Peritumoral inflammatory reaction in non-melanoma skin cancers - histological and immunohistochemical study.

Non-melanoma skin cancers (NMSCs) are the most frequent types of cancer in white skin populations, all over the world. In the last 40 years, there was observed a rapid increase of their incidence, because of the UV radiations exposure and weather changes. Although its morbidity is a relatively modest one, the direct social costs of NMSCs are quite substantial due to a high incidence. Due to these reasons, numerous studies try to clarify the etiopathogenic mechanisms of NMSCs, to elaborate treatment and prevention measures. In the last years, a special attention was given to the relation between inflammation and skin cancer. In our study, we performed a histological and immunohistological evaluation of the inflammatory reaction on a number of 73 surgical exeresis pieces coming from the patients diagnosed with NMSCs. Of these, 21 were squamous cell carcinomas (SCCs) and 52 basal cell carcinomas (BCCs). The peritumoral inflammatory reaction in NMSCs was an extremely variable one in intensity and distribution, from one case to another and even from one area to another within the same tumor, thus proving the complexity of the relations between tumor cells and the cells of the immune system. By comparing the intensity of the inflammatory reaction between the two main types of NMSCs, there was observed that in SCCs the inflammatory reaction was more intense in comparison to BCCs. Also, in SCC there was highlighted a more abundant inflammatory infiltrate in poorly differentiated carcinomas, in comparison to the well-differentiated ones. The presence of the immune system cells (T-lymphocytes, macrophages, mast cells) among the tumoral cells, in a direct contact with these, makes us believe that between the two categories of cells there may appear mechanisms of intercellular communication, distinct from the mechanisms of paracrine signaling.

A rare complication of CMV infection in Crohn's disease - hemophagocytic syndrome: a case report.

We report a case of CMV (cytomegalovirus) infection in a Crohn's disease patient, resulting in severe hemophagocytic syndrome and death. A 63-year-old man with a 10-year history of ileal and colonic Crohn's disease presented with general malaise, loss of appetite and weight loss over the last month. He was in clinical remission for two years, with maintenance therapy 5-Aminosalicylic acid (5-ASA)-derived Mesalamine. The patient had no prior immunomodulators or suppressive treatment. A colonoscopy was performed and we found appearance suggestive of active Crohn's disease, confirmed by histopathological examination. A diagnosis of an exacerbation of Crohn's disease was established. Although the specific treatment was initiated, patient's general condition degraded progressively and diarrheal stools appeared, followed by an episode of massive gastrointestinal bleeding - hematochezia. We performed a new colonoscopy and the pathological examination revealed Crohn's ileocolitis with superimposed CMV infection. Despite the initiation of Ganciclovir alongside with other intensive care measures, he increasingly deteriorated and chest X-ray confirmed multilobar pneumonia. The occurrence of rapidly progressing pancytopenia and evidence for disseminated intravascular coagulopathy as well as hyperferritinemia, raised the suspicion of hemophagocytic syndrome confirmed by bone marrow aspiration. Hence, CMV-associated hemophagocytic syndrome in the context of recent corticotherapy for Crohn's disease was established. There is enough evidence that supports the gravity of the CMV infection in the case of inflammatory bowel disease (IBD) patients, especially the ones on immunomodulator treatment. The hemophagocytic syndrome reactively occurs in patients with infections in cases of immunodeficiency, displaying a hematological aspect of multiple organ dysfunction syndrome.

A rare case of multiple clear cell acanthoma with a relatively rapid development of the lower legs.

Clear cell acanthoma, firstly described by Degos as "an epidermal tumor with a particular aspect", although quite a rare lesion, raised an important interest because it may be easily confused with other dermatologic lesions, in the absence of a histopathological examination. Its clinical aspect is of a solitary nodule, with a red-brown varying color, with a size of 3 mm to 2 mm, sometimes covered with a thin scall. We present a case of a multiple rare cell acanthoma (seven nodular formations), having a rapid development (about two months) diagnosed in a 71-year-old patient within the lower 1/3 of the right shin.

Gastric eosinophilia--clinical and morphological correlations.

Eosinophils of the gastrointestinal tract are involved in the host immune response that occurs in the presence of the pathogens in the digestive lumen, taking part in maintaining the homeostasis of the gastrointestinal epithelium. Their involvement in inflammatory processes of chronic gastritis is less known. In our study, we identified the presence of eosinophils in chorion gastric mucosa (lamina propria) in over 34% of chronic gastritis. Eosinophils were more numerous in atrophic gastritis with intestinal metaplasia. More than 65% of chronic gastritis associated with Helicobacter pylori also had eosinophils in the gastric mucosa.

Modifications of the marginal paradentium to a case of Angle Class III/1 malocclusion.

Angle Class III malocclusions are not so frequently met but they raise big problems of treatment. The analyzed case represents a 14-year-old patient that came to the dental consulting room with an Angle Class III malocclusion determined by the excess of the somatotropic pituitary hormone and a gingival hyperplasia more emphasized at the level of inferior frontal teeth. The patient followed a fixed appliance treatment, the straight-wire technique. All along the treatment and after it, the hyperplasia and the gingival inflammation not only maintained but they even got worse. Thus, an improper hygiene associated with a severe Angle Class III malocclusion maintains and aggravates the gingivitis. The histological and immunohistochemical study of the gingiva revealed important epithelial modifications that led to an epithelial hypertrophy with a tendency toward acanthosis and to severe epithelial erosions. An inflammatory chronic process (rich in lymphocytes, plasma cells and macrophages full of angiogenesis vessels) and an intense reaction of the fibroblastic cells appeared in the gingival corium.

Synchronous diagnosis of signet ring cell colon carcinoma and transitional carcinoma of the left distal ureter.

The presence of synchronous multiple primary carcinomas, although recognized, remains very uncommon. Their etiopathogeny is unclear. The wide spread of imaging techniques currently facilitates diagnosis of simultaneous tumors. We present the rare case of a signet ring cell colon carcinoma coexisting with a transitional cell carcinoma (TCC) of the ureter, which debuted with symptoms of intestinal obstruction in a 75-year-old male patient, with no prior relevant history. Computed tomography showed signs of a tumor mass on the transverse colon, as well as left hydronephrosis with a tumor in the lower third of the ureter, which prompted for immediate emergency surgery. After the appropriate surgical maneuvers, tissue collected from both tumors underwent usual histological preparation and Hematoxylin-Eosin staining, as well as multiple immunostaining with a complex panel of markers. The patient had a favorable postoperative course and during a six-month follow-up, we did not detect any signs of illness.

Cerebral microvascular changes induced by rich cholesterol and saturated fatty acid diet in Wistar rats.

UNLABELLED: The impact of an excess of fatty acids in the diet on cardiovascular diseases has been studied and discussed both in human and animal studies. Generally, excessive saturated fats increase the risk, while unsaturated fats are considered less harmful. Our aim was to perform an experimental study in order to analyze how fatty diet quality (unsaturated vs. saturated fatty acids) influences atherogenesis. MATERIALS AND METHODS: In our experimental study, 18 adult Wistar rats were randomly divided into two equal groups. One group was subjected to a rich unsaturated fatty acid diet (untar) and the other group to a rich saturated one (palm oil). Three animals from each group were sacrificed after 12, 18, and 48 weeks. The brain was removed and microscopically examined after Hematoxylin-Eosin, Orcein and Masson's trichrome classical staining, and after immunohistochemical marking using the anti-alpha smooth muscle actin antibody. RESULTS: Rats sacrificed after 12 weeks revealed modicum lesions, as intimal vacuoles or minute intraluminal thrombosis, and cerebral parenchymal edema. After 18 weeks, some of rats subjected to a rich saturated fatty acid diet presented vacuoles found in all arteriolar wall layers, and a tendency towards parietal thrombosis. In rats subjected to a rich unsaturated fatty acid diet, the subintimal arteriolar vacuolization was associated with an intramural and adventitial fibrosis. In rats sacrificed after 48 weeks, lesional polymorphism was pronounced, but in rats subjected to a rich unsaturated fatty acid diet complete luminal thrombosis was followed by a an organized thrombus with multiple capillary channels. Although in Wistar rats atherosclerosis appeared only after intensive changes in diet, different experimental studies showed that, in transgenic rats, rich saturated fatty acid diet induced progressive atherosclerotic lesions, resembling those observed by us, but also some aspects described in human pathology. CONCLUSIONS: Our experimental study reveals differences in atherogenesis under saturated vs. unsaturated fatty diet.

The synergy between lasers and adipose tissues surgery in cervicofacial rejuvenation: histopathological aspects.

BACKGROUND AND AIMS: Nowadays patients want a long-lasting youthful appearance but through a less invasive approach. Our unique approach, "AdipoLASER reJuvenation (ALJ)", involves a variety of less invasive techniques based on simultaneous laser resurfacing, and lipolysis together with adipose tissue graft and redistribution. Recently, we added to this platelet-rich plasma therapy. We conducted a study aiming to emphasize the histopathological changes occurred following these procedures. PATIENTS AND METHODS: Between 2011-2012, we included 50 patients that were preparing for abdominoplasty (tummy tuck) in which we applied ALJ procedures, in two comparative zones of inferior abdomen. Histological examination varied from 10 days to four months, according to the time of the abdominoplasty. RESULTS: There was a notable histological difference between stimulated and non-stimulated fat graft regarding adipose cells structure and number, neocollagenesis, and dermal matrix remodeling. CONCLUSIONS: The low level laser therapy effect (LLLT) of the fractional CO2 laser combined with the effect of the growth factors derived from activated platelets (PRP) prolonged the life and improved the take of the facial fat graft, increase collagen formation and lead to a better remodeling of the dermal matrix. This unique surgical combination of all four approaches in our ALJ with additional PRP offers a real less invasive but strongly visible - yet natural result - as an alternative to the classic facelift.

The effect of ultraviolet radiation on the cornea - experimental study.

Ultraviolet (UV) radiation in high doses may have harmful effects on the eye. The sources of UV radiation are the sun, as well as some artificial sources such as UV lamps or voltaic arcs. Chronic exposure to UV can cause damage to the anterior pole of the eye, ranging from minor (pterygium) to serious photokeratitis. In our study, we applied a UV dose of 6.5 J/cm(2) in the wavelength range of 290-400 nm, for five consecutive days per rat anterior pole of the eye. Seven days after the last dose of radiation, the animals were sacrificed, harvesting both the irradiated and the non-irradiated eye. Histological and immunohistochemical examination of the lesions revealed that the greatest damage to the epithelium was recorded prior to and 2/3 of the remaining corneal stroma. The epithelial lesions we found varied from pseudokeratosis and detachment of the Bowman epithelium membrane to deep epithelial necrosis. Within the corneal stroma, we observed the formation of interstitial edema with disruption of the collagen structure. We also noticed the presence of an inflammatory infiltrate composed mainly of lymphocytes and CD68+ and CD163+ macrophages, as well as the occurrence of vascular devices. These consisted of angiogenesis capillaries with structured wall composed mainly of endothelial CD34+ precursor cells and a basal membrane rich in collagen IV fibers.

Role of innate immune receptors TLR2 and TLR4 as mediators of the inflammatory reaction in human visceral adipose tissue.

White adipose tissue from different locations is characterized by significant differences in the structure of adipocyte "secretoma". Fat accumulation in the central-visceral depots is usually associated with a chronic inflammatory state, which is complicated by the metabolic syndrome. Recently, the adipose tissue was emerged to have an essential role in the innate immunity, adipocytes being considered effector cells due to the presence of the Toll-like receptors (TLRs). In this study, we compared the expression of TNF-α, TLR2 and TLR4 in peripheral-subcutaneous and central-peritoneal adipose depots in three different conditions - lean, obese and obese diabetic - using immunohistochemistry. Our results suggest a correlation between the incidence of the stromal vascular cells and adipocytes TNF-α and TLR4 in the visceral depots in strong correlation with adipose tissue expansion. TLR2 positive cells were seen in the peripheral depots from all groups without any association with fat accumulation. These results focus on the existence of a new pathogenic pathway, the activation of TLR4, for the involvement of visceral adipose tissue in the activation and maintenance of the inflammatory cascade in obesity.

Histological and immunohistochemical changes of the myocardium in dilated cardiomyopathy.

Dilated cardiomyopathy is a major cause of heart failure and a major cause of morbidity and mortality. It is a multifactorial disease that includes both hereditary and acquired forms. It is estimated that around 20-35% of patients with dilated cardiomyopathy have hereditary forms. It is the third most common cause of heart failure and the most common cause of heart transplant. Dilated cardiomyopathy can be a secondary condition of many diseases such as coronary heart disease, diabetes, pheochromocytoma, infections, malnutrition, ingestion of toxic substances (alcohol, cocaine), ingestion of chemotherapeutic drugs, autoimmune diseases. In our study, we aimed to describe the changes of myocardial cells and interstitial connective tissue in patients clinically diagnosed with alcoholic dilated cardiomyopathy. The material studied consisted of heart fragments sampled from the left ventricle (LV) during necropsy from a total of 28 patients, aged between 58 and 73 years, with a clinical and laboratory diagnosis of dilated cardiomyopathy, hospitalized in the Cardiology Center of the Emergency County Hospital of Craiova in 2009 and 2010. In dilated cardiomyopathy, myocardial muscle fibers appeared slightly elongated or wavy, with hypochromatic, heterogeneous, vacuolar sarcoplasm, by a decrease of myofibril numbers. Lipofuscin granules were frequently seen in the sarcoplasm. Nuclear changes were consistent with sarcoplasmic alterations. Changes of the interstitial connective tissue were sometimes extensive and sometimes barely noticeable. The most common alteration of this structure was the onset and development of a mainly perivascular collagen fibrillogenetic process.

Hypoxia induced VEGF synthesis in visceral adipose depots of obese diabetic patients.

VEGF is one the pro-inflammatory adipokines synthesized by the "adipose secretoma" of obese subjects as a response to hypoxic conditions; but the main function of VEGF is angiogenesis, being recognized as the most important factor increasing blood capillaries in the adipose tissue by stimulating endothelial cell growth. In this paper, we propose a comparative study of the vascular response to VEGF synthesis in the subcutaneous and central-peritoneal adipose depots in lean, obese and obese diabetic patients. We used CD31 to label the endothelial cells in order to evaluate the response of the vascular network to VEGF synthesis. Our results showed an increase of VEGF protein synthesis in obese and obese-diabetic patients compared to lean subjects where the protein was absent. The positivity for VEGF in obese diabetic samples was observed in numerous structures from the adipose depots, both in the stromal vascular fraction--blood vessels and stromal cells--as well as in the cytoplasm of adipocytes. Positivity in the vascular wall was observed more frequently in areas of perivascular and intralobular fibrosis. Obese and diabetic patients showed similar incidence of CD31 immunoreactivity with lean subjects in both subcutaneous and peritoneal depots. In conclusion, human adipose depots show a different incidence of VEGF positive cells in relation with their disposal and the metabolic status. VEGF synthesis in visceral adipose tissue is inefficient being not followed by angiogenesis to counterbalance tissue hypoxia. We suggest that may be a pathogenic link between the degrees of intralobular fibrosis in adipose depots and VEGF expression.

The importance of tumor proliferation markers in assessing lesions of the palatine tonsil.

Oropharyngeal cancer, and especially squamous cell carcinoma, is one of the most common cancers worldwide, and its incidence is increasing, with the palatine tonsil being one of the main locations. The etiopathogenic factors, together with its location as well as the available immunohistochemical methods, make this type of cancer an accessible one in terms of diagnosis. However, it is usually diagnosed in late stages. Therefore, we tried to elucidate the causes of treatment failures and development of local recurrence. For this, we reassessed the proliferative pattern of tonsil lesions using the anti-p53, anti-PCNA and anti-Ki67 antibodies on 73 tonsil fragments collected after curative surgery on adults aged between 28 and 86 years. Following the reevaluation of the histopathological examination using markers for cell proliferation, the diagnosis was modified in 16 cases, representing about 22% of the cases take into study. By using immunohistochemical markers in the histopathological examination the diagnosis is improved, leading to a more appropriate therapeutical approach.

The unexpected evolution of a case of diffuse large B-cell non-Hodgkin lymphoma.

The diffuse large B-cell lymphoma (DLBCL) represents the most common type of aggressive non-Hodgkin's lymphoma with a heterogeneous morphology, biology and clinical presentation. Gene expression profiling studies identified three distinct molecular subtypes of DLCBL arisen from B-cells at different stages of differentiation: germinal center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, primary mediastinal B-cell lymphoma (PMBL). The most relevant oncogenic pathways in diffuse large B-cell lymphoma are: deregulated B-cell receptor/proliferation signaling, BCL6 and NF-kB constitutive expression, defects in apoptosis and neoangiogenesis. The treatment of DLBCL has been completely modified in the last ten years by combination of anti-CD20 monoclonal antibody (rituximab) and CHOP chemotherapy, which is now the first line therapy. In the last years, there have been reported several cases of progressive multifocal leukoencephalopathy (PML) at patients with rheumatoid arthritis treated with rituximab. Progressive multifocal leukoencephalopathy is possible as an adverse reaction to rituximab at patients treated with R-CHOP for diffuse large B-cell lymphoma.

Immunohistochemical expression of growth factors in the exocrine pancreas of patients with chronic liver diseases.

Acute viral hepatitis has been reported to cause acute pancreatitis. It was also reported that exocrine pancreatic function is damaged in chronic liver disease (CLD). Growth factors stored in the extracellular matrix and released in the course of pancreatic degradation are major mediators of inductive processes. The immunostaining technique was used to evidence the changes of the expression of the growth factors in different pancreatic cells. VEGF and FGF-beta are involved in the angiogenesis processes and in the evolution of the pancreatic interstitial tissue in case of chronic pancreatitis. Theses markers can also be used for the diagnosis of pancreatitis, but their value is variable. They stimulate the pancreatic star cells, the myofibroblasts and play an important role in the genesis of the extracellular matrix and in the repairing of the tissue after the aggression. TGF beta is important for its role in cellular differentiation and growth and in the development of the fibrosis in liver and other organs. The present paper studies the immunohistochemical expression of these growth factors in pancreatic cells.

Acquired aplastic anemia: correlation between etiology, pathophysiology, bone marrow histology and prognosis factors.

UNLABELLED: Aplastic anemia is a clonal disease of stem cell characterized by peripheral blood pancytopenia with hypocellular bone marrow. In most cases acquired aplastic anemia is an autoimmune, T-cell mediated disease (hematopoiesis is mediated by a population of CD8+ T-cells which produce inhibitory cytokines - TNF-alpha, IFN-gamma, IL-6 which suppress hematopoiesis by affecting the mitotic cycle and cell killing by inducing apoptosis). In some cases radiation, medical drugs and chemicals, viruses induce depletion of hematopoietic stem cells by direct toxicity; immune diseases induce complex immune reactions leading to bone marrow failure. Symptoms and signs are represented by fatigue, pallor induces by anemia, infections induce by neutropenia, and bleedings induce by thrombocytopenia. In peripheral blood is present pancytopenia and bone marrow are characterized by hypocellularity, fat cells hyperplasia, residual lymphocytosis, plasmocytosis and mastocytosis. The aim of this study was to establish the correlation between etiology, pathophysiology, bone marrow histology and negative prognosis factors at 16 patients with acquired aplastic anemia (seven with severe aplastic anemia and nine with moderate aplastic anemia) hospitalized in Clinic of Hematology from Craiova between 2003-2008. Eight cases presented idiopathic aplastic anemia and eight cases secondary aplastic anemia (two of them with pure red cell aplasia). CONCLUSIONS: The unfavorable evolution, correlated with etiology and pathophysiology, had been seen at the patients with severe idiopathic aplastic anemia and severe secondary aplastic anemia associated with viral infections and insecticides exposure. Pure red cell aplasia was associated in our study with B19 parvovirus infection or malignant thymoma. The negative prognosis factors in acquired aplastic anemia, correlated with laboratory findings and a low survival, were: severe neutropenia, platelets count less than 10 000/microL, corrected reticulocytes less than 1%, hypocellularity of bone marrow <10%, persistence of pancytopenia at 30 days after initiating therapy.

Hypothesis of microfractures by buckling theory of bone's trabeculas from vertebral bodies affected by osteoporosis.

Osteoporosis has become in recent years a public health problem considered a true "silent epidemic", by increasing the number of osteoporosis fractures in the world as a result of increased number of persons 3rd group of age by increasing life expectancy and reducing physical effort and the emergence of sedentary occupations, increasing incidence of obesity, diabetes, liver disease and kidney by applying widely corticosteroid therapy. Starting from the macroscopic and microscopic aspects of the bone spongy tissue affected by osteoporosis, from vertebral bodies, we try to explain the modality of damaging the bone micro-structure by buckling phenomenon, knowing that the bone tissue has at trabecular level, an elasticity degree and supports high levels of mechanical forces.

Histopathologic and immunohistochemical aspects of the renal parenchyma in patients with glomerulonephritis developed in locked-up spaces.

A number of 38 renal biopsies and 13 necroptic pieces removed from 51 prisoners were available for our study. From 51 cases, 21 patients were diagnosed with actual chronic glomerulonephritis, 19 patients with non-specific chronic glomerulonephritis, four patients with renal amyloidosis, and seven patients with glomerulonephritis lesions associated to pielonephritis.

Glomerulopathies in locked-up persons. Histopathologic and clinic study.

The diseases of the urinary apparatus are frequently-enough inside the locked-up spaces of the penitentiaries. Among them, glomerulonephritis and pyelonephritis take a special place, by their late diagnosis and their lasting evolution. The authors clinically and paraclinically investigated a number of 214 locked-up male persons aged between 18-57 years, presenting various clinical forms of glomerulonephritis. Histopathological exams performed in 51 patients confirmed the diagnosis.

Microscopic assays regarding the renal damage following a post-combustional shock.

Over a period of three years (2000-2003) 39 autopsies were performed on patients with burns. Among them a number of 11 men and 28 women were aged between 28-92 years, the total burnt body surface was of 20% to 95%. Of all the cases nine patients died during the first 24-36 hours since the accident happened, presenting a burnt surface of more than 70%. In these cases, the renal lesions were minor but critical, presenting symptoms of acute renal failure (ARF). Subsequently, a number of 25 patients died within 1-4 weeks since the accident. Renal lesions were complex with tubular necrosis, lymphocyte infiltration and micro-abscesses. The burnt body surface of these patients was of 41-85%. In three cases, when death occurred within four weeks of hospitalization, the patients presented damages to other organs as well (multiple organs failure--MOF). The kidneys displayed tubular necrosis, fibrous micro-thrombi and infarct areas. In two cases coagulation intravascular dissemination occurred in patients with burnt body surface of 45-70% and aged of 42 and 60 years. Micro-thrombi and infarct areas dominated the renal lesions.