Hodgkin's‐like PTLD versus true Hodgkin's disease

The editorial by Ranganathan and Jaffe (1) that accompanied our article on Hodgkin lymphoma after post-transplant lymphoproliferative disease (PTLD) (2) in a recent issue of Pediatric Transplantation was quite informative; however, we would like to point out some oversights in the editorial discussion and offer some clarifications. The editorial authors have highlighted the issue of true Hodgkin’s disease (HD) vs. Hodgkin’s like PTLD (HL-PTLD). We have noted that the editorial questions our diagnosis of true Hodgkin’s disease, or what we classified as Hodgkin lymphoma according to the World Health Organization classification schema (3). It appears that the authors of the editorial did not ascertain our complete phenotype as described. They accurately outlined the fact that CD30 and CD15 positivity is seen in Hodgkin lymphoma and that CD30 without CD15 expression strongly favors the diagnosis of HL-PTLD (4). It appears, however, that they did not realize that the large atypical Reed-Sternberg (R-S) cells in our case were CD15 positive, as was stated in our article (page 89, para 2 and Fig. 1c). Secondly, they mentioned that strong CD20 positivity would be unusual for Hodgkin lymphoma. CD20 positivity is a well-documented finding in classical Hodgkin lymphoma and has been described in up to 30–40% of cases (4–7). Additionally, classical Hodgkin lymphoma typically demonstrates a variable pattern and intensity of CD20 staining of the R-S cells, as was seen in our case. Thirdly, they stated we did not comment as to whether or not Epstein-Barr encoded RNA (EBER) 2 expression was restricted to the large atypical cells. This assertion is true. The restricted of the EBER positivity to only the large atypical cells was implied but not explicitly stated in our article. In our case EBER positivity was, in fact, restricted to the R-S cell population and was positive in only a subpopulation of R-S cells. In PTLD, EBER positivity is often more wide spread, involving B-cells of variable morphology, not just the large atypical cell population. Another finding not explicitly stated, but one that warrants clarification, is that CD45 staining in the large atypical cells, where ascertainable, was negative. CD45 negativity would be a very unusual finding in B-cell PTLD. In summary, our case demonstrated a small lymphocytic infiltrate comprised of predominantly T-cells (original article page 89, para 2) with scattered large atypical cells demonstrating R-S morphology (as shown in Fig. 1a of the original article). These large atypical R-S cells were CD30 positive (Fig. 1b of the original article), CD15 positive (Fig. 1c of the original article), variably positive for CD20 and CD45 negative. EBER positivity was restricted to the R-S as shown in Fig. 1d of the original article. In a patient with a history of transplantation, it is indeed difficult to distinguish between PTLD vs. classical Hodgkin lymphoma. However, we maintain that the morphologic and phenotypic features in our case favor the diagnosis of classical Hodgkin lymphoma, and that there are a number of features that mitigate against the diagnosis of HL-PTLD.