Comparison of pS6 staining across CD subtypes and other lymphoproliferative diseases. (A) pS6 across different CD subtypes. A second cohort of iMCD-TAFRO patients (cohort 2, n = 10) was compared with iMCD-NOS (n = 6), HHV-8–associated MCD (HHV8 MCD, n = 4), and UCD (n = 7). The proportion of pS6 staining was similar across both clinical subtypes of iMCD as well as HHV-8–associated MCD. Comparison between the combined iMCD cases (n = 16) and the UCD cases (n = 4) showed nonsignificant increase in pS6-staining of the germinal center (P = .17), mantle zone (P = .065), and interfollicular space (P = .089). Of note, a 1-tailed test comparing expression in the interfollicular space of iMCD to UCD would have been significant, but the a priori hypothesis involved testing for difference, not directional difference. (B) The second cohort of iMCD-TAFRO patients and the iMCD-NOS cases were combined and compared with a control group of sentinel lymph nodes, a second control group of reactive lymph nodes, and to 3 other diseases involving lymphoproliferation and inflammatory lymphadenopathy: SLE, HL, and ALPS. pS6 could only be assessed in the interfollicular space of the HL cases due to disruption of the remainder of lymph node architecture. ALPS and iMCD had similar pS6 staining; the iMCD group had significantly higher staining in the interfollicular space compared with SLE, HL, reactive nodes, and sentinel nodes (P = .001, .01, .032, and .019, respectively). (C-H) Representative images of pS6-stained (brown) lymph node tissue (with blue hematoxylin counterstain) for (C) reactive lymph nodes, (D) SLE, (E) HL, (F) iMCD-TAFRO, (G) ALPS, and (H) UCD. Scale bars, 200 µm. *P < .05, **P < .01.