Cytogenetics in the management of mature B-cell non-Hodgkin lymphomas: Guidelines from the Groupe Francophone de Cytogénétique Hematologique (GFCH).

Non-Hodgkin lymphomas (NHL) consist of a wide range of clinically, phenotypically and genetically distinct neoplasms. The accurate diagnosis of mature B-cell non-Hodgkin lymphoma relies on a multidisciplinary approach that integrates morphological, phenotypical and genetic characteristics together with clinical features. Cytogenetic analyses remain an essential part of the diagnostic workup for mature B-cell lymphomas. Karyotyping is particularly useful to identify hallmark translocations, typical cytogenetic signatures as well as complex karyotypes, all bringing valuable diagnostic and/or prognostic information. Besides the well-known recurrent chromosomal abnormalities such as, for example, t(14;18)(q32;q21)/IGH::BCL2 in follicular lymphoma, recent evidences support a prognostic significance of complex karyotype in mantle cell lymphoma and Waldenström macroglobulinemia. Fluorescence In Situ Hybridization is also a key analysis playing a central role in disease identification, especially in genetically-defined entities, but also in predicting transformation risk or prognostication. This can be exemplified by the pivotal role of MYC, BCL2 and/or BCL6 rearrangements in the diagnostic of aggressive or large B-cell lymphomas. This work relies on the World Health Organization and the International Consensus Classification of hematolymphoid tumors together with the recent cytogenetic advances. Here, we review the various chromosomal abnormalities that delineate well-established mature B-cell non-Hodgkin lymphoma entities as well as newly recognized genetic subtypes and provide cytogenetic guidelines for the diagnostic management of mature B-cell lymphomas.

The complex karyotype in hematological malignancies: a comprehensive overview by the Francophone Group of Hematological Cytogenetics (GFCH).

Karyotype complexity has major prognostic value in many malignancies. There is no consensus on the definition of a complex karyotype, and the prognostic impact of karyotype complexity differs from one disease to another. Due to the importance of the complex karyotype in the prognosis and treatment of several hematological diseases, the Francophone Group of Hematological Cytogenetics (Groupe Francophone de Cytogénétique Hématologique, GFCH) has developed an up-to-date, practical document for helping cytogeneticists to assess complex karyotypes in these hematological disorders. The evaluation of karyotype complexity is challenging, and it would be useful to have a consensus method for counting the number of chromosomal abnormalities (CAs). Although it is not possible to establish a single prognostic threshold for the number of CAs in all malignancies, a specific consensus prognostic cut-off must be defined for each individual disease. In order to standardize current cytogenetic practices and apply a single denomination, we suggest defining a low complex karyotype as having 3 CAs, an intermediate complex karyotype as having 4 CAs, and a highly complex karyotype as having 5 or more CAs.

[Vulvar mass in neonatal period : spot the difference]. / Diagnostic différentiel d'une masse vulvaire en période néonatale.

We report the cases of two female newborns who present, at the first day, a interlabial mass. In both cases, the antenatal scans were normal, and the clinical examination in the delivery room didn't reveal any other abnormality. Similar features may suggest the same diagnosis. However, in the first case, it is a paraurethral cyst which causes the bulging of vaginal introitus whereas, in the second infant, it is an imperforated hymen. Paraurethral cysts are uncommon and even more so among infants. The diagnosis is primarily clinical, and ultrasound confirms the diagnosis and verifies the absence of other associated anomalies. These cysts usually resolve spontaneously. Rarely, they can lead to urinary retention. The second diagnosis, imperforate hymen, is the most common congenital malformation of the female genital tract. It can lead to hydrocolpos with the upstream accumulation of vaginal secretion and sometimes induce a hydrometrocolpos, with vaginal and uterine dilatation. The resulting mass can cause obstruction of surrounding urinary or digestive structures. Surgical management is generally necessary.

Nous rapportons le cas de deux nouveau-nés de sexe féminin qui présentaient une masse au niveau vulvaire, dans les premiers jours de vie. Dans les deux cas, le reste de l'examen clinique était sans particularité et aucune anomalie n'avait été décelée en anténatal. Les présentations cliniques semblables peuvent faire évoquer le même diagnostic. Pourtant, dans le premier cas, c'est un kyste para-urétral qui cause la masse alors que, dans le second, c'est une imperforation de l'hymen. Ces deux pathologies sont peu fréquentes chez les nourrissons. Leur diagnostic est avant tout clinique et l'échographie permet à la fois de confirmer celui-ci et de vérifier l'absence d'autres anomalies. La plupart du temps, les kystes para-urétraux régressent spontanément. Cependant, ils peuvent parfois être la cause d'une rétention urinaire. En cas d'imperforation de l'hymen, la réalisation d'un acte chirurgical est, par contre, nécessaire afin d'éviter des complications plus tardives. Un hydrocolpos peut y être associé, il est dû à la rétention de sécrétions vaginales en amont. La masse engendrée peut provoquer une obstruction des structures avoisinantes.

Immune checkpoint inhibitors versus second line chemotherapy for patients with lung cancer refractory to first line chemotherapy.

PURPOSE: Anti Programmed Death-ligand (PD1/PD-L1) directed immune-checkpoint-inhibitors (ICI) are widely used to treat patients with advanced non-small cell lung cancer (NSCLC) who progress after first line chemotherapy. The best strategy after early progression under first line has not been specifically studied. PATIENTS AND METHODS: We conducted a multicenter, retrospective study including all consecutive NSCLC patients progressing within the first 3 months following introduction of first-line chemotherapy and being treated with second line ICI monotherapy or chemotherapy between March 2010 and November 2017. We analysed the clinicopathological data and outcome under second line chemotherapy vs. second line ICI: objective response rate (ORR), progression-free survival (PFS), overall survival (OS. RESULTS: We identified 176 patients with refractory disease, 99 who received subsequent immunotherapy and 77 undergoing chemotherapy. The 2 populations were comparable regarding the main prognostic criteria, median age was 60, main histology was adenocarcimoma (68.2%). PFS was not significantly different between both treatments 1.9 [1.8-2.1] versus 1.6 month [1.4-2.0] (P=0.125). Compared to chemotherapy, ICI treated patients had a superior OS (P=0.03) (Median [95% CI] OS 4.6 [2.8-6.7] versus 4.2 months [3.4-5.9] and a non-significant improvement in ORR (17.2% versus 7.9%, respectively, P=0.072). Poor performance status (ECOG PS≥2) and a higher number of metastatic sites (≥3) were associated with poorer prognosis. KRAS-mutated patients did not seem to benefit more from ICI than chemotherapy. CONCLUSIONS: ICI appears to be the preferred second-line treatment for patients who are refractory to first line chemotherapy.

The importance of using 3D ultrasound during pelvic organ prolapse surgery in relation to pre- and post-operative quality of life questionnaires.

AIM: The main aim of this study is to evaluate the interest of three-dimensional ultrasound perineal in the measurement of the levator hiatus area as an objective reflection of the surgical correction of pelvic organ prolapse (POP). Our hypothesis is that POP surgery decreases the size of the levator hiatus area. MATERIALS AND METHODS: A longitudinal and prospective study was conducted between April and July 2017 in the Department of Gynaecology & Obstetrics at University Hospital of Angers. Surgery was performed either by laparoscopy (sacrocolpopexy) or vaginal surgery (with or without the use of mesh). All patients were handed an information letter and signed an informed consent before being included in the study. A questionnaire was fullfilled before and one month after surgery. A clinical evaluation using the simplified POP-Q classification and a perineal 3D ultrasound were carried out before and after surgery by the same professional. The levator hiatus area was assessed before and after surgery in order to evaluate the impact of surgery on the levator hiatus area. Simplified POP-Q measurements and responses to PFDI-20 and PFDI-7 questionnaires were also collected. RESULTS: A total of 18 patients were included in the study and four were excluded. Seven underwent laparoscopic surgery and seven underwent vaginal surgery. The levator hiatus area decreased substantially from 20.87 to 16.55cm2 on mean (p=0.0001) at rest. Regarding patient satisfaction, the PFDI-20 score improved after surgery from 89.36 to 37.87 on mean (p=0.006), but the PFIQ-7 score did not reveal any significant changes (p=0.096). For the clinical examination, we used the simplified POP-Q with Ba measurement from 2.3 to -1.92cm (p=0.005) or Bp from -1.5 to -2.46cm, which is not a significant change (p=0.14). Points C (or D in cases with a history of hysterectomy) changed from -3.1 to -6.15cm (p=0.03). CONCLUSION: The levator hiatus area seems to decrease after POP surgery. 3D ultrasound seems a new and complementary procedure that allowed to evaluate objectively the levator hiatus area and thus the clinical findings of the surgery.

Factors associated with pregnancy after in vitro fertilization in infertile patients with posterior deep pelvic endometriosis: A retrospective study.

INTRODUCTION: The management of posterior deep endometriosis is not consensual. This is due to a great heterogeneity of data from the literature. Many series were small and overall, predictors of pregnancy were not all included and analyzed by multivariate analysis. We conducted this study to evaluate the factors associated with pregnancy during the first two in vitro fertilization (IVF) attempts in infertile women with posterior deep endometriosis. MATERIAL AND METHODS: 230 women were included in this retrospective observational study, between January 1st, 2007 and September 30th, 2013, at the University Hospital of Lille. A large set of variables were recorded and their association with the chance of pregnancy was analyzed by multivariate analysis (MVA), including patients' features, endometriosis items, surgery procedures and IVF data. RESULTS: After 2 IVF attempts, 48.7% of the 230 women achieved a pregnancy, including 39.1% of ongoing pregnancies. Logistic regression analysis retained five variables significantly associated to the chance of pregnancy: oocyte retrieval number (OR=0.468 (0.296-0.739) p=0.001), age (OR=0.888 (0.811-0.974) p=0.011), single embryo transfer number (OR=1.494 (1.036-2.153) p=0.031), presence of a recto-uterine nodule (OR=0.454 (0.235-0.877) p=0.019) and IVF technique (OR=0.509 (0.272-0.951) p=0.034). CONCLUSION: The presence of a recto uterine nodule is associated with a lower chance of pregnancy after IVF. It has to be checked by prospective studies whether the finding of a recto-uterine nodule whose pejorative effect has not been reported so far should encourage to perform surgery before IVF in patients with deep endometriosis.

Sentinel lymph node biopsy without axillary lymphadenectomy after neoadjuvant chemotherapy is accurate and safe for selected patients: the GANEA 2 study.

PURPOSE: GANEA2 study was designed to assess accuracy and safety of sentinel lymph node (SLN) after neo-adjuvant chemotherapy (NAC) in breast cancer patients. METHODS: Early breast cancer patients treated with NAC were included. Before NAC, patients with cytologically proven node involvement were allocated into the pN1 group, other patient were allocated into the cN0 group. After NAC, pN1 group patients underwent SLN and axillary lymph node dissection (ALND); cN0 group patients underwent SLN and ALND only in case of mapping failure or SLN involvement. The main endpoint was SLN false negative rate (FNR). Secondary endpoints were predictive factors for remaining positive ALND and survival of patients treated with SLN alone. RESULTS: From 2010 to 2014, 957 patients were included. Among the 419 patients from the cN0 group treated with SLN alone, one axillary relapse occurred during the follow-up. Among pN1 group patients, with successful mapping, 103 had a negative SLN. The FNR was 11.9% (95% CI 7.3-17.9%). Multivariate analysis showed that residual breast tumor size after NAC ≥ 5 mm and lympho-vascular invasion remained independent predictors for involved ALND. For patients with initially involved node, with negative SLN after NAC, no lympho-vascular invasion and a remaining breast tumor size 5 mm, the risk of a positive ALND is 3.7% regardless the number of SLN removed. CONCLUSION: In patients with no initial node involvement, negative SLN after NAC allows to safely avoid an ALND. Residual breast tumor and lympho-vascular invasion after NAC allow identifying patients with initially involved node with a low risk of ALND involvement.

Surgery using plasma energy for deep endometriosis: A quality of life assessment.

OBJECTIVE: The principal objective of our study was to assess women's quality of life (QoL) after surgery for Deep Endometriosis (DE), according to the surgical technique used. MATERIAL AND METHODS: Qualitative single-center survey in the department of obstetrics and gynecology, Angers University Hospital Center, France. All women who underwent surgery for DE from January 2011 to December 2015 were contacted by phone. The Endometriosis Health Profile-5 score was used to assess QoL before and after the surgery. Fifty-two women (response rate=86%) were included and classified into 3 groups according to the surgical technique used: simple shaving, shaving exclusively or in part by plasma vaporization (plasma), and resection. RESULTS: The 3 groups were comparable for surgical history, preoperative QoL score, and characteristics of endometriotic lesions (size and site). All DE symptoms and QoL scores improved significantly after the surgery, all techniques combined (P<0.01). QoL scores for women who had plasma shaving or complete resection were significantly higher than those for women with simple shaving (respectively, 375 [225-800] and 450 [-50 to 725] vs 275 [-100 to 600]; P=0.04). Self-image significantly improved only in the plasma group (P=0.03). The complete resection group had longer hospitals stays than the other groups (P=0.001), as well as a higher surgical revision rate (23% vs 0%; P=0.02). CONCLUSION: Plasma and complete resection improved QoL similarly for women with DE, both more than shaving alone. The advantage of plasma vaporization lies in the lesser morbidity and better self-image, both better than in women with resection.

About a case of traumatic separation of the cervix from the uterine corpus, diagnosed in a context of infertility.

This article reports a case of cervico-isthmic disjunction unnoticed during childhood, diagnosed in a context of primary infertility and endometriosis, and surgically treated. It is an uncommon condition. The diagnosis is most often made as part of an assessment of primary amenorrhea in a young woman with a history of severe pelvic trauma. It is suspected after imaging assessment and confirmed intraoperatively. The treatment consists in an anastomosis between the cervix and the uterine body, after individualizing these two structures, around a drain guiding healing. After this surgery, multiple pregnancies have been successfully carried out.

Incidental findings in CT imaging of coronary artery bypass grafts: results from a Canadian multicenter prospective cohort.

OBJECTIVE: To assess the prevalence and clinical significance of incidental findings identified during computed tomography imaging of coronary artery bypass grafts. RESULTS: This prospective study includes 144 patients undergoing coronary graft patency assessment using computed tomography. Incidental findings were classified as significant if they were considered to need an immediate action or treatment, short-term work-up or follow-up, or minor. A total of 211 incidental findings were present in 109 (75.7%) patients. Seventy-one incidental findings (33.6%) were cardiac and 140 (66.4%) were extracardiac. Most common cardiac incidental findings were atrial dilatation [39 patients, 48 incidental findings (67.6%)] and aortic valve calcifications (7 patients, 9.9%). Among the 140 extracardiac incidental findings, the most common were lung nodules (51 patients, 54 nodules, 38.6%), and emphysema (21 patients, 15%). Thirty-six (25.7%) extracardiac incidental findings were significant and notably, 23 (63.9%) were lung nodules. Follow-up was recommended in 37 cases, among which all patients with significant lung nodules (23 patients, 62.2%). In conclusion, most common computed tomography incidental findings in patients with coronary grafts were lung nodules and emphysema.

[Lung dose constraints for normo-fractionated radiotherapy and for stereotactic body radiation therapy]. / Doses aux organes à risque en radiothérapie conformationnelle et en radiothérapie stéréotaxique : les poumons.

Radiation-induced lung disease (RILD) is common after radiation therapy and represents cornerstone toxicities after treatment of thoracic malignancies. From a review of literature, the objective of this article was to summarize clinical and non-clinical parameters associated with the risk of RILD in the settings of normo-fractionated radiotherapy and stereotactic body radiation therapy (SBRT). For the treatment of lung cancers with a normo-fractionated treatment, the mean lung dose (MLD) should be below 15-20Gy. For a thoracic SBRT, V20Gy<10% and MLD<6Gy are recommended. One should pay attention to central tumors and respect specific dose constraints to the bronchial tree. The recent technological improvements may represent an encouraging way to decrease lung toxicities. Finally, our team developed a calculator in order to predict the risk of radiation pneumonitis.

NUP98 is rearranged in 3.8% of pediatric AML forming a clinical and molecular homogenous group with a poor prognosis.

Pediatric acute myeloid leukemia (AML) is a rare disease whose prognosis is highly variable according to factors such as chromosomal abnormalities. Recurrent genomic rearrangements are detected in half of pediatric AML by karyotype. NUcleoPorin 98 (NUP98) gene is rearranged with 31 different fusion partner genes. These rearrangements are frequently undetected by conventional cytogenetics, as the NUP98 gene is located at the end of the chromosome 11 short arm (11p15). By screening a series of 574 pediatric AML, we detected a NUP98 rearrangement in 22 cases (3.8%), a frequency similar to CBFB-MYH11 fusion gene (4.0%). The most frequent NUP98 fusion gene partner is NSD1. These cases are homogeneous regarding their biological and clinical characteristics, and associated with bad prognosis only improved by bone marrow transplantation. We detailed the biological characteristics of these AML by exome sequencing which demonstrated few recurrent mutations (FLT3 ITD, WT1, CEBPA, NBPF14, BCR and ODF1). The analysis of the clonal structure in these cases suggests that the mutation order in the NUP98-rearranged pediatric AML begins with the NUP98 rearrangement leading to epigenetic dysregulations then followed by mutations of critical hematopoietic transcription factors and finally, activation of the FLT3 signaling pathway.

[Superficial ulnar artery: Case report]. / À propos d'un cas d'artère ulnaire superficielle.

The anatomical variations of arterial axes of the upper limb are not uncommon and must be known to allow for safe surgical procedures and in order to limit the morbidity of these procedures. The superficial ulnar artery represents, after the variations in origin of the radial artery, the second most frequent variation in this area. When present, reconstructive procedures may be modified, especially when harvesting forearm free flaps, in order to choose this vessel as nourishing pedicle. The authors present the case of a superficial ulnar artery revealed intraoperatively while harvesting a radial forearm free flap, and a review of their cases in order to assess the frequency of this variation, and correlate it to literature.

Unilateral adrenal hemorrhagic infarction in essential thrombocythemia.

Adrenal hemorrhage is a rare disease associated with various conditions. We report a case of a 68-year-old woman with abdominal and back pain. The diagnostic work-up showed a left adrenal gland infarction associated with essential thrombocythemia. Treatment consisted in painkillers and treating the underlying condition in order to prevent further thrombotic events.

Study of the concordance between p16 immunohistochemistry and HPV-PCR genotyping for the viral diagnosis of oropharyngeal squamous cell carcinoma.

OBJECTIVE: The diagnosis of HPV-related oropharyngeal cancer in clinical practice is based on p16 immunohistochemistry and PCR detection of viral DNA (HPV-PCR). The primary objective of this study was to evaluate the concordance between these 2 diagnostic tests. The secondary objective was to study the clinical characteristics of these patients. MATERIALS AND METHODS: This single-centre prospective study was conducted between February 2010 and July 2012. Immunohistochemical analysis of p16 and HPV-PCR were performed on tumour biopsies. Concordance was evaluated according to Cohen's kappa coefficient and was interpreted according to the Landis and Koch scale. The patients' clinical data were analysed as a function of the diagnostic test results. RESULTS: Seventy-one patients were included in this study. The prevalence of HPV was 43.7% according to p16 and 31% according to HPV-PCR. The concordance study revealed a kappa coefficient of 0.615. A tumour of the tonsil or base of the tongue was detected in 100% of p16+/HPV-PCR+ cases. Smoking and alcohol abuse were significantly less frequent among HPV+ patients regardless of the method of detection. These patients were older and presented tumours with a lower grade of histological differentiation. CONCLUSION: p16 immunohistochemistry or HPV-PCR used alone appear to be insufficient. These results confirm the high prevalence of HPV-related oropharyngeal squamous cell carcinoma (OSCC) and the previously reported specific clinical and histological features, apart from age. It appears essential for future clinical trials to be stratified according to smoking and tumour HPV status, defined by means of reliable virological tests targeting E6/E7 mRNA and no longer a simple positive response to the p16 marker, as is frequently the case at the present time. New tests suitable for use in routine practice therefore need to be developed.

[Surgery for deep infiltrating endometriosis before in vitro fertilization: no benefit for fertility?]. / Chirurgie pour endométriose pelvienne profonde avant fécondation in vitro : pas de bénéfice pour la fertilité ?

OBJECTIVE: Does surgery for deep infiltrating endometriosis (DIE) before in vitro fertilization (IVF) improve pregnancy and birth rate? PATIENTS AND METHODS: Cohort study of 177 consecutive patients with DIE related infertility and receiving IVF. Patients were divided into 3 groups according to surgical management decided during multidisciplinary team meeting. Group no surgery (NS) (n=65), group complete surgery (CS) with complete resection of all lesions (n=49) and group incomplete surgery (IS) with gestures improving ovaries accessibility for IVF and/or facilitating embryonic implantation (n=63). Pre-surgery clinical, MRI lesion locations, and history of IVF characteristics were analyzed with logistic regression. RESULTS: There was no significant difference in general and IVF characteristics and in the severity of endometriosis among the three groups (P=0.43). Overall pregnancy and birth rates after IVF were 45.8% and 33.3%, respectively and were not different among the 3 groups (P=0.59 and P=0.49). Four major complications during oocytes retrievals were observed in NS group, one in IS group and none in CS group. Presence of an inter-utero-rectal lesion at MRI decreased the rate of pregnancy (OR=0.49 [0.25, 0.97]). DISCUSSION AND CONCLUSIONS: Surgery for deep infiltrating endometriosis does not improve pregnancy and birth rates before IVF. This inter-utero-rectal extensive lesion might explain IVF failures by ovarian difficult access and difficulties in embryonic transfers. Further studies should explore the impact of surgical excision of inter-utero-rectal lesion on oocyte retrieval and embryonic transfer.

[When should an orthoptic evaluation be prescribed in the management of orbital floor fracture? A prospective study of 47 fractures]. / Quand demander un examen orthoptique dans la prise en charge des fractures du plancher de l'orbite ?

INTRODUCTION: We evaluated the indication of orthoptic evaluation for the management of orbital floor fractures in a prospective series. MATERIAL AND METHOD: Forty-seven patients presenting with an orbital floor fracture were included in our prospective study. Consultations in orthoptics and maxillo-facial surgery were regularly carried out. Diplopia and motility were systematically assessed as well as a coordimetric examination according to Hess-Lees's technique. RESULTS: Nineteen percent of coordimetric motility disorders were observed among asymptomatic patients, after trauma. No diplopia or clinical motility disorder were observed 1 and 2 months after trauma, and coordimetric examinations came back to normal 2 and 3 months after trauma respectively for non-operated (26) and operated (21) patients. CONCLUSIONS: An orthoptic evaluation is necessary for the management of orbital floor fractures to diagnose the type of diplopia, motility disorders, and to indicate a coordimetric examination if diplopia is present. We suggest this orthoptic evaluation for patients presenting with diplopia between 5 and 10 days following trauma, 1 month after trauma for non-surgical treatment and 2 months after trauma for surgical treatment.

Charcot spinal arthropathy in a diabetic patient.

We report a case of Charcot spinal arthropathy in a diabetic patient and emphasize the clinical reasoning leading to the diagnosis, discuss the differential diagnosis, and insist on the crucial role of the radiologist and pathologist which allows the distinction between Charcot spinal arthropathy and infectious or tumoural disorders of the spine.

Severe symptomatic hypomagnesaemia induced by the chronic use of proton pump inhibitors: a case report of a patient with Zollinger-Ellison syndrome.

The association between proton pump inhibitor (PPI) therapy and hypomagnesaemia has been recognized since 2006. We report the case of a 51-year-old woman who developed severe symptomatic hypomagnesaemia after a long-term PPI therapy given for recurrent peptic ulcer disease. Hypomagnesaemia could only partially be resolved during substitution therapy, but was corrected after withdrawal of the PPI. Recurrence of hypomagnesaemia occurred after retreatment with PPIs, supporting the causal relationship. An underlying gastric acid hypersecretion (Zollinger-Ellison syndrome) was highly suspected and eventually controlled by a combination of a histamine 2-receptor antagonist and octreotide, without the need for further PPI therapy after 2 years of follow-up.