Intracellular and extracellular rhomboid shaped crystalline inclusions in a case of IgG lambda restricted plasma cell myeloma: a case report and review of the literature

The presence of crystalline inclusions in plasma cell myeloma is a rare phenomenon and cases have been reported with rod, needle, and rectangular shaped crystals. Here, we present a case of IgG lambda restricted plasma cell myeloma with rhomboid shaped intracellular crystalline inclusions and extracellular crystal depositions in the bone marrow. Since rhomboid crystal depositions can be seen in other clinical conditions such as pseudogout, this case invites consideration of plasma cell myeloma in the differential diagnosis of patients with rhomboid crystalline deposition in the bone marrow and in sites/organs other than the bone marrow

Primary Cutaneous Follicle Centre Lymphoma with Hodgkin and Reed-Sternberg Like Cells: A Case Report and Review of the Literature

An elderly woman with a complex medical history presented with a left forearm mass that slowly developed for several months. The excisional biopsy of this skin mass was remarkable for involvement by a follicle centre cell derived lymphoma with a nodular and diffuse pattern associated with a subset of scattered Hodgkin and Reed-Sternberg like cells. Fluorescence in situ hybridization studies did not detect the presence of IgH-bcl2 fusion transcript, and molecular studies were negative for immunoglobulin heavy chain gene rearrangements and EBV DNA sequences. Hodgkin and Reed-Sternberg like cells are rarely reported in FLs, and the association with primary cutaneous follicle centre lymphoma is extremely rarely seen. To our knowledge, our case is the second case of primary cutaneous follicle centre lymphoma with Hodgkin and Reed-Sternberg like cells

Bone marrow-specific loss of ABI1 induces myeloproliferative neoplasm with features resembling, human myelofibrosis

Although the pathogenesis of primary myelofibrosis (PMF) and other myeloproliferative neoplasms (MPNs) is linked to constitutive activation of the JAK-STAT pathway, JAK inhibitors have neither curative nor MPN-stem cell-eradicating potential, indicating that other targetable mechanisms are contributing to the pathophysiology of MPNs. We previously demonstrated that Abelson interactor 1 (Abi-1), a negative regulator of Abelson kinase 1, functions as a tumor suppressor. Here we present data showing that bone marrow-specific deletion of Abi1 in a novel mouse model leads to development of an MPNlike phenotype resembling human PMF. Abi1 loss resulted in a significant increase in the activity of the Src family kinases (SFKs), STAT3, and NF-κB signaling. We also observed impairment of hematopoietic stem cell self-renewal and fitness, as evidenced in noncompetitive and competitive bone marrow transplant experiments. CD34 + hematopoietic progenitors and granulocytes from patients with PMF showed decreased levels of ABI1 transcript as well as increased activity of SFKs, STAT3, and NF-κB. In aggregate, our data link the loss of Abi-1 function to hyperactive SFKs/STAT3/NF-κB signaling and suggest that this signaling axis may represent a regulatory module involved in the molecular pathophysiology of PMF

Primary Cutaneous Follicle Centre Lymphoma with Hodgkin and Reed-Sternberg Like Cells: A Case Report and Review of the Literature

An elderly woman with a complex medical history presented with a left forearm mass that slowly developed for several months. The excisional biopsy of this skin mass was remarkable for involvement by a follicle centre cell derived lymphoma with a nodular and diffuse pattern associated with a subset of scattered Hodgkin and Reed-Sternberg like cells. Fluorescence in situ hybridization studies did not detect the presence of IgH-bcl2 fusion transcript, and molecular studies were negative for immunoglobulin heavy chain gene rearrangements and EBV DNA sequences. Hodgkin and Reed-Sternberg like cells are rarely reported in FLs, and the association with primary cutaneous follicle centre lymphoma is extremely rarely seen. To our knowledge, our case is the second case of primary cutaneous follicle centre lymphoma with Hodgkin and Reed-Sternberg like cells

Heterozygous Hemoglobin Sherwood Forest Causing Polycythemia

Hemoglobin (Hb) Sherwood Forest is a rare high-affinity hemoglobin first described in 1977, arising from an Arg to Thr substitution at codon 104 of the beta chain. This hemoglobin variant has been identified in few individuals and has been associated with a compensatory erythrocytosis in the homozygous state. Prior scarce case reports have noted that heterozygotes for this variant are phenotypically normal. Here we present a patient who was evaluated in our hematology clinic for chronic erythrocytosis and was found to be heterozygous for Hb Sherwood Forest. No other primary or secondary cause of his polycythemia was identified. This is the first described case of heterozygous Hemoglobin Sherwood Forest causing erythrocytosis

TAFRO Syndrome Associated with EBV and Successful Triple Therapy Treatment: Case Report and Review of the Literature

TAFRO syndrome is a rare constellation of symptoms: thrombocytopenia, anasarca, reticulin fibrosis of the bone marrow, renal dysfunction, and organomegaly. Its pathogenesis involves an excessive and inappropriate cytokine storm, most notably from IL-6, causing multiorgan failure; however, its etiology is undetermined. Starting in 2012, TAFRO syndrome was first identified in Japan as an atypical variant of Castleman’s disease. Previous reports include various different treatment protocols with inconsistent survival outcomes. Here we report the first known American, EBV positive but HIV and HHV-8 negative, male with TAFRO syndrome. He was successfully treated with an unusual three-drug regimen including tocilizumab, etoposide, and rituximab. We review the literature of TAFRO syndrome, discuss its possible viral etiology, and propose an original treatment regimen

Oil Red O positive vacuolated blasts in a case of CD45 negative, CD19 negative B-lymphoblastic leukemia

AbstractB-lymphoblastic leukemia is a clonal hematopoietic disorder of precursors B-lymphoblasts being most frequently encountered in children. Expression of CD19, a pan B-cell marker is noted in the majority of the cases with lack of CD19 expression being extremely rarely reported in the medical literature. We report the very rare case of a B-lymphoblastic leukemia with a triple negative immunophenotype: CD19 negative, CD45 negative and CD10 negative with vacuolated lymphoblasts and an aleukemic presentation in a 20-year-old man

Similar outcomes in Asian and Western patients with diffuse large B-cell lymphoma treated with R-CHOP

13siLittle is known on racial differences in patients with diffuse large B-cell lymphoma (DLBCL). The aim of this retrospective study is to compare characteristics, prognostic factors and outcomes of Asian and Western patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). METHODS: Patient-level data was collected from 8 centers. All patients were diagnosed with DLBCL and treated with R-CHOP. Patients were divided into Asian and Western, according to the country of report. Comparisons and univariate/multivariate survival analyses were performed. RESULTS: 712 patients, 455 Asian and 257 Western patients were included. Westerners were more likely to present with elevated LDH (64% vs. 48%, p<0.01) and advanced stage (58% vs. 49%, p<0.01). After a median follow-up of 36 months, there was no difference in progression-free (PFS; p=0.33) or overall survival (OS; p=0.69). There were no PFS or OS differences between races when evaluating separately each age-adjusted International Prognostic Index category. In the multivariate analyses, performance status and stage were associated with PFS and OS in both races. CONCLUSIONS: There are no differences in prognostic factors, PFS and OS between Asian and Western patients with DLBCL treated with R-CHOP.nonenoneJorge J. Castillo;Natalie Sinclair;Brady E. Beltrán;Moo-Kon Song;Ivana Ilic;Sirpa Leppa;Heidi Nurmi;Ritsuko Seki;Silvia Uccella;Jun-Min Li;Diana O. Treaba;Dariusz Stachurski;James N. ButeraJorge J., Castillo; Natalie, Sinclair; Brady E., Beltrán; Moo Kon, Song; Ivana, Ilic; Sirpa, Leppa; Heidi, Nurmi; Ritsuko, Seki; Uccella, Silvia; Jun Min, Li; Diana O., Treaba; Dariusz, Stachurski; James N., Buter

Subcutaneous checkpoint inhibition is equivalent to systemic delivery when combined with nelitolimod delivered via pressure-enabled drug delivery for depletion of intrahepatic myeloid-derived suppressor cells and control of liver metastases

Background Toll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop adaptive immune responses. Their ability as immunomodulators to enhance the activity of checkpoint inhibitors (CPI) in treating liver tumors is limited in part by the distinctive biology of intrahepatic myeloid-derived suppressor cells (MDSC) and challenges with tumor-specific therapeutic delivery. We have shown that the regional delivery of type C TLR9 agonist via pressure-enabled drug delivery (PEDD) system improves delivery to the tumor, enhances depletion of MDSCs and overall, stimulates the immune system in combination with or without CPI. Currently, CPIs are delivered intravenously, although there is a growing interest in its subcutaneous (SQ) administration. We compared nelitolimod formerly known as SD-101 administered using PEDD in combination with systemic (Sys) or SQ CPI in murine liver metastases (LM).Methods The LM model was developed by injecting MC38-Luc cells via the spleen of 8–12 week old male C57/BL6 mice followed by splenectomy. After a week, fluorescently labeled nelitolimod (10 µg/mouse) was delivered via PEDD and co-administered anti-programmed cell death-1 (α-PD-1) either via Sys or SQ. Tumor burden was monitored by in vivo imaging system. Serum cytokine levels were analyzed by Luminex. Tissues were harvested on Day 3 (D3) or Day 10 (D10) post-PEDD to enrich CD45+ cells and were analyzed via NanoString targeted transcriptomics (D3) or flow cytometry (FC, D10) to interrogate immune cell populations (D10). For NanoString analysis, the innate immune panels were selected, and for FC, MDSCs (CD11b+Gr1+), B cells (B220+), dendritic cells (DC, CD11c+), T (CD3+) cells, and M1-like macrophages (F4/80+CD38+Egr2−) were quantified.Results Nelitolimod delivered via PEDD resulted in changes in innate and adaptive immune cells within LM, including depletion of liver MDSC and increased M1-like macrophages in the liver, which are supportive of antitumor immunity. While CPI monotherapy failed to control tumor progression, nelitolimod and CPI combination improved LM control, survival and antitumor immunity beyond the nelitolimod monotherapy effect, irrespective of CPI delivery route.Conclusion The SQ route of CPI delivery was equivalent to Sys in combination with nelitolimod, suggesting SQ-CPI may be a rational choice in combination with PEDD of nelitolimod for liver tumor treatment