Langerhans cells are one subset of hematopoietic cells, thought to derive from monocyte-macrophage lineage. They are specialized dendritic cells in skin or mucosal sites devoted to antigen presentation to T cells upon activation. They are then thought to migrate to lymph node through lymphatics. Physiologically, Langerhans cells can respond in a non-clonal fashion to certain reactive stimuli such as smoking, in the lung [8
]. Alternatively, they can proliferate in a clonal pattern, forming tumors designated as LCH and much less commonly as LCS. LCH can also be associated with other disease processes such as malignant lymphoma, and myasthenia gravis [10
], but there is still debate about whether these represent a clonal or non-clonal reactive process in those situations.
LCH and LCS have been believed to originate from myeloid stem cells [12
] rather than lymphoid stem cells, but some recent experimental and clinical evidence has argued against this belief [17
]. Furthermore, some clinical reports have suggested that both B- and T-cell neoplasms can transdifferentiate into LCH and LCS after prolonged treatment of the original disorders [19
], suggesting that in these hematolymphoid neoplasms the tumor cells have some potential for lineage plasticity, somewhat comparable to the leukemias with lineage plasticity, acute leukemias of ambiguous lineage in the 2008 WHO hematolymphoid tumour classication. Because of its linkage to the T-cell receptor molecules surface membrane CD3 is felt to be the most specific T lineage marker along with cytoplasmic epsilon chain, although CD3 epsilon chain can be expressed in cytoplasm of NK cells and thymocytes. Furthermore aberrant CD3 expression has been reported in other hemotopoietic tumours such as diffuse large B cell lymphoma, primary mediastinal large B cell lymphoma, plasmablastic lymphoma and classical Hodgkin’s lymphoma [24
] but not in histiocytic sarcoma. In addition, LCH can co-exist with T cell lymphoblastic lymphoma in the same tissue, making the correct diagnosis difficult [28
In our case, because of the expression of cytoplasmic CD3 and CD4, we performed T cell receptor (TCR) gene arrangement studies for gamma, delta and beta chains by PCR to rule out the possibility of T cell lineage transdifferentiation or lineage plasticity. The results failed to demonstrate a clonal rearrangement pattern, suggesting that the LCS tumor cells had an aberrant cytoplasmic CD3 expression rather than a T cell transdifferentiation phenomenon.
As a rare subtype of sarcoma, LCS has a poor prognosis [30
]. Although the prognostic factors in LCS were not known, they might include prognostic factors common to other rare sarcomas, such as patient age, tumor size, tumor cell grade, proliferation rate, and/or stage. [31
]. DNA ploidy had been proposed as one of the prognostic factors in some subtypes of sarcoma [31
], although another study does not show ploidy status to be an independent prognostic factor [35
]. The prognostic role of DNA ploidy in LCS had never been explored. In our case, due to the rarity of LCS and finesse of the technique, DNA ploidy study was not performed.
Among the reported LCS cases [1
], patients had a predominantly female distribution with a median age of 39
years old, ages ranging from 10 to 72
years. Our patient, at 86 was thus the oldest reported to date.