Contemporary Approach to the Diagnosis and Classification of Myelodysplastic Neoplasms/Syndromes-Recommendations From the International Consortium for Myelodysplastic Neoplasms/Syndromes (MDS [icMDS]).

Myelodysplastic neoplasms/syndromes (MDS) are a heterogeneous group of biologically distinct entities characterized by variable degrees of ineffective hematopoiesis. Recently, 2 classification systems (the 5th edition of the World Health Organization Classification of Haematolymphoid tTumours and the International Consensus Classification) further subcharacterized MDS into morphologically and genetically defined groups. Accurate diagnosis and subclassification of MDS require a multistep systemic approach. The International Consortium for MDS (icMDS) summarizes a contemporary, practical, and multimodal approach to MDS diagnosis and classification.

Idiopathic myointimal hyperplasia of the mesenteric veins: A systematic review and individual patient data regression analysis.

BACKGROUND AND AIM: Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is an uncommon cause of colonic ischemia for which surgical treatment is typically curative. We describe clinical, radiologic, and endoscopic findings in IMHMV patients to provide clinicians with a framework for pre-surgical identification of this rare disease. METHODS: We performed a systematic review of seven databases for IMHMV cases and identified additional cases from Yale New Haven Hospital records. To identify features specifically associated with colonic ischemia due to IMHMV, we performed multivariate logistic regression analysis incorporating data from a large cohort of patients with biopsy-proven ischemic colitis. RESULTS: A total of 124 patients with IMHMV were identified (80% male, mean age 53 years, 56% Caucasian). Presenting symptoms were most commonly abdominal pain (86%) and diarrhea (68%). The most affected areas were the sigmoid colon (91%) and rectum (61%). Complications associated with diagnostic delay occurred in 29% of patients. Radiologic vascular abnormalities including non-opacification of the inferior mesenteric vein were observed in 35% of patients. Of the patients, 97% underwent curative surgical resection. Compared with non-IMHMV colonic ischemia, IMHMV was significantly associated with younger age, male sex, absence of rectal bleeding on presentation, rectal involvement, and mucosal ulcerations on endoscopy. CONCLUSION: IMHMV is a rare, underreported cause of colonic ischemia that predominantly involves the rectosigmoid. Our findings suggest younger age, rectal involvement, and absence of rectal bleeding as clinical features to help identify select patients presenting with colonic ischemia as having higher likelihood of IMHMV and therefore consideration of upfront surgical management.

Mast cell sarcoma: clinicopathologic and molecular analysis of 10 new cases and review of literature.

Mast cell sarcoma (MCS) is an exceedingly rare form of mastocytosis characterized by invasive malignant mast cell growth and metastatic potential. Diagnosis of MCS is very challenging due to its marked morphologic variations and significant immunophenotypic overlap with other neoplasms. In this study, we undertook an extensive study of 10 cases of MCS from our series, with review of additional 24 cases from the literature, to better clarify the clinicopathologic and molecular features of MCS. From the analyses of our 10 cases, MCS equally involved males and females with a median age of 54.5 years (range 1-63). The bone was the most common site of involvement, as noted in 9/10 of cases. Two patients had prior germ cell tumors (mediastinal germ cell tumor and ovarian dysgerminoma), and concurrent systemic mastocytosis was noted in one of nine patients. Serum tryptase levels were elevated in 6/7 of patients, and 3/9 of patients had mast cell activation symptoms. Morphologically, the tumor cells were typically large and pleomorphic with frequent reactive eosinophils. By immunohistochemical staining, MCS consistently expressed CD43 (8/8), CD117 (10/10), and mast cell tryptase (10/10), as well as CD13 (3/3) and CD33 (10/10), with variable positivity of CD2 (1/9), CD25 (4/9), CD30 (5/8), and CD68 (5/9). Notably, KIT D816V was not detected in nine cases in our study, although two cases had other mutations of KIT gene. Seven out of eight patients received chemotherapy with or without radiotherapy. However, the response was poor, and four out of eight patients died within a median follow-up interval of five months. Taken together, there are no standardized therapeutic regimens available for MCS at this time, and the prognosis is dismal. Therefore, it is critical to further investigate and characterize this rare entity, with the hope of improving diagnostic accuracy and providing more effective, targeted therapies.

Human herpesvirus 8-negative effusion-based large B-cell lymphoma: a distinct entity with unique clinicopathologic characteristics.

Rare cases of human herpesvirus 8 (HHV8)-negative effusion-based large B-cell lymphoma (EB-LBCL) occur in body cavities without antecedent or concurrent solid mass formation. In contrast to HHV8 + primary effusion lymphoma (PEL), EB-LBCL has no known association with HIV or HHV8 infection. However, the small sample sizes of case reports and series worldwide, especially from non-Japanese regions, have precluded diagnostic uniformity. Therefore, we conducted a retrospective, multi-institutional study of 55 cases of EB-LBCL and performed a comprehensive review of an additional 147 cases from the literature to identify distinct clinicopathologic characteristics. In our study, EB-LBCL primarily affected elderly (median age 80 years), immunocompetent patients and manifested as lymphomatous effusion without a solid component. The lymphomatous effusions mostly occurred in the pleural cavity (40/55, 73%), followed by the pericardial cavity (17/55, 31%). EB-LBCL expressed CD20 (53/54, 98%) and PAX5 (23/23, 100%). Most cases (30/36, 83%) were of non-germinal center B-cell subtype per the Hans algorithm. HHV8 infection was absent (0/55, 0%), while Epstein-Barr virus was detected in 6% (3/47). Clinically, some patients were managed with drainage alone (15/34, 44%), while others received rituximab alone (4/34, 12%) or chemotherapy (15/34, 44%). Eventually, 56% (22/39) died with a median overall survival (OS) of 14.9 months. Our findings were similar to those from the literature; however, compared to the non-Japanese cases, the Japanese cases had a significantly higher incidence of pericardial involvement, a higher rate of chemotherapy administration, and longer median OS. Particularly, we have found that Japanese residence, presence of pericardial effusion, and absence of MYC rearrangement are all favorable prognostic factors. Our data suggest that EB-LBCL portends a worse prognosis than previously reported, although select patients may be managed conservatively. Overall, EB-LBCL has distinct clinicopathologic characteristics, necessitating the establishment of separate diagnostic criteria and consensus nomenclature.

Concomitant factor VIII inhibitor and lupus anticoagulant in an asymptomatic patient.

Acquired hemophilia A, caused by autoantibodies that bind to and neutralize the activity of coagulation factor VIII (FVIII), almost universally presents as a severe bleeding diathesis. Lupus anticoagulants (LAs), autoantibodies directed against phospholipids or protein-phospholipid complexes, manifest clinically with an increased risk of thrombosis. While these autoantibodies are uncommon, the distinctive clinical presentation in conjunction with the typical laboratory findings often enable straightforward identification of the underlying autoantibody. However, the presence of a concomitant acquired FVIII inhibitor and LA is exceedingly rare with fewer than 20 documented cases. All prior patients presented with life-threatening hemorrhage, thrombosis, or both, prompting comprehensive hematologic evaluation and subsequent identification of the pathologic antibodies. We describe a novel case of a patient with no signs of hemorrhage or thrombosis who was incidentally found to have both a FVIII inhibitor and LA during evaluation of a prolonged partial thromboplastin time (PTT). This finding resulted in FVIII inhibitor-directed management, including immunosuppressive therapy. The unique presentation of an incidental FVIII inhibitor and LA in an asymptomatic patient without thrombotic or bleeding complications highlights the potential challenge in elucidating the etiology of a prolonged PTT, as LAs and FVIII inhibitors both prolong the PTT, and each entity can interfere with assays designed to detect the presence of the other autoantibody. This case underscores the importance of recognizing that patients with major underlying disturbances in their hematologic physiology, but in whom clinical symptoms have yet to manifest, may potentially be overlooked until such symptoms are evident.

Incidental Discovery of a Patient with the Bombay Phenotype.

Bombay phenotype, an exceptionally rare blood type in individuals outside of Southeast Asia, occurs in approximately 1 in 1,000,000 individuals in Europe. This blood phenotype is characterized by the absence of the H antigen on red blood cells (RBCs) and in secretions. As the H antigen is the structure on which the ABO system is built, individuals lacking this antigen are unable to produce A or B antigens and appear as type O on routine ABO phenotyping. H deficiency does not cause ill effect; however, these individuals produce an anti-H alloantibody capable of causing severe acute hemolytic transfusion reactions when exposed to RBCs that express the H antigen. In this case study, we highlight the incidental discovery of a patient with Bombay phenotype in a North American hospital system, expected test results, the immunologic and genetic basis underlying the Bombay and para-Bombay phenotypes, and methods to ensure availability of compatible blood.

Viral anti-inflammatory serpin reduces immuno-coagulopathic pathology in SARS-CoV-2 mouse models of infection.

SARS-CoV-2 acute respiratory distress syndrome (ARDS) induces uncontrolled lung inflammation and coagulopathy with high mortality. Anti-viral drugs and monoclonal antibodies reduce early COVID-19 severity, but treatments for late-stage immuno-thrombotic syndromes and long COVID are limited. Serine protease inhibitors (SERPINS) regulate activated proteases. The myxoma virus-derived Serp-1 protein is a secreted immunomodulatory serpin that targets activated thrombotic, thrombolytic, and complement proteases as a self-defense strategy to combat clearance. Serp-1 is effective in multiple animal models of inflammatory lung disease and vasculitis. Here, we describe systemic treatment with purified PEGylated Serp-1 as a therapy for immuno-coagulopathic complications during ARDS. Treatment with PEGSerp-1 in two mouse-adapted SARS-CoV-2 models in C57Bl/6 and BALB/c mice reduced lung and heart inflammation, with improved outcomes. PEGSerp-1 significantly reduced M1 macrophages in the lung and heart by modifying urokinase-type plasminogen activator receptor (uPAR), thrombotic proteases, and complement membrane attack complex (MAC). Sequential changes in gene expression for uPAR and serpins (complement and plasminogen inhibitors) were observed. PEGSerp-1 is a highly effective immune-modulator with therapeutic potential for severe viral ARDS, immuno-coagulopathic responses, and Long COVID.

The first reported case of Staphylococcus pettenkoferi prosthetic joint infection.

Staphylococcus aureus and Staphylococcus epidermidis are among the most frequent causes of prosthetic joint infections (PJIs). Staphylococcus pettenkoferi, a coagulase-negative Staphylococcal species first described in 2002, has been detected in fewer than 20 patients with true infection (15 cases of bacteremia and 1 case of osteomyelitis). This organism has never been implicated in a PJI, likely owing in part to the difficulty in identification via biochemical methods. S. pettenkoferi is almost universally reported to be a contaminant when detected. We report the first case of a PJI caused by S. pettenkoferi, highlighting its infectious potential in specific patient populations.

Splenic Abscess in the New Millennium: A Descriptive, Retrospective Case Series.

Background: Splenic abscess is a rare infection often resulting from hematogenous spread. Immunocompromised states are commonly comorbid, and the microbiology is heterogeneous. Methods: We conducted a retrospective review of 33 cases identified by convenience sampling. Cases were treated in our institution's hospital system between May 2012 and February 2021 and classified as proven or probable based on predetermined criteria. Results: The median age was 57 years, and 58% were men. Common underlying diseases included diabetes mellitus (30%), pancreatic disease (30%), and hematological malignancy (15%). The most common mechanism of pathogenesis was hematogenous spread (n = 13). Escherichia coli, enterococcal spp., and anaerobes were frequently implicated. One case was discovered at autopsy and excluded from subsequent analyses. The median duration of antimicrobial therapy (range) was 45 (5-525) days, and the median length of index hospitalization was 20 days. Percutaneous drainage by interventional radiology was common (17 of 32; 53%), and 6 patients underwent splenectomy. Treatment success was achieved in 14 of 32 cases (44%), with clinical stability in 3 of 32 cases (9%). Failures occurred in 13 of 32 (41%) cases, 2 of whom died from splenic abscesses. Two patients (2 of 32) were lost to follow-up. Conclusions: To our knowledge, this is the largest North American series since the turn of the century and the first to distinguish between proven and probable cases. As reflected in our series, patients with splenic abscess may require prolonged hospitalizations and courses of antimicrobial therapy. Improvements in management are needed.

Unexpectedly low hemoglobin A1c in a patient with chronic lymphocytic leukemia.

Glycated hemoglobin (HbA1c) assays are currently utilized to monitor patients with diabetes mellitus type 2 (T2DM). These assays employ various methods, some of which are more prone to interference than others. Commonly recognized causes of interference include hemoglobin variants and conditions that result in reduced red blood cell survival such as hemolytic anemia and certain medications. Enzymatic assays represent one of the predominant methods for HbA1c testing for practical reasons. Herein, we describe a potentially novel interference in an enzymatic HbA1c assay by neoplastic lymphocytes in a patient with chronic lymphocytic leukemia. We hypothesize that the marked number of neoplastic lymphocytes are interfering in the enzymatic steps inherent to this assay, resulting in a discordantly low HbA1c result. Awareness of this possibility and further investigation into the precise mechanism by which this interference is occurring are warranted.

Pyomyositis and Infectious Myositis: A Comprehensive, Single-Center Retrospective Study.

BACKGROUND: Pyomyositis is a bacterial infection of skeletal muscle that classically leads to abscess formation. A related, but distinct, entity is infectious myositis. The epidemiology of these infections has changed in recent years. METHODS: To better characterize both pyomyositis and infectious myositis, we conducted a retrospective study at our tertiary care institution. We identified 43 cases of pyomyositis and 18 cases of infectious myositis treated between January 2012 and May 2020. RESULTS: The mean age of patients was 48 years, and 66% were male. Diabetes mellitus affected one third of patients, and 16% had other immunocompromising comorbidities. Staphylococcal species accounted for 46% of all infections, and common symptoms included muscle pain (95%) and subjective fever (49%). Altered mental status was a presenting symptom in 16% of cases. Approximately half of all patients received >1 class of antibiotic, and the median length of antimicrobial therapy was 18 days. Open and percutaneous drainage procedures figured prominently in the management of these infections, with 28% of patients requiring multiple procedures. Pathology specimens were available for 12 of 61 cases. Overall, the treatment success rate was 84%. CONCLUSIONS: Gram-positive bacteria accounted for most infections at our institution, and management commonly involved open or percutaneous drainage procedures. Future studies that prospectively evaluate treatment strategies for pyomyositis and infectious myositis are warranted.

Diffuse large B-cell and follicular lymphoma presenting as a slowly growing compressive goiter: A case report and literature review.

INTRODUCTION: Neck ultrasonography with fine-needle aspiration cytology (FNAC) is the diagnostic modality of choice for clinicians who routinely work up a thyroid mass. Distinguishing chronic lymphocytic infiltration from a lymphoproliferative process with FNAC in patients with Hashimoto's thyroiditis presenting with a goiter can be particularly challenging. CASE DESCRIPTION: A 58 y.o. female with a history of a goiter showing interval growth and compressive symptoms over 18 months, was treated with a thyroid lobectomy. Surgical pathology demonstrated a thyroid lymphoma (TL) with mixed follicular and diffuse large B cell (DLBCL) components, not initially diagnosed by FNAC. Staging workup showed the involvement of chest lymph nodes only, consistent with Stage IIE disease. She was treated with combination chemotherapy and immunotherapy, followed by involved-field radiotherapy. DISCUSSION: TL often arises in a background of chronic lymphocytic thyroiditis which can make its histological diagnosis a challenge. The disease is heterogeneous in histological subtype and progression. CONCLUSION: While TL usually presents as a rapidly growing neck mass, indolent types can present as a slow growing mass with subsequent transformation. Patients may benefit from avoiding unnecessary diagnostic steps, including surgery, and potential delays in treatment by performing a core needle biopsy when a lymphoproliferative process cannot be excluded if FNAC was initially performed.