Y Saeki

Immune checkpoint inhibitors (ICIs) exert clinical efficacy against various types of cancers by reinvigorating exhausted CD8 + T cells that can expand and directly attack cancer cells (cancer-specific T cells) among tumor-infiltrating lymphocytes (TILs). Although some reports have identified somatic mutations in TILs, their effect on antitumor immunity remains unclear. In this study, we successfully established 18 cancer-specific T cell clones, which have an exhaustion phenotype, from the TILs of four patients with melanoma. We conducted whole-genome sequencing for these T cell clones and identified various somatic mutations in them with high clonality. Among the somatic mutations, an SH2D2A loss-of-function frameshift mutation and TNFAIP3 deletion could activate T cell effector functions in vitro. Furthermore, we generated CD8 + T cell–specific Tnfaip3 knockout mice and showed that Tnfaip3 function loss in CD8 + T cell increased antitumor immunity, leading to remarkable response to PD-1 blockade in vivo. In addition, we analyzed bulk CD3 + T cells from TILs in additional 12 patients and identified an SH2D2A mutation in one patient through amplicon sequencing. These findings suggest that somatic mutations in TILs can affect antitumor immunity and suggest unique biomarkers and therapeutic targets.

Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma (CTCL), presents with various clinical and histopathological manifestations. When associated with pseudocarcinomatous hyperplasia (PCH), marked keratinization and verrucous lesions that mimic verrucous carcinoma (VC) can appear. Reports of PCH associated with MF are scarce and misdiagnosis as VC or squamous cell carcinoma (SCC) can occur.1 We present a case of MF with PCH that required a reevaluation of the initial diagnosis.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal, diffuse, large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumen of small blood vessels, with no lymphadenopathy or masses. Herein, we report a cutaneous variant of IVLBCL that is rare in Asia. A healthy 73-year-old Japanese woman presented to our hospital with painful erythematous indurations and telangiectasia of the lower extremities, which was confirmed on dermoscopy. Physical examination revealed no systemic involvement, and laboratory parameters were within normal ranges. No abnormal fluorodeoxyglucose (FDG) uptake was detected on 18FDG positron emission tomography/computed tomography. Histopathological examination revealed proliferation and dilatation of blood vessels in the subcutis layer, occluded by CD20-positive atypical lymphoid cells. Thus, the patient was diagnosed with a cutaneous variant of IVLBCL without systemic symptoms. In conclusion, it is important to confirm telangiectasia using dermoscopy and perform skin biopsies in patients presenting with sudden-onset erythematous induration.