A Novel Algorithm for Evaluating Bone Metastatic Potential of Breast Cancer through Morphometry and Computational Mathematics.

Bone metastases represent about 70% of breast cancer metastases and are associated with worse prognosis as the tumor cells acquire more aggressive features. The selection and investigation of patients with a high risk of developing bone metastasis would have a significant impact on patients' management and survival. The patients were selected from the database of Carol Davila Clinical Nephrology Hospital of Bucharest. Their tumor specimens were pathologically processed, and a representative area was selected. This area was scanned using an Olympus VS200 slide scanner and further analyzed using QuPath software v0.4.4. A representative group of approximately 60-100 tumor cells was selected from each section, for which the following parameters were analyzed: nuclear area, nuclear perimeter, long axis and cell surface. Starting from these measurements, the following were calculated: the mean nuclear area and mean nuclear volume, the nucleus to cytoplasm ratio, the length of the two axes, the long axis to short axis ratio, the acyclicity and anellipticity grade and the mean internuclear distance. The tumor cells belonging to patients known to have bone metastasis seemed to have a lower nuclear area (<55 µm2, p = 0.0035), smaller long axis (<9 µm, p = 0.0015), smaller values for the small axis (<7 µm, p = 0.0008), smaller mean nuclear volume (<200 µm3, p = 0.0146) and lower mean internuclear distance (<10.5 µm, p = 0.0007) but a higher nucleus to cytoplasm ratio (>1.1, p = 0.0418), higher axis ratio (>1.2, p = 0.088), higher acyclicity grade (>1.145, p = 0.0857) and higher anellipticity grade (>1.14, p = 0.1362). These parameters can be used for the evaluation of risk category of developing bone metastases. These results can be useful for the evaluation of bone metastatic potential of breast cancer and for the selection of high-risk patients whose molecular profiles would require further investigations and evaluation.

Transdifferentiations and heterogeneity in the stromal niches of uterine leiomyomas.

Uterine leiomyomas, also known as uterine fibroids (UFs), are benign smooth muscle cells tumors, the most frequent tumors in women. Even though UFs are monoclonal tumors, they contain a heterogeneous and versatile cells population. There are scarce proofs about the processes of transdifferentiation that might occur in UFs, modify the tumor microenvironment and support blood and lymph vessels formation. The stromal niches of the UFs harbor cells with angiogenic∕lymphangiogenic, as well as with vasculogenic∕lymphvasculogenic potential, which belong to a phenotypic continuum between the endothelial and mesenchymal lineages. Within these niches, the expressions of CD44 and podoplanin were less investigated and regarded as markers of such processes of transdifferentiation.

Surgical pathology, management and outcome in the vulvar melanoma associated with abdominal mass - a case report.

Vulvar malignant melanomas are extremely rare neoplasms, representing less than 3% of all cancers in women, 9% of all external genital tract malignancies and 9% of all primary vulvar malignancies. We present the case of a 60-year-old Caucasian patient, who has been admitted in the Clinic of Obstetrics and Gynecology with polymorphic, vulvar local, pelvic-abdominal, genitourinary and general symptoms, being diagnosed with nodular and superficial spreading vulvar melanoma and multiple voluminous uterine leiomyoma with various degenerations. Our study presents the approach of this case in terms of surgical pathology, management, prognosis and outcome. Surgical treatment is the central element of therapeutic management. Vulva melanomas are in general a relatively unpredictable unfavorable prognosis. The sizes of the tumor, the thickness and micro-staging are essential factors for prognosis.

Efficacy of 7-Day and 14-Day Triple Therapy Regimens for the Eradication of Helicobacter pylori: A Comparative Study in a Cohort of Romanian Patients.

Objective. This study compared the eradication rates of of Helicobacter pylori (HP) infection by a 7-day and 14-day anti-HP regimen. Materials and Methods. An open, randomized, prospective study was performed to evaluate the response to anti-HP treatment in adult HP-positive patients following a 7-day course (Regimen A) of a proton pump inhibitor in association with clarithromycin and amoxicillin compared to a 14-day course (Regimen B). Gastric biopsies were performed at baseline and two months after anti-HP treatment. Results. Seventy-eight patients aged 18-64 years (28 males, 50 females) diagnosed with HP infection were included. Fifty-two (66.7%) patients received Regimen B and 26 (33.3%) Regimen A. The overall eradication rate was 70.5%. Better treatment response (p < 0.01) was seen in Regimen B (44/52, 84.2% versus 11/26, 42.3%). Significant improvement in histological features was seen in regimen B. There has been significant overall reduction in endoscopic aspects of gastric and duodenal lesions in both regimens. Younger patients ≤35 years had a better response to Regimen B. Better treatment response was seen in women, urban residents, and those with tertiary level of education in both groups. Conclusion. 14-day anti-HP regimen offered a significant better overall eradication of HP in study population.

Unusual finding of a mediastinal T-cell lymphoma in a 13-year-old patient - a case report.

T-cell lymphoblastic lymphoma is an aggressive malignancy that represents 85% of all lymphoblastic lymphomas. It usually occurs in late childhood, adolescence and young adulthood with a 2:1 male preponderance and it presents with pleural effusion and respiratory symptoms and in rare cases vena cava syndrome can be encountered. We present the case of a 13-year-old patient who was referred to our clinic from a local hospital where he was diagnosed with a mediastinal tumor. The patient presented with thoracic pain, fever, coughing and fatigability for a month prior to admission, after having underwent surgery for abdominal pain (appendectomy). On admission to our hospital, a thoracic computed tomography (CT) scan was performed and showed the presence of an anterior mediastinal mass measuring 109/76/140 mm, well defined, which came in close contact with the superior vena cava, the ascending aorta and the pulmonary artery, right pleural effusion and a collapsed lung on the right side. The decision was taken to perform a tumor biopsy and a right pleural drain was placed. The patient's post-operative evolution was favorable with the remission of the respiratory symptoms. The histopathological result showed the presence of T-cell lymphoblastic lymphoma and the patient was then transferred to the oncology ward where he underwent chemotherapeutic treatment, with a favorable outcome. T-cell lymphoblastic lymphoma is an aggressive type of lymphoma and it is usually hard to diagnose considering the fact that the symptoms are often vague. It is essential to establish the diagnosis without delay and start appropriate chemotherapeutic treatment.

c-kit positive cells and networks in tooth germs of human midterm fetuses.

Numerous studies have attempted to characterize the dental pulp stem cells. However, studies performed on prenatal human tissues have not been performed to evaluate the in situ characterization and topography of progenitor cells. We aimed to perform such a study using of antibodies for CD117/c-kit and multiplex antibody for Ki67+ caspase 3. Antibodies were applied on samples dissected from five human midterm fetuses. Positive CD117/c-kit labeling was found in mesenchymal derived tissues, such as the dental follicle and the dental papilla. The epithelial tissues, that is, dental lamina, enamel organ and oral epithelia, also displayed isolated progenitor cells which were CD117/c-kit positive. Interestingly, CD117/c-kit positive cells of mesenchymal derived tissues extended multiple prolongations building networks; the most consistent of such networks were those of the dental follicle and the perivascular networks of the dental papilla. However, the mantle of the dental papilla was also positive for CD117/c-kit positive stromal networks. The CD117/c-kit cell populations building networks appeared mostly with a Ki67 negative phenotype. The results suggest that CD117/c-kit progenitor cells of the prenatal tooth germ tissues might be involved in intercellular signaling.

The mandibular ridge oral mucosa model of stromal influences on the endothelial tip cells: an immunohistochemical and TEM study.

This study aimed to evaluate by immunohistochemistry and transmission electron microscopy (TEM) the morphological features of the oral mucosa endothelial tip cells (ETCs) and to determine the immune and ultrastructural patterns of the stromal nonimmune cells which could influence healing processes. Immune labeling was performed on bioptic samples obtained from six edentulous patients undergoing surgery for dental implants placement; three normal samples were collected from patients prior to the extraction of the third mandibular molar. The antibodies were tested for CD34, CD117(c-kit), platelet derived growth factor receptor-alpha (PDGFR-α), Mast Cell Tryptase, CD44, vimentin, CD45, CD105, alpha-smooth muscle actin, FGF2, Ki67. In light microscopy, while stromal cells (StrCs) of the reparatory and normal oral mucosa, with a fibroblastic appearance, were found positive for a CD34/CD44/CD45/CD105/PDGFR-α/vimentin immune phenotype, the CD117/c-kit labeling led to a positive stromal reaction only in the reparatory mucosa. In TEM, non-immune StrCs presenting particular ultrastructural features were identified as circulating fibrocytes (CFCs). Within the lamina propria CFCs were in close contact with ETCs. Long processes of the ETCs were moniliform, and hook-like collaterals were arising from the dilated segments, suggestive for a different stage migration. Maintenance and healing of oral mucosa are so supported by extensive processes of angiogenesis, guided by ETCs that, in turn, are influenced by the CFCs that populate the stromal compartment both in normal and reparatory states. Therefore, CFCs could be targeted by specific therapies, with pro- or anti-angiogenic purposes.

Immunolocalization of 200 kDa neurofilaments in human cardiac endothelial cells.

Neurofilaments usually associated with neural tissues are the type IV family of intermediate filaments. Nestin, which is a type VI intermediate filament, is a well known marker of endothelial cells in newly formed blood vessels and is developmentally and structurally related to type IV intermediate filaments. We aimed to determine whether or not cardiac endothelial cells (ECs) label with antibodies for neurofilaments (200 kDa, Novocastra-Leica, clone RT97), as is already known for nestin. We used cardiac samples (sinoatrial nodes/right atrial walls) from cadavers of normal and diabetic donors (6 normal adults, 10 type II diabetic adults, 1 child) for neurofilament immune labeling. Positive labeling of endothelial cells, microvascular and endocardial, was obtained in all samples. As this is the first such evidence, we can only presume that the neurofilament positive labeling of endothelial cells may be due to interactions of nestin and neurofilaments. Further studies are needed to evaluate the hypothesis we reached and, in order to explore whether or not neurofilament antibodies can qualify as markers of angiogenesis.

Morphologic features of the fetal mandibular condyle: layers, canals and microvascular pattern.

During organogenesis the mandibular condyle is divided by a fibrovascular septum, the persistence of which in the growing cartilage can lead to a bifid condyle. In this study we have evaluated the morphology of 3rd trimester human fetal temporomandibular (TMJ) specimens in order to determine the pattern of the vascular morphology associated with the layers and vascular canals (VCs) of the developing condyle (covering layers and condyle proper). Eleven human fetuses of 27-38cm crown-rump length were used for histological (hematoxylin-eosin, Van Gieson stain) and immunohistochemical evaluation (antibodies for bcl2 and CD34) and another two of 24 and 31cm, for TMJ microvasculature studies after black ink injections. With increasing fetal age, the intermediate loose lamina (LL) of the condylar proliferative layer evolves from a vascular-mesenchymal to a fibrillar pattern, via a transitory stage of a clear space that may be misdiagnosed as lower joint cavity (LJC). Within the condyle proper VCs may be present on its entire sagittal length, deepening variably towards the erosive zone and opened superiorly in the LL loose layer. Vessels of the evolving LL enter the condyle, directly or through the VCs; these vessels retract peripherally with increasing age and the intrinsic vessels of the condyle supplied from the erosive zone become prevalent. Vascular morphogenesis at the level of the LL seems comparable to that at the level of the LJC where characteristic glomeruli regress with increasing age. Lack of vascular regression and closure of central V-shaped defects of the condyle, as observed in 2/22 condyles, may represent a developmental substrate for condylar bifidism or a predisposing condition weakening the condyle, and making it more sensitive to trauma in childhood.