STEPTRACKERHEMATOLOGY + ONCOLOGY | PATHOLOGY | HIGH-YIELD REVIEW

Hodgkin Lymphoma

A few malignant Reed-Sternberg cells in a crowd of reactive cells — contiguous nodal spread, B symptoms, and excellent cure rates.

FOCUS ON
Reed-Sternberg cells are CD15⁺ CD30⁺, "owl-eyed", and a minority of the tumor. Know the subtypes. Nodular sclerosis is most common (young women, mediastinum). Mixed cellularity is EBV-linked with eosinophils. Lymphocyte-predominant has popcorn cells that are CD20⁺ and CD15⁻/CD30⁻. Contrast with NHL.
SUBTYPE / TOPIC
HISTOLOGY
WHO
CLUE
Reed-Sternberg cell
the tumor cell
Large B-cell–derived cell with bilobed, mirror-image nuclei and huge nucleoli ("owl eyes"); CD15⁺, CD30⁺, CD45⁻, usually CD20⁻.
Secretes cytokines that recruit lymphocytes, eosinophils (IL-5), plasma cells, histiocytes
Tumor cells are a small minority of the mass
Clinical picture
Painless cervical or mediastinal nodes; contiguous spread (staged with Ann Arbor).
Bimodal age: young adults and > 55
B symptoms: fever, night sweats, > 10% weight loss; pruritus; rarely alcohol-induced node pain
Nodular sclerosis
most common (~70%)
Collagen bands divide the node into nodules; lacunar cells (RS variants sitting in clear spaces).
Adolescents and young adults, often women
Anterior mediastinal mass; good prognosis
Mixed cellularity
Many RS cells in a mix of eosinophils, plasma cells, histiocytes.
Older men; HIV; EBV⁺ in most
Abdominal nodes, spleen; intermediate prognosis
Lymphocyte-rich
Few RS cells among many small lymphocytes.
Older adults
Best prognosis of classic types
Lymphocyte-depleted
Many RS cells, few lymphocytes, fibrosis.
Elderly, HIV, low-resource settings
Worst prognosis; rare
Nodular lymphocyte-predominant
non-classic
"Popcorn" (LP) cells: CD20⁺, CD15⁻, CD30⁻.
Young men; cervical or axillary nodes
Excellent prognosis; may transform to DLBCL
Treatment & late effects
ABVD chemotherapy ± radiation; high cure rate.
Doxorubicin → cardiomyopathy · bleomycin → lung fibrosis · chest radiation → breast cancer, CAD
Secondary AML and solid tumors years later
Paraneoplastic
Cytokine and antibody effects.
Hypercalcemia (macrophage calcitriol), eosinophilia, anti-Tr cerebellar degeneration, minimal change disease
Nephrotic syndrome in a young adult with nodes

Mechanism — a minority directs the crowd

Crippled germinal-center B cellNF-κB on; EBV in some
→
Reed-Sternberg cellCD15, CD30
→
CytokinesIL-5, IL-13, chemokines
→
Reactive cells flood inEosinophils, T cells, plasma cells
→
Fibroblasts (TGF-β)Collagen bands

Hodgkin vs non-Hodgkin

FEATURE
HODGKIN
NON-HODGKIN
Spread
Contiguous, node to node
Noncontiguous, often extranodal
Tumor cells
Few RS cells in reactive background
Sheets of monoclonal cells
B symptoms
Common
Less common
Mediastinum
Nodular sclerosis
T-lymphoblastic, primary mediastinal B
Markers
CD15, CD30
CD20 (B), CD3 (T)
Prognosis
Usually excellent
Varies widely

How it's tested

COMMON CONFUSIONCD30 also marks ALCL. RS cells add CD15 and lack CD45; ALCL has hallmark horseshoe nuclei and often ALK.
THE TRAPA 35-year-old woman with breast cancer had chest radiation for Hodgkin lymphoma at 19. The breast cancer is a late radiation effect, not a coincidence.
YOUR APPROACHFind RS cells (CD15/CD30), then use age, sex, site and background cells (bands, eosinophils, EBV) to name the subtype.

If you see… think…

Young woman, mediastinal mass, collagen bands, lacunar cells → nodular sclerosis HL
Older man, EBV⁺, eosinophil-rich node → mixed cellularity HL
Owl-eye cells CD15⁺ CD30⁺ → Reed-Sternberg cells
Popcorn cells, CD20⁺, CD15⁻ CD30⁻ → nodular lymphocyte-predominant HL
Neck node that aches after alcohol → Hodgkin lymphoma
Fever, drenching night sweats, weight loss → B symptoms
Breast cancer years after mantle-field radiation → late effect of HL treatment
Lymphoma with peripheral eosinophilia → IL-5 from RS cells
Young adult with itching and neck nodes → Hodgkin lymphoma