Menke, David M.

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.

Abstract Introduction: Intravascular lymphoma (IVL) is an extra nodal non-Hodgkin lymphoma with tropism for vascular endothelium. It is characterized by growth of large cells within the lumen of small to medium sized blood vessels. Central nervous system (CNS) and skin are predominantly involved. This report represents a retrospective single-institution review of IVL. Methods: We identified patients (pts) with IVL evaluated at Mayo Clinic Cancer Center between January 2003 and December 2018. Demographic, clinical, radiologic, pathologic, and therapeutic data were extracted. Statistical analysis of overall survival (OS) and progression free survival (PFS)] was performed using Kaplan-Meier method. Results: Total number of pts was 55; 22% (12/55) had CNS-only IVL, 14.5% (8/55) had CNS and non-CNS IVL, and 63.6% (35/55) had non-CNS IVL. Eighty seven percent (47/54) pts were B cell type, 11% (6/54) were T cell type, one pt had NK cell type IVL and another was unknown. Four pts were diagnosed by autopsy. Median age at diagnosis was 68 years (range, 40-85). Sixty-four percent were males. ECOG performance status was &lt;2 in 66%. The median follow-up time from diagnosis was 63 months [CI 95%, 9-NR], and 47% (26/55) were alive. The most common diagnostic biopsy sites were bone marrow (BM) 45% (25/55), skin 25% (14/55), and brain 29% (16/55). Twenty-nine patients had a PET scan. Seventy nine percent (23/29) had abnormal PET findings, with mean SUV of 8.6 (range 2.5-19.1). Of the 35 pts with non-CNS IVL, 76% (16/21) had abnormal PET; furthermore, the diagnosis was made with biopsies of the following sites: bone marrow 54% (19/35), skin 40% (14/35), lung 14% (5/35), liver 5.7% (2/35), spleen 2.8% (1/35), and omentum 2.8% (1/35). Forty-six percent (13/28) received CNS prophylaxis and ten percent (3/55) had relapse in CNS. Two out of the three pts who had CNS relapse had received CNS prophylaxis. The median time to CNS relapse in non-CNS IVL was 9 months. The most common first-line regimen was high-dose methotrexate+ rituximab containing regimen 62% (10/16) in IVL with CNS involvement and RCHOP (60%) (17/28) in non-CNS IVL. Seventeen percent of (8/48) pts received autologous stem cell transplant (ASCT) and 63% (5/8) pts were transplanted in first complete remission (CR1), and 3 pts after the first relapse. Median OS (mOS) for the whole cohort was 57 months, [CI 95%, 9-NR], and median PFS was 7 months [CI 95%, 2-NR]. There was no significant difference in mOS between groups; CNS-only IVL- 9 months (CI 95%, 1-NR), non-CNS IVL -62 months (CI 95%, 20-NR) vs combined CNS and non-CNS IVL- 4 months (CI 95%, 3-NR). mOS for those who received ASCT in CR1 was not reached (CI 95%, 10-NR) vs 51 months in non-transplant group (CI 95%, 3-NR) p=0.24. In pts with non-CNS IVL, there was no significant difference in mOS between CNS prophylaxis subgroup (NR: CI 95%, 57-NR) vs no-CNS prophylaxis subgroup (20 months: CI 95%, 0-NR), p=0.12. In those with CNS IVL mOS for early diagnosis (0-30 days from symptom onset to diagnosis was NR (CI 95%, 3-NR) vs mOS for late diagnosis (&gt;30 days {31-14,440})-5months (CI 95% 1-NR), p=0.29]. Conclusion: 1. BM was most frequently involved in our patients. We suggest that BM biopsy should be part of diagnostic testing when IVL is suspected. 2. Most cases are of B-cell linage, consistent with reported literature. All non-B cell cases were in non-CNS locations. 3. PET scans were abnormal in more than 70% of cases indicating that this imaging modality is vital in the diagnosis due to odd location and small size of lesions. 4.Overall prognosis in the literature was poor with most patients surviving &lt;1 year. Our cohort has mOS of 57 months. The reason(s) for better survival in our cohort could not be definitively determined. 5. CNS involvement had an overall trend towards poor prognosis; however, those diagnosed early had better outcomes; this did not reach statistical significance due to small sample size. 6. mOS was not reached for those transplanted CR1. There was a trend towards a better survival associated with CNS prophylaxis versus no prophylaxis in non-CNS IVL. 7. We suggest that CNS-centric therapeutic approach and intensive consolidation with ASCT should be considered in managing IVL. Figure 1 Figure 1. Disclosures Nowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Habermann: Incyte: Other: Scientific Advisory Board; Seagen: Other: Data Monitoring Committee; Tess Therapeutics: Other: Data Monitoring Committee; Morphosys: Other: Scientific Advisory Board; Loxo Oncology: Other: Scientific Advisory Board; Eli Lilly & Co.,: Other: Scientific Advisor. Witzig: Karyopharm Therapeutics, Celgene/BMS, Incyte, Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm Therapeutics: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Tun: Mundipharma, Celgene, BMS, Acrotech, TG therapeutics, Curis, DTRM: Research Funding; Gossamer Bio, Acrotech: Consultancy.

Primary cutaneous γδ T-cell lymphoma (PCGD-TCL) is an extremely rare and aggressive T-cell neoplasm with complex heterogeneity. We present a series of two patients who presented with firm, subcutaneous nodules and were diagnosed with PCGD-TCL. In both cases, biopsies demonstrated a both superficial and deep adnexotropic infiltrate comprised of angiocentric, medium- to large-sized atypical lymphocytes. The infiltrate extended into the panniculus. Immuno–histochemical stains highlighted atypical lymphocytes that expressed CD3, CD8 and CD56 but were negative for EBV ISH. A brisk histiocytic response with focal aggregation into granulomas was highlighted with a PG-M1 stain. The atypical lymphocytes were positive for gene rearrangements on a TCR delta stain and negative for βF-1. CT and PET scan in one of the two patients demonstrated diffuse, subcutaneous, ground-glass foci; hypermetabolic soft tissue nodules; and lymphadenopathy in the lungs, as well as splenomegaly. A diagnosis of histiocyte-rich PCGD-TCL was rendered. A histiocyte-rich, granulomatous variant of γδ T-cell lymphoma is extremely rare. Its potentially misleading resemblance to inflammatory granulomatous conditions could pose a diagnostic pitfall in this already challenging condition. This variant may resemble granulomatous mycosis fungoides and granulomatous slack skin syndrome, but it has a distinct, aggressive clinical outcome.

AbstractEBV‐positive HHV8‐negative EBL is part of the spectrum of EBV‐positive diffuse large B‐cell lymphoma NOS. This entity can be labeled as primary age‐related EBV‐associated EBL and appears to respond well to rituximab and thoracentesis.

AbstractThis case illustrates an unusual presentation of paraneoplastic myositis in stage IV follicular lymphoma managed with high‐dose steroids, a previously unreported entity in the literature.

Alveolar soft-part sarcoma is a highly vascular soft-tissue tumor that is uniformly malignant. It comprises less than 1 per cent of all soft-tissue sarcomas. Patients with alveolar soft-part sarcoma most frequently are aged 15 to 35 years, and the soft tissues of the lower extremities typically are affected. In the pediatric population, it most frequently occurs in the head and neck and particularly affects the tongue and orbit. Alveolar soft-part sarcoma has been described as a primary lesion in the trunk, upper extremities, and retroperitoneum; more novel locations include the mediastinum, female genital tract, stomach, bone, and larynx. Numerous case reports describe alveolar soft-part sarcoma in diverse anatomic locations, but this report is, to our knowledge, the first documentation of primary alveolar soft-part sarcoma of the liver. We describe a 47-year-old woman with such a manifestation. Despite surgical resection and numerous chemotherapeutic regimens, this patient had widespread metastasis and died approximately 2 years after the diagnosis was established.

Lymphangiomas of the colon are historically rare benign tumors. Only 331 cases have been reported in the world medical literature between 1931 and 2004. With widespread use of colonoscopy, however, they are being found more frequently. We report the case of a 74-year-old woman in whom a colonoscopy revealed a 3 x 4-cm submucosal lesion in the cecum that was eventually diagnosed as a lymphangioma. A CT of the abdomen showed a soft-tissue mass in the cecum and a low-density hepatic lesion. An endoscopic ultrasound of the colon showed a 3 x 4-cm hypoechoic lesion with internal septa arising from the submucosal layer of the cecum. This lesion resembled a vascular malformation; therefore a biopsy specimen was not taken. Pathologic findings of a specimen taken after a subsequent right hemicolectomy identified a submucosal lymphangioma. Published reports indicate that colonoscopy cures most lesions smaller than 2.5 cm in diameter. Resection should be reserved for larger lesions or those in patients exhibiting protein-losing enteropathy.

Adrenal masses have varying presentations. Most commonly, adrenal masses are discovered incidentally on CT or MRI during an evaluation for an unrelated complaint. Although the majority of these are nonfunctional cortical adenomas, hormonally active tumors and adrenocortical carcinoma must also be considered in the differential diagnosis. Rarely, retroperitoneal tumors may mimic an adrenal mass. We report a case of a 49-year-old man with anemia and weight loss who was found to have a large retroperitoneal mass arising from the adrenal gland. Surgical treatment involved en bloc resection of the right kidney, adrenal gland, segments 7 and 8 of the liver, and a portion of the right hemidiaphragm. Final pathology revealed a low-grade myofibrosarcoma. We believe that this is the first case report of a myofibrosarcoma of the adrenal gland. Myofibrosarcomas are rare malignant tumors composed of myofibroblasts that arise from the deep soft tissues. These tumors have a predilection for the head and neck, trunk, or extremities. Myofibrosarcomas can be differentiated from other sarcomas by immunohistochemical staining and pathologic features. We will briefly discuss the workup of an adrenal mass and focus on the diagnosis of myofibrosarcoma.