Oral Tongue Cancer in a Patient with Fanconi Anemia: A Case Report and Literature Review

Abstract

Purpose: Fanconi anemia (FA) is a rare genetic disorder characterized by congenital anomalies, progressive bone marrow failure and high susceptibility to solid tumors, especially head and neck squamous cell carcinoma (HNSCC). Management of FA patients with head and neck cancer is a challenge due to increased risk of surgery, poor tolerance of chemotherapy, and severe myelotoxicity of radiotherapy.

Patients and methods: We present a case of a 33-year-old man with carcinoma of oral tongue (T1N2M0), who experienced prolonged and profound bone marrow failure as a consequence of concurrent cisplatin/radiation. The young patient who developed HNSCC without risk factors, the myelotoxicity after exposure to platinum-based agent cisplatin and the further evaluation of phenotypic characteristics raised suspicion of FA. Whole exome sequencing performed for the patient and parents ultimately established the diagnosis of FA.

Results: Genetic testing in 23 FANC genes revealed two novel heterozygous mutations, c.367C>T and c.3971_3972delCGinsTT in FANCA gene of the patient, which were inherited from his father and mother, respectively. Radiotherapy with reduced dose has successfully alleviated the symptoms of tumor invasion and progression, and the radiation-related side effects were acceptable. Unfortunately, the patient eventually died of locoregional disease progression.

Conclusion: This case highlights the importance of considering the diagnosis of FA in young patients who develop HNSCC in the absence of risk factors, thus permitting more effective oncological treatment strategies and improved outcomes. In conclusion, any decision on different modalities of management in such patients should be based on a balance between locoregional control and therapeutic toxicity.

Keywords: cisplatin; fanconi anemia; head and neck squamous cell carcinoma; radiotherapy; toxicity.

Figure 1

DCE-MRI of the maxillofacial region showed the mass located at the right side of tongue dorsum. (A) DCE-MRI before the treatment with concurrent cisplatin/radiation, the tumor size measured 1.6 X 1.4 X 1.7 cm. (B) DCE-MRI during the 8 months of bone marrow recovery therapy with cessation of concurrent cisplatin/radiation, the tumor size had increased to 3.7 X 3.0 X 3.1 cm. (C) DCE-MRI after completion of 21 fractions of reduced-dose radiotherapy, the tumor size had decreased to 3.2 X 2.3 X 2.8 cm. The white arrows indicated the location of the tumor. DCE-MRI, dynamic contrast-enhanced magnetic resonance imaging.

Figure 2

A pathological biopsy demonstrated highly differentiated squamous cell carcinoma. (A) Hematoxylin-eosin, original magnification 40X. (B) Hematoxylin-eosin, original magnification 200X.

Figure 3

(A and B) Physical examination showed generalized hyperpigmentation of the skin and a thumb malformation of the right hand, accompanied by a few café au lait spots, particularly of the upper extremities.

Figure 4

Fanconi anemia complementation group A gene sequence diagram of the patient. (A) c.367C>T was detected in the patient and his father. (B) c.3971_3972delCGinsTT was detected in the patient and his mother. Variants were indicated with arrows; wt, wild type.

Figure 5

Pedigree of the family. Filled and open symbols denoted affected and healthy individuals, respectively. An arrow indicated the index patient; diagonal line indicated deceased status. The mutation status was shown next to each symbol; wt, wild type.