Expression of G protein-coupled oestrogen receptor in melanoma and in pregnancy-associated melanoma.

BACKGROUND: The hormone sensitivity of melanoma and the role of 'classical' oestrogen receptor (ER) α and ß in tumour progression have been intensively studied with rather contradictory results. The presence of 'non-classical' G protein-coupled oestrogen receptor (GPER) has not been investigated on human melanoma tissues. OBJECTIVE: To analyse the expression of GPER, ERα and ERß in pregnancy-associated (PAM) and in non-pregnancy-associated (NPAM) melanomas in correlation with traditional prognostic markers and disease-free survival (DFS). METHODS: Receptor protein levels were tested using immunohistochemistry in 81 formalin-fixed paraffin-embedded melanoma tissues. PAMs (n = 38) were compared with age- and Breslow thickness-matched cases (n = 43) including non-pregnant women (NPAM-W) (n = 22) and men (NPAM-M) (n = 21). The association between receptor expression and DFS was analysed by uni- and multivariate Cox proportional hazards regression. RESULTS: G protein-coupled oestrogen receptor was detected both in PAMs and NPAMs. In 39 of the 41 (95.1%) GPER-positive melanomas, GPER and ERß were co-expressed. GPER/ERß-positive melanomas were significantly more common in PAM compared to NPAM (P = 0.0001) with no significant difference between genders (P = 0.4383). In PAMs, the distribution of GPER and ERß was similar (78.4% vs. 81.6%; P = 0.8504), while in NPAM, ERß was the representative ER (60.5% vs. 27.9%; P = 0.0010) without gender difference (59.1% vs. 61.9%). GPER-/ERß-positive melanomas were associated with lower Breslow thickness, lower mitotic rate and higher presence of peritumoral lymphocyte infiltration (PLI) compared to GPER-/ERß-negative cases (P = 0.0156, P = 0.0036 and P = 0.0001) predicting a better DFS (HR = 0.785, 95% CI 0.582-1.058). Despite the significantly higher frequency of GPER and ERß expression in PAM, no significant difference was found in DFS between PAM and NPAM. All but one case failed to show ERα expression. CONCLUSIONS: The presence of GPER and its simultaneous expression with ERß can serve as a new prognostic indicator in a significant subpopulation of melanoma patients.

Folliculotropic mycosis fungoides: clinicopathological analysis of 17 patients.

BACKGROUND: Folliculotropic mycosis fungoides (FMF) represents a variant of MF characterized by hair follicle invasion of mature, CD4-positive small lymphoid cells with cerebriform nuclei. The disease displays resistance to standard treatment modalities and has an unfavourable course. OBJECTIVE: Clinical analysis of 17 patients with FMF collected between 2005 and 2012, investigation of tumour cells and involved hair follicle. METHODS: Re-evaluation of clinical data, wide panel immunohistochemistry investigation on paraffin-embedded biopsy material, T-cell receptor gene rearrangement analysis of the samples. RESULTS: Male and older age group predominance, frequent head-neck involvement, acneiform lesions, keratotic plugs, cysts, nodules, follicular papules, alopecia and classic mycosis fungoides-like plaques represented the main clinical characteristics. Treatment response showed a wide range from transient complete response to therapy resistance and death due to the disease. The pathological alterations: folliculotropism, mild epidermotropism, follicular plugging, mucinous degeneration of hair follicle, basaloid hyperplasia, syringotropism were similar to those observed previously. The first case of a CD8-positive folliculotropic mycosis fungoides - with unusual clinical presentation - is reported here. Nestin overexpression of mesenchymal cells of the isthmic and suprabulbar regions of hair follicle and the reappearance of dermal nestin-expressing cells were observed in association with immature dendritic cell hyperplasia. Altered CK19 expression was detected suggesting a potential role of follicular keratinocytes in the disease process. It was found that a proportion of neoplastic T cells constantly express programmed death-1 receptor in our patients contrary to classic mycosis fungoides. CONCLUSION: The spectrum of the clinical manifestation and the course of folliculotropic mycosis fungoides are broad and differ from classic mycosis fungoides. Folliculotropic neoplastic T-cell proliferation is associated with activation of inflammatory reactive T- and B-lymphoid cells, mesenchymal cells and changes in the hair follicle.

A new model for arteriosclerosis. An electron-microscopic study of the lesions induced by i.v. administered fat.

Lesions in the arterial wall induced in rats by means of intravenous injection of Lipofundin-S were studied by electron microscopy. The morphological changes in this model are the enlargement of the subendothelial space, proliferation of smooth muscle and accumulation of basement membrane-like material. These changes are a closer model for the fibro-proliferative aspects of human atherosclerosis than those seen in short-term (2-3 month) cholesterol feeding. Moreover, such changes are produced in 8 days rather than 2-3 month. These factors indicate that the Lipofundin-S model may be of value in testing anti-atherosclerotic drugs.

Development of arteriosclerosis after i.v. administered fat in rabbits.

In our previous studies performed in rats sclerotic alterations were induced in the vessel wall by Lipofundin-S 20% (Braun, Melsungen) administration for 8 or 16 days, respectively. In order to elucidate eventual species dependency, studies on rabbits were also performed. Alterations were examined in rabbits after Lipofundin treatment for 8 days. Electron microscopic studies revealed the accumulation of granular basement membrane-like material in the subendothelial space due to the activity of immigrated smooth muscle cells. The formation of elastic granules and elastic laminae was also observed among others due to the coalescence of microfibrillary structures formed from glycoseaminoglycans. The lesion developed was similar to that observed in the rat, the only difference was that in the rabbit the accumulation of the collagen fibres was more prominent. Results of our studies obtained in rabbits appear to support our previous findings: Lipofundin-S treatment induces aortic smooth muscle cell mobilization, fibrillogenesis and enlargement of the subendothelial space, namely sclerotic manifestations are induced.

Actinic granuloma in alcoholic liver disease.

Actinic granuloma is a rare condition. Its acceptance as a defined disease has been queried several times. The authors observed a classic case in a patient with alcoholic cirrhosis of the liver and diabetes. The possible role of metabolic disturbances in the pathogenesis of this syndrome is reviewed.

[Skin diseases associated with chronic hepatitis C]. / Krónikus C hepatitishez társult börbetegségek.

The authors are discussing hepatic and extrahepatic pathologic processes caused by hepatitis C virus (HCV) infection and they focus their interest to the skin disorders appearing in the presence of chronic, active HCV infections. The trigger of the immunologic processes leading to dermatologic manifestations are the activated T cells (CD8 + cytotoxic T lymphocytes), cytokins, and also the expansion of certain B cells. Pathologic immunologic phenomena may initiate various dermatologic manifestations. Immunoglobulins, immuncomplexes generated by the disease itself are manifested as various forms of cutan vasculitis. In the present series of patients (pts), HCV related skin disorders known from the literature were diagnosed in eleven cases and they were representing 7 different disease entities. These were palpable purpura (3 pts), urticaria, prurigo and alopecia areata (2-2 pts), lichen ruber planus, pruritus and vitiligo (1-1 patient respectively). The case reports of 2 pts, one with palpable purpura (vasculitis purpurica), one with prurigo and vitiligo are presented in details.

[CD30 positive large T-cell primary cutaneous lymphoma]. / CD30 pozitív, nagy T-sejtes primer cutan lymphoma.

The primary cutaneous CD30 positive large cell lymphoma is a rare tumor, confined to the skin. The characteristic clinical picture is a large, often exulcerating sometimes spontan regressing tumor or nodule. Dense infiltration of large, anaplastic or non-anaplastic T or non T, non B cell of the dermis is characteristic. Generalization, lymph node or internal manifestation is rare, the prognosis is favourable. A 25-year-old male patient is presented, in whom generalised skin symptoms-itching, reddish-brownish papules with central necrosis developed. Two years later general symptoms-fever, fatigue, lymph node and spleen enlargement, increased in white blood cell count with prominent eosinophilia, increase in CD4 number occurred. The histology and immunohistology of the skin and peripheral lymph node showed large, anaplastic, CD30 positive T cell infiltration. CHOP, then BACOP treatment resulted in regression of the skin and the internal symptoms.

[Interferon-alpha and PUVA therapy for mycosis fungoides]. / Mycosis fungoides interferon-alfa- és PUVA-kezelése.

14 patients suffering from early stage mycosis fungoides were treated with interferon alpha 2-a and PUVA/1 patient in stage I a, 3 patients in stage I b, 4 patients in stage II a and 6 patients in stage II b/during 3-21 months time course. Interferon alpha 2-a was administered 3 times a week, in escalating dose from 3 MU to 9 MU, determining the individual maximal tolerated dose. All of the patients responded well to the treatment. Partial remission was observed after 4-13 weeks of treatment. Total remission developed in 8 cases, after 8 weeks- 9 months of the treatment. Side effects occurred frequently: weight loss, pain, fever, fatigue, leucopenia, thrombopenia, liver enzyme elevation. Because of the side effects the dose of the interferon was reduced individually, the dose reduction did not cause relapse.

[A new model for arteriosclerosis. Electron microscopic study of the reaction of the arterial wall following lipofundin-S administration]. / Uj arteriosclerosis modell. Lipofundin-S adagolást követö érfali reactio elektronmikroszkópos vizsgálata.

The vascular wall injury in rats induced by intravenous administration of Lipofundin-S has been studied by electron microscopy and alterations occurring in the aortic wall has been described. Morphological changes revealed in thi model are similar to the fibroblastic atherosclerotic lesion which is well known in the human pathology. A further advantage of this new model is the shortness of the experimental period. Considering the above mentioned facts Lipofundin model seems to be particularly useful for testing medicaments used in the therapy of atherosclerosis.

Characteristic features of the smooth muscle cell migration in vascular wall injury.

Characteristic features of the smooth muscles cell migration and ghost body formation observed in vascular lesions induced by intravenous administration of Lipofundin-S (Braun, Melsungen) were studied and compared to lesions seen in other models. Phenomena revealed can be explained by alterations of the cell environment. The cell, producing ghost body looses a part of the cytoplasm and complies with the new environment. Thus ghost bodies play an active part in maintaining the equilibrium between the cell and its environment.

[Smooth muscle cell migration in lesions of the vascular wall]. / Az érfalkárosodás kapcsán kialakuló simaizomsejt vándorlás jellegzetességei.

Characteristic features of the smooth muscle cell migration and ghost body formation observed in vascular lesions induced by intravenous administration of Lipofundin-S were studied and compared to lesions seen in other models. Phenomena revealed can be explained by alterations of the cell environment. The cell, producing ghost body looses a part of the cytoplasm and complies with the new environment. Thus ghost bodies play an active part in maintaining the equilibrium between the cell and it's environment.

Further studies on the intravenously administered fat arteriosclerosis model.

30 rats were divided into 3 experimental groups. These included 8 days of Lipofundin treatment + 8 days recovery period (Group I), 16 days of Lipofundin treatment (Group II), and 16 days of Lipofundin treatment + 8 days recovery period (Group III). After sacrifice semi-thin and ultra-thin sections prepared from the aorta segments were examined light and electron microscopically. In addition to the development of alterations characteristic of the Lipofundin-model, the accumulation of collagen fibres was also observed. After 16 days of Lipofundin treatment the alterations were much more advanced than after 8-day treatment. Subsequent migration of smooth muscle cells through the newly formed internal elastic lamina was apparent and led to thickening of the sclerotic plaque. When the 16-day Lipofundin treatment was followed by a recovery period of 8 days prior to sacrifice, no signs of regression were seen. The alterations were present in unchanged form and the only difference was in the extent of accumulation of collagen fibres.

[Ultrastructural changes in the aorta following damage to the transport through the vessel wall]. / Aorta elváltozások ultrastruktúrája az érfali transzport zavarát követöen.

Be the ligature of lymphatic vessels lymphostasis has been produced and the consequences of it in the myocardium were studied. Lymphatics of the myocardium in lymphostasis were compared with those in the normal one. It was found that the space between lymphatics and myocardial fibers filled mainly with connective tissue due to accumulation of oedema fluid enlarges and the collagen fibers disintegrate. At the same time accumulation of fluid and dilatation of lymphatics takes also place. Pinocytotic activity of endothelial cells increases. Due to oedema vacuolization of myocardial cells occurs. Disturbance of the capillary circulation leads to swelling of endothelial cells and narrowing the capillary lumen. This lies on the basis of hypoxia and fatty degeneration of the myocardium. The coronary vessels have also shown alterations. In the subendothelial space accumulation of plasma constituents, in the smooth muscle cells of the vessel wall oedema was found. Thus, lymphostasis in the myocardium results in significant alterations.

[Mechanism of the development of lymphogenic cardiomyopathy as revealed by electron microscopy]. / A lymphogen cardiomyopathia kialakulásának mechanizmusa ultrastructuralis vizsgálatok alapján.

Lymphostasis in the aortic wall has been produced experimentally. It has been proved that the disturbance of the lymph circulation results in changes of the aortic wall e.g. oedematic transformation of muscle cells, demarcation of parts of them, formation of ghost bodies and eventually total necrosis of muscle cells. The necrosis of muscle cells usually is followed by proliferation and development of sclerosis.

Dystrophic epidermolysis bullosa complicated by cutaneous squamous cell carcinoma and pulmonary and renal amyloidosis.

A 25-year-old woman with Hallopeau-Siemens recessive dystrophic epidermolysis bullosa had generalized blistering, scarring and milia since birth. In the course of the disease, acral pseudosyndactyly developed, and the patient suffered from corneal erosions, oesophageal strictures, malabsorption, recurrent severe pneumonias and nephrotic syndrome. In addition, she had severe anaemia, sideropaenia, hypocalcaemia, heavy proteinuria and hypoalbuminaemia. A rapidly growing skin squamous cell carcinoma developed on the neck that spread to axillary and cervical lymph nodes. Recurrent hypocalcaemic tetanic convulsions and dyspnoea and a pneumonia refractory to antibiotics led to the premature demise of the patient. Autopsy revealed extensive amyloidosis of the renal, hepatic and splenic tissues. AA type amyloid deposits were detected in the renal glomeruli and in the lung, explaining the patient's unusually severe pulmonary infections. In essence, the patient had severe recessive dystrophic epidermolysis bullosa, complicated by squamous cell carcinoma, recurrent pneumonias and nephrotic syndrome due to secondary amyloidosis of the kidney and lung. The possibility of secondary pulmonary amyloidosis should be considered in severe dystrophic epidermolysis bullosa patients with recurrent pulmonary infections.