LAUSR

T-cell receptor (TCR) is associated with diverse antigen recognition in T-cells [1]. Peripheral T-cell lymphomas (PTCLs) are the neoplastic counterpart of postthymic T-cells [2] and usually express either αβ-TCR or γδ-TCR. However, rare cases of PTCLs that lack TCR, termed as TCR-silent PTCL, have also been reported [2–5]. A 72-year-old man presented with a 1-month history of intermittent fever and general malaise. Laboratory investigation showed pancytopenia (white blood cell count, 1.2 × 103/μL; hemoglobin level, 11.1 g/dL; and platelet count, 73 × 103/μL) and 16% of atypical lymphocytes (Fig. 1a). Serum lactate dehydrogenase and ferritin levels were increased (749 IU/L and 15,090 μg/L, respectively), and disseminated intravascular coagulation was noted. Epstein-Barr virus (EBV) DNA levels in the peripheral blood were not elevated. Bone marrow examination showed a small population of atypical lymphocytes (Fig. 1b). Hemophagocytosis, which collectively suggested hemophagocytic lymphohistiocytosis (HLH), was also noted (Fig. 1c). Positron emission tomography/computed tomography detected a diffusely increased uptake in the enlarged spleen, liver, and bones (Fig. 1d). Bone marrow biopsy analysis was inconclusive; therefore, we performed splenectomy. The white pulp of the spleen was infiltrated by neoplastic lymphoid cells, which were immunohistochemically positive for CD45 and CD2 but negative for CD20, CD79a, CD10, CD3, CD4, CD8, CD5, CD56, granzyme B, TIA-1, and EBVencoded RNA on in situ hybridization. Monoclonal rearrangements of the TCR-β genes were detected (Fig. 1e), whereas neither TCR-αβ nor TCR-γδ was expressed (Fig. 1f). Chromosomal examination showed abnormalities of 86 ~ 89,XXY, + X,-Y, + 3,i(3)(q10) × 2,-4,-5,-7,9,add(9)(p11),add(9)(p11) × 2,-13,-13,?add(14)(p11.2),15,add(16)(q12-13) × 2,-22, + 4 ~ 7mar[cp5]/46,XY[5]. These findings confirmed PTCL, not otherwise specified with TCR-silent subtype. Notably, the fever subsided after splenectomy, and cytopenia and coagulopathy were dramatically improved. The findings of HLH remained in remission with splenectomy; however, the improvement was transient for 2 months. Once the disease relapsed, chemotherapy including dose-adjusted EPOCH (etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin), GDP (gemcitabine, dexamethasone, and cisplatin), and pralatrexate had only a short effect, and remission could not be sustained. In the present case of TCR-silent PTCL, CD3, CD4, and CD8 were concomitantly absent, suggesting that the lymphoma cells were derived from thymocytes that have yet to express TCR and CD3 [2]. These “immature” T-cells are usually mortal, but leukemic transformation potentially let them avoid cell death [3]. Clinically, the TCR-silent subtype is a predictor of poor prognosis in PTCLs, because it has a predominant extranodal presentation and an aggressive clinical course [3, 4]. There has been no previous investigation of the causative factors for its aggressive phenotype, but the present case, in which HLH was the hallmark of disease progression, may provide insights into the pathophysiology of TCR-silent PTCL: HLH in aggressive PTCL is usually * Yasushi Onishi [email protected]