Micronodular thymic carcinoma with lymphoid hyperplasia: relevance of immunohistochemistry with a small panel of antibodies for diagnosis-a RYTHMIC study.

Micronodular thymic carcinoma with lymphoid hyperplasia (MNTCLH) is a rare form of thymic carcinoma. We present the experience of RYTHMIC, the French national network devoted to the treatment of thymic epithelial tumors through multidisciplinary tumor boards with a review of all tumors by pathologists for classification and staging. Six cases of MNTCLH were diagnosed during a review of 1007 thymic epithelial tumors. Histologically, epithelial cells with atypia and mitoses formed micronodules that were surrounded by an abundant lymphoid background with follicles. There was neither obvious fibro-inflammatory stroma nor necrosis. Spindle cells areas were common. Initial diagnosis was micronodular thymoma in two cases, cellular atypia being overlooked, eclipsed by the micronodular pattern. Immunohistochemistry with a panel of five antibodies showed that cytokeratins (AE1-AE3) and p63-positive epithelial cells also expressed CD5 and that there was no TdT-positive cells within the tumors. CD20 highlighted the lymphoid hyperplasia. Additionally epithelial cells also expressed CD117 and diffusely Glut 1. Twenty-seven micronodular thymomas with lymphoid stroma diagnosed during the same period did not show the CD5 and CD117 positivities seen in MNTCLH and contained TdT-positive lymphocytes. Three of the 6 patients with MNTCLH had adjuvant radiotherapy. Three patients with follow-up information were alive without recurrence at 38, 51, and 95 months. Our study shows that immunohistochemistry, such as that used in the RYTHMIC network with a small panel of antibodies, may easily help to confirm the correct diagnosis of MNTCLH, a rare and low-aggressive form of thymic carcinoma, and avoid the misdiagnosis of micronodular thymoma.

Impact of expert pathologic review of thymic epithelial tumours on diagnosis and management in a real-life setting: A RYTHMIC study.

BACKGROUND: Classification of thymic epithelial tumours (TETs) is known to be challenging; however, the level of discordances at a nationwide level between initial and expert diagnosis and their clinical consequences are currently unknown. RYTHMIC is a national network dedicated to the management of TET based on initial histological diagnosis, followed by an additional expert review of all cases. Our aim was to evaluate the discordances between initial and expert diagnoses and whether they would have led to different clinical management. PATIENTS AND METHODS: We conducted a retrospective analysis of the cohort of patients discussed at RYTHMIC tumour board from January 2012 to December 2016. Assessment of disagreement was made for histological typing and for staging. The discordances were classified as major or minor based on whether they would have changed or not the proposed therapeutic strategy, respectively. Follow-up of the patients with major discordances was conducted until December 2018. RESULTS: Four hundred sixty-seven patients were reviewed, and 183 (39%) discordances were identified either related to histological subtype (132) and/or stage (72). Major discordances were identified in 27 patients (6%). They included 16 patients with TET for whom treatment recommendation based on the central review would have been post-operative radiotherapy, whereas it had not been the case. However, follow-up did not show any progression among the 15 patients with high-grade histology and/or stage resected thymomas. On the other hand, among the remaining 11 patients including 7 with a diagnosis other than TET, the overall management or follow-up would have been completely different with the expert diagnosis. CONCLUSION: Our real-life cohort reveals a high level of discordances considering TET diagnosis and supports expert review for optimal clinical management.

[Thymoma and squamous thymic carcinoma diagnosis; experience from the RYTHMIC network]. / Diagnostic des thymomes et carcinomes thymiques malpighiens ; expérience du réseau RYTHMIC.

The RYTHMIC network, supported by the French National Cancer Institute is dedicated to the management of patients with thymic epithelial tumors through regional and national multidisciplinary tumor boards. Tumor board decisions are based on the initial pathology diagnoses. However, following clinical inclusion in the network, a central pathology review is organized, implicating a panel of pathologists, for histotype and stage classification, which is different from a classical second opinion from pathologist to pathologist for a difficult case. Thanks to the participation of all French pathologists, more than 1000 cases have been reviewed by the panel. The aim of this review is to share with the French pathology community, the experience of the group. It underlines the importance of macroscopy and surgeon-pathologist involvement to allow a good central review, the main histopathological and immunophenotypical patterns of the most frequent thymomas and thymic carcinoma types, the differential diagnoses, as well as the difficulties for the panel to reproducibly assess on slides, stage, for some cases.

Desquamative interstitial pneumonia induced by metal exposure. A case report and literature review.

BACKGROUND: Forms of interstitial pneumonia secondary to exposure to an air-contaminant are varied and so far, insufficiently described. OBJECTIVES/METHODS: We report here a case of a 57-year-old patient managed in our department for the exploration of MRC grade 2 dyspnoea and interstitial pneumonia. He mentioned multiple occupational and domestic exposures such as hens' excrements, asbestos and metal particles; he also had a previous history of smoking. RESULTS: High-resolution computed tomography showed ground glass opacities predominating in posterior territories and surrounding cystic lesions or emphysematous destruction. The entire etiological assessment revealed only macrophagic alveolitis with giant multinucleated cells on the bronchoalveolar lavage. A surgical lung biopsy allowed us to refine the diagnosis with evidence of desquamative interstitial pneumonia and pulmonary granulomatosis. Finally, the analysis of the mineral particles in the biopsy revealed abnormally high rates of Zirconium and Aluminium. We were therefore able to conclude to a desquamative interstitial pneumonia associated with pulmonary granulomatosis linked to metal exposure (Aluminium and Zirconium). The clinical, functional and radiological evolution was favorable after a systemic corticosteroid treatment with progressive decay over one year. CONCLUSION: This presentation reports the first case to our knowledge of desquamative interstitial pneumonitis related to exposure to Zirconium and the third one in the context of Aluminium exposure. The detailed analysis of the mineral particles present on the surgical lung biopsy allows for the identification of the relevant particle to refine the etiological diagnosis, to guide the therapeutic management and to give access to recognition as an occupational disease. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 79-84).

Successful Terbinafine Treatment for Cutaneous Phaeohyphomycosis Caused by Trematosphaeria grisea in a Heart Transplanted Man: Case Report and Literature Review.

Phaeohyphomycosis is a chronic infectious disease caused by dematiaceous fungi. It is characterized by the presence of pigmented septate mycelia within tissues. In the case of superficial infection, the lesion(s) chronically evolve(s) toward painless pseudo-tumor(s) of the soft parts. We report herein the original case of a heart transplanted man who exhibited phaeohyphomycosis of the left hand, with no mention of travels in endemic areas. Trematosphaeria grisea was identified as the causative agent, which is quite innovative since this species has been rather described in mycetoma. The antifungal treatment initially based on isavuconazole alone was not sufficient to cure the patient. In contrast, its association with local terbinafine ointment allowed total clinical improvement. This finding is unusual as diagnosis of phaeohyphomycosis caused by T. grisea is uncommon in nontropical countries, and as the outcome appeared successful by the means of add-on therapeutic strategy with terbinafine.

Recurrent chromosomal rearrangements of ROS1, FRK and IL6 activating JAK/STAT pathway in inflammatory hepatocellular adenomas.

BACKGROUND: Inflammatory hepatocellular adenomas (IHCAs) are benign liver tumours characterised by an activation of the janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway caused by oncogenic activating mutations. However, a subset of IHCA lacks of identified mutation explaining the inflammatory phenotype. METHODS: 657 hepatocellular adenomas developed in 504 patients were analysed for gene expression of 17 genes and for mutations in seven genes by sequencing. 22 non-mutated IHCAs were analysed by whole-exome and/or RNA sequencing. RESULTS: We identified 296 IHCA (45%), 81% of them were mutated in either IL6ST (61%), FRK (8%), STAT3 (5%), GNAS (3%) or JAK1 (2%). Among non-mutated IHCA, RNA sequencing identified recurrent chromosome rearrangement involving ROS1, FRK or IL6 genes. ROS1 fusions were identified in 8 IHCA, involving C-terminal part of genes highly expressed in the liver (PLG, RBP4, APOB) fused with exon 33-35 to 43 of ROS1 including the tyrosine kinase domain. In two cases a truncated ROS1 transcript from exon 36 to 43 was identified. ROS1 rearrangements were validated by fluorescence in situ hybridisation (FISH) and led to ROS1 overexpression. Among the 5 IHCA with FRK rearrangements, 5 different partners were identified (MIA3, MIA2, LMO7, PLEKHA5, SEC16B) fused to a common region in FRK that included exon 3-8. No overexpression of FRK transcript was detected but the predicted chimeric proteins lacked the auto-inhibitory SH2-SH3 domains. In two IHCA, we identified truncated 3'UTR of IL6 associated with overexpression of the transcript. CONCLUSION: Recurrent chromosomal alterations involving ROS1, FRK or IL6 genes lead to activation of the JAK/STAT pathway in IHCAs.

Immune biomarkers in thymic epithelial tumors: expression patterns, prognostic value and comparison of diagnostic tests for PD-L1.

BACKGROUND: Immunotherapy is currently under investigation in B3 Thymoma (TB3) and Thymic Carcinoma (TC). PD-L1 expression has been evaluated on a limited number of patients with selected antibodies. We aimed to analyze cohort of TB3 and TC with a panel of antibodies to assess the prevalence of PD-L1 expression, its prognostic value and to set up a reproducible test. METHODS: We retrospectively studied 103 patients samples of FFPE histologically confirmed TB3 (n = 53) and TC (n = 50) by expert pathologists within the RYTHMIC national network. We compared PD-L1, PD1, CD8 and PD-L2 expression and performed correlation with tumor types and patients outcomes. Four PD-L1 antibodies were tested, three of them validated as companion tests in lung cancer, one tested on two automates on whole section of tumors. We evaluated the percentage and intensity of both epithelial and immune stained cells. RESULTS: TB3 epithelial cells had a higher and more diffuse expression of PD-L1 than TC regardless the antibodies tested (p < 0.0001). Three out of four antibodies targeting PD-L1 tested on the DAKO autostainer gave similar staining. Concordance between antibodies was lower for PD-L1 staining on immune cells with no significant difference between TB3 and TC except on E1L3N antibody. PD-L2 antibody stained no tumor epithelial cells. High PD-L1 expression was correlated with a better overall survival for TB3 and was not correlated with tumor staging. CONCLUSION: Frequent PD-L1 expression, particularly in TB3, paves the way for immunotherapy in TET (Thymic Epithelial Tumor). Otherwise, we have set up three reproducible LDT (laboratory-developed test) for four PD-L1 antibodies.

Natural history of liver adenomatosis: A long-term observational study.

BACKGROUND & AIMS: Liver adenomatosis (LA) is characterized by the presence of at least 10 hepatocellular adenomas (HCAs), but the natural history of this rare liver disorder remains unclear. Thus, we aimed to reappraise the natural history and the risk of complications in a cohort of patients with at least 10 HCAs. METHODS: We analyzed the natural history of 40 patients with LA, excluding glycogen storage disorders, in a monocentric cohort. Pathological examination was performed, with immunostaining and molecular biology carried out on surgical specimens or liver biopsies. RESULTS: Forty patients (36 female) were included with a median follow-up of 10.6 (1.9-26.1) years. Six (15%) patients had familial LA, all with germline HNF1A mutations. Median age at diagnosis was 39 (9-55) years. Thirty-three (94%) women had a history of oral contraception, and 29 (81%) women had a pregnancy before LA diagnosis. Overall, thirty-seven (93%) patients underwent surgery at diagnosis. Classification of HCAs showed 46% of patients with HNF1A-mutated HCA, 31% with inflammatory HCA, 3% with sonic hedgehog HCA, 8% with unclassified HCA. Only 15% of the patients demonstrated a "mixed LA" with different HCA subtypes. Hepatic complications were identified in 7 patients: 1 patient (3%) died from recurrent hepatocellular carcinoma after liver transplantation; 6 (15%) had hemorrhages, of which 5 occurred at diagnosis, with 1 fatal case during pregnancy, and 2 occurred in male patients with familial LA. Four patients (10%) had repeated liver resections. Finally, 4 (10%) patients developed extrahepatic malignancies during follow-up. CONCLUSIONS: The diversity in HCA subtypes, as well as the occurrence of bleeding and malignant transformation during long-term follow-up, underline the heterogeneous nature of LA, justifying close and specific management. In patients with germline HNF1A mutation, familial LA occurred equally frequently in males and females, with a higher rate of bleeding in male patients. LAY SUMMARY: Liver adenomatosis is a rare disease characterized by the presence of 10 or more hepatocellular adenomas that may rarely be of genetic origin. Patients with liver adenomatosis have multiple adenomas of different subtypes, with a risk of bleeding and malignant transformation that justify a specific management and follow-up.

Primary cutaneous large B-cell lymphomas: relevance of the 2017 World Health Organization classification: clinicopathological and molecular analyses of 64 cases.

AIMS: We applied the 2017 World Health Organization (WHO) classification criteria to categorise a series of 64 primary cutaneous large B-cell lymphomas (PCLBCLs), containing a majority (≥80%) of large cells and a proliferative rate of ≥40%, raising the problem of the differential diagnosis between PCLBCL, leg type (PCLBCL-LT) and primary cutaneous follicle centre lymphoma, large cell (PCFCL-LC). The aims were to determine the reproducibility and prognostic relevance of the 2017 WHO criteria. METHODS AND RESULTS: Morphology and phenotype identified 32 PCLBCLs-LT and 25 PCFCLs-LC; seven cases (11%) remained unclassified. Morphology was less reproducible than immunophenotype. Pertinent markers for the differential diagnosis were MUM1, FOXP1, CD10, and IgM. bcl-2 and bcl-6 were expressed by both PCFCLs-LC and PCLBCLs-LT at substantial levels. Neither Ki67 expression nor p63 expression was of diagnostic value. MYD88 was found to be mutated only in PCLBCLs-LT (n = 22, 69%). According to Hans/Hans modified algorithms, 23 of 25 PCFCLs-LC had germinal centre (GC) status, and the 32 PCLBCLs-LT had non-GC status. Overall survival was poorer for PCLBCLs-LT than PCFCLs-LC (P = 0.0002). Non-GC cases had poorer overall survival than GC cases (P = 0.0007). In PCLBCLs-LT, MYC expression was associated with cutaneous relapses (P = 0.014). When GC/non-GC status was applied to unclassified cases, only a single case remained discordant. CONCLUSIONS: Our results support the 2017 WHO classification criteria for PCLBCL diagnosis. The Hans modified algorithm using CD10 and MUM1 distinguished PCFCLs-LC from PCLBCLs-LT with optimal diagnostic value without requiring bcl-6 immunolabelling (poorly reproducible). Rare unclassified cases may constitute a provisionally heterogeneous subgroup for which GC/non-GC status (relevant for prognosis) may guide therapeutic decisions.

Interest of variations in microRNA-152 and -122 in a series of hepatocellular carcinomas related to hepatitis C virus infection.

AIM: Hepatocellular carcinoma (HCC) is a common outcome of chronic hepatitis C virus (HCV) infection and constitutes the main burden of this disease. The molecular mechanisms underlying the development of HCC are multiple and might involve certain microRNA (miR). As discordant results have been reported concerning the detection of expression of miR-152 and miR-122 in HCC, our aim was to measure the levels of both miRs in serum and liver samples. METHODS: We analyzed miR-152 and miR-122 expression by reverse transcription-quantitative polymerase chain reaction in a serum cohort from 14 HCV-infected patients who developed HCC, 20 HCV+ patients without HCC, and 19 control patients. We also studied miR-152 and miR-122 in an independent tissue cohort from 11 normal livers, and from paired HCC and non-tumor adjacent livers of 11 HCV-infected patients and 12 non-infected patients. RESULTS: In serum samples, higher levels of miR-122 were found in non-HCC HCV+ compared to HCC HCV+ and control groups, whereas miR-152 was detectable in a lower range in HCC HCV+ compared to non-HCC HCV+ and control groups. We found higher signals for miR-122 and miR-152 in non-tumor liver and HCC tissues compared to control tissues. Hepatocellular carcinoma etiology had no detectable influence on miR-122 expression, whereas miR-152 was increased in HCV+ tissue samples. CONCLUSIONS: Detection of low values of circulating miR-152 is a potentially interesting marker of hepatocarcinogenesis in HCV+ patients, in contrast to miR-122, which varies according to hepatocyte damage.

Diagnostic performance of contrast-enhanced CT-scan in sinusoidal obstruction syndrome induced by chemotherapy of colorectal liver metastases: Radio-pathological correlation.

PURPOSE: Sinusoidal obstruction syndrome (SOS) is a likely side effect of colorectal liver metastases (CRLM) chemotherapy. This study aimed to assess computed tomography scan (CT-scan) performance for SOS diagnosis for patients receiving neoadjuvant chemotherapy (NC) prior to CRLM surgery, comparing obtained results with pathological gold standard. METHODS: Preoperative CT-scans of 67 patients who had received a NC prior to liver resection for CRLM from 2011 to 2016 were retrospectively analysed. Positive diagnosis and severity of SOS were established after consensual review of the slides by three pathologists. Preoperative CT-scans were separately interpreted by two radiologists and evocative signs of SOS were sought, defined according to a literature review and operators experience. In order to identify SOS predictors, univariate analysis and multivariate logistic regression were used to study CT-scan signs and pathological results correlation. RESULTS: Twenty-nine patient (43%) had an SOS, 22 (33%) were low-grade and 7 (10%) were high-grade. All patient had received a median of 6 cures (3-27) containing Oxaliplatin for 53 (79%) of them. In univariate analysis, hepatic heterogeneity (p<0.001), puddle-like or micronodular appearance (p<0.001), peripheral distribution of heterogeneity (p=0.085), clover-like sign (p=0.02), splenomegaly (p=0.0026), spleen volume increase ≥30% (p=0.04) or splenic length increase ≥15% (p=0.04), as well as the subjective impression of the observer (P<0.001) were significantly associated with SOS diagnosis. In multivariate analysis, clover-like sign (OR 1.87, 95% CI 1.18-2.95, p=0.0081), increase in spleen volume ≥30% (OR 1.29, 95% CI 1.01-1.64, p=0.04), and the peripheral distribution of heterogeneity (OR 1.53, 95% CI 1.21-1.94, p<0.001) were independent SOS predictors. The area under the ROC curve was 0.804. The inter-observer agreement for SOS diagnosis was moderate (Kappa=0.546). CONCLUSION: CT-scan can detect suggestive signs of SOS in patients receiving chemotherapy for CRLM. By integrating clinical and biological information into CT-scan data, it may be fruitful to create a positive diagnostic and severity score for chemotherapy-induced SOS.

Cutaneous Kaposi sarcoma during treatment with superpotent topical steroids and methotrexate for bullous pemphigoid: three cases.

Iatrogenic Kaposi sarcoma (KS) has previously been reported in patients with bullous pemphigoid (BP), in relation to systemic steroids. To report three cases of previously unreported cutaneous KS during treatment with superpotent topical steroids (STS) and methotrexate (MTX). All patients were elderly men with BP treated with STS for 2 to 32 months (cumulative doses: 2,700-9,150 g) before MTX was introduced (dosage: 10-12.5 mg/week). KS occurred one to nine months after the combined therapy. In one case, KS rapidly resolved after withdrawal of MTX. In two cases, vinblastine and/or radiotherapy were required to achieve regression of KS. Human herpes virus 8 (HHV8) latency-associated nuclear antigen was not expressed in BP lesions biopsied prior to development of KS (n = 3), but HHV8 DNA was detected in BP lesions from the patient with the most aggressive KS. Several predisposing factors were identified, including sex and age, high cumulative doses of STS, combination with MTX, and impaired immune status. In such cases, serum antibodies against HHV8 infection may be investigated in BP patients before introduction of MTX in order to guide clinical monitoring.

Molecular Classification of Hepatocellular Adenoma Associates With Risk Factors, Bleeding, and Malignant Transformation.

BACKGROUND & AIMS: Hepatocellular adenomas (HCAs) are benign liver tumors that can be assigned to molecular subtypes based on inactivating mutations in hepatocyte nuclear factor 1A, activating mutations in ß-catenin, or activation of inflammatory signaling pathways. We aimed to update the classification system for HCA and associate the subtypes with disease risk factors and complications. METHODS: We analyzed expression levels of 20 genes and sequenced exon regions of 8 genes (HNF1A, IL6ST, CTNNB1, FRK, STAT3, GNAS, JAK1, and TERT) in 607 samples of 533 HCAs from 411 patients, collected from 28 centers mainly in France from 2000 and 2014. We performed gene expression profile, RNA sequence, whole-exome and genome sequence, and immunohistochemical analyses of select samples. Molecular data were associated with risk factors, histopathology, bleeding, and malignant transformation. RESULTS: Symptomatic bleeding occurred in 14% of the patients (85% of cases were female, median age, 38 years); 7% of the nodules were borderline between HCA and hepatocellular carcinoma, and 3% of patients developed hepatocellular carcinoma from HCA. Based on molecular features, we classified HCA into 8 subgroups. One new subgroup, composed of previously unclassified HCA, represented 4% of HCAs overall and was associated with obesity and bleeding. These tumors were characterized by activation of sonic hedgehog signaling, due to focal deletions that fuse the promoter of INHBE with GLI1. Analysis of genetic heterogeneity among multiple HCAs, from different patients, revealed a molecular subtype field effect; multiple tumors had different mutations that deregulated similar pathways. Specific molecular subtypes of HCA associated with various HCA risk factors, including imbalances in estrogen or androgen hormones. Specific molecular subgroup of HCA with ß-catenin and sonic hedgehog activation associated with malignant transformation and bleeding, respectively. CONCLUSIONS: Using sequencing and gene expression analyses, we identified a subgroup of HCA characterized by fusion of the INHBE and GLI1 genes and activation of sonic hedgehog pathway. Molecular subtypes of HCAs associated with different patients' risk factors for HCA, disease progression, and pathology features of tumors. This classification system might be used to select treatment strategies for patients with HCA.

Glut-1 intensity and pattern of expression in thymic epithelial tumors are predictive of WHO subtypes.

OBJECTIVES: Glucose-transporter-1 (Glut-1) may be a useful marker for differentiating B3 thymomas and thymic carcinomas. Since the literature is limited, we undertook a study to evaluate its diagnostic value in a series of thymic epithelial tumors. MATERIALS AND METHODS: Glut-1 expression was studied by the group of pathologists linked to the French national oncological network RYTHMIC. Immunostaining was performed on a whole section of one paraffin block in a series of 92 successive surgical specimens. Patterns (focal, zonal, diffuse) and intensity of Glut-1 expression were assessed and compared with WHO histological subtypes. RESULTS: Expression was mainly restricted to epithelial cells. Immature T-lymphocytes were negative. A diffuse, moderate or strong staining was observed in most thymic carcinomas (15/16). In B3 thymomas (10/11) and in B3 thymomas borderline to thymic carcinomas (5/6), a moderate to strong zonal staining was observed at distance from vessels and fibrous septa. This pattern sometimes created the aspect of an anastomosing network in large cellular lobules. In B1 thymomas, immunostaining highlighted foci of medullary differentiation (7/8). B2 thymomas (n=25) were heterogeneous, with a spectrum of patterns ranging between those of B1 and B3 thymomas. Type A thymomas (n=5) mostly presented a weak positivity but one aggressive case showed zonal moderate/strong positivity. Most AB thymomas (15/17) showed weak to moderate immunostaining in spindle cell areas. In micronodular thymomas (n=3), epithelial cells and B-lymphocytes were weakly positive while follicular dendritic cells were strongly highlighted. One metaplastic thymoma displayed diffuse and moderate positivity. CONCLUSION: Glut-1 expression globally depended on histological subtypes and the staining patterns (diffuse or zonal) were different between thymic carcinomas and type B3 thymomas. A comparative study of Glut-1 expression in atypical versus conventional type A thymomas appears warranted. Otherwise, restriction to epithelial cells makes likely a correlation with clinical assessment of glucose uptake in lymphocyte-poor tumors.

[Cutaneous lymphoproliferations: proposal for the use of diagnostic algorithms based on 2760 cases of cutaneous lymphoproliferations taken from the INCa networks (LYMPHOPATH and GFELC) over a two-year period]. / Lymphoproliférations cutanées : proposition d'algorithmes diagnostiques à partir de l'expérience sur 2ans des réseaux INCa (LYMPHOPATH et GFELC) sur 2760 lymphoproliférations cutanées.

INTRODUCTION: Taking as a base our retrospective study of 2760 cases of cutaneous lymphoproliferations from the LYMPHOPATH and GFELC networks, we analyzed the doubtful and discordant cases between non-expert and expert pathologists, and the interest of clinicopathological confrontation. MATERIAL AND METHODS: We defined the main diagnostic difficulties presented by cutaneous lymphoproliferations. We then designed and tested the algorithms on 20 random cases with 20 pathologists, in order to be used by any pathologist (not necessarily specialised in dermatopathology). RESULTS: The problematic differential diagnoses most frequently encountered are the following: MF or reactive dermatose; lymphoma without any other precision or reactive infiltrate; small B cell lymphoproliferation: lymphoma or reactive infiltrate; phenotyping of large B cell lymphoproliferation. We also analyzed less common problematic differential diagnoses, on the grounds that they are over- or under- diagnosed. Our test had a 72% success rate among the 20 randomly tested cases. The use of several algorithms for the same case is possible. DISCUSSION: Our study shows that an expert second-opinion is of interest in the area of cutaneous lymphoproliferations. A second opinion is useful for distinguishing a small B cell lymphoma from a HLR, and for defining a final diagnosis when the first pathologist doubts between lymphoma and reactive infiltrate. However, we demonstrate that for the problem MF or reactive dermatose, an initial clinicopathological confrontation produces more results than a second-opinion pathology review. CONCLUSION: This is the first study of cutaneous lymphoproliferations that, without excluding reactionary infiltrates, concentrates on doubtful and discordant diagnoses between non expert and expert pathologists, and which has produced tested diagnostic algorithms.

Gastroesophageal reflux disease is a risk factor for severity of organizing pneumonia.

BACKGROUND: The link between organizing pneumonia (OP) and gastroesophageal reflux disease (GERD) is not well known. There is little evidence in the literature to establish a causal link between GERD and OP. OBJECTIVES: The aim of the study was to assess the hypothesis that OP is more severe when it is associated with GERD and that it leads to more frequent relapses. METHODS: In a retrospective study on 44 patients suffering from OP, we compared the clinical, radiological and histological characteristics of 2 groups, 1 composed of patients with GERD (n = 20) and the other of patients without GERD (n = 24). RESULTS: The GERD group was distinguished by a higher number of patients with migratory alveolar opacities on chest radiography and thoracic computerized tomography (14/20 vs. 9/24; p = 0.03 and 18/20 vs. 13/24; p = 0.01), greater hypoxemia [60 (42-80) vs. 70 (51-112) mm Hg; p = 0.03], greater bronchoalveolar lavage cellularity [0.255 (0.1-1.8) vs. 0.150 (0.05-0.4) g/l; p = 0.035] and more frequent relapses (14/20 vs. 9/24; p = 0.03). CONCLUSIONS: OP associated with GERD is more severe and results in more frequent relapses. Microinhalation of gastric secretions might induce lung inflammation leading to OP and relapse. We suggest that typical symptoms of GERD such as pyrosis should be investigated in OP.