Hematological malignancy (HM) is developed in 2–6% patients with primary mediastinal germ cell tumor (MGCT). Symptoms of HM associated with MGCT usually appear after diagnosis of MGCT. Patients with MGCT underlying HM have poor prognosis. We report an extremely rare autopsy case of simultaneous presentation of MGCT, myelodysplastic neoplasm (MDS) with low blasts, and myeloid sarcoma (MS). A 27-year-old man presented with intermittent fever, general fatigue, and cough. Computed tomography revealed 11 cm mass in anterior mediastinum, hepatosplenomegaly, and gastric, pericholedochal, and mesenteric lymphadenopathies. The mass compressed the left pulmonary artery. Laboratory examination revealed thrombocytopenia (59,000 /mm³). Serological tests revealed elevated alpha-fetoprotein 7,219 ng/mL and human chorionic gonadotropin 899 IU/L. Bone marrow aspiration smear showed presence of micromegakaryocytes and blast count of 1.2%. G-banding detected monosomy 13 and complex karyotype. The autopsy revealed that MGCT was mainly composed of teratoma and also included yolk sac tumor, seminoma, and choriocarcinoma components. Transformation to acute myeloid leukemia was not observed in the bone marrow but CD33 and MPO-positive immature myeloid blasts proliferated in the lymph nodes, liver, spleen, and small intestine. Loss of p53 expression was observed in bone marrow and extramedullary immature myeloid blasts. Next gene sequencing detected TP53 c.919+3del splice site variant and KRAS N116H. It is important to consider HMs when extramediastinal lesions or thrombocytopenia appear in patients with MGCT.

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Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the management of relapsed/refractory large B-cell lymphoma. However, evidence in the ultra-elderly population remains scarce. We report a 90-year-old woman with relapsed/refractory diffuse large B-cell lymphoma transformed from follicular lymphoma who received lisocabtagene maraleucel. Despite advanced age, preserved cognition, intact instrumental activities of daily living, and acceptable organ reserve supported her candidacy for CAR T-cell therapy. Cytokine release syndrome (CRS) developed as grade 1 (day 1, 38.0 °C) and grade 2 (day 3, hypoxemia to 6 L/min), which resolved after early tocilizumab and dexamethasone. No immune effector cell–associated neurotoxicity syndrome or infectious complications occurred. Grade 2–4 cytopenia persisted transiently but was managed with supportive care, and she was discharged on day 28. To our knowledge, this represents the first reported case of a nonagenarian Asian patient successfully treated with CAR T-cell therapy, highlighting the feasibility and tolerability of this approach and emphasizing the importance of geriatric assessment and prompt CRS management for safe delivery in the very elderly.

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Objective

This study aims to review the clinicopathological features, molecular profiles, and clinical behavior of gastric LCH to increase diagnostic accuracy and improve the understanding of its prognosis.

Methods

We analyzed five cases of gastric LCH and integrated clinical, endoscopic, and pathological data. Diagnoses were confirmed via immunohistochemistry (S-100, CD1a, and Langerin). BRAF-V600E mutation status was assessed by PCR in three patients. A literature review of 17 additional cases was included for a comprehensive analysis.

Results

Patients presented with nonspecific symptoms such as abdominal pain. Endoscopy predominantly revealed solitary polyps (<1 cm) or mucosal thickening, primarily in the gastric body. Histology revealed characteristic neoplastic cells with grooved nuclei and eosinophilic cytoplasm, accompanied by eosinophil infiltration. All patients were positive for S-100, CD1a, and Langerin. The BRAF-V600E mutation was detected in all three tested cases. Systemic involvement occurred in two patients. Treatment ranged from surveillance to chemotherapy. All patients were alive after follow-up (8–62 months), with most patients showing no progression.

Conclusion

Gastric LCH typically presents as a small, solitary polyp. S-100, CD1a, and Langerin positivity was observed by immunohistochemistry. The high frequency of BRAF-V600E mutations provides a diagnostic adjunct and potential therapeutic target. Gastric LCH patients have a good prognosis and long overall survival when the cancer is a localized lesion. However, systemic involvement may necessitate chemotherapy, and regular follow-up is recommended.

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy with no established standard treatment. Recently, the combination of venetoclax (VEN) and azacitidine (Aza) has shown promising efficacy in elderly or unfit patients; however, clinical data in Japanese patients remain limited. We report two Japanese cases with BPDCN that responded favorably to VEN plus Aza therapy. The first case involved a 50-year-old man who relapsed shortly after Hyper-CVAD/MA therapy with leukemic transformation. Despite requiring dose reductions due to prolonged cytopenia and infections, he achieved a complete response after eight cycles of VEN plus Aza. The second case was an 81-year-old man with widespread skin and bone marrow lesions. He showed a marked clinical response after only 7 days of treatment, although therapy was discontinued due to COVID-19 infection. Both cases demonstrate that VEN plus Aza therapy can induce rapid and clinically meaningful responses even in short or attenuated regimens in patients with refractory or elderly BPDCN. However, cytopenias and infections are significant limitations, warranting that individualized dosing may be necessary depending on patient characteristics, including ethnicity and body size. Our findings support the consideration of VEN plus Aza as a feasible therapeutic option for patients with BPDCN.

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Pseudoprogression comprises a transient increase in tumor burden caused by immune cell infiltration or inflammatory responses after immunotherapy, including chimeric antigen receptor T-cell therapy and the use of bispecific antibodies. Although pseudoprogression has been reported following several immunotherapy types, cases of pseudoprogression associated with elranatamab remain rare. Herein, we describe the case of a 67-year-old woman with relapsed/refractory multiple myeloma who developed pseudoprogression of extramedullary lesions following treatment with elranatamab. On day 4 of therapy, the patient presented with left periorbital swelling and lagophthalmos. Computed tomography (CT) revealed the enlargement of multiple extramedullary lesions in this patient. Dexamethasone administration improved the ocular symptoms. Lagophthalmos recurred after administration of the second dose of elranatamab but responded to dexamethasone. On day 13, a CT-guided biopsy of the chest wall lesion revealed dense T cell infiltration within the tumor tissue, consistent with pseudoprogression rather than true progression. The patient’s serum M-protein levels decreased within 2 weeks of treatment initiation. At 2 months, follow-up CT demonstrated a reduction in the extramedullary lesions, and the patient achieved a very good partial response. This case highlights that pseudoprogression may occur during elranatamab therapy, similar to that which may occur with other T-cell-redirecting immunotherapies. Differentiating pseudoprogression from true progression is clinically important, as misinterpretation may lead to premature discontinuation of effective therapy. Careful clinical evaluation, integration of imaging findings, and histopathological confirmation (whenever feasible) are essential for the appropriate management of such cases.

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A 73-year-old woman presented with cervical lymphadenopathy. A biopsy of the affected lymph node showed the diagnosis of adult T-cell leukemia/lymphoma (ATLL). While treatment was planned, she developed rapid-onset consciousness disturbance and gait disorder 1 week before the initiation of therapy, leading to emergency hospitalization. Computed tomography showed a hypodense lesion in the midbrain, and a cerebrospinal fluid analysis showed ATLL cells, resulting in a diagnosis of central nervous system infiltration of ATLL. High-dose methotrexate plus cytarabine therapy was administered. However, this therapy was ineffective, and the patient died on hospital day 21. An autopsy showed that the midbrain tumor was an Epstein–Barr virus-positive primary central nervous system lymphoma. Although there have been reports of primary central nervous system lymphoma developing during the treatment course of ATLL, to the best of our knowledge, this is the first reported case of concurrent onset of both diseases.

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Extranodal NK/T-cell lymphoma (ENKTL) is an Epstein–Barr virus (EBV)-positive lymphoma of the NK- or cytotoxic T-cell lineage. According to the World Health Organization Classification of Hematolymphoid Tumors, Fifth Edition (WHO-HAEM5), EBV-positive cases lacking cytotoxic molecules cannot be classified as ENKTL. To the best of our knowledge, this is the first documented case of primary gastric EBV-positive T-cell lymphoma lacking the expression of cytotoxic molecules. A 76-year-old woman initially presented with a disease confined to the stomach, with subsequent contiguous extension into the duodenum. Biopsies revealed small- to medium-sized atypical T cells with pale cytoplasm and irregularly folded nuclei, as well as intravascular infiltration. Tumor cells were positive for CD3, TCRβF1, and CD4 and negative for CD56, TIA-1, granzyme B, perforin, and PD-L1. EBV-encoded RNA in situ hybridization highlighted neoplastic T cells. These findings did not fulfill the criteria for any T/NK cell entity of WHO-HAEM5 including ENKTL and peripheral T-cell lymphoma not otherwise specified (PTCL, NOS). Targeted sequencing revealed TET2 multihit mutations, suggesting clonal hematopoiesis–linked pathogenesis. Given the patient's age and tumor location, we administered a reduced dose of DeVIC, followed by radiotherapy, achieving partial remission. This case expands the spectrum of EBV-associated T-cell lymphomas and highlights the need for additional cases to refine the classification and management.

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Hodgkin-like ALK-negative anaplastic large cell lymphoma (ALCL) is a morphologically challenging variant that closely resembles classical Hodgkin lymphoma (CHL), particularly in cytological specimens. Fine-needle aspiration (FNA) cytology of Hodgkin-like ALCL has been rarely reported; therefore, detailed cytomorphological analysis is valuable for diagnostic practice and education. We report a rare case of Hodgkin-like ALCL in a 75-year-old Japanese man who presented with a progressively enlarging right axillary mass. Initial FNA cytology revealed scattered large atypical cells with Hodgkin and Reed–Sternberg-like morphology in an inflammatory background, strongly suggesting CHL. However, retrospective review identified subtle yet important diagnostic clues that had initially been overlooked, including nuclear irregularities and atypia in small- to medium-sized background cells, distinctive distribution patterns of atypical cells, and the presence of vascular stromal fragments.

Histopathologic examination confirmed ALCL with a characteristic immunophenotype (CD30+, CD15+, PAX5−, Granzyme B+, CD4+, CD25+, EMA+, ALK−). The absence of PAX5 expression was a key discriminator, effectively excluding CHL despite the striking morphological resemblance. This case highlights the diagnostic pitfalls in differentiating Hodgkin-like ALCL from CHL in cytological preparations and emphasizes the importance of systematically evaluating background cellular composition beyond the conspicuous large atypical cells. Careful assessment of nuclear morphology and cell distribution patterns can provide valuable diagnostic clues to prevent misdiagnosis. This rare cytological presentation offers critical educational insights for cytopathologists and underscores the diagnostic value of FNA cytology, particularly when integrated with immunophenotypic analysis and retrospective morphological review in evaluating morphologically challenging lymphoid malignancies.

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