<aside> 💡 RS cells that are CD15+, CD30+, PAX5+, LMO2+, CD45-, CD19-, CD20-, CD79a-

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Epidemiology

• Accounting for less than 1% of all cancers.
• In most economically developed countries, there is a bimodal age distribution, with one peak occurring in the third decade of life and the second, smaller, peak occurring after age 50 years.
• In less economically developed countries, HL is less common but predominantly affects children, most of whom are boys.
  • Mixed cellularity HL (MCHL) and lymphocyte-depleted HL are more commonly seen.
• EBV genome fragments have been found in RS cells from approximately 40% of patients with HL. The prognosis of EBV-positive cHL has tended to be better than EBV-negative cHL, but the presence of EBV does not influence therapy selection.

• The incidence of HL is higher in patients with human immunodeficiency virus (HIV) infection, although cHL is not considered an AIDS-defining illness.
  • Most commonly of the mixed cellularity subtype.
  • Associated with B symptoms and with advanced stage, commonly because of bone marrow involvement.

Subtypes

Classical HL: 95%

Nodular sclerosis HL (NSHL)

• 70% of cHL
• Female ≥ male
• Adolescent and young adults
• Lacunar-type RS cells and collagen band
• The mediastinum is commonly involved, particularly in young female

Mixed-cellularity HL (MCHL)

• 20% to 25% of cHL
• Male > female
• Bimodal age distribution in young children and older adults
• Often presents at higher stages than NS CHL
• May be skip lesions because of hematogenous spread of disease.
• More likely to be associated with EBV (~75%) and HIV infection

Lymphocyte-rich HL

• 5% of cHL
• Distinct absence of eosinophils and neutrophils
• The subtype of CHL that most closely resemble NLPHL
• Presents at low stage and demonstrates a more indolent course, similar to NLPHL

Lymphocyte-depleted HL:

• <1% of cHL
• The RS cells are extremely pleomorphic, almost sarcomatoid appearing
• Most common in older people, in HIV-positive individuals, and in nonindustrialized countries
• Predilection for abdominal organs, spleen, liver and bone marrow without peripheral adenopathy
• The stage is usually advanced at diagnosis
• EBV is positive in the majority of cases

Nodular form of lymphocyte-predominant HL (NLPHL): 5%

• Pan-B markers positive (CD19, 20, 22, 79a, PAX5), κ >>> λ light-chain, CD45+, CD15-, CD30-, BCL6+, CD10-
• Presence of large neoplastic lymphocytes termed LP cells, and a host response rich in small lymphocytes and macrophages. LP cells have distinctly indented or lobulated nuclei (sometimes termed “popcorn cells” because of their appearance) delicate chromatin, small nucleoli, and pale-staining cytoplasm.
  • Small lymphocytes that are immediately adjacent to the LP cells forming rosettes around the LP cells.

• Histologic patterns: classic B-cell–rich nodular, serpiginous nodular, nodular variant with prominent extranodular LP cells, T-cell–rich nodular, and T-cell–rich DLBCL-like.
  • Recognition of areas within the tumor that show a diffuse growth pattern (T-cell–rich DLBCL-like) is important as these may reflect a more aggressive behavior.