Go, Ronald S.

Abstract Erdheim-Chester disease (ECD) is a rare systemic histiocytic neoplasm, with cardiac morbidities, including cardiovascular (CV) risk factors and cardiac conditions, playing a significant yet poorly understood role in the disease burden. This study evaluated the prevalence, characteristics, and prognosis of ECD in patients with (ECD-C) and without cardiac involvement (ECD-noC) and compared the burden of cardiac morbidities with matched controls. Patients diagnosed with ECD between 1990 and 2021 at a tertiary center were included, with cardiac involvement centrally assessed using radiographic studies. Cardiac morbidities were compared with a control group without ECD, matched for age, sex, body mass index, and smoking history. Among 104 patients with ECD, 39 (37%) had cardiac involvement. Patients with ECD-C had higher rates of hypertension (67% vs 46%), hyperlipidemia (67% vs 40%), heart failure (36% vs 8%), and pericardial effusion (28% vs 2%) than those with ECD-noC. Compared with the matched non-ECD cohort, patients with ECD had higher prevalence of coronary artery disease (20% vs 7%), heart failure (18% vs 4%), and antihypertensive drug use (55% vs 40%). Notably, patients with ECD-C had inferior progression-free survival (PFS) from frontline therapy compared with patients with ECD-noC (5-year PFS, 28.3% vs 70.5%). These findings highlight the burden of CV risk factors and cardiac conditions in ECD, even without a clinical diagnosis of ECD-C. Importantly, this cardiac morbidity burden is substantial for patients with ECD-C compared with ECD-noC. Our findings highlight the need for comprehensive cardiac risk assessment and management strategies to improve patient outcomes.

Abstract Immune thrombocytopenia (ITP) carries an increased risk of thrombosis, which may be further amplified by splenectomy and thrombopoietin receptor agonists (TPO-RAs). Although each intervention has been individually studied for its thrombotic risk, data are lacking on the safety of postsplenectomy TPO-RA use. We conducted a retrospective cohort study of adult patients with ITP who underwent splenectomy between 2011 and 2024. Patients were stratified on the basis of postsplenectomy TPO-RA use. The primary outcome was incidence of thrombosis. Secondary outcomes included bleeding, mortality, and hematologic response. Time-to-event analyses and multivariate Cox regression were performed. Among 88 patients, 37 (42%) patients received TPO-RAs after splenectomy. Thrombosis occurred in 17 patients in the TPO-RA group vs 14 patients in the non–TPO-RA group (P = .07). The 10-year cumulative incidence of thrombosis was numerically higher in the TPO-RA group (57% vs 36%), with clustering of events within the 3 months of postsplenectomy TPO-RA initiation. Venous events predominated; arterial events were rare. No significant differences were observed in bleeding or mortality rates between groups. Platelet counts alone did not independently affect bleeding or thrombosis. TPO-RA use after splenectomy was not significantly associated with increased thrombosis risk. However, early initiation may coincide with a high-risk period, and the sustained numerical difference in cumulative incidence throughout follow-up highlights potential clinical relevance. These findings support the need for individualized thromboprophylaxis and prospective evaluation of TPO-RA safety in this setting.

Mesenchymal dendritic cell neoplasms represent a distinct category of hematologic malignancies that challenge traditional classifications of histiocytic and classical dendritic/Langerhans cell neoplasms. Historically grouped under the broader umbrella of dendritic cell neoplasms, these entities differ significantly in their ontogeny, histopathologic features, molecular alterations, and clinical behavior. They are categorized into three main subtypes including follicular dendritic cell sarcoma, fibroblastic reticular cell tumor, and EBV-positive inflammatory follicular dendritic cell sarcoma/fibroblastic reticular cell tumor. They originate from mesenchymal stromal cells, and genetic alterations activating the NF- κβ pathway are frequent in follicular dendritic cell sarcomas. Immunophenotypic characterization is critical to distinguish these from other hematologic malignancies including histiocytic and classical dendritic/Langerhans cell neoplasms and other solid (non-hematopoietic) cancers. This review recapitulates current knowledge on existing classifications, details their diverse ontogeny from classical dendritic cell neoplasms, and provides insights into their clinicopathologic characteristics to improve diagnostic accuracy. We detail two case studies that demonstrate the challenges involved in the histopathologic diagnosis of these rare tumors, necessitating a comprehensive workup. Integrating developmental biology into practical diagnostic algorithms is essential to improve recognition and classification of these underdiagnosed neoplasms, ultimately guiding timely management.

Abstract Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder infrequently complicated by delayed-onset pituitary disease. A 41-year-old female presented with papular, acneiform skin lesions. Shave biopsy demonstrated a superficial dermal epithelioid cell proliferation with S100, CD1a, and langerin positivity on immunohistochemistry and a BRAF p.N486_P490del inframe deletion-gain of function pathogenic variant on next-generation sequencing. The skin lesions spontaneously resolved. One year later, she developed progressive fatigue, fevers, anorexia, menstrual irregularities, polyuria, and polydipsia. Laboratory workup was consistent with panhypopituitarism. Pituitary magnetic resonance imaging noted mass-like thickening and enhancement of the infundibulum extending toward the hypothalamus. After treatment with cobimetinib, magnetic resonance imaging findings resolved but endocrinopathies persisted, requiring indefinite hormone therapy. This case demonstrates the full spectrum of endocrinopathies of LCH-induced pituitary disease and is an unusual circumstance of LCH with delayed-onset panhypopituitarism.

11549 Background: Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with a subset associated with unicentric Castleman disease (UCD). However, the impact of CD association on clinicopathologic features and survival outcomes remains unclear. This study aims to elucidate differences in disease characteristics and outcomes in FDCS with and without CD to guide future research and clinical practice. Methods: We retrospectively analyzed 41 FDCS patients seen at Mayo Clinic between January 2000 and December 2024. Patients were categorized into CD-related (n = 9) and FDCS-only (n = 32) groups. Demographic, clinical, pathological, and survival data were compared. Kaplan-Meier survival analyses were used to evaluate overall survival (OS) and progression-free survival (PFS). Epstein-Barr virus-associated inflammatory FDCS were excluded. Results: The CD-related group was younger at diagnosis (46.0 vs. 58.0 years, p = 0.041). Among those with CD-related FDCS, FDCS was diagnosed concurrently as CD in 6/9 (66.7%) and after the diagnosis of CD in 3/9 (33.3%). The FDCS-only patients were more likely to have extranodal disease (71.9% vs. 22.2%) and to have metastasis (62.5% vs 22.2%). One CD-related FDCS patient had paraneoplastic pemphigus. Among 11 patients with next-generation sequencing (NGS) results, 9 had pathogenic mutations. The most common pathogenic mutations included CDKN2A, CDKN2B, and TRAF3 copy number losses. Surgery was the preferred first-line intervention in FDCS-only and CD-related FDCS groups (19/32, 59.4% vs. 6/9, 66.7%). Eight out of 32 (25.0%) of the FDCS-only group received chemotherapy at first-line, most commonly Gemcitabine/Docetaxel or Adriamycin/Ifosphamide. While Gemcitabine/Docetaxel was the most preferred in the second line, different regimens were pursued in the third and later lines of therapy, including Pembrolizumab, Pazopanib, and stem cell transplant. Five out of 6 patients in the CD-related FDCS group received either adjuvant radiation or chemotherapy, which led to complete remission during the follow-up periods. The median follow-up was 22.4 months for the whole population. There was a trend for better OS and PFS among CD-related FDCS patients. The respective 2-year OS rates were 100% and 66.7%, and 2-year PFS rates were 57.1% and 43.1% for CD-related FDCS and FDCS-only patients, respectively. Conclusions: This study provides novel insights into clinicopathologic differences and survival trends for FDCS. Our data would suggest a less aggressive disease course among CD-related FDCS, which implies the need for different treatment strategies for CD and non-CD-related FDCS. Further research is warranted to elucidate these mechanisms, such as multi-omic analysis on benign FDC proliferation in the microdissected UCD areas and the adjacent FDCS cells to determine factors associated with progression to sarcoma.

9021 Background: Home call is an expected trainee responsibility in many hematology-oncology (HO) training programs although the specific duties and frequency vary. Home call is associated with sleep deprivation and burnout . The Accreditation Council for Graduate Medical Education (ACGME) outlines that home call should not prevent adequate rest or personal time and that the clinical time spent must be counted toward duty hours. However, little is known about the educational value or impact of home call. We sought to analyze the volume, perceived value, and effects of oncology home call on HO fellows. Methods: We completed a review of the pager log of the outpatient/after hours oncology pager (OP) at a single 2059 bed tertiary medical center from 1/1/23-12/31/24. The HO fellow carries the OP afterhours and on weekends except for 7am-12pm on Saturday/Sunday. The pager receives all consult calls from the emergency department and inpatient teams requesting verbal communication (in addition to the electronic order), critical results, and outpatient patient calls on matters related to oncology (hematology not included). Patient calls are not triaged and are routed through the hospital operator directly to the OP. Overnight home call is maximum 3 times per week without a post call day. An optional survey was distributed to fellows in May 2024 to assess fellows’ experiences with the OP using a 5-point Likert scale and free response. Results: There were 80,672 and 87,605 oncology patient visits in 2023 and 2024 respectively at the analyzed institution. The OP received a total of 7,239 pages over the analyzed period. Fellows received a mean of 5.8 pages per weeknight call shift and 8.8 pages per weekend call shift. The survey response rate was 19/33 (42%) HO fellows. Respondents were 58% male and included first (42%), second (26%), and third year (32%) fellows. 89% of respondents reported that most pages overnight were from outpatients and 0 respondents felt that answering patient calls required a physician. Most fellows (79%) did not report educational value from holding the OP and 63% of fellows felt that holding the OP negatively impacted their performance at work the next day. For nights that received more than 3 calls, 95% fellows reported feeling not well rested. In addition, a majority of negative impact on their wellness including anxiety and inability to exercise or socialize when holding the OP. Conclusions: The results from our single-institution study indicate that home call could represent a major opportunity to improve the wellness of trainees without negatively impacting their education. More research is needed to understand what the primary contributors are for the negative experiences and perceptions while developing sustainable systems and approaches for efficiently handling oncology pager traffic.