Cancer as the Initial Presentation in Patients with Fanconi’s Anemia.

Background: Patients with Fanconi’s Anemia (FA) have very high risks of developing leukemia and solid tumors. Cancer is thought to follow the diagnosis of FA in most patients, but we know about several patients in whom a cancer diagnosis led to the diagnosis of FA.

Hypotheses: FA patients who present with cancer comprise a substantial proportion of the FA patients who have cancer. Undiagnosed FA may contribute significantly to apparently sporadic cancer patients who are atypically young and lack usual risk factors.

Experimental Design: A systematic review of the medical literature.

Methods: Medline search terms were “Fanconi Anemia” and “Cancer,” “Leukemia” or “Myelodysplastic Syndrome (MDS).” Malignancies after stem cell transplant were excluded.

Results: 90 patients were reported with a solid tumor, 117 with leukemia, and 61 with MDS (11 of whom developed leukemia). These events preceded the diagnosis of FA in ~25% of patients. The median ages at diagnosis of FA were 9, 23, and 12 years respectively. 40% of the tumors were squamous cell carcinomas of the head, neck, or esophagus (HNSCC), and 10% each were brain, Wilms, and gynecologic tumors. The relative frequency of the tumor types was similar whether the first diagnosis was cancer or FA. 90% of the leukemias were acute myeloid leukemia (AML). Among FA patients with tumors as adults (>18 years old), the age at cancer diagnosis was similar whether cancer occurred first or FA was diagnosed first (median ages 31 and 27), but the age at FA was significantly older when cancer came first (32 vs 11 yrs). Among FA patients with tumors <18 years old, those with cancer first had cancer younger than those with FA first (median ages 2 vs 6 years), while the age at diagnosis of FA was similar (2 vs 1 years). In both the <18 and >18 year old patients with leukemia or MDS, these complications occurred at similar ages whether they preceded or followed the diagnosis of FA.

Conclusions: This literature review is limited by over-reporting of patients who presented with cancer and were then identified as FA, and under-reporting of patients who presented with cancer in whom FA was never diagnosed. The magnitude of these biases cannot be determined from the literature, or from cohorts of patients known to have FA. We propose that a systematic evaluation for FA should be done in young, risk-factor negative HNSCC patients, to determine the contribution of FA to this subset of cancer in the general population. Heightened awareness of features of FA may also be helpful in the diagnosis of FA in patients with brain, Wilms, and gynecologic tumors.