title: Time Trends in Rates of Hodgkin Lymphoma Histologic Subtypes: True Incidence Changes or Evolving Diagnostic Practice?
abstract: 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%).
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cancer Prevention Institute of California, Fremont, California. Department of Health Research and Policy (Epidemiology), Stanford University School of Medicine, Stanford, California. sally.glaser@cpic.org.
authors.forename: Sally L
authors.initials: SL
authors.lastname: Glaser
authors.affiliation: Cancer Prevention Institute of California, Fremont, California. Department of Health Research and Policy (Epidemiology), Stanford University School of Medicine, Stanford, California.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Clarke
authors.affiliation: Cancer Prevention Institute of California, Fremont, California. Department of Health Research and Policy (Epidemiology), Stanford University School of Medicine, Stanford, California.
authors.forename: Theresa H M
authors.initials: TH
authors.lastname: Keegan
authors.affiliation: Department of Health Research and Policy (Epidemiology), Stanford University School of Medicine, Stanford, California. Health Sciences Practice, Exponent, Inc., Menlo Park, California.
authors.forename: Ellen T
authors.initials: ET
authors.lastname: Chang
authors.affiliation: Department of Pathology, City of Hope National Medical Center, Duarte, California.
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D005260:Female; D006689:Hodgkin Disease / Q000453:epidemiology* / Q000473:pathology; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D011379:Prognosis; D012189:Retrospective Studies; D018426:SEER Program; D017678:Sex Distribution; D014481:United States / Q000453:epidemiology; D055815:Young Adult