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.