Hodgkin lymphoma

Overview - The Reed-Sternberg Show

• Bimodal age distribution: Peaks at 15-35 years and >55 years.
• Characterized by the Reed-Sternberg (RS) cell: A large, malignant B-cell.
  • Morphology: Binucleated or bilobed nucleus with prominent eosinophilic nucleoli ("owl-eye" inclusions).
  • Immunophenotype: Typically CD15+ and CD30+. (Negative for CD45 & CD20).
• 📌 Mnemonic: 2 x 15 = 30 for positive markers.

⭐ The vast majority of the tumor mass in Hodgkin lymphoma is composed of reactive, non-neoplastic inflammatory cells (lymphocytes, eosinophils, plasma cells), not the malignant RS cells themselves.

Pathophysiology - Finding the Owl's Eyes

• Hallmark Cell: The neoplastic Reed-Sternberg (RS) cell is diagnostic.
  • Derived from germinal center B-cells.
  • Large cell with a bilobed nucleus and prominent eosinophilic nucleoli, creating the classic "owl's eye" appearance.
• Immunophenotype: RS cells are characteristically CD15+ and CD30+. They are negative for most B-cell markers like CD20.
• Tumor Microenvironment: RS cells are rare (~1-2% of tumor mass). They secrete cytokines that recruit a vast, non-neoplastic inflammatory infiltrate, forming the bulk of the lymphoma.

⭐ Epstein-Barr Virus (EBV) is implicated in ~45% of classical Hodgkin lymphoma cases. EBV proteins can drive B-cell proliferation and contribute to the development of RS cells.

Classification - The Hodgkin Family

• Classical Hodgkin Lymphoma (cHL): Accounts for ~95% of cases. Defined by the presence of diagnostic Reed-Sternberg cells.
  • Nodular Sclerosis (NSHL): The most common subtype (~70%). Typically affects young adults, particularly women. Histology shows fibrous collagen bands and lacunar cells (a variant of RS cells).
  • Mixed Cellularity (MCHL): Represents ~25% of cases. Strong association with EBV infection (~70%). The background infiltrate is rich in eosinophils and plasma cells.
  • Lymphocyte-Rich (LRHL): An uncommon subtype (~5%) with an excellent prognosis.
  • Lymphocyte-Depleted (LDHL): The rarest form (<1%), carrying the worst prognosis. Often seen in older adults and individuals with HIV.

⭐ Exam Favorite: The classic Reed-Sternberg cells of cHL have a distinct immunophenotype: they are positive for CD15 and CD30, but negative for the pan-leukocyte marker CD45 and the B-cell marker CD20.

• Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): A distinct entity making up ~5% of cases. It is characterized by lymphocytic and histiocytic (L&H) cells, often called "popcorn cells". These cells are CD20+ and CD45+ but negative for CD15/CD30.

Staging & Treatment - Mapping the Battle

• Ann Arbor Staging:
  • Stage I: Single lymph node region.
  • Stage II: ≥2 node regions, same side of diaphragm.
  • Stage III: Nodes on both sides of diaphragm.
  • Stage IV: Disseminated extralymphatic sites.
  • Modifiers: A (asymptomatic) vs. B (fever, night sweats, weight loss).

⭐ In early-stage favorable classic Hodgkin lymphoma, radiation therapy (RT) is often combined with a shortened course of chemotherapy (e.g., 2 cycles of ABVD) to minimize long-term toxicity.

• Pathognomonic Reed-Sternberg (RS) cells are large, binucleated B-cells with an "owl-eyed" appearance.
• RS cells secrete cytokines, causing B symptoms (fever, night sweats, weight loss) and attracting a reactive cellular infiltrate.
• Typically presents as painless lymphadenopathy with a contiguous, predictable spread to adjacent node groups.
• Nodular sclerosis is the most common subtype, often affecting young women and characterized by fibrous bands.
• Generally has an excellent prognosis with high cure rates.