NON‐MEDIASTINAL CASES OF GREY ZONE LYMPHOMA: A PATHOLOGICAL AND CLINICAL SERIES OF 17 CASES FROM THE LYSA
Bibliographic record
Abstract
Introduction: Mediastinal grey zone lymphomas (MGZL) present an intermediate morphology between classical Hodgkin lymphoma (CHL) and primary mediastinal large B cell lymphoma (PMBCL). Cases without mediastinal involvement or non-MGZL (NMGZL) have been described, but their classification remains controversial. The aim of this study was to describe their clinico-pathological characteristics. Methods: Within the LYSA-P and LYMPHOPATH network, we collected a series of GZL centrally reviewed by expert hematopathologists. A total of 135 cases classified as CHL-like (N = 90, morphology closer to CHL and an immunophenotype (IP) to PMBCL), PMBCL-like (N = 45, morphology closer to PMBCL and an IP to CHL) were collected. Clinical and follow-up data were available for 108 patients (pts): 17 NMGZL (16%) and 91 MGZL. Additional immunohistochemistry, for MAL protein and B cell markers, and fluorescence in situ hybridization using break-apart probes to assess structural alterations of the CIITA and PDL1-2 (Programmed death-ligand) gene loci were performed. Results: Among the 17 NMGZL, 12 had a CHL-like morphology with various inflammatory backgrounds and a variable degree of fibrosis. EBV positivity of the malignant cells was found in 3/11 cases (EBER) and 4/9 expressed MAL. The remaining 5 cases presented with a PMBCL-like-morphology with scant fibrosis and an inflammatory background. EBV was found in 1/5 cases, 1/3 expressed MAL, 2/5 did not expressed CD20. Compared to MGZL, there were no significant differences in subtype distribution (CHL/PMBCL-like) or with regards to EBV positivity (p = 0.48 and 0.78 chi2 test, respectively). CIITA break could be observed in 4/10 cases (2/2 PMBCL-like and 2/8 CHL-like). PDL1/2 abnormalities could be observed in 8/12 NMGZL cases (6/9 CHL-like and 2/3 PMBCL-like, figure 1): 3/12 with a break and 7/12 with a CNV (gain in 3 cases and amplification in 4). PDL1 expression was observed in 6 cases (1/3 PMBCL-like and 5/7 CHL-like). None of the cases expressed PDL2. Regarding the clinical data, the median age was 55 y, significantly older than MGZL cases (34 y, p = .01). All the 17 pts with NMGZL had nodal involvement, 9 (53%) a stage III/IV, 7 presented an extra-nodal site (3 with more than extra-nodal 1 site involved): spleen (n = 5), bone marrow (n = 3), bone (n = 2), liver (n = 3), lung (n = 3). A bulky disease (> 10 cm) was present in 5 pts (31%). The age adjusted IPI score was >1 in 7 pts (41%). Age was the only parameters that significantly differed between NMGZL and MGZL pts. Among the 17 pts, 8 received R-CHOP, 5 an intensified R-CHOP (R-ACVBP), 4 ABVD. CR was reached in 14 pts, 1 of them relapsed at 167 m with a MGZL. Three pts (18%) were primary refractory (progression <1y). The median EFS was 72 m. Although a trend towards a better outcome could be observed, there were no significant differences in EFS or OS between MGZL and NMGZL (p = 0.3 and 0.1, respectively). Keywords: Hodgkin lymphoma (HL); primary mediastinal large B-cell lymphoma (PMLBCL).
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".