Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma, comprising approximately 5–7% of cases. Unlike classical HL, NLPHL is characterized by CD20-positive “popcorn” cells (LP cells), lacks Epstein-Barr virus association, and tends to follow an indolent course. Accurate diagnosis is critical, as the therapeutic approach differs substantially. We report an early-stage NLPHL case in a young woman managed successfully without chemotherapy, emphasizing the value of histopathological precision and risk-adapted therapy.

A 33-year-old woman presented with a painless cervical swelling. Physical examination revealed enlarged left cervical and supraclavicular lymph nodes. She had no B symptoms such as fever, night sweats, or weight loss. Blood counts and biochemistry were within normal limits. An excisional biopsy of a lymph node was performed, followed by immunohistochemistry and whole-body 18F-FDG PET-CT for staging. Bone marrow aspiration and biopsy were also conducted to rule out marrow involvement.

Histopathological examination demonstrated nodular architecture containing scattered lymphocyte-predominant (LP) cells. Immunophenotyping revealed strong CD20 and Pax5 expression, with negativity for CD3 and CD15. CD21 staining highlighted an expanded follicular dendritic cell meshwork, confirming the diagnosis of NLPHL.

PET-CT showed FDG-avid lymph nodes localized to the left cervical and supraclavicular regions, with a maximum SUV of 27.9. No pathological uptake was seen in the mediastinum, abdomen, bones, or spleen. Bone marrow biopsy was normocellular without evidence of infiltration. The disease was staged as Stage IA (non-bulky), CD20-positive NLPHL.

The patient was treated with rituximab monotherapy (375 mg/m2 weekly for 4 doses), followed by involved-field radiotherapy (30 Gy) to the involved nodal regions. Given her age and reproductive status, fertility preservation was discussed before initiating treatment. The plan aimed to minimize long-term toxicity while maintaining curative potential.

This case illustrates several important themes. First, accurate histological subtyping allowed for a deviation from standard chemotherapy-based HL protocols. Second, the use of rituximab and radiotherapy alone is an emerging and evidence-supported strategy for early-stage NLPHL, particularly in CD20-positive, non-bulky cases. Third, the patient’s demographic—young and female—makes chemotherapy-free management especially attractive given concerns about fertility and late effects. Finally, the case has strong educational value, highlighting the need to distinguish NLPHL from classical HL and indolent B-cell lymphomas, both histologically and metabolically.

This case demonstrates how a rare Hodgkin lymphoma subtype can be successfully managed with a chemotherapy-free, targeted approach. It reinforces the importance of accurate subtyping and risk-adapted treatment in delivering personalized care, especially in young patients where fertility and quality of life are key considerations