[Necrobiosis lipoidica. Variants on a theme]. / Necrobiosis lipoidica. Kasuistische Vielfalt einer Diagnose.

A 69-year-old patient presented with different skin lesions all of which belonged to group of necrobiosis lipoidica. The initial histologic diagnosis was actinic granuloma O'Brien. A subsequent biopsy was interpreted as granulomatous necrobiosis lipoidica. The history of these necrobiotic variants is reviewed and exemplarily depicted with this case. Necrobiosis lipoidica is part of the spectrum of granulomatous skin disorders. Although its etiology is unclear, an association with diabetes mellitus is often discussed. Multiple therapeutic options exist, but standardized guidelines for treatment are missing.

Clinical histochemical and immunohistochemical investigation of the capillary basal membrane in chronic venous insufficiency.

Present investigations regarding the pathogenesis of chronic venous insufficiency (CVI) are focusing on microvascular changes. The aim of our investigation was to examine the correlation between the thickness of pericapillary type IV collagen depositions, basal membrane alterations and transcutaneous oxygen tension (TcPO2) in CVI-patients. Histochemical and immunohistochemical investigation of the capillary basal membrane was performed on 15 biopsies from normal controls, as well as 30 patients with CVI stage I and III (classification by Widmer & Stähelin). In all subjects TcPO2 was measured just prior to biopsy procedures in exactly the same area where the specimen was subsequently excised. The microscopically measured thickness of the collagen IV layer and the basal membrane was increased significantly in patients with CVI. Specimens from normal controls showed a collagen IV layer thinner than 0.1 micron. Patients with CVI stage III revealed strong collagen IV depositions between 0.2 and 0.3 microns. Comparison between TcPO2 and histological findings in the measured ares showed oxygen pressure varying from 62 mmHg (SEM 4.94 mmHg) in normal controls, down to 13 mmHg (SEM 3.39 mmHg) in patients with thick collagen IV layers. Besides an increased collagen IV layer, microvascular thrombosis and a thickened basal membrane have to be considered for impaired capillary perfusion.

[Subungual keratoacanthoma]. / Subunguales Keratoakanthom.

Subungual keratoacanthomas (SKA) differ in clinical presentation, biological behaviour and the therapy needed from keratoacanthomas in other localizations. Against the backdrop of two personal observations and a review of the literature, the authors describe clinical and histological features and also the differential diagnosis and therapy and this rare benign neoplasm. Patients present with a rapidly growing, painful subungual mass, which causes destruction of the underlying bone and usually does not regress spontaneously. Histological differentiation from squamous cell carcinoma is essential as the prognosis and treatment are different. SKA is treated by local excision and curettage. Erosions of the underlying distal phalanx usually heal spontaneously. However, persistent recurrences after subtotal excision often necessitate amputation of the distal phalanx.

[Radiation sensitivity of the normal bile duct during high dose rate afterloading irradiation with Iridium 192. Experimental studies in pigs]. / Strahlenempfindlichkeit des gesunden Gallengangs bei High-dose-rate-Afterloadingbestrahlung mit Iridium 192. Experimentelle Untersuchungen am Schwein.

This animal study was designed to assess the tolerance of the normal bile duct to a single intraluminal high-dose-rate afterloading irradiation. This information is essential for treatment recommendations in irradiation therapy of malignant bile duct stenoses. In 16 pigs bile duct catheters were inserted surgically. Over these devices single intraductal doses of 7.5 Gy and 15 Gy were applied using an iridium-192 source. After a period of two to three months the bile ducts and the surrounding structures were investigated by means of cholangiography, angiography, and macropathological and histological investigations. A single intraductal dose of 7.5 Gy leads to a slightly scarred shrinkage of the bile duct with sclerosis and obliteration of the capillary vessels. Vasculitis and necrosis of the bile duct wall are still evident three months after irradiation. A single dose of 15 Gy leads to severe lesions with widespread necroses of the bile duct wall which tend to bleed, and result in a high degree of shrinkage of the bile duct. The radiation damage is most prevalent near the papilla and in the narrow segments near the liver. Single intraluminal high-dose-rate afterloading doses of 7.5 and 15 Gy cause significant lesions and complications at the bile ducts. As the intact bile duct is the Achilles heel of intraductal therapy, considerably lower single doses are recommended for a fractioned treatment.

[Cutaneous angiosarcoma after telecobalt irradiation]. / Kutanes Angiosarkom nach Telekobaltbestrahlung.

Cutaneous angiosarcomas are rare neoplasms. They occur most frequently on areas of skin exposed to sunlight in the elderly, or in long-standing lymphoedema (Stewart-Treves syndrome). Radiation is an important aetiological factor. With only 1 exception, the 34 published cases of cutaneous angiosarcoma on the trunk were caused by irradiation of internal tumours, occurring between 4 and 50 years after the irradiation treatment. The prognosis quoad vitam is poor. The tumours should be removed surgically. When they are inoperable, irradiation is an alternative therapeutic option. The aim of this paper is to show the histological differential diagnosis of cutaneous angiosarcomas and to demonstrate problems with the treatment.

[HMB 45 positive balloon cells in combined nevi]. / HMB 45-positive blasige Zellen in kombinierten Nävi.

The combined naevus is made up of two components, one resembling a melanocytic naevus, the other a blue naevus. Clinically, these naevi do not give any obvious cause for concern. Histological examination shows that the combined naevus consists of a superficial melanocytic naevus and a deep-seated spindle cell blue naevus. There is a rare variant in which the pigmented spindle cells of the "blue" naevus are replaced by large balloon cells varying in melanin content. These combined naevi, because of the large cells with abundant cytoplasm, closely resemble malignant melanoma. As a further aid to diagnosis we used the monoclonal antibody HMB 45. In our study, the vesicular cells in all seven combined naevi examined reacted strongly with HMB 45. It is suggested that HMB 45 is not always helpful in differentiating between melanoma and naevi.

[Grzybowski type eruptive keratoacanthomas and ectropion. A therapeutic problem]. / Eruptive Keratoakanthome Typ Grzybowski und Ektropium. Ein therapeutisches Problem.

Eruptive Grzybowski-type keratoacanthoma is a rare variant of multiple keratoacanthoma and is not accompanied by internal malignancies. Up to now only 16 cases of eruptive Grzybowski-type keratoacanthoma have been described in the literature. Eruptive and solitary keratoacanthomas cannot be distinguished histologically. The multiplicity of skin lesions may be due to a genetic background. Our patient presented with multiple eruptive keratoacanthomas, ectropion and a mask-like face. Conservative treatment, e.g. with etretinate, did not lead to any improvement of symptoms in this case. Therefore surgical therapy was recommended for the patient's ectropion.

Immunohistochemical investigation of pericytes in chronic venous insufficiency.

Patients with chronic venous insufficiency show typical glomerulum like alterations of cutaneous capillaries. Objective of this study was to determine any changes of the alignment of pericytes around cutaneous capillaries in CVI patients. Skin biopsies from the area of the medial malleolus were taken from 42 patients with CVI, 5 healthy individuals and 11 cadavers without history of CVI. Sections were stained with HHF35, anti alpha and gamma muscle actin with the avidin-biotin-peroxidase method (ABC) and anti vimentin with the alkaline phosphatase anti-alkaline phosphatase technique (APAAP). The stage of stasis dermatosis was assessed and sections were examined for pericyte changes. Among the collective of 42 patients with CVI, 31 patients showed slight or severe pericyte changes, 11 patients were without changes. None of the sections from cadavers or healthy patients showed any pericyte changes. Pericytes are among other functions possibly involved in microvasculature regulation and wound healing. Thus destruction of the pericyte envelope might lead to microcirculatory dysfunction. This could be one of the causes that lead to leg ulcers in CVI.

Immunohistochemical investigation of dermal capillaries in chronic venous insufficiency.

Skin biopsies from the area of the medial malleolus of 24 patients with chronic venous insufficiency, of 5 patients without signs or history of chronic venous insufficiency and of seven corpses without manifestation of chronic venous insufficiency, were sectioned and stained with hematoxylin and eosin and with Ki-67, a monoclonal antibody expressed in the nuclei of proliferating cells. Hematoxylin- and eosin-stained sections of all specimens were assessed blindly to determine the state of capillary increase in stasis dermatosis. Twenty-four patients were found to have different stages of stasis dermatosis. During the examination of the Ki-67 frozen sections, close attention was paid to the capillary bed of all sections for any Ki-67-positive nuclei in capillary cells. None of the three groups showed positive staining of nuclei in capillary cells. This finding proves that there is no capillary proliferation, but an elongation and distension of the capillaries.

[Cutaneous myofibroma--late manifestations]. / Kutanes Myofibrom--Spätmanifestation.

Infantile myofibromatosis is a rare, but nevertheless well-known, entity that was first described in 1954 in Stout's classic article on juvenile fibromatosis. Usually the tumour mass is noted at birth or during the first weeks of life. Solitary lesions are at least twice as common as multiple lesions. A case of a 17-year-old woman with a tumour macroscopically resembling a basal cell epithelioma is presented. This tumour did not develop until the patient was 17 years old and cannot be distinguished histologically from an infantile myofibroma. Because of the very late appearance of this tumour the term "cutaneous myofibroma" is proposed for it. In young patients with a basal cell epithelioma-like lesion the diagnosis of cutaneous myofibroma has to be considered.

Pericapillary fibrin cuff: a histological sign of venous leg ulceration.

The incidence of pericapillary fibrin cuffs was investigated in 49 biopsies of venous leg ulcers and 67 biopsies of leg ulcers of non-venous etiology. Pericapillary fibrin cuffs were seen in 28 biopsies (57.1%) of venous leg ulcers, but only in 11 biopsies (16.4%) of non-venous leg ulcers. In the venous leg ulcers pericapillary fibrin cuffs occurred predominantly near the ulcer surface and around dilated capillaries. Dilation of the capillaries and inflammation probably contribute more to the pathogenesis of pericapillary fibrin cuffs than venous hypertension.

[ACPA reaction in atypical Wegener's disease. Diagnostic test]. / ACPA-Reaktion bei atypischem Morbus Wegener. Diagnoseweisender Test.

Clinical and biopsy findings in six patients (aged 29-64 years), suspected of having Wegener's granulomatosis, were not diagnostic. Cardinal signs were skin necroses, isolated deficits of cranial nerves, sudden amaurosis, renal failure with shunt sepsis and lung opacities suspicious of tumour. Only positive tests for anti-cytoplasmatic antibodies (ACPA) in serum made the diagnosis and led to appropriate treatment. This simple yet highly specific immunofluorescence test should be performed in every case of vasculitis of uncertain cause, even if typical clinical signs of Wegener's granulomatosis are at first absent.

[Intracavitary high-dose-rate-afterloading-radiotherapy in the esophagus of the pig]. / Intrakavitäre High-Dose-rate-Afterloading-Strahlentherapie im Schweineösophagus.

The tolerance of sound esophageal mucosa to intracavitary high dose rate afterloading contact therapy with unique doses of 6 Gy and 12 Gy, respectively, was investigated in 15 pigs. Whereas no macroscopic or microscopic alterations of the mucosa are found after 6 Gy, a unique application of 12 Gy produces most severe side effects such as vascular occlusion due to fibrosis of the intima, formation of fistulas, and perforations of the esophagus wall. Future investigations will have to aim at the elaboration of schemes for dosage and fractionation.

[Pulmonary changes in AIDS]. / Lungenveränderungen bei AIDS.

We reviewed retrospectively the clinical records of 28 patients with AIDS staged group IV according to CDC-criteria. Among these, 19 had pulmonary disease: most of them (n = 17) had pneumocystis carinii pneumonia (Pcp). 12/17 patients with proven Pcp displayed typical x-ray findings with diffuse perihilar interstitial infiltration sparing lung periphery. 3/17 had atypical features and 2 normal chest x-ray findings. These data are important to identify patients with pulmonary complications of AIDS.

[Histopathologic changes in several opportunistic infections in AIDS]. / Histopathologische Veränderungen einiger opportunistischer Infektionen bei AIDS.

Opportunistic infections are frequent in AIDS patients, particularly in the last phase of the disease, when they occur both singly and in combination with other conditions (for example KAPOSI's sarcoma). These opportunistic infections are the cause of death in over 90% of cases. Their incidence ist proof of cellular immunodeficiency. Based on our observations (17 cases at the two institutes since 1984) we present and discuss the histopathological changes of some important opportunistic infections (notably Pneumocystis carinii pneumonia, Mycobacteriosis (MAI), Cryptosporidium Cytomegalovirus and Toxoplasmosis gondii infection).

Involvement of tumor necrosis factor in endotoxin-triggered neutrophil adherence to sinusoidal endothelial cells of mouse liver and its modulation in acute phase.

Tumor necrosis factor (TNF) has been shown to mediate lipopolysaccharide-induced neutrophil adhesion to liver sinusoidal endothelium in vivo. Female NMRI mice received either 5 micrograms lipopolysaccharide (R595) per animal alone (model A) or together with 116 mumol D-galactosamine (model B). One hour after injection, TNF activity in the serum was detectable to an equal extent in both models. Neutrophils in the liver, which had been identified by chloroacetate esterase staining of liver sections and quantitated by light microscopy, started to increase at 1 h and were elevated 10-fold above baseline at 6 h after application in (A) and (B). If 0.5 micrograms TNF instead of lipopolysaccharide was injected alone (model C) or together with D-galactosamine (model D), neutrophil influx into the liver was comparable to that observed in (A) or (B). Alanine aminotransferase activity in the serum was nearly normal in (A) and (C) 6 h after injection, while it reached levels up to 50-fold above baseline in models (B) and (D). This reflects the well-known D-galactosamine sensitization against lipopolysaccharide or TNF. Furthermore, degranulation of a large number of intrasinusoidal neutrophils could be observed 9 h after lipopolysaccharide-galactosamine injection. The administration of 116 mumol D-galactosamine per animal alone led neither to a measurable TNF activity in the serum nor to an increase in alanine aminotransferase activity or number of liver neutrophils. If the animals had received 50 microliter turpentine subcutaneously 24 h prior to lipopolysaccharide, TNF or D-galactosamine injection, the induced acute-phase reaction suppressed the increase of liver neutrophils in all models. Acute-phase reaction also prevented neutrophil degranulation and the rise of alanine aminotransferase in (B) to a great extent, while serum TNF activity was only minimally affected. It is concluded that TNF mediates neutrophil adhesion to the sinusoidal endothelium in vivo and that acute-phase reactants prevent lipopolysaccharide- or TNF-induced neutrophil influx into the liver.

[Castleman's lymphoma. Differential diagnosis of mediastinal tumors]. / Das Castleman-Lymphom. Zur Differentialdiagnose der Mediastinaltumoren.

This report describes two cases of Castleman's disease (male 48 yrs, female 33 yrs). Two intrathoracic lymphomas were accidentally discovered during routine x-ray examination. Histologically, follicular hyperplasia, prominent interfollicular vascularity and sheets of mature plasma cells (intermediate variant) were seen. The etiology of this benign lymphoma remains unknown. Its significance lies in its differential diagnosis from malignant tumours.

Bone formation by cancer metastases: case report and review of literature.

The formation of heterotopic bone tissue in malignant tumors or in their metastases is extremely rare. In a 60 years old male patient with bronchogenic carcinoma (adenocarcinoma) extensive bone formation was observed within multiple metastases in the skeletal muscles. On the basis of the microscopic findings, the mechanism of bone formation by malignant tumors is discussed. Obviously, proliferation of local mesenchymal tissue and differentiation of mesenchymal cells to osteoblasts is induced by the tumor cells.