Primary pure spindle cell carcinoma (sarcomatoid carcinoma) of the ovary: A case report with immunohistochemical study

BACKGROUND: In the ovary, sarcomatoid carcinoma has been reported only as mural nodules in epithelial malignant or borderline serous or mucinous cystic neoplasms, and in teratomas. In this paper we report a rare case of a solid sarcomatoid carcinoma of the ovary, without accompanying component of giant cells, pleomorphic cells, or glandular and other epithelial structures. CASE PRESENTATION: This case report refers to a sarcomatoid carcinoma of the ovary in in a 57 year-old woman with abdominal pain. Macroscopically, the neoplasm was a 15x10x5 cm ovarian mass that featured gray white solid fleshy areas, interspersed with areas of necrosis, hemorrhage and cystic spaces filled with thick fluid. The epithelial differentiation of the tumor was demonstrated by strong and diffuse reactivity to CAM5.2 and focal immunoreactivity to EMA. A diagnosis of malignant mesenchymal tumor was excluded due to negativity for desmin, smooth muscle actin, caldesmon, CD34, CD10, and myoglobin. Neural, neuroendocrine neoplasm, melanoma and Perivascular Epithelioid Cell Tumor (PEComa) were excluded because of negativity for S100, chromogranin, synaptophysin and HMB45. CONCLUSION: Primary ovarian spindle cell carcinoma is a rare neoplasm, which must be considered in the differential diagnosis of solid ovarian mass with spindle cell appearance. This case adds to our knowledge of the biological behavior of these rare neoplasms. The distinction from true sarcomas and carcinosarcomas is important because of the more favorable prognosis of the spindle cell carcinomas. However their diagnosis necessitates a careful tissue sampling and immunohistochemical staining

Primary alveolar soft part sarcoma of uterine corpus: a case report with immunohistochemical, ultrastructural study and review of literature

Background Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignancy. ASPS usually occurs most commonly in the deep soft tissues of the thigh and buttock or the head and neck regions. ASPS that originate from the uterine corpus are even more rare, with only 10 previous cases reported in the English literature. Case presentation In our case, the alveolar features were completely lost and the tumour shows a solid, non-alveolar pattern and the nuclei have marked variation in nuclear size, and multinucleation. The correct pathological diagnosis has been made by immuno- histochemical and ultrastructural features, which rvealed overexpression of TFE3 and peculiar cytoplasmic crystalline inclusions. In this paper, an additional case of primary ASPS of uterine corpus is reported with immunohistochemical, ultrastructural study and review of literature in the effort to delineate its clinical and pathological features. In this unusual site, the diagnosis can be problematic because ASPS can mimic other primary or metastatic uterine neoplasms. Conclusions Thus, in this unusual presentation an essential diagnostic marker is the nuclear over-expression of TFE3 as well as ultrastructural study, which reveals the presence of peculiar cytoplasmic crystalline inclusions

miR-199a-3p increases the anti-tumor activity of palbociclib in liver cancer models

Palbociclib is in early-stage clinical testing in advanced hepatocellular carcinoma (HCC). Here, we investigated whether the anti-tumor activity of palbociclib, which prevents the CDK4/6-mediated phosphorylation of RB1 but simultaneously activates AKT signaling, could be improved by its combination with a PI3K/AKT/mTOR inhibitor in liver cancer models. The selective pan-AKT inhibitor, MK-2206, or the microRNA-199a-3p were tested in combination with palbociclib in HCC cell lines and in the TG221 HCC transgenic mouse model. The combination palbociclib/MK-2206 was highly effective, but too toxic to be tolerated by mice. Conversely, the combination miR-199a-3p mimics/palbociclib not only induced a complete or partial regression of tumor lesions, but was also well tolerated. After 3 weeks of treatment, the combination produced a significant reduction in number and size of tumor nodules in comparison with palbociclib or miR-199a-3p mimics used as single agents. Moreover, we also reported the efficacy of this combination against sorafenib-resistant cells in vitro and in vivo. At the molecular level, the combination caused the simultaneous decrease of the phosphorylation of both RB1 and of AKT. Our findings provide pre-clinical evidence for the efficacy of the combination miR-199a-3p/palbociclib as anti-HCC treatment or as a new approach to overcome sorafenib resistance

Pleural tuberculosis: medical thoracoscopy greatly increases the diagnostic accuracy

Our objective was to evaluate the efficacy of a standardised work-up in the diagnosis of pleural tuberculosis (TB) that included fibreoptic bronchoscopy and medical thoracoscopy. A consecutive series of 52 pleural TB patients observed during the period 2001-2015 was evaluated retrospectively. 20 females, mean (range) age 39.7 (18-74) years, and 32 males, mean (range) age 45.75 (21-83) years, were included (28 non-EU citizens (53.8%)). The diagnosis of TB infections was established by identification (using stains, culture or molecular tests) of Mycobacterium tuberculosis in the pleura, sputum and/or bronchial specimens, or by evidence of caseous granulomas on pleural biopsies. Patients with and without lung lesions were considered separately. The diagnostic yield of the microbiological tests on pleural fluid was 17.3% (nine out of 52 patients). Among the 18 patients with lung lesions, bronchial samples (washing, lavage or biopsy) were positive in 50% of cases (nine patients). Cultures of pleural biopsies were positive in 63% of cases (29 out of 46 patients); pleural histology was relevant in all patients. Without pleural biopsy, a diagnosis would have been reached in 15 out of 52 patients (28.6%) and in four of them only following culture at 30-40 days. An integrated diagnostic work-up that includes all the diagnostic methods of interventional pulmonology is required for a diagnosis of pleural TB. In the majority of patients, a diagnosis can be reached only with pleural biopsy

Amniotic membrane-mesenchymal stromal cells secreted factors and extracellular vesicle-miRNAs: Anti-inflammatory and regenerative features for musculoskeletal tissues

Human amniotic membrane-derived mesenchymal stromal cells (hAMSCs) are easily obtained in large quantities and free from ethical concerns. Promising therapeutic results for both hAMSCs and their secreted factors (secretome) were described by several invitro and preclinical studies, often for treatment of orthopedic disorders such as osteoarthritis (OA) and tendinopathy. For clinical translation of the hAMSC secretome as cell-free therapy, a detailed characterization of hAMSC-secreted factors is mandatory. Herein, we tested the presence of 200 secreted factors and 754 miRNAs in extracellular vesicles (EVs). Thirty-seven cytokines/chemokines were identified at varying abundance, some of which involved in both chemotaxis and homeostasis of inflammatory cells and in positive remodeling of extracellular matrix, often damaged in tendinopathy and OA. We also found 336 EV-miRNAs, 51 of which accounted for more than95% of the genetic message. A focused analysis based on miRNAs related to OA and tendinopathy showed that most abundant EV-miRNAs are teno- and chondro-protective, able to induce M2 macrophage polarization, inhibit inflammatory Tcells, and promote Treg. Functional analysis on IL-1beta treated tenocytes and chondrocytes resulted in downregulation of inflammation-associated genes. Overall, presence of key regulatory molecules and miRNAs explain the promising therapeutic results of hAMSCs and their secretome for treatment of musculoskeletal conditions and are a groundwork for similar studies in other pathologies. Furthermore, identified molecules will pave the way for future studies aimed at more sharply predicting disease-targeted clinical efficacy, as well as setting up potency and release assays to fingerprint clinical-grade batches of whole secretome or purified components

Comparison of EV-free fraction, EVs, and total secretome of amniotic mesenchymal stromal cells for their immunomodulatory potential: a translational perspective

Amniotic mesenchymal stromal cells (hAMSCs) have unique immunomodulatory properties demonstrated in vitro and in vivo in various diseases in which the dysregulated immune system plays a major role. The immunomodulatory and pro-regenerative effects of MSCs, among which hAMSCs lie in the bioactive factors they secrete and in their paracrine activity, is well known. The mix of these factors (i.e., secretome) can be either freely secreted or conveyed by extracellular vesicles (EV), thus identifying two components in the cell secretome: EV-free and EV fractions. This study aimed to discern the relative impact of the individual components on the immunomodulatory action of the hAMSC secretome in order to obtain useful information for implementing future therapeutic approaches using immunomodulatory therapies based on the MSC secretome. To this aim, we isolated EVs from the hAMSC secretome (hAMSC-CM) by ultracentrifugation and validated the vesicular product according to the International Society for Extracellular Vesicles (ISEV) criteria. EVs were re-diluted in serum-free medium to maintain the EV concentration initially present in the original CM. We compared the effects of the EV-free and EV fractions with those exerted by hAMSC-CM in toto on the activation and differentiation of immune cell subpopulations belonging to both the innate and adaptive immune systems.We observed that the EV-free fraction, similar to hAMSC-CM in toto, a) decreases the proliferation of activated peripheral blood mononuclear cells (PBMC), b) reduces the polarization of T cells toward inflammatory Th subsets, and induces the induction of regulatory T cells; c) affects monocyte polarization to antigen-presenting cells fostering the acquisition of anti-inflammatory macrophage (M2) markers; and d) reduces the activation of B lymphocytes and their maturation to plasma cells. We observed instead that all investigated EV fractions, when used in the original concentrations, failed to exert any immunomodulatory effect, even though we show that EVs are internalized by various immune cells within PBMC. These findings suggest that the active component able to induce immune regulation, tested at original concentrations, of the hAMSC secretome resides in factors not conveyed in EVs. However, EVs isolated from hAMSC could exert actions on other cell types, as reported by others

Repeated radiofrequency ablation for management of patients with cirrhosis with small hepatocellular carcinomas: a long-term cohort study. Hepatology 53

In most patients with cirrhosis, successful percutaneous ablation or surgical resection of hepatocellular carcinoma (HCC) is followed by recurrence. Radiofrequency ablation (RFA) has proven effective for treating HCC nodules, but its repeatability in managing recurrences and the impact of this approach on survival has not been evaluated. To this end, we retrospectively analyzed a prospective series of 706 patients with cirrhosis (ChildPugh class B7) who underwent RFA for 859 HCC 35 mm in diameter (1-2 per patient). The results of RFA were classified as complete responses (CRs) or treatment failures. CRs were obtained in 849 nodules (98.8%) and 696 patients (98.5%). During follow-up (median, 29 months), 465 (66.8%) of the 696 patients with CRs experienced a first recurrence at an incidence rate of 41 per 100 person-years (local recurrence 6.2; nonlocal 35). Cumulative incidences of first recurrence at 3 and 5 years were 70.8% and 81.7%, respectively. RFA was repeated in 323 (69.4%) of the 465 patients with first recurrence, restoring disease-free status in 318 (98.4%) cases. Subsequently, RFA was repeated in 147 (65.9%) of the 223 patients who developed a second recurrence after CR of the first, restoring disease-free status in 145 (98.6%) cases. Overall, there were 877 episodes of recurrence (1-8 per patient); 577 (65.8%) of these underwent RFA that achieved CRs in 557 (96.5%) cases. No procedure-related deaths occurred in 1,921 RFA sessions. Estimated 3-and 5-year overall and disease-free (after repeated RFAs) survival rates were 67.0% and 40.1% and 68.0 and 38.0%, respectively. Conclusion: RFA is safe and effective for managing HCC in patients with cirrhosis, and its high repeatability makes it particularly valuable for controlling intrahepatic recurrences. (HEPATOLOGY 2010;000:000-000.) H epatocellular carcinoma (HCC) is the third leading cause of death from cancer worldwide. 1 Most HCC patients have underlying cirrhosis, which complicates management of their cancer and is often the direct cause of death. 2 Internationally endorsed guidelines currently recommend surgical resection for early-stage HCCs in patients with well-preserved liver function. 3,4 When surgery is not possible

Extragenital Müllerian adenosarcoma with pouch of Douglas location

Background: Of all female genital tract tumors, 1-3% are stromal malignancies. In 8-10% of cases, these are represented by Mullerian adenosarcoma an extremely rare tumor characterized by a stromal component of usually low-grade malignancy and by a benign glandular epithelial component. Variant that arises in the pouch of Douglas is scarcely mentioned in the medical literature.Case Presentation: A 49-year-old para-0 woman, was seen at our OB/GYN-UNIT because she complained vaguely of pelvic pain. She had a mass of undefined nature in the pouch of Douglas. A simple excision of the mass showed low-grade Mullerian adenosarcoma with areas of stromal overgrowth. One and a half year after surgery, at another hospital, a mass was detected in the patient's posterior vaginal fornix and removed surgically. Six months later she came back to our observation with vaginal bleeding and mass in the vaginal fornix. We performed radical surgery. The pathological examination showed recurrent adenosarcoma. Surgical treatment was supplemented by radiation therapy.Conclusions: The case of Mullerian adenosarcoma reported here is the third known so far in the literature that was located in the pouch of Douglas. To date, only two other such cases have been reported, including one resulting from neoplastic degeneration of an endometriotic cyst