Elongated linear vessels simulating branching vessels and diffuse structureless orange areas as prominent dermoscopic features of diffuse flat facial and extrafacial granuloma faciale: A case series.

Dermoscopy can be an important help for the diagnosis of skin cancers and inflammatory cutaneous diseases. The list of the dermoscopic features reported in granuloma faciale is wide and includes vascular and non-vascular features. We report here three cases of diffuse flat facial and extrafacial granuloma faciale that exhibited elongated linear vessels simulating branching vessels and diffuse structureless orange areas. The differential diagnosis between flat-type granuloma faciale, basal cell carcinoma and cutaneous sarcoidosis can be extremely difficult, making histology mandatory before any treatment.

Fetal Presentation of Walker-Warburg Syndrome with Compound Heterozygous POMT2 Missense Mutations.

Background: Walker-Warburg syndrome (WWS) (OMIM #236670) is an autosomal recessive disorder characterized by congenital muscular dystrophy, hydrocephalus, cobblestone lissencephaly, and retinal dysplasia. The main genes involved are: POMT1, POMT2, POMGNT1, FKTN, LARGE1, and FKRP. Case report: We present a fetus with WWS showing at ultrasound severe triventricular hydrocephalus. Pregnancy was legally terminated at 21 weeks +2 days of gestation. In vivo and postmortem magnetic resonance revealed corpus callosum agenesis and cerebellar hypoplasia. Cobblestone lissencephaly was observed at post-mortem. Next generation sequencing (NGS) of 193 genes, performed on fetal DNA extracted from amniocytes, detected two heterozygous mutations in the POMT2 gene. The c.1238G > C p.(Arg413Pro) mutation was paternally inherited and is known to be pathogenic. The c.553G > A p.(Gly185Arg) mutation was maternally inherited and has not been previously described. Conclusion: Compound heterozygous mutations in the POMT2 gene caused a severe cerebral fetal phenotype diagnosed prenatally at midgestation allowing therapeutic pregnancy termination.

Multiple perianal ulcers due to suppositories.

We report a case of long-standing inexplicable perianal ulcers. After exclusion of an inflammatory, infectious or neoplastic origin, a thorough personal history revealed that for many years the patient had been using analgesic suppositories containing indomethacin, caffeine, and prochlorperazine dimaleate, four to five times a week, for migraine. On stopping the suppositories, there was complete healing within 12 weeks. We hypothesize that vasoconstriction and vascular damage were the pathogenetic mechanisms behind the perianal ulcers.

Thoracoscopic lung metastasectomies: a 10-year, single-center experience.

INTRODUCTION: The ideal surgical treatment for pulmonary metastasectomy remains controversial. Minimally invasive surgery may offer advantages for quality of life outcomes, with equivalent oncologic long-term results. The purpose of our study was to confirm the validity of the thoracoscopic approach for pulmonary metastasectomy. METHODS: We retrospectively reviewed 164 patients who underwent 212 lung metastasectomies from January 2000 to December 2010. Complete curative pulmonary resections were performed in 159 (96.95 %) cases; 126 patients developed lung metastases from epithelial tumors: 28 from sarcoma, 7 from melanoma, and 3 from germ cell tumors. The mean disease-free interval (DFI) was 38.75 months. Fifty-four patients underwent a major VATS resection (53 thoracoscopic lobectomies and 1 pneumonectomy), and 110 patients underwent a wedge resection/segmentectomy. Lymph node sampling was performed in 117 cases. RESULTS: After a mean follow-up of 38 months, 87 patients (53 %) had died. All resection margins were tumor-free at final pathological examination. Multivariate analysis not confirmed in our series a better prognosis for patients with a particular histologic type and also DFI, age, number of metastases, and type of surgery did not statistically influence long-term survival. CONCLUSIONS: Thoracoscopic surgery is an acceptable procedure, safe and efficacious, with a 5-year overall survival that is equivalent to open surgery.

Biologically driven cut-off definition of lymphocyte ratios in metastatic breast cancer and association with exosomal subpopulations and prognosis.

High neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) are respectively associated with systemic inflammation and immune suppression and have been associated with a poor outcome. Plasmatic exosomes are extracellular vesicles involved in the intercellular communication system that can exert an immunosuppressive function. Aim of this study was to investigate the interplay between the immune system and circulating exosomes in metastatic breast cancer (MBC). A threshold capable to classify patients according to MLR, NLR and PLR, was computed through a receiving operator curve analysis after propensity score matching with a series of female blood donors. Exosomes were isolated from plasma by ExoQuick solution and characterized by flow-cytometry. NLR, MLR, PLR and exosomal subpopulations potentially involved in the pre-metastatic niche were significantly different in MBC patients with respect to controls. MLR was significantly associated with number of sites at the onset of metastatic disease, while high levels of MLR and NLR were found to be associated with poor prognosis. Furthermore, exosomal subpopulations varied according to NLR, MLR, PLR and both were associated with different breast cancer subtypes and sites of distant involvement. This study highlights the nuanced role of immunity in MBC spread, progression and outcome. Moreover, they suggest potential interaction mechanisms between immunity, MBC and the metastatic niche.

Unexpected intrauterine fetal death in parvovirus B19 fetal infection.

Parvovirus B19 infection during pregnancy can be transmitted to the fetus through the placenta. The consequences for the health of the fetus are very variable and can be very serious. They include intrauterine fetal death (IUFD) and miscarriage, which can lead to medico-forensic questions. For the most part, cases of IUFD take place during the second trimester of gestation and present an anatomopathologic picture characteristic of fetal infection with hydrops, placental edema, serous effusion, and erythroblastosis with nuclear inclusions. Endocardial fibroelastosis, medullar and thymic hypoplasia, and hepatic hemosiderosis are frequently present. In the third trimester, the cases are less frequent, not accompanied by hydrops, and can depend more on placental compromise than on direct infection of the fetus. We present 5 cases of IUFD resulting from parvovirus B19 and we discuss the pathogenetic and anatomopathologic aspects and obstetric liability. In 4 cases, the IUFD took place suddenly, in the absence of symptoms, in women who had not previously shown any symptom of the viral infection. In one case, the patient was hospitalized following an ultrasound diagnosis of fetal hydrops and IUFD took place 5 days after admission. Of these cases 3 were verified in the second trimester and 2 in the third trimester. Only the cases of the second trimester and one of the 2 cases of the third trimester presented the characteristic aspects of fetal infection. The other case of third trimester was characterized by placental involvement.

Lactate Dehydrogenase (LDH) Response to First-Line Treatment Predicts Survival in Metastatic Breast Cancer: First Clues for A Cost-Effective and Dynamic Biomarker.

Background: Elevated plasmatic lactate dehydrogenase (LDH) levels are associated with worse prognosis in various malignancies, including metastatic breast cancer (MBC). Nevertheless, no data are available on the prognostic role of LDH as a dynamic biomarker during first-line treatment in unselected MBC. Methods: We reviewed data of 392 women with MBC to evaluate the association between LDH variation after 12 weeks of first-line treatment and survival. The prognostic impact was tested by multivariate Cox regression analysis. Results: Plasmatic LDH was confirmed as an independent prognostic factor in MBC. Patients who maintained elevated LDH levels after 12 weeks of first-line treatment experienced worse progression-free survival (PFS, HR 2.88, 95% CI: 1.40-5.89, p = 0.0038) and overall survival (OS, HR 2.61, 95% CI 1.16-5.86, p = 0.02) compared to patients with stable normal LDH levels, even after adjustment for other prognostic factors. Notably, LDH low-to-high variation emerged as an unfavorable prognostic factor for PFS (HR 3.96, 95% CI 2.00-7.82, p = 0.0001). Conclusions: Plasmatic LDH and its variation during first-line treatment predict PFS and OS in MBC, providing independent prognostic information. It would be worthwhile to prospectively evaluate the association between LDH variation and therapeutic benefit in MBC, and explore how it may affect treatment strategies.

Medico legal aspects of self-injection of metallic mercury in cases of suicide or self-harming.

Metallic mercury may be self-injected for suicidal or self-harm purposes or sometimes for superstitious or other inadvisable reasons. Local tissue or systemic consequences such as mercurialism can frequently occur in cases of subcutaneous or deep injection, while death due to pulmonary embolism and cardiac, brain, hepatic or renal toxicity may occur in cases of high dosage intravenous administration. The aim of this review is to focus on the diagnostic difficulties facing coroners and forensic pathologists when the courts require confirmation that evidence of self-injection of metallic mercury is the result of suicide or self-harming. Forensic examination performed on the corpses of victims who died in or out of hospital or on surviving injured or intoxicated victims showing signs of mercurialism, demands the careful evaluation of the death scene, of all related circumstances and of the clinical and autopsy data. Close interaction between forensic pathologists and toxicologists is also needed to identify and quantify mercury levels in blood, urine and tissue.

The rope sign: a case of interstitial granulomatous dermatitis with arthritis.

Interstitial granulomatous dermatitis with arthritis (IGDA), also known as Ackerman's syndrome, is a rare cutaneous disease classically characterized by the triad of cutaneous cords, a typical histologic infiltrate mainly constituted by histiocytes and arthritis/connective tissue disease. Here we report the case of IGDA with the typical clinical and histological features in a patient affected by lupus erythematosus. In this article we underline that IGDA may have a variety of different clinical and histological features. The rope sign is typical but infrequent, while histology is usually characteristic and shows a dermal inflammatory infiltrate, with a predominance of histiocytes, localized interstitially and in a palisaded array between collagen fibres, that show signs of degeneration. Clinical and histological differential diagnoses are discussed.

Anti-zinc transporter protein 8 autoantibodies significantly improve the diagnostic approach to type 1 diabetes: an Italian multicentre study on paediatric patients.

BACKGROUND AND AIM: Anti-ZnT8 antibodies (ZnT8A) were recently proposed as a new independent serological marker in Type 1 diabetes (T1D), leading to a significant improvement of the positive predictive value of autoantibody measurement in this setting. The aim of this retrospective multicentre study was to investigate ZnT8A as a complement to the current T1D autoantibody assays in a large cohort of paediatric Italian patients. METHODS: ZnT8A were assessed by ELISA in 213 T1DM paediatric patients referred to six different centres in North-East Italy. Fifty-four were analysed at disease onset, 79 within 4 years from diagnosis and 80 after 5 or more years from diagnosis. Retrospective data about islet cell autoantibodies (ICA), anti-insulin (IAA), anti-glutamate decarboxylase (GADA) and anti-protein tyrosine phosphatase IA-2 (IA-2A) antibodies were collected and compared. RESULTS: Overall, ZnT8A showed positive results in 106/213 (49.8 %) T1D patients and were found in 10 (4.7 %) subjects previously classified as autoantibody negative based on the existing markers (GADA, IA-2A, IAA and ICA), increasing the overall diagnostic sensitivity from 85.9 to 90.6 %. ZnT8A disclosed the same sensitivity (61.1 %) at disease onset as GADA (61.1 %) and higher than IA-2A (53.7 %), with only GADA showing much persistence in the long-term follow-up. Focusing on patients at disease onset, all the ICA positive were associated with at least one positive autoantibody among GADA, IA-2A and ZnT8A, 16.7 % of whom presenting only anti-ZnT8-positive antibodies. CONCLUSION: This study confirms ZnT8A as an important additional and independent diagnostic marker of T1D and supports its introduction in the routine diagnostic process to replace less sensitive methods and improve the overall autoantibody sensitivity.

Anti-DFS70 antibodies: a useful biomarker in a pediatric case with suspected autoimmune disease.

Antidense fine speckles 70 (anti-DFS70) antibodies, a peculiar antinuclear antibody (ANA) pattern by indirect immunofluorescence, is frequently observed in ANA-positive individuals with no evidence of systemic autoimmune rheumatic disease. They may be found in many different inflammatory conditions and in healthy individuals. We herein report a case of an 8-year-old girl presenting with generalized edema, hypertension, hepatomegaly, and a history of pharyngitis, which occurred 3 weeks earlier. Laboratory analysis revealed low complement C3 (6 mg/dL), microhematuria, and proteinuria. A diagnosis of acute glomerulonephritis was made. Anti-dsDNA, antiextractable nuclear antigens, and antineutrophil cytoplasmic antibodies were negative. However, a highly positive (1:640) ANA immunofluorescence test with dense fine speckles pattern was found. The presence of anti-DFS70 immunoglobulin G antibodies was confirmed by a specific immunoassay. In conclusion, the presence of isolated anti-DFS70 antibodies may be useful to exclude an autoimmune pathogenesis in those children with a positive ANA test and a clinical picture possibly attributable to systemic autoimmune rheumatic disease. This will avoid further unnecessary investigation with the potential for incorrect diagnosis and possibly harmful treatment.