A 79-year-old man was presented with bilateral axillary
lymphadenopathy. The biopsied nodes were obliterated by vague
nodules, composed of non-cohesive proliferation of giant cells,
including Reed-Sternberg cells, and various inflammatory cells (panel
A; x10 objective, inset; x100 objective). In addition, a single well
demarcated Langerhans cell (LC) cluster was identified as a “tumor
in tumor” pattern (panel B; red arrows, x10 objective, inset; x100
objective). Immunohistochemistry and ISH revealed the giant cells to
be positive for CD15 (panel C; x40 objective), CD30, PAX5, and EBER.
The LCs were positive for CD207 (Langerin) (panel D; x20 objective),
and CD1a. BRAF V600E-expressing cells were absent. A diagnosis of
classic Hodgkin lymphoma (mixed cellularity type) with possible LC
histiocytosis was given (Figure 1A). The patient is free of disease for
27 months after chemotherapy
The interpretation that LCH is a neoplastic disorder derived
from LCs has been accepted as in WHO classification, revised 4th ed,
(WHO- 2017) [1], for example. For diagnosing LCH, CD207 / Langerin
expression should be confirmed immunohistochemically, in addition
to histologic findings (Figure 1B). Although clonality of LCH was
previously suggested only in a part of the female cases, a recurrent
BRAF V600E mutation was recently found in more than a half of
patients with LCH [2], and the possibility of its neoplastic nature
has been increasing. However, there are still some arguments about
the possibility of being an inflammatory process [3]. One study has
shown that some of the BRAF V600E-negative LCH cases had BRAF
V600E mutation (Figure 1C). It implies that BRAF V600E should be
assessed by direct sequencing [4]. Also, the frequency of MAPK2K1
mutation appears to be high in BRAFV 600E mutation-negative LCH
cases [5].
The development of LCH with lymphoid and myeloid neoplasms
is known as one of a feature of LCH [6]. Egeler, et al. reported 91
patients with LCH having other neoplasia (Figure 1D). In their series,
39 patients had lymphoma consisting of 25 patients with “Hodgkin’s
disease” at that time [7]. Reactive or neoplastic nature of LC
proliferation and clonal relation between it and CHL in our case are
unclear, because BRAF V600E was immunohistochemically negative
in both processes [8-14]. Very focal LC proliferation hampered
further study. Accumulation of such cases is required to characterize
significance of “tumor in tumor” of this combination.
Weiss LM, et al. (2008) Tumours derived from Langerhans cells. In: Swerdlow SH, et al (Eds.)., WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised (4th)., Lyon. IARC Press, pp. 470-72.