A rare case of follicular lymphoma transformed to a high-grade B-cell lymphoma in orbit

Transformation of lymphoma is an infrequent phenomenon, and involvement of the eye as such is even uncommon. Histological transformation in patients with follicular lymphoma who were previously treated with immune-chemotherapy carry a poor outcome. Here, we illustrate such a case with aggressive histological transformation from a low-grade lymphoma

Isolated Ocular Manifestation of Relapsed Chronic Myelogenous Leukemia Presenting as Myeloid Blast Crisis in a Patient on Imatinib Therapy: A Case Report and Review of the Literature

Blast phase in chronic myelogenous leukemia (CML) has rarely been reported to involve extramedullary sites like skin, lymph nodes, and central nervous system. Clinical history, characteristic hematologic findings (elevated leukocyte counts, myelocytic predominance, and basophilia), and Philadelphia chromosome are of high diagnostic significance especially in isolated extramedullary presentations. We describe a unique case of CML relapse with blast phase involving the eye. A 66-year-old man with a known diagnosis of CML on imatinib and in molecular remission for 3 years presented with a painful blind eye. Histologic examination revealed diffuse involvement of choroid, iris, vitreous humor, and the optic nerve by blast cells. The blasts expressed CD34, aberrant TdT, and a myeloid phenotype (CD13, CD33, and CD117). Fluorescence in situ hybridization (FISH) of vitreous fluid detected BCR-ABL1 gene rearrangement. Additionally, trisomy 8 and gains of 9 and 22 were seen which were not present in the initial diagnostic marrow study 3 years ago. At relapse, the bone marrow, peripheral blood, and the cerebrospinal fluid were not involved by CML. Patient received induction chemotherapy and single dose prophylactic intrathecal methotrexate and was maintained on antityrosine kinase therapy and eventually underwent allogenic stem cell transplantation

Aurora-A and Polo-Like Kinases are Important Diagnostic and Therapeutic Markers in Hodgkin Lymphoma and Mimics

Background: Aurora-A (AA) and Polo-like kinases (PLK) are mitotic kinases that regulate the G2/M phase of the cell cycle. It has been demonstrated that AA acts as an upstream regulator of PLK, mediating its phosphorylation in the presence of a cofactor named Bora. PLK is activated by AA to promote checkpoint recovery in mitosis. AA and PLK are implicated in the tumorigenesis of solid tumors, and, recently, in B- and T-cell non Hodgkin lymphomas (NHL). They play a key role in tumor proliferation and disease progression in highly aggressive B-cell NHL. They also serve as indicators of disease activity and are thus attractive potential therapeutic targets. Expression of AA and/or PLK has not yet been assessed in Classic Hodgkin Lymphoma (CHL) and its mimics. This study assesses AA and PLK expression in different CHL types, such as nodular sclerosis type, mixed cellularity type, and lymphocyte rich type, and their mimics: nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal B-cell lymphoma (PMBL).Design:We assessed 27 CHL cases, 16 NLPHL cases, and 8 PMBL cases for AA and PLK expression by immunohistochemistry. CHL cases included the following: 8 mixed cellularity CHL, 1 lymphocyte rich CHL, and 18 nodular sclerosis CHL. A mouse monoclonal AA-antibody (1:1000 dilution, Abcam, UK) and a PLK-antibody (1:500 dilution, Cell Signaling Technologies, USA) were used. Each case was semi-quantitatively graded for percentage of positive cells (\u3c50% vs. \u3e50%), for staining intensity (1-3+), and for localization (nuclear vs. cytoplasmic). Immunohistochemical analysis was performed independently by 2 pathologists (KMH and KVI). Statistical analysis was performed using Fisher\u27s exact test.Results:AA was expressed in 100% of CHL and NLPHL cases. AA stained predominantly cytoplasm of tumor cells in both NLPHL and CHL. PLK was expressed in 100% of NLPHL and 96% of CHL cases (1 mixed cellularity type CHL did not stain for PLK). PLK showed both nuclear and cytoplasmic staining for both NLPHL and CHL. In contrast, only 37% of PMBL cases were positive for AA and PLK (Table 1). In the CHL group, cases with more than 50% of tumor cells expressing PLK tended to present with higher stage and extranodal disease. In the NLPHL group, PLK correlated with higher stage (III-IV) disease at presentation (p=0.044). No statistically significant differences were found in either intensity or localization of AA or PLK within or between NLPHL and CHL cohorts.Aurora-A PositiveAurora-A NegativePLK PositivePLK NegativeClassic Hodgkin Lymphoma270261Nodular Lymphocyte Predominant Hodgkin Lymphoma160160Primary Mediastinal B-cell Lymphoma3535Table 1. AA and PLK positivity in CHL, NLPHL, and PMBL.AA was expressed in CHL but not PMBL (p=0.0002)PLK was expressed in CHL but not PMBL (p=0.0009)AA was expressed in NLPHL but not PMBL (p=0.0013)PLK was expressed in NLPHL but not PMBL (p=0.0013). Conclusion: AA and PLK are commonly expressed in CHL and NLPHL but not in PMBL. Thus, they are useful markers in the distinction of CHL or NLPHL from PMBL. PLK is a useful marker for the prognostication of NLPHL. AA and PLK are attractive potential therapeutic targets in the treatment of CHL and NLPHL. Additional studies are underway to characterize an array of hematopoietic lesions known to overlap with CHL.https://scholarlycommons.henryford.com/merf2019clinres/1027/thumbnail.jp

Primary CNS T-cell Lymphomas: A Clinical, Morphologic, Immunophenotypic, and Molecular Analysis.

Primary central nervous system (CNS) lymphomas are relatively rare with the most common subtype being diffuse large B-cell lymphoma. Primary CNS T-cell lymphomas (PCNSTL) account for 1 mutation, and none showed overlapping mutations. These included mutations in DNMT3A, KRAS, JAK3, STAT3, STAT5B, GNB1, and TET2 genes, genes implicated previously in other T-cell neoplasms. The outcome was heterogenous; 2 patients are alive without disease, 4 are alive with disease, and 6 died of disease. In conclusion, PCNSTLs are histologically and genomically heterogenous with frequent phenotypic aberrancy and a cytotoxic phenotype in most cases

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570