Tertiary lymphoid structures are confined to patients presenting with unifocal Langerhans Cell Histiocytosis.
Langerhans cell histiocytosis (LCH) is a neoplastic myeloid disorder with a thus far poorly understood immune component. Tertiary lymphoid structures (TLS) are lymph node-like entities which create an immune-promoting microenvironment at tumor sites. We analyzed the presence and clinical relevance of TLS in n = 104 H&E-stained, therapy-naive LCH lesions of non-lymphoid origin and applied immunohistochemistry to a smaller series. Lymphoid-follicular aggregates were detected in 34/104 (33%) lesions. In line with the lymphocyte recruitment capacity of MECA-79(+) high endothelial venules (HEVs), MECA-79(+)-expressing-LCH lesions (37/77, 48%) contained the most CD3(+) T-lymphocytes (p = 0.003). TLS were identified in 8/15 lesions and contained T-and B-lymphocytes, Follicular Dendritic Cells (FDC), HEVs and the chemokines CXCL13 and CCL21 representing key cellular components and TLS-inducing factors in conventional lymph nodes (LN). Lymphoid-follicular aggregates were most frequently detected in patients presenting with unifocal LCH (24/70, 34%) as compared to patients with poly-ostotic or multi-system LCH (7/30, 23%, p = 0.03). In addition, patients with lymphoid-follicular aggregates-containing lesions had the lowest risk to develop new LCH lesions (p = 0.04). The identification of various stages of TLS formation within LCH lesions may indicate a key role for the immune system in controlling aberrant histiocytes which arise in peripheral tissues.
Immunology Laboratory, Willem Alexander Children's Hospital, Leiden University Medical Center , Leiden, the Netherlands.
Willemijn T
WT
Quispel
Immunology Laboratory, Willem Alexander Children's Hospital, Leiden University Medical Center , Leiden, the Netherlands.
Eline C
EC
Steenwijk
Immunology Laboratory, Willem Alexander Children's Hospital, Leiden University Medical Center , Leiden, the Netherlands.
Vincent
V
van Unen
Immunology Laboratory, Willem Alexander Children's Hospital, Leiden University Medical Center , Leiden, the Netherlands.
Susy J
SJ
Santos
Department of Pathology, Leiden University Medical Center , Leiden, the Netherlands.
Lianne
L
Koens
Department of Molecular Cell Biology and Immunology, VU University Medical Center , Amsterdam, the Netherlands.
Reina
R
Mebius
Division of Hematology/Oncology, University of Toronto/Hospital for Sick Children , Toronto, Canada.
R Maarten
RM
Egeler
Immunology Laboratory, Willem Alexander Children's Hospital, Leiden University Medical Center , Leiden, the Netherlands.
Astrid G S
AG
van Halteren
High endothelial venules; Langerhans cell histiocytosis; inflammatory; lymphocytes; lymphoid aggregates; myeloid neoplastic; prognosis; tertiary lymphoid structures