Extramedullary Solitary Plasmacytoma with Anaplastic Features of the Nasopharynx.

Extramedullary plasmacytomas (ESPs) are rare forms of plasma cell dyscrasias and usually are seen in the upper aerodigestive tract. ESPs with anaplastic features are extremely rare, and no treatment guidelines exist. We present a 75-year-old gentleman presented with left nasal blockage, and on examination, a polypoid left nasal mass was seen. He was, then, referred to ENT after a CT scan revealed a mass in the left nasopharynx for a biopsy. The preliminary reports suggested a high-grade lymphoma; however, after further testing, it was revealed to be an anaplastic plasma cell neoplasm. PET scan, bone marrow biopsy, serum and urine protein electropheresis, serum immunofixation and light chains were all unremarkable for systemic disease. Differential diagnosis included plasmablastic lymphoma, NK/T cell lymphoma-nasal type, and squamous cell cancers of the head and neck. He was treated with radiation alone given his comorbidities. Given there are no treatment guidelines, we would like to highlight this rare case and discuss different potential management options such as radiation, chemotherapy, surgery, or a combination of different modalities.

A Rare Case of Chronic Myelogenous Leukemia Presenting as T-Cell Lymphoblastic Crisis.

Chronic Myelogenous Leukemia in blast crisis can manifest as either myeloid (more common) or lymphoid blast crisis. Most lymphoblastic crises are of B-cell lineage. T-cell blast crisis is extremely rare, with only a few reported cases. We present a case of a middle-aged man who was diagnosed with CML on peripheral blood and bone marrow biopsy. Because of a generalized lymphadenopathy noted at the time of diagnosis, a lymph node biopsy was also performed, which revealed a T-cell lymphoblastic leukemia/lymphoma, BCR/ABL1 positive, with clonal evolution. This is a very rare manifestation of CML in blast crisis with no standard treatment and with poor outcomes despite chemotherapy or allogeneic stem cell transplant. Given its rarity, it would be difficult to develop standard chemotherapy protocols. We believe the treatment for this condition should be similar to any lymphoid blast crisis. The patient was treated with induction chemotherapy (hyper-CVAD regimen) plus dasatinib for 3 cycles followed by sibling-donor allogeneic stem cell transplant and is currently on maintenance dasatinib and has minimal residual disease at this time.

Follicular large cleaved cell (centrocytic) lymphoma: an unrecognized variant of follicular lymphoma.

The World Health Organization classification of lymphoma recommends the subdivision of follicular lymphoma (FL) into 3 grades (FL1-3) based on the average number of centroblasts per high-power field in the neoplastic follicles, but does not recognize a form of FL characterized by a predominance of large cleaved cells (centrocytes) without enough centroblasts to meet the World Health Organization criteria for FL3. We have classified such cases as follicular large cleaved cell lymphoma (FLC) and, herein, describe the pathologic and clinical features of 72 cases of this entity. The features of FLC include a follicular growth pattern with pale follicles at low magnification and frequent follicular and/or interfollicular fibrosis. Cytologically, the cells are predominantly large cleaved cells with moderately coarse to fine chromatin, absent or inconspicuous nucleoli, and small to moderate amounts of pale cytoplasm. The mean nuclear diameter of the large cleaved cells was 10.1µ, approximately twice that of small lymphocytes and similar to centroblasts. The t(14;18) was present in 83% of the cases, and a high proportion expressed BCL2 (84%), BCL6 (100%), and CD10 (88%) and had high Ki67 proliferation (81%). The clinical features of patients with FLC were similar to those with other types of FL, and survival was excellent with anthracycline-based chemotherapy plus rituximab. FLC is a variant of follicular lymphoma which should be recognized in future lymphoma classifications because the diagnosis of FLC may be important for the selection of therapy.

Reprogramming of COPD lung fibroblasts through formation of induced pluripotent stem cells.

Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) eliminates many epigenetic modifications that characterize differentiated cells. In this study, we tested whether functional differences between chronic obstructive pulmonary disease (COPD) and non-COPD fibroblasts could be reduced utilizing this approach. Primary fibroblasts from non-COPD and COPD patients were reprogrammed to iPSCs. Reprogrammed iPSCs were positive for oct3/4, nanog, and sox2, formed embryoid bodies in vitro, and induced teratomas in nonobese diabetic/severe combined immunodeficient mice. Reprogrammed iPSCs were then differentiated into fibroblasts (non-COPD-i and COPD-i) and were assessed either functionally by chemotaxis and gel contraction or for gene expression by microarrays and compared with their corresponding primary fibroblasts. Primary COPD fibroblasts contracted three-dimensional collagen gels and migrated toward fibronectin less robustly than non-COPD fibroblasts. In contrast, redifferentiated fibroblasts from iPSCs derived from the non-COPD and COPD fibroblasts were similar in response in both functional assays. Microarray analysis identified 1,881 genes that were differentially expressed between primary COPD and non-COPD fibroblasts, with 605 genes differing by more than twofold. After redifferentiation, 112 genes were differentially expressed between COPD-i and non-COPD-i with only three genes by more than twofold. Similar findings were observed with microRNA (miRNA) expression: 56 miRNAs were differentially expressed between non-COPD and COPD primary cells; after redifferentiation, only 3 miRNAs were differentially expressed between non-COPD-i and COPD-i fibroblasts. Interestingly, of the 605 genes that were differentially expressed between COPD and non-COPD fibroblasts, 293 genes were changed toward control after redifferentiation. In conclusion, functional and epigenetic alterations of COPD fibroblasts can be reprogrammed through formation of iPSCs.

Benign and Malignant Hematological Manifestations of Chronic Hepatitis C Virus Infection.

Chronic hepatitis C virus (HCV) infection, that affects 3% of world's population, is associated with several hematological manifestations mainly benign cytopenias, coagulopathy and lymphoproliferative diseases. Immune or non-immune-mediated thrombocytopenia is a major challenge in chronic HCV infected patients especially in the setting of an advanced liver disease, with average prevalence of nearly 24%. Although several treatment modalities such as steroids, intravenous immunoglobulin, splenectomy and immunosuppresants have been tried with some success, their efficacy is not impressive and can result in an increase in viral load or other thrombotic complications. Even though a recent phase 2 study has shown promising role of a platelet growth factor, eltrombopag, in boosting platelets counts prior to antiviral treatment, its use in pre-operative setting had unexpected complications. Unlike thrombocytopenia, anemia and neutropenia are more frequently seen in treated patients and are often the result of antiviral therapy. HCV infection also pre-disposes to lymphoproliferative diseases, mainly non-Hodkings lymphomas, likely as a result of chronic antigenic stimulation and mutation of several genes involved in carcinogenesis. Understanding of the role of HCV infection in these conditions has therapeutic implications. Whereas antiviral therapy has shown therapeutic role in HCV-associated indolent lymphomas, monitoring of hepatic function and viral load is important in the management of diffuse large B-cell lymphoma in HCV-infected patients. Although our knowledge about the HCV infection and hematological manifestations has substantially grown in last few decades, further studies are important to advance our therapeutic approach.

Crypt apoptotic count reproducibility in small bowel allograft biopsies.

Enumeration of crypt apoptotic bodies (AB) is used in the diagnosis of acute cellular rejection (ACR) in small bowel allografts. Due to differing definitions, there is a potential for variation in AB numbers between pathologists that may affect diagnosis. Thirty biopsies from allografts were obtained: 10 negative for ACR, 10 indeterminate, and 10 with mild ACR. Three pathologists blindly reviewed each case twice and counted the maximal AB number per 10 crypts. Intraobserver kappa ranged from 0.423 to 0.913 and interobserver kappa from 0.478 to 0.686 depending on AB definition. Intraobserver diagnosis agreement based on classical AB number occurred in 81 of 90 instances (90%) and in 77 of 90 using the liberal definition (85%), P < .01). There was substantial intraobserver and moderate to substantial interobserver agreement in crypt AB counts. However, both intraobserver and interobserver variability would have led to diagnostic discrepancies in a small subset of cases.