CASE REPORT: A 59-year-old man was diagnosed with acute promyelocytic leukaemia. Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved remission. Four years later, the disease relapsed and he was given idarubicin, mitoxantrone and ATRA followed by maintenance chemotherapy (ATRA, mercaptopurine and methotrexate). He achieved a second remission for the next 11 years. During a follow-up later, his full blood picture showed leucocytosis, anaemia and leucoerythroblastic picture. Bone marrow examination showed hypercellular marrow with trilineage dysplasia, 3% blasts but no abnormal promyelocyte. Fluorescence in-situ hybridisation (FISH) study of the PML/RARA gene was negative. Karyotyping result revealed complex abnormalities and monosomal karyotype (MK). A diagnosis of therapy-related myelodysplastic syndrome/myeloproliferative neoplasm with unfavourable karyotypes and MK was made. The disease progressed rapidly and transformed into therapy-related acute myeloid leukaemia in less than four months, complicated with severe pneumonia. Despite aggressive treatment with antibiotics and chemotherapy, the patient succumbed to the illness two weeks after the diagnosis.
DISCUSSION AND CONCLUSION: Diagnosis of t-MN should be suspected in patients with a history of receiving cytotoxic agents. Karyotyping analysis is crucial for risk stratification as MK in addition to complex aberrant karyotypes predicts unfavourable outcome. Further studies are required to address the optimal management for patients with t-MN.
CASE REPORT: We described a patient with ET whose disease evolved into MDS with fibrosis and complex karyotype after 15 years of stable disease. She was asymptomatic and was on hydroxyurea (HU) treatment until recently when she presented with worsening anaemia. Physical examination showed mild splenomegaly. Full blood picture showed leukoerythroblastic picture with presence of 3% circulating blasts and background of dysplastic features such as hypogranular cytoplasm and nuclear hyposegmentation of neutrophils. The bone marrow aspiration was haemodiluted but revealed presence of 6% blast cells, trilineage dysplasia and predominant erythroid precursors (60%). Trephine biopsy showed no excess of blast cells and normal quantity of erythroid precursors, but there was increased in fibrosis (WHO grade 2) and presence of dysmegakaryopoeisis such as nuclear hypolobation, multinucleation and micromegakaryocytes. Cytogenetic study showed complex karyotype; monosomy of chromosome 2, chromosome 5, chromosome 18 and presence of a marker chromosome (42~44, XX,-2,-5,-18,+mar). Fluorescence in situ hybridisation (FISH) showed 5q deletion (CSF1R and EGR1).
CONCLUSION: The findings were consistent with transformation of ET to MDS with fibrosis and complex karyotype. ET progression to MDS is considered rare. The presence of complex karyotype and fibrosis in MDS are associated with unfavourable outcome.
Methodology: This was a cross-sectional study. Thirty-four (34) Turner patients were examined for Turner-specific clinical features. The karyotype, clinical features at presentation, age at diagnosis and physiologic features were retrieved from their medical records.
Results: Patients with 45,X presented at a median age of 1 month old with predominantly lymphoedema and webbed neck. Patients with chromosome mosaicism or structural X abnormalities presented at a median age of 11 years old with a broader clinical spectrum, short stature being the most common presenting clinical feature. Cubitus valgus deformity, nail dysplasia and short 4th/5th metacarpals or metatarsals were common clinical features occurring in 85.3%-94.1% of all Turner patients. Almost all patients aged ≥2 years were short irrespective of karyotype.
Conclusion: Although short stature is a universal finding in Turner patients, it is usually unrecognised till late. Unlike the 45,X karyotype, non-classic Turner syndrome has clinical features which may be subtle and difficult to discern. Our findings underscore the importance of proper serial anthropometric measurements in children. Awareness for the wide spectrum of presenting features and careful examination for Turner specific clinical features is crucial in all short girls to prevent a delay in diagnosis.