Jawhar Mohamad, Schwaab Juliana, Horny Hans-Peter, Sotlar Karl, Naumann Nicole, Fabarius Alice, Valent Peter, Cross Nicholas C P, Hofmann Wolf-Karsten, Metzgeroth Georgia, Reiter Andreas
Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany.
Eur J Clin Invest. 2016 May;46(5):392-7. doi: 10.1111/eci.12607. Epub 2016 Mar 21.
Bone marrow (BM) histology/immunohistochemistry, KIT D816V mutation analysis and serum tryptase measurements are mandatory tools for diagnosis of systemic mastocytosis (SM).
Within the 'German Registry of Disorders on Eosinophils and Mast Cells', we identified 65 patients with SM who had two consecutive BM biopsies. The first biopsy was evaluated by a local pathologist (LP) and the second biopsy by a reference pathologist (RP) of the 'European Competence Network on Mastocytosis (ECNM)'.
Final diagnoses by RP were SM (n = 27), SM or aggressive SM (ASM) with associated clonal haematological non-mast cell lineage disease [(A)SM-AHNMD, n = 34)] or mast cell leukaemia ± AHNMD (n = 4). In 15 of 65 patients (23%), initial diagnoses by LP were incorrect (by overlooking SM), for example primary myelofibrosis (n = 3), myelodysplastic/myeloproliferative neoplasm unclassified (n = 3) or B-cell lymphoma (n = 2). Fourteen of 15 patients (93%) with incorrect diagnosis had an advanced SM, mostly (A)SM-AHNMD. In the 50 concordantly diagnosed patients, immunohistochemical markers for quantitative assessment of mast cell infiltration, for example CD117 (KIT) or CD25, were applied by LP in only 34 of 50 patients (68%), and mutational analysis for KIT D816V was performed or recommended in only 13 of 50 patients (26%). Finally, the subclassification of SM was discordant because LP did not diagnose AHNMD in nine of 50 (18%) patients.
In summary, adequate diagnosis and subclassification of SM requires an in-depth evaluation of the BM by experienced haematopathologists (preferably in a reference centre) in combination with molecular genetics, serum tryptase level and clinical parameters.
骨髓（BM）组织学/免疫组织化学、KIT D816V突变分析及血清类胰蛋白酶检测是系统性肥大细胞增多症（SM）诊断的必备手段。
在“德国嗜酸性粒细胞和肥大细胞疾病登记处”，我们确定了65例接受过两次连续骨髓活检的SM患者。第一次活检由当地病理学家（LP）评估，第二次活检由“欧洲肥大细胞增多症能力网络（ECNM）”的参考病理学家（RP）评估。
RP的最终诊断为SM（n = 27）、伴有相关克隆性血液非肥大细胞谱系疾病的SM或侵袭性SM（ASM）[（A）SM-AHNMD，n = 34]或肥大细胞白血病±AHNMD（n = 4）。65例患者中有15例（23%）LP的初始诊断不正确（因漏诊SM），例如原发性骨髓纤维化（n = 3）、未分类的骨髓增生异常/骨髓增殖性肿瘤（n = 3）或B细胞淋巴瘤（n = 2）。15例诊断错误的患者中有14例（93%）患有晚期SM，大多为（A）SM-AHNMD。在50例诊断一致的患者中，LP仅对50例患者中的34例（68%）应用了用于定量评估肥大细胞浸润的免疫组织化学标志物，如CD117（KIT）或CD25，且仅对50例患者中的13例（26%）进行了或建议进行KIT D816V突变分析。最后，SM的亚分类不一致，因为LP在50例患者中的9例（18%）中未诊断出AHNMD。
总之，SM的充分诊断和亚分类需要经验丰富的血液病理学家（最好在参考中心）结合分子遗传学、血清类胰蛋白酶水平和临床参数对骨髓进行深入评估。
