The Pathological Spectrum of Systemic Anaplastic Large Cell Lymphoma (ALCL)

Montes-Mojarro, Ivonne A.; Steinhilber, Julia; Bonzheim, Irina; Quintanilla-Martı́nez, Leticia; Fend, Falko

doi:10.3390/cancers10040107

Cited by 54 publications

(67 citation statements)

References 146 publications

(185 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In nearly half of the patients (46.0%), simultaneous involvement of both lymph nodes and extranodal organs was found on PET/CT in the present study. Among the extranodal organs, bone was demonstrated to be the most commonly involved organ, which is inconsistent with previously published articles have shown that the skin is the most common extranodal involvement site [4,20]. In our results, the skin was Fig.…”

Section: Discussioncontrasting

confidence: 99%

18F-FDG PET/CT imaging findings in anaplastic large cell lymphoma, a rare subtype of lymphoma

et al. 2020

View full text Add to dashboard Cite

Objective: To investigate the 18 F-FDG PET/CT imaging manifestations for anaplastic large cell lymphoma (ALCL), a rare subtype of T/NK cell lymphoma. Methods: Fifty patients with ALCL, including 32 anaplastic lymphoma kinase (ALK)-positive patients and 18 ALKnegative patients, were enrolled. The positive detection, maximal standardized uptake value (SUV max), and distribution of nodal and extranodal involvement were recorded and analysed. Fifty patients with diffuse large B cell lymphoma (DLBCL) were collected as a control group. Results: ALCL lesions were demonstrated to be 18 F-FDG-avid tumours with a mean SUVmax of 19.4 ± 12.6. Most (76%) ALCL patients presented with stage III-IV disease, and nodal and extranodal involvement occurred in 74.0 and 72.0% of the patients, respectively. ALCL and DLBCL showed many similarities in tumour stage, 18 F-FDG uptake and tumour involvement (P > 0.05), although the preferred extranodal organs of involvement (bone and the gastrointestinal tract, respectively) were different (P < 0.05). Compared to ALK-negative lesions, a higher uptake of 18 F-FDG was found in the ALK-positive lesions (SUVmax: 22.1 ± 14.3 vs. 15.1 ± 6.6, t = 2.354, P = 0.023). ALK-positive ALCL was more likely to involve the lymph nodes than ALK-negative ALCL (84.3% vs. 55.5%, χ 2 = 4.973, P = 0.043), while ALK-negative ALCL was more prone to involve the extranodal organs compared to ALK-positive ALCL (88.9% vs. 62.5%, χ 2 = 3.979, P = 0.046). Conclusion: The present study demonstrated that ALCL is a systemic 18 F-FDG-avid lymphoma with many imaging manifestations similar to DLBCL on PET/CT. The present study also showed that ALK expression actually influenced tumour 18 F-FDG uptake and lesion distribution. These findings may be useful to improve the understanding of the biological characteristics of ALCL.

show abstract

Section: Discussioncontrasting

confidence: 99%

18F-FDG PET/CT imaging findings in anaplastic large cell lymphoma, a rare subtype of lymphoma

et al. 2020

View full text Add to dashboard Cite

show abstract

“…To correlate the expression of the JAK-STAT signaling pathway with immunohistochemical and serological factors of disease pathology, we investigated EBV seropositivity, and expression of immunophenotype markers as defined with IHC ( Figure 6). Lower pY-STAT3 expression was associated with negative CD3 (37.7% and 75.4% mean pSTAT3 expression, p < 0.001, t-test), CD5 (42.8% and 68.4%, p = 0.03, t-test), CD7 (45.2% and 64.6%, p = 0.01) and positive CD30 phenotype ( Figure S4A) designating ALCL immunophenotype as reported in Figure 2 [30]. No association with EBV seropositivity ( Figure S4B), CD4 (p = 0.86, t-test) or CD8 (p = 0.35, t-test) immunophenotype nor MIB proliferation index (r = 0.20, p = 0.19, Pearson correlation) was noted.…”

Section: Stat3 Phosphorylation Is Associated With Jak1/stat3 Mutationmentioning

confidence: 72%

STAT3 Mutation Is Associated with STAT3 Activation in CD30+ ALK− ALCL

Andersson

Brück

Braun

et al. 2020

Cancers

View full text Add to dashboard Cite

Peripheral T-cell lymphomas (PTCL) are a heterogeneous, and often aggressive group of non-Hodgkin lymphomas. Recent advances in the molecular and genetic characterization of PTCLs have helped to delineate differences and similarities between the various subtypes, and the JAK/STAT pathway has been found to play an important oncogenic role. Here, we aimed to characterize the JAK/STAT pathway in PTCL subtypes and investigate whether the activation of the pathway correlates with the frequency of STAT gene mutations. Patient samples from AITL (n = 30), ALCL (n = 21) and PTCL-NOS (n = 12) cases were sequenced for STAT3, STAT5B, JAK1, JAK3, and RHOA mutations using amplicon sequencing and stained immunohistochemically for pSTAT3, pMAPK, and pAKT. We discovered STAT3 mutations in 13% of AITL, 13% of ALK + ALCL, 38% of ALK − ALCL and 17% of PTCL-NOS cases. However, no STAT5B mutations were found and JAK mutations were only present in ALK -ALCL (15%). Concurrent mutations were found in all subgroups except ALK + ALCL where STAT3 mutations were always seen alone. High pY-STAT3 expression was observed especially in AITL and ALCL samples. When studying JAK-STAT pathway mutations, pY-STAT3 expression was highest in PTCLs harboring either JAK1 or STAT3 mutations and CD30 + phenotype representing primarily ALK − ALCLs. Further investigation is needed to elucidate the molecular mechanisms of JAK-STAT pathway activation in PTCL.Cancers 2020, 12, 702 2 of 17 diagnoses [1]. The most prevalent PTLCs are PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic lymphoma kinase-negative (ALK − ALCL), and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK + ALCL) [2,3].Despite generally favorable response rates to chemotherapy, remissions are often not durable, and as such the natural history of PTCL is characterized by relapses and refractory disease. For this reason, upfront hematopoietic stem cell transplantation (HSCT) is often recommended in first remission for patients who are fit and have chemo-sensitive disease [4]. For patients who are not suitable for transplantation, chances of long-term disease control are very limited, with an average progression-free survival (PFS) of 5.5 months [5]. In this setting, optimal therapeutic approaches remain undefined representing an unmet clinical need.Recent advances in the molecular and genetic characterization of PTCL have helped to delineate differences and similarities between the various subtypes [6]. Several recurrent mutations have been identified in small subsets of patients potentially enabling more accurate disease classification and guide treatment decisions. In AITL, the three most commonly identified genetic lesions occur in the Tet methylcytosine dioxygenase 2 gene (TET2), the Ras homolog gene family, member A (RHOA), and the isocitrate dehydrogenase 2 gene (IDH2). Besides AITL, TET2 mutations can be seen with a high frequency also in PTCL-NOS with a T follicular helper cell phenotype [7]. RHOA, a small GTPase participating i...

show abstract

“…Malignant transformation by ALK involves several mechanisms including hyper-activation of Ras/MAPK-, PI3K-and STAT3 signaling pathways as well as increased expression of transcriptional regulators and stem-cell factors, which shifts the affected cell to a more undifferentiated state [69][70][71][72] . In this study, we conducted a genomewide deficiency screen in Drosophila to identify modifiers of Alk signaling, resulting in the identification of many known and anticipated signaling molecules, such as Ras/Raf/ERK network components (MESR3, Cnk, Aveugle), PI3K21B, STAT92E, and the protein serine/threonine phosphatase Alphabet which is in agreement with previous screening efforts 73 .…”

Section: Discussionmentioning

confidence: 99%

Identification of the Wallenda JNKKK as an Alk suppressor reveals increased competitiveness of Alk-expressing cells

Wolfstetter

Pfeifer

Backman

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Anaplastic lymphoma kinase (Alk) is a receptor tyrosine kinase of the insulin receptor super-family that functions as oncogenic driver in a range of human cancers such as neuroblastoma. In order to investigate mechanisms underlying Alk oncogenic signaling, we conducted a genetic suppressor screen in Drosophila melanogaster. Our screen identified multiple loci important for Alk signaling, including members of Ras/Raf/ERK-, Pi3K-, and STAT-pathways as well as tailless (tll) and foxo whose orthologues NR2E1/TLX and FOXO3 are transcription factors implicated in human neuroblastoma. Many of the identified suppressors were also able to modulate signaling output from activated oncogenic variants of human ALK, suggesting that our screen identified targets likely relevant in a wide range of contexts. Interestingly, two misexpression alleles of wallenda (wnd, encoding a leucine zipper bearing kinase similar to human DLK and LZK) were among the strongest suppressors. We show that Alk expression leads to a growth advantage and induces cell death in surrounding cells. Our results suggest that Alk activity conveys a competitive advantage to cells, which can be reversed by over-expression of the JNK kinase kinase Wnd.

show abstract

The Pathological Spectrum of Systemic Anaplastic Large Cell Lymphoma (ALCL)

Cited by 54 publications

References 146 publications

18F-FDG PET/CT imaging findings in anaplastic large cell lymphoma, a rare subtype of lymphoma

18F-FDG PET/CT imaging findings in anaplastic large cell lymphoma, a rare subtype of lymphoma

STAT3 Mutation Is Associated with STAT3 Activation in CD30+ ALK− ALCL

Identification of the Wallenda JNKKK as an Alk suppressor reveals increased competitiveness of Alk-expressing cells

Contact Info

Product

Resources

About