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Q1. 55 y/o male patient presented with pancytopenia, neutropenia and splenomegaly. His bone marrow immunophenotypic profile were strongly positive for CD20, CD11c, CD25, CD103 and CD123; the leukemic cells were negative for CD5, CD10, CD27 and CD43. What is the most possible diagnosis?

  • (A) Chronic lymphocytic leukemia
  • (B) Splenic marginal zone lymphoma
  • (C) Splenic diffuse red pulp small B-cell lymphoma
  • (D) Hairy cell leukemia
  • (E) Follicular lymphoma
點此顯示正解

(D) Hairy cell leukemia

詳解

Analysis

1) Why (D) Hairy Cell Leukemia is the CORRECT answer:

The immunophenotypic profile described is pathognomonic for hairy cell leukemia (HCL). The patient demonstrates the classic "HCL immunologic score" with positivity for CD20, CD11c, CD25, CD103, and CD123 (scoring 4/4 on the HCL immunologic score), combined with negativity for CD5, CD10, and CD271234. This constellation of markers is seen in 98% of HCL cases and is highly specific for this diagnosis34. The clinical presentation of pancytopenia, neutropenia, and splenomegaly further supports HCL, which characteristically presents with cytopenias (including monocytopenia), splenomegaly, and bone marrow involvement12[^8].

Figure 2: Flow cytometry finding of fine needle aspirate. A, CD 19 and CD 20 positive cell population. B, The tumour cells showing light chain restriction as the cells express only lamba chain. C, The cells are negative for CD5 and CD 10. D, The cells are positive for CD 200. E, The cells are positive both for CD 11 and CD 25. F, The cells are positive for CD 123

The figure above demonstrates the characteristic flow cytometry pattern of HCL, showing CD19/CD20 positivity, light chain restriction, negativity for CD5 and CD10, and positivity for CD200, CD11c, CD25, and CD123—matching the case presentation.

2) Why the other options are INCORRECT:

(A) Chronic lymphocytic leukemia (CLL) is incorrect because CLL characteristically expresses CD5 and CD23 (both negative in this case) and shows weak expression of CD20, CD22, and surface immunoglobulin45[^11]. While CLL can express CD11c and CD25, the intensity is significantly less than HCL, and CLL does not express CD103 or CD1235[^10]. The HCL immunologic score would be 0-1 in CLL, not 434.

(B) Splenic marginal zone lymphoma (SMZL) is incorrect because SMZL typically shows negative or weak CD103 expression (usually negative), negative CD123, and CD25 positivity in only a minority of cases[9][10]. SMZL cells have morphologically distinct "villous lymphocytes" with polar short villi and typically express CD27, which is negative in this case[9][10]. The HCL immunologic score in SMZL is typically 0-1[^9].

(C) Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is incorrect because SDRPL shows inconsistent CD103 expression (38%), rare CD123 expression (16%), and rare CD25 expression (3%)[9][10]. SDRPL has a low HCL immunologic score and can be distinguished from HCL by a CD200/CD180 median fluorescence intensity ratio of ≤0.5[9][10].

(E) Follicular lymphoma is incorrect because follicular lymphoma characteristically expresses CD10 (negative in this case) and BCL6, and does not express the characteristic HCL markers CD103, CD11c, CD25, or CD123[^10]. Follicular lymphoma typically presents with lymphadenopathy rather than isolated splenomegaly and pancytopenia.

Table 1[^10]

The table above comprehensively compares the immunophenotypic features distinguishing HCL from its mimics, demonstrating why only HCL fits the described profile.

詳解 · 中文翻譯

1) 為什麼 (D) 毛細胞白血病是正確答案：

描述的免疫表型是毛細胞白血病（HCL）的病理特徵性標誌。患者表現出經典的「HCL 免疫學評分」，CD20、CD11c、CD25、CD103 和 CD123 陽性（HCL 免疫學評分為 4/4），結合 CD5、CD10 和 CD27 陰性1234。此標誌物組合在 98% 的 HCL 病例中見到，對此診斷具有高度特異性34。全血球減少、中性粒細胞減少及脾腫大的臨床表現進一步支持 HCL，其特徵性表現為血球減少（包括單核細胞減少）、脾腫大和骨髓累及12[^8]。

圖中所示證明了 HCL 的特徵性流式細胞術模式，顯示 CD19/CD20 陽性、輕鏈限制性、CD5 和 CD10 陰性及 CD200、CD11c、CD25 和 CD123 陽性 — 與病例表現相符。

2) 為什麼其他選項不正確：

(A) 慢性淋巴細胞白血病（CLL）不正確，因為 CLL 特徵性表達CD5 和 CD23（本例均陰性）且顯示 CD20、CD22 和表面免疫球蛋白的弱表達45[^11]。儘管 CLL 可表達 CD11c 和 CD25，其強度明顯低於 HCL，且 CLL 不表達 CD103 或 CD1235[^10]。CLL 中的 HCL 免疫學評分為 0-1 而非 434。

(B) 脾邊緣區淋巴瘤（SMZL）不正確，因為 SMZL 通常顯示 CD103 表達陰性或弱（通常陰性）、CD123 陰性及CD25 陽性僅在少數病例中[9][10]。SMZL 細胞形態學上具有獨特的「絨毛狀淋巴細胞」，具有極性短絨毛，通常表達 CD27，本例陰性[9][10]。SMZL 中的 HCL 免疫學評分通常為 0-1[^9]。

(C) 脾瀰漫紅髓小 B 細胞淋巴瘤（SDRPL）不正確，因為 SDRPL 顯示 CD103 表達不一致（38%）、CD123 表達罕見（16%） 及CD25 表達罕見（3%）[9][10]。SDRPL 有低的 HCL 免疫學評分，可通過 CD200/CD180 中位螢光強度比 ≤0.5 與 HCL 區分[9][10]。

(E) 濾泡性淋巴瘤不正確，因為濾泡性淋巴瘤特徵性表達CD10（本例陰性）及 BCL6，不表達特徵性 HCL 標誌物 CD103、CD11c、CD25 或 CD123[^10]。濾泡性淋巴瘤通常表現為淋巴結腫大而非孤立脾腫大和全血球減少。

表 1[^10] 上表全面比較了區分 HCL 與其模擬物的免疫表型特徵，證明了為何只有 HCL 符合所述特徵。

參考文獻 (AMA)

  1. Falini B, Tiacci E. Hairy-Cell Leukemia. The New England Journal of Medicine. 2024;391(14):1328-1341. doi:10.1056/NEJMra2406376. PMID:39383460. ↩↩↩↩

  2. Blombery P, de Jong D, Ferry JA, et al. Closing the Gap Between Biology and Classification in Splenic B-Cell Lymphomas. Histopathology. 2025;86(1):69-78. doi:10.1111/his.15323. PMID:39403047. ↩↩↩↩

  3. Troussard X, Maître E, Paillassa J. Hairy Cell Leukemia 2024: Update on Diagnosis, Risk-Stratification, and Treatment-Annual Updates in Hematological Malignancies. American Journal of Hematology. 2024;99(4):679-696. doi:10.1002/ajh.27240. PMID:38440808. ↩↩↩↩↩↩

  4. Troussard X, Maître E, Cornet E. Hairy Cell Leukemia 2022: Update on Diagnosis, Risk-Stratification, and Treatment. American Journal of Hematology. 2022;97(2):226-236. doi:10.1002/ajh.26390. PMID:34710243. ↩↩↩↩↩↩↩↩

  5. Suneel R, Rajasekaran S, Kaur H, et al. Diagnosis of Hairy Cell Leukaemia by Fine Needle Aspiration Cytology of Lymph Node. Diagnostic Cytopathology. 2021;49(4):E167-E171. doi:10.1002/dc.24627. PMID:33002340. ↩↩↩↩

  6. Robbins BA, Ellison DJ, Spinosa JC, et al. Diagnostic Application of Two-Color Flow Cytometry in 161 Cases of Hairy Cell Leukemia. Blood. 1993;82(4):1277-87. PMID:7688993. https://pubmed.ncbi.nlm.nih.gov/7688993. ↩

  7. Batata A, Shen B. Immunophenotyping of Subtypes of B-Chronic (Mature) Lymphoid Leukemia. A Study of 242 Cases. Cancer. 1992;70(10):2436-43. doi:10.1002/1097-0142(19921115)70:103.0.co;2-c. PMID:1384948. ↩

Slide annotations

Positive: CD11c, CD25, CD103, CD123 TRAP, annexin A

Figures