The Reemergence of Measles: What Every Pathologist Needs to Know

Mary K. Klassen-Fischer, MD; Ann M. Nelson, MD; Ronald C. Neafie, MS; Fides A. Neafie, MD; Aaron Auerbach, MD, MPH; Thomas P. Baker, MD; Allen P. Burke, MD; Anandita A. Datta, MD; Teri J. Franks, MD; Iren Horkayne-Szakaly, MD; Ernest E. Lack, MD; Michael R. Lewin-Smith, MD; Alejandro Luiña Contreras, MD; Rubina H. Mattu, MD; Walter L. Rush, MD; Paul C. Shick, DDS, Yang Zhang, MD; Francisco J. Rentas, PhD; Joel T. Moncur, MD, PhD


Am J Clin Pathol. 2023;159(1):81-88. 

In This Article

Abstract and Introduction


Objectives: Present-day pathologists may be unfamiliar with the histopathologic features of measles, which is a reemerging disease. Awareness of these features may enable early diagnosis of measles in unsuspected cases, including those with an atypical presentation. Using archived tissue samples from historic patients, a unique source of histopathologic information about measles and other reemerging infectious diseases, we performed a comprehensive analysis of the histopathologic features of measles seen in commonly infected tissues during prodrome, active, and late phases of the disease.

Methods: Subspecialty pathologists analyzed H&E-stained slides of specimens from 89 patients accessioned from 1919 to 1998 and correlated the histopathologic findings with clinical data.

Results: Measles caused acute and chronic histopathologic changes, especially in the respiratory, lymphoid (including appendix and tonsils), and central nervous systems. Bacterial infections in lung and other organs contributed significantly to adverse outcomes, especially in immunocompromised patients.

Conclusions: Certain histopathologic features, especially Warthin-Finkeldey cells and multinucleated giant cells without inclusions, allow pathologists to diagnose or suggest the diagnosis of measles in unsuspected cases.


A rubeola (measles) vaccine became available in 1963; before then, infection was nearly ubiquitous during childhood. According to the Centers for Disease Control and Prevention, before the vaccine became available, approximately 3 to 4 million people were infected per year in the United States; of these, an estimated 48,000 required hospitalization, 1,000 developed encephalitis, and 400 to 500 died.[1–3] Widespread vaccination resulted in disease elimination in the United States in 2000 except for rare, imported cases and isolated outbreaks in unvaccinated communities; most countries in the developed world have had a similar experience. Consequently, most pathologists practicing today in industrialized nations have little or no experience with measles.

Measles is reemerging in the United States and other nations. The causes of the increase in the percentage of unvaccinated people in developed countries include vaccine hesitancy, decreased well-child visits during the coronavirus disease 2019 pandemic, and decreased vaccination rates among immigrants and travelers from countries with dysfunctional health care systems exacerbated by poverty, refugee crises, political instability, and climate change.[4–8] Familiarity with the histopathologic findings in measles enables pathologists to make an early diagnosis of measles in unsuspected cases. For example, diagnostic viral cytopathic changes may be observed in a child's appendectomy or tonsillectomy specimen before the appearance of a rash, Koplik spots, or conjunctivitis Figure 1 (Supplemental Figures 1 and 2; all supplemental materials can be found at American Journal of Clinical Pathology online), allowing earlier isolation to prevent infection among contacts. Also, characteristic histopathologic features may be identified in surgical or autopsy specimens from immunosuppressed individuals who did not mount an adequate antibody response and, therefore, did not develop a rash.[9] Our institution is a unique resource for analysis of the histopathology of measles because of the availability of numerous historical specimens and the cooperative efforts of subspecialists.

Figure 1.

Patient with characteristic rash of measles and cough.