Two cases of chronic myelomonocytic leukemia combined with monoclonal gammopathy of undetermined significance and a literature review

To describe myelodysplastic syndrome(MDS)/myeloproliferative neoplasm(MPN) combined with monoclonal gammopathy of undetermined significance(MGUS) in order to investigate the potential association between these 2 diseases. Two cases of confirmed chronic myelomonocytic leukemia(CMML) combined with MGUS were reported. In addition, prior publications of cases with combined MDS or MPN with MGUS were reviewed. The first case was of a 77-year-old man whose routine blood tests showed abnormal hemogram results. The diagnosis was CMML combined with Ig M monoclonal gammopathy, and the disease course was 4 years. The CMML gradually progressed and the patient presented with anemia, thrombocytopenia, autoimmune hemolysis, and an increase in the number of immature cells in the bone marrow. Although the MGUS caused fluctuations in the concentrations of Ig M, no Ig M-associated organ damage was observed. Eventually, this patient died from a lung infection. The second case was of a 78-year-old man who sought treatment because of fever and a cough. An increase in the number of monocytes was discovered in the peripheral blood. Bone marrow smear results suggested obvious active granulocytes and an increase in the percentages of promyelocytes, myelocytes, and metamyelocytes. Unhealthy granulocytes and immature monocytes could also be observed, and the percentage of monocytes was increased. In addition, serum Ig G levels were increased, and immunofixation electrophoresis results showed Ig G-κ type M proteins. The diagnosis was CMML combined with Ig G monoclonal gammopathy. These diseases were stable and follow-up was conducted for 1 year after diagnosis. The cases in this study combined with those that were reviewed in the relevant literature indicate that the presence of these 2 diseases in the same patient might not be a coincidence. The development of the 2 diseases in case 1 was different, and we speculate that they might have had different clonal origins. Whether CMML is a risk factor for MGUS and the role of clonal plasma cells in the occurrence and development of MDS and MDS/MPN requires further studies on a larger number of cases.

Central and peripheral neurological involvement in monoclonal gammopathies of undetermined significance

Several studies have suggested a pathogenetic role of paraproteinaemias in PNS damage. Over the few last years, the presence of symptomatic or subclinical PNS lesions in CNS diseases like multiple sclerosis has been described. On the other hand, CNS demyelinating lesions and cervical atrophy have been re- ported in patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Very few cases of MGUS associated with CNS disease alone or with both CNS and PNS disease have been re- ported. Since 1999, we have been studying 16 patients (8 M, 8 F), with a mean age 60.2 ± 13.4, affected by MGUS associated with symptomatic neurological central and/or peripheral diseases. Patients affected with lymphomas, lupus erithematosus and other immunological diseases were excluded. Involvement of both PNS and CNS was not associated to a particular type of paraproteinemia: monoclonal IgM were found in 8 patients;monoclonal IgG in 6 patients and mono- clonal IgA in 1 patient and Igl in 1 patient. High anti- nervous system autoantibodies were found in 10/16 patients and antiMAG antibodies were detected in patients with paraproteinemic demyelinating neuropathy (PDN). High reactivity anti-nervous system might support the hypothesis of a pathogenetic role of MGUS in these neurological diseases. Nevertheless, at present, we cannot exclude that there is only a circumstantial association between MGUS and neurological damages, particularly concerning CNS.

Typing of Four Cases of Monoclonal Gammopathy: A Revival of Immunosubstraction Role

Monoclonal gammopathy of undetermined significance (MGUS) is characterized by increased production of an immunoglobuling (Ig) from a clone of plasma cells and is a pre-malignant disorders in subjects older than 50 years. The prevalence of MGUS in Caucasian population is still not determined. MGUS is characterized by the presence of a monoclonal-protein(M-protein) (IgG and IgA) lower than 30 g/L, bone marrow plasma cell percentage lower than 10%, and absence of clinical signs related to multiple myeloma (MM). MGUS can be responsible for damage to organs through the production of toxic M proteins that may have autoantibody activity or deposit pathologically in the organ tissues. Many techniques are available for the characterization of M-proteins. These techniques can involve different expenses, skills, labor time, and sensitivity in detecting monoclonal proteins also at low-level. Detection of M-proteins needs of assays based on high-resolution electrophoresis and im-munofixation (or immunosubtraction). We show suggestive clinical cases where the subjects involved had not an apparent disease but they showed an interesting pattern in electrophoresis. All cases were investigated by capillary’s electrophoresis and immunofixation to confirm or not the clinical suspect, and then if the immunofixation is not exhaustive, additionally immunosubstraction is done. However in some cases, the interpretation of the peaks is not so easy. Clinical and scientific data provided evidences that immunofixaction technique can fail the identification of monoclonal components. In that cases, we opted for the immunosubtraction method as a third level test, in that cases when immunofixation failed the identification of a monoclonal protein.

不同浆细胞病分型患者骨髓浆细胞的流式特征分析

目的探讨根据国际骨髓瘤工作组(International Myeloma Working Group,IMWG)标准不同浆细胞病分型患者骨髓浆细胞数量及免疫表型的差异。方法回顾性分析2019年6月12日至2023年9月5日在复旦大学附属中山医院厦门医院诊治的浆细胞病患者血清学及骨髓流式结果。结果纳入102例浆细胞病患者,男性63例,女性39例,发病年龄22~85岁,其中意义未明的单克隆丙种球蛋白血症46例,冒烟型骨髓瘤5例,多发性骨髓瘤39例,轻链淀粉样变性12例。所有患者均伴有M蛋白,包含IgG型58例、非IgG型44例。所有患者骨髓均可检测到浆细胞,其中79例患者骨髓检测到异常浆细胞,63例患者骨髓检测到正常浆细胞,40例患者骨髓同时检测到正常及异常浆细胞。52例患者骨髓的异常浆细胞表达CD56,12例患者骨髓异常浆细胞表达CD117。不同疾病组间的性别、年龄差异无统计学意义。不同疾病组间的M蛋白类型及浓度、血清受累/非受累游离轻链、骨髓总浆细胞(包括正常及异常浆细胞)/有核细胞、骨髓异常浆细胞/有核细胞、骨髓异常浆细胞/骨髓总浆细胞、骨髓正常浆细胞/骨髓总浆细胞的差异均有统计学意义(P均<0.05)。不同疾病组中异常浆细胞CD56的表达存在统计学差异(P=0.009),而CD117的表达差异无统计学意义。结论轻链淀粉样变性患者骨髓克隆性浆细胞的比例、克隆性浆细胞/骨髓总浆细胞、异常浆细胞CD56表达比例与意义未明单克隆丙种球蛋白血症相仿,而与多发性骨髓瘤患者有显著差异。

单克隆丙种球蛋白血症639例临床观察分析

目的了解M蛋白的分型及临床意义,提高认识和诊断水平。方法通过对1998年1月至2005年12月上海交通大学医学院附属新华医院血液科诊治及少量外院送检标本M蛋白阳性者共639例结合临床对年龄、性别和疾病分布,以及多发性骨髓瘤(MM)与意义未明或继发性单克隆丙种球蛋白(MGUS)的特点进行分析。结果639例M蛋白血症中IgG型409例(64.0%)、IgA型80例(12.5%)、IgM型79例(12.4%)、IgD型4例(0.6%)、轻链型27例(4.2%,其中κ9例、λ18例)、双克隆型27例(4.2%)、单克隆型13例(2.0%)。该组患者病种分布,MM115例(18.0%)、华氏巨球蛋白血症(WM)13例(2.0%)、肾原发性淀粉样变性(AL)1例、非霍奇金淋巴瘤(NHL)19例(3.0%)、慢性淋巴细胞白血病(CLL)5例(0.8%)、MGUS473例(74.0%)、寡克隆13例(2.0%)。结论M蛋白血症是一种亚临床现象,主要见于MM及淋巴细胞增殖性疾病,意义未明或继发者检出率有增加趋势。

意义未明单克隆丙种球蛋白病的ICD-10编码分析

在ICD-10第三卷中采用主导词"丙"查到单克隆丙种球蛋白病的编码是D47.2;意义未明的单克隆丙种球蛋白病的编码是D89.2。回顾某院收治的1例意义未明的单克隆丙种球蛋白病(MGUS)患者的临床表现、骨髓病理改变和治疗,并复习相关文献,分析意义未明的单克隆丙种球蛋白病的临床特征与其它类型丙球蛋白病的区别,特别是与单克隆丙种球蛋白病的区别,单克隆丙种球蛋白血症是一组由B细胞克隆性增殖所致的疾病,其共同特点为分泌具有相同结构的免疫球蛋白分子或其片段,即M蛋白。MGUS的诊断标准包括:(1)血清中M-蛋白浓度<3g.dl^(-1);(2)骨髓中浆细胞<10%;(3)尿中极少或无M-蛋白;(4)扁骨中没有溶骨性损害;(5)无相应的贫血、高钙血症或肾功能不全^([3])。仔细阅读病案,按照国际疾病分类原则进行准确的ICD-10编码。提示意义未明的单克隆丙种球蛋白病与单克隆丙种球蛋白病要分开编码,需要在使用的字典库中扩充编码D89.2未确定意义的单克隆丙球蛋白病,这样可避免编码员在电脑系统查找中,在没有在卷三查找的情况下,把D89.2未确定意义的单克隆丙球蛋白病,错编码成D47.2单克隆丙种球蛋白病。编码员阅读病案,提高医学知识和国际疾病分类专业技能,是准确进行编码的关键。