Clinical significance and predictive risk factors for event-free survival at 24 months in patients with PTCL, NOS.

Peripheral T cell lymphoma, not otherwise specified (PTCL, NOS), is a heterogeneous and aggressive type of non-Hodgkin's lymphoma with a bleak prognosis. This study was designed to assess the value of EFS24 as an alternative clinical endpoint and identify prognosis-related factors in PTCL, NOS. Patients diagnosed with PTCL, NOS were retrospectively collected and slides were reviewed by two hematopathologists. EFS was defined as the time from diagnosis to the occurrence of disease progression after initial treatment, retreatment, or death. Subsequent overall survival (OS) was defined from EFS24 or time of progression, if it occurred within 24 months, to the last follow-up or death. 97 cases with complete follow-up were selected. Approximately 66 patients (68.04%) failed to achieve ES24, with the median OS of 12.17 months, and 5-year OS rate of 15.17%. While patients who reached EFS24 had a median OS of 60.57 months and a 5-year OS rate of 68.77%. Multivariate Cox analysis indicated that bone marrow involvement and elevated ß2 Microglobulin (ß2-MG) were associated with a poor prognosis. B symptoms, extranodal involvement more than one site, and a high Ki67 index were significant factors in predicting the failure of EFS24. EFS24 can help stratify the subsequent outcomes of PTCL, NOS. Patients who achieve EFS24 have a favorable prognosis, although it does not reach that of the general population. On the other hand, patients who do not achieve EFS24 have an extremely poor prognosis. Therefore, EFS24 can be used for patient risk stratification, patient counseling, and study design.

Immunophenotypic classification regarding prognosis in peripheral T cell lymphoma, NOS, and nodal T follicular helper T cell lymphoma, angioimmunoblastic-type.

This study aimed to determine the clinicopathological predictive factors of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), and nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFH, AI-type). In this single-centered, retrospective study, medical records of 59 patients who were diagnosed with PTCL, NOS, or nTFH, AI-type from March 2007 to September 2022 were reviewed. The clinicopathological variables, including immunohistochemistry(IHC) subgroups, distinguishing TBX21 from the GATA3 subgroups were analyzed. Overall, 28 patients (75.7%) in the TBX21 group were PTCL, NOS. There were 9 (24.3%) patients in the GATA3 group. In univariable analyses, lymphoma subtype, age, and performance status were associated with progression-free survival (PFS), and overall survival (OS). In multivariable analyses, lymphoma subtype, and performance status were related to PFS and OS (P = 0.012, P < 0.001, P = 0.006, and P < 0.001, respectively). The GATA3 subgroup tended to have a worse prognosis in univariable analyses; however, it became more insignificant in multivariable when lymphoma subtype and performance status were adjusted (P = 0.065, P = 0.180, P = 0.972, and P = 0.265, respectively). The double-positive group showed variable prognoses of better PFS and worse OS. PD-1 and PD-L1 were associated with the EBV in situ hybridization (P = 0.027, and P = 0.005), and PD-1 was associated with CD30 expression (P = 0.043). This study demonstrated the potential of IHC classification to predict prognosis for PTCL, NOS, as well as nTFH AI-type, although further validation is necessary. Treatments targeting CD30, PD-1, and PD-L1 appear promising for lymphoma treatment.

Predictive model for treatment outcomes of peripheral T-cell lymphoma, not otherwise specified, in Taiwanese patients.

PURPOSE: We aimed to explore the clinical outcomes and prognostic factors for PTCL-NOS patients in the real world. METHODS: Clinical data were retrospectively collected from adult patients with PTCL-NOS treated at a single center in Taiwan. RESULTS: 104 PTCL-NOS patients with a median age of 53.0 years were enrolled. Patients with the International Prognostic Index (IPI) or prognostic index for peripheral T-cell lymphoma (PIT) scores of zero had a longer overall survival (OS) and progression free survival (PFS), while patients with IPI or PIT scores ≥1 did poorly. For patients who are eligible for transplantation, the use of pralatrexate as salvage chemotherapy has shown better OS (2-year OS 83.3% vs. 24.4%, P = 0.011) compared to patients who did not. By multivariate analysis, age >60 years, male, B symptoms, ECOG >1, lung involvement, and thrombocytopenia were independent adverse factors for OS. Incorporating factors in multivariate analysis, we established a novel predictive index for PTCL-NOS which efficiently stratifies patients into low (0-1 factor), intermediate-1 (2 factors), intermediate-2 (3 factors), and high risk (4-6 factors) groups with 2-year OS rates of 81.5%, 32.9%, 8.8%, and 0%, respectively (P < 0.001). CONCLUSION: PTCL-NOS patients have a dismal prognosis in Taiwan. Novel agents may improve the outcomes of PTCL-NOS patients. The usefulness of the novel prognostic index for PTCL-NOS needs further validation.

[Discordant lymphoma of diffuse large B-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified in a human T-cell leukemia virus type-I carrier].

A 69-year-old man was diagnosed with diffuse large B-cell lymphoma (DLBCL) negative for Epstein-Barr virus-encoded small nuclear RNA 1 (EBER-1) in October 2011, when he was also diagnosed as having a human T-cell leukemia virus type-I (HTLV-1) carrier. He achieved complete response after six courses of R-CHOP therapy. In February 2015, the patient had high fever and markedly elevated serum lactate dehydrogenase (LDH) level. Bone marrow examination revealed infiltration of CD4-positive T-cell malignancy. Based on the tentative diagnosis of adult T-cell leukemia/lymphoma, modified LSG15 therapy was initiated. His symptoms and serum LDH level quickly improved after the start of treatment. During the treatment, HTLV-1 proviral DNA integration was reported negative, allowing his final diagnosis to be peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Despite discontinuation of chemotherapy in the middle of the second course due to the patient's preference, complete remission was reached. He remains in clinical remission at 28 months after the treatment discontinuation. Discordant lymphoma of DLBCL and PTCL-NOS in HTLV-1 carrier has not been well characterized and will be discussed with a literature review.

PD-L1 expression on tumor or stromal cells of nodal cytotoxic T-cell lymphoma: A clinicopathological study of 50 cases.

Inhibitors of programmed cell-death 1 (PD-1) and programmed cell-death ligand 1 (PD-L1) have revolutionized cancer therapy. Nodal cytotoxic T-cell lymphoma (CTL) is characterized by a poorer prognosis compared to nodal non-CTLs. Here we investigated PD-L1 expression in 50 nodal CTL patients, with and without EBV association (25 of each). We identified seven patients (14%) with neoplastic PD-L1 (nPD-L1) expression on tumor cells, including three males and four females, with a median age of 66 years. One of the seven cases was TCRαß type, three were TCRγδ type and three were TCR-silent type. Six of the seven cases exhibited a lethal clinical course despite multi-agent chemotherapy, of whom four patients died within one year of diagnosis. Morphological findings were uniform, with six cases showing centroblastoid appearance. Among nPD-L1+ cases, two of three examined had structural variations of PD-L1 disrupting 3'-UTR region. Notably, all of the TCRγδ-type nodal CTL cases showed nPD-L1 or miPD-L1 positivity (3 and 10 cases, respectively). TCRγδ-type cases comprised 42% of nPD-L1+ cases (P = 0.043 vs. PD-L1- ), and 35% of miPD-L1+ cases (P = 0.037 vs. PD-L1- ). The results indicate that PD-L1+ nodal CTL cases, especially of the TCRγδ type, are potential candidates for anti-PD-1/PD-L1 therapies.

Phase II Trial Using Romidepsin after Gemcitabine, Dexamethasone, and Cisplatin Therapy in Elderly Transplant-Ineligible Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma: Study Protocol.

Romidepsin is an important therapeutic option for patients with peripheral T-cell lymphoma (PTCL). However, the timing of romidepsin administration remains controversial. Romidepsin was launched in Japan as a consolidation therapy agent after conventional salvage chemotherapy with gemcitabine, dexamethasone, and cisplatin (GDP). GDP therapy will be administered every 3 weeks. If complete response, partial response, or stable disease is confirmed after 2-4 GDP cycles, romidepsin will be administered every 4 weeks. The primary endpoint is a 2-year progression-free survival rate. Patients participating in this study and undergoing treatment can expect results similar to or better than those of conventional therapies.

Reappraisal of nodal Epstein-Barr Virus-negative cytotoxic T-cell lymphoma: Identification of indolent CD5+ diseases.

Nodal cytotoxic molecule (CM)-positive peripheral T-cell lymphoma (CTL) has recently been recognized as a clinicopathologically distinct disease. To further characterize this disease, here we compared 58 patients with Epstein-Barr virus (EBV)-negative CTL to 48 patients with EBV-positive CTL. The two groups did not differ in histopathology, T-cell receptor (TCR) expression or rearrangement incidences, or survival curves. However, patients with EBV-negative CTL less frequently showed hepatic involvement (P = .007), B symptoms (P = .020), hemophagocytosis (P = .024), and detectable CD4 (P = .002) and CD5 (P = .009). Univariate and multivariate analyses identified three factors that independently predicted favorable survival, onset age <60 years (P = .002), CD5 expression (P = .002), and mixed morphology (P = .013), TCRαß was not an independent predictor (P = .30), but was strongly linked with long survivorship among patients younger than 60 years old. A prognostic model incorporating these factors worked well for prognostic delineation, independently of the International Prognostic Index (P = .007 vs P = .082) and Prognostic Index for PTCL (P = .020 vs P = .15). Moreover, this constellation of findings indicated two nodal indolent diseases: CD5+ TCRαß (n = 13), and CD5+ NK-cell type lacking TCR expression or clonal TCRγ rearrangement (n = 4). The survival curves for these two groups were significantly superior to others (n = 29, P < .001). These diseases appear to be unique in their indolent clinical behavior, and should be managed differently from other diseases.

Rapidly progressive renal failure due to tubulointerstitial infiltration of peripheral T-cell lymphoma, not otherwise specified accompanied by uveitis: a case report.

BACKGROUND: Rapid decline in renal dysfunction due to primary renal lymphoma, or secondary renal lymphoma by infiltration from a primary origin, is extremely rare. There are notably few reports indicating infiltration of T-cell lymphoma into the kidney. CASE PRESENTATION: A 61-year-old woman with a sudden body rash and liver dysfunction was brought to our hospital presenting with a dull headache and blurred vision. Laboratory tests revealed rapidly progressive renal failure. Histological examination of the kidney and skin indicated infiltration of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Infiltration of PTCL-NOS to the liver and spleen, and presence of Uveitis masquerade syndrome were suspected. Imaging showed that the lesion was limited to extralymphatic organs. Renal function was improved with administration of steroids, including pulse steroid therapy, before administering cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) therapy. CONCLUSIONS: This is the first reported case of rapidly progressive renal failure caused by perivascular tubulointerstitial nephritis with the direct invasion of PTCL-NOS. In our case, a single steroid dose showed dramatic results with respect to renal symptoms.

CHOP or THP-COP regimens in the treatment of newly diagnosed peripheral T-cell lymphoma, not otherwise specified: a comparison of doxorubicin and pirarubicin.

The CHOP regimen consisting of cyclophosphamide, doxorubicin (DOX), vincristine and prednisolone has been the most used regimen for peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Pirarubicin [tetrahydropyranyladriamycin (THP)], a derivative of DOX, is an anthracycline with reportedly less cardiotoxicity than DOX. Here, we confirmed the efficacy of THP-COP using THP instead of DOX in the treatment of PTCL-NOS. The study protocol employed a retrospective, consecutive entry design. We retrospectively analysed 56 patients with PTCL-NOS who had received THP-COP or CHOP. These regimens were performed every 21 days. Twenty-nine patients received THP-COP, and 27 received CHOP. There were no significant differences in known prognostic factors, including in the International Prognostic Index (IPI) and the prognostic index for T-cell lymphoma (PIT), between the two groups. Complete remission rates in patients with THP-COP and CHOP were 52% in both groups; the 3-year overall survival (OS) rates were 67% and 52% (p = 0.074), and the 3-year progression-free survival (PFS) rates were 51% and 29% (p = 0.070), respectively. In patients with low IPI (low or low-intermediate), THP-COP had significantly better 3-year OS (100% vs. 64%; p < 0.001) and 3-year PFS (75% vs. 33%; p < 0.05) than CHOP. Similar differences between THP-COP and CHOP were observed in patients with a low PIT (groups 1 or 2). Our study showed that THP-COP produced results equivalent to CHOP regarding efficacy and safety in patients with PTCL-NOS. In patients with low IPI or PIT, THP-COP resulted in significantly better prognosis. Copyright © 2015 John Wiley & Sons, Ltd.

Comparison of clinicopathological characteristics between T-cell prolymphocytic leukemia and peripheral T-cell lymphoma, not otherwise specified.

OBJECTIVES: T-cell prolymphocytic leukemia (T-PLL) is a very rare, aggressive T-cell neoplasm. Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is also a highly aggressive lymphoma. These two diseases can often be confused with each other; therefore, we aimed to determine the clinical and pathological differences between T-PLL and PTCL-NOS. METHODS: We analyzed 15 T-PLL and 91 PTCL-NOS patients and also compared clinical features between T-PLL and PTCL-NOS with leukemic presentation. Peripheral blood images and biopsy specimens were analyzed, and treatment responses were determined via imaging modalities. The clinicopathological characteristics were statistically compared. RESULTS: T-PLL cells were smaller in size than those of PTCL-NOS with leukemic presentation (P=.0068); moreover, PTCL-NOS cells with leukemic presentation were smaller than those of PTCL-NOS without leukemic presentation (P=.0017). Immunophenotypic patterns in T-PLL and PTCL-NOS were similar. Five-year overall survival rates of T-PLL and all PTCL-NOS patients were 57.5% and 36.8%, respectively. No significant differences were found in clinical manifestations or prognoses; T-PLL and PTCL-NOS with leukemic presentation had essentially equivalent characteristics. CONCLUSION: T-PLL and PTCL-NOS may share common biological and clinical characteristics in Japanese patients.

Primary Cutaneous Peripheral T-Cell Lymphoma in a Sporotrichoid Pattern: A Case Report.

We present the extraordinary case of a 72-year-old man with a history of primary cutaneous peripheral T-cell lymphoma not otherwise specified (pcPTCL-NOS) previously controlled with topical agents who developed tumours in a sporotrichoid pattern. Culture of the tumours was negative, and histopathology showed findings consistent with recurrent pcPTCL. The tumours were successfully treated with localised radiation therapy. Sporotrichoid lesions are an extremely rare and atypical presentation of cutaneous lymphoma, with only 2 other cases reported in the literature. Our case reinforces the need to include cutaneous lymphoma in the differential diagnosis of nodules on the extremities spreading in a sporotrichoid pattern. Clinical recognition of this atypical presentation of cutaneous lymphoma allows for prompt, effective treatment, which might include localised radiation therapy.

Clinical and prognostic differences between ALK-negative anaplastic large cell lymphoma and peripheral T cell lymphoma, not otherwise specified: a single institution experience.

Clinical differences between anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALK(-) ALCL) and peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), remain unclear. The aim of this study was to compare the clinical and prognostic features of these two lymphoma types. We retrospectively analyzed 167 patients with ALK(-) ALCL (n = 48) and PTCL-NOS (n = 119). Compared with ALK(-) ALCL patients, PTCL-NOS patients exhibited distinct differences in clinical features with a propensity for more advanced stages, frequent extranodal involvement, and a poor performance status, leading to a higher risk group according to the International Prognostic Index or Prognostic Index for PTCL-NOS. Patients with ALK(-) ALCL were associated with a higher complete response rate (47.9 vs. 31.0 %; P = 0.041) after initial chemotherapy than patients with PTCL-NOS. The prognosis was significantly different between two subtypes, with a 5-year overall survival (OS) rate of 57.9 % for ALK(-) ALCL and 23.9 % for PTCL-NOS (P = 0.002). The subgroup analysis showed significant differences in OS and progression-free survival between the two subtypes in early-stage diseases, but not in advanced-stage diseases. We conclude that patients with ALK(-) ALCL showed favorable clinical features, higher chemosensitivity, and a superior outcome than those with PTCL-NOS.

A case of peripheral T-cell lymphoma in which therapy-related myelodysplastic syndrome developed and a second autologous transplantation was performed.

We report a case of therapy-related myelodysplastic syndrome (MDS), which developed 9 years after autologous peripheral blood stem cell transplantation (PBSCT) for peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). A 65-year-old male was diagnosed with PTCL-NOS. After 6 cycles of the CHOP (cyclophosphamide [CPA], doxorubicin, vincristine, and prednisone) regimen, he achieved a first complete response (CR). He relapsed 33 months later and received salvage chemotherapy, which consisted of the CHASE regimen (CPA, high-dose cytarabine, dexamethasone, and etoposide). During the recovery phase of the first cycle of CHASE, his peripheral blood stem cells (PBSCs) were harvested and frozen in 2 bags. After 2 courses of CHASE, he underwent autologous PBSCT, which involved the use of the LEED preconditioning regimen (melphalan, CPA, etoposide, and dexamethasone) and one of the frozen bags. This resulted in a second CR. At 39 months after PBSCT, he relapsed with a tumor in his right arm. After it was resected, he received eight cycles of brentuximab vedotin and 45 Gy of involved-field irradiation concurrently and achieved a third CR. Nine years after autologous PBSCT, he was diagnosed with MDS with excess blasts 2 (MDS-EB-2). His disease progressed to acute myeloid leukemia after 2 courses of azacitidine therapy. He successfully underwent a second autologous PBSCT involving the busulfan and melphalan preconditioning regimen and the other frozen bag, which had been stored for 9 years. He has been in complete cytogenetic remission for 1 year since the second autologous PBSCT.

Phase II Trial of Romidepsin as Consolidation Therapy after Gemcitabine, Dexamethasone, and Cisplatin in Elderly Transplant-Ineligible Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma.

Romidepsin is an important therapeutic option for patients with peripheral T-cell lymphoma (PTCL). However, the timing of romidepsin administration remains controversial. The objective of this study was to characterize the safety and efficacy of romidepsin as consolidation therapy after gemcitabine, dexamethasone, and cisplatin (GDP) therapy (GDPR). This study of patients treated between March 2019 and March 2021 was registered with the Japan Registry of Clinical Trials (registration number: jRCT0000000519). If complete response, partial response, or stable disease was confirmed after 2-4 GDP cycles, romidepsin was administered every 4 weeks for 1 year. Seven patients with relapsed/refractory (R/R) PTCL (T-follicular helper phenotype [n = 1] and angioimmunoblastic T-cell lymphoma [n = 6]) were included in this prospective study (PTCL-GDPR). After a median follow-up of 34 months of patients in PTCL-GDPR, the 2-year overall survival rate was 71%, and the overall response rate after treatment was 57%. Common adverse events in patients with PTCL-GDPR included hematological toxicities such as neutropenia, which improved with supportive treatment. There were no treatment-related mortalities. GDPR might be safe and effective in elderly transplant-ineligible patients with R/R PTCL; however, further investigation is required.

Clinicopathological comparison between PTCL-TBX21 and PTCL-GATA3 in Japanese patients.

AIM: Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is a heterogeneous disease that can be classified into the PTCL-TBX21 and PTCL-GATA3 subtypes. METHODS: In this study, we compared the clinicopathological features of PTCL-NOS in a Japanese cohort, classified using an IHC algorithm. RESULTS: One hundred patients with PTCL-NOS were categorized as having PTCL-TBX21 (n = 55), PTCL-GATA3 (n = 24), or PTCL-unclassified (n = 21). When comparing PTCL-TBX21 and PTCL-GATA3, PTCL-TBX21 showed significantly lower CD4 positivity (p = 0.047), lower counts of high endothelial venules (p = 0.032), and a tendency for a better response to initial treatment (p = 0.088). Gene expression analysis using the nCounter system showed higher expression of tumor immunity-related genes, such as PD-L1, LAG3, and IDO1, in PTCL-TBX21 than in PTCL-GATA3. PTCL-GATA3 had significantly worse overall survival (OS) than those with PTCL-TBX21 (p = 0.047), although a similar tendency was observed for progression-free survival (PFS) (p = 0.064). PTCL-GATA3 was a prognostic factor for OS in univariate analysis (HR 2.02; 95% CI, 1.09-3.77; p = 0.027), although multivariate analysis did not show significance (HR 2.07; 95% CI, 0.93-4.61; p = 0.074). In the PFS analysis, PTCL-GATA3 was an independent prognostic factor by univariate analysis (HR 1.96; 95% CI, 1.08-3.56; p = 0.027) and multivariate analysis (HR 2.34; 95% CI, 1.07-5.11; p = 0.032). CONCLUSION: The classification of PTCL-NOS into PTCL-TBX21 and PTCL-GATA3 is useful for predicting the prognosis of Japanese patients and stratifying the administration of tumor immune checkpoint inhibitors in clinical practice.

Immunogenetic Background of Chronic Lymphoproliferative Disorders in Romanian Patients-Case Control Study.

BACKGROUND AND OBJECTIVES: The implications of the genetic component in the initiation and development of chronic lymphoproliferative disorders have been the subject of intense research efforts. Some of the most important genes involved in the occurrence and evolution of these pathologies are the HLA genes. The aim of this study is to analyze, for the first time, possible associations between chronic lymphoproliferative diseases and certain HLA alleles in the Romanian population. MATERIALS AND METHODS: This study included 38 patients with chronic lymphoproliferative disorders, diagnosed between 2021 and 2022 at Fundeni Clinical Institute, Bucharest, Romania, and 50 healthy controls. HLA class I and class II genes (HLA-A/B/C, HLA-DQB1/DPB1/DRB1) were investigated by doing high resolution genotyping using sequence specific primers (SSP). RESULTS: Several HLA alleles were strongly associated with chronic lymphoproliferative disorders. The most important finding was that the HLA-C*02:02 (p = 0.002, OR = 1.101), and HLA-C*12:02 (p = 0.002, OR = 1.101) have a predisposing role in the development of chronic lymphoproliferative disorders. Moreover, we identified that HLA-A*11:01 (p = 0.01, OR = 0.16), HLA-B*35:02 (p = 0.037, OR = 0.94), HLA-B*81:01 (p = 0.037, OR = 0.94), HLA-C*07:02 (p = 0.036, OR = 0.34), HLA-DRB1*11:01 (p = 0.021, OR = 0.19), and HLA-DRB1*13:02 (p = 0.037, OR = 0.94), alleles have protective roles. CONCLUSIONS: Our study indicates that HLA-C*02:02 and HLA-C*12:02 are positively associated with chronic lymphoproliferative disorders for our Romanian patients while HLA-DRB1*11:01, HLA-DRB1*13:02, and HLA-B*35:02 alleles have a protective role against these diseases.

Decoding the diagnostic dilemma: Peripheral T­cell lymphoma presenting as acute pancreatitis: A case report.

Peripheral T cell lymphoma (PTCL) is a rare form of non-Hodgkin lymphoma characterized by the origin of mature T-cells. PTCL demonstrates atypical clinical features and involves both nodal and extra-nodal sites. The diagnosis and treatment of PTCL can prove to be challenging, as it is often detected at advanced stages and is resistant to conventional chemotherapy treatments. The present report describes a 55-year-old male patient who presented with acute pancreatitis, and imaging suggested a soft tissue mass in the pancreatic head indicating pancreatic adenocarcinoma. Further investigation through ultrasound-guided biopsy led to the diagnosis of pancreatic PTCL not otherwise specified.

Clinicopathological implications of immunohistochemical expression of TBX21, CXCR3, GATA3, CCR4, and TCF1 in nodal follicular helper T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified.

BACKGROUND: The classification of nodal peripheral T-cell lymphoma (PTCL) has evolved according to histology, cell-of-origin, and genetic alterations. However, the comprehensive expression pattern of follicular helper T-cell (Tfh) markers, T-cell factor-1 (TCF1), and Th1- and Th2-like molecules in nodal PTCL is unclear. METHODS: Eighty-two cases of nodal PTCL were classified into 53 angioimmunoblastic T-cell lymphomas (AITLs)/nodal T-follicular helper cell lymphoma (nTFHL)-AI, 18 PTCLs-Tfh/nTFHL-not otherwise specified (NOS), and 11 PTCLs-NOS according to the revised 4th/5th World Health Organization classifications. Immunohistochemistry for TCF1, TBX21, CXCR3, GATA3, and CCR4 was performed. RESULTS: TCF1 was highly expressed in up to 68% of patients with nTFHL but also in 44% of patients with PTCL-NOS (p > .05). CXCR3 expression was higher in AITLs than in non-AITLs (p = .035), whereas GATA3 expression was higher in non-AITL than in AITL (p = .007) and in PTCL-Tfh compared to AITL (p = .010). Of the cases, 70% of AITL, 44% of PTCLTfh/ nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the TBX21 subtype; and 15% of AITL, 38% of PTCL-Tfh/nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the GATA3 subtype. The others were an unclassified subtype. CCR4 expression was associated with poor progression-free survival (PFS) in patients with PTCL-Tfh (p < .001) and nTFHL (p = .023). The GATA3 subtype showed poor overall survival in PTCL-NOS compared to TBX21 (p = .046) and tended to be associated with poor PFS in patients with non-AITL (p = .054). CONCLUSIONS: The TBX21 subtype was more prevalent than the GATA3 subtype in AITL. The GATA3 subtype was associated with poor prognosis in patients with non-AITL and PTCL-NOS.

Prognostic indices for peripheral T-cell lymphoma - not otherwise specified and adult T-cell leukemia/lymphoma: From past to future.

Several prognostic indices have been reported for peripheral T-cell lymphoma (PTCL) and adult T-cell leukemia/lymphoma (ATL). The clinical features and prognosis of PTCL differ in a specified pathological diagnosis, whereas those of ATL are more diverse, even in the same clinical subtypes of acute, lymphoma, chronic, and smoldering. The establishment of a prognostic index is important not only for a risk-stratified treatment approach, but also for the preliminary evaluation of therapeutic findings by novel modalities, particularly in rare and aggressive diseases such as ATL. Five prognostic indices for PTCL-not otherwise specified and 6 prognostic indices for ATL are discussed herein. Recent advances in molecular analyses have facilitated prognostication using molecular profiles. In addition to the external validation of these prognostic indices, which are mostly established by clinical information, the development of novel indices by incorporating molecular profiles is warranted to improve the outcomes of patients through the selection of optimal treatments.

Indolent T-cell lymphoproliferative disorder of gastrointestinal tract with unusual clinical courses: report of 6 cases and literature review.

Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (iTLPD-GI) is a rare neoplasm usually having an indolent clinical course and easily misdiagnosed as inflammatory bowel disease or other T-cell lymphomas. A subset of the disorders that progressed to overt peripheral T-cell lymphoma have been reported, and the etiology and pathogenesis are poorly understood. The current study retrospectively examined the pathological, molecular, and clinical features of 6 cases of iTLPD-GI. Hematoxylin and eosin staining, immunohistochemistry, in situ hybridization, T-cell receptor gene rearrangement, and next-generation sequencing (NGS) were performed with the diseased tissues. All the 6 patients were immunocompetent Chinese men, who presented with recurrent abdominal pain and diarrhea for 4 to 13 years. Histologically, the intestinal tissue was expanded by lymphoid infiltration, composed of small-to-medium-sized lymphocytes with gland intact. The neoplastic cells were CD4 - /CD8 + with expression of TIA1 and variable granzyme B in five cases, and the other one was CD4 + /CD8 - . Two of the 5 patients progressed to more aggressive T-cell lymphoma and died of disease with complications. NGS identified TET2 and DDX3X mutations in patient 1, and BIRC6 and REV3L mutations in patient 2. Literature review indicated that iTLPD-GI with CD4 - /CD8 + immunophenotype was more commonly reported in Chinese cases. Our limited data indicated CD4-/CD8 + iTLPD-GI have similar potential to progress to more aggressive T-cell lymphoma as that of CD4 + /CD8 - , and gradually increased expression of granzyme B and Ki-67 may be early signs of the disease progression. Gain of novel gene mutations may be indicators of the pathogenesis.