Library

Notes: A 64-year-old man presented with a bullous eruption which clinically and histopathologically resembled dermatitis herpetiformis. However, direct immunofluorescence analysis showed IgG deposits at the basement membrane zone, indicating a relationship with bullous pemphigoid or epidermolysis bullosa acquisita. Indirect immunofluorescence studies on salt-split skin showed binding of IgG mainly on the dermal side of the blister. Immunoblot analysis revealed a novel 200 kDa dermal antigen that could be associated with a major pathogen in this blistering a disease. The histopathological similarity to dermatitis herpetiformis and the immunofluorescence findings indicating bullous pemphigoid or epidermolysis bullosa acquisita seem typical of a distinct subepidermal blistering disease characterized by this 200 kDa antigen. However, the pathogenetic role of autoantibodies against this antigen should be further elucidated before confirming whether this case represents a novel subepidermal blistering disease or a special variant of bullous pemphigoid.

Notes: Patients with melanoma metastatic to the skin show variable prognosis. Though some may survive for quite a long time, some die of disseminated disease within 1 year of removal of cutaneous metastases. The aim of this study was to find out whether there are any histological criteria indicating particular poor outcome. Clinical and histological features of 344 melanoma lesions metastatic to the skin were assessed and their prognostic relevance was investigated. H&E stained histological slides were scanned for the presence of morphological criteria expressing certain tumor cell - stroma interactions: capsule formation (CAPSULE), formation of intratumoral septa (NEWSEPTA), simple invasion between collagen of reticular dermis (DERM-SIMPLE), or subcutis (SCSIMPLE), preservation of preexistent collagen (PRECOLL) or fatty tissue (PREFAT) and, finally, histological site of metastasis. Additionally, anatomical location of the metastases, time between removal of primary tumor and metastases, age and sex of patients were recorded. The metastases were divided into two groups: lesions of patients who died within 1 year after resection (n=59) and lesions from patients with a longer survival (n=285).Metastases which were associated with death within one year were significantly more often found in male patients (54.2% versus 34.7%), in younger patients (mean age 51.1±14.1 years versus 58.8 ± 15.3 years), had developed earlier after the primary tumor (mean time of 21.7±19.9 months versus 43.3±27.4 months) and were more often found at distant sites than in localregional sites (45.7% versus 30.5%), and were more often involved in the subcutis (74.5% versus 56.1%). From a histological point of view, DERMSIMPLE (80% versus 46%; p〈0.001) and PRECOLL (82.8% versus 57.6; p〈0.01) were more frequent in metastases of poor outcome. The same was true for SCSIMPLE (50% versus 25.6%; p〈0.01) and PREFAT (68.1% versus 46.8%; p〈0.05) in lesion with subcutaneous growth, whereas CAPSULE (54.5% versus 75%) was less frequently seen.In conclusion, melanoma deposits metastatic to the skin with particular poor outcome differ clinically and histologically from other cutaneous melanoma metastases. This should be taken into account in the design of therapeutic clinical trials.

Notes: The distribution of OKM 5-positive dendritic cells in the epidermis was investigated in 75 cases of inflammatory dermatoses and in 14 cases of normal human skin by immunohistochemical and morphometric methods. Furthermore 6 cases of normal human skin, 14 cases of nevocellular nevi, 26 cases of malignant melanoma, 7 cases of contact dermatitis and 6 cases of mycosis fungoides have been examined with special emphasis on the expression of OKM 5 antigen on keratinocytes. OKM 5-positive dendritic cells were present in normal human epidermis at a density of 46 ± 3.4 cells/mm2section area. However, there was a significant increase in cutaneous drug eruptions (166±17.2 cells/mm2; U-test: p 〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:03036987:CUP60:les" location="les.gif"/〉 0.05). Concerning OKM 5-positive keratinocytes, a mean percentage of 10.2%± 5.0% OKM 5-positive keratinocytes was found in nevocellular nevi, compared to 0.5%± 0.5% in the adjacent skin. The corresponding values for malignant melanomas were 52.5%± 3.4% (lesional epidermis) and 7.1%± 2.2% (adjacent epidermis). There were significant differences of both lesional and adjacent epidermis between nevi and melanomas (U-test: p 〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:03036987:CUP60:les" location="les.gif"/〉 0.05). Our cases of contact dermatitis revealed a mean percentage of 19.3%± 6.7% OKM 5-positive keratinocytes, whereas in mycosis fungoides the corresponding value represents 42.7%± 6.2%. The differences between the percentage of OKM 5-positive keratinocytes in normal epidermis and contact dermatitis as well as mycosis fungoides were significant (U-test). These 2 different distribution patterns of OKM 5 antigen, namely OKM 5-positive dendritic cells in the epidermis and OKM 5 expression on keratinocytes, may further contribute to the immunologic role of the epidermis.

Notes: Morphometry was carried out on H & E stained paraffin sections of 29 cases of contact dermatitis (CD) and 35 cases of mycosis fungoides (MF) (patch stage 12; plaque stage 11; tumor stage 12); 9 nuclear parameters, mean thickness of the infiltrate and 5 stereological parameters were assessed for each slide. Application of a non-parametric discriminant analysis (k-nearest neighbour method) which is based on median of nuclear areas, mean maximal nuclear diameter, volume density and numerical density of nuclei provided discrimination between CD and patch stage MF at an efficiency of 82.9% (specifity 86.7%, sensitivity 61.5%). Efficiency of discrimination between CD and plaque stage was 92.5% (specifity 89.7%, sensitivity 91.7%) and between CD and tumor stage 100% when discriminant analysis was based on the mean thickness of the infiltrate. Although unequivocal discrimination between CD and MF cannot be achieved in each individual case, morphometry on routine paraffin material obviously provides additional objective criteria for the diagnosis of early MF.

Notes: In the majority of human cells the transferrin receptor (TFR) plays an important role by mediating the cellular iron uptake. The TFR is especially expressed by proliferating cells and has been found in high amounts in malignant tumors. The distribution of the TFR in frozen sections of 89 skin biopsies of normal skin and of various cutaneous tumors was investigated using an anti-TFR monoclonal antibody (OKT9) and a 3-step immunoperoxidase method. Our results indicate that in normal human skin the TFR shows a characteristic microanatomical distribution in the basal cell layer correlated to the architectural pattern of the dermal-epidermal interface. In cutaneous lymphomas of high grade malignancy the TFR was expressed in virtually all cells compared to only 25–75% in low grade lymphomas. Malignant melanomas were strongly positive in the whole tumor tissue, whereas benign melanocytic nevi were largely negative. Obviously the immunohistochemical demonstration of the TFR may serve as prognostic indicator or diagnostic aid, respectively.

Notes: Summary Epstein-Barr virus (EBV) is a gamma DNA herpes virus which is thought to play a part in the pathogenesis of some non-Hodgkin's lymphomas in individuals with or without immunodeficiency. We investigated 16 lymph nodal and 12 cutaneous anaplastic large cell lymphomas (ALCLs) (Ki-1 +), all of which were in patients without immunodeficiency, for the presence of EBV genomes. The highly sensitive polymerase chain reaction (PCR) technique was employed for detection of viral DNA in extracts from formalin-fixed, paraffin-embedded tissue sections. In addition, we performed radioactive and non-radioactive in situ hybridization (ISH) for localization of EBV at the single cell level. EBV-DNA was demonstrated by PCR in five cases of nodal ALCLs (31 %). All cutaneous ALCLs were negative. EBV-encoded small nuclear RNAs (EBERs) could be identified by ISH in the tumour cells of one of the five EBV-DNA-positive patients. Our results further support the concept that EBV may be involved in the development of a proportion of nodal ALCLs, hut not in cutaneous ALCLs.

Notes: A series of 25 cutaneous B-cell lymphoid proliferations was analyzed for the presence of the (14;18) translocation using the polymerase chain reaction, functional sequences of rearranged chromosomes 14 and 18 were amplified in vitro, and t (14;18) specific sequences were detected in 1 of 14 primary cutaneous B-cell lymphomas, in 1 of 14 primary nodal B-cell lymphomas and in none of 3 B-cell pseudolymphomas. These results indicate that the t (14;18) may occur in a small subset of primary cutaneous lymphoma. However, the difference in incidence of the t (14;18) between primary nodal and primary cutaneous lymphomas suggests that different molecular mechanisms are involved in the pathogenesis of these lymphomas.

Notes: A 47-year-old patient with the previous history of a giant cell tumor of the left femur presented with 3 cutaneous nodules located on the face. Histologic examination revealed skin metastases of a giant cell tumor of bone, with dermal and subcutaneous nodules characterized by multinucleate giant cells and mononuclear cells. The patient died 10 months later from widespread metastases to the lung and brain. A panel of enzymoand immunohistochemical markers reactive with osteoclastic, fibroblastic and histiocytic determinants was tested on the cutaneous lesions. The results indicated osteoclastic lineage of the multinucleate giant cells whereas the mononuclear cells showed features of fibroblastic differentiation. Cutaneous metastasis from a giant cell tumor of bone is an extraordinary event and so far has only been reported once.

Notes: Confocal laser scanning microscopy (CLSM) is a new optical microscopic technique, which offers significant advantages over conventional microscopy. CLSM is microscopy of optical sections. Light, which is emitted from regions other than the focal plane, is cut off by introducing a diaphragm in the beam path. The result is an optical “slice”, which shows more details because the blurring from out of focus haze disappears. It has been repeatedly used in experimental, but also in diagnostic dermatopathology. The “in vivo” confocal microscopy, applied directly to the intact skin provides details of living cells in the superficial layers comparable to that of fixed and stained tissue. While the extent of its future applications is hard to predict, its potential for applications in dermatology appears enormous, particularly for studies of fixed or living tissues, where it is desirable to obtain clear images many micrometers below the surface of the tissue under examination.