Kinase-negative Anaplastic Large Cell Lymphoma Research Articles

Extranodal NK/T-Cell Lymphoma Predominantly Composed of Anaplastic Cells: A Frequently Misdiagnosed and Highly Aggressive Variant.

Extranodal NK/T-cell lymphoma (ENKTL) is a non-Hodgkin lymphoma associated with the Epstein-Barr virus that primarily affects individuals in East Asia and indigenous populations in Central and South America. Morphologically, ENKTL typically consists of medium-sized cells or a combination of small and large cells. This report presents 10 cases characterized by predominantly anaplastic cells with diffuse expression of CD30, resembling anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALK-negative ALCL) and demonstrating highly aggressive behavior. The cohort included 9 males and 1 female, ranging in age from 29 to 65 years (median age: 47y). Eight patients presented with nasal disease, while 2 had non-nasal disease. Five patients had stage I/II disease, and the remaining 5 had stage III/IV disease. Morphologically, necrosis was observed in 9 cases, angiocentric-angiodestructive growth in 3 cases, and pseudoepitheliomatous hyperplasia in 2 cases. Anaplastic cells predominated in all cases, with some displaying eccentric, horseshoe-shaped, or kidney-shaped nuclei (referred to as "Hallmark" cells). The morphology profile was monomorphic in 3 cases and polymorphic in 7 cases. Immunohistochemically, all cases tested positive for cytotoxic granule markers (TIA1 and granzymeB) and Epstein-Barr virus-encoded RNA. Cytoplasmic expression of CD3ε and CD56 was observed in 9 of 10 cases. Interestingly, most cases (7 of 8) exhibited variable expression of MuM1, ranging from 10% to 90%. All cases showed diffuse positivity for CD30 but were negative for ALK, resulting in 3 cases being initially misdiagnosed as ALK-negative ALCL. Compared with nonanaplastic cases, anaplastic cells predominant ENKTL had a significantly higher frequency of "B" symptoms, bone marrow involvement, hemophagocytic lymphohistiocytosis, and higher Ki67 proliferative index. These findings provide valuable information for pathologists, expanding their understanding of the cytologic spectrum of ENKTL. This rare variant of ENKTL, characterized by the predominance of anaplastic cells and diffuse CD30 expression, exhibits high aggressiveness and should be differentiated from ALK-negative ALCL. Awareness of this uncommon variant is crucial in preventing misdiagnosis and ensuring the timely initiation of therapy.

Allogeneic Blood or Marrow Transplantation with Post-Transplantation Cyclophosphamide for Peripheral T Cell Lymphoma: The Importance of Graft Source

The use of post-transplantation cyclophosphamide (PTCy) for graft-versus host-disease (GVHD) prophylaxis has revolutionized allogeneic blood or marrow transplantation (alloBMT), but there is limited published experience in peripheral T cell lymphoma (PTCL). We sought to assess outcomes in patients with PTCL who underwent alloBMT with PTCy. We reviewed the charts of all adult patients age ≥18 years who underwent alloBMT with nonmyeloablative conditioning and PTCy-based GVHD prophylaxis at the Sidney Kimmel Comprehensive Cancer Center between January 2004 and December 2020. Sixty-five patients were identified. The median age was 59 years (range, 24 to 75 years). Lymphoma histology included PTCL not otherwise specified (n=24), anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (n=14), angioimmunoblastic T cell lymphoma (n=7), enteropathy-associated T cell lymphoma (n=6), hepatosplenic T cell lymphoma (n=4), and others (n=10). Eleven patients were in first complete remission (17%); the remaining patients were in first partial remission or underwent salvage therapy to at least PR prior to transplantation. Forty-eight patients underwent alloBMT from a haploidentical related donor (74%), 10 from a fully matched donor (15%), and 7 from a mismatched unrelated donor (11%). All patients received fludarabine, cyclophosphamide, and total body irradiation (TBI). The graft source was bone marrow (BM) in 46 patients (71%) and peripheral blood (PB) in 19 patients (29%); all patients in the BM cohort received 200 cGy TBI, and most patients in the PB cohort (15 of 19) received 400 cGy TBI. GVHD prophylaxis comprised PTCy, mycophenolate mofetil, and a calcineurin inhibitor or sirolimus. With a median follow-up of 2.8 years (range, 290 days to 14.2 years), the 2-year progression-free survival (PFS) for the entire cohort was 49% (95% confidence interval [CI], 38% to 64%), and the 2-year overall survival (OS) was 55% (95% CI, 44% to 69%). Outcomes were significantly improved in those receiving PB compared to those receiving BM, including a 2-year PFS of 79% (95% CI 63% to 100%) versus 39% (95% CI, 27% to 56%), 2-year OS of 84% (95% CI, 69% to 100%) versus 46% (95% CI, 33% to 63%), and 1-year cumulative incidence of relapse of 5% (95% CI, 0 to 16%) versus 33% (95% CI, 19% to 46%), with no difference in GVHD and nonrelapse mortality. AlloBMT with PTCy is safe and well-tolerated in patients with PTCL. Our data suggest that increasing the TBI dose to 400 cGy and using PB allografts may offer improved disease control and better survival outcomes, though additional studies are needed to confirm these findings.

ROLE OF THE DENTAL SURGEON ON DIAGNOSIS OF LYMPHOMAS IN HIV PATIENTS: A RARE INTRAORAL ANAPLASTIC LARGE CELL LYMPHOMA

Malignancies in patients with human immunodeficiency virus (HIV) are well documented in the literature. Although the head and neck region is rarely involved, this can signal initial HIV infection or its worsening, and the dental surgeon is the main professional for intraoral diagnoses. Some are extremely rare tumors like anaplastic large cell lymphoma. In 2020, a 49-year-old male with a 4-month diagnosis of HIV infection presented with an ulcerated lesion on the retromolar region achieving the tonsillar pillar with no malignancy on the first incisional biopsy. Because of its appearance, another biopsy was performed, confirming the anaplastic lymphoma kinase-negative anaplastic large cell lymphoma diagnosis, not hypothesized at first sight. The patient had a great response with chemotherapy and hematopoietic cell transplantation with total remission of the intraoral tumor. The early diagnosis of a rare high-morbidity tumor allowed a precocious treatment and recovery of the patient.

Systemic ALK-negative anaplastic large cell lymphoma with distinctive myxoid change and DUSP22 rearrangement.

Systemic anaplastic lymphoma kinase-negative (ALK-) anaplastic large cell lymphoma (ALCL) comprises a genomically heterogeneous disease that is considered a distinct entity by the 2016 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. Other than lymph nodes, systemic ALK- ALCL may affect extranodal tissues, sites where the inflammatory background may be especially prominent. In this scenario, myxoid change is exceptional in systemic ALK- ALCL. We describe a rare case of systemic ALK- ALCL with distinctive myxoid changes, carrying specific chromosomal aberrations that affect the clinical outcome. Careful morphological, immunohistochemical, and molecular workup is mandatory because a myxoid background should not be a reason to ignore the possibility of a lymphoma. Finally, extensive correlation with staging and the detection of prognostic biomarkers such as DUSP22 and TP63 rearrangements are essential for the diagnosis and prediction of clinical outcome in ALK- ALCL.

Autologous hematopoietic stem cell transplantation in tandem with anti-CD30 CAR T-cell infusion in relapsed/refractory CD30+ lymphoma.

7532 Background: Long-term outcome is unfavorable for patients with relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL) who are resistant to salvage chemotherapy, even followed by autologous stem cell transplantation (ASCT). Long-term survival is most likely achieved in patients who are sensitive to salvage therapy and have a complete response (CR) before ASCT, while outcome is poor in patients with residual disease. Although CD30-directed chimeric antigen receptor (CAR30) T-cell therapy induces high response rates in these patients, the duration of response is limited. Methods: We conducted an open-label, single-center and single-arm pilot study to explore the safety and efficacy of ASCT in tandem with CAR30 T-cell infusion in r/r CD30+ lymphoma (Chinese Clinical Trial Registry, number ChiCTR 2100053662). Patients will receive BEAM as preconditioning. HSCs are infused at day zero and followed by the infusion of 3rd generation CAR30 T cells in the next week. Between June 1, 2019 to May 1, 2021, 6 patients enrolled, including 5 with cHL and 1 with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALCL). The median age was 24 years. No patient had a prior history of ASCT. Three patients (50.0%) relapsed ≥ 2 times and 3 patients (50.0%) had primary refractory diseases. All had a Deauville score of 4 or 5, and 5 patients (83.3%) had a stable or progressive disease (SD/PD) to previous treatments at enrollment. Results: CD34+ cells were infused at day zero with a median dosage of 3.9 (IQR, 3.2-6.1) × 106 /kg and followed by the infusion of CAR30 T cells with a median dosage of 7.6 (IQR, 5.5-9.7 ) ×106 /kg at +2 to +6 days. Cytopenias represented the most commonly severe advers events (≥ grade 3). The engraftments of neutrophil or platelet occured at a median time of 13.5 (IQR,12.3-14.0 ) days or 11.5 (IQR, 11.0-12.8) days, respectively, suggesting rapid multilineage engraftments post-ASCT. Cytokine release syndrome (CRS) was observed in 5 (83.3%) patients, all of which were grade 1. No neurotoxicity or severe infection was observed. At month 3 after HSC infusion, all patients achieved objective responses, including 5 (83.3%) with a CR and 1 with a patial response (PR). With a median follow-up of 18.2 (range, 9.9-32.1) months, the median PFS and OS were not reached. At January 31, 2022, the data-cutoff date, all patients maintained their responses and remained alive without disease relapse or progression. Of note, responses were sustained in all 5 patients who had a SD/PD at enrollment. Conclusions: Our work demonstrates tandem administration of ASCT and CAR30 T-cell therapy was well-tolerated and highly active in r/r HL and ALCL, even in PET-positive or chemorefractory patients who were expected to have inferior outcome after ASCT, although further large-scale validation in prospective clinical trial is warranted. Clinical trial information: ChiCTR2100053662.

Solitary pink papule in an elderly man

Solitary pink papule in an elderly man

High-Dose Chemotherapy With Autologous Stem Cell Transplantation in a Case of Refractory Peripheral T Cell Lymphoma With Tracheoesophageal Fistula: A Case Report

A 46-year-old woman with a sore throat was diagnosed with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma that had spread from the piriform fossa to the cervical esophagus. Tracheoesophageal fistula developed after induction chemotherapy. Because conservative repair was not applicable, intensified chemotherapy, including autologous stem cell transplantation was performed with the fistula remaining open. Laryngopharyngectomy and cervical esophagectomy were performed 6 months after transplantation. The optimal strategy for refractory lymphoma with active tracheoesophageal fistula remains undetermined. To the best of our knowledge, this is the first report describing the successful treatment of a patient with tracheoesophageal fistula who received high-dose chemotherapy supported by autologous stem cell transplantation.

ALK-negative anaplastic large cell lymphoma: features and outcomes of 235 patients from the International T-Cell Project

AbstractAnaplastic lymphoma kinase–negative anaplastic large cell lymphoma (ALK– ALCL) is an aggressive neoplasm of T-cell/null-cell lineage. The T-Cell Project is a global prospective cohort study that consecutively enrolled patients newly diagnosed with peripheral T-cell lymphoma, registered through a centralized computer database between September 2006 and February 2018. Of 1553 validated cases from 74 sites in 13 countries worldwide, 235 were reported as ALK– ALCL. The median age at diagnosis was 54 years (range, 18-89 years), with a male predominance (62%). Stage III to IV disease was identified in 71% of patients, bulky disease and bone marrow involvement were uncommon, and 66% of patients presented with a low (0-1) International Prognostic Index score. Of all treated patients, 85% received multiagent initial chemotherapy, and 8% were consolidated with autologous hematopoietic cell transplantation. The initial overall and complete response rates were 77% and 63%, respectively. After a median follow-up of 52 months (95% confidence interval [CI], 41-63), the median progression-free survival (PFS) and overall survival (OS) were 41 months (95% CI, 17-62) and 55 months (95% CI, 36-75), respectively. The 3- and 5-year PFS rates were 52% and 43%, and the 3- and 5-year OS rates were 60% and 49%. Treatments containing both anthracycline and etoposide were associated with superior OS (P = .05) but not PFS (P = .18). In this large prospective cohort study, outcomes comparable to those previously reported in the retrospective International Peripheral T-Cell Lymphoma Project were observed. The study underscores the need for introducing novel platforms for ALK– ALCL and establishes a benchmark for future clinical trials. This trial was registered at www.clinicaltrials.gov as #NCT01142674.

Primary anaplastic lymphoma kinase-negative anaplastic large cell lymphoma of cervical spine presenting with quadriplegia: A case report and literature review

Background: An anaplastic large cell lymphoma (ALCL) involving the cervical spine and leading to quadriplegia is very rare.Case Description: A 48-year-old immunocompetent male presented with quadriplegia that warranted an anterior cervical corpectomy/fusion. He was previously being presumptively treated for cervical disease attributed to tuberculosis. The histopathology and immunohistochemistry revealed an ALCL that was anaplastic lymphoma kinase (ALK) negative. The patient had a favorable response to surgery followed by CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisolone) chemotherapy.Conclusion: ALK-negative ALCL presenting with quadriplegia due to primary involvement of cervical spine is extremely rare, but must be diagnosed and appropriately managed.

Abstract CT041: The efficacy and safety of Geptanolimab (GB226) in patients with relapsed/refractory peripheral T cell lymphoma (PTCL): A multicenter, open-label, single-arm, phase 2 trial

Abstract Background: There was an unmet medical need for treatment in patients with relapsed/refractory (R/R) peripheral T cell lymphoma (PTCL). This multicenter, open-label, single-arm, phase 2 trial aimed to evaluate the efficacy and safety of Geptanolimab (GB226), an anti-programmed cell death 1 (PD-1) antibody, in patients with R/R PTCL(NCT03502629). Methods: The study was initiated in July 2018 and patients with R/R PTCL were recruited from 32 sites in China. Patients were treated with Geptanolimab (intravenous infusion, 3 mg/kg) once every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR). The secondary endpoints included duration of response (DOR), time to response (TTR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and immunogenicity. Treatment response was assessed according to Lugano 2014 criteria by the independent review committee. Patients were followed up every 6 weeks for the first year, and every 12 weeks thereafter. Results: By Aug 15, 2019, a total of 102 patients were recruited and treated with Geptanolimab. As of Nov 1, 2019, the median follow-up was 3.98 months (0.30,15.63). The ORR was 36.3% (37/102; 95%CI: 26.98%-46.39%), including of 11 (10.8%) patients achieved CR and 26 (25.5%) patients achieved PR. DCR was 55.9% (57/102; 95%CI: 45.71%-65.71%). The median DOR, TTR, and PFS were 6.83 months (95%CI: 5.13-not reached [NR]), 4.04 months (95% CI: 1.48-8.52), and 2.69 months (95%CI: 1.74-4.21), respectively. The median OS has not been reached. Subgroup analyses showed that the efficacy was consistent across different age, gender, clinical stage, and previous treatment lines. Patients could benefit from Geptanolimab after failure of Chidamide (an oral histone deacetylase [HDAC] inhibitor) treatment with an ORR of 33.3% (8/24). The ORR of patients with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALCL ALK-), ALCL ALK+, extranodal NK-/T-cell lymphoma, nasal type (ENKTL), PTCL-not otherwise specified (PTCL-NOS), and other types were 58.3% (7/12), 42.9% (3/7), 40.9% (9/22), 28.2% (11/39), and 31.8% (7/22) respectively. Treatment-related AEs (TRAEs) occurred in 80.4% of patients, with common TRAEs (incidence ≥10%) of white blood cell count reduction (18.6%), fever (14.7%) and anemia (13.7%). The incidence of grade ≥3 TRAEs and treatment-related serious AEs was 23.5% and 15.7%, respectively. Immune-related AEs (irAEs) occurred in 36 (35.3%) patients. 11 (10.8%) patients had grade ≥3 irAEs. Conclusions: Geptanolimab (GB226), an anti-PD-1 antibody, can be an effective treatment for R/R PTCL, with an acceptable safety profile. Citation Format: Yuankai Shi, Jianqiu Wu, Zhen Wang, Liling Zhang, Zhao Wang, Mingzhi Zhang, Hong Cen, Zhigang Peng, Yufu Li, Lei Fan, Ye Guo, Liping Ma, Jie Cui, Yuhuan Gao, Haiyan Yang, Hongyu Zhang, Lin Wang, Weihua Zhang, Huilai Zhang, Liping Xie, Ming Jiang, Hui Zhou, Yuerong Shuang, Hang Su, Xiaoyan Ke, Chuan Jin, Xin Du, Xin Du, Li Liu, Yaming Xi, Zheng Ge, Ru Feng, Yang Zhang, Shengyu Zhou, Fan Xie, Chao Gao. The efficacy and safety of Geptanolimab (GB226) in patients with relapsed/refractory peripheral T cell lymphoma (PTCL): A multicenter, open-label, single-arm, phase 2 trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT041.

Brentuximab vedotin for refractory anaplastic lymphoma kinase-negative anaplastic large cell lymphoma in leukemic phase with RUNX3 overexpression.

Anaplastic lymphoma kinase (ALK)- negative anaplastic large cell lymphoma (ALCL) is an aggressive CD30-positive non- Hodgkin lymphoma. ALK-ALCL rarely manifests with extensive bone marrow and peripheral blood involvement (known as “leukemic phase”). A 54-year-old woman was diagnosed with ALK-ALCL in leukemic phase, characterized by an extremely poor prognosis. Lymphoma cells in this case showed chromosomal translocation 1p36.1- encoded RUNX3 and overexpression of its protein. She was refractory to CHOP and salvage chemotherapy. Fortunately, she achieved complete remission with three cycles of Brentuximab vedotin (BV) and underwent umbilical cord blood transplantation. However, she died due to treatment-related mortality on day 129. The autopsy findings showed no lymphoma cells. Treatment strategy for ALK-ALCL is controversial, but the efficacy of BV in CD30-positive peripheral T-cell lymphoma not only as salvage regimens, but also in first line, has been reported in recent years. BV may be an effective option for ALK-ALCL in leukemic phase.

The role of autologous stem cell transplantation in patients with nodal peripheral T-cell lymphomas in first complete remission: Report from COMPLETE, a prospective, multicenter cohort study.

The role of autologous stem cell transplantation (ASCT) in the first complete remission (CR1) of peripheral T-cell lymphomas (PTCLs) is not well defined. This study analyzed the impact of ASCT on the clinical outcomes of patients with newly diagnosed PTCL in CR1. Patients with newly diagnosed, histologically confirmed, aggressive PTCL were prospectively enrolled into the Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE) study, and those in CR1 were included in this analysis. Two hundred thirteen patients with PTCL achieved CR1, and 119 patients with nodal PTCL, defined as anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), or PTCL not otherwise specified, were identified. Eighty-three patients did not undergo ASCT, whereas 36 underwent consolidative ASCT in CR1. At the median follow-up of 2.8 years, the median overall survival was not reached for the entire cohort of patients who underwent ASCT, whereas it was 57.6 months for those not receiving ASCT (P = .06). ASCT was associated with superior survival for patients with advanced-stage disease or intermediate-to-high International Prognostic Index scores. ASCT significantly improved overall and progression-free survival for patients with AITL but not for patients with other PTCL subtypes. In a multivariable analysis, ASCT was independently associated with improved survival (hazard ratio, 0.37; 95% confidence interval, 0.15-0.89). This is the first large prospective cohort study directly comparing the survival outcomes of patients with nodal PTCL in CR1 with or without consolidative ASCT. ASCT may provide a benefit in specific clinical scenarios, but the broader applicability of this strategy should be determined in prospective, randomized trials. These results provide a platform for designing future studies of previously untreated PTCL.

CHOP versus GEM-P in previously untreated patients with peripheral T-cell lymphoma (CHEMO-T): a phase 2, multicentre, randomised, open-label trial

SummaryBackgroundOutcomes with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like chemotherapy in peripheral T-cell lymphoma are poor. We investigated whether the regimen of gemcitabine, cisplatin, and methylprednisolone (GEM-P) was superior to CHOP as front-line therapy in previously untreated patients.MethodsWe did a phase 2, parallel-group, multicentre, open-label randomised trial in 47 hospitals: 46 in the UK and one in Australia. Participants were patients aged 18 years and older with bulky (tumour mass diameter >10 cm) stage I to stage IV disease (WHO performance status 0–3), previously untreated peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, enteropathy-associated T-cell lymphoma, or hepatosplenic γδ T-cell lymphoma. We randomly assigned patients (1:1) stratified by subtype of peripheral T-cell lymphoma and international prognostic index to either CHOP (intravenous cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [maximum 2 mg] on day 1, and oral prednisolone 100 mg on days 1–5) every 21 days for six cycles; or GEM-P (intravenous gemcitabine 1000 mg/m2 on days 1, 8, and 15, cisplatin 100 mg/m2 on day 15, and oral or intravenous methylprednisolone 1000 mg on days 1–5) every 28 days for four cycles. The primary endpoint was the proportion of patients with a CT-based complete response or unconfirmed complete response on completion of study chemotherapy, to detect a 20% superiority of GEM-P compared with CHOP, assessed in all patients who received at least one cycle of treatment and had an end-of-treatment CT scan or reported clinical progression as the reason for stopping trial treatment. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov (NCT01719835) and the European Clinical Trials Database (EudraCT 2011-004146-18).FindingsBetween June 18, 2012, and Nov 16, 2016, we randomly assigned 87 patients to treatment, 43 to CHOP and 44 to GEM-P. A planned unmasked review of efficacy data by the independent data monitoring committee in November, 2016, showed that the number of patients with a confirmed or unconfirmed complete response with GEM-P was non-significantly inferior compared with CHOP and the trial was closed early. At a median follow-up of 27·4 months (IQR 16·6–38·4), 23 patients (62%) of 37 assessable patients assigned to CHOP had achieved a complete response or unconfirmed complete response compared with 17 (46%) of 37 assigned to GEM-P (odds ratio 0·52, 95% CI 0·21–1·31; p=0·164). The most common adverse events of grade 3 or worse in both groups were neutropenia (17 [40%] with CHOP and nine [20%] with GEM-P), thrombocytopenia (4 [10%] with CHOP and 13 [30%] with GEM-P, and febrile neutropenia (12 [29%] with CHOP and 3 [7%] with GEM-P). Two patients (5%) died during the study, both in the GEM-P group, from lung infections.InterpretationThe number of patients with a complete response or unconfirmed complete response did not differ between the groups, indicating that GEM-P was not superior for this outcome. CHOP should therefore remain the reference regimen for previously untreated peripheral T-cell lymphoma.FundingBloodwise and the UK National Institute of Health Research.

Immunohistochemical assessment of the diagnostic utility of PD-L1: a preliminary analysis of anti-PD-L1 antibody (SP142) for lymphoproliferative diseases with tumour and non-malignant Hodgkin-Reed-Sternberg (HRS)-like cells.

The programmed death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important role in tumour cells escape from immune control. PD-L1 immunohistochemistry is a useful predictor of immunotherapy response, but is still not used widely in the diagnostic setting. Here we describe results using PD-L1 immunohistochemistry during routine diagnostics in lymphoma. Ninety-one lymphoproliferative disease cases sharing tumour and non-malignant Hodgkin-Reed-Sternberg (HRS)-like cells with and without Epstein-Barr virus (EBV) association were investigated by immunohistochemistry for PD-L1 (clone SP142). PD-L1 expression was present in more than 5% of tumour or non-malignant HRS-like cells in 100% of EBV+ classical (C) Hodgkin lymphoma (HL) (n=10) and EBV-negative nodular sclerosis CHL (n=8); 40% of EBV+ diffuse large B cell lymphoma, not otherwise specified (DLBCL-NOS) (n=20); and 4% of nodal peripheral T cell lymphoma of follicular helper T cell type (PTCL-TFH) (n=22). In contrast, nodular lymphocyte-predominant HL (n=4), lymphocyte-rich CHL (n=6), EBV+ hyperplasia (n=8), plasmablastic lymphoma (n= 3) and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (n=5) seldom exhibited PD-L1 in their large cells. Assessing PD-L1 positivity in tumour and non-malignant large cells was helpful in differentiating between CHL versus nodal PTCL-TFH (P<0.0001) or EBV+ DLBCL-NOS (P=0.0052) and between EBV+ DLBCL-NOS versus nodal PTCL-TFH (P=0.0052), with PD-L1 expression indicating the first diagnosis in each of those sets. Immunohistochemical evaluation of PD-L1 expression in tumour and non-malignant HRS-like large cells may be useful for assessing either immune escape or immunodeficiency in their pathogenesis.

A case report of anaplastic lymphoma kinase-negative anaplastic large-cell lymphoma characterized by skin panniculitis in children

A case report of anaplastic lymphoma kinase-negative anaplastic large-cell lymphoma characterized by skin panniculitis in children

The role of stem cell transplant for lymphoma in 2017.

The role of stem cell transplant for lymphoma in 2017.

Detection of an early adult T-cell leukemia-lymphoma clone in lymph nodes with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma involvement

A 58-year-old man was admitted to our hospital with systemic lymphadenopathy and was diagnosed with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALCL) by lymph node biopsy. Although he was a human T-cell leukemia virus type I (HTLV-1) carrier, Southern blot analysis of the lymph node did not show monoclonal integration of HTLV-1 provirus deoxyribonucleic acid (DNA). He achieved complete remission after chemotherapy and subsequently, autologous peripheral blood stem cell transplantation (auto-PBSCT) was performed. Fifteen months after the auto-PBSCT, abnormal lymphocytes in the peripheral blood gradually increased. Southern blot analysis revealed monoclonal integration of HTLV-1 provirus DNA and monoclonal rearrangement of TRB. He was diagnosed with chronic type adult T-cell leukemia-lymphoma (ATL), which immediately progressed to the acute type. He died of tumor progression despite intensive chemotherapy. We analyzed genomic alterations of the ALCL and ATL cells using array comparative genomic hybridization. We found that the genomic alteration pattern differed between the two diseases. T-cell receptor clonality analysis using polymerase chain reaction (PCR) showed that the T-cell clone of the ATL was present in the lymph nodes with ALCL involvement, but not in peripheral blood. This finding suggests that lymph nodes can serve as a niche for ATL development.

Recurrent Systemic Anaplastic Lymphoma Kinase–Negative Anaplastic Large Cell Lymphoma Presenting as a Breast Implant–Associated Lesion

A woman aged 48 years presented with fevers, chills, weight loss, and night sweats. She had significant lymphadenopathy of the left neck as well as the left axilla. Her history was significant for bilateral breast augmentation with textured silicone implants more than 25 years ago. Excisional biopsy of a cervical lymph node revealed large, atypical cells positive for CD4 and CD30 and negative for Epstein-Barr virus-encoded ribonucleic acid, CD2, CD3, CD5, CD7, CD8, CD15, CD20, pan-keratin, S100, anaplastic lymphoma kinase (ALK), and paired box 5. These findings were consistent with Ann Arbor stage IIIB ALK-anaplastic large cell lymphoma (ALCL). The patient was started on 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone. She initially had no signs or symptoms of breast involvement; however, after developing seroma during the clinical course, the patient underwent capsulectomy and removal of the intact, textured silicone implants. Pathological evaluation demonstrated ALK-ALCL in the left breast capsule with cells displaying a significant degree of pleomorphism with binucleated forms and numerous mitoses. Fluorescence in situ hybridization confirmed the tumor was negative for t(2;5). She presented 8 weeks later showing evidence of recurrent systemic disease.

Anaplastic Large-Cell Lymphoma in Aids

AIDS-related malignancies may alter clinical courses and result in death in critically ill patients. We present a case of a newly diagnosed AIDS patient with Pneumocystis jiroveci pneumonia, Epstein-Barr virus, and cytomegalovirus infections who was found to have widely metastatic kinase-negative anaplastic large-cell lymphoma. This case demonstrates the diversity in the malignant presentation of HIV-infected patients, outside of the more commonly observed non-Hodgkin lymphomas.

Identification of putative pathogenic microRNA and its downstream targets in anaplastic lymphoma kinase-negative anaplastic large cell lymphoma.

Anaplastic large cell lymphomas (ALCL) are tumors of T/null-cell lineage characterized by uniform CD30 expression. The 2008 World Health Organization classification subdivided ALCLs into 2 groups: anaplastic lymphoma kinase (ALK)-positive (established entity) and ALK-negative (proposed new entity) ALCL. The genetic basis for the pathogenesis of newly categorized ALK- ALCL is poorly understood. In this study, we used microRNA microarray analysis to identify differentially expressed microRNAs in ALK+ and ALK- ALCL. ALK- ALCL showed significantly higher expression of miR-155 (0.888 ± 0.228) compared with ALK+ ALCL (0.0565 ± 0.009) on microarray and by quantitative real-time polymerase chain reaction in ALK- ALCL compared with ALK+ ALCL (P < .05) with a strong correlation between the 2 platforms (R = 0.9, P < .0003). A novel in situ hybridization method allows direct visualization of expression patterns and relative quantitation of miR-155 (mean score, 2.3 versus 1.3; P = .01) for the first time in tissue sections of ALCL. Among computationally predicted targets of miR-155, we identified ZNF652 (r = -0.57, P = .05), BACH1 (r = 0.88, P = .02), RBAK (r = 0.81, P = .05), TRIM32 (r = 0.92, P = .01), E2F2 (r = 0.81, P = .05), and TP53INP1 (r = -0.31, P = .03) as genes whose expression by quantitative real-time polymerase chain reaction correlated significantly with the level of miR-155 in ALCL tumor tissue.