Comprehensive immunohistochemical analysis based on the origin of leiomyosarcoma.

Diagnostic criteria, biological behavior, and treatment approaches of leiomyosarcomas (LMS) may differ according to the origin of the tumor. This is important in terms of patient's management, especially in tumors located in the peritoneum and retroperitoneal sites. In our study, we aimed to demonstrate the immunophenotypic characteristics of uterine and extra-uterine LMS using a large antibody panel, and to determine whether they potentially play a role in the differences among these tumor groups. Between 2006 and 2018, 29 uterine and 42 extra-uterine primary LMS were included in this study. Using tissue samples taken from the areas that best represented the tumor, an immunohistochemical study was performed on the blocks prepared by tissue micro-array method with estrogen and progesterone receptor (PR), WT-1, SMA, desmin, caldesmon, calponin, p16, p53, MDM2, CDK4, bcl-2, cyclin D1, fascin, EMMPRIN, FOXM1, c-erb-B2, c-Myc, PAX8, and CD117. Staining results of uterine and extra-uterine LMS were evaluated with these 20 antibodies. In uterine LMS compared with extra-uterine LMS, estrogen receptor (48% vs. 12%), PR (62% vs. 21%), desmin (79% vs. 50%), and EMMPRIN (69% vs. 45%) staining rate was detected higher. In extra-uterine LMS, caldesmon (88% vs. 69%), c-Myc (33% vs. 10%), and cyclin D1 (52% vs. 28%) were stained higher than uterine LMS (p < 0.05). No significant staining difference was detected with other antibodies. We concluded that estrogen receptor, PR, desmin, EMMPRIN, caldesmon, c-Myc, and cyclin D1 antibodies may help to determine primary origin of the tumor in LMS cases.

A case report and literature review of cutaneous intravascular large B-cell lymphoma presenting clinically as panniculitis: a difficult diagnosis, but a good prognosis.

Intravascular large B-cell lymphoma is a rare, non-mass-forming, extranodal large B-cell lymphoma subtype characterized by the presence of tumor cells in the lumens of vessels. It is divided into two major types: classical and Asian. Patients presenting only with skin involvement are mostly female, at a younger age than classical intravascular large B-cell lymphoma patients, and have a better prognosis. Since the diagnosis of cases with isolated skin involvement is difficult, keeping this entity in mind, performing a careful microscopic examination, and applying new, effective treatment regimens will make it possible to achieve better clinical outcomes in these cases.

Histopathological evaluation of mesenchymal stem cells in the healing of anastomosed carotid arteries.

The objective of this study was to evaluate the influence of mesenchymal stem cells on the healing of experimental carotid artery anastomoses histopathologically. Twenty-four female Sprague-Dawley rats were used in this study. After random separation of the subjects into two groups, in both groups carotid arteries were transected and anastomosed in end-to-end fashion. Anastomoses were locally treated with 1 ml 0.09% NaCl, and 1 ml mesenchymal stem cell suspension (1×106 cells) in control and trial groups, respectively. Anastomoses were wrapped with an 8 mm sheet of surgicel and soaked with BioGlue in order to sequestrate the stem cells. After patencies were confirmed via Doppler USG, surgical site was closed with 2/0 silk sutures. Histopathological evaluation was carried out after 4 weeks. In respect to endothelial continuity, vessel patency (along with presence or absence of restenosis), integrities of internal and external elastic laminae, muscularis and adventitia; no statistically significant differences were present between the trial and control groups. In Trial and Control Groups, luminal thrombus was present in 8 (66.6%) and 3 (25%) of the 12 subjects, respectively. The difference was statistically significant (P < 0.05). Recanalization was present in 6 subjects in trial group; 1 subjects in Control Group, respectively. Our results suggest that local administration of mesenchyme stem cell does not have a positive influence on success of an anastomosis.

Economic burden of thromboembolic and hemorrhagic complications in non-valvular atrial fibrillation in Algeria (the ELRAGFA study).

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with substantial public health and economic impact on healthcare systems due to the prevention and management of thromboembolic and hemorrhagic complications. In Algeria, stroke is a leading cause of death, representing 15.6% of all deaths in 2012. Current data on the epidemiology and costs associated with non-valvular AF (NVAF) in Algeria are not available. METHODS: A three-step approach was undertaken to estimate the economic burden of NVAF in Algeria. First, a literature review identified the epidemiological burden of the disease. Second, expert clinicians practicing in Algerian hospitals were surveyed on consumed resources and unit costs of treatment and management of complications and prevention. Finally, these data were combined with event probabilities in an economic model to estimate the annual cost of NVAF prevention and complications for the Algerian healthcare system. RESULTS: Based on literature and demographics data, it was estimated that there are currently 187,686 subjects with NVAF in Algeria. Seventy per cent of this population was treated for prevention, half of which were controlled. Cost of prevention was estimated at 203 million DZD (€1.5 million) for drugs and 349 million DZD (€2.6 million) for examinations. Mean hospitalization costs for complications ranged between 123,500 and 435,500 DZD (€910-3,209), according to the type and severity of complications. Hospitalization costs for thromboembolic and hemorrhagic complications were estimated at 8,313 million DZD (€62 million), half of which was for untreated patients. Finally, the economic burden of NVAF was estimated at 8,865 million DZD (>€65 million) annually. CONCLUSION: The economic burden of NVAF is important in Algeria, largely driven by untreated and INR-uncontrolled patients. There is a lack of information on the Algerian healthcare system that could increase uncertainty around this assessment, but it clearly establishes the importance of NVAF as a public health concern.

The effect of dutasteride on microscopic and macroscopic changes of testosterone replacement treatment on prostate tissue.

Testosterone replacement therapy has a growing interest in daily practice; however, debates on its safety for prostate cancer still continue. Dutasteride-a 5α-reductase inhibitor-was shown to be effective in preventing prostate cancer. We therefore aimed to evaluate the effect of testosterone replacement therapy and dutasteride treatment on prostate tissue in castrated rats. Rats were randomised in four groups after bilateral orchidectomy as follows: Group I received testosterone + dutasteride, Group II received only testosterone, Group III had no medical treatment, and Group IV was the control group. After 3 months, rats were sacrificed and laboratory and histopathological examinations were performed. In Groups I and II, prostate volume, T and DHT levels were significantly higher compared to Group III and controls. Groups I and II had also significantly greater preneoplastic histopathological signs; however, in intergroup analyses, Group I showed less premalignant changes compared to Group II. We concluded that dutasteride was effective when combined with testosterone therapy in preventing premalignant histopathological changes in prostate tissue. Further evidence is needed to confirm our findings.

A Skeptical Approach to the Management of Persistent Oral Ulceration in a Child.

The diagnosis of oral lesions is sometimes difficult due to both the clinician's limited experience with the conditions that may cause the lesions and their similar appearances, especially in children. Correctly establishing a definitive diagnosis is of major importance to clinicians who manage patients with oral mucosal diseases. In patients with Fanconi anaemia (FA), oral ulcers occur frequently, which are quite variable, and may lead to a misdiagnosis or failure to diagnose. Here, we report the case of a 15-year-old boy who was examined for squamous cell cancer of the tongue and diagnosed as having FA without any haematological manifestations. While surgery could not be done, both radiotherapy and chemotherapy had to be decreased. He died of progressive disease 6 months after the diagnosis. Unexplained ulcers in a child with a duration longer than 2 weeks should be further evaluated, especially for FA, even without the presence of anaemia.

Perivascular Epithelioid Cell Tumor (PEComa) of the Uterine Cervix in a Patient with Tuberous Sclerosis Complex: A Literature Review.

Perivascular epithelioid cell tumors (PEComa) are a rare type of mesenchymal tumor arising from perivascular epithelial cells. These tumor cells are a co-expression of both melanocytic and myogenic antigens, such as HMB 45 and smooth muscle actin, and at least in some patients, are located around vessels. PEComas has been reported at various sites, including visceral organs, soft tissue, the prostate gland and broad ligaments. In the female reproductive system, the uterine corpus is the most common site of involvement. Some cases are related to tuberous sclerosis complex. Cervical PEComa with tuberous sclerosis complex is presented in the case of a 41 year-old and the literature is reviewed. There have been only eight cases of cervical PEComas and only one other case associated with tuberous sclerosis complex reported to date.

Leiomyoma With Bizarre Nuclei: Clinical and Pathologic Features of 30 Patients.

Leiomyoma with bizarre nuclei (LBN) have significant cytologic atypia, but high mitotic rate and tumor cell necrosis are absent. Although it is a benign leiomyoma variant, recurrent cases have been described. In this study, we investigated the clinical and pathologic features of LBN and compared them with related studies. A total of 30 patients diagnosed with LBN in our department were included in this study. In all cases, clinical data (age, complaint, surgery type), macroscopic features (size, location, number of leiomyomas, necrosis, and hemorrhage), microscopic features (bizarre cell distribution, bizarre cell density, cellularity, mitotic rate, tumor margin, necrosis, nuclear pseudoinclusions, karyorrhectic nuclei, prominent eosinophilic nucleoli with perinucleolar clearing, cytoplasmic eosinophilic inclusions, staghorn vessels, and alveolar-type edema), and follow-up data (recurrence and survival period) were evaluated. The mean age of the patients was 49.76 yr (range: 38-89 yr). Twenty-two patients (73%) had undergone hysterectomy and 8 patients (27%) had undergone myomectomy. The mean tumor diameter was 6.12 cm (range: 0.5-25 cm). The tumor was intramural in 11 patients (37%), subserosal in 7 patients (23%), and submucosal in 4 patients (13%). Microscopically, the bizarre cell distribution was focal in 8 patients (27%), multifocal in 12 patients (40%), and diffuse in 10 patients (33%). Bizarre cell density was low in 15 patients (50%), intermediate in 8 patients (27%), and high in 7 patients (23%). The mean mitotic count was 1.4 (0-4) in 10 high-power fields, and the tumor margin was regular in all cases. We observed pseudoinclusions in 24 of 30 (80%) tumors, karyorrhectic nuclei in 21 of 30 tumors (70%), prominent eosinophilic nucleoli with perinucleolar clearing in 12 tumors (40%), cytoplasmic eosinophilic inclusions in 11 tumors (37%), staghorn vessels in 9 tumors (30%), and alveolar-type edema in 9 tumors (30%). In addition, we examined the follow-up records of 26 patients (average duration: 58.1 mo). One patient had a smooth muscle tumor in the L3-L4 paravertebral region at 67 mo after hysterectomy. This tumor did not share similar microscopic and immunohistochemical findings to the patient's earlier uterine tumor. The definitive diagnosis of uterine smooth muscle tumors is important for the determination of the prognosis of the patient and the most appropriate therapeutic approach. As in several recent studies, our series has shown that LBN has a benign clinical course. However, other malignant morphologic criteria such as high mitotic rate and tumor cell necrosis should be excluded in the diagnosis of LBN.

EMMPRIN (CD147) Expression in Smooth Muscle Tumors of the Uterus.

Smooth muscle tumors of the uterus are the most common mesenchymal tumors of the gynecologic tract. The vast majority of these are benign leiomyomas that present no diagnostic difficulty. Because some benign smooth muscle tumors may degenerate and uncommon variants exist, the diagnosis can be challenging in some cases. The goal of this research was to investigate EMMPRIN expression in leiomyomas, leiomyoma variants, and leiomyosarcomas (LMS) to determine whether it has a potential role in differential diagnosis. EMMPRIN expression was investigated with immunohistochemistry in 103 uterine smooth muscle tumors, which included 19 usual leiomyomas, 52 leiomyoma variants, and 32 LMS. They were evaluated on the basis of staining extent, intensity, and also their combined score, and the groups were compared. EMMPRIN expression was present in 3 of 19 (15.7%) usual leiomyomas, 23 of 52 (44.3%) leiomyoma variants, and 28 of 32 (87.5%) LMS. There were statistically significant differences in staining extent and intensity, and also for their combined scores, between the LMS and benign groups. Although uterine smooth muscle tumors are usually diagnosed easily with conventional diagnostic criteria, the differentiation of LMS from some variants of leiomyoma can be challenging based soley on morphology. EMMPRIN may be a valuable immunohistochemical marker for differentiating LMS from benign smooth muscle tumors in problematic cases.

Expression of Glypican 3 in low and high grade urothelial carcinomas.

BACKGROUND: Glypican-3 (GPC3) is an oncofetal protein which is encoded by GPC3 gene and takes role in the regulation of cell division and apoptosis. Overexpression of GPC3 has been reported in some types of cancer such as hepatocellular carcinoma (HCC), melanoma, squamous cell carcinoma of the lungs and testicular germ cell tumors. The aim of this study was to investigate the immunohistochemical expression of GPC3 in the non-neoplastic urothelium and in urothelial carcinoma (UC). We also aimed to explore the alterations in the GPC3 expression according to the grade and the invasiveness of UC. METHODS: GPC3 expression was studied in 108 UC cases by using immunohistochemistry. Each section was evaluated in terms of the extensiveness and intensity of GPC3 staining. Scores of immunostaining were correlated with tumor grade and stage. RESULTS: GPC3 expression was observed in 38 cases (35.2%). GPC3 expression was positive in 43.6% of high and in 13.3% of low grade UC (p: 0.003). In 19 UC cases biopsy also harbored non-neoplastic urothelium which showed no staining for GPC3. The difference in staining percentages between low and high grade UCs, suggests that GPC3 staining could be used as an adjunctive marker in cases where the distinction between the low and high grade tumors is difficult. In addition, lack of staining in the non-neoplastic urothelial areas in 19 cases raises the possibility of the use of GPC3 staining for the distinction between neoplastic and non-neoplastic urothelium, especially in punch biopsy samples. CONCLUSIONS: Based on our results potential role of GPC3 in urothelial carcinogenesis warrants further investigation, especially the potential use of GPC3 for therapeutic and diagnostic purposes. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2260833001522844.

Attention! Cardiac tamponade may be caused by underlying Castleman's disease.

Castleman's disease is a rarely observed lymphoproliferative disease. In the literature, various signs and symptoms of the disease have been reported; one of these is secondary cardiac tamponade. We describe the case of a 41-year-old man who developed cardiac tamponade during examination, and who was later diagnosed with Castleman's disease, based on his lymph node biopsies.

The relationship of T helper-2 pathway components interleukin-4, interleukin-10, immunoglobulin e, and eosinophils with prognostic markers in non-hodgkin lymphoma: a case-control study.

OBJECTIVE: Increased risk for non-Hodgkin lymphoma (NHL) is associated with infections and environmental agents. We hypothesized that these factors chronically trigger the T helper-2 (Th2) pathway and result in lymphoma. We investigated the role of the Th2 pathway by exploring the relationships between components of the Th2 pathway, interleukin (IL)-10, IL-4, immunoglobulin E (IgE), and eosinophils, and prognostic markers of NHL. MATERIALS AND METHODS: Thirty-one NHL patients and 27 healthy controls were enrolled. IL-10, IL-4, IgE, and eosinophils were measured. IL-4 and IL-10 were analyzed with the enzyme amplified sensitivity immunoassay method. RESULTS: High IL-10 levels were correlated with several poor prognostic features, short early survival, and lymphopenia. There was a positive correlation between albumin and IL-4 levels and a negative correlation between IL-10 and albumin. There was no relationship related with eosinophils and IgE. We found remnant increased IL-4, which could be a clue for the triggering of the Th2 pathway in the background. CONCLUSION: There is a need for differently designed studies to detect the place of the Th2 pathway in NHL.

Fascin and EMMPRIN expression in primary mucinous tumors of ovary: a tissue microarray study.

OBJECTIVES: The aim of this study was to compare the expressions of fascin and EMMPRIN in primary malignant, borderline and benign mucinous ovarian tumors, and to investigate the relationship of these markers with tumor progression and their applicability to differential diagnosis. MATERIALS AND METHODS: An immunohistochemical study was performed for fascin and EMMPRIN using the tissue microarray technique. Eighty-one cases were included in the study; there were 37 benign, 25 borderline and 19 malignant primary mucinous ovarian tumors. For each case, a total staining score was determined, consisting of scores for extent of staining and intensity of staining. The cases were allocated to negative, weakly positive and strongly positive staining categories, according to the total staining score. RESULTS: Both of the markers were significantly negative in benign tumors as compared with borderline and malignant tumors. There was no significant difference between borderline and malignant groups for both markers. Sixty-eight percent of malignant tumors were stained positive by fascin, while this rate was 40% for borderline mucinous tumors. All malignant tumors were strongly stained positive for EMMPRIN, while this rate was 92% for borderline mucinous tumors. The rest of the cases stained weakly positive. No significant difference in staining score was found between fascin and EMMPRIN expression. CONCLUSIONS: In ovarian primary mucinous tumors, fascin and EMMPRIN may play an important role in tumor progression from benign tumor to carcinoma. In that context, EMMPRIN and fascin expression may have potential application in the differential diagnosis of some diagnostically problematic mucinous ovarian tumors. However, the differential diagnostic applicability of EMMPRIN appears to be more limited than that of fascin due to its wide spectrum of staining in mucinous ovarian tumors.

Mantle cell lymphoma mimicking rectal carcinoma.

Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma. After the (11;14) translocation was identified as its constant finding in 1992, MCL was recognized as a separate subgroup of non-Hodgkin lymphoma (NHL). In MCL, extranodal involvement may be observed in the bone marrow, the spleen, the liver, and the gastrointestinal system (GIS). Cases of MCL that present with a massive and solitary rectal mass are rare in the literature. In this case report, our aim was to present an MCL patient with a rarely observed solitary rectal involvement mimicking rectal carcinoma and to discuss treatment options for this patient.

Effects of paroxetine on cutaneous wound healing in healthy and diabetic rats.

OBJECTIVE: The aim of this study was to evaluate the histologic effects of acute paroxetine administration on wound healing in healthy and streptozotocin-induced diabetic rats. DESIGN: This study has a randomized controlled experimental design. SETTING: Healthy (n = 32) and diabetic (n = 32) rats were further divided into 2 groups of saline or paroxetine administration. PARTICIPANTS: Sixty-four male Sprague-Dawley rats were used in this study. INTERVENTIONS: Paroxetine was injected intraperitoneally every day. Full-thickness excision wounds were created with a 4-mm dermal punch on the back of all rats. The healing wound area was removed with a 6-mm dermal punch at postwounding days 1, 3, 7, and 14. MAIN OUTCOME MEASURES: Polymorphonuclear leukocyte, mononuclear inflammatory cell, fibroblast, and blood vessel counts and epithelialization were evaluated under light microscope. MAIN RESULTS: There was no statistically significant difference observed in the polymorphonuclear leukocyte, mononuclear inflammatory cell, and blood vessel counts in the healthy and diabetic rats with and without paroxetine administration. The number of fibroblasts was significantly higher at postwounding day 14 of the paroxetine-administered healthy rats compared with the saline-administered healthy rats (P = .04). However, the number of fibroblasts did not show any difference by paroxetine administration in the diabetic rats. There was no statistically significant difference in epithelialization regarding all the postwounding days, but complete epithelialization was observed in all rats on postwounding day 14 in the healthy and paroxetine-administered group. CONCLUSION: Short-term paroxetine administration may enhance cutaneous wound healing by increasing the number of fibroblasts and causing better epithelialization over time in healthy rats but not in diabetic rats.

Comparison of oversized artery and vein grafts for interpositional pedicle lengthening in rat femoral artery.

Vessel grafting is commonly used for revascularization or pedicle lengthening. Although veins are more commonly used, they can form aneurysms when bridging an arterial gap. This can lead to thrombosis, and the risk is increased when there is a size discrepancy. This study reports the long-term results of arterial lengthening via size discrepant carotid artery and femoral vein grafts in a rat femoral artery model (1:1.5 ratio). A total of 28 rats were used in this study, divided into two groups of 14. By the 21st day, one anastomosis in each group has been found to be thrombosed. Long-term patency rates were the same for both groups (93.3%). Radiologic imaging showed that size match in the carotid artery grafts was excellent despite of slightly fusiform dilatation, but in the vein groups, pronounced aneurismal deformation and distortion in the anastomosis was seen. Histologic analysis revealed that in the arterial grafts, endothelial continuity was smooth and mural inflammation was less than that of the vein grafts. Organized or recanalized mural thrombi were seen in 38.5% in the vein grafts, whereas in arterial grafts there were none.