[Nodular lymphocyte predominant Hodgkin lymphoma (paragranuloma of Poppema) in children: Case report, review of the literature and treatment]. / Lymphome de Hodgkin nodulaire à prédominance lymphocytaire (paragranulome de Poppema) chez l'enfant : à propos d'un cas, revue de la littérature et traitement.

We present the case of a 12 year old child with a limp. The diagnostic work-up reveals splenomegaly, multifocal bone involvement and abdominal adenopathies. A biopsy of an intra-abdominal lesion shows a lymphoid mass with a nodular architecture composed of poorly defined nodules. We identify large cells with irregular, sometimes poly-lobulated nuclei with a particular immunohistochemical profile. Those "pop-corn" cells are positive for CD20, CD79a, pax-5 and bcl-6 and are negative for CD15, CD30, bcl-2, TdT, CD56 and EMA. There is a diffuse follicular helper T cell population that is located in between the tumour cells. The overall picture is indicative of a nodular lymphocyte predominant Hodgkin lymphoma. Advanced stage of this disease is rare in children and there is currently little data to guide optimal treatment. Because of a stage IV disease, the patient is treated with chemotherapy after which complete metabolic remission is observed. 3.5 years after the initial diagnosis, our patient relapses. He is treated with chemotherapy and an autologous peripheral blood stem cell transplantation. He remains in complete remission since then. This case illustrates the favorable prognosis of the disease even after relapse.

[Marginal zone lymphoma associated with Reed-Sternberg cells: A challenge for the pathologist]. / Lymphome de la zone marginale ganglionnaire associé à des cellules de Reed-Sternberg : un challenge pour le pathologiste.

We report the case of a 46-year-old male patient presenting with a Claude Bernard-Horner Syndrome. Clinical evaluation showed a clonal B-cell population, lambda restricted. PET-scan captured femoral and axillary lymph nodes. Therefore the diagnosis of a marginal zone lymphoma was posted for which an attitude of watchful waiting was suggested. Eighteen months later, the patient developed an inguinal adenopathy. This lymph node led to the diagnosis of a nodular sclerosing Hodgkin lymphoma. Initial treatment with ABVD showed a good response, but the patient relapsed after eight months. A second biopsy confirmed the diagnosis of a marginal zone lymphoma but also identified giant Reed-Sternberg cells, (CD15+, CD30+ and CD20+). The initial biopsy was revised. This last diagnosis of a nodal marginal zone lymphoma with presence of Reed-Sternberg cells is rarely described in the literature. Several scientific theories can be found. Some cases described a transformation of non-Hodgkin lymphoma that presented Reed-Sternberg cells, other cases mentioned a collision or composite tumor. An accidental finding of Reed-Sternberg cells can be seen by after an infectious disease such as EBV. The presence of only Reed-Sternberg cells in a non-Hodgkin lymphoma is not sufficient to make a diagnosis of collision tumor.

Clinical application of targeted next-generation sequencing for colorectal cancer patients: a multicentric Belgian experience.

International guidelines made RAS (KRAS and NRAS) status a prerequisite for the use of anti-EGFR agents for metastatic colorectal cancer (CRC) patients. Daily, new data emerges on the theranostic and prognostic role of molecular biomarkers; this is a strong incentive for a validated, sensitive, and broadly available molecular screening test. Next-generation sequencing (NGS) has begun to supplant other technologies for genomic profiling. We report here our 2 years of clinical practice using NGS results to guide therapeutic decisions. The Ion Torrent AmpliSeq colon/lung cancer panel, which allows mutation detection in 22 cancer-related genes, was prospectively used in clinical practice (BELAC ISO 15189 accredited method). The DNA of 741 formalin-fixed paraffin-embedded CRC tissues, including primary tumors and metastasis, was obtained from 14 different Belgian institutions and subjected to targeted NGS. Of the tumors tested, 98% (727) were successfully sequenced and 89% (650) harbored at least one mutation. KRAS, BRAF and NRAS mutations were found in 335 (46%), 78 (11%) and 32 (4%) samples, respectively. These mutation frequencies were consistent with those reported in public databases. Moreover, mutations and amplifications in potentially actionable genes were identified in 464 samples (64%), including mutations in PIK3CA (14%), ERBB2 (0.4%), AKT1 (0.6%), and MAP2K1 (0.1%), as well as amplifications of ERBB2 (0.3%) and EGFR (0.3%). The median turnaround time between reception of the sample in the laboratory and report release was 8 calendar days. Overall, the AmpliSeq colon/lung cancer panel was successfully applied in daily practice and provided reliable clinically relevant information for CRC patients.

IL-10 in vivo gene expression in a cell-induced animal model of proliferative vitreoretinopathy.

Due to inhibitory activities on cell-mediated immune responses, interleukin-10 (IL-10) has been proposed as a good candidate to treat inflammatory eye disease and proliferative vitreoretinopathy (PVR). In this study we evaluate the effect of human IL-10 (hIL-10) expression in a cell-induced animal model of PVR. Rabbit dermal fibroblasts were genetically modified by infection with retroviral particles carrying the neomycin resistance gene (neoR) alone or in combination with the hIL-10 gene. PVR was induced in rabbits by intravitreal injections of RDF hIL-10 or RDF neo. Some rabbits received instead injections of soluble recombinant hIL-10 (rhIL-10). PVR was graded by fundoscopy. Eyes were enucleated for histology at day 28. ELISA was performed to measure hIL-10 production in RDF supernatants and in vitreous samples, 24 h after injection. Results showed that in vitro hIL-10 production by RDF was 24,500 pg/10(6) cells/ml/24 h. In vivo IL-10 secretion was detected in all rabbits injected with RDF hIL-10 but was undetectable in control rabbits. Similar clinical grades of PVR were found in rabbits injected with RDF hIL-10 or RDF neo. Histology showed that all eyes injected with RDF hIL-10 had significant inflammatory infiltration whereas only one control eye was clearly inflamed. Rabbits injected with soluble rhIL-10 had normal fundoscopy and normal histology. In conclusion, our results show that in vivo, in a cell-induced model of PVR, hIL-10 has no effect in the clinical progression of PVR. Histology, however, shows that pro-inflammatory effects seem to overcome its suppressive properties.

Diffuse large B-cell lymphoma with fibrillary matrix.

Diffuse large B-cell lymphoma (DLBCL) with fibrillary matrix is an extremely rare variant of non-Hodgkin's lymphoma (NHL) whose pathological features are poorly known. Here, we report on our experience with such a condition arising in a 71-yr-old woman. Our findings not only demonstrate that DLBCL with fibrillary matrix actually represents a peculiar subtype of DLBCL, but they also illustrate that the cytologic and flow cytometric features in this disorder can be deceptive enough as to mislead even the most experienced cytopathologist.

Mixed adenoneuroendocrine carcinoma of the colon: molecular pathogenesis and treatment.

BACKGROUND/AIM: We report a case of a mixed adenoneuroendocrine carcinoma developed in a colorectal adenocarcinoma with lymph node and liver metastases exclusively emanating from the neuroendocrine carcinoma component. The patient underwent right hemicolectomy and postoperatively received chemotherapy with cisplatin and etoposide and subsequent high-dose induction chemotherapy, followed by autologous stem cell transplantation. Following this treatment, there was a complete remission. Currently, thirty months after treatment, the patient is in unmaintained complete remission. Comparative exome sequencing of germline DNA and DNA from the two separate malignant components revealed six somatic changes in cancer consensus genes. Both components shared somatic mutations in Adenomatous polyposis coli (APC), Kirsten rat sarcoma viral oncogene homolog (KRAS), B-cell CLL/lymphoma 9 (BCL9) and Forkhead Box P1 (FOXP1) genes. Mutation in SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (SMARCA4) was only found in the neuroendocrine carcinoma component. The finding of several identical somatic mutations in both components supports a clonal relationship between the neuroendocrine carcinoma and the adenocarcinoma. We suggest that a mutation in SMARCA4 could be responsible for the transformation of the adenocarcinoma component into the neuroendocrine phenotype.

Chronic lymphocytic leukemia mimicking recurrent carcinoma of the breast: case report and review of the literature.

Secondary localization of chronic lymphocytic leukemia (CLL) in breast is rare, while concurrent invasive ductal carcinoma and CLL manifesting as a collision tumor in breast is extremely rare. The observation of a CLL infiltration closely associated with a distinct breast neoplasm with the absence of any other localization for the leukemia is an indisputable argument for a relationship between the two diseases. The presence of both tumors is not simply due to chance. This association (CLL and carcinoma) has also been described in other organs. Hereafter, we report a second case of an 80 year-old woman in whom a leukemic infiltrate was confined to the region immediately surrounding poorly differentiated primary breast carcinoma, and we will discuss the association between CLL and carcinoma.