YIJOM-4784; No of Pages 4

Int. J. Oral Maxillofac. Surg. 2019; xxx: xxx–xxx

https://doi.org/10.1016/j.ijom.2021.08.022, available online at https://www.sciencedirect.com

Case Report
Head and Neck Oncology

Synchronous oral cavity M. Uddin1, A. Bowen1, G. Betts2,

S. Sainuddin1
1
Department of Oral and Maxillofacial

malignancy in identical Surgery, Manchester Royal Infirmary,

Manchester, UK; 2Department of Adult
Histopathology, Manchester Royal Infirmary,
Manchester, UK

twins—unusual coincidence
of similarities
M. Uddin, A. Bowen, G. Betts, S. Sainuddin: Synchronous oral cavity malignancy in
identical
twins—unusual coincidence
of similarities. Int. J. Oral Maxillofac. Surg. 2019; xxx: xxx–xxx. ã 2021 International
Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights
reserved.

Abstract. The multifactorial nature of head and neck squamous cell carcinoma (HNSCC)
has led to increased efforts in establishing various risk factors. Well-known
environmental risk factors for HNSCC include tobacco use, heavy alcohol consumption,
immunosuppression, and more recently human papillomavirus infection. Familial
clustering has been observed in cancers occurring at other sites, but not so much with oral
squamous cell carcinoma (OSCC) without exposure to shared environmental risk
factors. An unusual case of identical twins who presented with OSCC involving an
identical site and exhibiting similar histological features is reported here. The two Key words: mouth neoplasms; squamous cell
patients underwent identical surgery with curative intent, culminating in good outcomes. carcinoma; twins; histology; genetics.
It appears that no other cases of identical twins with a similar presentation in time,
anatomical site, and histopathology have been reported in the literature. Accepted for publication

Head and neck cancer is the sixth most
common cancer worldwide1. Head and
neck squamous cell carcinoma
(HNSCC) involving the mucosal sur-
faces of the oral cavity, oropharynx,
and larynx comprises more than 90%
of these cancers2. Well-known environ-
mental risk factors include tobacco use,
heavy alcohol consumption, immuno-
suppression, and human papillomavirus carcinoma (OSCC) within the cohort
infection2. HNSCC is primarily caused was very low4.
by sporadic somatic DNA mutations,
and as such, is not generally considered
to be an inheritable disease3. Although a Case reports
recent large study of Nordic twins con-
Patient 1
firmed a significant familial risk for the
development of cancers in general, the A 51-year-old woman with a low BMI of
reported incidence of oral squamous cell 16 kg/m2, presented with a 12-week his-

0901-5027/000001+04 ã 2021 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Please cite this article in press as: Uddin M, et al. Synchronous oral cavity malignancy in identical twins—unusual coincidence of
similarities, Int J Oral Maxillofac Surg (2021), https://doi.org/10.1016/j.ijom.2021.08.022
YIJOM-4784; No of Pages 4
2 Uddin et al.
Fig. 1. Patient 1: (A) intraoral photograph taken in the operating theatre, showing the tumour in
the left floor of the mouth; (B) preoperative MRI scan showing the tumour in the left floor of the
mouth (red arrow).
Fig. 2. Patient 2: (A) preoperative photograph showing the tumour in the left floor of the mouth
(red arrow); (B) preoperative MRI scan showing the tumour in the left floor of the mouth (red
arrow).
tory of a painful non-healing ulcer in the
left floor of the mouth (FOM). She
reported smoking 20 to 30 tobacco roll-
up cigarettes per day and consuming
roughly 250 units of alcohol a week. Clin-
ical examination revealed a 2.5-cm indu-
rated ulcer in the left FOM/ventrolateral
tongue (Fig. 1).
Patient 2
A week later, the twin sister of patient 1
was seen regarding a similar ulcer in the
left FOM persisting for 12 weeks. Patient
2 also had a BMI of 16 kg/m2. In contrast,
however, she reported smoking only 10
cigarettes a day and consuming 5 units of
alcohol a week. Clinical examination also
revealed a 2.5-cm indurated lesion in the
left FOM/ventrolateral tongue (Fig. 2).
Diagnosis and treatment
Histopathological analysis of incisional
biopsies confirmed well-differentiated
squamous cell carcinoma with a clinical
stage of cT2N0M0 in both patients. The
Please cite this article in press as: Uddin M, et al. Synchronous oral cavity malignancy in identical twins—unusual coincidence of
similarities, Int J Oral Maxillofac Surg (2021), https://doi.org/10.1016/j.ijom.2021.08.022
cases were discussed independently at the
regional head and neck oncology multi-
disciplinary team (MDT) meeting. In line
with current UK national guidelines, pri-
mary surgical intervention was recom-
mended5. Both patients underwent
tumour resection, selective neck dissec-
tion, and regional pedicled flap recon-
struction.
Histopathology
Postoperative histopathology reported
keratinizing well-differentiated squamous
cell carcinoma with severe epithelial dys-
plasia in the adjacent oral mucosa in both
cases (Figs. 3 and 4). Both tumours were
completely excised and were noted to be
of a similar size: 21 mm with a depth of
invasion of 2.9 mm in patient 1 and 17 mm
with a depth of invasion of 6.2 mm in
patient 2. There was a mild peritumoural
lymphocytic inflammatory response, but
neither showed evidence of lymphovascu-
lar or perineural invasion. The neck dis-
section specimens of patients 1 and 2
contained 21 lymph nodes and 22 lymph
nodes, respectively, all of which were
disease-free, culminating in a shared path-
ological staging of pT2N0M0 squamous
cell carcinoma.
Recovery and follow-up
The postoperative recommendation of the
MDT was for clinical surveillance alone.
Both patients are currently disease-free at
19 months following surgery.
Discussion
The familial risk of developing OSCC in
the presence of a diagnosed first-degree
relative has been reported widely. How-
ever, only when taking shared environ-
mental risk factors (SERFs) into account
does this group of patients exhibit a sta-
tistically significant familial risk6,7. This is
explained by the fact that OSCCs are
considered to be caused by the accumula-
tion of somatic mutations resulting from
exposure to environmental risk factors.
Within the literature, only two other
case reports have described the develop-
ment of OSCC in twins. Covington and
Bulls8 reported a case of tongue cancer
affecting monozygotic twins; however,
the site of disease was not identical. Bhas-
kar et al.9 encountered twin brothers who
developed OSCC in the same site; howev-
er, the onset of disease was more than 10
years apart.
What led these two women to develop
identical cancers, at the same time? Whilst
the patients in this report will have had
SERFs during their youth, they have led
quite different lifestyles since becoming
estranged at a very young age. It is possi-
ble that they acquired somatic mutations
from shared exposures early in life, well
before the presentation of cancer, helping
to explain the homogeneous positions of
their lesions. It is also established that
somatic mutations can be detected in his-
tologically normal tissues before the de-
velopment of cancer10. However, the
accumulation of somatic mutations is also
directly associated with increasing age11,
which then makes it unusual that they
developed identical cancers at a younger
age than would normally be observed12.
The cumulative risk attributed to smoking
can be regarded as fairly similar in both
patients based on their reported consump-
tion. However, considering the increased
risk of developing oral cancer related to
the volume of alcohol consumed, it is
interesting that both patients presented
with similarly advanced cancers within a
week of each other, despite the fact
that patient 1 reported a significantly
YIJOM-4784; No of Pages 4

Synchronous oral malignancy in identical twins 3

the disease in both patients. The presence

of severe dysplasia on the adjacent oral
mucosa was also noted; however this
could be considered routine given the high
incidence of dysplasia in relation to FOM
cancers16.
It appears that no other cases of identi-
cal twins with a similar presentation in
time, anatomical site, and histopathology
have been reported in the literature. The
early diagnosis for these twins culminated
in a positive outcome with identical single
modality treatment.
It is accepted that exposure to environ-
mental factors, most notably smoking and
alcohol, has a causative role in OSCC of
the FOM. This report supports the concept
that an inherited genetic predisposition to
Fig. 3. Patient 1: micrograph showing keratinizing squamous cell carcinoma forming jagged developing OSCC of the FOM may also
infiltrative invasive nests. There is an associated stromal response (*) surrounding the invasive exist. Identifying the precise genetic fac-
islands, with mild associated lymphocytic inflammation. Surface dysplasia is present in the tors that contribute to an increased risk
adjacent epithelium (inset image). (40 magnification.). might ultimately contribute to the devel-
opment of novel therapeutic strategies.
Furthermore, this could also help to in-
form counselling protocols that enable
patients and their families to make more
informed choices to reduce their risk, and
also identify individuals who may benefit
from surveillance protocols.

Funding
No funding was required.

Competing interests
The authors have no conflicts of interest.

Ethical approval
Not required.

Fig. 4. Patient 2: micrograph showing keratinizing squamous cell carcinoma with an infiltrative
pattern of invasion. There is an associated stromal response (*) with mild associated lympho- Patient consent
cytic inflammation. Adjacent severe epithelial dysplasia is illustrated in the inset image.
Resection specimens from the two patients exhibited clear similarities in the tumour differenti- Informed consent was obtained from the
ation and surrounding stromal response when the histomorphology was compared. (40 patients for publication of the photo-
magnification.). graphs.

higher alcohol intake in comparison to
patient 213.
An alternative plausible explanation is
that these women share a constellation of
genetic, or epigenetic, factors giving them
an inherent predisposition for the devel-
opment of OSCC through as yet undeter-
mined mechanisms. This would then be in
keeping with the observation that familial
cancers are more often associated with an
early age of onset14. The evidence for
inheritable predisposition for the develop-
ment of OSCC is building. Huang et al.15
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Address:
Moeez Uddin
Department of Oral and Maxillofacial Sur-
gery
Peter Mount Building
Manchester Royal Infirmary
Oxford Rd
Manchester
M13 9WL
UK
Tel: +44 07531927938
Moeez-Ud-Din.Uddin@mft.nhs.ukMoeez-
Ud-Din.Uddin@mft.nhs.uk,
Alex.Bowen@mft.nhs.uk,
Guy.Betts@mft.nhs.uk,
Sajid.Sainuddin@mft.nhs.uk