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PubMed1999

Expression and localization of thymidine phosphorylase/platelet-derived endothelial cell growth factor in skin and cutaneous tumors.

Thymidine phosphorylase/platelet-derived endothelial cell growth factor (TPase/PD-ECGF) is a catabolic enzyme that has been shown to be chemotactic for endothelial cells in vitro and angiogenic in vivo. TPase/PD-ECGF expression is increased in a variety of tumors. In the skin, TPase is active in normal keratinocytes in vitro and in vivo. Our objective was to study the expression and localization of TPase/PD-ECGF by immunohistochemical analysis in normal skin and cutaneous tumors and to correlate this information with enzymatic activity of TPase. TPase/PD-ECGF expression was observed in keratinocytes with intense staining of the infundibulum of hair follicles but no staining of hair bulbs. Expression localized primarily to the nucleus of keratinocytes in the basal layer but was more intense and cytoplasrmic in suprabasal keratinocytes. Increased expression of TPase/PD-ECGF in differentiated cells was confirmed by in vitro studies of TPase activity. In cutaneous tumors, there was positive staining for TPase/ PD-ECGF in squamous cell carcinomas (10/10), eccrine poromas (3/4), eccrine syringomas (4/4), trichoepitheliomas (1/3), and tumors of the follicular infundibulum (2/3) and melanomas (5/8). There was no staining of any intradermal nevi (0/2), basal cell carcinomas (0/10) or Merkel cell carcinoma (0/1). We conclude TPase/PD-ECGF is found throughout the epidermis and its expression increases with differentiation of keratinocytes. In cutaneous tumors, expression of TPase/PD-ECGF may be linked to the cell of origin of the tumor as well as the tumor's degree of differentiation.

Antibody Specificity↗
PubMed1998

Merkel complexes of human digital skin: three-dimensional imaging with confocal laser microscopy and double immunofluorescence.

Three-dimensional (3-D) reconstruction of images provided by confocal scanning laser microscopy (CSLM) is a powerful tool in a morpho-functional approach to cutaneous innervation studies. To investigate mechanoreceptors in the hand, a study of Merkel complexes was performed in human finger. A double fluorescent-conjugated immunolabeling with antibodies against neurofilament (NF 200) and cytokeratin (CK 20) on floating, thick cutaneous samples (80 to 100 microm), was used. After acquisition of serial optical planes by CSLM, reconstruction was performed with 3-D reconstruction software tools. Merkel cells were clearly labeled with CK 20, whereas nerve components were only NF 200 reactive. The cells, localized on the basal lamina of the epidermis, were usually arranged in clusters of five to eight cells. Each cell was connected to a nerve process ramification originating from a unique fiber. Quantitative data, compiled from a sample of 25 Merkel complexes, gave a mean cell diameter of 13 +/- 1 microm and a mean nerve fiber size of 3 +/- 1 microm. Surface measurements were done on a single reconstructed cluster with a mean and standard error which only refers to the optical 3-D resolution. It gives a surface of 12 +/- 1 microm2 for the contact zone between cell and nerve fiber and a cluster area of about 500 microm2. The great precision of reconstructed images provides a detailed analysis of spatial relationships between abutting nerve fibers and Merkel cells. Data interpretation is improved with complementary ultrastructural and physiological studies results, and this allows an accurate investigation of cutaneous sensory endings.

Antibodies↗
PubMed2004

Cutaneous findings in chronic lymphocytic leukaemia.

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is a malignancy characterized by clonal expansion of B lymphocytes with distinct morphology and immunophenotype. The dermatological literature relating to CLL is sparse. A global descriptive survey of a large number of CLL patients has not previously been published. OBJECTIVES: To report the spectrum of dermatological conditions seen in a large series of CLL patients. METHODS: Skin complications in patients with established CLL were identified retrospectively from clinical and photographic records, principally a database of over 750 consecutive cases. These events were classified, enumerated and compared. RESULTS: Forty patients with 125 skin manifestations were identified and studied. Forty-one manifestations had documented clinical or histological atypia. In 21 of these 41 complications there had been no prior immunosuppressive therapy. We observed that cutaneous malignancies frequently presented atypically both clinically and histologically. There were 18 patients with 56 instances of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), and clinical atypia was more common with SCC than with BCC. Other cutaneous findings included varicella zoster (n = 6), leukaemia cutis (n = 3), acute graft-versus-host disease (n = 5), cutaneous drug eruptions (n = 9), multiple warts (n = 3), herpes simplex (n = 3), cutaneous T-cell lymphoma (n = 2), eosinophilic folliculitis (n = 2), malignant melanoma (n = 2) and Merkel cell tumour (n = 2). CONCLUSIONS: We have identified a range of dermatological conditions in CLL patients, with a tendency to atypical presentations. The atypia was independent of prior chemotherapy.

Acute Disease↗
PubMed2005

UV-induced skin cancer: similarities--variations.

Skin cancer, the most common cancer world wide, encompasses different tumor entities, the keratinocyte-derived basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) as well as the neuroectodermal malignant melanoma (MM) and the neuroendocrine Merkel cell carcinomas (MCC). While knowledge is significantly increasing about genetic changes contributing to BCCs and MMs, our understanding for the development and progression of SCCs and MCCs is still fragmentary. This review, thus, aims, on the one hand to summarize the present knowledge without claiming completeness and, on the other hand, to provide information on the HaCaT in vitro skin carcinogenesis model that is used to evaluate the functional consequence of genetic aberrations believed to play a role in skin cancer development and progression.

Basal Cell Carcinoma↗
PubMed2004

Lymphatic mapping for staging of head and neck cancer.

Lymphatic mapping with sentinel lymph node (SLN) biopsy can accurately stage the nodal basins in patients with melanoma of the trunk and extremities and has become a routine, well-accepted diagnostic method for melanoma at these anatomic locations. Melanoma of the head and neck (16% of all cases of melanoma) is complex and difficult to manage because of the rich abundant interlacing lymphatic drainage patterns, as well as watershed areas, which can lead to unusual and unexpected drainage patterns. Radioguided surgery in combination with blue dye facilitates localization of the SLN in the head and neck; however, this type of radioguided surgery is an evolving technique of some difficulty and thus requires careful coordination among the surgeon, nuclear medicine physician, and pathologist. Applications of this technique to other sites in the head and neck are currently being investigated for conditions including squamous cell carcinoma (SCC) of the oral cavity, thyroid cancer, and Merkel cell cancer. More studies of patients with head and neck cancer are needed--and technical issues must be resolved--before radioguided surgery can be recommended as the standard of care for these patients.

Carcinoma, Merkel Cell↗
PubMed1998

Diagnosis and differential diagnosis of small-cell lesions of the liver.

The objective of this study was to evaluate the cytologic spectrum of small cell lesions of liver as diagnosed by fine-needle aspiration (FNA). Of 304 FNAs of liver that were performed in our institution between 1990 and 1994, 29 were classified as small-cell lesions. The final diagnoses were as follows: small-cell undifferentiated carcinoma (10), neuroendocrine carcinoma (9), cloacogenic carcinoma (1), Merkel-cell carcinoma (1), cholangiocarcinoma (1), metastatic adenocarcinoma (4), small-cell sarcoma (1), lymphoma (2). Relevant clinical history and immunocytochemistry were helpful in making the final diagnosis in some cases. The diagnosis and differential diagnosis of small cell lesions of the liver are discussed in detail in this report.

Adenocarcinoma↗
PubMed1996

Excision of selected skin tumours using Mohs' micrographic surgery with horizontal paraffin-embedded sections.

Histological interpretation of frozen sections made during Mohs' micrographic surgery may be difficult, depending on the morphological and staining characteristics of the tumour and on the nature of the associated inflammatory infiltrate. We have employed an adaptation of micrographic surgery in which horizontal, formalin-fixed, paraffin-embedded sections were used to improve histological assessment in the excision of 18 non-melanoma skin tumours in which frozen sections had been or were likely to be unsatisfactory. We describe our experience of this method in the management of squamous cell carcinomas (11), extramammary Paget's disease (two), microcystic adnexal cell carcinomas (two), dermatofibrosarcoma protuberans (two), and primary cutaneous neuroendocrine carcinoma (Merkel cell carcinoma) (one). The use of horizontal paraffin-embedded sections lengthens the duration of the procedure but facilitates accurate assessment of histological sections in selected tumours.

Adult↗
PubMed2000

Immunohistochemistry of small round-cell tumors.

The term "small round-cell tumor" describes a group of highly aggressive malignant tumors composed of relatively small and monotonous undifferentiated cells with high nuclear to cytoplasmic ratios. This group includes Ewing's sarcoma (ES), peripheral neuroepithelioma (aka, primitive neuroectodermal tumor or extraskeletal ES), peripheral neuroblastoma ("classic-type"), rhabdomyosarcoma, desmoplastic small round-cell tumor, lymphoma, leukemia, small-cell osteosarcoma, small-cell carcinoma (either undifferentiated or neuroendocrine), olfactory neuroblastoma, cutaneous neuroendocrine carcinoma (aka, Merkel-cell carcinoma), small-cell melanoma, and mesenchymal chondrosarcoma. Their clinical presentations often overlap, thus making a definitive diagnosis problematic in some cases. Yet, a clear understanding of their clinicopathologic features usually allows for a confident diagnosis, especially if immunohistochemistry is used. The following is a review of the immunohistochemistry of this small round-cell tumor group.

Biomarkers, Tumor↗
PubMed2006

Pax-5 immunoexpression in various types of benign and malignant tumours: a high-throughput tissue microarray analysis.

BACKGROUND: Pax-5 belongs to the Pax gene family transcription factors that play an important role in organogenesis and in B cell ontogeny. It is expressed in B cell non-Hodgkin's lymphoma (B-NHL), Hodgkin's lymphoma (HL) and neuroendocrine carcinomas. However, its expression in other tumour types is not fully explored. AIMS AND METHODS: To determine Pax-5 expression in other tumour types, immunohistochemistry was performed on 3758 benign and malignant tumours using multiple tumour microarrays, as well as on whole sections. RESULTS: Pax-5 was expressed in 108/118 (91.5%) B-NHLs, in 60/70 (85.7%) HLs and in 0/7 T cell lymphomas. In addition, Pax-5 was seen in 24/34 (70.6%) Merkel cell carcinomas, 42/53 (79.2%) small cell carcinomas, 1/164 (0.6%) breast carcinomas, 2/204 (1%) endometrial adenocarcinomas and 1/452 (0.2%) urothelial carcinoma of the bladder. CONCLUSION: Despite its expression in a small subset of malignancies of epithelial origin, Pax-5 is still a good and reliable immunomarker in diagnosing B-NHL, HL and neuroendocrine carcinomas.

Biomarkers, Tumor↗