1Department of Medicine, Faculty of Medicine, Tbilisi State Medical University, Georgia.
2Department of Medicine, University of Traditional Medicine, Yerevan, Armenia
Classical Hodgkin lymphoma (cHL) is a biologically complex B-cell neoplasm characterized by the presence of malignant Hodgkin and Reed–Sternberg (HRS) cells embedded within a heterogeneous inflammatory microenvironment. We present the case of a 23-year-old male diagnosed with the nodular sclerosis subtype of cHL, who initially presented with painless cervical lymphadenopathy. Histopathological evaluation of bone marrow and cervical lymph node biopsies confirmed CD30-positive neoplastic cells, consistent with cHL. Baseline staging was performed using complete blood counts and PET imaging. The patient underwent first-line chemotherapy with the ABVD regimen (Adriamycin, Bleomycin, Vinblastine, Dacarbazine), accompanied by prophylactic pegylated G-CSF. The treatment was well-tolerated, with no acute adverse events, and the patient was discharged with structured follow-up, infection prophylaxis, and supportive care measures. This case highlights the clinical presentation, diagnostic workflow, and therapeutic management of nodular sclerosis cHL in young adults, illustrating the efficacy of contemporary chemotherapy regimens and the critical role of vigilant supportive care in optimizing patient outcomes.
Classical Hodgkin lymphoma (CHL) constitutes approximately 10% of all lymphomas and is traditionally classified into four histopathologic subtypes: nodular sclerosis, mixed cellularity, lymphocyte-rich (also known as lymphocyte predominance), and the exceedingly rare lymphocyte-depleted variant (3). Among these, nodular sclerosis is the most prevalent, whereas mixed cellularity tends to present with more disseminated or advanced-stage disease. Together, these two subtypes account for nearly 80% of all CHL cases (3). Clinically, CHL is considered one of the most curable hematologic malignancies, with the majority of patients achieving durable remission following standard first-line chemotherapy regimens—often ABVD or related protocols—sometimes combined with involved-site radiotherapy depending on stage and risk stratification (1). The nodular sclerosis subtype (NS-CHL) is characterized by distinctive architectural and stromal features within the lymph node. Thick, collagen-rich fibrotic bands traverse the tissue, subdividing the lymphomatous infiltrate into nodules composed of inflammatory cells and scattered neoplastic Hodgkin and Reed–Sternberg (HRS) cells (3). These fibrotic bands reflect a marked expansion and activation of fibroblasts within the tumor microenvironment, driven in part by cytokines and growth factors released by both HRS cells and surrounding immune cells (2). The resulting fibroblast proliferation, extracellular matrix remodeling, and deposition of collagen contribute not only to the characteristic nodular appearance but also to the unique tumor biology of NS-CHL, influencing local immune interactions and the structural organization of the malignant niche (2,3).
METHODS AND MATERIALS
A 23-year-old male with newly diagnosed classical Hodgkin lymphoma, nodular sclerosis subtype, was admitted for chemotherapy. Diagnosis was confirmed by bone marrow and cervical lymph node biopsy demonstrating CD30-positive neoplastic cells. Baseline evaluation included complete blood count, biochemical panel, and PET scan. The patient received cycle 1A of ABVD chemotherapy (Adriamycin 25 mg/m², Bleomycin, Vinblastine 6 mg/m², Dacarbazine 375 mg/m²) with pegylated G-CSF 6 mg subcutaneously the following day. Supportive care included hydration, infection prophylaxis, and patient education. Follow-up was scheduled for assessment of treatment response and subsequent chemotherapy cycles.
Case Presentation
A 23-year-old male was newly diagnosed with Classical Hodgkin’s Lymphoma and admitted for initiation of chemotherapy with the ABVD regimen (Adriamycin, Bleomycin, Vinblastine, Dacarbazine). The patient had no history of fever, vomiting, diarrhea, chest pain, palpitations, or bleeding manifestations, and reported no drug allergies. He initially presented in June 2022 with swelling over the right side of the neck associated with sore throat. Bone marrow aspiration and biopsy suggested Classical Hodgkin’s Lymphoma – Nodular Sclerosis type, with CD30 positivity in neoplastic cells. A repeat bone marrow aspiration and biopsy confirmed the diagnosis from the right cervical lymph node. A PET scan was performed, with the report pending at the time of admission. After detailed discussion with the patient and family and obtaining informed consent, he was admitted for initiation of chemotherapy. On physical examination, the patient was conscious, oriented, and not in acute distress. ECOG performance status was 1. Vital signs were stable with a blood pressure of 110/70 mmHg, pulse 75/min, respiratory rate 20/min, SpO? 98% on room air, and temperature 37°C. General examination revealed a well-nourished young male. HEENT evaluation showed anicteric sclerae, clear conjunctivae, intact extraocular movements, patent nares, clear oropharynx, and a normal tongue. Cervical examination revealed palpable, rubbery, nontender lymphadenopathy. Chest examination was unremarkable with clear lung fields. Cardiovascular examination revealed normal S1 and S2 without murmurs. Femoral adenopathy was noted on genitourinary examination. Neurological assessment showed the patient alert and oriented ×3, cranial nerves II–XII intact, with a slow but normal gait. Musculoskeletal and abdominal examinations were unremarkable, with no hepatosplenomegaly and positive bowel sounds. Skin was normal. The patient was adequately hydrated before and after chemotherapy. He was premedicated and received cycle 1A of ABVD chemotherapy, which included Adriamycin 25 mg/m², Bleomycin, Vinblastine 6 mg/m², and Dacarbazine 375 mg/m². Pegylated G-CSF 6 mg was administered subcutaneously the following day. The patient tolerated chemotherapy well without acute adverse events. Baseline investigations, including prior bone marrow biopsies and PET scan, were reviewed and attached in patient records. At discharge, the patient was stable and advised to continue oral medications including folic acid 5 mg once daily and Nurokind once daily. He was instructed to report immediately to the nearest hospital in case of fever >100°F, sore throat, severe fatigue, or other emergencies. Guidance was provided for management of febrile neutropenia, blood transfusion (PRC if Hb <7 g/dL, platelets if <20,000), weekly CBC monitoring, and catheterization in case of urinary retention. Additional preventive measures included careful hand and oral hygiene, consumption of freshly prepared food, maintaining hydration, stool softeners if required, and avoiding contact with individuals with respiratory infections. Physical activity was advised as tolerated. The patient was scheduled for follow-up in the clinical hematology outpatient department with CBC and PET scan reports [Fig.1], and cycle 1B of ABVD chemotherapy was planned based on review of results. He was discharged in a stable condition, with instructions to continue close monitoring and promptly report any acute clinical changes.
Fig.1
DISCUSSION
Hodgkin lymphoma (HL) is a biologically complex and multifactorial lymphoid malignancy arising predominantly from B lymphocytes, with approximately 1–2% of cases originating from T-cell lineages (4). Neoplastic transformation occurs within germinal centers, where precursor cells acquire genetic and epigenetic abnormalities that disrupt normal somatic hypermutation, immunoglobulin gene rearrangement, and apoptosis (4). Failure of these aberrant germinal center B cells to undergo programmed cell death, combined with pathological interactions within the lymph node microenvironment, leads to the development of Hodgkin and Reed–Sternberg (HRS) cells. In classical HL (cHL), nodular sclerosis may present in an early “cellular phase,” characterized by at least one identifiable sclerotic band, reflecting initial fibroblast proliferation and extracellular matrix deposition (5). HRS cells—comprising mononuclear Hodgkin cells and multinucleated Reed–Sternberg cells—are typically sparse within dense, heterogeneous inflammatory background rich in T lymphocytes, eosinophils, macrophages, plasma cells, fibroblasts, and stromal elements (6). These malignant cells derive from germinal center B cells with aberrant immunoglobulin gene mutations (6). Despite harboring nonfunctional immunoglobulin genes, HRS cells evade apoptosis through constitutive activation of survival pathways—including NF-κB, JAK/STAT, and PI3K/AKT—driven by genetic alterations and cytokine-mediated signaling networks. HRS cells secrete cytokines such as TGF-β and IL-5, which promote eosinophil recruitment and fibroblast activation, as well as IL-13, GM-CSF, and TNF-α, which facilitate microenvironmental support, immune evasion, and stromal remodeling (6). Immunophenotypically, HRS cells express CD30 and CD15 while lacking B-cell markers (CD20) and CD45, and they characteristically display aneuploidy rather than recurrent chromosomal translocations (6). Clinically, patients typically present with painless supradiaphragmatic lymphadenopathy, most often involving cervical or mediastinal nodes (6). Approximately one-third exhibit systemic “B symptoms,” including unexplained weight loss, fever, and drenching night sweats, reflecting cytokine-mediated systemic inflammation (6). Additional symptoms such as pruritus, alcohol-induced pain, and fatigue may occur. Diagnosis requires a multimodal approach. A complete blood count evaluates cytopenias and inflammatory abnormalities, while an excisional lymph node biopsy remains essential for definitive identification of HRS cells. PET/CT is central to initial staging, interim response assessment, and end-of-treatment evaluation (6). Bone marrow biopsy may be indicated in suspected advanced-stage disease to evaluate morphological, immunophenotypic, cytogenetic, and molecular abnormalities (7). Although therapy historically relied on chemotherapy with or without radiotherapy, the advent of immunotherapy has expanded treatment options, particularly in relapsed or refractory HL (1). Staging follows the Ann Arbor classification with Cotswolds modifications (6). Stage I denotes involvement of a single lymph node region or single lymphoid structure, whereas Stage II involves two or more regions on the same side of the diaphragm, with possible contiguous extranodal extension (IIE). Stage III indicates lymph node involvement on both sides of the diaphragm, potentially including splenic disease (IIIS) or contiguous extranodal spread (IIIE). Stage IV reflects diffuse or disseminated extranodal involvement, commonly affecting the bone marrow, liver, lungs, or bones. Additional modifiers include “A” and “B” for absence or presence of systemic symptoms, “X” to denote bulky disease—typically defined as a mediastinal mass >1/3 thoracic diameter or nodal mass ≥10 cm—and “E” for direct extranodal extension (6). PET/CT is indispensable for modern staging, enabling identification of metabolically active disease, subclinical extranodal sites, and early treatment response prediction via Deauville scoring. Contemporary risk stratification incorporates inflammatory biomarkers, the number of involved nodal regions, and prognostic indices such as the International Prognostic Score, refining treatment intensity and long-term toxicity reduction. Treatment of cHL relies on risk-adapted multimodal therapy integrating chemotherapy, radiotherapy, and selected immunotherapeutic agents (2). ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) remains the standard first-line regimen. Full-dose ABVD administered without granulocyte colony-stimulating factor has historically increased the risk of neutropenic complications and treatment delays (9), yet remains highly effective across disease stages. In early-stage disease, ABVD followed by involved-field radiotherapy achieves 5-year overall survival rates exceeding 95% (8), and PET-adapted approaches allow reduction or omission of radiotherapy in selected patients. For high-risk or advanced-stage disease, intensified regimens such as BEACOPP (baseline or escalated) may improve progression-free survival, albeit with increased hematologic toxicity. Brentuximab vedotin combined with AVD (BV-AVD) has emerged as an alternative frontline regimen in stage III–IV disease, reducing bleomycin-associated pulmonary toxicity and improving progression-free outcomes (2). Radiotherapy has evolved from extensive-field to involved-site radiation therapy (ISRT), significantly reducing long-term toxicity without compromising disease control. It is primarily used in early-stage favorable disease, residual PET-avid masses, and cases of bulky disease. Immunotherapy, particularly anti–PD-1 inhibitors such as nivolumab and pembrolizumab, has reshaped management of relapsed/refractory HL by exploiting PD-1/PD-L1 overexpression driven by 9p24.1 amplification (2). Brentuximab vedotin, an anti-CD30 antibody–drug conjugate, is also central to salvage therapy and is often used prior to autologous stem cell transplantation (ASCT). ASCT remains the curative standard for relapsed HL, while allogeneic transplantation is reserved for relapse following ASCT or multiply refractory disease. Supportive care emphasizes infection prevention, surveillance for treatment-related toxicities, and continuity of hematologic/oncologic care. Patient education, monitoring for cytopenias and organ-specific toxicities, and reliable follow-up are essential components of comprehensive HL management.
CONCLUSION
In summary, Hodgkin lymphoma is a biologically and clinically heterogeneous malignancy arising predominantly from B lymphocytes, characterized by the presence of Hodgkin and Reed–Sternberg cells within a complex inflammatory microenvironment. Its clinical behavior, histopathology, and molecular features, particularly in the nodular sclerosis subtype, reflect intricate interactions between neoplastic cells and the surrounding stroma. Accurate diagnosis relies on histopathology, immunophenotyping, and advanced imaging, while staging—guided by the Ann Arbor system with PET/CT integration—remains essential for risk stratification and treatment planning. Modern management employs risk-adapted, multimodal therapy, integrating combination chemotherapy, targeted radiotherapy, and immunotherapy, which has substantially improved survival outcomes. Despite excellent prognosis in most patients, individualized approaches that consider disease stage, tumor burden, systemic symptoms, and molecular markers are critical to optimizing therapeutic efficacy while minimizing long-term toxicity. Continued advances in molecular characterization and immunotherapeutic strategies hold promise for further improving outcomes and achieving durable remission in patients with Hodgkin lymphoma.
CONFLICTS OF INTEREST
There is no conflicts of interest.
ACKNOWLEDGEMENT
We thank the authors for their valuable contributions to this project. Generative AI was used for language purposes only.
Ethical approval
Ethical approval was not required for this study.
Declaration of patient consent
Patient consent was acquired.
Financial support and sponsorship
Nil.
REFERENCE
Saira Susan Thomas*, Pallippat Thumban Kheif Mamu, Manjima Sunil, Nodular Sclerosis Classical Hodgkin Lymphoma in a Young Adult: A Comprehensive Case- Based Review of Pathophysiology, Diagnosis, and Contemporary Management, Int. J. Sci. R. Tech., 2025, 2 (12), 76-80. https://doi.org/10.5281/zenodo.17817508
10.5281/zenodo.17817508
