The clinical significance of increased large cells in marginal zone lymphoma.

Marginal zone lymphoma (MZL) is a primary, indolent small B-cell lymphoma. Subtypes include nodal, splenic, and those of extranodal mucosa-associated lymphoid tissue (MALT). These are slow growing and generally exhibit low rates of transformation to diffuse large B-cell lymphoma (DLBCL). At initial diagnosis, there can be an increase in large cells (LCs) that does not meet criteria for DLBCL. Prior studies have noted this finding, but the clinical significance of these LCs has not been well established. A total of 161 cases of MZL from 1994 to 2021 were evaluated, including all subtypes. There were 33 cases with increased LCs (>10 LCs per high-power field [hpf]), with the majority containing >15 LCs/hpf (28/33) and 128 cases without increased LCs. Cases with increased LCs were significantly more likely to have a Ki-67 proliferation index of ≥30% (P < .0001). Overall survival was not significantly different between the groups but progression-free survival was significantly worse in the LC group (P < .0001). MZL with increased LCs was also associated with a higher stage at diagnosis (P = .0035), was more likely to transform to DLBCL (P = .0016), and had a greater frequency of relapse (P < .0001). Subgroup analysis showed that both nodal and MALT LC groups had a worse progression-free survival and a higher rate of relapse than their standard nodal and MALT lymphoma counterparts, but only within the MALT subgroup did the LC cases present at a higher stage and have a higher rate of transformation to DLBCL than the standard cases. Although larger studies are needed for validation, these results suggest that the presence of LCs in MZL may serve as a useful prognostic indicator and potentially help guide clinical decision-making.

Intravascular Lymphoma - The Creepy Crawler: A Case Series and Brief Literature Review.

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal B-cell lymphoma, which has traditionally been associated with poor outcomes. Despite increasing recognition, IVLBCL requires a high degree of clinical suspicion on the part of the clinician for its diagnosis. CASE SERIES: We present four patient cases: A 69-year-old female with constitutional symptoms and cognitive decline; a 78-year-old female with kidney injury and constitutional symptoms whose disease rapidly progressed to multiorgan failure and death; a 70-year-old asymptomatic female with an incidentally found, enlarged thyroid; and a 63-year-old male with cytopenia and constitutional symptoms. Retrospective chart analysis was performed on these four patients diagnosed with IVLBCL at our Institute to identify the pathognomonic features of the disease and compare these to the published evidence. IVLBCL has a heterogeneous presentation, as seen in our four patients. The disease is characterized by the exclusive presence of malignant cells inside the blood vessels and lack of organ infiltration. Traditional preliminary diagnostic modalities such as imaging are usually inconclusive, given the paucity of lymphomatous aggregates. A bone marrow biopsy, random skin biopsies, or a focal organ biopsy in appropriate cases is required for diagnosis. Immunosuppression might play a role in the pathogenesis. Timely initiation of aggressive cancer-directed therapy was associated with improved outcomes. Monitoring for disease response and relapse continues to be a challenge. CONCLUSION: Our mini-series highlights the significance of timely diagnosis and intervention in IVLBCL and emphasizes the importance of further research to determine its association with immunosuppression.

M2 Macrophages in Crystal Storing Histiocytosis Associated with Plasma Cell Myeloma.

Crystal Storing Histiocytosis (CSH) is a rare entity occurring in association with underlying lymphoproliferative disorders and plasma cell neoplasms. It denotes accumulation of immunoglobulin crystals in the histiocyte cytoplasm. In this study, we report a patient with plasma cell myeloma who presented with bilateral comminuted femur fractures. Histological examination of fracture tissue revealed hypercellular (~100%) marrow with extensive involvement by sheets of histiocytes with abundant eosinophilic cytoplasm admixed with scattered plasma cells. Intracytoplasmic diamond and rhomboid crystals within histiocytes were demonstrated by electron microscopy. Immunohistochemistry highlighted monotypic plasma cells with kappa restriction, representing 20-30% of marrow cellularity; however, non-polarizable cytoplasmic striations in histiocytes were negative for light chain expression. A diagnosis of crystal-storing histiocytosis associated with plasma cell myeloma was rendered. Further evaluation of these macrophages is positive for CD163 and COX2 and shows pSTAT3 with variable nuclear staining in some histiocytes. This case demonstrates that numerous M2 macrophages are present as crystal storing histiocytosis; and this knowledge might convey prognostic and therapeutic significance for the patients with crystal storing histiocytosis.

Case Report and Literature Review of Nodular Hiradenoma, a Rare Adnexal Tumor That Mimics Breast Carcinoma, in a 20-Year-Old Woman.

Nodular hidradenoma is an uncommon cutaneous adnexal tumor arising from sweat glands. In the skin, it usually presents as a solitary dermal nodule; excision is curative in most cases. In rare instances, it may present as a breast mass and can mimic breast carcinoma clinically and radiologically, causing diagnostic dilemmas for the treating physician and pathologist. Herein, we discuss a case of nodular hidradenoma in a 20-year-old Hispanic woman as a rapidly growing mass in the breast that mimicked breast carcinoma. We discuss the rare presentation of this uncommon tumor and the differential diagnosis of this entity, as well as the results of our literature review on the topic.

Pancreatic Acinar Metaplasia in Distal Esophageal Biopsies Is Associated With Chronic Nonsteroidal Anti-inflammatory Drug Use.

CONTEXT.­: The cause of pancreatic acinar metaplasia (PAM) at the distal esophagus/esophagogastric junction is still controversial. Whereas some authors believe it is congenital, others believe it is acquired because of inflammation of the gastric cardia, and more recently it was proposed to be due to chronic proton pump inhibitor use based on a study in rats. OBJECTIVE.­: To determine whether there is correlation between chronic proton pump inhibitor use and PAM in humans. We also investigated the correlation between several clinical and pathologic factors and PAM. DESIGN.­: Four hundred forty-four consecutive biopsies from the distal esophagus/esophagogastric junction were reviewed for the presence of PAM, which was then correlated with several clinical and pathologic findings. RESULTS.­: Pancreatic acinar metaplasia was found in 71 patients (16%). Pancreatic acinar metaplasia was significantly associated with patient age younger than 51 years ( P < .001), chronic carditis ( P = .01), and chronic proton pump inhibitor use ( P = .008). Surprisingly, we also found significant association between PAM and chronic nonsteroidal anti-inflammatory drug use ( P < .001). These associations, including that with chronic nonsteroidal anti-inflammatory drug use, remained significant in multivariate analysis. CONCLUSIONS.­: Our findings confirm the previous reports of significant association between PAM and chronic carditis and the findings from animal studies of association with chronic proton pump inhibitor use. The strong association with chronic nonsteroidal anti-inflammatory drug use has not been previously reported and warrants further studies.

Intra-Pericardial Use of Recombinant Factor VIIa in a Patient With Acute Hemorrhagic Pericardial Effusion Following Transcutaneous Aortic Valve Replacement-A Case Report.

Perioperative bleeding can be a serious life-threatening complication in adult patients undergoing cardiac surgery, given the older age and additional comorbidities present in this patient population. The standard treatment options include transfusion of blood components and surgical re-exploration. We report the first case of an elderly female patient treated with local administration of recombinant factor VIIa (rFVIIa) for intractable hemorrhagic pericardial effusion, which developed following a transcutaneous aortic valve replacement (TAVR) procedure for severe aortic stenosis. No thromboembolic phenomena or adverse effects were observed. Local administration of rFVIIa is an efficacious treatment option for cardiac surgery patients as opposed to systemic administration of rFVIIa, use of massive blood products, or surgical re-exploration.

Morphoproteomics Identifies SIRT1 and EZH2 Pathways as Commonalities in B-cell Acute Lymphoblastic Leukemia: Pathogenetic Implications and Opportunities for Therapeutic Intervention.

B-cell acute lymphoblastic leukemia (ALL) represents a malignant process in which bone marrow-derived lymphoblasts retain their undifferentiated state. Genetic testing has revealed either no identifiable cytogenetic and genomic abnormalities in such patients or a wide range of aberrations that may or may not contribute to the block in differentiation and the associated proliferation of the malignant lymphoblasts in cases of B-cell ALL. In this study, we applied morphoproteomics to a representative spectrum of cases of newly diagnosed B-cell ALL in order to identify pathways that are known to be associated with the maintenance of the undifferentiated state while promoting proliferation. Our results showed nuclear expression in a majority of the lymphoblasts from bone marrow clot preparations of each of the study cases for both silent mating type information regulation 2 homolog 1 (SIRT1), an NAD+ histone deacetylase and enhancer of Zeste homolog 2 (EZH2), a histone methyltransferase. These represent pathogenetic pathways capable of blocking differentiation and promoting proliferation of the B-cell ALL lymphoblasts. Data mining of the National Library of Medicine's MEDLINE Database and Ingenuity Pathway analysis revealed agents of relatively low toxicity-melatonin, metformin, curcumin and sulforaphane-that are capable of inhibiting directly or pharmacogenomically one or both of the SIRT1 and EZH2 pathways and should, in a combinatorial fashion, remove the block in differentiation and decrease the proliferation of the B-cell ALL lymphoblasts.

Philadelphia chromosome-negative acute myeloid leukemia with 11q23/MLL translocation in a patient with chronic myelogenous leukemia.

Although defined by the presence of t(9;22), chronic myelogenous leukemia (CML) can have other concurrent additional cytogenetic changes, especially during disease progression. Additional chromosomal changes (ACAs) in CML often occur in Philadelphia chromosome (Ph)-positive cells and are associated with disease acceleration and treatment resistance. Occasionally chromosomal changes occur in Ph-negative cells and this phenomenon is often transient and does not correlate with disease progression. Very rarely myelodysplastic syndrome or acute leukemia can develop in Ph-negative cells. In this study, we report an unusual case of acute myeloid leukemia (AML) with 11q23/MLL translocation emerging from Ph-negative cells in a patient with CML.