The hallmark of tuberculosis (TB) is the formation of immune cell-enriched aggregates called granulomas. While granulomas are pathologically diverse, their tissue-wide heterogeneity has not been spatially resolved at the single-cell level in human tissues. By spatially mapping individual immune cells in every lesion across entire tissue sections, we report that in addition to necrotizing granulomas, the human TB lung contains abundant non-necrotizing leukocyte aggregates surrounding areas of necrotizing tissue. These cellular lesions were more diverse in composition than necrotizing lesions and could be stratified into four general classes based on cellular composition and spatial distribution of B cells and macrophages. The cellular composition of non-necrotizing structures also correlates with their proximity to necrotizing lesions, indicating these are foci of distinct immune reactions adjacent to necrotizing granulomas. Together, we show that during TB, diseased lung tissue develops a histopathological superstructure comprising at least four different types of non-necrotizing cellular aggregates organized as satellites of necrotizing granulomas.

No abstract

Context.— There is a global decline in medical graduates pursuing pathology careers, resulting in a broadening gap between workforce demand and supply. Objective.— To determine causes of low popularity of pathology as a career and develop strategies to avoid a workforce crisis. Design.— An online survey was distributed and yielded 1247 responses, including 609 Australian medical students from 10 medical schools, 119 prevocational doctors from 10 major teaching hospitals in New South Wales, 175 residents, and 344 pathologists throughout Australia. Results.— Compared with pathology-uninterested peers, students and prevocational doctors interested in pathology careers were more likely to value research opportunities (57 of 166 [34.3%] pathology-interested respondents versus 112 of 521 [21.5%] pathology-uninterested respondents; odds ratio [OR] = 1.91, P < .001), have children (19 of 165 respondents [11.5%] versus 22 of 522 respondents [4.2%]; OR = 2.96, P < .001), and self-identify as introverted (87 of 167 respondents [52.1%] versus 179 of 526 respondents [34%]; OR = 2.1, P < .001). Those uninterested in pathology were more likely to value patient interaction (363 of 524 respondents [69.3%] versus 71 of 166 respondents [42.8%]; OR = 3.02, P < .001). Lack of exposure to pathology was the most-cited reason for rejecting pathology (after lack of patient interaction). There was poor understanding of the role of pathologists and low confidence in the ability to interpret histopathology reports among medical students and prevocational doctors. Negative stereotypes regarding pathologists were identified. Conclusions.— Active interventions increasing exposure of medical students and prevocational doctors to pathology as a career, as well as promotion of research opportunities and potential for work–life balance, are needed to address pending workforce shortages.

SummaryThe histopathological hallmark of tuberculosis (TB) is the formation of immune cell enriched aggregates called granulomas, but the scope of granuloma heterogeneity in human TB is unknown. By spatially mapping individual immune cells across large regions of TB lung tissue, we report that in addition to necrotizing granulomas, the human TB lung contains abundant non-necrotizing leukocyte aggregates surrounding areas of necrotizing tissue. These cellular lesions were more diverse in composition than necrotizing lesions and could be stratified into four general classes based on cellular composition and spatial distribution of B cells and macrophages, indicating there are foci of distinct immune reactions adjacent to necrotizing granulomas. We further show that the specific cellular composition of non-necrotizing structures correlates with their proximity to necrotizing lesions. Together, our study shows that during tuberculosis diseased lung tissue develops a histopathological superstructure comprising at least four different types of non-necrotizing cellular aggregates organized as satellites of necrotizing granulomas.