Introduction
Li-Fraumeni syndrome is mainly caused by pathogenic germline mutations of the TP53 gene, most commonly missense mutations. GermlineTP53c.566C>T mutation results in the missense mutation at codon (A189V). This mutation has been observed in late-onset cancer such as multiple primary colon tumours, breast cancer and fallopian tube carcinoma.1-3 Moreover, it classified as a variant with uncertain significance. Recently, it was found not to be rare.4 However, the association between this mutation and haematological malignancy has been unclear. Herein, we report a case of germline TP53c.566C>T mutation which was incidentally diagnosed during the treatment of acute myeloid leukaemia (AML).
Case history/examination
A 53-year-old Japanese woman presented with a 2-month history of general fatigue and vomiting. In addition, she experienced dizziness for 3 days and presented with a high fever on the admission day. She had no previous history of malignancy. Some of her family members developed late-onset cancers (Figure 1). Her mother (FⅡ-3) had breast cancer at the age of 51 years. Her uncle (FⅡ-5) developed stomach and colorectal cancer at the age of 60 and 62 years, respectively. Her grandmother (FⅠ-4) died from colorectal cancer at the age of 62 years. She visited other hospitals for diagnosis and treatment. Examination results revealed leucocytosis (with a high number of blast cells), severe anaemia and thrombocytopenia. Computed tomography scan showed acute appendicitis and peritonitis. Hence, she was referred to our hospital for the treatment of AML and appendicitis.
The initial laboratory evaluation of the peripheral blood revealed the following: white blood cell count: 90.3 × 109/L (99% blast cells), haemoglobin level: 4.5 g/dL, and platelet count: 5.0 × 109/L. The patient’s C-reactive protein level was elevated at 33.17 mg/μl
Based on the pathologic examination, the bone marrow aspirate exhibited hypercellularity with 87% of blast cells. Chromosome analysis of leukaemia cells revealed a complex karyotype (46, XX, add(4)(q21), add(10)(p11.2)[9]/46, idem, add(14)(q22)[3]/46, XX [3]). Approximately 87% of the leukaemia cell population tested positive for CD34, HLADR, myelopeloxydasemyeloperoxidase and CD33. Meanwhile, the blast cell population tested negative for CD13 and CD38.