The co occurrence of a myeloid and plasma cell neoplasm is an incompletely understood phenomenon with few cases reported in the literature.

Coccidioidomycosis is a fungal infection that is often asymptomatic in immunocompetent individuals. When symptoms do occur, they often resemble a mild, flu-like illness. However, this disease can become clinically severe and disseminate, especially in immunocompromised patients or other high-risk groups. Failure to consider coccidioidomycosis in the differential diagnosis may lead to missed or delayed diagnosis, resulting in postponement of appropriate treatment.

The incidence of brain metastasis (BM) is gradually increasing, and the prognosis and therapeutic effect are poor. The emergence of immunotherapy has brought hope for the development of BM treatments. This study revealed that compared with primary cancers, BMs have a colder and more acidic tumor microenvironment (TME), resulting in reduced protein levels of mesothelin (MSLN), a promising target for chimeric antigen receptor-T (CAR-T) cell therapy for triple-negative breast cancer (TNBC) with BMs. These factors could significantly decrease the efficiency of MSLN-CAR-T cells in TNBC BMs. Pantoprazole (PPZ) administration at the most commonly used dose in the clinic notably increased the pH of the TME, inhibited lysosomal activity, increased the membrane levels of the MSLN protein and improved the killing ability of MSLN-CAR-T cells both in vitro and in vivo. Similar results were obtained in non-small cell lung cancer BMs. Hence, when administered in combination with CAR-T cells, PPZ, which increases the protein levels of target antigens, may constitute a new immunotherapeutic strategy for treating solid tumors with BMs.

Deep venous thrombosis (DVT) is a complication of myeloproliferative neoplasms (MPNs). However, DVTs in unusual sites such as portal vein thrombosis (PVT) are rare and may be the first clinical manifestation of occult MPNs. There is a need for increasing awareness of such manifestations; so, here we discuss a patient who presented with new portal vein thrombosis, underwent further studies, was ultimately diagnosed with JAK2 positive MPN, and started on appropriate treatment with improvement of thrombosis and controlled hematocrit.

Germline pathogenic variants in DDX41 have recently been described in association with myelodysplastic syndrome and acute myeloid leukemia in older populations. However, this pathogenic variant has rarely been described in the pediatric population. This report represents a novel case of newly diagnosed myeloid neoplasm in a 9-year-old patient presenting with essential thrombocythemia-like features and was proven to have JAK2 V617F pathogenic variant, constitutional balanced paracentric inversion on q-arm of chromosome 7, and a germline heterozygous DDX41 pathogenic variant. This is the first reported case of a pediatric patient who presented with the constellation of these clinical features, histologic findings, and genetic alterations.

Background Lactate is an important metabolite derived from glycolysis under physiological and pathological conditions. The Warburg effect reveals the vital role of lactate in cancer progression. Numerous studies have reported crucial roles for lactate in cancer progression and cell fate determination. Lactylation, a novel posttranslational modification (PTM), has provided a new opportunity to investigate metabolic epigenetic regulation, and studies of this process have been initiated in a wide range of cancer cells, cancer-associated immune cells, and embryonic stem cells. Conclusion Lactylation is a novel and interesting mechanism of lactate metabolism linked to metabolic rewiring and epigenetic remodeling. It is a potential and hopeful target for cancer therapy. Here, we summarize the discovery of lactylation, the mechanisms of site modification, and progress in research on nonhistone lactylation. We focus on the potential roles of lactylation in cancer progression and cell fate determination and the possible therapeutic strategies for targeting lysine lactylation. Finally, we suggest some future research topics on lactylation to inspire some interesting ideas.

Post-transplant lymphoproliferative disorders (PTLD) are heterogenous lymphoproliferative disorders that develop as a consequence of immunosuppression in transplant recipients. We sought to determine if subtypes of PTLD correlated with different outcomes. We performed a retrospective review of PTLD occurring in pediatric heart transplant recipients. A total of 558 children and infants underwent cardiac transplantation at our institution between 1985 and 2019 and were followed until March 2021. Forty-nine of 558 patients developed PTLD (8.8%). As compared to older children (>one year of age), infant recipients (<three months of age) were less likely to develop PTLD. Monomorphic PTLDs (M-PTLD, 61%) was the most common subtype at initial diagnosis, followed by non-destructive (21%), polymorphic (14%), and classic Hodgkin lymphoma (cHL, 4%). Patients who underwent transplantation at a young age (<three months) had significantly lower rates of M-PTLD or cHL and a longer time from transplant to PTLD diagnosis as compared to children older than one year at transplant (p = 0.04). Although not reaching statistical significance, patients with a shorter time to PTLD diagnosis showed a trend toward higher rates of M-PTLD or cHL. As expected, the overall survival (OS) of patients with M-PTLD or cHL was significantly lower than patients with non-destructive or polymorphic PTLD.

A 23-year-old man presented with skin that bruised easily, pancytopenia, recent fatigue, fever, and loss of appetite, along with a nontender, brown-purple, left anterior pretibial mass of 2 years' duration (top).Computed tomography showed diffuse lymphadenopathy involving the inguinal, mesenteric, retroperitoneal, mediastinal, and axillary regions.A biopsy of the mass showed a dense monomorphous infiltrate of medium-sized blastoid cells with small or inconspicuous nucleoli (bottom).The lesion diffusely involved the dermis and extended into the subcutaneous tissue but spared the epidermis.Flow cytometry immunophenotyping of peripheral blood neoplastic cells (bottom [inset]) showed high-level expression of CD123 together with expression of CD4, CD56, CD45RA, and CD43 but a lack of expression of any other myelomonocytic or lymphoid lineage-associated markers. THE BEST DIAGNOSIS IS:a. adult T-cell leukemia/lymphoma b. blastic plasmacytoid dendritic cell neoplasm c. diffuse large B-cell lymphoma

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.

Mantle cell lymphoma (MCL) is a rare and aggressive non-Hodgkin’s B cell lymphoma characterized by the translocation t(11;14) (q13;32) and overexpression of CCND1. MCL is immunophenotypically identified as CD20+, CD5+, CyclinD1+, CD43+, CD10−, BCL6−, and CD23−. It is often distinguished from B cell lymphomas of germinal center cell origin by the absence of CD10 expression. Here we report the unique clinicopathologic features of a patient with CD10+ MCL with gastrointestinal involvement and review current literature identifying this unique immunophenotype.

Chronic myeloid leukemia (CML) is a common myeloproliferative neoplasm (MPN). However, CML presenting with isolated thrombocytosis and lacking all the typical features of CML is quite rare. The purpose of this report is to demonstrate the importance of BCR::ABL1 testing for correct diagnosis and treatment even when the presenting features are unusual for CML. We report a case of isolated thrombocytosis with subsequently discovered alternative splicing of JAK2 resulting in skipping of exon 15 in the peripheral blood as the initial presentation of CML in a 67-year-old male with metastatic hepatocellular carcinoma, with BCR::ABL1 detected in the bone marrow aspirate. Bone marrow aspirate was collected in EDTA for evaluation and testing. Bone marrow clot and core sections were obtained and the core was decalcified, then each was fixed in neutral-buffered formalin (10%). The clot and core were embedded in formalin and sectioned at 4 microns for evaluation. Bone marrow aspirate and biopsy demonstrated markedly increased megakaryocytes with clustering. The chromosome analysis demonstrated t(9;22) and molecular studies for BCR::ABL1 were positive. JAK2 , MPL , and CALR mutations were negative. The patient did not show a response to hydroxyurea (HU) as the initial treatment. His platelet count normalized within 1 month after treatment with Tyrosine kinase inhibitor (TKI) Imatinib. This report highlights the importance of pursuing BCR::ABL1 testing in the workup of patients with isolated thrombocytosis, even in the presence of abnormal JAK2 transcripts and unusual bone marrow features.

Background: Plasmablastic lymphoma (PBL) is a rare, highly aggressive lymphoma of plasma cell differentiation. It commonly presents as an Epstein-Barr virus (EBV)+ oral lesion in an immunodeficient patient, predominately human immunodeficiency virus (HIV)+ patients. These aggressive lesions often demonstrate an immunoblastic or plasmablastic morphology with a typical immunohistochemical profile. The current case is unique due to the location at presentation, immunohistochemical features, and unknown presence of HIV infection in a young adult male. Case Presentation: We present an unexpected case of PBL found in a rare extra-oral location in a young adult male with undiagnosed HIV infection presenting as a perianal hemorrhoid mass/abscess. Swift treatment for HIV and the PBL resulted in complete remission and markedly improved CD4 counts. Conclusions: This case highlights the importance of testing for HIV along with acquiring a thorough social/clinical history when a PBL is encountered. Although the overall prognosis of PBL is dismal with a median survival of about 6-11 months, a timely accurate diagnosis and prompt chemotherapy with an appropriate regimen along with antiretroviral therapy (ART) may still achieve a successful outcome with a relatively reasonable long-term remission like in our reported case.

Post-transplant lymphoproliferative disorders (PTLDs) are lymphoid or plasmacytic proliferations ranging from polyclonal reactive proliferations to overt lymphomas that develop as consequence of immunosuppression in recipients of solid organ transplantation (SOT) or allogeneic bone marrow/hematopoietic stem cell transplantation. Immunosuppression and Epstein–Barr virus (EBV) infection are known risk factors for PTLD. Patients with documented histopathologic diagnosis of primary PTLD at our institution between January 2000 and October 2019 were studied. Sixty-six patients with PTLD following SOT were followed for a median of 9.0 years. The overall median time from transplant to PTLD diagnosis was 5.5 years, with infant transplants showing the longest time to diagnosis at 12.0 years, compared to pediatric and adolescent transplants at 4.0 years and adult transplants at 4.5 years. The median overall survival (OS) was 19.0 years. In the monomorphic diffuse large B-cell (M-DLBCL-PTLD) subtype, median OS was 10.7 years, while median OS for polymorphic subtype was not yet reached. There was no significant difference in OS in patients with M-DLBCL-PTLD stratified by quantitative EBV viral load over and under 100,000 copies/mL at time of diagnosis, although there was a trend towards worse prognosis in those with higher copies.

Hematologic malignancies are known to be associated with numerous cytogenetic and molecular genetic changes. In addition to morphology, immunophenotype, cytochemistry and clinical characteristics, these genetic alterations are typically required to diagnose myeloid, lymphoid, and plasma cell neoplasms. According to the current World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues, numerous genetic changes are highlighted, often defining a distinct subtype of a disease, or providing prognostic information. This review highlights how these molecular changes can alter mitochondrial bioenergetics, cell death pathways, mitochondrial dynamics and potentially be related to mitochondrial genetic changes. A better understanding of these processes emphasizes potential novel therapies.

Plasma cell myeloma type posttransplant lymphoproliferative disorder (PTLD) is a rare subtype of monomorphic B-cell/plasmacytic-type PTLD. Only 10 cases of monomorphic plasmacytic-type PTLD have been previously reported in pediatric transplant recipients (kidney, liver, small bowel-liver, and heart). We present a case of Epstein-Barr virus positive monomorphic plasma cell myeloma type PTLD that developed 10 months after cardiac transplant in an 18-month-old boy. The bone marrow showed replacement by about 20% to 40% lambda-restricted plasmacytoid lymphocytes and plasma cells (by immunohistochemistry and flow cytometry, respectively). His serum free lambda to kappa light chain ratio was >300, comparable to that seen in myeloma in nontransplant patients. The neoplastic cells were Epstein-Barr virus small RNA positive by in situ hybridization. He was treated with rituximab in combination with ganciclovir, intravenous immune globulin, and discontinuation of immunosuppressants. However, he succumbed to septic shock and multiorgan failure 1 month after diagnosis.

Background Pulmonary carcinoid tumorlets (PCT) are incidental histologic or radiologic discoveries that are localized neuroendocrine tumors whose proliferation is associated with chronic pulmonary inflammatory processes. This study assessed the imaging findings and histological appearances of PCT co-existing with chronic pulmonary inflammatory processes. Material/Methods We performed a retrospective study of 14 patients with incidentally-found PCT with co-existing chronic pulmonary inflammatory processes who underwent preoperative X-rays and CT between 1 January 2003 and 31 December 2012. The clinical symptoms, X-rays, CT imaging findings, and histological appearances were retrospectively evaluated. Results Twelve women and 2 men were found to have PCT, with a mean age of 55.29±13.90 years (range 25–74 years) at diagnosis. Among these 14 patients, hemoptysis, cough, chest pain, expectoration, and chest tightness were found in 9 (64.3%), 5 (35.7%), 4 (28.6%), 3 (21.4%), and 1, respectively. For most patients, we could not find any small nodules on the X-ray or CT images. However, indirect imaging findings of bronchiectasis (85.7%, 12/14), atelectasis (57.1%, 8/14), inflammation (92.8%, 13/14), tuberculosis (7.1%, 1/14), and lung cancer (7.1%, 1/14) were found in all 14 patients. Conclusions PCT occurs most commonly in middle-aged women who have chronic pulmonary inflammatory processes such as bronchiectasis, atelectasis, and inflammation. Although there are no specific symptoms or direct imaging findings in these patients, our results showed that patients who have bronchiectasis, atelectasis, or recurrent pulmonary infection are at increased risk for PCT.

OBJECTIVES:Whole-arm translocations are relatively rare among hematological malignancies. There are a few reports on der(18;21)(q10;q10). This is a recurrent but rare abnormality. Only about 11 cases harboring der(18;21)(q10;q10) have been reported. However, combined der(18;21) (q10;q10) and gain of chromosome 21 is even rarer, with only three cases reported. The previous cases were with AML, AML-M2, and aCML diagnosis. We report the first case of Ph-like, B-lymphoblastic leukemia (B-ALL) with +21 and der(18;21)(q10;q10) which resulted in loss of 18p and a gain of 21q. We address tumorigenesis and morphological characteristics of hematological malignancies involving der(18;21)(q10;q10), along with a review of the literature.

Abstract Objectives To describe a case of plasmablastic lymphoma with an atypical immunophenotype in an unusual location. Methods We received this specimen for routine processing after the patient underwent an incision and drainage surgery. The specimen was sent to hematopathology for workup of lymphoma. We then ordered several special stains and molecular tests to confirm our diagnosis of plasmablastic lymphoma. Results Histologic examination of the tissue reveals sheets of large plasmablastic cells with eccentrically located round nuclei, prominent nucleoli, and cartwheel chromatin. Frequent apoptotic bodies and mitotic figures are present. Immunohistochemistry shows strong, diffuse positivity for leukocyte common antigen CD45, CD10, plasmacytic markers (MUM1, CD79a) and negativity for B-cell markers (CD20, PAX5) and CD138. The Ki-67 proliferation index is very high (>90%) and Epstein-Barr virus encoded small RNA (EBER) in situ hybridization is diffusely positive. Molecular FISH testing for aggressive B-cell lymphoma genetic abnormalities is positive for MYC gene rearrangement in 68% of nuclei and the loss of one copy of the BCL2 gene on chromosome 18 in 64% of nuclei. Conclusion This case of plasmablastic lymphoma is unique due to its atypical presentation as a perianal mass in a young patient with undiagnosed HIV. Usually, this lymphoma presents as an oral lesion in an older patient with HIV. In addition, immunohistochemistry showed an unusual immunophenotype (CD138–, MUM1+, CD45+, CD10+). Most plasmablastic lymphomas are CD138+, MUM1+, and CD45– but this specimen is CD138–, MUM1+, and CD45+. Further testing shows EBER positivity, a positive HIV test, and MYC gene rearrangement, which confirms our diagnosis of a plasmablastic lymphoma. Of note, genetic analysis also reveals a loss of one copy of the BCL2 gene on chromosome 18 in 64% of nuclei.

BACKGROUND Gelsolin amyloidosis is a very rare systemic disease presenting with a pathognomonic triad of corneal lattice dystrophy, cutis laxa, and polyneuropathy. The disease is mostly restricted to a Finnish population with known mutations (G654A, G654T) in exon 4 of the gelsolin gene. The mutations lead to errors in protein processing and folding, and ultimately leads to deposition of an amyloidogenic fragment in the extracellular space, causing the symptoms of disease. CASE REPORT We present a case of gelsolin amyloidosis in a male of African descent with an atypical clinical presentation including fevers, skin rash, polyneuropathy, and anemia. Gelsolin amyloidosis was diagnosed based on mass spectrometry of tissue samples. Importantly, a novel mutation in the gelsolin gene (C1375G) in exon 10 was found in this patient. His atypical presentation can possibly be attributed to the presence of a novel mutation in the gelsolin gene as the likely underlying cause of the syndrome. PCR primers were used to amplify the gelsolin gene from genomic DNA. Purified PCR products were then shipped to Eton Biosciences (San Diego, CA) for sequencing. CONCLUSIONS This study carries several important lessons relevant to the practice of medicine. First, the differential diagnosis for multisystem disease presentations should always include amyloidosis. Second, despite what has been uncovered about the molecular biology of disease, there is always more that can be discovered. Finally, further work to verify the link between this mutation and the clinical syndrome is still needed, as are effective treatments for this disease.