|LETTER TO THE EDITOR
|Year : 2015 | Volume
| Issue : 1 | Page : 38-39
Leukemic transformation in Fanconi's anemia
R Bhagat1, J Ahluwalia2, N Varma2
1 Department of Pathology, PGIMER, Chandigarh, India
2 Department of Hematology, PGIMER, Chandigarh, India
|Date of Web Publication||3-Feb-2016|
Department of Pathology, PGIMER, Chandigarh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Bhagat R, Ahluwalia J, Varma N. Leukemic transformation in Fanconi's anemia. Indian J Cancer 2015;52:38-9
Fanconi anemia (FA) is an inherited bone marrow failure syndrome associated with congenital abnormalities, hypersensitivity to deoxyribonucleic acid (DNA) cross-linking agents and progressive bone marrow failure leading to death. These patients have a predisposition to acute myeloid leukemia and specific solid tumors.,
A 4-year-old male presented in the pediatric hematology clinic with history of weakness and fever. On examination, he was found to have the classical phenotypic features of FA namely microcephaly, short stature, finger deformities and retracted testes. There was a history of a previous sibling dying of a similar problem.
Bone marrow examination and chromosomal breakage studies were consistent with a diagnosis of Fanconi's anemia assosciated aplastic anemia. Patient was on regular follow-up in the institute. He was again admitted in an emergency at the age of 16 years with severe thrombocytopenia along with intracranial and intraocular bleeds. Hematological examination showed hemoglobin of 70 g/L and platelet count of 12 × 109/L. Total leucocyte count was 1.5 × 109/L with a differential leukocyte count of blasts 18% and 39% monocytes. Bone marrow examination revealed a hyper cellular marrow with a reduced number of megakaryocytes [Figure 1]. There were 47% blasts, 30% monocytes, 05% myelocytes and 07% polymorphs. Few of blasts show faint myeloperoxidase (MPO) positivity.
|Figure 1: Bone marrow showing blasts with a moderate amount of cytoplasm and conspicuous cytoplasm (May Grunwald Giemsa stain, ×40)|
Click here to view
Flow cytometry showed positivity for myeloid markers (CD13, CD33, anti-MPO) and monocytic markers (CD14, CD64) [Figure 2] and also CD34, Human Leucocyte antigen – DR and dim CD45 positivity while they are negative for CD 10, CD19, CD20, CD3, CD8, CD7, cytoplamic CD3 and Tdt. A final diagnosis of acute myelomonocytic leukemia in a known case of Fanconi's anemia was given.
FA is an autosomal recessive disorder characterized by cellular hypersensitivity to DNA cross-linking agents resulting in chromosomal breaks and predisposition of cancer.
These patients are more prone to develop both hematological and non-hematological malignancies. Among the hematological malignancies, acute myeloid leukemia (AML) was most common followed by myelodysplastic syndrome.
The FA-related leukemia differs from leukemia in the general population in several important ways. In FA patients, 94% of the leukemia are myeloid and only 6% were lymphoid, compared with 84% of the leukemia being lymphoid in non-FA children. The age distribution of leukemia in FA patients was normally distributed around a mode of 14 years, in contrast to the general population in which the incidence of AML is higher in infants, declines around age 10 and then rises slightly in the late teens. There were relatively more M4 and M6 AMLs and fewer M1 and M2 in the FA group.
Finally, because patients with FA have high cancer risks, they may provide a population in which the role of new screening modalities can be rapidly validated. These patients should be encouraged to participate in clinical trials designed to develop more effective cancer screening strategies.
Unfortunately, cancer management in FA patients is much more difficult than in the general population because of their increased sensitivity to chemotherapy with DNA cross linkers and the variable, but potential increased side-effects from radiotherapy.
| » References|| |
Nathan DG, Oskin SH, Look AT, Ginsburg D. Haematology of Infancy and Childhood. 7th
ed. Philadelphia : Elsevier Health Sciences; 2009.
Yamashita T, Nakahata T. Current knowledge on the pathophysiology of Fanconi anemia: From genes to phenotypes. Int J Hematol 2001;74:33-41.
Ries LA, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, et al
., editors. SEER Cancer Statistics Review, 1973-1998. Bethesda, MD: National Cancer Institute; 2001.
Alter BP. Radiosensitivity in Fanconi's anemia patients. Radiother Oncol 2002;62:345-7.
[Figure 1], [Figure 2]