Division of Hematopathology. Mayo Clinic College of Medicine, 200 1st Street SW, Rochester, MN 55905, USA.
Am J Clin Pathol. 2010 Jun;133(6):942-8. doi: 10.1309/AJCP3Z2AKUWRGTNM.
The diagnosis of polycythemia vera (PV) requires the integration of clinical and laboratory findings, bone marrow morphologic features, and JAK2 analysis. JAK2(V617F) (exon 14) mutation is found in 95% of PV cases. Functionally similar mutations in JAK2 exon 12 have also been described, but a thorough bone marrow study has not been done. We identified 7 PV cases with exon 12 mutations; all had hypercellular bone marrow with erythroid hyperplasia. Small, atypical megakaryocytes predominated; atypical megakaryocyte lobation and abnormal chromatin distribution was identified in all cases. Rare clusters of megakaryocytes could be found but were typically subtle. Because JAK2 exon 12-positive PV cases lack the classic myeloproliferative morphologic features, bone marrow samples from the patients may be difficult to classify as myeloproliferative neoplasms. Clinically suspected PV with low serum erythropoietin and absent JAK2(V617F), together with the bone marrow findings of erythroid hyperplasia and subtle megakaryocytic atypia, should prompt an evaluation for an exon 12 mutation.
真性红细胞增多症（PV）的诊断需要整合临床和实验室发现、骨髓形态特征和 JAK2 分析。95%的 PV 病例中存在 JAK2(V617F)（外显子 14）突变。也已经描述了 JAK2 外显子 12 中功能相似的突变，但尚未进行彻底的骨髓研究。我们鉴定了 7 例具有外显子 12 突变的 PV 病例；所有病例均有核细胞增多的骨髓，伴有红细胞增生。小而典型的巨核细胞占优势；所有病例均存在异常染色质分布和巨核细胞分叶异常。偶尔可以发现巨核细胞簇，但通常不明显。由于 JAK2 外显子 12 阳性的 PV 病例缺乏典型的骨髓增殖性形态特征，因此患者的骨髓样本可能难以分类为骨髓增殖性肿瘤。临床上怀疑为 PV，血清促红细胞生成素水平低且不存在 JAK2(V617F)，同时伴有红细胞增生和微妙的巨核细胞异型性，应提示进行外显子 12 突变评估。
