Background: Histologic subtypes of classical Hodgkin lymphoma [cHL; e.g., nodular sclerosis, mixed cellularity, not otherwise specified (NOS)] are epidemiologically and prognostically distinctive. Therefore, unexplained, ongoing incidence rate declines for mixed cellularity and increases for NOS require examination. Methods: We analyzed detailed histology-specific Hodgkin lymphoma incidence rates in 1992 through 2011 U.S. SEER data (n = 21,372) and reviewed a regional subset of 2007 through 2011 NOS pathology reports for insight into diagnostic practices. Results: cHL rates were stable until 2007, then decreased for whites [annual percent change (APC) and 95% confidence interval (CI), -3.6% (-5.6% to -1.5%)]. Nodular sclerosis rates declined after 2007 by 5.9% annually, with variation by gender, age, and race/ethnicity. In 1992 through 2011, mixed cellularity rates declined [APC -4.0% (-4.7% to -3.3%)], whereas NOS rates rose [5.3% (4.5%-6.2%)] overall and in most patient groups. The 2007-2011 NOS age-specific rates were more similar to mixed cellularity rates for 1992-1996 than 2007-2011. Trends in combined rates were minimal, supporting increasing misclassification of mixed cellularity, lymphocyte depletion, and specific nodular sclerosis subtypes as NOS. Eighty-eight of 165 reviewed NOS pathology reports addressed classification choice. Twenty (12.1%) justified the classification, 21 (12.7%) described insufficient biopsy material, and coders missed specific subtype information for 27 (16.4%). Conclusion: Recent nodular sclerosis rate declines largely represent true incidence changes. Long-term rate decreases for mixed cellularity and other less common subtypes, and increases for NOS (comprising ~30% of cHL cases in 2011), likely reflect changes in diagnostic and/or classification practice. Impact: Diminishing histologic subtyping undermines future surveillance and epidemiologic study of Hodgkin lymphoma. Guideline-based use of excisional biopsies and more coding quality control are warranted.
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