Classical Hodgkin lymphoma (cHL) is a B-cell malignancy that typically presents with painless lymphadenopathy and constitutional symptoms. Extranodal involvement is uncommon, particularly within the nervous system. Simultaneous neural foraminal extension with spinal canal infiltration and great-vessel encasement is exceptionally rare. A 44-year-old man presented with fever, dyspnea, neck swelling, fatigue, and right upper limb neuropathic pain suggestive of C7–T1 radiculopathy. Imaging revealed a large anterior mediastinal mass encasing the aortic arch with associated cervical and mediastinal lymphadenopathy. Core biopsy was non-diagnostic due to fibrosis, while excisional lymph node biopsy confirmed classical Hodgkin lymphoma, nodular sclerosis subtype with CD15+, CD30+ immunophenotype. Bone marrow biopsy showed no lymphomatous involvement. HIV testing was negative. FDG PET/CT demonstrated hypermetabolic cervical and mediastinal disease with extension into the C7–T1 neural foramina and spinal canal, along with T1 vertebral body osseous involvement, consistent with Stage IVB disease (IPS score: 2). The patient achieved complete metabolic response following six cycles of ABVD chemotherapy without surgical decompression or radiotherapy. Neurological manifestations of cHL are rare and usually result from direct extension into adjacent neural structures. This case illustrates the diagnostic challenges associated with atypical presentations, particularly when neurological symptoms coexist with mediastinal disease. It highlights the limitations of core needle biopsy in fibrotic lesions and reinforces the importance of excisional biopsy. This case expands the spectrum of recognized presentations of cHL by documenting a rare concurrent presentation of great-vessel encasement, neural foraminal extension, and vertebral osseous involvement as an initial manifestation. The diagnostic challenges posed by fibrotic lesions underscore the critical importance of excisional biopsy for definitive diagnosis. Clinicians should maintain a high index of suspicion for lymphoma in the differential diagnosis of mediastinal masses associated with radiculopathy and recognize that chemotherapy alone achieves excellent outcomes even in cases with apparent neural compromise.
Erika Seaquist, Anna Majapuro-Hirvonen, Rashelle Van Wagoner, Brent Rutland
Secondary immunodeficiency (SID) is an increasingly recognized complication among patients with hematologic malignancies and targeted cellular therapies, including CAR-T therapy, contributing to recurrent infections, increased healthcare utilization, and reduced HRQoL. Recent literature, guideline recommendations, real-world evidence (RWE), and selected clinical studies were reviewed to evaluate current approaches to intravenous and subcutaneous immunoglobulin replacement therapy (IgRT; IVIG and SCIG, respectively) in hematologic malignancy-associated SID. Both IVIG and SCIG provide effective humoral immune support, while current evidence indicates that SCIG provides more consistent steady-state IgG concentrations with reduced peak-to-trough fluctuations and fewer systemic adverse events. Emerging evidence also supports pharmacokinetically informed approaches that integrate IgG concentrations, infection burden, clinical response, and individual patient characteristics to guide long-term IgRT management. IgRT remains an important component of supportive treatment for patients with hematologic malignancy-associated SID who have documented hypogammaglobulinemia and recurrent, severe, or persistent infections. Current evidence supports both IVIG and SCIG as effective treatment options, with SCIG offering advantages for many patients requiring long-term therapy through more consistent IgG exposure, fewer systemic adverse events, and the convenience of home-based administration. Future IgRT strategies should emphasize evidence-informed patient selection, therapeutic monitoring, immune reconstitution, and responsible stewardship of plasma-derived immunoglobulin resources. Additional prospective studies are needed to define optimal monitoring strategies, treatment duration, and criteria for initiation and discontinuation to further improve long-term outcomes.
Melissa Ha, Shafagh Parsazad, Luke T. Dang, Elham Vali Betts, Denis M. Dwyre, Ananya Datta Mitra
Non-neoplastic histiocytic proliferations in the bone marrow represent a heterogeneous group of reactive processes that can pose significant diagnostic challenges for pathologists. These proliferations are typically driven by underlying conditions such as infections (e.g., mycobacterial, fungal, or viral), inflammatory or autoimmune disorders, lysosomal storage disorders such as Gaucher disease, hemophagocytic syndromes, drug effects, and malignancy-associated cytokine activation. Morphologically, they may manifest as increased histiocytes with or without hemophagocytosis, granuloma formation, or accumulation of pigmented macrophages (e.g., sea-blue histiocytes), often in the context of altered marrow cellularity. One of the key diagnostic pitfalls lies in distinguishing reactive histiocytic proliferations from neoplastic entities, including histiocytic sarcoma or marrow involvement by hematologic malignancies with histiocytic differentiation. Features such as cytologic atypia, destructive growth patterns, and immunophenotypic aberrancies must be carefully assessed, but even these can overlap in reactive conditions, particularly in the setting of intense immune activation. Ancillary studies, including immunohistochemistry and molecular testing, are often necessary and must be interpreted in the appropriate clinical and morphologic context. For practicing pathologists, awareness of these reactive patterns is essential to avoid overdiagnosis and inappropriate clinical management. A systematic approach that integrates morphology, clinical history, laboratory findings, and ancillary studies is critical. Multidisciplinary communication is often necessary, particularly in complex cases where histiocytic proliferation is a secondary manifestation of systemic disease. In this article we have described the morphologic findings of non-neoplastic histiocytic proliferations in the bone marrow in an attempt to guide in the appropriate diagnosis of these entities in the appropriate clinical context.
Blood transfusion is still among the most commonly used life-saving procedures in contemporary medicine, but identifying the ideal transfusion threshold remains a significant clinical hurdle across various patient groups. In the last twenty years, growing evidence has moved clinical practice from liberal to restrictive transfusion approaches, backed by randomized controlled trials showing similar or better outcomes with reduced hemoglobin thresholds in various clinical situations. Nonetheless, considerable uncertainties remain concerning the relevance of restrictive strategies in at-risk groups, such as patients experiencing acute coronary syndromes, traumatic brain injuries, chronic cardiovascular conditions, blood cancers, obstetric bleeding, and critically ill patients with multiple comorbidities. Additionally, a heightened awareness of complications from transfusions, shortages of donor blood, effects of storage lesions, immunomodulatory responses, and economic limitations has strengthened initiatives to enhance patient blood management while maintaining sufficient oxygen delivery. This narrative review thoroughly analyzes the changing evidence regarding restrictive and liberal blood transfusion approaches, emphasizing their physiological foundations, clinical effectiveness, safety characteristics, and difficulties in implementation across key medical and surgical fields. The review combines results from key randomized clinical trials, modern international guidelines, and recent meta-analyses, highlighting both the advantages and shortcomings of existing evidence. Special focus is placed on ongoing controversies, such as personalized transfusion limits, targeted hemotherapy, indicators of tissue oxygen levels, transfusion practices in resource-constrained environments, and the application of artificial intelligence in clinical decision-making.
