Open Journal of Stomatology, 2011, 1, 45-49 OJST
doi:10.4236/ojst.2011.12008 Published Online June 2011 (
Published Online June 2011 in SciRes.
Fanconi anemia manifesting as a squamous cell carcinoma of
the mandible: a case report
A. Pinar Erdem 1, G. Ikikarakayali1, N. Yalman2, G. Ak3, M. A. Erdem 4, M. B. Bilgic5, E. Sepet1
1Department of Pedodontics, Dentistry Faculty, Istanbul University, Istanbul, Turkey;
2Department of Medical Biology, Istanbul University, Istanbul, Turkey;
3Department of Oral Surgery and Medicine, Dentistry Faculty, Istanbul University, Istanbul, Turkey;
4Department of Oral and Maxillofacial Surgery, Dentistry Faculty, Istanbul University, Istanbul, Turkey;
5Department of Pathology, Istanbul University, Istanbul, Turkey.
Received 16 March 2011; revised 20 April 2011, accepted 3 May 2011.
Progressive bone marrow failure and development of
malignancies, particularly acute myeloid leukemia and
solid tumors the most important features of Fan-
coni’s Anemia (FA). This paper reports the case of a
16-year-old patient with FA who developped squa-
mous cell carcinoma of the mandible, ten years after
the bone marrow transplantation (BMT).
Keywords: Squamous Cell Carcinoma; Fanconi’s
Anemia; Mandible; Bone Marrow Transplantation
Fanconi’s anemia is an autosomal recessive disorder cha-
racterized by constitutional aplastic anemia and conge-
nital abnormalities [1]. FA is defined by chromosomal
breakage in which many patients present with pancyto-
penia, hypoplastic bone marrow, hyperpigmentation of
the skin, skeletal malformations, small stature, hypogo-
nadism, and chromosomal aberrations [2]. FA is char-
acterized by a high degree of genomic instability and
predisposition to cancer development [3]. The most im-
portant features of FA are progressive bone marrow
failure and development of malignancies, particularly
acute myeloid leukemia and solid tumors [4,5]. Such
patients are prone to the development of hematological
malignancies and squamous cell carcinoma, especially
of the head and neck [2,6,7].
FA is characteristically defined by its cellular hyper-
sensitivity to DNA cross-linking agents such as diepoxy-
butane and mitomycin [2,8]. Based on the presence of
mutations in one of the FA genes, FA can be divided
into 8 complementation groups (A-G, including D1 and
D2), with each group having in common the cellular
hypersensitivity to cross-linking agents [9,10]. Current
therapy regimen consists of supportive treatment and
androgens, steroids and cytokines. But allogenic bone
marrow transplantation is the definite treatment of
choice for FA patients with progressive bone marrow
failure. FA patients are at risk for secondary malignan-
cies, for example leukemia, squamous cell carcinoma and
hepatocellular carcinoma [11,12]. The risk of squamous
cell carcinoma development is especially high in the
anogenital region as well as the head and neck region
A review of the literature revealed 40 cases of SCC in
FA patients. 14 of these cases involved oral carcinoma,
with tongue being the most frequently affected site. In
this review, all of the reported SCC in FA patients origi-
nated in mucosal and mucocutaneous sites, especially
oral (n = 25) and anogenital sites (n = 8) and the esopha-
gus (n = 6), with the exception of two patients with mul-
tiple cutaneous involvement [1].
We report SCC of the mandible in a patient with FA.
Only one case of SCC of the mandible in a patient with
FA patient was reported in 1980 by Vaitiekaitis AS et al.
This is a report of a second case.
We report the case of a 16-year-old boy with squamous
cell carcinoma (SCC) of the mandible. On January 2,
2008 he was referred to Istanbul University, Faculty of
Dentistry with a mass on the right side of the mandible.
FA with an unknown complementation group had been
diagnosed at the age of 5 years. He is the second child of
the consangenious marriage. He underwent BMT at
1998 with marrow donated by her HLA-identical sister
who did not have FA. Pre-transplant conditioning con-
sisted of cyclophosphamide 20 mg/kg + total body irra-
diation (TBI) 750 cGy (n:11). At 1998 before the BMT
the dosage of the medicine regimen was changed as
A. P. Erdem et al. / Open Journal of Stomatology 1 (2011) 45-49
Copyright © 2011 SciRes. OJST
cyclophosphamide 20 mg/kg + TBI 500 cGy + antithy-
mocyte globulin (ATG) 10 mg/kg (n:2) He suffered from
graft-versus-host disease (GvHD) (grade II-III) and had
complete hematologic reconstitution during transplant-
ation. For GvHD prophlaxis, they used CSA, because of
GvHD, PRD was given to the patient. This was treated
with cyclosporin A. Four weeks after BMT, CMV infec-
tion had occured. In accordance to this, pnömonia and
cerebral disorder were observed. For treatment of these
disorders, gansikolvir + CMV Ig G was given to the pa-
tient. Between 1999-2003 Cy 40 mg/kg + Bu 6 mg/kg +
ATG 20 mg/kg was applied. He did not come to his me-
dical controls between 2004 - 2008. When he came in
2008, blood observations were repeted. Full blood count
was found normal. According to the microbiological
observations in 2008, anti-CMV Ig G was found positive.
Oral examination disclosed caries of molar teeth, pe-
riodontitis and restricted oral opening. There was a fun-
gating purulent lesion of the right side of the mandible
(Figure 1(a) and (b)). He had severe mucositis
interrupting his oral feeding. The panaromic radiograph
of the patient was shown in Figure 2.
The lesion was examined with CT and MR imaging
and diagnosed as SCC after an incisional biopsy. Micro-
scopic findings of biopsy include two elastic tissue parti-
Figure 1. Intraoral view of the lesion.
Figure 2. Radiographic view of the patient.
cules; size of big one was 0.8 × 0.5 × 0.2 cm. 1/Y. Histo-
pathologic images of the lesion were shown in Figure
3(a) and (b).
Three times of the radiotherapy (totally 32 GY, exter-
nal) was applied and radiation injury (burn) was occured
as a complication. Radiotherapy treatment was stopped,
he refused to be fed with nasogastric cathater. He died
few months later because of malnutrition. An autopsy
was not obtained.
We report a rare case of oral SCC originating in the
mandible of a 16-year-old male patient with chronic graft-
versus-host disease 10 years after HLA-identical sibling
bone marrow transplantation for FA. The case highlights
the problems of malignant change in FA and also the
increased risk of second malignancy after BMT.
FA is a highly heterogeneous syndrome, in which ho-
mozygotes may show congenital anomalies and hemato-
logical problems. The main cause of morbidity and mor-
tality are aplastic anemia, myelodysplasia and Although
acute myeloid leukemia is the most commonly found
malignancy, solid tumors represent about 40% of neo-
plasms observed which develop at older ages in patients
surviving the hematologic abnormalities [5].
Kuttler in 2003 referred that 19 of 754 patients in the
International Fanconi Anemia Registry (3%) had hard
neck squamous cell carcinoma (HNSCC) [3]. The male:
female ratio of HNSCC in normal population is 2:1
while Reed asserted the reversed ratio in FA patients
[13]. FA patients develop SCC at significantly earlier
age than the general population. Kenedy and Hart re-
ported an average age of 27 years in FA patients [14]
and the average time between age of FA diagnosis and
cancer development is 10.5 years [15].
As observed in the case presented in this paper, SCC
associated with FA develops earlier than in general
population and shows a more aggressive behaviour. Fur-
thermore, in contrast to FA-nonaffected individuals,
predisposing risk factors for head and neck cancer, like
A. P. Erdem et al. / Open Journal of Stomatology 1 (2011) 45-49
Copyright © 2011 SciRes. OJST
Figure 3. Histopathologic images of the lesion.
tobacco and alcohol abuse, are rare in these patients.
Jansisyanont reported that the commonest localizations
of SCC in FA patients in descending order are: tounge,
anogenital region, pharynx, larynx, oral [5] mucosa,
mandible and skin [16].
In this report, development of malignancy occured 10
years after BMT, which is a longer period than that
observed by Deeg et al. who reported that malignancy
development occured in a peak between 8 and 9 years
after BMT [5].
Although FA appears to be genetically heterogeneous,
all cases display abnormalities of DNA repair. A gene
defective in one of the four subsets of FA patients has
been defined. Defects in this gene are thought to play a
role in the development of neoplasia in FA patients.
However, many other factors may also contribute to the
development of malignancies. Some of the authors
suggested that patients that have endured BMT have a
greater incidence of malignancies development. In these
patients, there are four additional factors including pre-
transplant total body irradiation, cyclophosphamide treat-
ment, chronic GvHD, and prolonged immunosuppresive
treatment after transplantation [2,15-17].
Most patients who develop malignancy after BMT also
have chronic GvHD. Additionally, some authors observed
the development of such tumors on sites initially in-
volved with GvHD-related inflammatory processes [5].
It was proposed that TBI and certain treatments for
acute GvHD were risk factors in the development of
secondary tumors. Lishner et al., also reported solid tu-
mors in patients with chronic GvHD after BMT for a
variety of conditions including aplastic anemia [18]. A
single patient with FA who developed SCC of the
tounge at age 29, 10 yeras after BMT complicated by
chronic GvHD, has been reported [19]. A 12 year old
boy with FA developed SCC of the tounge 74 months
after BMT [20]. It was estimated by the same investi-
gators that there is a 22-fold higher risk of solid tumor
development in patients transplanted for aplastic anemia
(AA) than in the general population. Salum et al;
reported the case of a 12-year-old patient with FA who
had been submitted to BMT at the age of 5 and exhibited
oral lesions characteristic of chronic GvHD. Eleven
years after the BMT, he developed SCC of the tongue
with an aggressive behavior, which was considered an
untreatable condition [5]. Millen et al, reported a case of
oral SCC originating in the buccal mucosa of an
18-year-old fe- male patient with chronic GvHD 9 years
after HLA-identical sibling BMT for FA. They su-
pported that the patient could be seen to have had
multiple risk factors including genetic predisposition,
pretransplant conditioning with both cyclophosphamide
and TBI, chronic GvHD and prolonged immunosu-
ppresive treatment [18]. The patient presented in this
case report showed GvHD following the bone marrow
transplantation, four weeks later CMV sepsis was
Abdelsayed et al. advocated that oral cancer in pa-
tients with GvHD may have an aggressive biologic po-
tential with increased tendency for recurrence and deve-
lopment of new lesions [5].
Spardy et al. suggested that FA patients have an
incresed risk for SCC at sites of predilection for infec-
tion with high-risk human papillomavirus types includ-
ing the oral cavity and the anogenital tract. They esta-
blished that the FA pathway as an early host cell re-
sponse to high-risk HPV infection [21].
The patients with FA may be particularly susceptible
to HPV-induced carcinogenesis [3]. HPV vaccines,
which are currently under development, might help to
prevent HPV infection in both the cervix and the oro-
pharynx [22].
A. P. Erdem et al. / Open Journal of Stomatology 1 (2011) 45-49
Copyright © 2011 SciRes. OJST
Mario AJA Hermsen et al., examined oral SCC tissue
from two FA patients by comparative genomic hybri-
dization. Both tumors, which were negative for human
papilloma as well as Epstein-Barr viral sequences,
showed multiple alterations with a high proportion of
whole-arm chromosomal gains and losses. In contrast to
the suggestions above; some other authors put forward
that, the process leading to early occurence of oral can-
cer in FA patients follows a similar pathway as in non-
FA cancer patients, which would support a caretaker
function for FA genes in the protection against oral car-
cinogenesis [23].
The patient was tested for HPV by PCR and DNA
sequencing. Tumor was detected with oncogenic 15
types of HPV (HPV-16, HPV-11, HPV- 16, HPV-18,
HPV-31, HPV-33, HPV-35, HPV-39, HPV-45, HPV-51,
HPV-52, HPV-56, HPV-58, HPV-59, HPV-68). In this
case report, the human papillomavirus status was found
negative according to comparative genomic hybridiza-
tion (sample was taken from serum).
The treatment of malignancies in FA patients with
Had and Neck SCC is similar to the general population
with similar pathologies. The aim is the tumour resection
oncologic radicality. The main preoperative problem in
patients wih FA is the associated bone marrow failure,
requiring preoperative haematologic consultations. The
possibility of blood and platelet transfusion before sur-
gery must be considered. The first approach in FA pa-
tients is surgical resection of primary HNSCC with neck
dissection and reconstruction if necessary. Generally, FA
patients withstand surgical procedures very well. A fur-
ther concern for the surgeon is the development of post-
operative complications, including wound infections and
haematoma [3,15,16]. In this case report, following the
tomographic examination, it was decided as a primer
carcinoma with lemph metastasis that couldn’t be re-
sected.The patient that couldn’t be applied chemothe-
rapy underwent local radiotherapy with occular shielding.
After third dosage of the radiotherapy, radiation injury
(burn) was occured as a complication. Radiotherapy
treatment was stopped, he refused to be fed with naso-
gastric cathater. He died few months later because of
This case highlights the susceptibility of FA patients to
malignant tumour development. The applicability of
BMT is increasing and surviving cohorts are expanding
in number, so the incidence of secondary malignancy is
likely to rise. Early intervention may be translated into
improved survival, or at least may reduce the necessity
for more aggresive surgical approaches. We agree with
the potocol proposed by Kutler [3]. He suggests a care-
ful biannual screening of the oral cavity and oropharynx
that should start between the ages of 15 and 20. However,
in patients with FA with history of leucoplakia or re-
current oral lesions, head and neck examinations are
recommended every six or eight weeks.
We thank to Dr Hüseyin Kemal Türköz for his support for the
evaluation of the histopathologic images. (Department of Pathology,
University of Marmara, School of Medicine).
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