Jiang, Liuyan

The MN1::ETV6 gene fusion resulting from t(12;22)(p13;q12) has been rarely reported in myeloid neoplasms. We describe a 69-year-old male with newly diagnosed acute myeloid leukemia (AML) with erythroid differentiation and t(12;22)(p13;q12) demonstrated by conventional chromosome studies. Subsequent fluorescence in situ hybridization studies demonstrated a balanced ETV6 gene rearrangement (at 12p13). To further characterize this translocation, whole-genome sequencing was performed which confirmed t(12;22) with breakpoints involving the MN1 and ETV6 genes. Herein, we describe our case and review the literature to summarize the clinical and laboratory findings in patients with this rare but recurrent MN1::ETV6 gene fusion observed in myeloid neoplasms. Importantly, this case expands the clinical spectrum associated with the MN1::ETV6 gene fusion to include AML with erythroid differentiation. Lastly, this case demonstrates the importance of moving toward more comprehensive molecular testing to fully characterize the driver events in neoplastic genomes.

7575 Background: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is a rare and aggressive Epstein-Barr virus driven lymphoma, which is most prevalent in East Asia and Latin America. There have been very few large studies outside of Asia. Therapeutic and survival outcomes have not been well characterized in the US. Methods: The National Cancer Database was queried for patients who were diagnosed at aged ≥18 years between 2004 and 2019. Patients who were lost to follow-up were excluded. Kaplan-Meier and multivariate Cox regression analyses were performed. Results: The cohort consists of 2,036 evaluable patients with 68% males, 74% Caucasian, 22% Hispanic Caucasian and 9% African American. The median age at diagnosis was 54 (18-90) years. The median follow up was 71 months (95% CI 66.8-75.7). Early-stage disease (I and II) was reported in 64% while advanced stage disease (III and IV) constituted 36%. Treatment groups include chemotherapy alone (29%), radiation alone (10%), combined modality therapy (CMT-chemoradiation) (42%). The median overall survival (OS) for the whole cohort was 27 months (95% CI 20.6-33.7). Median OS was better in patients with early stage compared to advanced stage disease (90 vs. 6 months, P < 0.001). Among therapeutic groups in early-stage disease, CMT (N = 616) had significantly better median OS than radiation alone (N = 152) or chemotherapy alone (N = 168) (194 vs. 34 vs. 14 months, P < 0.001). No significant difference was seen between radiation alone and chemotherapy alone (P = 0.617). Among patients treated with CMT, chemotherapy-first CMT (N = 134) had better OS than radiation-first CMT (N = 347) (median OS not reached vs. 194 months, P = 0.017). In the advanced stage disease, chemotherapy-treated patients (N = 418) had better median OS compared to patients who did not receive chemotherapy (N = 103) (7.6 vs 1.3 months, P < 0.001). Among patients who received chemotherapy, patients consolidated with SCT (N = 59) had better median OS compared to the patients who received chemotherapy only (N = 353) (63 vs 6 months, P < 0.001) In multivariate analysis, factors associated with worse OS were age (HR 1.021 95% CI 1.015-1.026; P < 0.001) and B-symptoms (HR 1.463 95% CI 1.276-1.678; P < 0.001). Whereas factors associated with better OS were early stage (HR 0.450 95% CI 0.387-0.524, P < 0.001), radiation therapy (HR 0.526 95% CI 0.458-0.603, P < 0.001) and chemotherapy (HR 0.546 95% CI 0.473-0.630, P < 0.001). Conclusions: The study represents one of the largest studies on ENKTL in the US. Early-stage disease is highly curable with CMT with chemotherapy-first sequencing being superior to radiation-first sequencing. Advanced stage disease is associated with extremely poor prognosis overall but is associated with a significant improvement in OS with consolidative SCT with possible role of consolidative RT in advanced stage.

Objectives: The diagnosis of lymphoma on cytologic preparations and core needle biopsies (CNBs) is often challenging due to limited material that precludes additional ancillary testing for accurate classification. We describe our institutional experience with patients who ultimately received a diagnosis of lymphoma using cytologic preparations and CNB material along with additional ancillary testing. Material and Methods: All patients whose cytology material (fluids, cytologic smears, and cell block) and CNB resulted in a diagnosis of lymphoma, atypical lymphoid population, or suspicious for lymphoma were retrieved. Diagnoses of lymphoma followed the established nomenclatures of the World Health Organization (WHO). For all cases, the ancillary test profiles were captured and summarized. Results: Of 389 cases identified, 17 (4.4%) were diagnosed as atypical lymphoid cells and 31 (7.9%) were suspicious for lymphoma resulting in an indeterminate rate of 12.3%. The rest of the malignant cases (341; 87.7%) were classified using 2017 WHO lymphoid classification system. Six low-grade and 26 high-grade B-cell lymphomas were not further classified because of limited tissue. B-cell lymphomas were the largest category (73.0%): Primarily diffuse large B-cell lymphoma (21.4%), followed by follicular lymphoma (17.5%) and chronic lymphocytic leukemia/small lymphocytic lymphoma (10.9%). A total of 140 cases (36.0%) had flow cytometry results, but 30 specimens (21.4%) were insufficient. Cytogenetic and molecular studies were performed for 78 cases (20.0%). Conclusion: Full classification of lymphomas is possible with combined cytologic preparations and CNB material and it is an attractive first sampling modality in the diagnostic process for this disease group.

Abstract Extramedullary disease in acute myeloid leukemia (AML), also known as myeloid sarcoma (MS), is an uncommon presentation of de novo AML. We analyzed medical records of patients in the Mayo Clinic database spanning between 1996 and 2021 who were diagnosed with de novo extramedullary AML. Survival outcomes were analyzed using Kaplan-Meier and Cox-proportional hazard models for univariate and multivariate analysis, respectively. With a median follow-up of 20.7 months, 83 patients with de novo MS were identified; 49 presented with synchronous MS and 34 with isolated MS. Next generation sequencing (NGS) revealed RTK-RAS pathway mutations in 44% of patients. Median overall survival (OS) was 25.3 months and 17.8 months in isolated and synchronous MS, respectively (p = 0.49). Variables associated with improved OS on univariate analysis included treatment with intensive chemotherapy (p < 0.001), normal or favorable risk karyotype (p = 0.001), age less than 60 years (p = 0.001), and a complete response to treatment at extramedullary sites (p < 0.0001). On multivariate analysis, normal or favorable risk karyotype (p = 0.001), age less than 60 (p = 0.01), and a complete extramedullary response (p = 0.001) were associated with improved OS. Localized therapy did not provide added survival benefit in isolated MS. Genomic stratification, age, and extramedullary site response are predictive of survival outcomes.

Abstract Intravascular lymphoma (IVL) is a rare extranodal non‐Hodgkin lymphoma. We performed a retrospective analysis of 55 IVL patients who were treated at our institution 2003–2018. Median age at diagnosis was 68 years, and 64% were males. The most frequent presenting symptoms were skin rash 43% and weight loss 30%. MRI brain on IVL patients with CNS involvement (CNS‐IVL) showed multifocal involvement in 76% (13/17). 89% (17/19) of non‐CNS‐IVL patients with abnormal FDG‐PET had biopsy of an avid lesion resulting in definitive diagnosis. The top diagnostic biopsy site was the bone marrow (45%). 56% had multiorgan involvement. Based on CNS involvement, 36.5% (20/55) had CNS‐IVL and 63.5% (35/55) had non‐CNS‐IVL. CNS‐IVL group consists of clinically isolated CNS involvement (CNS‐only IVL) (22%;12/55) and mixed clinical CNS and peripheral site involvement (M‐IVL) (14.5%; 8/55). Non‐CNS‐IVL group consists of clinically isolated skin involvement (skin‐only IVL) (9%; 5/55) and peripheral IVL with or without skin involvement (P‐IVL); (54.5%; 30/55). Skin involvement was predominantly in the lower extremities. Pathologically, 89% (48/54) were B‐cell IVL. Rituximab + high‐dose methotrexate‐based regimen were used in 75% (12/16) of CNS‐IVL patients and RCHOP in 60% (17/28) of non‐CNS‐IVL patients. Estimated 5‐year progression free survival (PFS) and overall survival (OS) for the entire cohort were 38.6% and 52%, respectively. Skin‐only IVL was associated with excellent survival. Platelet count <150x10 9 /L, age > 60Y, and treatment without Rituximab were poor prognostic factors. Further research is necessary to identify novel therapies.

Polarization of tumor associated macrophages (TAMs) has been shown to have prognostic significance in different cancer types. This study evaluates the macrophage subtypes that predominates in GMF. Cases of GCTCL from 2007–2020 were identified (n = 6), clinical data was extracted from the electronic medical record, and all pathology slides were reviewed to confirm the diagnosis. Immunohistochemistry (IHC) studies were performed to characterize M1 and M2 macrophage polarization. CD68 (PGM1), pSTAT1, and CD163 were used as pan macrophage, M1, and M2 markers, respectively. The macrophages with positive staining at hot spot per high power field were counted and recorded for data analysis. The average age of patients was 60.5 years [range, 21–78], five patients (83%) were women and 1 (17%) was a man. Five patients were Caucasian (83%), and 1 was Black/African American (17%). Two patients had late stage GMF with M2 (CD163) predominance and the other three had early stage GMF with M1 (pSTAT1) predominance. Our study suggests that macrophage polarization present in GMF tends to be M1 in early stages and M2 in advanced stages. Additional studies are needed to further elucidate the microenvironment of macrophages present in GMF. Such findings may lead to prognostic and therapeutic advances in GMF.

AbstractExtramedullary multiple myeloma is seen in advanced and aggressive disease and occurs due to plasma cell infiltration of sites other than the bone marrow. Myelomatous ascites or pleural effusion is seen in less than 1% of cases and can be differentiated from infectious etiologies based on fluid cytology.

AbstractWaldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is often differentiated from myeloma based on the presence of lytic bone lesions (LBL). However, WM/LPL can present with LBL, and management is poorly understood. We describe a case of an 81‐year‐old woman with LPL who presented with LBL and was successfully treated with chemoimmunotherapy.

Extramedullary multiple myeloma is seen in advanced and aggressive disease and occurs due to plasma cell infiltration of sites other than the bone marrow. Myelomatous ascites or pleural effusion is seen in less than 1 % of cases and can be differentiated from infectious etiologies based on fluid cytology.