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Peripheral T cell lymphomas are rare malignancies with aggressive course, with several different subtype described in the 2016 WHO classification. Their distribution across the world is heterogenous, with marked difference between Western and Asian country. Their clinical presentation often comprise extra-nodal involvement, B symptoms and immune system disorder which can lead to wrong diagnosis orientation. Make a right diagnosis need a experienced pathologist in close collaboration with clinical datas. Peripheral T cell lymphomas are in general associated with poor prognosis when treated with anthracyclines-based regimen, and several studies and trials focused on the use of intensified regimen or novel targeted agents, whose proper indication still remain to be clarified.

HHV-8 is an oncogenic Gammaherpesvirinae discovered in 1994 during the HIV pandemic. It is the causative agent of Kaposi's sarcoma, and is also associated with the occurrence of several aggressive B lymphoproliferative disorders. Most of them occur in an immunosuppression setting, usually due to HIV infection. Multicentric HHV8-associated Castleman's disease and KSHV Inflammatory Cytokine Syndrome (KICS) are primarily reactive entities with prominent systemic features. They illustrate the cytokinic storm induced by HHV-8 in its cell host. On the other hand, HHV-8 can drive proliferation and lymphomagenesis of its plasmablastic cell host, and is associated with a risk to develop aggressive lymphomas with plasmacytic differenciation. Primary effusion lymphoma usually localizes in body cavities and may affect other extra-nodal sites ; its prognostic is poor. Diffuse large B-cell lymphoma HHV-8, NOS affect more commonly nodes and blood and evolve from infected cell of HHV-8 associated Castleman disease. On the contrary, germinotropic lymphoproliferative disorders presents mainly as localized adenopathy with indolent course, and show polyclonality. Histology plays a key role in distinguishing these different entities and need expert reviewing, especially since they may be associated with each other. Besides lymphoproliferative disorders, HHV8 is associated with various hematological manifestations. The aim of this review is to provide an update on the presentation, diagnosis, and management of immunologic and hematologic complications associated with HHV-8.

In several instances, our group has reported opposite findings to others when analyzing the genetic features of primary cutaneous T-cell or B-cell lymphomas (CTCL or CBCL). This was especially the case for the absence of NAV3 rearrangements in CTCL, the low rate of BCL2 or MYC rearrangement in primary cutaneous follicle center lymphomas (CFCL) or primary cutaneous large B-cell lymphomas, leg-type (CLBCL, LT), respectively. Here, we review bias accounting for such discrepancies. Primary cutaneous lymphoma usually present with characteristic clinical and pathological features which serve as universal criteria for initial diagnosis and treatment. When required, extensive staging including CT scan, blood analysis and for some groups bone marrow staging, is mandatory to eliminate a secondary CTCL or CBCL. Early spreading may change the initial diagnosis and a long-term follow-up is also necessary to determine the risk for extracutaneous involvement. Non-uniform inclusion criteria and follow-up time may contribute to discrepancies, especially for studies claiming for a high rate of BCL2 rearrangement in CBCL. Most CBCL or CTCL usually display an indolent course except for aggressive subtypes arising de novo such as Sezary syndrome (SS), tumor or transformed mycosis fungoides (T-MF) or CLBCL-LT. Borderline cases between indolent and aggressive cutaneous lymphomas exist and may be called for example as leukemic CTCL or CBCL, not-otherwise specified (NOS) leading to heterogeneous terminology between centers. Moreover, aggressive CL are rare occurring mainly in adults or elderly that limits therapeutic options and comparison of small groups in retrospective series. The distribution of diagnosis between the three main primary CBCL including marginal-zone lymphoma (MZL), CFCL and CLBCL, LT has considerably evolved and its heterogeneity between centers may also hamper uniform findings. Our proposal to classify large CBCL according to germinal center or non-germinal center origin has so far not been validated by others while in systemic lymphomas genomic profiling appears mandatory to identify patients with impaired prognosis. In the most frequent cutaneous lymphomas, no highly recurrent genetic mutation is commonly used for diagnosis purpose. Some genetic lesion such as CCND1 rearrangement in mantle cell lymphoma can serve a positive criteria of secondary skin involvement. Alternatively, exceptional primary anaplastic large cell lymphoma (ALCL) bear ALK rearrangement preventing to use such criteria as a hallmark of secondary skin ALCL. BCL2 rearrangement in primary CFCL contributes to identify patients at risk for extracutaneous spreading. Most reports found negative data for NAV3 rearrangement in CTCL that may not be a primary oncogenic driver but a secondary event. Interestingly, MYC rearrangement or double-hits may have a low impact on prognosis in CBCL while they are usually associated with impaired prognosis in systemic or nodal lymphomas. Alternatively, some highly recurrent mutation such as those of MYD88 in CLBCL, LT should be routinely assessed. While clinical presentation will remain a basis for CL diagnosis and treatment, it is now time to integrate molecular profiling in research studies or clinical trials to standardize diagnosis and to identify patients which will exhibit therapeutic resistance to conventional first-line treatment.

Peripheral T cell lymphomas are rare malignancies with aggressive course, with several different subtype described in the 2016 WHO classification. Their distribution across the world is heterogenous, with marked difference between Western and Asian country. Their clinical presentation often comprise extra-nodal involvement, B symptoms and immune system disorder which can lead to wrong diagnosis orientation. Make a right diagnosis need a experienced pathologist in close collaboration with clinical datas. Peripheral T cell lymphomas are in general associated with poor prognosis when treated with anthracyclines-based regimen, and several studies and trials focused on the use of intensified regimen or novel targeted agents, whose proper indication still remain to be clarified.

Background Immunophenotype of primary cutaneous diffuse large B-cell lymphoma, leg-type (PCLBCL-LT) suggests a germinal center-experienced B lymphocyte (BCL2+ MUM1+ BCL6+/−). Objectives As maturation history of B-cell is “imprinted” during B-cell development on the immunoglobulin gene sequence, we studied the structure and sequence of the variable part of the genes (IGHV, IGLV, IGKV), immunoglobulin surface expression and features of class switching in order to determine the PCLBCL-LT cell of origin. Methods Clonality analysis with BIOMED2 protocol and VH leader primers was done on DNA extracted from frozen skin biopsies on retrospective samples from 14 patients. The clonal DNA IGHV sequence of the tumor was aligned and compared with the closest germline sequence and homology percentage was calculated. Superantigen binding sites were studied. Features of selection pressure were evaluated with the multinomial Lossos model. Results A functional monoclonal sequence was observed in 14 cases as determined for IGHV (10), IGLV (2) or IGKV (3). IGV mutation rates were high (>5%) in all cases but one (median:15.5%), with superantigen binding sites conservation. Features of selection pressure were identified in 11/12 interpretable cases, more frequently negative (75%) than positive (25%). Intraclonal variation was detected in 3 of 8 tumor specimens with a low rate of mutations. Surface immunoglobulin was an IgM in 12/12 cases. FISH analysis of IGHM locus, deleted during class switching, showed heterozygous IGHM gene deletion in half of cases. The genomic PCR analysis confirmed the deletions within the switch μ region. IGV sequences were highly mutated but functional, with negative features of selection pressure suggesting one or more germinal center passage(s) with somatic hypermutation, but superantigen (SpA) binding sites conservation. Genetic features of class switch were observed, but on the non functional allele and co-existing with primary isotype IgM expression. Conclusion These data suggest that cell-of origin is germinal center experienced and superantigen driven selected B-cell, in a stage between germinal center B-cell and plasma cell.

Background Our aim was to evaluate whether the cell of origin (COO) as defined by the Hans algorithm and MYC/BCL2 coexpression, which are the two main biological risk factors in elderly patients treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP), maintain their prognostic value in a large prospective clinical trial. Patients and methods We evaluated 285 paraffin-embedded samples from patients (60–80years of age) enrolled in the Lymphoma Study Association trial LNH03-6B who were treated with R-CHOP. We correlated the COO defined by the transcriptome according to the Wright algorithm with that defined by the Hans algorithm in a subset of 62 tumors with available frozen tissue samples. Results The non-germinal center B-cell-like phenotype according to the Hans algorithm and BCL2 expression (but not MYC and BCL2 coexpression) predicted worse progression-free survival [hazard ratio (HR)=1.78, P = 0.003 and HR = 1.79, P = 0.003, respectively] and overall survival (HR = 1.85, P = 0.005 and HR = 1.67, P = 0.02, respectively) independently of the International Prognostic Index. The correlation between the Hans algorithm and the Wright algorithm was 91%, with an almost perfect concordance according to a kappa test (0.81). Conclusions Our results suggest that immunohistochemically defined COO remains a useful tool for predicting prognosis in diffuse large B-cell lymphoma when performed under optimized standardized conditions and that BCL2 expression may help to identify elderly patients at risk for relapse and who could potentially respond to anti-BCL2 targeted agents. In this prospective phase III trial, the coexpression of MYC and BCL2 does not appear to predict worse survival. Clinical trial Number NCT00144755

This letter aims to estimate the effective scattering albedo ( $\omega _{p}$ ) over the tropical forests using L-band (1.4 GHz) microwave remote sensing. It is carried out using Soil Moisture and Ocean Salinity (SMOS) mission data over five years (2011–2015). We find similar values of $\omega _{p}$ computed over the Congo and Amazon forests. The $\omega _{p }$ values depend slightly on the polarization. The values of $\omega _{p }$ at H-polarization and at 52° ± 5° (40° ± 5°) of incidence angle are within the range 0.064 – 0.069 ± 0.01 (0.061 – 0.067 ± 0.012). At V-polarization, the values of $\omega _{p }$ are slightly lower (0.060 – 0.061 ± 0.013 at 52° ± 5° of incidence angle and 0.052 – 0.055 ± 0.013 at 40° ± 5° of incidence angle). These findings should contribute to a better calibration of the value of $\omega _{p }$ over the tropical forests in both the SMOS and SM active and passive retrieval algorithms, leading to increase the SM retrieval accuracy over heterogeneous pixels.

International audience; Mediastinal gray zone lymphoma, B-cell lymphomas with intermediate features between classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma, have not been well described in the literature. We report the clinical characteristics and outcomes of a large retrospective series of 99 cases centrally reviewed by a panel of hematopathologists, with a consensus established for the diagnosis. Cases were defined as classical Hodgkin lymphoma-like morphology (64.6%) with primary mediastinal B-cell lymphoma immunophenotype, primary mediastinal B-cell lymphoma-like morphology (30.3%) with classical Hodgkin lymphoma or composite (5.1%) (synchronous occurrence of classical Hodgkin lymphoma and primary mediastinal B-cell lym-phoma). The median age was 32 years (13-83 years); 55% were women. Thirteen of 81 evaluable cases (16%) were Epstein-Barr virus-positive. Twenty-eight percent of patients presented primary refractory disease (progression under first-line treatment or relapse within one year). The 3-year event-free and overall survival rates were 63% and 80%, respectively. Patients treated with a standard regimen (RCHOP/ABVD) had worse event-free survival (P=0.003) and overall survival (P=0.02) than those treated with a dose-intensive chemotherapy (high-dose RCHOP/escalat-ed BEACOPP). Rituximab added to chemotherapy was not associated with better event-free survival (P=0.55) or overall survival (P=0.88). Radiotherapy for patients in complete remission had no impact on event-free survival. In multivariate prognostic analysis, ECOG-PS and anemia were the strongest factors associated with a shorter event-free survival and overall survival, respectively. In conclusion, this report describes the largest series of mediastinal gray zone lymphoma. Our data suggest that a dose-intensive treatment might improve the outcome of this rare and aggressive disease.

International audience

Autoimmune manifestations are common in splenic marginal zone lymphoma (SMZL) and are sometimes the presenting feature of the disease. Autoimmune cytopenia (anemia, thrombocytopenia) are the most frequently reported autoimmune conditions. However, other immunological manifestations may be associated with SMZL.We report a retrospective case series of six patients with SMZL associated with autoimmunity.Auto-immune manifestations were the presenting feature of lymphoma in four cases. Auto-immune manifestations included auto-immune cytopenia in three cases (two hemolytic anemia and one pancytopenia), thyroiditis in two cases, systemic lupus and Still's disease in one case each. Antinuclear antibodies were detected with a titre of 1/250 in three cases, and with a titre of 1/32,000 in the patient with systemic lupus. Testing for DNA antibodies was negative in all cases. Two patients had a circulating lupus anticoagulant, with portal venous thrombosis following splenectomy in one case. One patient had hypogammaglobulinemia. A monoclonal gammopathy was detected in three patients. All patients had spleen enlargement. Immunophenotyping of blood peripheral lymphocyte was typical in five out of the six cases. Bone marrow was infiltrated in five out of the six cases. Diagnosis was obtained by the combination of immunophenotyping and bone marrow histopathology in five cases, and by splenic histopathology in the remaining case. Hepatitis C virus serology was negative in all patient.Autoimmune disease as systemic lupus or Still's disease may be associated with SMZL before its tumoral manifestations are evident. In this mode of presentation, spleen enlargement, hypogammaglobulinemia, monoclonal gammopathy, and multiple autoimmune diseases, should alert the physician.

Mantle cell lymphoma reached rarely ophtalmic sphere and salivary glands. CAS REPORT: We reported a dry syndrome seen in a 67 year-old patient. The first patological analysis of accessory salivary glands evoked a primary Gougerot-Sjögren syndrome. Secondary, he presented a mantle cell lymphoma.The pathological lack of specifity and the discovery of atypical Gougerot-Sjögren syndrome must encourage complementary immunohistochemical study of salivary glands biopsy.

Vascular anastomosis is still associated with a significant rate of early or delayed complications, particularly restenosis. We have previously demonstrated that non-penetrating clips can help prevent intimal hyperplasia. The aim of this study was to evaluate how well the use of mechanical clips prevents intimal hyperplasia while maintaining arterial vasomotor function.An aortic suture was performed in 38 rabbits. A standard closure was used for 15 sutures and a small vascular closure staple (VCS) for 23. Morphological analysis was performed with standard staining, histomorphometry and immunochemical staining for smooth muscle and endothelial cells. Vasomotor response was assessed using IntraVacularUltraSound with baseline luminal area and luminal area after injection of acetylcholine and nitroglycerin. Vasomotor response was assessed before suture and before removing the aorta.There was a significant improvement in operating time for closure with vascular staples (8 +/- 2 minutes versus 13 +/- 3 minutes) without thrombosis. We noted reduced intimal hyperplasia with staple closure (0.156 +/- 0.052 versus 0.087 +/- 0.042 mm, p0.01). There was no difference for the medial thickness and the intima/media ratio was significantly different. The luminal area after suture was significantly better after vascular staple closure (16.78 +/- 0.639 mm(2) versus 17.24 +/- 0.492 mm(2), p=0.016). Vascular response to acteylcholine and nitroglycerin was equivalent for the two groups.Vascular closure staples are efficient for arterial closure. These non-penetrating systems prevent intimal hyperplasia and maintain physiological arterial vasomotor response.

Cytogenetic analyses have revealed that mantle cell lymphomas (MCL) are closely associated with the t(11;14)(q13;q32). This translocation juxtaposes the immunoglobulin heavy chain gene (IGH) sequences with the BCL-1 locus, leading to up-regulation of the CCND1 gene and consequently to an overexpression of cyclin D1 protein. We studied 27 MCL with characteristic morphological and immunological (CD5+, CD10-, CD20+, CD23-) features and 2 controls (reactionnal lymphadenitis) to evaluate the feasibility and the interest of FISH analysis on interphase cells from frozen or paraffin-embedded tissues. Sections (CC) and touch preparations (EC) of frozen tissues and sections of paraffin-embedded tissues (CF) were successfully hybridized with the Vysis LSI IgH/CCND1 dual color dual fusion translocation probe. The touch preparations presented a lower cellularity than sections, therefore allowing an easier analysis. Hybridization spots intensities were found stronger in CC and EC than in CF. The percentages of t(11;14) positive cells were similar in CC, EC and CF from a same patient. The percentage of non hybridized cells, analogous in CC and EC, was higher in CF. However, the CF were directly analysed on microscope without the need of any numerical picture treatment. The t(11;14) was detected in all the cases (27/27) and positive cells percentages were always higher than the probe cut-off (5%). The FISH analysis on interphase cells appears a performing and rapid technique to detect t(11;14) in MCL on both frozen and paraffin-embedded tissue, thus extending its practical and diagnostic use.

Pyoderma gangrenosum is an ulcerative disease of the skin. The histopathological lesions are nonspecific, characterized by a diffuse neutrophilic infiltrate in the dermis. Pyoderma gangrenosum is associated with inflammatory, digestive or articular disease, or acute or chronic hemotology disorders in 50% of the cases, more rarely with monoclonal gammapathy. A visceral localization of pyoderma gangrenosum is rare, simulating a systemic disease or an underlying neoplasia. We report a case of cutaneous pyoderma gangrenosum with splenic and hepatic localizatios associated with an IgG monoclonal gammapathy. We emphasize the efficacy of immunosuppressor treatment and the importance of long-term monitoring of these patients.

Adult mediastinal lymphangiomas are rare lesions the diagnosis of which is difficult based on imaging studies. A retrospective study of CT, MR, and pathologic findings of mediastinal lymphangioma was performed in order to correlate pathological and imaging findings. Nine cases of adult lymphangiomas were identified in the records of our institution over a 12-year period. The CT, MR, and pathologic findings were reviewed. Lesions were classified pathologically as unilocular, cavernous, and intermediate types. Pathologic examination identified six cases of unilocular lesion, two cases of cavernous type, and one intermediate type. The CT features (n = 9) included a smoothly marginated non-enhancing mass of water attenuation (n = 7), a non-enhancing mass of soft tissue attenuation (n = 1), and an enhancing multiseptated mass (n = 1). Lesions were located in the anterior mediastinum (n = 2), right paratracheal (n = 4), subcarinal (n = 1), aortopulmonic window (n = 1) areas, and below the left hilum extending into the posterior mediastinum (n = 1). The MR features (n = 3) were characterized by an enhancing multicystic and multiseptated appearance, evocative of a cavernous type in two cases. The CT appearance of mediastinal thoracic lymphangioma is variable depending on the pathologic type. The most common unilocular type is a non-enhancing thin-walled mass on CT. A less frequent cavernous type can be suggested based on a multiseptated and loculated mass on CT and/or MR examination.

We describe the case of a teenager who developed fever, arthritis, cutaneous vasculitis and severe pancytopenia 3 weeks after the third vaccination boost with a recombinant hepatitis B vaccine. Bone marrow examination showed paucity of late myeloid elements and, subsequently, maturation arrest. Interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells from the patient was dramatically increased. An underlying immune predisposition (HLA-DR3) may have indirectly enabled the vaccine to trigger a hepatitis B virus-specific cytotoxic T-lymphocyte response. It is therefore possible that the pancytopenia was induced by a dysregulation of the CD8+ T-cell compartment via increased IFN-gamma production.

Parathyroid adenomas are common lesions and are considered to be the cause of most of the primary hyperparathyroidism cases. We report the case of a 73 year-old man who presented with a primary hyperparathyroidism. Clinical and histological explorations revealed the presence of an isolated parathyroid tumor containing exclusively clear cells and devoid of malignancy. This is the second reported case of clear cell parathyroid adenoma. Thus, in spite of its low occurrence, this diagnosis must be considered after rejection of the most frequent parathyroid clear cell hyperplasia and parathyroid carcinoma, or depending of the location, clear cell thyroid tumor and clear cell renal carcinoma metastasis.

Parotidean and ovarian lymphoma often indicate the existence of non-Hodgkin's lymphoma, involving 1-5% and 0.2% of the cases, respectively. EXEGENESIS: The authors report the case of a 70-year-old woman who presented B cell lymphoma of the parotid gland revealed by a rapid increase in the parotid size. CT scan showed the existence of a tumor located in the left ovary, later confirmed by biopsy. The proposed diagnosis was diffuse B cell type lymphoma with double glandular localization. Adenopathy and bone marrow involvement were both lacking.Lymphoma with glandular localizations always require diagnosis confirmation via histological examination and immunophenotyping, and must be considered as the local sign of a general disease.

Littoral cell angioma is a rare primitive vascular tumor of the spleen considered as benign. Its clinical presentation is non specific. The diagnostic is based on histological and immunohistological analysis. The lesion is composed of anastomosing vascular channels often featuring papillary projections. They are lined by tumoral cells which exhibit an immunoreactivity for vascular and histiomonocytic markers. We report one case of littoral cell angioma and we discuss the diagnosis and the histogenesis of this tumor.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 41 - N° 2 - p. 205

A retroperitoneal localization of Castleman's disease was characterized by angiolymphoid hyperplasia. This rare disease (58 cases of abdominal localization reported to date) raises a question of nosology. The clinical features are not specific. Localized forms in young patients involve deep lymph nodes and have a good prognosis after complete surgical exeresis. Inversely, the clinical picture is much more aggressive in multiple localizations involving preferentially superficial nodes with associated plasmocyte proliferation. The prognosis is mediocre in these forms. Although transition stages have been described due to the lack of any known aetiology, the question of nosology remains open: should the different forms be separated or identified simply as two pathological forms?