Extreme Peripheral Blood Plasmacytosis Mimicking Plasma Cell Leukemia as a Presenting Feature of Angioimmunoblastic T-Cell Lymphoma (AITL).

Angioimmunoblastic T-cell lymphoma (AITL) is one of four major subtypes of nodal peripheral T cell lymphoma, characterized by its cell of origin, the follicular helper T-cell (TFH). Patients typically present with prominent constitutional (B) symptoms, generalized lymphadenopathy, hepatosplenomegaly, cytopenias, and rash. Here we present a case of a 62-year-old male with progressive cervical adenopathy, fevers and weight loss presenting with extreme polyclonal plasmacytosis and high plasma EBV viral load. While the initial presentation appeared to mimic plasma cell leukemia or severe infection, lymph node biopsy and bone marrow biopsy confirmed a diagnosis of AITL. This case highlights the heterogeneity of the clinical presentation of AITL to enable physicians to more promptly recognize, diagnose and initiate treatment

Hepatitis B Virus and B-cell lymphoma: evidence, unmet need, clinical impact, and opportunities

Nearly a billion people worldwide are infected with the hepatitis B Virus (HBV) and about a third of them have chronic infection. HBV is an important cause of morbidity and mortality, including acute and chronic hepatitis and hepatocellular carcinoma (HCC). Screening and control of primary HBV infection through vaccination represent a major advance in global public health, but large sections of the world population, in both developed and underdeveloped countries, remain unscreened and unvaccinated. In addition to being a global cause of liver disease, an important role of HBV in lymphoma has also emerged. First, the high risk of HBV reactivation in previously infected patients receiving chemo-immunotherapy necessitates the systematic evaluation of HBV serological status in all non-Hodgkin's lymphoma (NHL) cases and preemptive antiviral therapy for those who may have chronic or occult HBV infection. Second, HBV has been shown to infect lymphocytes, namely B-cells, and has been associated with a higher risk of developing B-cell lymphoma, most clearly in countries where HBV is endemic. While the risk of HBV reactivation with chemoimmunotherapy in NHL is well known, the role and the impact of HBV as a global lymphoma risk factor and potential oncogenic driver in B-cells are very poorly understood. Here, we review the clinical and scientific evidence supporting an association between HBV and B-cell lymphoma, with a particular focus on diffuse large B-cell lymphoma (DLBCL) and provide an overview of the estimated impact of HBV infection on the biology and clinical course of DLBCL. We also discuss ways to gain a better insight into the unmet need posed by HBV in lymphoma and whether assessing immune responses to HBV, measuring viral loads, and detecting the presence of HBV-encoded proteins in tumor tissue could be integrated into the molecular and clinical risk stratification of patients with DLBCL

Treating cutaneous T-cell lymphoma with highly irregular surfaces with photon irradiation using rice as tissue compensator.

PurposeCutaneous T-cell lymphoma (CTCL) is known to have an excellent response to radiotherapy, an important treatment modality for this disease. In patients with extremity and digit involvement, the irregular surface and depth variations create difficulty in delivering a homogenous dose using electrons. We sought to evaluate photon irradiation with rice packing as tissue equivalence and determine clinical tolerance and response.Materials and methodsThree consecutive CTCL patients with extensive lower extremity involvement including the digits were treated using external beam photon therapy with rice packing for tissue compensation. The entire foot was treated to 30-40 Gy in 2-3 Gy per fraction using 6 MV photons prescribed to the mid-plane of an indexed box filled with rice in which the foot was placed. Treatment tolerance and response were monitored with clinical evaluation.ResultsAll patients tolerated the treatment without treatment breaks. Toxicities included grade 3 erythema and desquamation with resolution within 4 weeks. No late toxicities were observed. All patients had a partial response by 4 weeks after therapy with two patients achieving a complete response. Patients reported improved functionality after treatment. No local recurrence has been observed.ConclusionTissue compensation with rice packing offers a convenient, inexpensive, and reproducible method for the treatment of CTCL with highly irregular surfaces

Rational Targets of Therapy in Extranodal NK/T-Cell Lymphoma

Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive extranodal non-Hodgkin lymphoma (NHL) with poor outcomes, particularly in advanced-stage and relapsed/refractory disease. Emerging research on molecular drivers of ENKTL lymphomagenesis by next-generation and whole genome sequencing has revealed diverse genomic mutations in multiple signaling pathways, with the identification of multiple putative targets for novel therapeutic agents. In this review, we summarize the biological underpinnings of newly-understood therapeutic targets in ENKTL with a focus on translational implications, including epigenetic and histone regulatory aberrations, activation of cell proliferation signaling pathways, suppression of apoptosis and tumor suppressor genes, changes in the tumor microenvironment, and EBV-mediated oncogenesis. In addition, we highlight prognostic and predictive biomarkers which may enable a personalized medicine approach toward ENKTL therapy

The role of interleukin-15 in the development and treatment of hematological malignancies.

Cytokines are a vital component of the immune system that controls the activation and growth of blood cells. However, chronic overexpression of cytokines can trigger cellular events leading to malignant transformation. The cytokine interleukin-15 (IL-15) is of particular interest, which has been shown to contribute to the development and progression of various hematological malignancies. This review will provide an overview of the impact of the immunopathogenic function of IL-15 by studying its role in cell survival, proliferation, inflammation, and treatment resistance. We will also review therapeutic approaches for inhibiting IL-15 in blood cancers

Incidence of Cutaneous Melanoma and Merkel Cell Carcinoma in Patients With Primary Cutaneous B-Cell Lymphomas: A Population Study of the SEER Registry

Introduction: The increased incidence of cutaneous melanoma (CM) and Merkel cell carcinoma (MCC) in patients with hematologic malignancies (HM) is well established. While the risk of CM has been assessed in some subtypes of HM including cutaneous T-cell lymphoma, the incidence in patients with primary cutaneous B-cell lymphoma (PCBCL) has not been interrogated. Methods: Here we evaluated the standardized incidence ratio (SIR) of CM and MCC in 5,179 PCBCL patients compared to approximately 1.5 billion individuals in the general population using the Surveillance, Epidemiology and End Results (SEER) database. Among patients with PCBCL, we identified subgroups that were at increased risk for CM or MCC as a second primary cancer. Results: We found 36 cases of CM in the PCBCL cohort (SIR, 1.35; 95% CI, 0.94–1.86), among which SIR was significantly elevated for non-Hispanic White patients compared to the general population (SIR, 1.48; 95% CI, 1.03–2.06). Males had a significantly increased risk of developing CM after a diagnosis of PCBCL (SIR, 1.60; 95% CI, 1.10–2.26). We found that males in the age group of 50–59 were at increased risk for CM development (SIR, 3.02; 95% CI, 1.11–6.58). Males were at increased risk of CM 1–5 years after PCBCL diagnosis (SIR, 2.06; 95% CI, 1.18–3.34). Patients were at greater risk of developing MCC within 1 year of diagnosis of PCBCL (SIR, 23.60; 95% CI, 2.86–85.27), particularly in patients who were over the age of 80 (SIR, 46.50; 95% CI, 5.63–167.96). Males aged 60–69 with PCBCL, subtype marginal zone, were also at increased risk for MCC (SIR, 42.71; 95% CI, 1.08–237.99). Conclusion: There is an increased incidence of CM in White, middle-aged males within 5 years of diagnosis of PCBCL and an increased risk of MCC in elderly patients within 1 year of PCBCL diagnosis. These data suggest that certain subgroups of patients with PCBCL may require more rigid surveillance for CM and MCC

Incidence of cutaneous melanoma and Merkel cell carcinoma in patients with primary cutaneous B-cell lymphomas: A population study of the SEER registry

IntroductionThe increased incidence of cutaneous melanoma (CM) and Merkel cell carcinoma (MCC) in patients with hematologic malignancies (HM) is well established. While the risk of CM has been assessed in some subtypes of HM including cutaneous T-cell lymphoma, the incidence in patients with primary cutaneous B-cell lymphoma (PCBCL) has not been interrogated.MethodsHere we evaluated the standardized incidence ratio (SIR) of CM and MCC in 5,179 PCBCL patients compared to approximately 1.5 billion individuals in the general population using the Surveillance, Epidemiology and End Results (SEER) database. Among patients with PCBCL, we identified subgroups that were at increased risk for CM or MCC as a second primary cancer.ResultsWe found 36 cases of CM in the PCBCL cohort (SIR, 1.35; 95% CI, 0.94–1.86), among which SIR was significantly elevated for non-Hispanic White patients compared to the general population (SIR, 1.48; 95% CI, 1.03–2.06). Males had a significantly increased risk of developing CM after a diagnosis of PCBCL (SIR, 1.60; 95% CI, 1.10–2.26). We found that males in the age group of 50–59 were at increased risk for CM development (SIR, 3.02; 95% CI, 1.11–6.58). Males were at increased risk of CM 1–5 years after PCBCL diagnosis (SIR, 2.06; 95% CI, 1.18–3.34). Patients were at greater risk of developing MCC within 1 year of diagnosis of PCBCL (SIR, 23.60; 95% CI, 2.86–85.27), particularly in patients who were over the age of 80 (SIR, 46.50; 95% CI, 5.63–167.96). Males aged 60–69 with PCBCL, subtype marginal zone, were also at increased risk for MCC (SIR, 42.71; 95% CI, 1.08–237.99).ConclusionThere is an increased incidence of CM in White, middle-aged males within 5 years of diagnosis of PCBCL and an increased risk of MCC in elderly patients within 1 year of PCBCL diagnosis. These data suggest that certain subgroups of patients with PCBCL may require more rigid surveillance for CM and MCC

Bio-Ecological Features Update on Eleven Rare Cartilaginous Fish in the Central-Western Mediterranean Sea as a Contribution for Their Conservation

Cartilaginous fish are commonly recognized as key species in marine ecosystems for their fundamental ecological role as top predators. Nevertheless, effective management plans for cartilagi- nous fish are still missing, due to the lack of knowledge on their abundance, distribution or even life-history. In this regard, this paper aims at providing new information on the life-history traits, such as age, maturity, reproductive period, in addition to diet characteristics of eleven rare cartilagi- nous fish inhabiting the Central-Western Mediterranean Sea belonging to the orders Chimaeriformes (Chimaera monstrosa), Hexanchiformes (Heptranchias perlo and Hexanchus griseus), Myliobatiformes (Aetomylaeus bovinus and Myliobatis aquila), Rajiformes (Dipturus nidarosiensis and Leucoraja circu- laris), Squaliformes (Centrophorus uyato, Dalatias licha and Oxynotus centrina) and Torpediniformes (Tetronarce nobiliana), useful for their assessment and for future management actions. Particularly, the present paper provides for the first time the age estimation of D. nidarosienis and L. circularis which were both found capable of becoming older than ten years. In addition, the present study updates the sizes of first maturity of C. uyato and D. licha, which appeared to be capable of reproducing earlier than what was previously hypothesized, representing very valuable information for a better understanding of these rare species populations status and, eventually, their conservation. On the basis of the stomach content analysis, it was possible to identify five different predator groups

Targeting the Bcl-2 Family in B Cell Lymphoma

Although lymphoma is a very heterogeneous group of biologically complex malignancies, tumor cells across all B cell lymphoma subtypes share a set of underlying traits that promote the development and sustain malignant B cells. One of these traits, the ability to evade apoptosis, is essential for lymphoma development. Alterations in the Bcl-2 family of proteins, the key regulators of apoptosis, is a hallmark of B cell lymphoma. Significant efforts have been made over the last 30 years to advance knowledge of the biology, molecular mechanisms, and therapeutic potential of targeting Bcl-2 family members. In this review, we will highlight the complexities of the Bcl-2 family, including our recent discovery of overexpression of the anti-apoptotic Bcl-2 family member Bcl-w in lymphomas, and describe recent advances in the field that include the development of inhibitors of anti-apoptotic Bcl-2 family members for the treatment of B cell lymphomas and their performance in clinical trials