The myelodysplastic syndromes (MDS) are characterized by proliferation of hematopoietic stem cells with abnormalities of differentiation leading to peripheral blood cytopenia and a preleukemic state. About 10–35% of MDS evolve to acute leukemia. The mechanism of transformation of MDS to acute myeloid leukemia (AML) includes many factors, and prediction of the transformation is not yet clear. We report a case of leukemic transformation of MDS with multi-muscle involvement and whole-body 2-[F18] fluoro-2-deoxy-d-glucose positron emission tomography (F18-FDG PET).

A 52-year-old female, presenting with high fever for 10 days, chills, frequent micturition, and urgency, was admitted to the regional hospital on 10 April 2009. A hematologic study showed pancytopenia (exact values were not known). Blood hemoculture showed Escherichia coli. Blood transfusion and treatment for septicemia were given, and after a week, she was relieved of the above-mentioned symptoms. However, her blood counts did not become normal. After a week, the patient was transferred to Nanfang Hospital. On admission, the physical examination was normal. Blood counts showed moderate pancytopenia (hemoglobin 92 g/l, WBC 1.57 × 10⁹/l and platelets 92 × 10⁹/l). On 20, 22 and 27 April, bone marrow aspiration biopsy was performed repeatedly, and the percentage of blast cells from bone marrow was 12.55%, 22.5%, and 26.5%, respectively. The additional blood films were negative for cytologic evidence of acute leukemia. On 20 April, flow cytology detected 13.50% blast cells from bone marrow, which had CD34⁺, CD2⁺, and CD41⁺phenotype, and bone marrow biopsy microscopically revealed that granulocyte and megakaryocyte series reduced, and a fraction of plasma cells diffusing encroached that were MPO⁺, CD38⁺, CD138⁺, CD68⁺, CD61⁺, CD3⁺, CD45RO⁺, CD20⁺, CD79a⁺. However, 4.49% blast cells were detected that had CD34⁺, CD2⁺, CD7⁺, CD117⁺, CD71⁺, HLA-DR⁺phenotype on 27 April, and it microscopically disclosed scattering immature mononuclear cells which were MPO⁺, CD68⁺, and CD61⁺. Therefore, F18-FDG PET of whole body was carried out on 5 May, which manifested no evidence of malignancy, including that of bone marrow [Figure 1]. The final diagnosis could not be made because of the patient's resolution to give up treatment. She was intermittently transfused blood without any other treatment for about 10 months since she had been discharged. On 25^th March, she was hospitalized with fever of 3 days duration accompanied by swelling and pain of the right upper leg and stern. On physical examination, there was axillary lymphadenopathy. Routine blood analysis showed serious pancytopenia (hemoglobin 81 g/l, WBC 0.67 × 10⁹/l, platelets 35 × 10⁹/l). Bone marrow aspiration displayed that immature monocytes accounted for 25.0%, Periodic acid-schiff stain (PAS) (+), Peroxidase stain (POX) (+), considering AML. Flow cytometry detected 28.60% blast cells, which had CD34⁺, CD13⁺, CD64⁺, CD11b⁺, HLA-DR⁺ phenotype, from bone marrow. Bone marrow biopsy was suggestive of megakaryocytic tumor. The number of bone marrow cells was not enough to implement karyotype examination. Ultrasound showed that bilateral arteries and veins of pelvic limb were easy and smooth. Whole-body lymphoimaging showed that lymph fluid circulation was unobstructed and soft tissues of the right lower limb were swollen [Figure 2]. F18-FDG PET of whole body showed spotted and focal increased uptake in ribs, vertebrae, ilium, humerus, femur, tibia, and high intensity foci of FDG uptake in right axillary, mediastinal, bilaterally lung portal, peritoneal, right communistic and external iliac lymph nodes. Moreover, a significant lesion of increased metabolism infiltrated muscles of right rear upper legs, right gluteus maximus and medius [Figure 3]. According to the above outcomes and physical examination, the final diagnosis was inclined to be AML. As a result, treatment with CAG chemotherapy regimen was started. During the course of chemotherapy, intumescence of right upper leg and stern conspicuously lessened. However, after less than a week, the patient died from cerebral hemorrhage and hernia.

The case reported here was that of an old woman presenting with pancytopenia, chromosome clonal abnormality, fluctuation of the percent of blast cells at 20%, and negative evidence of malignancy in whole-body F18-FDG PET. After about 10 months, the blast cells accounted for about 25%, the morphology of which was similar to that of the previous ones, and F18-FDG PET demonstrated diffusing increased uptake in the right upper leg and lymph nodes, and patchy high uptake of bone marrow. In this case, the main differential diagnosis of pancytopenia was between leukemia and MDS. The percent of blast cells of bone marrow is critical to differentiate leukemia and MDS. In this patient, retrospectively, it is speculated that it was the transformation from MDS to AML in April 2009, which might have led to inconsistent bone biopsies, aspirations and immunophenotypes. Immunophenotyping demonstrated that blast cells were of myeloid lineage, which is consistent with the earlier reports.[¹–³] Therefore, close follow-up was recommended.

To the best of our knowledge, few studies about multi-muscle of leg involvement have been reported, and obviously the diagnostic value of F18-FDG PET in the fields of MDS and AML has been attributed to reduced F18-FDG PET uptake in the bone marrow. It was reported that F18-FDG PET performed in a patient with MDS showed diffusing increased uptake of bone marrow of the whole body, which transformed into AML after 2 months, showing that F18-FDG PET may be an indicator for transformation of MDS to AML.[⁴] In this case, F18-FDG PET detected tumor burden and was positive for extramedullary infiltration in AML phase, which is compatible with the previous reports,[⁵] but was negative for malignancy of bone marrow in the state of transformation phase, which is not concordant with the previous reports. Agool and others[⁶–⁸] reported that homogeneous increased uptake of bone marrow was seen in eight MDS patients in 3’-deoxy-3’-[F18]-fluorothymidine positron emission tomography (F18-FLT PET), which, in comparison to F18-FDG PET, is more related to the rate of DNA synthesis and cycling activity and provides visual and quantitative information on the entire bone marrow compartment. Perhaps it is more sensitive than F18-FDG PET in forecasting transformation of MDS to AML. The value of F18-FDG or F18-FLT PET as an indicator in predicting the transformation of MDS to AML needs to be explored in the future, and F18-FDG or F18-FLT PET can reflect extramedullary infiltration and bone marrow cellularity of whole body, compared with invasive, regional biopsies and aspirations.

Source of Support: Nil.

Conflict of Interest: None declared.