Pelkey Lauren J, Graham David M, Zakem Michael H, Muza-Moons Michelle M
Medicine, Ascension Genesys Hospital, Grand Blanc, USA.
Pathology, University of Michigan Health-West, Wyoming, USA.
Cureus. 2022 Feb 21;14(2):e22422. doi: 10.7759/cureus.22422. eCollection 2022 Feb.
Chronic myelomonocytic leukemia (CMML) is a clonal myeloid neoplasm characterized by sustained peripheral blood monocytosis and variable dyspoiesis. We present a case of a 64-year-old male who presented with severe non-bloody diarrhea, peripheral blood neutrophilia, and monocytosis. He was diagnosed with myeloproliferative CMML type 0 and ulcerative colitis (UC). Next-generation DNA sequencing of a bone marrow sample demonstrated mutations of the TET2, ASXL1, NRAS, and SRSF2 genes along with low-level JAK2^V617F mutation. Both TET2 and SRSF2 mutations are associated with systemic inflammatory and autoimmune disease (SIAD), which includes UC. The patient's UC was managed successfully with vedolizumab infusions. The patient's concurrent CMML was monitored with a "wait and watch" approach. After five months, the patient asymptomatically tested positive for coronavirus disease 2019 (COVID-19). Seven months after his diagnosis of CMML, the patient presented in severe respiratory distress with acute left upper quadrant pain, splenomegaly, and multiorgan failure. A peripheral blood smear demonstrated marked leukocytosis (283 x 10^9 /L) with 39% blasts/promonocytes without Auer rods. The patient was diagnosed with acute myeloid leukemia with myelomonocytic features (AMML). In this report, we discuss the diagnosis of combined CMML and SIAD, mechanisms of immunoregulatory dysfunction that have been suggested to result in CMML progression, and the clinicopathologic significance of the patient's molecular abnormalities.
慢性粒单核细胞白血病（CMML）是一种克隆性髓系肿瘤，其特征为持续性外周血单核细胞增多和不同程度的造血异常。我们报告一例64岁男性患者，表现为严重的非血性腹泻、外周血中性粒细胞增多和单核细胞增多。他被诊断为0型骨髓增殖性CMML和溃疡性结肠炎（UC）。骨髓样本的二代DNA测序显示TET2、ASXL1、NRAS和SRSF2基因发生突变，同时伴有低水平的JAK2^V617F突变。TET2和SRSF2突变均与包括UC在内的全身炎症和自身免疫性疾病（SIAD）相关。患者的UC通过维多珠单抗输注成功得到控制。患者并发的CMML采用“观察等待”方法进行监测。五个月后，患者无症状地检测出2019冠状病毒病（COVID-19）呈阳性。在诊断为CMML七个月后，患者出现严重的呼吸窘迫，伴有急性左上腹疼痛、脾肿大和多器官功能衰竭。外周血涂片显示明显的白细胞增多（283×10^9 /L），其中39%为原始细胞/早幼单核细胞，无Auer小体。患者被诊断为具有粒单核细胞特征的急性髓系白血病（AMML）。在本报告中，我们讨论了CMML与SIAD合并症的诊断、已被认为导致CMML进展的免疫调节功能障碍机制以及患者分子异常的临床病理意义。
