Anaplastic Large Cell Lymphomas: A Study of 75 Pediatric Patients

dʼAmore, Emanuele S.G.; Menin, Andrea; Bonoldi, Emanuela; Bevilacqua, P.; Cazzavillan, S.; Donofrio, Vittoria; Gambini, Claudio; Forni, Marco; Gentile, Antonella; Magro, Gaetano; Boldrini, Rosaria; Pillon, Marta; Rosolen, Angelo; Alaggio, Rita

doi:10.2350/06-04-0082.1

Cited by 27 publications

(5 citation statements)

References 54 publications

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“…Association of extranodal sites is relatively common, with up to 50% of bone marrow involvement detected by reverse transcription-polymerase chain reaction (RT-PCR) [ 6 , 12 ]. In a report by d’Amore et al, up to 46% of patients had extranodal involvement, defined as at least one of the following sites: visceral involvement, skin, bone marrow, bone, soft-tissue, central nervous system; in contrast, 90% had a typical nodal presentation of lymphoma [ 13 ]. The Children’s Cancer Study, from the United Kingdom group, analyzed 72 patients from 1990 to 1996, with a median age of 11.8 years who were treated for ALCL.…”

Section: Discussionmentioning

confidence: 99%

Soft-Tissue Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma in a Child Unmasked by COVID-19

Lozano-Jaramillo¹,

Millan-Arreola²,

Esquer-Cota³

et al. 2023

J Hematol

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Anaplastic large cell lymphoma (ALCL) is children’s most common mature T-cell neoplasm. The majority is positive for anaplastic lymphoma kinase (ALK). Initial presentation as a soft-tissue pelvic mass without nodal involvement is rare and can be easily misdiagnosed. We report a case of a 12-year-old male presenting with pain and movement restriction in the right extremity. Computed tomography (CT) scan revealed a solitary pelvic mass. Initial biopsy examination concluded rhabdomyosarcoma. After developing pediatric multisystemic inflammatory syndrome due to coronavirus disease 2019 (COVID-19), central and peripheral lymph node enlargement appeared. New cervical adenopathy and pelvic mass biopsies were performed. Immunohistochemistry concluded an ALK-positive ALCL with a small-cell pattern. The patient was treated with brentuximab-based chemotherapy and eventually improved. Differential diagnosis of pelvic masses in children and adolescents must include ALCL. An inflammatory trigger may promote the appearance of a typical nodal disease, previously absent. Attention is warranted during histopathological examination to avoid diagnostic errors.

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Section: Discussionmentioning

confidence: 99%

Soft-Tissue Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma in a Child Unmasked by COVID-19

Lozano-Jaramillo¹,

Millan-Arreola²,

Esquer-Cota³

et al. 2023

J Hematol

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“…When compared to the CD30-negative cases, there was no significant correlation of CD30 with other immunostaining, patient's age or site of involvement. Cautiously, it is a potential difficulty for distinguishing between CD56-, CD30+ ENKTL and CD56+ anaplastic large cell lymphoma (ALCL), since 15% of ALCLs can be positive for CD56 [46]. In this situation, presence or absence of EBV or ALK protein may be helpful for making a definite diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Aberrant antigenic expression in extranodal NK/T-cell lymphoma: a multi-parameter study from Thailand

et al. 2011

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BackgroundExtranodal NK/T-cell lymphoma, nasal type (ENKTL) is not common worldwide, but it is the most common T- and NK-cell lymphomas in many Asian countries. Immunophenotypic profiles were studied based on limited series. The authors, therefore, studied on ENKTL according to characterize immunophenotypic profiles as well as the distribution of EBV subtype and LMP-1 gene deletion.MethodsBy using tissue microarray (TMA), immunohistochemical study and EBV encoded RNA (EBER) in situ hybridization were performed. T-cell receptor (TCR) gene rearrangement, EBV subtyping, and LMP-1 gene deletion were studied on the available cases.ResultsThere were 22 cases eligible for TMA. ENKTL were positive for CD3 (91%), CD5 (9%), CD7 (32%), CD4 (14%), CD56 (82%), TIA-1 (100%), granzyme B (95%), perforin (86%), CD45 (83%), CD30 (75%), Oct2 (25%), and IRF4/MUM1 (33%). None of them was positive for βF1, CD8, or CD57. TCR gene rearrangement was negative in all 18 tested cases. EBV was subtype A in all 15 tested cases, with 87% deleted LMP-1 gene. Cases lacking perforin expression demonstrated a significantly poorer survival outcome (p = 0.008).ConclusionsThe present study demonstrated TIA-1 and EBER as the two most sensitive markers. There were a few CD3 and/or CD56 negative cases noted. Interestingly, losses of CD45 and/or CD7 were not uncommon while Oct2 and IRF4/MUM1 could be positive in a subset of cases. Based on the present study in conjunction with the literature review, determination of PCR-based TCR gene rearrangement analysis might not be a useful technique for making diagnosis of ENKTL.

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“…Not surprisingly, GzB is expressed in a number of T/NK cell neoplasms including anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) [8–11], ALK- ALCL [8–10], and nasal-type NK/T cell lymphoma [10, 12], as well as other lymphoid cancers including some Hodgkin lymphoma [13–15] and multiple myeloma [16]. GzB expression can also be found in cell lines and/or primary tumours of non-lymphoid origin including acute myeloid leukemia [17], prostate cancer [18] and some carcinomas of the breast [19] and urothelium [6].…”

Section: Introductionmentioning

confidence: 99%

“…This lymphoma expresses GzB in cytotoxic granules along with perforin and T cell-restricted intracellular antigen-1 (TIA-1) [8–11]. Lymphoma cells typically possess T cell receptor gene rearrangements [8, 11, 21]; however, the expression of many T cell markers is variable in ALK+ ALCL [11, 21, 22]. A defining feature of ALK+ ALCL is chromosomal translocations or inversions involving the ALK tyrosine kinase gene [23, 24].…”

Section: Introductionmentioning

confidence: 99%

Expression of granzyme B sensitizes ALK+ ALCL tumour cells to apoptosis-inducing drugs

Pearson

Zhang

et al. 2014

Mol Cancer

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BackgroundThe serine protease Granzyme B (GzB) is primarily expressed by cytotoxic T lymphocytes and natural killer cells, and functions in allowing these cells to induce apoptosis in virally-infected or transformed cells. Cancers of both lymphoid and non-lymphoid origin also express GzB, and in some cases this expression has been linked to pathogenesis or sensitizing tumour cells to cell death. For example, GzB expression in urothelial carcinoma was implicated in promoting tumour cell invasion, whereas its expression in nasal-type NK/T lymphomas was found to correlate with increased apoptosis. GzB expression is also a hallmark of the non-Hodgkin lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL). Given the fact that ALK+ ALCL exhibits high levels of apoptosis and is typically responsive to conventional chemotherapy, we examined whether GzB expression might play a role in sensitizing ALK+ ALCL tumour cells to apoptosis.MethodsALK+ ALCL cell lines stably expressing GzB or non-targeting (control) shRNA were generated and apoptosis was examined by anti-PARP western blotting and terminal deoxynucleotidyl transferase dUTP nick end labelling. Both spontaneous apoptosis and apoptosis in response to treatment with staurosporine or doxorubicin were investigated. In order to assess whether additional granzymes might be important in promoting cell death in ALK+ ALCL, we examined whether other human granzymes were expressed in ALK+ ALCL cell lines using reverse-transcriptase PCR and western blotting.ResultsExpression of several GzB shRNAs in multiple ALK+ ALCL cell lines resulted in a significant decrease in GzB levels and activity. While spontaneous apoptosis was similar in ALK+ ALCL cell lines expressing either GzB or control shRNA, GzB shRNA-expressing cells were less sensitive to staurosporine or doxorubicin-induced apoptosis as evidenced by reduced PARP cleavage and decreased DNA fragmentation. Furthermore, we found that GzB is the only granzyme that is expressed at significant levels in ALK+ ALCL cell lines.ConclusionsOur findings are the first to demonstrate that GzB expression sensitizes ALK+ ALCL cell lines to drug-induced apoptosis. This suggests that GzB expression may be a factor contributing to the favourable response of this lymphoma to treatment.

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Anaplastic Large Cell Lymphomas: A Study of 75 Pediatric Patients

Cited by 27 publications

References 54 publications

Soft-Tissue Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma in a Child Unmasked by COVID-19

Soft-Tissue Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma in a Child Unmasked by COVID-19

Aberrant antigenic expression in extranodal NK/T-cell lymphoma: a multi-parameter study from Thailand

Expression of granzyme B sensitizes ALK+ ALCL tumour cells to apoptosis-inducing drugs

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