1Department of Laboratory Medicine, Pusan National University Hospital, Busan, Korea.
2Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.
3Division of Hematology-Oncology, Department of Internal Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea.
As chemotherapy for the treatment of plasma cell myeloma (PCM) includes alkylating agents, the incidence of therapy-related myeloid neoplasms such as acute myeloid leukemia, myelodysplastic syndrome (MDS), and myeloproliferative neoplasm due to prior PCM chemotherapy has increased. Several studies reported the mutagenic effect of some PCM treatment regimens on the development of MDS . By contrast, cases with simultaneous presentation of PCM and MDS unrelated to prior chemotherapy are far less frequently observed than cases with MDS related to prior chemotherapy . A recent study reported that in a period of 14 years, only 14 cases of monoclonal gammopathy and MDS unrelated to chemotherapy or radiotherapy were reported, representing 12 cases of monoclonal gammopathy of undetermined significance (MGUS) and 2 cases of smoldering myeloma (SM) . We report a case of simultaneous presentation of symptomatic PCM and MDS unrelated to prior chemotherapy.
An 80-year-old woman was admitted to our hospital because of chest pain that developed 1 day prior to admission. She had been treated for bronchial asthma with a bronchodilator and leukotriene antagonist for 2 years but had no medical history related to hematologic malignancy. The patient's hemogram results at admission were as follows: white blood cell count, 0.95×109/L; hemoglobin level, 8.0 g/dL; mean corpuscular volume, 105.9 fL; and platelet count, 29.0×109/L. The patient's biochemical test results at admission were as follows: serum protein level, 6.8 g/dL; serum albumin level, 2.8 g/dL; serum creatinine level, 1.54 mg/dL; serum calcium level, 7.4 mg/dL; and serum lactate dehydrogenase level, 719 IU/L. In the examination of a peripheral blood smear, pancytopenia with rouleaux formation was observed. Bone marrow aspirates showed hypocellular marrow without an increase in the number of myeloblasts but showed increased infiltration of plasma cells at a frequency of 14.9% (Fig. 1A). In addition, megakaryocytic dysplasias such as separated nuclei (Fig. 1A) and hypolobulated nuclei (Fig. 1B and C) were found, accounting for 30% of the total number of megakaryocytes. Erythroid dysplasias such as binucleation and delayed mitosis were also found (Fig. 1C and D), as well as mild granulocytic dysplasias such as hyposegmentation, accounting for 15% and 10% of the total numbers of erythroid and granulocytic lineage cells, respectively. Examination of a bone marrow biopsy specimen (Fig. 1E) revealed 35% cellular marrow with diffuse infiltration of plasma cells in the immunohistochemical stain for CD138 expression (DAKO, Glostrup, Denmark; Fig. 1F).
Both serum and urine immunofixation analyses using Hydragel IF K20 kit (Sebia, Cedex, France) were performed, and the results showed the presence of monoclonal gammopathy of IgA and lambda type. The subsequently performed serum electrophoresis using Capillarys Protein(E) 6 kit (Sebia, France) showed the presence of monoclonal gammopathy accompanied by M-peaks of 1.27 g/dL. All radiological evaluation results did not show definite evidence of osteolytic lesion. The results of a subsequently performed karyotype analysis showed 46,XX, del(20)(q11.2)/46,XX, indicating the presence of del(20)(q11.2) clone, at a frequency of 75%. Fluorescence in situ hybridization analysis results showed nuc ish(D20S108X1)[156/200], indicating the presence of heterozygous 20q12 deletion, at a frequency of 78%. As the patient showed pancytopenia accompanied with multilineage dysplasia, MDS-related chromosomal abnormality, and monoclonal gammopathy with an increase in serum creatinine level, she was finally diagnosed with the simultaneous presentation of symptomatic PCM and MDS and refractory cytopenia with multilineage dysplasia (RCMD) that were unrelated to prior chemotherapy. After the diagnosis, she developed gram-negative septicemia and died 8 days after the admission.
Our case had similar features regarding the type of MDS-related chromosomal abnormality as those of cases reported in previous studies. Most MDS cases accompanied by MGUS/SM showed a low risk of chromosomal abnormalities, and our case also showed del(20)(q11.2), which is a well-known chromosomal abnormality related to good prognosis in MDS . In addition, our case did not show any history of prior chemotherapy or radiotherapy, which supports the occurrence of simultaneous MDS and symptomatic PCM. Notably, compared with previously reported cases, our case presented unique clinical features that are worth reporting . Our case developed symptomatic PCM, which has not been reported yet, and showed poor prognosis.
In conclusion, we report a rare case of simultaneous presentation of symptomatic PCM and MDS RCMD unrelated to prior chemotherapy or radiotherapy. A more extensive study would be required to investigate the clinical characteristics and outcomes in patients with such a condition.
Bone marrow findings showing both features of plasma cell myeloma and myelodysplastic syndrome. The arrows indicate megakaryocytes with separated (