搜索结果：Case reports in hematology

Treatment-free remission (TFR) has become an important therapeutic goal in chronic myeloid leukemia (CML). Although the outcomes of TFR following adenosine triphosphate (ATP)-competitive tyrosine kinase inhibitors (TKIs) have been established, data on TFR after asciminib discontinuation remain limited. In this study, we report the case of a man in his 60s with chronic-phase CML who experienced molecular relapse 8 months after a second TFR attempt following asciminib treatment. The patient was diagnosed with CML approximately 15 years earlier and achieved deep molecular response 4.5 (MR4.5), representing a 4.5-log reduction in BCR::ABL1 transcripts, with first-line imatinib. After the first TFR attempt, major molecular response (MMR) was lost, and ponatinib was initiated but discontinued because of cerebral infarction. Asciminib was subsequently introduced as third-line therapy at a dose of 40 mg twice daily, and BCR::ABL1 transcripts remained undetectable for more than 3 years. Based on the sustained deep molecular response and patient preference, asciminib was discontinued. Eight months after discontinuation, however, loss of MR4.0 (BCR::ABL1 > 0.01% IS) was detected. This threshold was used to guide treatment reinitiation, rather than waiting for loss of MMR as recommended by the ELN guidelines, in the view of the clinical context of a second TFR attempt following prior failure. Imatinib was reintroduced, leading to the reachievement of a deep molecular response. This case underscores the importance of careful patient selection and long-term molecular monitoring following TFR attempts, including those involving novel TKIs such as asciminib.

Double minutes (dmins), a form of extrachromosomal DNA (ecDNA), represent a rare cytogenomic event in myeloid neoplasms and are most commonly associated with amplification of oncogenes such as MYC or KMT2A. Dmins derived from the 11q24 region that exclude KMT2A are exceedingly uncommon, and their pathogenic significance remains poorly understood. We report a 74-year-old female initially diagnosed with myelodysplastic syndrome (MDS) with isolated del(5) (q13q33) and mutations in TP53 and SF3B1. After eight years and treatment with lenalidomide with excellent clinical response, she developed progressive cytopenias and transformation to acute myeloid leukemia, myelodysplasia-related (AML-MR). Cytogenomic analysis at the time of leukemic transformation revealed del(5) (q13q33) in all 20 metaphase cells analyzed and loss of the EGR1 (5q31.2) gene in 94% of interphase nuclei by fluorescence in situ hybridization (FISH). Notably, 18 of 20 metaphase cells also harbored dmins, ranging from 2 to 22 copies per cell. Array-based comparative genomic hybridization and single nucleotide polymorphism array (array-CGH + SNP) identified a 5.57 Mb amplification of chromosome 11q24.2-q25 encompassing at least 40 genes, including FLI1 and ETS1 but excluding KMT2A. Metaphase FISH confirmed localization of the amplified 11q24 segment within the dmins, and immunohistochemistry demonstrated nuclear FLI1 expression in myeloblasts. The patient was treated with combination azacitidine and venetoclax and an investigational immunotherapy within a clinical trial. This case represents the third reported instance of dmins derived from the 11q24 region involving FLI1 and ETS1 and the first identified in the context of AML evolved from del(5q) MDS. Dmins in myeloid neoplasms have been linked to genomic instability, clonal evolution, and therapeutic resistance. Amplification and expression of FLI1 in blasts, a hematopoietic transcription factor implicated in leukemogenesis and poor prognosis in AML, suggest a potential pathogenic role for 11q24-derived dmins in disease progression. Our findings expand the spectrum of dmin-associated oncogenic amplifications in myeloid neoplasms and highlight FLI1 and ETS1 as recurrent targets of 11q24-derived ecDNA amplification. Recognition of such rare events underscores the importance of integrative cytogenomic profiling for uncovering novel mechanisms of leukemic transformation and potential therapeutic targets.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a rare, adult-onset autoinflammatory disease that has only been described since late 2020. Given the rarity of the disease and the absence of established treatment guidelines, management remains challenging and largely based on clinical experience and case reports. This paper reports the first documented case of VEXAS syndrome in Lebanon. A 73-year-old man presented with fever, severe asthenia, erythematous skin lesions, and anemia, initially diagnosed as giant cell arteritis. Following a diagnosis of VEXAS syndrome, he was treated with corticosteroids and methotrexate but developed refractory anemia and required erythropoietin therapy. Tocilizumab was introduced to manage inflammation, but the patient's condition remained challenging due to corticosteroid dependence and myelodysplastic syndrome (MDS). Given the patient's comorbidities and intermediate-risk MDS, azacitidine was initiated as a therapeutic option. Despite initial neutropenia and infections, adjustments to the azacitidine regimen led to significant clinical and hematologic improvements. The patient achieved complete remission, became transfusion-independent, and maintained stable hemoglobin levels. This case highlights the efficacy of azacitidine in managing VEXAS syndrome with MDS, particularly among patients ineligible for hematopoietic stem cell transplantation, offering a potential pathway to sustained remission and reduced corticosteroid dependence.

Hemolytic uremic syndrome is a rare thrombotic microangiopathy characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. While commonly reported in children, adult-onset presentations are less frequent and often atypical, leading to diagnostic delays. This case underscores the importance of repeated evaluation when classical features are absent initially. A 50-year-old woman was admitted with diarrhea, vomiting, abdominal pain, and visible hematuria. Initial findings included severe thrombocytopenia and Stage 3 acute kidney injury but no evidence of hemolysis. Blood cultures grew Escherichia coli sensitive to piperacillin-tazobactam. Despite intensive care management for septic shock, renal function deteriorated and renal replacement therapy was required. On Day 9 of admission, delayed hemolysis became evident with schistocytes on blood smear, undetectable haptoglobin, and hemoglobin decline from 125 g/L at baseline to 87 g/L. These findings confirmed delayed-onset hemolytic uremic syndrome. ADAMTS13 activity was not tested because TTP was considered clinically unlikely based on stable coagulation parameters and absence of neurological features. Supportive care, including renal replacement therapy and blood products, was provided, and the patient's renal function normalized before discharge. This case highlights the diagnostic complexity of adult-onset hemolytic uremic syndrome, particularly when hemolysis develops late. Clinicians should maintain a high index of suspicion in adults presenting with unexplained acute kidney injury and thrombocytopenia, even in the absence of early hemolytic markers. Serial blood film reviews and multidisciplinary input are essential to avoid missed or delayed diagnosis. Early recognition enables timely supportive care and consideration of targeted therapies to prevent irreversible renal damage and long-term complications.

Splenic marginal zone lymphoma (SMZL) is a rare subtype of non-Hodgkin lymphoma. It often follows an indolent course presenting with splenomegaly. Treatment varies from clinically monitoring to splenectomy, chemotherapy, and rituximab treatments. Wandering spleen is an even rarer condition with less than 500 cases reported in the literature, often resulting from laxity in the suspensory ligaments supporting the spleen. Wandering spleen most commonly affects women of childbearing age and children. Treatment for this can be either nonsurgical or surgical with splenopexy or splenectomy. A 75-year-old female initially presented from Mexico for evaluation of splenomegaly and abdominal distension. Computer tomography (CT) scan of the abdomen and pelvis showed a pelvic mass, and labs showed leukocytosis with lymphocytic predominance. The pelvic mass was later confirmed as a wandering spleen. Flow cytometry on peripheral blood was diagnostic for SMZL. The patient was diagnosed with wandering spleen secondary to SMZL and treated with splenectomy. Wandering spleen is very rare and is typically associated with pregnancy, splenomegaly, or inborn errors of the ligaments supporting the spleen. This is only the fifth case reported in the literature of wandering spleen secondary to a lymphoma and the first reported with SMZL. This case offers a simultaneous presentation of two very rare conditions presenting in an atypical fashion. SMZL commonly presents in this age group; however, wandering spleen is rarely seen at this age. Additionally, this patient's first-line treatment for her SMZL was nontraditional with only a splenectomy with no rituximab administered due to the risk of torsion and infarction of the wandering spleen.

We report a case of hemophagocytic lymphohistiocytosis (HLH) secondary to disseminated Bacillus Calmette-Guérin (BCG) infection in an 80-year-old man treated with intravesical BCG for non-muscle-invasive bladder cancer. The patient presented with several weeks of constitutional symptoms including night sweats, fatigue, weight loss, confusion, and pancytopenia. Laboratory studies revealed profound inflammation, coagulopathy, and hepatocellular injury. HLH was suspected clinically and supported by a high H-score. Extensive infectious and autoimmune workup was negative. Mycobacterium bovis was subsequently isolated from urine and bone marrow cultures, which confirmed a diagnosis of disseminated BCG infection. The patient was treated with a combination of antimycobacterial therapy (isoniazid, rifampin, and ethambutol), intravenous immunoglobulin (IVIG), corticosteroids, and anakinra. Anakinra, an interleukin-1 receptor antagonist, was used both to minimize high-dose steroids, given the protracted inflammatory response anticipated with Mycobacterium infection, and to prevent steroid-related complications related to cardiac surgery. This therapeutic strategy was associated with improvement of cytopenias, normalization of inflammatory markers, and gradual clinical recovery. This case highlights the rare but serious complication of HLH triggered by disseminated BCG and suggests that targeted immunomodulation with anakinra may be a useful adjunct in selected, complex presentations of infection-associated HLH.

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by increased platelet destruction and impaired platelet production. While thrombopoietin receptor agonists (TPO-RAs), including romiplostim and eltrombopag, have significantly improved ITP management, some patients remain relapsed to multiple lines of therapy, necessitating alternative approaches. Avatrombopag, a second-generation TPO-RA, has shown promising efficacy and a favorable safety profile, yet its role in cases unresponsive to prior TPO-RAs remains underexplored. We report the case of a 37-year-old woman with relapsed severe ITP, unresponsive to corticosteroids, IVIG, rituximab, romiplostim, eltrombopag, vincristine, cyclosporine, and splenectomy. Despite multiple treatments, her platelet count remained critically low, with persistent bleeding symptoms. Given the failure of standard therapies, avatrombopag was initiated at 20 mg daily, resulting in a rapid platelet response, increasing from 14 × 109/L to 72 × 109/L within 9 days. The platelet count peaked at 848 × 109/L, necessitating dose adjustments, after which it stabilized within the target range (100-300 × 109/L). The patient tolerated avatrombopag well, with no thromboembolic events or significant adverse effects reported. This case demonstrates the efficacy of avatrombopag in a patient unresponsive to multiple prior therapies, including other TPO-RAs and splenectomy. Further studies are warranted to determine optimal treatment sequencing and long-term outcomes for patients in this challenging subgroup.

A 56-year-old woman with a history of C4-C5 myelomeningocele repair as a newborn and cervical syringomyelia presented with one week of rapidly worsening bilateral lower extremity weakness and numbness, saddle anesthesia, and bladder incontinence. MRI of the entire spine revealed a 1.5 × 0.5 cm homogenously enhancing intramedullary lesion at T7-T8 with associated cord edema and rostral syrinx formation. MRI of the brain and FDG PET-CT scan were unremarkable. She was taken to the operating room for a T6-T8 laminectomy and biopsy. H&E staining revealed a relatively dense mononuclear-cell infiltrate, which comprised numerous medium-sized cells with round, irregular, or reniform nuclei, slightly dispersed chromatin, and relatively abundant eosinophilic, and occasionally, somewhat vacuolated cytoplasm. Immunohistochemical staining was strongly positive for CD163, PU.1, CD68, and ALK. FISH studies demonstrated ALK rearrangement in 70% of nuclei. Next-generation sequencing including both DNA and RNA testing on a formalin-fixed, paraffin-embedded tissue sample detected a KIF5B/ALK gene fusion. She received radiotherapy with 2000 cGY in 200 cGy fractions to T6-T9 with no change in lesional size or enhancement. She was started on the ALK inhibitor alectinib. Subsequent MRI showed a complete response. She has had no evidence of disease recurrence on alectinib for 18 months. ALK-positive histiocytosis is a recently described distinct clinicopathologic entity. Our case is notable for older age at diagnosis, isolated intramedullary involvement, and radioresistance but later marked targeted-therapy response, thus furthering the understanding of the spectrum of ALK-positive histiocytosis biology.

A 65-year-old man presented to the hospital with multiorgan failure in the setting of recently being started on atezolizumab for his small cell lung cancer. His main clinical findings were white blood cell count of 18.9 K/μL (48% neutrophils, 32% lymphocytes, 15% monocytes, and 0% eosinophils), creatinine of 10.3 mg/dL (increased from a baseline of 1.5), transaminitis with AST of 1365 and ALT of 388, total bilirubin of 2.3, a lactic acid above 11 (the upper detectable limit of our analyzer), and a serum bicarbonate of 2.8. Imaging was only notable for splenomegaly. Upon presentation, he was intubated for airway protection and admitted to the intensive care unit. Over 3 days, he was treated for severe septic shock with multiple blood pressure medications, antibiotics, continuous renal replacement therapy (CRRT), and stress dose steroids. On Day 4, his CRRT machine began clotting with a yellow, lipidic film, leading us to consider HLH. His ferritin and triglycerides were largely elevated, and hemolysis labs showed destruction of cells, making HLH the leading diagnosis. He was started on high-dose steroids while the full interleukin panel was pending. The IL-2 soluble receptor came back elevated, confirming the diagnosis of HLH. Before this panel returned, he received one dose of tocilizumab with high-dose steroids before dying. This case is unique as it is the fourth documented case of secondary HLH due to the immune checkpoint inhibitor, atezolizumab. This presentation of HLH was also difficult due to the lack of fever, hepatomegaly, and cytopenias commonly seen as the presenting symptoms in HLH. Prompt initiation of treatment for HLH is critical, and due to this challenging presentation, this patient did not receive steroids and tocilizumab until Days 4 and 5, respectively.

Leukemia cutis (LC) is characterized by dermal infiltration of leukemic blasts and typically occurs in patients with known leukemia. Rarely, LC is identified at the time of initial diagnosis of systemic disease, especially acute myeloid leukemia (AML). We describe a case of LC identified at the initial diagnosis of AML consistent with therapy-related disease in a patient with metastatic non-small-cell lung cancer (NSCLC) previously treated with cytotoxic chemotherapy and immunotherapy. A 78-year-old woman with Stage IV NSCLC (adenocarcinoma, no actionable mutations, PD-L1 negative) initially received carboplatin, pemetrexed, and pembrolizumab, complicated by neutropenic fever. She later enrolled in the SHERLOC trial (MM-121 + docetaxel), discontinued due to colitis and neutropenia. Maintenance therapy with pembrolizumab was continued intermittently alongside stereotactic body radiation and cryoablation. After several years of disease control, follow-up PET/CT demonstrated new adrenal and iliac bone lesions concerning for progression. Shortly thereafter, she developed multiple pruritic, erythematous plaques on her extremities, accompanied by fatigue, weight loss, and cytopenias. Laboratory evaluation showed leukocytosis, macrocytic anemia, and severe thrombocytopenia, with peripheral smear revealing 72% circulating blasts. Punch biopsy confirmed LC, demonstrating dermal infiltration by myeloid blasts (CD4, CD43, CD68, and MPO positive). Flow cytometry and bone marrow biopsy established AML with > 75% myeloblasts. Next-generation sequencing identified DNMT3A, U2AF1, and PPM1D mutations. Conventional cytogenetic analysis was noninformative because no metaphase cells were obtained, AML FISH was normal, and PML-RARA FISH was negative, findings consistent with therapy-related AML. The patient received hydroxyurea, transfusion support, and tumor lysis prophylaxis. Given her age, ECOG 1, adverse-risk mutations, and personal preference, she declined further chemotherapy and transitioned to hospice. LC at the time of initial AML diagnosis is uncommon and portends poor prognosis. Clinicians should remain vigilant for new skin lesions and cytopenias in cancer survivors previously exposed to chemotherapy, as early recognition of extramedullary AML may expedite timely diagnosis and care planning.

Relapse of acute myeloid leukemia (AML) typically occurs within the first 3 years following treatment, with very late relapses being rare and often presenting extramedullary. We report a unique case of extramedullary AML relapse occurring 13 years after allogeneic hematopoietic stem cell transplantation. The patient developed a myelosarcoma, prompting molecular and histological investigation to determine the origin and mutational landscape of the disease. Next-generation sequencing (NGS) was performed on archived bone marrow samples from the initial AML diagnosis in 2007 and on the relapsed tumor tissue from 2021. The 2007 sample contained nine somatic variants, while the 2021 myelosarcoma harbored four variants. Only a single somatic mutation, a frameshift alteration in the HNRNPK gene, located on 9q21, was shared across both timepoints, suggesting a potential founder event and supporting the hypothesis of clonal evolution. Chimerism analysis and histopathological findings confirmed that the relapse originated from the patient rather than from donor-derived hematopoiesis. This case underscores the importance of long-term vigilance in AML survivors, especially in those receiving chronic immunosuppression, as impaired immune surveillance may allow for reemergence of malignant clones. The persistent HNRNPK mutation across both disease phases may point to a rare but critical driver of leukemogenesis and relapse. Our findings highlight the utility of comprehensive molecular profiling in elucidating disease dynamics and informing personalized monitoring strategies.

Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm that typically presents in infancy or early childhood, classified as a locally aggressive/borderline vascular tumor. It most commonly involves superficial and deep soft tissues, often demonstrating infiltrative growth into adjacent muscle and bone, whereas retroperitoneal or intraabdominal presentations are less frequent. KHE is frequently complicated by Kasabach-Merritt phenomenon (KMP), a severe consumptive coagulopathy characterized by profound thrombocytopenia, microangiopathic hemolytic anemia, and hypofibrinogenemia with life-threatening sequelae. We report a case of a male neonate who developed KMP secondary to an abdominal KHE without overlying cutaneous involvement. Diagnosis was established through integration of clinical features, imaging findings, hematological evaluation, and confirmatory biopsy. This patient was managed with a multimodal regimen of sirolimus, corticosteroids, and vincristine, resulting in significant clinical improvement. This case underscores both the diagnostic complexity and therapeutic challenges of KHE complicated by KMP, particularly when lesions occur in deep anatomical sites. Given the rarity of this condition, current management strategies rely largely on expert consensus and case-based experience, though recent randomized trial and consensus have established sirolimus-based regimens as highly effective first-line therapy.

Breast cancer is the most commonly diagnosed malignancy among women worldwide. While survival outcomes have improved substantially over time, recurrence remains a significant concern, especially in estrogen receptor-positive (ER+) disease. Although most recurrences occur within five years of initial treatment, ER+ tumors carry a persistent risk of late relapse due to tumor dormancy. Very late recurrences occurring decades after remission are rare and poorly characterized. We present the case of a 96-year-old female with a history of right-sided breast cancer treated with mastectomy and adjuvant radiation therapy at age 50, who presented 46 years later with a palpable chest wall mass near her prior mastectomy scar. Imaging revealed an irregular hypoechoic lesion extending into the pectoralis muscle (BIRADS-5). Core biopsy demonstrated moderately differentiated infiltrating lobular carcinoma that was strongly ER+, progesterone receptor-negative, and HER2 non-amplified. Staging studies revealed no evidence of distant metastatic disease. Given the patient's advanced age, comorbidities, and prior radiation exposure, surgical and radiation approaches were deferred. Following multidisciplinary tumor board discussion and shared decision-making, primary endocrine therapy with tamoxifen was initiated. The patient demonstrated clinical regression within three months and tolerated therapy well. This case represents one of the longest reported intervals between initial remission and breast cancer recurrence, highlighting the prolonged biologic potential of dormant ER-positive tumor cells. Clinicians should maintain vigilance for recurrence even decades after treatment, particularly in hormone receptor-positive disease.

T-cell lymphomas are rare, comprising 10%-15% of non-Hodgkin lymphomas (NHLs). Their etiology remains unclear, and pathophysiology varies widely among subtypes. Sarcoid-like reactions (SLRs) have been reported in approximately 7.3% of NHLs, including T-cell lymphomas, and can closely resemble sarcoidosis clinically/histologically. This overlap complicates diagnosis, particularly when secondary myelofibrosis-a rare and poorly understood complication-arises. Myelofibrosis has also been observed in sarcoidosis, further blurring the distinction between these entities. Treatment for T-cell lymphoma-associated secondary myelofibrosis is not standardized, with predominantly CHOP-based regimens showing variable efficacy. This warrants further research to guide diagnostic and management frameworks. We report the case of a 57-year-old male with known systemic sarcoidosis who developed recurrent symptomatic hypercalcemia and new-onset transfusion-dependent pancytopenia. Initial evaluation revealed bone marrow fibrosis with noncaseating granulomas, raising concern for sarcoidosis-driven secondary myelofibrosis. However, repeat bone marrow biopsy demonstrated T-cell lymphoma with a SLR. Primary myelofibrosis was excluded, supporting a secondary lymphoma-driven process. The patient is currently undergoing treatment with BV-CHP with close hematologic monitoring. T-cell lymphoma-associated SLR can closely mimic sarcoidosis and should be considered in the differential, particularly in patients with atypical presentations or cytopenias. Despite similar clinical and histological features, the underlying pathophysiology differs, necessitating thorough molecular and immunophenotypic evaluation. Though rare, this entity can lead to secondary myelofibrosis, underscoring the importance of excluding a primary myeloproliferative process. Further research is needed to define optimal therapy, with BV-CHP representing a promising option in the evolving landscape of T-cell lymphoma management.

Double-unit cord blood transplantation (dCBT) is an established strategy to enhance progenitor cell dose and accelerate hematopoietic recovery when a matched sibling or unrelated donor is unavailable. While dCBT typically results in the dominance of a single unit, the persistence of donor-donor mixed chimerism is an exceptionally rare clinical phenomenon. This case report describes a unique therapeutic strategy where persistent donor-donor chimerism following dCBT was utilized to redefine the recipient's HLA profile for a subsequent successful allogeneic transplantation. A 38-year-old patient with diffuse large B-cell lymphoma experienced disease relapse following autologous peripheral blood stem cell transplantation. After achieving a second remission through salvage chemotherapy, the patient underwent dCBT due to the absence of a compatible HLA-matched donor. Fifteen months posttransplantation, the disease relapsed again; however, further salvage therapy successfully induced a third remission. Notably, HLA analysis revealed persistent donor-donor mixed chimerism with one unit maintaining clear dominance. Because no suitable matches existed for the patient's native HLA type, the dominant donor's HLA genotype was utilized as the new target for donor selection. This shift facilitated the identification of a matched allogeneic peripheral blood stem cell transplantation (allo-PBSCT) donor. The patient subsequently underwent a second allo-PBSCT based on the dominant donor's HLA profile. The procedure resulted in robust engraftment and complete donor chimerism without the occurrence of graft-versus-host disease. The patient has remained in relapse-free survival for over 4 years. This case demonstrates that in the rare event of persistent donor-donor chimerism post-dCBT, the emergent dominant HLA genotype can serve as a viable and effective target for donor selection, providing a life-saving alternative for patients who lack native HLA-matched donors.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by excessive cytokine release from activated T cells and macrophages. Primary HLH, or familial HLH (FHL), results from genetic mutations affecting cytotoxic lymphocyte function. We present a case of FHL Type 2 (FHL2) caused by compound heterozygous variants in the PRF1 gene, including one novel missense variant of p.Ala21Val (A21V). A 5-month-old boy presented with persistent fever, pancytopenia, coagulopathy, hepatosplenomegaly, and elevated ferritin, meeting the HLH-2004 diagnostic criteria. Bone marrow revealed hemophagocytosis, and NK cell activity was markedly reduced. Genetic analysis identified compound heterozygous PRF1 variants: A21V and p.Pro16Ser (P16S). Flow cytometric analysis demonstrated markedly reduced PRF1 protein expression in the patient's NK cells. The patient was treated with etoposide, dexamethasone palmitate, and cyclosporine, followed by cord blood transplantation. The patient has been in remission for over a year. The PRF1 A21V variant has not been described in the public database or the literature and is therefore considered a novel pathogenic variant for FHL2 with functional validation. Although the PRF1 P16S variant has been previously reported in the heterozygous state in an adult patient with primary HLH, our findings provide functional and clinical evidence supporting a contributory role of the P16S variant in autosomal recessive early-onset FHL2 when present in trans with the novel A21V variant. We identified a previously unreported PRF1 variant, A21V, and provided the first functional evidence of impaired perforin expression associated with A21V/P16S, highlighting the importance of functional validation of rare PRF1 variants in FHL2.

Vitamin B12 deficiency can cause severe intramedullary hemolysis and cytopenias. Myeloproliferative neoplasms (MPNs), particularly polycythemia vera (PV), are typically characterized by hyperproliferation but may remain undetected when masked by concomitant deficiencies. A 48-year-old woman presented with fatigue, weight loss, and pancytopenia. Laboratory tests showed severe macrocytic anemia, hemolysis, and markedly reduced vitamin B12 levels. Gastroscopy and antibody testing confirmed autoimmune atrophic gastritis with pernicious anemia. Bone marrow biopsy revealed hypercellularity, panmyelosis, and myelofibrosis (MF-2), initially interpreted as reactive. After vitamin B12 supplementation, cytopenias resolved; however, follow-up demonstrated polycythemia, leukocytosis, and thrombocytosis. Molecular analysis identified a JAK2 V617F mutation (variant allele fraction 40%), confirming PV with progression toward myelofibrosis. The patient was treated with phlebotomy, low-dose aspirin, and hydroxyurea, alongside continued vitamin B12 replacement. In addition, mild alpha-thalassemia was diagnosed in the course of an increasingly microcytic hypochromic blood count. Severe vitamin B12 deficiency may mask an underlying MPN, as well as other hematologic disorders like alpha-thalassemia. Close follow-up after hematologic recovery is essential to avoid delayed diagnosis of coexisting hematologic malignancies and disorders. This case presents a combination of complex and extremely rare hematological scenarios, where various hematological disorders exert conflicting influences on red blood cell indices, making diagnosis challenging.

Paraneoplastic neurological syndromes (PNS) are an uncommon complication of malignancy, characterized by autoantibody generation against neuronal structures, causing a spectrum of neurological syndromes affecting the central, peripheral, and/or autonomic nervous systems. PNS in lymphoma is exceedingly rare and there is limited evidence on the features, incidence, and severity of these neurological sequelae secondary to malignancy. Here, we report on a case of isolated diffuse motor neuropathy secondary to underlying nodular-sclerosis classical Hodgkin's lymphoma (cHL) in a 71-year-old male. This patient initially presented to the hospital with 3 months of progressive generalized weakness, weight loss, gait instability, and a rash. A broad workup revealed evidence of diffuse lymphadenopathy, which was characterized as nodular-sclerosis cHL on biopsy. Concurrent neurological workup demonstrated generalized axonal motor neuropathy on nerve conduction studies with negative serologies for a panel of paraneoplastic autoantibodies, but positive Asialo-GM1 titers, a marker of autoimmune myopathy. The patient was initiated on doxorubicin, vinblastine, and dacarbazine (AVD) for their lymphoma and received two doses of IVIg for their motor neuropathy, which did not reoccur. The patient was transitioned to brentuximab + nivolumab for 4 cycles, followed by nivolumab + AVD for 6 cycles with a complete response and no evidence of disease. Asialo-GM1-associated isolated diffuse motor neuropathy in Hodgkin's lymphoma has not been previously reported in the literature. In this case report, we review the 2021 updated diagnostic criteria for the diagnosis of paraneoplastic neurological syndromes in the context of this patient presentation to highlight an instance where these guidelines do not fully capture the wide spectrum of PNS.

Wunderlich syndrome (WS) is a spontaneous, nontraumatic intrarenal or perirenal hemorrhage most commonly related to renal neoplasms, vascular disorders, infection, cyst rupture, or anticoagulation. Clinical severity ranges from self-limited bleeding to hemorrhagic shock. We report a 58-year-old woman with triple-negative myelofibrosis (MF) who was started on hydroxyurea (HU) 500 mg/day and low-dose acetylsalicylic acid (ASA). On Day 60, she presented with bilateral perirenal and intrarenal hemorrhage confirmed by contrast-enhanced abdominal computed tomography. ASA was discontinued and bleeding ceased spontaneously. One month later, she represented with recurrent bilateral hemorrhage without ASA exposure and marked neutrophilic leukocytosis. Concomitant purpuric skin lesions, positive antinuclear antibodies (ANA, 1:160), and low C3 levels raised suspicion for a HU-associated vasculitic process; HU was discontinued. Coagulation parameters at the time of bleeding (INR: 1.2, aPTT: 26.4 s, fibrinogen: 348 mg/dL, and D-dimer: 0.6 μg/mL) were not consistent with disseminated intravascular coagulation. Despite supportive management, the patient's condition deteriorated and she died shortly thereafter. The exact cause of death could not be definitively determined. To our knowledge, this is the first reported case of WS in a patient with MF receiving HU therapy. Clinicians should consider WS in HU-treated patients presenting with acute flank pain or hematuria and evaluate for potential vasculitic features.