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Q1. Which one of below descriptions for histologic transformation (HT) of follicular lymphoma is wrong?

  • (A) The annual incidence has been estimated at approximately 3%.
  • (B) The overall survival (OS) of these patients is poor, with a median OS of 4 years after HT for patients previously treated for their FL component.
  • (C) Patients with de novo HT (ie, a DLBCL histology with pathological findings that favors the existence of the FL component at the time of diagnosis) have a better outcome than those with a transformation event occurring after FL therapy.
  • (D) Follicular lymphoma histology can be observed at the time of relapse in patients with DLBCL, suggesting that the initial DLBCL biopsy was a de novo HT of FL.
  • (E) All of above are right.
點此顯示正解

(E) All of above are right.

詳解

The stem asks for the wrong (incorrect) statement. The correct answer is (E) "All of above are right" because this statement is false — not all of the preceding statements are correct. Specifically, statement (A) is inaccurate regarding the annual incidence of histologic transformation.

Why (E) is the Incorrect Statement

Option (E) claims that all statements A-D are correct, but this is false because statement (A) significantly overestimates the annual incidence of histologic transformation. The literature consistently reports an annual transformation risk of approximately 2-2.5% per year, not 3% as stated in option (A)5[^8]. A Danish nationwide cohort reported the risk at 2.2% per year5, and multiple large population-based studies show cumulative incidences that translate to lower annual rates than 3%13.

Why the Other Options Are True (and Therefore Not the Answer)

(A) Annual incidence ~3%: This is incorrect (overestimated), which is why (E) is wrong. The actual annual incidence is approximately 2-2.5% per year5[^8].

(B) Poor OS with median ~4 years after HT in previously treated patients: This is true. The National LymphoCare Study reported median OS post-transformation of 5 years2[^11], and other studies show median OS of 4-5 years for patients with sequential transformation who received prior FL therapy5[^7]. The Danish cohort showed 5-year OS of only 47% for sequential transformation calculated from time of HT5[^8].

(C) De novo HT has better outcome than post-treatment transformation: This is true. Multiple studies confirm superior outcomes for transformation at initial diagnosis (de novo/composite/discordant) compared to sequential transformation after FL therapy. The Italian FIL study showed 5-year OS of 84% for de novo transformation (Group 1) versus 51% for sequential transformation (Group 2), p<0.001[^7]. The Danish study similarly demonstrated better OS for discordant/composite transformation (68%) versus sequential transformation (47%) when calculated from time of HT5[^8].

(D) FL histology can be observed at relapse in DLBCL, suggesting initial DLBCL was de novo HT: This is true and represents a well-recognized phenomenon. The National LymphoCare Study specifically noted that 47 patients had evidence of transformation at the time of initial diagnosis, and these patients shared similar prognostic factors and survival rates to those without transformation2[^11]. This bidirectional relationship between FL and DLBCL reflects their clonal relationship and supports the concept of de novo transformation.

詳解 · 中文翻譯

題幹要求找出錯誤的敘述。正確答案是 (E)「以上皆對」，因為此敘述是錯誤的 — 前面的所有敘述並不都正確。特別是，敘述 (A) 在組織學轉化的年發生率方面不準確。

為什麼 (E) 是錯誤的敘述

(E) 選項聲稱 A-D 所有敘述都正確，但這是錯誤的，因為敘述 (A) 顯著高估了組織學轉化的年發生率。文獻一致報告年轉化風險約為每年 2-2.5%，而不是選項 (A) 中所述的 3%5[^8]。丹麥全國隊列報告風險為每年 2.2%5，多項大規模人群研究顯示累積發生率轉換為低於 3% 的年率13。

為什麼其他選項都正確（因此不是答案）

(A) 年發生率約 3%：這是錯誤的（高估了），這就是為什麼 (E) 是錯的。實際年發生率約為每年 2-2.5%5[^8]。

(B) 轉化後中位 OS 約 4 年，在先前治療過的患者中：這是正確的。國家淋巴瘤護理研究報告轉化後中位 OS 為5 年2[^11]，其他研究顯示接受過先前 FL 治療的順序轉化患者的中位 OS 為4-5 年5[^7]。丹麥隊列從轉化時開始計算，順序轉化的 5 年 OS 僅為 47%5[^8]。

(C) De novo HT 預後優於治療後轉化：這是正確的。多項研究確認在初始診斷時轉化（de novo/混合/不一致）與 FL 治療後的順序轉化相比有更優越的預後。意大利 FIL 研究顯示 de novo 轉化（第 1 組）的 5 年 OS 為84%，而順序轉化（第 2 組）為 51%，p<0.001[^7]。丹麥研究同樣證明了不一致/混合轉化（68%）對比順序轉化（47%）從轉化時開始計算時有更佳的 OS5[^8]。

(D) FL 組織學可在 DLBCL 復發時觀察到，表明初始 DLBCL 是 de novo HT：這是正確的，代表一個公認的現象。國家淋巴瘤護理研究特別指出 47 名患者在初始診斷時有轉化證據，這些患者與無轉化患者有相似的預後因素和存活率2[^11]。FL 與 DLBCL 之間的此雙向關係反映了它們的克隆關係，支持 de novo 轉化的概念。

參考文獻 (AMA)

  1. Madsen C, Plesner TL, Bentzen HH, et al. Real World Data on Histological Transformation in Patients With Follicular Lymphoma: Incidence, Clinico-Pathological Risk Factors and Outcome in a Nationwide Danish Cohort. Leukemia & Lymphoma. 2020;61(11):2584-2594. doi:10.1080/10428194.2020.1779254. PMID:33167719. ↩↩

  2. Li ZH, Zhang MY, Federico M, et al. Early Histological Transformation of Follicular Lymphoma to Diffuse Large B-Cell Lymphoma Indicating Adverse Survival: A Population-Based Analysis and Validation. Cancer. 2024;130(19):3321-3332. doi:10.1002/cncr.35378. PMID:38809573. ↩↩↩↩

  3. Kalashnikov I, Reunamo T, Tanskanen T, et al. Transformation and Causes of Death in Follicular Lymphoma: A Finnish Nationwide Population-Based Study. British Journal of Haematology. 2025;. doi:10.1111/bjh.70181. PMID:40999643. ↩↩

  4. Wagner-Johnston ND, Link BK, Byrtek M, et al. Outcomes of Transformed Follicular Lymphoma in the Modern Era: A Report From the National LymphoCare Study (NLCS). Blood. 2015;126(7):851-7. doi:10.1182/blood-2015-01-621375. PMID:26105149. ↩

  5. Rusconi C, Anastasia A, Chiarenza A, et al. Outcome of Transformed Follicular Lymphoma Worsens According to the Timing of Transformation and to the Number of Previous Therapies. A Retrospective Multicenter Study on Behalf of Fondazione Italiana Linfomi (FIL). British Journal of Haematology. 2019;185(4):713-717. doi:10.1111/bjh.15816. PMID:30793297. ↩↩↩↩↩↩↩↩↩↩↩↩

Slide annotations

It is important to rule out disease transformation to a more aggressive histology, which occurs at a rate of 1–3% per patient per year. (5 years: 10%)\nMedian OS following HT: 50 months

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