Classification of stillbirths is an ongoing dilemma

Aim: To compare different classification systems in a cohort of stillbirths undergoing a comprehensive workup; to establish whether a particular classification system is most suitable and useful in determining cause of death, purporting the lowest percentage of unexplained death. Methods: Cases of stillbirth at gestational age 22–41 weeks occurring at the Department of Gynecology and Obstetrics of Foggia University during a 4 year period were collected. The World Health Organization (WHO) diagnosis of stillbirth was used. All the data collection was based on the recommendations of an Italian diagnostic workup for stillbirth. Two expert obstetricians reviewed all cases and classified causes according to five classification systems. Results: Relevant Condition at Death (ReCoDe) and Causes Of Death and Associated Conditions (CODAC) classification systems performed best in retaining information. The ReCoDe system provided the lowest rate of unexplained stillbirth (14%) compared to de Galan-Roosen (16%), CODAC (16%), Tulip (18%), Wigglesworth (62%). Conclusion: Classification of stillbirth is influenced by the multiplicity of possible causes and factors related to fetal death. Fetal autopsy, placental histology and cytogenetic analysis are strongly recommended to have a complete diagnostic evaluation. Commonly employed classification systems performed differently in our experience, the most satisfactory being the ReCoDe. Given the rate of “unexplained” cases, none can be considered optimal and further efforts are necessary to work out a clinically useful system

Malignant Fibrous Histiocytoma of the Kidney Treated with Nephrectomy and Adjuvant Radiotherapy: A Case Report

Malignant fibrous histiocytoma (MFH) usually presents in the extremities or retroperitoneum. Cases involving the kidney are rare and portend a poor prognosis. Although radical nephrectomy is the most beneficial curative choice for this neoplasm, patients are often treated with adjuvant chemotherapy due to high risk of local recurrence and distant metastases. We describe a case of a 68-year-old woman affected by MFH, treated with both nephrectomy and radiotherapy without systemic therapy showing an unexpected twenty-four-month postsurgery survival outcome

The role of human papillomavirus in the pathogenesis of head & neck squamous cell carcinoma: an overview

Cancer statistics report an increased incidence of OSCC and OPSCC around the world. Though improvements in screening and early diagnosis have dramatically reduced the incidence of this neoplasm in recent years, the 5-year-disease-free survival, is still poor, specially for oropharyngeal cancer, despite the great scientific and financial efforts. Recently, several papers showed that HPV may be involved at least in the pathogenesis of a subgroup of oral and cervical SCC, leading to distinct molecular characteristics compared with HPV-negative ones. Nevertheless, OPSCCs associated with HPV infection seem to show a better prognosis and affect younger patients (< 40 yrs.), especially females. Therefore, there is the need to properly assess oropharyngeal SCC subgroups: 1) not HPV associated/classic oral SCC: less responsive to anticancer drugs: needs novel post-surgical treatment; 2) HPV associated/oral SCC: needs several management options and suitable "target" therapy against the virus, and/or immune-stimulating therapy. Further issues are: 1) the disclosure of putative targets for more efficient molecular therapy, which may work as cervical cancer post-surgical treatment, in anticipation of the effects of "global prevention" performed by WHO anti-HPV vaccination programs; 2) careful identification of precancerous lesions in both sites; dysplasia is currently treated by excisional or ablative procedures, which don't consider the concept of field carcinogenesis. In fact, it is probable that near or far from an excised precancerous lesion new foci of cell transformation may exist, which are not yet macroscopically evident, but, if detected, would put the patient into a high risk subgroup

Lack of association between celiac disease and dental enamel hypoplasia in a case-control study from an Italian central region

<p>Abstract</p> <p>Background</p> <p>A close correlation between celiac disease (CD) and oral lesions has been reported. The aim of this case-control study was to assess prevalence of enamel hypoplasia, recurrent aphthous stomatitis (RAS), dermatitis herpetiformis and atrophic glossitis in an Italian cohort of patients with CD.</p> <p>Methods</p> <p>Fifty patients with CD and fifty healthy subjects (age range: 3–25 years), matched for age, gender and geographical area, were evaluated by a single trained examiner. Diagnosis of oral diseases was based on typical medical history and clinical features. Histopathological analysis was performed when needed. Adequate univariate statistical analysis was performed.</p> <p>Results</p> <p>Enamel hypoplasia was observed in 26% cases vs 16% in controls (p > 0.2; OR = 1.8446; 95% CI = 0.6886: 4.9414). Frequency of RAS in the CD group was significantly higher (36% vs 12%; p = 0.0091; OR = 4.125; 95% CI = 1.4725: 11.552) in CD group than that in controls (36% <it>vs </it>12%). Four cases of atrophic glossitis and 1 of dermatitis herpetiformis were found in CD patients <it>vs </it>1 and none, respectively, among controls.</p> <p>Conclusion</p> <p>The prevalence of enamel hypoplasia was not higher in the study population than in the control group. RAS was significantly more frequent in patients with CD.</p

Report of a case of discoid lupus erythematosus localised to the oral cavity: immunofluorescence findings.

Discoid Lupus Erythematosus (DLE) is a chronic disease with a typical cutaneous involvement. This pathology rarely involves mucosa: oral cavity is interested in 20% of DLE patients. We describe a case of oral DLE in a 50-year-old woman with an anamnesis for autoimmune disorders. This study shows the helpful role of immunofluorescence in the diagnosis of autoimmune diseases. The first diagnostic step was the clinical observation of the oral mucosa: the lesion area was erythematous, athrophic and hyperkeratotic. The patient then underwent laboratory examination. We utilized human epithelial cells (Hep-2010) for Indirect Immuno-Fluorescence (IIF). Moreover, the biopsy site for Direct Immuno-Fluorescence (DIF) and histopathological analysis was the untreated oral lesion. IIF detected an increase of Anti-Nuclear Antibody (ANA) and positivity for SSA-RO. By DIF, we observed IgG/IgA/fibrinogen along basal layer. Multiple biopsies reported signs of chronic basal damage. Steroid systemic therapy induced a considerable lesion regression. We suggest the use of immunofluorescence with the integration of further data to improve diagnosis of rare diseases and to establish a suitable therapy

RAS/BRAF mutational status in familial non‑medullary thyroid carcinomas: A retrospective study

There are contrasting views on whether familial non‑medullary thyroid carcinomas (FNMTCs) are characterized by aggressive behavior, and limited evidence exists on the prognostic value of BRAF and RAS mutations in these tumors. Thus, in the present study, clinicopathological features were analyzed in 386 non‑medullary thyroid carcinomas (NMTCs), subdivided in 82 familial and 304 sporadic cases. Furthermore, the RAS and BRAF mutational statuses were investigated in a subgroup of 34 FNMTCs to address their clinical and biological significance. The results demonstrated that, compared with sporadic NMTCs, FNMTCs are characterized by significantly higher rates of multicentricity and bilaterality and are more frequently associated with chronic autoimmune thyroiditis. Notably, a statistically significant difference in the rates of multicentricity was observed by subgrouping familial tumors according to the number of relatives involved; those with ≥3 affected relatives were more likely to be multicentric. Furthermore, the FNMTC cohort exhibited higher rates of tumors &gt;4 cm in size with extrathyroidal or lymph node involvement. However, no significant difference was observed. Similarly, no differences were observed with respect to the age of onset or the patient outcome. The mutational profiling exhibited a rate of 58.8% for BRAF V600E mutations in familial tumors, which is at the upper limit of the mutational frequency observed in historical series of sporadic thyroid cancer. A high rate of NRAS mutations (17.6%) was also observed, mostly in the follicular variant histotype. Notably, compared with BRAF/RAS‑wild type FNMTCs, the familial carcinomas bearing BRAF or NRAS mutations exhibited slightly higher rates of bilaterality and multicentricity, in addition to increased frequency of locally advanced stage or lymph node involvement. The present data support the theory that FNMTCs are characterized by clinicopathological features that resemble a more aggressive phenotype and suggest that RAS/BRAF mutational analysis deserves to be further evaluated as a tool for the identification of FNMTCs with a potentially unfavorable prognosis

Epigenetic fingerprint in endometrial carcinogenesis: the hypothesis of a uterine field cancerization.

"Abstract. Transcriptional silencing by CpG island hypermethylation plays a critical role in endometrial carcinogenesis. In a collection of benign, premalignant and malignant endometrial lesions, a methylation profile of a complete gene panel, such steroid receptors (ERα, PR), DNA mismatch repair (hMLH1), tumor-suppressor genes (CDKN2A\/P16 and CDH1\/E-CADHERIN) and WNT pathway inhibitors (SFRP1, SFRP2, SFRP4, SFRP5) was investigated in order to demonstrate their pathogenetic role in endometrial lesions. Our results indicate that gene hypermethylation may be an early event in endometrial endometrioid tumorigenesis. Particularly, ERα, PR, hMLH1, CDKN2A\/P16, SFRP1, SFRP2 and SFRP5 revealed a promoter methylation status in endometrioid carcinoma, whereas SFRP4 showed demethylation in cancer. P53 immunostaining showed weak-focal protein expression level both in hyperplasic lesions and in endometrioid cancer. Non-endometrioid cancers showed very low levels of epigenetic methylations, but strong P53 protein positivity. Fisher exact test revealed a statistically significant association between hMLH1, CDKN2A\/P16 and SFRP1 genes methylation and endometrioid carcinomas and between hMLH1 gene methylation and peritumoral endometrium (p < 0.05). Our data confirm that the methylation profile of the peritumoral endometrium is different from the altered molecular background of benign endometrial polyps and hyperplasias. Therefore, our findings suggest that the methylation of hMLH1, CDKN2A\/P16 and SFRP1 may clearly distinguish between benign and malignant lesions. Finally, this study assessed that the use of an epigenetic fingerprint may improve the current diagnostic tools for a better clinical management of endometrial lesions.

Pro-inflammatory effect of cystic fibrosis sputum microparticles in the murine lung

BACKGROUND: The role of microparticles (MPs) in the inflammatory process of cystic fibrosis (CF) airways is not known. Here, we have studied the pro-inflammatory potential of CF MPs in a model of acute lung injury. METHODS: Swiss mice were subjected to intratracheal administration of MPs obtained from CF and primary ciliary diskinesia (PCD) patients. Histopathology, total and differential cell counts in bronchoalveolar lavage fluid were used to evaluate the inflammatory reaction in the lung. Lipopolysaccharide (LPS)-like activity of MPs was studied by Limulus amebocyte lysate assay. RESULTS: MPs obtained from acute CF patients determined peribronchial and perivascular inflammatory infiltrates similar to those elicited by LPS. This inflammation was granulocyte-dominated and higher than that determined by MPs obtained from stable CF, whereas PCD MPs caused a macrophage-dominated inflammation. While LPS-activity was not found in circulating blood MPs prepared from CF patients, it was present in MPs obtained from CF sputum and sputum CD66b(+) neutrophils. Finally, LPS-like activity was only detected in circulating MPs after incubation with LPS as well as in MPs obtained from LPS-stimulated neutrophils obtained from healthy donors. CONCLUSIONS: These data suggest that the pro-inflammatory potential of neutrophil-derived MPs in the CF airways may be subsequent to the binding of shedded LPS