scholarly journals DUSP22-IRF4 rearrangement in AIDS-associated ALK-negative anaplastic large cell lymphoma

2019 ◽  
Vol 12 (9) ◽  
pp. e230641 ◽  
Author(s):  
Mike Wang ◽  
Nour Kibbi ◽  
Nan Ring ◽  
Alexa Siddon ◽  
Francine Foss ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Anaplastic Large Cell Lymphoma ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Aggressive Lymphoma ◽  
Anaplastic Lymphoma ◽  
Increased Risk ◽  
Large Cell Lymphoma ◽  
Genetic Rearrangement

Patients with AIDS have increased risk of developing lymphomas, such as anaplastic large cell lymphoma (ALCL), which generally carry a poor prognosis. The DUSP-IRF4 genetic rearrangement in ALCL confers a favourable prognosis in HIV-negative patients; it is unknown how this interacts clinically with HIV/AIDS. A man aged 53 years presented with subcutaneous nodules on the scalp and axillae, and diffuse lymphadenopathy. Biopsy of subcutaneous nodule and lymph node showed large atypical anaplastic lymphocytes which were CD30+ and anaplastic lymphoma kinase-negative, consistent with primary systemic ALCL. In addition, he was found to be HIV-positive and diagnosed with AIDS. Genetic testing of the tissue revealed a DUSP22-IRF4 rearrangement. Complete remission was achieved with HyperCVAD and subsequent brentuximab vedotin monotherapy. We report a case of AIDS-associated primary systemic ALCL with a DUSP22-IRF4 rearrangement. AIDS-associated ALCL is an aggressive lymphoma, with a poor prognosis. However, the presence of the genetic rearrangement, previously unseen in this disease, drastically altered the disease course. This case highlights the value of genetic testing and identifies DUSP22-IRF4-associated ALCL in the setting of HIV-associated lymphoproliferative disorders.

scholarly journals TRAF1-ALK fusion indicates poor prognosis to ALK tyrosine kinase inhibitors in relapsed/refractory ALK-positive anaplastic large-cell lymphoma patients

2020 ◽  
Author(s):  
Diwen Pang ◽  
Ling Huang ◽  
Xinmiao Jiang ◽  
Feili Chen ◽  
Hanguo Guo ◽  
...  
Keyword(s):  
Anaplastic Large Cell Lymphoma ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Large Cell ◽  
Fusion Partner ◽  
Alk Inhibitors ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma ◽  
Alk Positive

Abstract Background Relapsed/refractory (R/R) anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) respond to ALK inhibitors, but resistance bears a poor prognosis. No biomarkers predict a long duration of response to ALK inhibitors. The ALK gene was first identified as the fusion partner of the nucleophosmin (NPM1) gene in recurrent t(2;5)(p23;q35) found in an ALCL subset. However, several distinct ALK fusions that result in highly different characteristics have also been described in lymphomas. Methods We retrospectively reviewed 43 patients with pathologically confirmed ALK-positive ALCL at Guangdong Provincial People’s Hospital from February 2007 through February 2020, including seven R/R patients who received ALK inhibitors (six with crizotinib and one with alectinib). We performed next-generation sequencing (NGS) with paraffin-embedded tissue for these seven R/R patients and one patient with a peripheral blood sample. We evaluated clinical characteristics and survival status. Results The median age of all patients was 29 (range 15–66) years. Most patients were male with advanced stage and B symptoms. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 60% and 70%, respectively with a median follow-up of 52.2 (range 2.4–168.6) months. Multivariate analyses revealed that only bone marrow involvement was an independent prognostic factor for PFS (P = 0.03) and OS (P = 0.03). Of the seven R/R patients, the median line number of therapies was four (range 3–7) and that of ALK inhibitor usage was three (range 2–5). The overall response rate was 100% (n = 7). The NGS identified four patients with the NPM1-ALK fusion and two with tumor necrosis factor receptor-associated factor 1 gene (TRAF1)-ALK fusion; the latter quickly developed resistance to chemotherapy and ALK inhibitors. Conclusions ALK inhibitors improved survival of patients with R/R ALK-positive ALCLs. TRAF1-ALK fusion may predict a poor clinical outcome to chemotherapy and ALK inhibitors. This ALK fusion may reflect a trend toward the aggressive behavior of lymphomas.

scholarly journals Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers?

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 253
Author(s):  
Federica Lovisa ◽  
Anna Garbin ◽  
Sara Crotti ◽  
Piero Di Battista ◽  
Ilaria Gallingani ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Enrichment Analysis ◽  
Heat Shock Protein 90 ◽  
Large Cell ◽  
Tenascin C ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma ◽  
Alk Positive

Over the past 15 years, several biological and pathological characteristics proved their significance in pediatric anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL) prognostic stratification. However, the identification of new non-invasive disease biomarkers, relying on the most important disease mechanisms, is still necessary. In recent years, plasmatic circulating small extracellular vesicles (S-EVs) gathered great importance both as stable biomarker carriers and active players in tumorigenesis. In the present work, we performed a comprehensive study on the proteomic composition of plasmatic S-EVs of pediatric ALCL patients compared to healthy donors (HDs). By using a mass spectrometry-based proteomics approach, we identified 50 proteins significantly overrepresented in S-EVs of ALCL patients. Gene Ontology enrichment analysis disclosed cellular components and molecular functions connected with S-EV origin and vesicular trafficking, whereas cell adhesion, glycosaminoglycan metabolic process, extracellular matrix organization, collagen fibril organization and acute phase response were the most enriched biological processes. Of importance, consistently with the presence of nucleophosmin (NPM)-ALK fusion protein in ALCL cells, a topological enrichment analysis based on Reactome- and Kyoto Encyclopedia of Genes and Genomes (KEGG)-derived networks highlighted a dramatic increase in proteins of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in ALCL S-EVs, which included heat shock protein 90-kDa isoform alpha 1 (HSP90AA1), osteopontin (SPP1/OPN) and tenascin C (TNC). These results were validated by Western blotting analysis on a panel of ALCL and HD cases. Further research is warranted to better define the role of these S-EV proteins as diagnostic and, possibly, prognostic parameters at diagnosis and for ALCL disease monitoring.

Primary Cutaneous CD30-Positive Anaplastic Large Cell Lymphoma in Childhood: Report of 4 Cases and Review of the Literature

2005 ◽  
Vol 8 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Shimareet Kumar ◽  
Stefania Pittaluga ◽  
Mark Raffeld ◽  
Michael Guerrera ◽  
Nita L. Seibel ◽  
...  
Keyword(s):  
T Cell ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Subcutaneous Tissue ◽  
Pediatric Population ◽  
Large Cell ◽  
Lymphoid Cells ◽  
Cell Phenotype ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma

We present the clinicopathologic findings in 4 children with primary cutaneous anaplastic large cell lymphoma (C-ALCL). The patients ranged in age from 13 months to 8 years, with 3 females and 1 male. All presented with a rapidly enlarging mass involving the skin and subcutaneous tissue. Histologic evaluation showed sheets of large pleomorphic lymphoid cells that were diffusely and strongly CD30+. Tumor cells were CD45+ in 1 of 4 cases. Cells were of T-cell phenotype, with variable positivity for CD3 (3 of 4 cases) and CD5 (2 of 4 cases). All 4 cases were positive for CD4 and clusterin. Staining for anaplastic lymphoma kinase was negative in all cases. No evidence of systemic involvement was noted at initial presentation or over a follow-up of 5 to 78 months, although 3 patients had cutaneous recurrences. Primary C-ALCL has only rarely been described in the pediatric population. The high-grade histologic appearance of this lymphoma belies its generally favorable clinical course and prognosis. Recognition of this entity and its differentiation from other T-cell lymphomas that secondarily involve the skin is important to avoid unnecessarily aggressive therapy in these children.

Anaplastic large cell lymphoma with axial skeletal lesions portends a poor prognosis

2015 ◽  
Vol 76 (10) ◽  
pp. 606-607
Author(s):  
Zahra Al-Asaadi ◽  
Sammour Fatin ◽  
Ketan Patel ◽  
Naren Chetty ◽  
Simon Dubrey
Keyword(s):  
Anaplastic Large Cell Lymphoma ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Large Cell Lymphoma ◽  
Skeletal Lesions

Anaplastic Large Cell Lymphoma Arising in Bone

2000 ◽  
Vol 124 (9) ◽  
pp. 1339-1343
Author(s):  
Mark A. Lones ◽  
Warren Sanger ◽  
Sherrie L. Perkins ◽  
L. Jeffrey Medeiros
Keyword(s):  
T Cell ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Correct Diagnosis ◽  
Cell Lineage ◽  
Antigen Expression ◽  
Large Cell ◽  
Null Cell ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma

Abstract Anaplastic large cell lymphoma (ALCL) represents approximately 2% of all non-Hodgkin lymphomas according to the recent Non-Hodgkin Lymphoma Classification Project. As defined in the revised European-American classification of lymphoid neoplasms (REAL), ALCL is a neoplasm of T-cell or null-cell lineage; 20% to 60% of cases are associated with the t(2;5)(p23;q35) translocation. ALCL commonly involves nodal as well as a wide variety of extranodal sites, although primary or secondary involvement of bone is rare. We describe the case of a 71-year-old man with stage IE T-cell ALCL, monomorphic variant, arising in the left anterior fifth rib and involving adjacent soft tissue without other sites of disease. The monomorphic histologic features hindered the initial recognition of this neoplasm as ALCL. However, strong uniform CD30 antigen expression and subsequent demonstration of the t(2;5)(p23;q35) translocation and anaplastic lymphoma kinase (ALK) immunoreactivity led to the correct diagnosis. We identified only 5 reported cases of T-cell and null-cell ALCL arising in bone and only 2 of these cases involved a single bone site. All 5 previously reported cases were ALCL of the classic type. We report a case of ALCL that is unique to our knowledge. This case of monomorphic ALCL was localized to bone and tumor cells contained the t(2;5)(p23;q35) translocation.

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