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Basal cell carcinoma (BCC) of the skin is a locally invasive, rarely metastasizing epithelial tumor. In the current study, the expression of E-cadherin, alpha- and beta-catenin and CD44V6 in normal epidermis and on BCC cells were investigated. A significantly reduced expression of alpha-catenin and CD44V6 and a slightly reduced expression of E-cadherin on BCC cells were observed compared with the overlying epidermis. Immunoelectron microscopy was used to investigate whether the decreased expression of E-cadherin and CD44V6 was due to either an absence or downregulation of specific membrane structures or due to an overall downregulation of these adhesion molecules in all membrane structures in BCC. E-cadherin and CD44V6 were expressed in adherens junctions, desmosomes, and complex interdigitating membrane structures both in normal epidermis and in BCC. A quantitative analysis showed that only a percentage of desmosomes was stained. In addition, the effect of pro-inflammatory cytokines, such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), was investigated in biopsy specimens of normal skin and BCC, using a biopsy culture system and immunohistochemistry. The expression of E-cadherin and CD44V6 was not significantly decreased after culturing BCC or normal skin biopsy specimens for 48 hours with or without recombinant human (rHu)IFN-gamma or rHuTNF-alpha. It may be concluded that the decreased expression of both E-cadherin and CD44V6, observed in light microscopy, was not attributable to the absence of specific specialized structures in BCC and most likely also not caused by downregulation by local cytokines, but rather by generic downregulation of both of these adhesion molecules during malignant transformation.

Basal cell carcinomas (BCCs) of the skin show varying degrees of peritumoural inflammatory infiltrate consisting mainly of T cells, but lack an effective T-cell-mediated immune response. This may be caused by the absence of the major histocompatibility complex (MHC) class I and II antigens, intercellular adhesion molecule-1 (ICAM-1), CD40 and CD80 (B7.1). Interferon-gamma (IFN-gamma) is known to induce or up-regulate their expression on epithelial cells, whereas interleukin-10 (IL-10) down-regulates their expression. The induction and up-regulation of HLA-ABC, HLA-DR, ICAM-1, CD40, and CD80 in BCC and normal skin from BCC patients were investigated in a culture system using recombinant human IFN-gamma (rHuIFN-gamma). The levels of IL-10 were determined in the supernatants after culture. The results showed that only ICAM-1 expression was significantly up-regulated on BCC cells. However, in the normal epidermis of BCC patients and in the epidermis overlying the tumour nests, significant up-regulation of ICAM-1, and CD40, and CD80 and slight up-regulation of HLA-DR were observed. No changes in HLA-ABC expression were observed in either normal skin or BCC. High levels of IL-10 were present in the supernatants of BCC biopsies after culture. It may be concluded that it is highly likely that the presence of IL-10 in BCC is directly or indirectly responsible for the complete lack of expression of HLA-DR, ICAM-1, CD40 and CD80 and the inconsistent expression of HLA-ABC on BCC cells in situ and may be a way of escaping immune survillance.

Background: Systemic hyalinoses are genetic generalized fibromatoses characterized by an accumulation of hyalin in the dermis. Two distinctive syndromes are recognized in the literature: infantile systemic hyalinosis (ISH) and juvenile hyaline fibromatosis (JHF). ISH and JHF are sometimes difficult to separate since they show significant overlap., Observations: We report on 3 children from two unrelated families suffering from JHF. The first child is severely handicapped by joint contracture, massive hyperplasia of the gingivae, diffuse skin papules and subcutaneous nodules occupying the scalp, face, perianal area, palms, soles and chest. At the same age, the second child only shows pearly skin papules on the face, groin and perianal area and gingival hyperplasia without joint stiffness or any other subjective complaint. The third patient, a brother of the second child, developed mild skin abnormalities by the end of the first year. The occurrence in siblings and consanguinity in the second family suggests autosomal recessive inheritance. Histological skin examination in the 3 cases showed hyaline deposition in the dermis and abnormal ultrastructure of fibroblasts. Biochemical findings showed mucopolysaccharide abnormalities in both families., Conclusion: Our patients do not only illustrate the different expressions of JHF but also show some overlap with ISH, suggesting a common cause for both disorders. Genetic studies will finally answer this question.

A large Dutch family had been known for many years to be affected with skin tumours labelled as adenoma sebaceum, which were inherited in an autosomal dominant fashion. Since this skin sign is considered pathognomonic for tuberous sclerosis complex, the condition in the family was labelled accordingly, in the absence of further clinical features of tuberous sclerosis complex-like mental retardation or epilepsy. The skin changes started at early puberty with small eruptions around the nose and progressed to larger tumours, with considerable variation in severity. Some affected members had required plastic surgical reconstruction following excision. Linkage analysis in this family was performed for the two chromosomal regions involved in tuberous sclerosis complex on chromosomes 9q34 and 16p13, but no positive linkage was found. On critical re-evaluation of the clinical and pathological data and renewed assessment, the working diagnosis was changed to autosomal dominant cylindromatosis. The recently published candidate region for cylindromatosis on chromosome 16q12-13 was subsequently proven to be positively linked with a lod score of 3.02 with marker D16S308. Review of pathological specimens confirmed the diagnosis of cylindromatosis. DNA analysis of tumour tissue showed loss of heterozygosity for the cylindromatosis CYLD1 locus. These results confirm the candidate locus for cylindromatosis on chromosome 16q12-13.

The peritumoural inflammatory infiltrate in basal cell carcinoma (BCC) of the skin consists mainly of T lymphocytes which hardly invade the tumour nests. The absence of intercellular adhesion molecule-1 (ICAM-1) on BCC cells may explain the lack of tumour-infiltrating cells and the lack of an active cell-mediated immune response in this tumour. In this study, the induction of ICAM-1 was investigated in BCC biopsies using recombinant human interferon-gamma (rHuIFN-gamma). The expression of interferon-gamma receptors (IFN-gamma R) in the biopsies was also investigated. The results showed that BCC cells expressed ICAM-1 after incubation with rHuIFN-gamma, but to a lesser degree than normal epidermal cells. The levels of shed ICAM-1 were significantly increased in the culture supernatants of tumour biopsies compared with those from normal skin biopsies, after culturing in the presence of rHuIFN-gamma. The expression of IFN-gamma R was significantly decreased on the tumour cells compared with the overlying epidermis. The decreased expression of IFN-gamma R on the tumour cells and the shedding of ICAM-1 into the peritumoural stroma may be a plausible mechanism by which the tumour cells are protected against an active cell-mediated immune response.

The comparative study reported here was undertaken in order to resolve the discrepancies in the detection of cytokeratin (Ck) 8 reported in previous studies. The expression of Ck 8 was compared in 6 basal cell carcinomas (BCCs) using immunohistochemical and immunoelectron microscopic techniques and a panel of 4 different commercially available monoclonal antibodies (MoAbs). The results of this comparative study demonstrated not only that the consistent expression of Ck 8 using one of the MoAbs in immunohistochemistry was confirmed by immunoelectron microscopy, but that the inconsistent expression of Ck 8 observed using two other MoAbs was also confirmed. One of the MoAbs did not show any staining at all. The inability of this MoAb to detect the expression of Ck 8 using either of the techniques also indicated that this MoAb may be directed against an epitope of Ck8 that is not detectable in BCC in situ.

The expression of low molecular weight cytokeratins (Cks) 7,8,18, 18 and high molecular weight cytokeratin 10 in 23 basal cell carcinomas (BCCs) was investigated using a panel of 14 different commercially available monoclonal antibodies (MoAbs) with specific anti-cytokeratin activity. Four of these MoAbs were directed against Ck 8. The results showed that Ck 8 was detected in all 23 BCCs using MoAb 4.1.18. Two of the MoAbs showed inconsistent staining for Ck 8 and one of them did not show any staining at all. Cytokeratins 7 and 19 were detected incosistently. Cytokeratins 18 and 10 were not detected in any of the 23 BCCs that were examined. The incosistent observations on the expression of Ck 8 in BCCs in this study could have been due to different epitopes of the different cytokeratins that were detected by the different MoAbs. The results of this study lead to recommendation that whenever possible a panel of different MoAbs directed against the same Ck(s) should be used in order to minimize the risk of obtaining incorrect experimental results.

A 4-year-old boy with subcutaneous tumours is described. These tumours were calcified and had secondary osteoma formation. In addition the patient showed poikiloderma on the face and less prominently on arms and legs. X-ray films of the distal metaphyses of the radius, ulna and tibia revealed irregular mineralisation. Repeated laboratory tests revealed no abnormalities of fat, bone and mineral metabolism. This patient showed a unique combination of symptoms. We propose to call this syndrome: COPS-syndrome (Calcinosis cutis, Osteoma cutis, Poikiloderma and Skeletal abnormalities).

This report deals with the reaction pattern(s) of two monoclonal antibodies (MoAbs) with normal skin and basal cell carcinomas (BCC). Using indirect immunoperoxidase (IIP) and indirect immunofluorescence (IIF) techniques, MoAb 12 G7 was observed to react with a determinant related to the cell membrane of the epidermal basal cells. In the IIP technique MoAb 12 G7 showed a positive reaction with 32 out of 34 BCC (94%), while in IIF all the 14 BCC that were studied were positive. In most cases only the cells at the periphery of the tumour nests were stained. MoAb 253 B7 reacted with cytoplasmic determinant(s) of the epidermal basal cells both in the IIF as well as in the IIP techniques. Using the IIP technique only 5 out of 34 BCC (15%) showed a positive reaction with this MoAb. Four of the 5 positively staining tumours showed aggressive histological features. Using IIF technique only 2 out of 14 BCC were positive. The results presented in this communication are discussed with regard to the possible expression of selective differentiation and tumor-associated determinant(s) in BCC.

We report a case of primary cutaneous adenoid cystic carcinoma in a 75-year-old man. Electron microscopy revealed similar features to those previously described in adenoid cystic carcinomas of salivary gland origin: wide intercellular spaces, pseudocysts containing replicated basement membrane-like material and true lumina lined by cytoplasmic membranes with numerous microvilli. Immunohistochemistry using antibodies to several cytoskeletal proteins (keratins and actin) indicated the presence of two epithelial tumour cell populations, one with the phenotype of myoepithelial cells, lining the pseudocysts and the periphery of the tumour fields, and another with the phenotype of acinar cells of the secretory coil of sweat glands. In addition, the tumour showed immunoreactivity for epithelial membrane antigen, but not carcinoembryonic antigen. A review of the literature on other cases of primary cutaneous adenoid cystic carcinoma showed that this tumour generally affects older patients with a female to male ratio of 4:1. The most common tumour site appears to be the scalp (40%), and the recurrence rate is 50%. Surgical treatment with extensive resection margins is recommended.

A case is described of malignant B-cell lymphoma with scleroderma-like manifestation. Using different monoclonals as B-cell markers the tumor appeared to be positive for surface immunoglobulins (SmIg) and for B2-antigen, but negative for intracytoplasmic immunoglobulin (CIg), BA2- and FMC7-antigens. Therefore, the tumor could be determined as a highly differentiated Sm-positive early B-cell type of B-cell lymphoma. In this clinically rare manifestation of cutaneous B-cell lymphoma aspects of the cell morphology and of cellular mediated immunity are briefly discussed.

A child with segmental neurofibromatosis is reported. The clinical, histopathological and ultrastructural characteristics of this rare condition are described. This entity is considered to be a localized form of von Recklinghausen's disease. The aetiology is not clear, but somatic mutation in early embryonic development may be important.

We report the case of a 30-year-old female patient with non-von Recklinghausen's neurofibromatosis. In our opinion it does not fit within a system of classification recently described. Clinically, the abnormality resembled a giant pigmented nevus; however, light- and electron microscopy findings were consistent with those of a neurofibroma. No other symptoms of classic neurofibromatosis or other diseases were present. The family history showed no evidence of neurofibromatosis. To the best of our knowledge this manifestation of non-von Recklinghausen's neurofibromatosis has not been previously described. The cause and the inheritance pattern of this variant are not clear.

The expression of the low molecular weight cytokeratins (K) 7, 8, 18, 19 and the high molecular weight cytokeratin 10 in 21 basal cell carcinoma (BCC) was studied using seven different monoclonal antibodies (MoAbs) with specific anti-cytokeratin activity. MoAbs RCK 105 (anti-K7), RPN 1164 (anti-low molecular weight cytokeratins of basic group), Ks 19.1 (anti-K19) and Cam 5.2 (anti-K8, K18, K19) reacted positively but inconsistently in the BCC that were examined. MoAbs 1166 (anti-K8) and RGE53 (anti-K18) did not react at all. MoAb RKSE 60 (anti-K10) did not react with the tumor cells. From the results of this study, it can be concluded that cytokeratins 7 and 19 are expressed in BCC (43% and 71%, respectively), whereas cytokeratin 8 is not expressed.

The expression of human leukocyte antigen-DR (HLA-DR) and beta 2-microglobulin on the tumor cells and their correlation (if any) to the degree and the composition of the peritumoral mononuclear infiltrate were studied in 37 basal cell carcinomas from 32 patients with an indirect immunoperoxidase technique. In 36 of 37 basal cell carcinomas (97%) there was no expression of HLA-DR on tumor cells of basal cell carcinoma. In 13 of 37 basal cell carcinomas (35%) beta 2-microglobulin was expressed on the tumor cells. Both a diffuse cytoplasmic and a membrane staining were observed in only six of these 13 basal a diffuse cytoplasmic and a membrane staining were observed in only six of these 13 basal cell carcinomas; in the other seven basal cell carcinomas only a diffuse cytoplasmic staining was observed. In all 37 basal cell carcinomas there was membrane staining for beta 2-microglobulin in the normal epidermis. The intensity of staining in the normal epidermis was always stronger than that in the tumor nests. There was a varying degree of peritumoral immune infiltrate in all basal cell carcinomas. It comprised mainly T cells (mean percentage 57 +/- 15). In the group of patients with basal cell carcinoma with moderate to heavy infiltrate the mean percentage of T cells was 63 +/- 13, which was significantly higher than the mean percentage of T cells (46% +/- 14%) in the group of patients with basal cell carcinoma with a mild infiltrate. This difference was mainly the result of an increase in T helper cells.(ABSTRACT TRUNCATED AT 250 WORDS)