Anti-inflammatory and immunomodulatory activity of Mangifera indica L. reveals the modulation of COX-2/mPGES-1 axis and Th17/Treg ratio.

In the context of inflammation and immunity, there are fragmented and observational studies relating to the pharmacological activity of Mangifera indica L. and its main active component, mangiferin. Therefore, we aimed to analyze the potential beneficial effects of this plant extract (MIE, 90 % in mangiferin) in a mouse model of gouty arthritis, to allow the evaluation of cellular immune phenotypes and the biochemical mechanism/s beyond MIE activity. Gouty arthritis was induced by the intra-articular administration of MSU crystals (200 µg 20 µl-1), whereas MIE (0.1-10 mg kg-1) or corresponding vehicle (DMSO/saline 1:3) were orally administrated concomitantly with MSU (time 0), 6 and 12 h after the stimulus. Thereafter, knee joint score and oedema were evaluated in addition to western blot analysis for COX-2/mPGES-1 axis. Moreover, the analysis of pro/anti-inflammatory cyto-chemokines coupled with the phenotyping of the cellular infiltrate was performed. Treatment with MIE revealed a dose-dependent reduction in joint inflammatory scores with maximal inhibition observed at 10 mg kg-1. MIE significantly reduced leukocyte infiltration and activation and the expression of different pro-inflammatory cyto-chemokines in inflamed tissues. Furthermore, biochemical analysis revealed that MIE modulated COX-2/mPGES-1 and mPGDS-1/PPARγ pathways. Flow cytometry analysis also highlighted a prominent modulation of inflammatory monocytes (CD11b+/CD115+/LY6Chi), and Treg cells (CD4+/CD25+/FOXP3+) after MIE treatment. Collectively, the results of this study demonstrate a novel function of MIE to positively affect the local and systemic inflammatory/immunological perturbance in the onset and progression of gouty arthritis.

Sarcomatoid larynx carcinoma differential clinical evolution, on field statistical considerations.

Spindle cell larynx carcinoma (SpCC) represents around 3% of laryngeal cancers. It is originated by a single cancer stem cell undergoing epithelial to mesenchymal transition. This explains the aggressiveness, the peculiar resistance to conventional therapy and the frequent relapses. We focused on this particular cancer subset characteristics in patients, in early and advanced stages primarily aiming to define and highlight the differences with Laryngeal Squamous Cell Carcinoma (LSCC) focusing on clinical features, treatments, follow-up and survival in a patient's cohort composed by comparable cases from two subgroups.

Poorly Differentiated Neuroendocrine Larynx Carcinoma: Clinical Features and miRNAs Signature-A New Goal for Early Diagnosis and Therapy?

Laryngeal neuroendocrine carcinomas (LNECs) are rare and highly heterogeneous malignancies presenting a wide range of pathological and clinical manifestations. Herein, we retrospectively characterize ten patients diagnosticated with LNEC, five of which were defined as well-moderately differentiated neuroendocrine carcinomas, and five that were defined as poorly differentiated neuroendocrine carcinomas, according to the latest WHO classification. Clinical features were analyzed and compared between the two subgroups together with a microRNA study which evidenced a peculiar signature likely related to poorly differentiated larynx neuroendocrine carcinomas. These findings may offer new useful insights for clinicians to improve diagnosis efficiency, therapy response, and patients' outcome for this aggressive neoplasm.

Vulvar lymphoedematous pseudotumours mistaken for aggressive angiomyxoma: report of two cases.

BACKGROUND: We describe 2 cases of vulvar pseudotumour due to lymphatic obstruction with chronic lymphoedema of unknown cause that presented as a solitary mass that mimicked aggressive angiomyxoma. MATERIAL AND METHODS: Both patients presented with a vulvar mass without medical history of trauma, surgery in the anogenital region or skin diseases. One patient was overweight (BMI = 26). Both surgically resected vulvar specimens were represented by a polypoid mass with a soft and a gelatinous cut surface. RESULTS: Histologically, the presence of an abundant oedematous stroma with spindle-shaped cells and numerous thin-walled small-to-medium vessels may be confused with an aggressive angiomyxoma. The diagnostic key was represented by the massive oedema, rather than myxoid stroma, with the presence of dilated, tortuous lymphatic channels (some surrounded by clusters of lymphocytes) in the dermis. CONCLUSION: The recognition of these lesions is important because they may be the cause of problems in differential diagnosis and therapeutic management. In fact, such lesions can be mistaken from both the clinical and histological perspective as a primitive tumour of the vulva-like aggressive angiomyxoma. However, these lesions are not true neoplasms and are likely due to lymphatic obstruction with lymphoedema. A simple surgical excision with vulvoplasty is curative.

Hepatoid carcinoma of the ovary with sex cord stromal tumor: a previously unrecognized association.

BACKGROUND: Hepatoid carcinoma (HC) of ovary is a rare type of epithelial tumor composed mainly of epithelioid cells with abundant acidophilic cytoplasm, histologically indistinguishable from hepatocellular carcinoma. We report a previously unrecognized case of HC of ovary concurrent with a Sertoli cell tumor. CASE REPORT: A 42-year-old woman patient with a long-term history of hepatitis C presented with a mass of left ovary without evidence of hepatic tumor. After initial diagnosis of primary ovarian carcinoma (FIGO Stage I), she had experienced a first recurrence in upper abdomen. Histologically, the primary tumor was composed of epithelioid cells with "hepatoid features" in association with a sex cord stromal tumor of Sertoli-type. Immunohistochemistry hepatoid cells stained positively for hepatocyte paraffin-1, alpha-fetoprotein and alpha-1 antitrypsin; moreover, Sertoli-type cells were positive for alpha-inhibin, calretinin and CD99. A final diagnosis of HC concurrent with Sertoli-type tumor was made. CONCLUSION: The occurrence of this unreported association of HC with Sertoli-like tumor, the problems of differential diagnosis and therapeutic management of these tumors are the subject of this presentation. A diagnosis of ovarian metastasis from hepatocellular carcinoma is easy in patients with known primary tumor of liver and should be always excluded in these cases as an hepatoid variant of yolk sac tumor. Immunohistochemistry is not useful in these cases. However, a combination of clinical and pathological features is necessary for a correct diagnosis.

Hepatocellular carcinoma metastatic to the kidney mimicking renal oncocytoma.

BACKGROUND: Renal metastases of hepatocellular carcinoma (HCC) are very rare. To our knowledge only five cases have been reported to the present; all had a well-known primary HCC. METHODS: We describe the clinico-pathological features of a rare case of HCC metastatic to the kidney in which the renal mass was the clinical debut of disease. The patient was a 54-year-old woman previously submitted to orthotopic liver transplantation, who underwent left nephrectomy for a renal mass. RESULTS: Histologically, the tumor was composed mainly of epithelioid cells with homogeneous acidophilic cytoplasm resembling oncocytoma or primary renal carcinoma with oncocytic features. A correct diagnosis was made on the basis of positive immunostaining for hepatocyte paraffin 1. CONCLUSIONS: Metastasis to the kidney is a rare complication that should be considered whenever a renal mass is present in patients with HCC. Since HCC may histologically resemble primary renal tumors such as oncocytoma, pathologists must be aware of this possibility above all in patients referred for liver transplantation and treated with immunosuppressant drugs. Immunohistochemistry is particularly helpful to establish a precise diagnosis in cases of doubt.

Monotypic epithelioid angiomyolipoma of the adrenal gland: an unusual site for a rare extrarenal tumor.

Epithelioid angiomyolipoma (AML) is an uncommon renal mesenchymal tumor with malignant potential and is frequently associated with tuberous sclerosis. Extrarenal AMLs are rare, and to the best of our knowledge, this is the first reported case of a primary monotypic epithelioid AML of adrenal gland in a patient without evidence of tuberous sclerosis. The patient is a 42-year old man who presented with retroperitoneal hemorrhage resulting from spontaneous rupture of adrenal mass. Histologically, the tumor showed a prominent component of epithelioid smooth muscle cells with slightly pleomorphic nuclei, sometimes with prominent nucleoli and eosinophilic cytoplasm resembling oncocytic tumors. Epithelioid cells were positive for melanoma (HMB45 and positive MelanA) and smooth muscle markers (alpha-smooth muscle-specific actin), but not for epithelial markers (cytokeratin, EMA). Differential diagnosis from renal cell carcinoma, adrenal gland carcinoma, and metastatic carcinoma is often challenging because of its epithelioid morphology. Because primary and secondary malignant tumors are much more common and aggressive neoplasms, establishing the correct diagnosis has important therapeutic and prognostic implications.

Nonpolypoid intestinal mantle cell lymphoma resembling MALT lymphoma with successful response to rituximab.

Two unusual cases of mantle cell lymphoma are reported. They involved the ileum and right colon without multiple lymphomatous polyposis and morphologically resembled an extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type.

Mucinous carcinoma of thyroid gland. Report of a primary and a metastatic mucinous tumour from ovarian adenocarcinoma with immunohistochemical study and review of literature.

Mucinous carcinoma of the thyroid gland is an uncommon tumour that from the histological point of view, resembles mucinous carcinoma of others sites. Although a mucinous appearance has sometimes been reported in association with cases of typical thyroid carcinoma, true mucinous carcinoma is exceptionally rare. We describe two cases of thyroid tumours with mucinous differentiation studied with immunohistochemistry. Both cases disclosed a similar histological appearance, with small nests and sheets of malignant epithelial cells associated with extensive extracellular mucin that substituted and entrapped the follicular parenchyma of the thyroid. Thyroglobulin and focally thyroid transcription factor (TTF) 1 were positive in one case. From these findings, we classified this tumour as primary mucinous thyroid carcinoma. Thyroglobulin and TTF-1 were negative in tumour cells of second case; on the contrary, positivity to the carcinoembryonic antigen and CA-125 was strong and generalized. However, successfully, the patient presented ascites associated to right ovarian mass. In this case, thyroid tumour represents the first clinical sign of an ovarian mucinous adenocarcinoma, and it has not been previously described in literature. Both patients died after few months to diagnosis. In conclusion, primary and secondary mucinous carcinoma are rare and unusual tumours of the thyroid gland that can be a cause of pitfall in differential diagnosis. In these cases, for a correct diagnosis, a complete clinical history, restricted histological criteria and immunohistochemical panel are necessary.

Non-Hodgkin lymphomas concurrent with HHV8-associated Kaposi's sarcoma in the same lymph node in AIDS and non-AIDS patients.

BACKGROUND: The association between lymphomas and Kaposi's sarcoma has been described since 1920. The simultaneous presence of the 2 pathologic entities within the same lymph node is a rare and interesting occurrence. In the few cases described, the presence of human herpesvirus 8 (HHV8) and Epstein-Barr virus (EBV) in the different neoplastic areas was investigated only by immunohistochemistry and in situ hybridization studies. METHODS: Two cases of concurrent non-Hodgkin lymphoma and Kaposi's sarcoma in the same lymph node are described: a diffuse large B cell lymphoma in an AIDS patient and a T cell-rich large B cell lymphoma in a HIV-negative patient, complete with the clinical, immunohistological and molecular features, the latter ones defined after isolation of the different neoplastic areas by laser capture microdissection. RESULTS: Polymerase chain reaction assays revealed HHV8 DNA sequences only in the microdissected Kaposi's sarcoma areas and EBV DNA sequences only in the lymphomatous areas in both cases, confirming the HHV8 infection only in the neoplastic sarcomatous cells and evidencing the EBV infection only in the lymphomatous cells. CONCLUSION: This study represents a further confirmation of the supposed different etiopathogenic mechanisms of the 2 neoplasias, suggesting a coincidental occurrence even when localized in the same lymph node, independently from HIV infection.

Inhibition of p110δ PI3K prevents inflammatory response and restenosis after artery injury.

Inflammatory cells play key roles in restenosis upon vascular surgical procedures such as bypass grafts, angioplasty and stent deployment but the molecular mechanisms by which these cells affect restenosis remain unclear. The p110δ isoform of phosphoinositide 3-kinase (PI3K) is mainly expressed in white blood cells. Here, we have investigated whether p110δ PI3K is involved in the pathogenesis of restenosis in a mouse model of carotid injury, which mimics the damage following arterial grafts. We used mice in which p110δ kinase activity has been disabled by a knockin (KI) point mutation in its ATP-binding site (p110δD910A/D910A PI3K mice). Wild-type (WT) and p110δD910A/D910A mice were subjected to longitudinal carotid injury. At 14 and 30 days after carotid injury, mice with inactive p110δ showed strongly decreased infiltration of inflammatory cells (including T lymphocytes and macrophages) and vascular smooth muscle cells (VSMCs), compared with WT mice. Likewise, PI-3065, a p110δ-selective PI3K inhibitor, almost completely prevented restenosis after artery injury. Our data showed that p110δ PI3K plays a main role in promoting neointimal thickening and inflammatory processes during vascular stenosis, with its inhibition providing significant reduction in restenosis following carotid injury. p110δ-selective inhibitors, recently approved for the treatment of human B-cell malignancies, therefore, present a new therapeutic opportunity to prevent the restenosis upon artery injury.

Oncocytic variant of mucoepidermoid carcinoma: a diagnostic challenge for the pathologist.

Oncocytic mucoepidermoid carcinoma of the salivary gland is rare. We report a 48-year-old man who presented with a slowly growing right parotid mass. A preoperative fine needle aspiration showed exclusively oncocytic cells and cellular debris. A first diagnosis of Warthin tumor or myoepithelioma was made. The patient underwent a superficial parotidectomy, and her postoperative course was uneventful. Histologically, the tumor was composed of solid nests and cystic gland containing clear mucoid material, lined predominantly with oncocytes and few mucous goblet cells. A final diagnosis of oncocytic variant of mucoepidermoid low-grade carcinoma was made. The recognition of this variant is important, because may be easy confused with most frequent benign tumor with oncocytic cells; in this case a complete surgical excision and long-term clinical follow-up are an adequate management.

Extramedullary hematopoietic proliferations, extraosseous plasmacytomas, and ectopic splenic implants (splenosis).

Hematopoietic proliferations are well known to present ectopically outside the bone marrow, either in benign or malignant form. As such, they present a distinct problem with respect to morphologic interpretation because of their uncommonality in extramedullary sites and their capacity to simulate other lesions histologically. This review considers extramedullary myeloid tumors ("granulocytic sarcoma," "erythroblastic sarcoma," "megakaryocytic sarcoma"), tumefactive extramedullary hematopoiesis, and the peculiar condition known as "splenosis," with consideration of their clinical, microscopic, and cytohistochemical chararacteristics.

Multicystic mesothelioma of the liver with secondary involvement of peritoneum and inguinal region.

A case of multicystic mesothelioma of the liver with secondary involvement of the pelvic peritoneum and the inguinal region is presented. The case is of interest because of its unusual location and peculiar biological behavior.

Glomus tumor of uncertain malignant potential on the forehead.

Malignant glomus tumors (GTs) are rare, and diagnosis requires consideration of specific histologic criteria. Glomus tumors that do not fulfill the histologic criteria for malignancy but show at least 1 feature other than nuclear atypia should be classified as GTs of uncertain malignant potential (GTUMPs). We report the case of a 74-year-old man with a slowly progressing, painful, 2.5-cm nodule on the forehead that was successfully treated via wide surgical excision and was later diagnosed as a GTUMP. Three-year follow-up showed no local recurrence or distant metastasis. Malignant GTs and GTUMPs are rare, and the nomenclature and classification of these tumors is controversial. These findings and the difficulty of differential diagnosis in a continuum between benignity and malignancy prompted our report.

Congenital megaurethra in a fetus with Meckel syndrome and in a fetus with female pseudoermanphroditism. The first report of these occurrences.

OBJECTIVE: the purpose of this paper is to report the first case of megaurethra in a fetus with Meckel syndrome and in a fetus with femal pseudoermaphroditism. RESULTS: the former case refers to a fetus of 13 weeks gestation with the three following prominent anomalies, observed by transonic scan and confirmed by autopsy: congenital megaurethra, anal atresia, single umbelical artery. The latter case refers to a fetus of 18 weeks gestation. Autopsy confirmed penile malformation and revealed ovaries in the abdomen. The karyotype was 46,XX with normal molecular karytype. The megaurethra was discovered by sonography at 18 weeks gestation. Autopsy confirmed penile malformation and revealed ovaries in the abdomen. The karyotype was 46,XX with normal molecular karyotype (Array-CGH, 1 Mb of resolution). METHODS: transonic scan, autopsy, karyotype, array-CGH. CONCLUSIONS: the first prenatal cases of two genetic syndromes with megaurethra have been reported, concening respectively a fetus with Meckel syndrome and a fetus with femal pseudoermaphroditism. The latter was confirmed by both autopsy and the normal female 46,XX karyotype.

CD90 expression in atypical meningiomas and meningioma metastasis.

OBJECTIVES: Meningiomas are slow-growing intracranial/intraspinal tumors, with a wide range of histopathologic variants. The more aggressive atypical and malignant types can disseminate via the venous system, lymphatic, system, or cerebrospinal fluid, with the lung and pleura being the most common sites of extracranial metastases. A case of metastatic meningioma with high expression of CD90 was spotted during a review of flow cytometry data for lung malignancies. Therefore, we have analyzed CD90 expression in a series of meningioma metastases with their corresponding primary tumors and in a series of 92 primary meningioma tumors. METHODS: In addition to flow cytometry and immunohistochemical analysis of the case, a series of meningiomas and relative metastases has been evaluated for CD90 immunohistochemical expression. Furthermore, an immunohistochemical analysis has been conducted in a tissue microarray, including typical and atypical meningiomas. RESULTS: CD90 had high expression in three of four cases of metastases and in their corresponding primary atypical meningioma. In addition, CD90 was significantly expressed in atypical rather than in typical meningiomas (P = .003). However, the correlation of CD90 with patient survival reveals only a trend of statistical association with extracranial metastases. CONCLUSIONS: CD90 is a biomarker overexpressed in atypical meningioma, with a potential role in metastatic switch of this tumor.

Spindle cell lipoma of the larynx.

Among the primary mesenchymal tumors of the hypopharynx and larynx, lipomas are rare. Macroscopically, they often resemble a retention cyst or laryngeal nodule. Spindle cell lipomas (SCLs) are an uncommon variant of lipoma. SCLs are extremely rare in the larynx; as far as we know, only 4 cases have been previously described in the literature. We present a new case of laryngeal SCL in a 65-year-old man who presented with a 1-year history of hoarseness, choking spells, stridor, and dyspnea. Examination revealed the presence of a large polyp on the left true vocal fold that had caused stenosis of the posterior glottis. The polyp was removed endoscopically, and the patient's stridor and dyspnea resolved. Histologically, the tumor was composed of bland, CD34-positive spindle cells with an abundant fibrous and myxoid stroma interspersed with mature fatty tissue. The patient was free of local recurrence at 2 years of follow-up.