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Q1. About follicular helper T-cell lymphoma, angioimmunoblastic type, which description is incorrect?

  • (A) Typically present with the acute onset of a systemic illness.
  • (B) Generalized lymphadenopathies are very common.
  • (C) It is predominantly CD8+ phenotype.
  • (D) It is characterized by TET2, DNMT3A, RHOA and IDH2 mutation.
  • (E) Has a better response to histone deacetylase inhibitors compared to peripheral T-cell lymphoma, NOS.
點此顯示正解

(C) It is predominantly CD8+ phenotype.

詳解

Explanation of the Correct Answer

(C) is FALSE because angioimmunoblastic T-cell lymphoma (AITL) is predominantly CD4+ T-helper cell origin, not CD8+. AITL derives from the monoclonal proliferation of T follicular helper (TFH) cells, which express a characteristic immunophenotype including CD4+, CXCL13, PD-1, ICOS, CD10, and BCL6123. Studies confirm that both T-cell populations in AITL express CD42, and the disease is defined by its TFH phenotype rather than cytotoxic CD8+ T-cell characteristics.

Why the Other Options Are TRUE

(A) TRUE: AITL typically presents with acute onset of systemic illness. Patients characteristically develop lymphadenopathy accompanied by systemic manifestations including skin rash, pleural effusion, ascites, and immune dysregulation with predisposition to autoimmunity and recurrent infections13. This constellation of features is sometimes referred to as "angioimmunoblastic syndrome"3.

(B) TRUE: Generalized lymphadenopathy is very common in AITL. The disease typically presents with lymphadenopathy as a cardinal feature1, reflecting the systemic nature of this aggressive T-cell lymphoma.

(D) TRUE: AITL is characterized by recurrent mutations in TET2, DNMT3A, RHOA, and IDH2. These mutations occur in a stepwise fashion, with early mutations involving epigenetic regulators (TET2, DNMT3A) occurring in hematopoietic stem cells, followed by subsequent changes involving signaling molecules (RHOA)12. Studies demonstrate TET2 mutations in 72% of cases, DNMT3A in 34%, and RHOA in 61% of AITL cases2. The RHOA p.G17V mutation is relatively specific to AITL, occurring in 50-70% of cases1. IDH2 R172K/S mutations are also characteristic and synergize with TET2 mutations to modulate TFH cell interaction with the tumor microenvironment4.

(E) TRUE: AITL demonstrates better response to histone deacetylase (HDAC) inhibitors compared to PTCL-NOS. In relapsed/refractory AITL, the pooled overall response rate to HDAC inhibitors was 44% (95% CI 35-53%), higher than other PTCL subtypes8. The phase III romidepsin-CHOP trial showed that while the overall analysis was negative, outcomes were improved specifically in the T follicular helper (TFH) subgroup of PTCL, with no benefit in non-TFH PTCL[^12]. The high prevalence of mutations in DNMT3A, TET2, and IDH2 in AITL supports an epigenetic origin, with a response rate of 73% reported among patients with T-cell lymphomas treated with romidepsin plus azacitidine[^9]. This superior response in AITL compared to PTCL-NOS reflects the biological rationale for targeting epigenetic dysregulation in this disease3[^10].

詳解 · 中文翻譯

正確答案解釋

(C) 假，因為血管免疫母細胞性 T 細胞淋巴瘤（AITL）是 主要 CD4+ T 幫助細胞來源，而非 CD8+。AITL 來源於 T 濾泡幫助（TFH）細胞 的單克隆增殖，表達特徵免疫表型，包括 CD4+、CXCL13、PD-1、ICOS、CD10 和 BCL6123。研究確認 AITL 中的兩個 T 細胞群都表達 CD42，疾病由其 TFH 表型定義而非細胞毒性 CD8+ T 細胞特徵。

其他選項為何真實

(A) 真實：AITL 通常呈現 急性發作全身疾病。患者特徵性地發展淋巴結腫大，伴隨包括皮疹、胸腔積液、腹水和免疫失調伴隨自身免疫傾向和反覆感染的全身表現13。此特徵集合有時稱為「血管免疫母細胞性症候群」3。

(B) 真實：廣泛淋巴結腫大在 AITL 中非常常見。疾病通常呈現淋巴結腫大為主要特徵1，反映此侵襲性 T 細胞淋巴瘤的全身性質。

(D) 真實：AITL 的特徵為 TET2、DNMT3A、RHOA 和 IDH2 中的反覆突變。這些突變以逐步方式發生，早期突變涉及遺傳調控因子（TET2、DNMT3A）發生在造血幹細胞，其後續變化涉及信號轉導分子（RHOA）12。研究證明 72% 的病例中的 TET2 突變、34% 中的 DNMT3A 和 61% AITL 病例中的 RHOA2。RHOA p.G17V 突變相對特異於 AITL，發生於 50-70% 的病例1。IDH2 R172K/S 突變也特有，與 TET2 突變協同調節 TFH 細胞與腫瘤微環境的相互作用4。

(E) 真實：AITL 相比 PTCL-NOS 對組蛋白去乙醯酶（HDAC）抑制劑表現出更好的反應。在復發/難治 AITL 中，HDAC 抑制劑的總體反應率池為 44%（95% CI 35-53%），高於其他 PTCL 亞型8。第三期 romidepsin-CHOP 試驗顯示，雖然整體分析為陰性，但結果在 PTCL 的 T 濾泡幫助（TFH）亞組中特別改善，在非 TFH PTCL 中無益處[^12]。AITL 中 DNMT3A、TET2 和 IDH2 突變的高患病率支持遺傳起源，報告了 73% 反應率在用 romidepsin 加地西他濱治療的 T 細胞淋巴瘤患者中[^9]。此 AITL 相比 PTCL-NOS 的優越反應反映針對此疾病遺傳失調的生物學基礎3[^10]。

參考文獻 (AMA)

  1. Tan B, Martin B, Fernandez-Pol S. Angioimmunoblastic T-Cell Lymphoma Diagnosed From Pleural Fluid by Integration of Morphologic, Immunophenotypic, and Molecular Findings. Diagnostic Cytopathology. 2021;49(12):E462-E466. doi:10.1002/dc.24861. PMID:34449978. ↩↩↩↩↩↩↩↩↩↩

  2. Yao WQ, Wu F, Zhang W, et al. Angioimmunoblastic T-Cell Lymphoma Contains Multiple Clonal T-Cell Populations Derived From a Common TET2 Mutant Progenitor Cell. The Journal of Pathology. 2020;250(3):346-357. doi:10.1002/path.5376. PMID:31859368. ↩↩↩↩↩↩↩↩

  3. Lage LAPC, Culler HF, Reichert CO, da Siqueira SAC, Pereira J. Angioimmunoblastic T-Cell Lymphoma and Correlated Neoplasms With T-Cell Follicular Helper Phenotype: From Molecular Mechanisms to Therapeutic Advances. Frontiers in Oncology. 2023;13:1177590. doi:10.3389/fonc.2023.1177590. PMID:37182145. ↩↩↩↩↩↩↩↩

  4. Leca J, Lemonnier F, Meydan C, et al. IDH2 and TET2 Mutations Synergize to Modulate T Follicular Helper Cell Functional Interaction With the AITL Microenvironment. Cancer Cell. 2023;41(2):323-339.e10. doi:10.1016/j.ccell.2023.01.003. PMID:36736318. ↩↩

  5. Yang P, Tao Y, Zhao A, et al. Efficacy and Safety of Histone Deacetylase Inhibitors in Peripheral T-Cell Lymphoma: A Systematic Review and Meta-Analysis on Prospective Clinical Trials. Frontiers in Oncology. 2023;13:1127112. doi:10.3389/fonc.2023.1127112. PMID:37384289. ↩

  6. Pantazis JC, Palmer AC. Cross-Resistance of Belinostat and Romidepsin in Non-T Follicular Helper Peripheral T-Cell Lymphoma Models Suggests Subtype-Specific Implications for Belinostat-Chop. Molecular Cancer Therapeutics. 2026;25(4):672-677. doi:10.1158/1535-7163.MCT-25-0941. PMID:41403140. ↩

  7. Bates SE. Epigenetic Therapies for Cancer. The New England Journal of Medicine. 2020;383(7):650-663. doi:10.1056/NEJMra1805035. PMID:32786190. ↩

  8. Tse E, Querfeld C, Ishitsuka K, Kwong YL. Emerging Therapeutic Strategies for Mature T-Cell and Natural Killer-Cell Lymphomas. The Lancet. Haematology. 2025;12(10):e823-e835. doi:10.1016/S2352-3026(25)00228-5. PMID:40961949. ↩↩

Slide annotations

Most common: TET2, DNMT3A, IDH2-R172 and RHOA

The TFH cell phenotype is defined by the presence of at least 2 or preferably 3 of the most frequently used TFH markers, PD1, CD10, BCL6, CXCL13, and ICOS, in addition to CD4

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