A ZP1 gene mutation in a patient with empty follicle syndrome: A case report and literature review.

Genuine empty follicle syndrome (gEFS) is a rare cause of female infertility; it is defined as the presence of cumulus-oocyte complexes (COCs) in follicular fluid but the absence of oocytes after denudation in an in vitro fertilization (IVF) programme. Mutations in one of the four genes encoding zona pellucida (ZP) proteins have been implicated in gEFS. The objectives of the present study were to explore the molecular basis of idiopathic infertility in a 35-year-old woman with gEFS (observed after four ovarian retrievals), compare her phenotype and genotype with those of other patients described in the literature, and discuss therapeutic approaches that could be adopted by reproductive health centres in this situation. Sequencing of the ZP genes revealed a new homozygous missense variant in ZP1: c.1097G > A;p.(Arg366Gln). The variant is located in the ZP-N domain, which is essential for ZP protein polymerization. An immunohistochemical assessment of an ovarian biopsy confirmed the absence of ZP1 protein. The novel variant appears to prevent ZP assembly, which would explain the absence of normal oocytes after denudation in our patient (and despite the retrieval of COCs). ZP gene sequencing should be considered for patients with a phenotype suggestive of gEFS. An etiological genetic diagnosis enables appropriate genetic counselling and a switch to an IVF programme (with a suitable denudation technique) or an oocyte donation programme.

Cutaneous involvement in relapsed multiple myeloma.

Cutaneous involvement in multiple myeloma with extramedullary disease is rare. We report the case of a refractory multiple myeloma patient who developed a cutaneous lesion. Histopathology revealed dermal immature plasma cell infiltrate with a lack of CD138 expression. This cutaneous location was associated with an aggressive clinical course and short survival.

Mass Spectrometry-Based Differentiation of Oral Tongue Squamous Cell Carcinoma and Nontumor Regions With the SpiderMass Technology.

Oral cavity cancers are the 15th most common cancer with more than 350,000 new cases and ~178,000 deaths each year. Among them, squamous cell carcinoma (SCC) accounts for more than 90% of tumors located in the oral cavity and on oropharynx. For the oral cavity SCC, the surgical resection remains the primary course of treatment. Generally, surgical margins are defined intraoperatively using visual and tactile elements. However, in 15-30% of cases, positive margins are found after histopathological examination several days postsurgery. Technologies based on mass spectrometry (MS) were recently developed to help guide surgical resection. The SpiderMass technology is designed for in-vivo real-time analysis under minimally invasive conditions. This instrument achieves tissue microsampling and real-time molecular analysis with the combination of a laser microprobe and a mass spectrometer. It ultimately acts as a tool to support histopathological decision-making and diagnosis. This pilot study included 14 patients treated for tongue SCC (T1 to T4) with the surgical resection as the first line of treatment. Samples were first analyzed by a pathologist to macroscopically delineate the tumor, dysplasia, and peritumoral areas. The retrospective and prospective samples were sectioned into three consecutive sections and thaw-mounted on slides for H&E staining (7 µm), SpiderMass analysis (20 µm), and matrix-assisted laser desorption ionization (MALDI) MS imaging (12 µm). The SpiderMass microprobe collected lipidometabolic profiles of the dysplasia, tumor, and peritumoral regions annotated by the pathologist. The MS spectra were then subjected to the multivariate statistical analysis. The preliminary data demonstrate that the lipidometabolic molecular profiles collected with the SpiderMass are significantly different between the tumor and peritumoral regions enabling molecular classification to be established by linear discriminant analysis (LDA). MALDI images of the different samples were submitted to segmentation for cross instrument validation and revealed additional molecular discrimination within the tumor and nontumor regions. These very promising preliminary results show the applicability of the SpiderMass to SCC of the tongue and demonstrate its interest in the surgical treatment of head and neck cancers.

Autochthonous leprosy in Europe: a case report and literature review.

Leprosy is currently uncommon in Europe: the diagnosed cases are almost all imported from endemic areas. We report on an autochthonous case of borderline lepromatous leprosy in a 71-year-old Portuguese woman. The case was complicated by a reversal reaction and then by erythema nodosum leprosum. A literature review identified 18 reported cases of European autochthonous leprosy since 2000; all but one were observed in Mediterranean countries. Therefore, active clusters of leprosy persist in Europe, particularly in Spain, Greece, Portugal, and Italy.

Iatrogenic cutaneous graft versus host disease.

A 65-year-old man with acute myeloid leukemia 6 was treated by bone marrow allograft, developed a systemic classic chronic graft versus host disease with hepatic, rheumatologic, ophthalmic, and muco-cutaneous involvement. He received systemic corticosteroid, ruxolitinib and extracorporeal photopheresis which resulted in complete remission. During follow-up the patient presented with viral cutaneous warts on his neck and submandibular area. After various subsequent topical treatments, he developed localized cutaneous GVHD without any general GVHD reactivation symptoms. To the best of our knowledge, there has been no description in the literature of a graft versus host disease developing after local immunomodulatory or cytotoxic treatments. Topical therapies are commonly used by dermatologists for superficial skin cancers and some viral skin lesions, in high risk populations such as organ transplant patients with regular follow-up.Practitioners should be made aware of a possible localized cutaneous GVHD reactivation induced by Koebner phenomenon after local therapy.

Can certain factors for recurrence of placenta-mediated pregnancy complications be identified after an initial small-for-gestational-age birth?

Introduction: After a small-for-gestational-age (SGA) birth, recurrence of placenta-mediated pregnancy complications (PMPCs) is a cause for anxiety when contemplating another pregnancy. We sought to identify factors potentially associated with this recurrence.Material and methods: This retrospective single-center observational study was conducted in a tertiary maternity unit between 1 January 2010 and 31 December 2017. We included all women having experienced a non-syndromic SGA birth and who were subsequently monitored for at least one other pregnancy in our institution. PMPCs were defined as recurrent SGA births, three consecutive first-trimester miscarriages, or preeclampsia.Results: Ninety-four women were included over a 7-year study period. Recurrent PMPCs were recorded in 30 (32%) cases, of which 29 featured recurrent SGA births. None of the following characteristics were significantly associated with recurrence: presence of preeclampsia during the initial pregnancy (six [20%] versus 25 [39%] cases in the recurrent PMPCs and non-recurrent PMPCs groups, respectively; p = .11), results of the histopathologic placental examination or thrombophilia screen, or implemented treatment during subsequent pregnancies.Conclusions: PMPCs recur frequently. No risk factor for recurrence was identified in our study. Results of etiologic assessments and treatments implemented after an initial SGA birth should therefore not modify level of clinical and ultrasound monitoring provided during subsequent pregnancies.Rationale: Recurrence of placenta-mediated pregnancy complications is a cause for anxiety when contemplating another pregnancy. We did not identify any risk factor after an initial small-for-gestational-age birth in our study; surveillance should therefore not be modified by the etiologic assessments' results.

[Immunohistochemical diagnosis of colonic spirochetosis with anti-treponema antibody in patients consulting for chronic diarrhea. Results of a prospective study conducted in 137 patients]. / Diagnostic immunohistochimique de la spirochétose colique avec l'anticorps anti-tréponème chez les patients consultant pour une diarrhée chronique. Résultats d'une étude prospective menée chez 137 patients.

AIM: To assess the incidence of colonic spirochetosis, diagnosed by immunohistochemical stain with anti-Treponema pallidum antibody, in a prospective study of colonic biopsies of patients presenting with chronic diarrhea. MATERIAL AND METHODS: From March 2017 to March 2018 the colonic biopsies of patients presenting with chronic diarrhea were stained with Hematoxylin Eosin and anti-Treponema pallidum antibody. The positive cases were also stained with Steiner stain. RESULTS: A total of 137 colonic biopsies were assessed and 3 cases were positive for immunohistochemical stain with anti-Treponema pallidum antibody (2% of the patients). One case was easy to diagnose with HE stain but the 2 other cases were not. The bacteria were stained with Steiner stain, but less easily seen than with the immunohistochemical stain. No patient was treated with antibiotics. DISCUSSION AND CONCLUSION: The colonic spirochetosis can be easily diagnosed by pathologists with immunohistochemical stain with anti-Treponema pallidum antibody. The bacteria are more easily diagnosed with immunohistochemical stain than with HE stain or Steiner stain. However, colonic spirochetosis is rarely diagnosed on colonic biopsies of patients presenting with chronic diarrhea (2% of the patients in our study). Due to the rarity of the entity, and the cost of immunohistochemical stain and the weak benefit for the patient (no patient in our study was treated with antibiotics for colonic spirochetosis) we cannot advise to perform systematic immunohistochemical stain with anti-Treponema pallidum antibody in all the colonic biopsies of patients presenting with chronic diarrhea.

Subacute cutaneous lupus erythematosus induced by nivolumab: two case reports and a literature review.

Nivolumab is widely used to treat several late-stage malignancies such as melanoma and non-small-cell lung cancer by inhibiting the interaction between the programmed cell death protein-1 and its ligand. By stimulating an antitumor immune response, it also leads to immune adverse events. Here. we report two cases of subacute cutaneous lupus erythematosus (SCLE) induced by nivolumab. Case 1: a 72-year-old woman with a stage IV melanoma. Two months after nivolumab discontinuation because of autoimmune hepatitis, the patient was in complete remission and pruritic nummular erythematous plaques appeared on the back and arms. Case 2: a 43-year-old man put under nivolumab for a metastatic non-small-cell lung cancer. After two cycles, an annular erythematous eruption appeared on the hands, arms, and chest. The hypothesis of SCLE was confirmed by biopsies showing lymphoid perivascular inflammatory infiltrates, with scarce C3 deposits along the basal layer of the epidermis in patient 2. Both patients tested positive for antinuclear antibodies and anti-SSA antibodies. Lesions were regressive under topical corticosteroids and hydroxychloroquine for the first patient and oral prednisone for the second patient. No systemic involvement was observed. The occurrence of SCLE 2 months after nivolumab discontinuation is evidence that the drug effect is prolonged because of the maintenance of programmed cell death protein-1 reception saturation for months. A causal relationship between SCLE and nivolumab is suggested by (i) the occurrence of SCLE after at least two cycles, (ii) the regression of lesions following treatment with corticosteroids and hydroxychloroquine, and (iii) the fact that it appeared after remission in our first patient.

Combining genomic analyses with tumour-derived slice cultures for the characterization of an EGFR-activating kinase mutation in a case of glioblastoma.

BACKGROUND: Epidermal growth factor receptor (EGFR) gene alterations and amplification are frequently reported in cases of glioblastoma (GBM). However, EGFR-activating mutations that confer proven sensitivity to tyrosine kinase inhibitors (TKIs) in lung cancer have not yet been reported in GBM. CASE PRESENTATION: Using next-generation sequencing, array comparative genomic hybridization and droplet digital PCR, we identified the p.L861Q EGFR mutation in a case of GBM for the first time. The mutation was associated with gene amplification. L861Q may be a clinically valuable mutation because it is known to sensitize non-small-cell lung cancers to treatment with the second-generation EGFR TKI afatinib in particular. Furthermore, we used slice culture of the patient's GBM explant to evaluate the tumour's sensitivity to various EGFR-targeting drugs. Our results suggested that the tumour was not intrinsically sensitive to these drugs. CONCLUSIONS: Our results highlight (i) the value of comprehensive genomic analyses for identifying patient-specific, targetable alterations, and (ii) the need to combine genomic analyses with functional assays, such as tumour-derived slice cultures.

[Severe acute alcoholic hepatitis]. / Hépatite alcoolique aiguë sévère.

All chronic and excessive consumer of alcohol with recent jaundice should be assessed using a Maddrey's score for severe acute alcoholic hepatitis. Corticosteroids are the first line of treatment, associated with an appropriate nutritional support and alcohol abstinence. Corticosteroids plus N-acetylcysteine combination improves short-term survival over corticosteroids alone, and could be proposed as a first line therapy. The response to treatment is evaluated at the 7th day of treatment, with the Lille model≤0.45. Prognostic of non-responders to corticosteroids with Lille model>0.45 is dramatically low with 23% survival at 6 month. Early liver transplantation in a selected group of patients with non-response to corticosteroids significantly improves 6th month and long-term survival.

[Venous invasions in colonic adenocarcinoma: Value of elastic stain]. / Invasions veineuses dans l'adénocarcinome colique : intérêt d'une coloration des fibres élastiques.

The aim of our study was to assess the value of Elastic stain in the diagnosis of venous invasion (VI) in colonic adenocarcinoma. MATERIAL AND METHODS: All patients who undergone surgery for colonic adenocarcinoma at the University Hospital of Amiens, between 2004 and 2007, were included. Hematein-phloxin-saffron (HPS) stained slides of colectomy specimens were reviewed by two pathologists. Tumor blocks were stained with Elastic Stain (Roche - Ventana®). The presence or absence of VI, their number and localization were correlated with overall survival. RESULTS: Two hundred and thirty-one cases were investigated and 3274 slides were examined. VI were more often diagnosed by Elastic Stain than HPS stain (66% vs. 40%). Ninety percent of VI were revealed within the first 6 HPS slides, and from the first 5 in Elastic Stain. The presence of VI revealed by Elastic Stain and/or HPS was significantly associated with decreased overall survival in multivariate analysis (P=0.029), especially for stage IIA tumors (P=0.016). Tumor differentiation (P=0.006) and pTNM stage (P=0.001) were also independent prognostic factors. The localization and the number of VI were not prognostic factors. CONCLUSION: Our study confirms the prognostic value of VI, revealed by an elastic stain, in colonic adenocarcinoma. A systematic elastic stain of all tumor blocks (number at least 5) could be considered in the future, during pathological examination of colectomy for adenocarcinoma.

Impact of homogeneous pathologic response to preoperative chemotherapy in patients with multiple colorectal liver metastases.

AIM: To analyze the homogeneity of pathologic response to preoperative chemotherapy (PRPC) after chemotherapy in patients with multiple liver metastases (LM). METHODS: From September 2011 to August 2014, patients with at least two LM undergoing preoperative chemotherapy prior to resection were included in this retrospective, single-center study. The endpoints were PRPC homogeneity (according to both the Rubbia-Brandt and MD Anderson classifications), the impact of PRPC on the MDT decision, factors associated with homogeneous PRPC and overall survival of patients with vs. without homogeneous PRPC. RESULTS: seventy-three patients with a total of 88 liver resections (including 15 two-stage procedures) were included in the study. The homogeneous PRPC rate was 55% according to the Rubbia-Brandt classification and 53% according to the MD Anderson classification. The MDT decision was modified by the PRPC in only 2.7% of patients (n = 2). CONCLUSION: The PRPC was homogeneous in only one half of patients and had very little influence on the MDT decision.

Increased tumor infiltration by mucosal-associated invariant T cells correlates with poor survival in colorectal cancer patients.

The infiltration of tumors by lymphocytes is a prognosis factor in colorectal cancer (CRC). The magnitude and quality of this infiltration have emerged as important component of the clinical outcome in these patients. Specifically, markers associated with functional cell-mediated immunity, i.e., a Th1 immune response, are independent markers of better prognosis, whereas Th17-associated components are deleterious and correlate with poorer survival. Mucosal-associated invariant T (MAIT) cells are a recently described T cell subset with tissue-homing properties. They display a restricted TCR repertoire specific for widely conserved microbial ligands, and display anti-bacterial properties upon release of Th1-like, Th17-like, and/or cytotoxic granules. MAIT-cell-specific transcripts have been found in kidney and brain cancer, but have not been studies in other sites. In this study, we retrospectively analyzed by confocal microscopy the presence of MAIT cells within colorectal tumors as compared with paired healthy tissues. We observed a significant although variable increase, both in density and in proportion of overall tumor-infiltrating T lymphocytes inside the tumors. Importantly, survival curves as well as multivariate analysis showed that patients displaying a higher recruitment of MAIT cells in their tumor, as compared with the neighboring healthy tissue, showed a less favorable clinical outcome. This study suggests that including MAIT-cell-specific markers or transcripts in the analysis of tumor-infiltrating lymphocytes could be a benefit to the diagnosis and follow-up of CRC patients.