We present the case of a 60-year-old Caribbean man with no significant past medical history who presented to the emergency department with a three-week history of progressive, diffuse abdominal pain associated with early satiety and unintentional weight loss. Vital signs were stable, and physical examination revealed abdominal distension and diffuse tenderness without peritoneal signs. Laboratory studies were notable for elevated lactate dehydrogenase and mild leukocytosis. Computed tomography followed by PET-CT imaging demonstrated multiple nodular soft tissue densities with increased fluorine-18 fluorodeoxyglucose (18F-FDG) uptake throughout the mesentery, peritoneum, and bilateral pleural surfaces, raising concern for peritoneal lymphomatosis. An ultrasound-guided biopsy of an omental implant was performed, revealing large atypical lymphoid cells positive for CD3, CD2, and CD4, and negative for CD5, CD7, and CD8, with a Ki-67 proliferation index of 90%, consistent with an aggressive peripheral T-cell lymphoma. Peripheral blood RT-PCR returned positive for human T-cell lymphotropic virus type 1 (HTLV-1), aligning with the diagnosis of acute adult T-cell leukemia/lymphoma (ATLL), stage IV. The patient's clinical course was rapidly progressive and marked by complications including spontaneous tumor lysis syndrome, recurrent episodes of malignant small bowel obstruction, and gram-negative bacteremia. While preparing for treatment with dose-adjusted etoposide phosphate, vincristine sulfate (Oncovin), cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunomycin) (EPOCH) chemotherapy, he suffered a cardiac arrest during central venous catheter placement. Despite resuscitation efforts, he sustained an anoxic brain injury and died 32 days after the initial presentation. This case highlights an aggressive presentation of ATLL with peritoneal involvement and underscores the challenges of rapid disease progression and acute complications, as well as the importance of considering endemic exposure history, utilizing PET-CT for identifying extranodal disease, and rapidly confirming diagnosis through biopsy.

Classification of cases of diffuse large B-cell lymphoma (DLBCL)/high-grade B-cell lymphoma (HGBL) with MYC and BCL6 rearrangements, referred to here as BCL6 double-hit lymphoma (DHL), is controversial. We assessed 60 cases of BCL6-DHL and compared this cohort to 224 cases of DHL with MYC and BCL2 rearrangements (BCL2-DHL) and 217 cases of DLBCL not otherwise specified. Compared with the DLBCL cohort, patients with BCL6-DHL had more aggressive clinical features such as frequent extranodal involvement, high-stage disease, a high International Prognostic Index score, and an elevated serum lactate dehydrogenase level (P < .01 for all). Compared with the BCL2-DHL cohort, patients with BCL6-DHL had similarly aggressive clinical features but a lower frequency of germinal center B-cell (GCB) immunophenotype and MYC and BCL2 double expression. Patients with BCL6-DHL showed overall survival (OS) intermediate between patients with DLBCL and BCL2-DHL. Following induction with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, patients with BCL6-DHL demonstrated poor OS similar to patients with BCL2-DHL and worse OS than that of patients with DLBCL (P = .024). However, among patients who received rituximab, etoposide phosphate, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH), there was no significant difference in OS among the 3 groups (P = .146). Gene expression profiling showed that 60% of BCL6-DHL cases had a double-hit (DH)-like signature compared with 10% of DLBCL-GCB and 93% of BCL2-DHL cases. The DH-like signature in BCL6-DHL cases was associated with a GCB immunophenotype. Based on these data, we suggest that BCL6-DHL cases are clinically more aggressive than DLBCL and patients may benefit from a more aggressive therapy than R-CHOP. The data also suggest that BCL6-DHL, as currently defined, is heterogeneous and that neoplasms with a GCB immunophenotype are more likely to have a DH-like signature and behave more aggressively. Last, we suggest that BCL6-DHL cases deserve to be recognized separately in a lymphoma classification to facilitate further understanding of these neoplasms and for optimal patient management.

IntroductionEtoposide phosphate is a chemotherapeutic agent used to treat various malignant neoplasms. Hypersensitivity reactions may occur with its use, and in rare cases, an anaphylactic reaction can manifest. Available options for patients experiencing hypersensitivity reactions include premedication, changing treatment, or undergoing desensitization. Various pediatric desensitization protocols have been described, ranging from six to fifteen steps, while published adult cases are rare.Case ReportWe report the case of a 61-year-old woman with small-cell lung cancer and brain metastases. In November 2019, she underwent the second cycle of cisplatin and etoposide phosphate treatment. While receiving etoposide phosphate, she experienced dyspnea and suffered a cardiorespiratory arrest, leading to cardiopulmonary resuscitation and subsequent admission to the Intensive Care Unit. Her acute tryptase levels were notably elevated at 18 µg/L (compared to a baseline tryptase level of 6,6 µg/L) during the reaction.Case ManagementWe implemented a 16-step desensitization protocol (without premedication) under close monitoring in an intermediate care unit. The protocol was successfully executed over three cycles until tumor progression mandated a modification in systemic treatment.DiscussionTo our knowledge, this is the first documented case of successful desensitization to etoposide phosphate in a patient who experienced cardiac arrest during a hypersensitivity reaction. Although protocols of varying lengths have been published, we emphasize the importance of individualizing each protocol to fit the severity of the reaction and the resources and experience of each unit.

Seven polyketides, including an undescribed depsidone (1) and six previously reported 3,6,8-trihydroxy-1-methylxanthone (2), 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (3), methyl3-chloro-6-hydroxy-2-(4-hy-droxy-2-methoxy-6-methylphenoxy)-4- methoxybenzoate (4), xylarianin A (5), 4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-hydro-xymethyl-2-cyclohexen-1-one (6) and alternariol (7), have been isolated from cultures of the mangrove-derived fungus Penicillium robsamsonii HNNU0006. The structure of compound 1 was elucidated by extensive spectroscopic analysis and X-ray crystallography. Furthermore, all the compounds were evaluated their cytotoxic activities, and compounds 1 and 7 showed weak cytotoxicity against two cell lines Vero and A549 with IC50 values ranging from 95.6 and 296.5 μM, relative to the positive control Etoposide phosphate with IC50 values of 24.5 and 18.7 μM, respectively.

E-cigarette-/vape-associated lung injury (EVALI) refers to damage to lung tissue occurring as a result of e-cigarette utilization or via vaping of inhaled nicotine products. Vaping refers to the practice of inhaling an aerosol derived from heating a liquid or gas containing substances such as nicotine, cannabinoids, flavoring, or additives. Battery-operated e-cigarettes or vape pens are the vessels commonly used in this practice. EVALI, first described in the literature in 2019, has a non-specific course, presenting initially with cough and dyspnea. It can progress, however, to interstitial lung disease or result in damage to the lung parenchyma with concomitant inflammation and fibrosis. Imaging findings reflect the development of this inflammation and fibrosis, often visualized as ground-glass opacities on computed tomography (CT) scans. Formal biopsies are not required to make the diagnosis of EVALI, and thus, a gap exists in the scientific literature with regard to the pathology of lungs exposed to non-tetrahydrocannabinol (THC) e-cigarettes. The following case details the clinical course of a 62-year-old male who presented to the outpatient pulmonology office with symptomology and exposure history consistent with EVALI, unique in presentation due to the timeline of his disease development. The patient initially presented to the clinic for the evaluation of a non-productive cough and exertional dyspnea beginning one year ago, with an associated new home oxygen requirement of 2 liters via nasal cannula. The patient's past medical history was relevant for diffuse large B-cell lymphoma treated with the chemotherapeutic regimen that consists of etoposide phosphate, prednisone, vincristine sulfate (Oncovin), cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), and rituximab, commonly known as EPOCH-R, as well as a social history relevant for a 35-pack-year smoking history. On further questioning, the patient revealed that following cessation of cigarette smoking, he began using non-THC e-cigarettes daily and had been doing so for 10 years prior to symptom onset. Imaging and biopsy findings consisted of a CT of the chest demonstrating concern for interstitial lung disease and an open lung biopsy demonstrating diffuse alveolar damage with eosinophilia. Given the patient's history, clinical symptoms, and imaging findings, a diagnosis of EVALI was established. This case was documented not only to increase awareness of the rising incidence of EVALI as the use of e-cigarettes and vapes becomes increasingly popular but also to further understand the inhalational injury sustained from non-THC e-cigarettes and other inhalational practices.

The occurrence of a secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) after CAR T-cell infusion is very rare and mostly fatal. Treatment recommendations for such a complication are not yet established. Here, we report the dramatic recovery of HLH/MAS following tisagenlecleucel infusion in a young patient with relapsed acute lymphoblastic leukemia using etoposide phosphate (EP). We propose that monitoring for the occurrence of HLH/MAS should be part of surveillance after CAR T-cell infusion and that EP treatment appears to be useful to control this severe and rare complication.

Gastrosplenic fistula is a rare and potentially fatal clinical entity unknown to most healthcare providers. Its diagnosis and management are challenging; and addressing it too late can have devastating consequences for patients. To increase awareness about this pathology, we hereby present a case of asymptomatic gastrosplenic fistula arising from a diffuse large B cell lymphoma in a 60-year-old Caucasian man with no significant medical history. The patient was successfully treated with open en-bloc splenectomy and partial gastrectomy. The patient was discharged from the hospital 3 days after the surgery. At 1-month postoperatively, the patient was asymptomatic and presented no complication of the surgery. He went on to finish six cycles of chemotherapy (R-EPOCH, rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride) and achieved complete metabolic response. At 2 years after the surgery, the patient remains asymptomatic and presents no sign of disease recurrence.

Medulloblastoma is the most common high-grade brain tumor in childhood. Medulloblastomas with c-myc amplification, classified as group 3, are the most aggressive among the four disease subtypes resulting in a 5-year overall survival of just above 50%. Despite current intensive therapy regimens, patients suffering from group 3 medulloblastoma urgently require new therapeutic options. Using a recently established c-myc amplified human medulloblastoma cell line, we performed an in-vitro-drug screen with single and combinatorial drugs that are either already clinically approved or agents in the advanced stage of clinical development. Candidate drugs were identified in vitro and then evaluated in vivo. Tumor growth was closely monitored by BLI. Vessel development was assessed by 3D light-sheet-fluorescence-microscopy. We identified the combination of gemcitabine and axitinib to be highly cytotoxic, requiring only low picomolar concentrations when used in combination. In the orthotopic model, gemcitabine and axitinib showed efficacy in terms of tumor control and survival. In both models, gemcitabine and axitinib were better tolerated than the standard regimen comprising of cisplatin and etoposide phosphate. 3D light-sheet-fluorescence-microscopy of intact tumors revealed thinning and rarefication of tumor vessels, providing one explanation for reduced tumor growth. Thus, the combination of the two drugs gemcitabine and axitinib has favorable effects on preventing tumor progression in an orthotopic group 3 medulloblastoma xenograft model while exhibiting a favorable toxicity profile. The combination merits further exploration as a new approach to treat high-risk group 3 medulloblastoma.