiation↗