Anti-Psoriasis Effect of Diclofenac and Celecoxib Using the Tail Model for Psoriasis.

Non-steroidal anti-inflammatory drugs (NSAIDs) showed effects in some hyperproliferative dermatologic pathologies. The aim of the study is the assessment of anti-psoriasis effect of diclofenac and celecoxib using a mice tail model. The topical application of substances on the proximal mice tails was performed for two weeks. The effects on the epidermal granular layer and mean epidermal thickness (excluding the stratum corneum) were evaluated using hematoxylin-eosin staining. Orthokeratosis degree and percentual drug activity were calculated. A positive control group treated with tretinoin and two negative controls (white soft paraffin and untreated mice) were used. Orthokeratosis degree significantly increased in all the NSAIDs groups (celecoxib 1%, 2% and diclofenac 1%, 2%) and in the tretinoin 0.05% group, versus negative controls. Celecoxib 1% and 2%, tretinoin 0.05% and white soft paraffin significantly increased mean epidermal thickness, versus untreated mice. The values obtained in the case of celecoxib 2% ointment regarding the orthokeratosis degree and percentual drug activity are providing premises for further investigations regarding this effect and the mechanisms of action involved. Celecoxib 2% had the greatest percentual drug activity and is a promising substance for the anti-psoriasis topical treatment. Along with the COX-2 inhibition, celecoxib might have an anti-psoriasis effect by other independent mechanisms.

Assessment of hormonal receptor immunoexpression and Her2 status in invasive breast cancer after conservative and radical surgery.

This study was conducted on 300 patients with infiltrative breast carcinoma, of which 112 cases underwent radical mastectomy, and 188 were conservatively operated. Forty-four patients experienced local relapses during the clinical follow-up. The immunohistochemical (IHC) study used the Labeled Streptavidin Biotin (LSAB)∕Horseradish peroxidase (HRP) method, which evaluated the estrogen receptor (ER) and progesterone receptor (PR), as well as human epidermal growth factor receptor 2 (Her2∕neu) expressions in tumor cells. After IHC analysis, all cases were classified into one of the following four immunophenotypes: ER+∕PR+ classical phenotype, ER-∕PR-, ER+∕PR- and ER-∕PR+ phenotypes. Correlating hormonal phenotypes with Her2 status, we found that Her2 is significantly associated more frequently with the ER+/PR- phenotype, while the absence of Her2 was associated more frequently with the ER+/PR+ phenotype but with no significant differences. Local recurrences were significantly more common in patients with absent ERs than those who had these receptors present in the primary tumor. Similarly, mammary tumors with absent PRs recurred significantly more frequently than those with PRs. The positivity of Her2 is significantly associated with the absence of PRs in both type of surgery (conservative or radical). Local recurrences are significantly correlated with both negative receptors phenotype, regardless of the type of surgery. IHC markers, represented by hormone receptors for estrogen and progesterone, and Her2 oncoprotein, can be useful for identifying patients who are at increased risk of local recurrences after conservative or radical surgery for breast cancer.

GPER and ERα expression in abnormal endometrial proliferations.

UNLABELLED: G-protein coupled estrogen receptor 1 (GPER), a particular extranuclear estrogen receptor (ER), seems not to be significantly involved in normal female phenotype development but especially associated with severe genital malignancies. This study investigated the GPER expression in different types of normal and abnormal proliferative endometrium, and the correlation with the presence of ERα. GPER was much highly expressed in cytoplasm (than onto cell membrane), contrary to ERα, which was almost exclusively located in the nucleus. Both ERs' densities were higher in columnar epithelial then in stromal cells, according with higher estrogen-sensitivity of epithelial cells. GPER and ERα density decreased as follows: complex endometrial hyperplasia (CEH) > simple endometrial hyperplasia (SHE) > normal proliferative endometrium (NPE) > atypical endometrial hyperplasia (AEH), ERα' density being constantly higher. In endometrial adenocarcinomas, both ERs were significant lower expressed, and widely varied, but GPER÷ERα ratio was significantly increased in high-grade lesions. CONCLUSIONS: The nuclear ERα is responsible for the genomic (the most important) mechanism of action of estrogens, involved in cell growth and multiplication. In normal and benign proliferations, ERα expression is increased as an evidence of its effects on cells with conserved architecture, in atypical and especially in malignant cells ERα's (and GPER's) density being much lower. Cytoplasmic GPER probably interfere with different tyrosine÷protein kinases signaling pathways, also involved in cell growth and proliferation. In benign endometrial lesions, GPER's presence is, at least partially, the result of an inductor effect of ERα on GPER gene transcription. In high-grade lesions, GPER÷ERα ratio was increased, demonstrating that GPER is involved per se in malignant endometrial proliferations.

Neuroendocrine tumor arising de novo in the left upper thigh: a case report.

Neuroendocrine tumors (NETs) originate in the neuroendocrine cells of the neural crest (Kulchitsky cells). If neuroendocrine tumors arising in the digestive tract or lung may occasionally result in skin metastases, primary soft tissue or skin NETs are infrequent. The current paper presents the case of an elderly woman patient with neuroendocrine tumors arising de novo in the left upper thigh, accompanied by lymph nodes metastases in the left groin and in the left pelvic sidewall, in close vicinity of the iliac vessels. The diagnosis of NET was performed based on immunohistochemical tests. Such tumors show a slow growth and, generally, have a good prognosis. It is emphasized that complete surgical excision, in some cases associated with adjuvant external radiotherapy is the optimal therapeutic modality in dealing with such lesions.

Cutaneous mastocytosis, problems of clinical diagnosis of four cases.

Mastocytosis is a rare disease characterized by a pathological increased of mast cells in one or more tissues, particularly in the skin, bone marrow, liver, spleen, lymph nodes and gastrointestinal tract. Cutaneous mastocytosis represents over 90% of cases found with predilection in children. The aim of the paper was to summarize the authors' clinical, histopathological and immunohistochemical observations on patients with cutaneous mastocytosis. We present four cases of cutaneous mastocytosis, sporadic form, customized by clinical presentation and age of onset: two installed in the neonatal period, a case with onset in infancy and another in adulthood. For the assessment of the severity and the effectiveness of the treatment, we used SCORMA Index. We performed in each patient histopathological examination of the skin (Hematoxylin-Eosin and Giemsa stains), the dosage of mediators (serum tryptase level, serum histamine levels, urinary histamine metabolites) and the balance of expansion (complete blood cell count, liver biological investigations, abdominal ultrasound, skeletal radiography, chest radiography). For the adult with mastocytosis, we performed abdominal scanner and cytological study of the bone marrow. Following investigations carried out in each case, we mentioned the diagnosis of cutaneous mastocytosis, and also excluded several diseases confounded by clinically and histologically aspect. Considering the fact that the balance expansion was negative, we excluded the diagnosis of systemic mastocytosis. The presence of anemia and protein energetic malnutrition in children with mastocytosis involves carrying out balance extension for the exclusion of a systemic form of the disease. Histopathological examination of the skin using special stains, the dosage of mediators (serum tryptase level, serum histamine levels, urinary histamine metabolites) and balance expansion establish the diagnosis of cutaneous mastocytosis and also exclude many confusions because of the clinical presentation.

The evaluation of p16 and Ki67 immunoexpression in ameloblastomas.

In this study, we investigated the p16 and Ki67 immunoexpression in 19 ameloblastomas in order to highlight some correlations of these markers with the aggressive variants of tumors. The p16 immunoreaction was present in 90.9% of cases; the highest scores are present in the typical follicular and in the intraluminal unicystic variant, at the opposite pole being the granular cells variant. In these cases, the maximum reaction was observed at the level of the stellated reticulum cells while the lowest reaction was present at the level of cubico-cylindrical peripheral cells of the neoplastic islands. The Ki67 immunoreaction was present in all cases, the highest scores being present in the typical follicular variant, opposite being the ameloblastoma with granular cells cases and that with acanthomatous differentiation type. The immunostained cells were located predominantly at the periphery of the tumoral islands but also in the stellated reticulum cells in the central area. The p16 and Ki67 markers may be useful for distinguishing different types of ameloblastomas in terms of aggressiveness.

VEGF, CD105 and α-SMA immunoexpression study in lips squamous cell carcinomas and associated dysplastic lesions.

This study analyzes the microvascular density (MVD) for CD105+ and α-SMA+ vessels and VEGF immunoexpression for 35 oral squamous cell carcinomas and for the associated dysplastic lesions of the lips. CD105+ MVD was superior in the advancing edge compared to the intratumoral area, no matter the analyzed clinico-pathological parameters (gender, age, differentiation degree, tumor stage) (p<0.05), MVD being significantly higher in poorly differentiated carcinomas (p<0.05). α-SMA+ MVD was also superior in the advancing edge compared to the intratumoral area (p<0.05), MVD values being significantly higher in well and moderately differentiated carcinomas (p<0.05). CD105+ MVD and α-SMA+ MVD were significantly lower compared to the analyzed tumor area (p<0.05), in the dysplastic lesions. VEGF score showed significantly higher values in well to moderately differentiated carcinoma and in the tumor area versus dysplastic associated lesions (p<0.05). CD105+ MVD and VEGF are markers able to characterize the angiogenic phenotype of carcinomas and of the dysplastic lesions of the lips, while α-SMA+ MVD quantification is useful in assessing the vascular maturity degree.

Ulcerated necrobiosis lipoidica to a teenager with diabetes mellitus and obesity.

Many skin lesions are associated with diabetes mellitus (DM) type 1 or 2, due to the use of antidiabetics or to metabolic and endocrine disorders caused by this disease. Necrobiosis lipoidica (NL) occurs more frequently in patients with DM. Painful ulcerations may occur on NL areas in about 20-25% of the cases and usually they are related to trauma. We present the case of a teenager, male, 17-year-old, having NL with multiple plaques, some of them spontaneously ulcerated after about 33 months of onset. He is known with type 1 DM from 2.5 years and the NL preceding the diagnosis of diabetes mellitus with about six months, presented erythematous-infiltrative skin plaques, some ulcerated for about three months, interesting both shins. Based on clinical, histopathological and paraclinical examinations, we established the following diagnoses: ulcerated NL, type 1 DM, moderate mixed dyslipidemia, class I obesity; commissural candidiasis, juvenile acne. Under treatment with Pentoxifyllinum, Sulodexidum, Ketotifenum and topical therapy with 0.2% Hyaluronic acid two months later, we have managed to heal two of the three ulcerated plaques and of the third has become superficial. We applied 0.5% Fluocortolonum on non-ulcerated plaques recording an improvement after two weeks of treatment. NL is a skin disease with a predilection for the shins, more frequent in patients with diabetes and is a part of palisading granulomatous dermatitis, which leads to skin atrophy. NL is found in the 0.3-1.2% of diabetic patients and is rare in children with diabetes (0.006%). It is more common in the patients with type 1 DM. The onset is in the third decade in diabetic patients and in the fourth decade in non-diabetics. There is no consensus concerning the treatment of NL, and the results are often modest. Antiplatelet agents, corticosteroids (local and general), immunomodulatory drugs, cyclins, wide synthetic antipaludics, heparin, Thalidomide are used. NL treatment is very difficult, especially in the ulcerated forms. Many of the drugs listed have proven efficacy only in isolated cases. Studies are necessary on large series of patients to determine the optimal therapy of NL.

Evaluation of new morphometric parameters of neoangiogenesis in human colorectal cancer using confocal laser endomicroscopy (CLE) and targeted panendothelial markers.

The tumor microcirculation is characterized by an abnormal vascular network with dilated, tortuous and saccular vessels. Therefore, imaging the tumor vasculature and determining its morphometric characteristics represent a critical goal for optimizing the cancer treatment that targets the blood vessels (i.e. antiangiogenesis therapy). The aim of this study was to evaluate new vascular morphometric parameters in colorectal cancer, difficult to achieve through conventional immunohistochemistry, by using the confocal laser endomicroscopy method. Fresh biopsies from tumor and normal tissue were collected during colonoscopy from five patients with T3 colorectal carcinoma without metastasis and were marked with fluorescently labeled anti-CD31 antibodies. A series of optical slices spanning 250 µm inside the tissue were immediately collected for each sample using a confocal laser endomicroscope. All measurements were expressed as the mean ± standard error. The mean diameter of tumor vessels was significantly larger than the normal vessels (9.46±0.4 µm vs. 7.60±0.3 µm, p = 0.0166). The vessel density was also significantly higher in the cancer vs. normal tissue samples (5541.05±262.81 vs. 3755.79±194.96 vessels/mm3, p = 0.0006). These results were confirmed by immunohistochemistry. In addition, the tortuosity index and vessel lengths were not significantly different (1.05±0.016 and 28.30±3.27 µm in normal tissue, vs. 1.07±0.008 and 26.49±3.18 µm in tumor tissue respectively, p = 0.5357 and p = 0.7033). The daughter/mother ratio (ratio of the sum of the squares of daughter vessel radii over the square of the mother vessel radius) was 1.15±0.09 in normal tissue, and 1.21±0.08 in tumor tissue (p = 0.6531). The confocal laser endomicroscopy is feasible for measuring more vascular parameters from fresh tumor biopsies than conventional immunohistochemistry alone. Provided new contrast agents will be clinically available, future in vivo use of CLE could lead to identification of novel biomarkers based on the morphometric characteristics of tumor vasculature.

Gastrointestinal stromal tumor, jejunal atresia and stenosis in a neonate.

Gastrointestinal stromal tumors could rise in different areas of the digestive tract, at any age, but very rarely in neonates. We present the case of a 5-day-old male, with intestinal stenosis and atresia (type II) operated for peritonitis. On the resected specimen, the histopathological examination revealed a small gastrointestinal tumor of 8 mm. The immunohistochemical analysis indicated a low malignant potential. He is currently at two years of oncologic follow-up with no evidence of disease.

Correlations of proliferation markers, p53 expression and histological findings in colorectal carcinoma.

AIM: To investigate the expression of PCNA, Ki-67 and p53 antibodies in colorectal carcinomas and to establish the relationship between these markers and some particular histological findings of colorectal carcinomas. MATERIAL AND METHODS: We determined immunohistochemically the expression of PCNA, Ki-67 and p53 antibodies in 41 cases of colorectal carcinomas. RESULTS: In adenocarcinomas, the tumor proliferative activity, detected with PCNA and Ki-67 antibodies, increased with the histological grade. Mucinous adenocarcinomas had a mean PCNA LI of 50% and a mean Ki-67 LI of 32%, while signet ring carcinomas had a mean PCNA LI of 70% and a mean Ki-67 LI of 45%. The proliferative activity in the foci of squamous metaplasia was lower than the proliferative activity of malignant areas in the analyzed adenocarcinomas. The p53 overexpression was detected in 24 cases (58.53%). In adenocarcinomas, the p53 positive rate increased with the dedifferentiation of these tumours. Only 16.66% of the cases of carcinomas with mucus secreting cells overexpressed p53, while adenocarcinomas overexpressed this protein in many more cases (65.71% of the cases). The overexpression of p53 was associated with the highest PCNA and Ki-67 LI. CONCLUSIONS: The foci of squamous metaplasia, present in colorectal adeno-carcinomas, do not seem to influence the increase of the tumours. The p53 overexpression was associated with non mucinos colorectal carcinomas and with the histological grade of colorectal adenocarcinomas. The p53 over expression tended to be more frequent in colorectal carcinomas with high proliferative activity.