REVIEW ARTICLE

Management of Mucosal Basal Cell Carcinoma of the Lip:

An Update and Comprehensive Review of the Literature
Tiffany Loh, BS,* Ashley G. Rubin, MD,† and Shang I Brian Jiang, MD‡

BACKGROUND Basal cell carcinoma (BCC) is the most common malignancy in the United States. Most BCCs occur
on cutaneous surfaces, but rare cases on the mucosal lip have also been documented. Because only a small number
of mucosal BCC (mBCC) cases have been reported, data on their clinical characteristics and management are limited.

OBJECTIVE To perform an updated literature review of the management of mBCCs on the lip.

METHODS A comprehensive literature review was conducted through a search of the PubMed database with the
key phrases “mucosal basal cell carcinoma,” “basal cell carcinoma mucosa,” and “basal cell carcinoma lip mucosa.”

RESULTS Forty-eight cases of mBCCs have been reported, and 35 had sufficient data for analysis. The
average age at presentation was 66.8 years, and 57% (n = 20) had a history of skin cancer. Most cases were
treated with surgical excision or Mohs micrographic surgery (MMS), with only 1 recurrence in the literature.
Furthermore, the authors present 8 additional cases of mBCCs successfully treated with MMS.

CONCLUSION Mucosal basal cell carcinomas are rare, and skin cancer history may be a risk factor. Because
the lip is a cosmetically and functionally important area, MMS may be the preferred treatment method for
mBCCs in this location.

Supported by the National Institute on Aging T35 grant AG26757. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the NIH or AFAR (American Federation for
Aging Research). The authors have indicated no significant interest with commercial supporters.

B asal cell carcinoma (BCC) is the most commonly

occurring cancer in the United States, accounting
for approximately 80% of all nonmelanoma skin
cancer (NMSC) cases.1,2 On a cellular level, BCCs
are derived from keratinocytes arising from the basal
layer of the epidermis.3–6 Although BCCs are generally
slow-growing and rarely metastasize, they can be
locally invasive and if left untreated, may destroy
surrounding tissue and be highly disfiguring.7–10
Basal cell carcinomas usually occur on sun-exposed
areas; UV radiation, specifically UV-B, is known to
be the primary predisposing factor for these
neoplasms.10–15 The majority of BCCs are found on
cutaneous surfaces, but rare cases of mucosal BCCs
(mBCCs) on the vermilion lip (VL) and oral mucosa
have also been reported. Historically, there has been
much debate about the origin of these tumors. Because
BCCs have typically been thought to originate from
pilar structures,16–18 the lack of hair follicles and sweat
glands in the VL and oral mucosa challenges this the-
ory in regard to mBCC development.19–21
Only a small number of mBCC cases have been repor-
ted, and there is limited knowledge about their clinical
presentation. Because BCCs constitute most skin cancer
cases in the United States, having a thorough under-
standing of different BCC subtypes is crucial to better
managing these types of carcinomas as a whole. In the
literature, there are 48 reported cases of BCCs involving

*School of Medicine, University of California, San Diego, La Jolla, California; †Carlsbad and Vista Dermatology, Vista,
California; ‡Department of Dermatology, University of California San Diego, La Jolla, California

© 2016 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.
· ·
ISSN: 1076-0512 Dermatol Surg 2016;42:1313–1319 DOI: 10.1097/DSS.0000000000000790

1313

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 MUCOSAL BCC REVIEW

the VL, mucosal lip (ML), or other mucosal surfaces of

TABLE 1. Demographics of 35 Cases From the
the oral cavity.18,22–41 With this updated review of the Literature
literature, the authors add 8 additional cases that
provide insight into the clinical characteristics, pre- Cases*, N = 35 (%)

sentation, and management of these tumors. Age (mean, SD) 66.8 (11.8)
Sex (n, %)
Male 18 (51)
Methods
Female 17 (49)
A comprehensive literature review was conducted by Location
performing a search of the PubMed database, using the Upper VL only 15 (43)
Upper VL + cutaneous skin 3 (9)
key phrases “mucosal basal cell carcinoma,” “basal cell
Lower VL only 9 (26)
carcinoma mucosa,” and “basal cell carcinoma lip Lower VL + cutaneous skin 2 (6)
mucosa.” References not indexed in PubMed were fol- Upper ML 0 (0)
lowed to acquire a complete record of published data. Lower ML 2 (6)
Translations of articles written in Spanish were obtained Other oral mucosa 4 (11)
through Google translate (http://translate.google.com). Lesion diameter 10.8 mm (6.3 mm SD)
Removal
The authors identified 23 publications reporting a total of
MMS 22 (62)
48 cases of mBCC involving the VL, ML, or other areas Wide excision 8 (23)
of the oral mucosa. In the review, the authors use the term Other 5 (14)
“vermilion lip” to include the vermilion border (VB) and MMS stages (mean, SD) 2.63 (0.6)
the outer mucosal surface of the lip.22 The Institutional Skin cancer history 20 (57)
Review Board (IRB) at the University of California, San Total percentages may not equate 100% due to rounding.
Diego (UCSD) approved the study protocol. *Percentages reflect the proportion of the variable.
ML, mucosal lip; MMS, Mohs micrographic surgery; SD,
standard deviation; VL, vermilion lip.
Epidemiology

Because BCCs on mucosal surfaces such as the VL/ML

colleagues22 also noted that 15 of 18 patients in
or other areas of the oral cavity are rare and not com-
their study presented with a history of skin cancer.
monly reported, the actual incidence is unknown.
Therefore, skin cancer history may be a risk factor for
Demographic information was available and compiled
the development of mBCCs.
for 35 of the 48 reviewed cases (Table 1). The incidence
of mBCCs involving the VL/ML or oral cavity was
evenly distributed between males (18 cases, 51%) and
females (17 cases, 49%). Age at presentation ranged
from 21 to 91, with an average of 66.8 years. Skin type
and ethnicity were not frequently reported.

At UCSD Dermatologic and Mohs micrographic sur-

gery (MMS) unit, 8 cases of mBCCs presented between
June 2007 and June 2014 (Figures 1–4), with 5
occurring in male patients and 3 in female subjects.
The average age at presentation was 76.9 years with
a range of 52 to 90 years (Table 2).

Notably, 7 of the 8 patients (83%) had a history of skin
cancer. Skin cancer history was not available for all 35
cases from the literature, but 20 (57%) of these cases
did report previous skin malignancy. Silapunt and
Figure 1. Left upper mucosal lip basal cell carcinoma
tumor, preoperative lesion (15 · 9 mm). Figures 1–4 pertain
to a case of basal cell carcinoma of the left upper mucosal
lip seen at University of California, San Diego during the
period of June 2007 to June 2014.

1314 DERMATOLOGIC SURGERY

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Figure 2. Left upper mucosal lip basal cell carcinoma
tumor, postoperative lesion (24 · 28 mm). Clear margins
were obtained after 3 Mohs micrographic surgery stages.
Pathogenesis
Traditionally, BCCs were thought to originate from
hair follicles and sweat glands, but normal vermilion
tissue lacks these structures.18,22,24,42,43 Therefore,
several theories have been proposed to explain BCC
presence on mucosal surfaces. Keen and Elzay38
suggested that ectopic epithelial implantation from
trauma could account for BCC on the vermilion zone
(VZ) that showed trichoepithelioma-like features. In
addition, the epidermis contains matrical cells, which
are considered to be pluripotent and may be able to
differentiate into various cell lines.32,44 Therefore, it
is possible for malignancies of the cutaneous skin
adjacent to the VB to spread into the VZ, especially in
cases that involve both cutaneous and mucosal surfa-
ces.18 Interestingly, however, of the 29 mBCC cases in
Figure 3. Repair of left upper mucosal lip basal cell carci-
noma tumor through mucosal advancement.
© 2016 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
LOH ET AL
Figure 4. Photomicrograph of left upper mucosal lip basal
cell carcinoma tumor.
the literature that involve the VL, only 5 extended to
the surrounding cutaneous skin, and the rest were
restricted to the VZ (Table 1). Therefore, the theory of
tumor spread from cutaneous tissue into the VZ does
not explain the presentation of these particular cases.
Other theories suggest an origin from heterotopic
sebaceous glands or primary epithelial germ cells.18,22
Ectopic sebaceous glands, known as Fordyce spots,
and minor salivary glands in the VZ18 may represent
potential sources of malignant cells that give rise to VL
mBCCs.
Clinical Presentation
Most mBCCs appear to involve the VZ, most of which
occur on the upper VL. Of the 29 cases in the literature
that involve the VZ, 64% (n = 18) had lesions on the
upper lip, 15 of which were restricted to the VZ and
did not involve surrounding cutaneous skin. Other
locations included: lower VL (31%, n = 11), lower ML
(6%, n = 2), upper ML (0%, n = 0), and other oral
mucosal sites (11%, n = 4). At UCSD, 6 of the 8 cases
were on the upper VL/ML and 2 on the lower VL. Only
2 cases involved cutaneous skin around the VZ.
Clinically, mBCCs on the lip often present as ulcer-
ated, bleeding, or crusted lesions, which may resemble
herpes simplex presentation.22 Because herpes
simplex virus is also the most frequent diagnosis of
an ulcerated lip, initial misdiagnoses of BCCs in the
VZ as a herpes simplex flare may occur.22
42:12:DECEMBER 2016 1315
 MUCOSAL BCC REVIEW

TABLE 2. Cases Seen at UCSD MMS Center

mBCC Cases*, N = 8 (%) Non-mBCC Cases, N = 3,881 (SD)

Age (mean, SD) 76.9 (15.2) —
Sex (n, %)
Male 5 (63) —
Female 3 (38) —
Location
Upper VL 3 (38) —
Upper VL + cutaneous skin 2 (25) —
Lower VL 2 (25) —
Lower VL + cutaneous skin 0 (0) —
Upper ML 1 (13) —
Lower ML 0 (0) —
Skin cancer history 7 (88) —
Average preoperative Size I† 7.9 mm (5.30 SD) 8.450 (5.3)
Average preoperative Size II‡ 9.6 mm (6.05 SD) 11.086 (7.5)
Average postoperative Size Ix 15.6 mm (10.3 SD) 16.224 (9.6)
Average postoperative Size IIk 23.0 mm (18.6 SD) 20.387 (12.1)
Average diff. 1¶ 7.8 mm (5.6 SD) 7.7745 (6.7)
Average diff. 2** 13.4 mm (14.3 SD) 9.3401 (8.2)
Average number of stages 2.0 (0.76 SD) —

Total percentages may not equate 100% due to rounding.

*Percentages reflect the proportion of the variable.
†Smallest measurement of preoperative size of lesion.
‡Largest measurement of preoperative size of lesion.
xSmallest measurement of postoperative size of lesion.
kLargest measurement of postoperative size of lesion.
¶Difference between postoperative Size I and preoperative Size I.
**Difference between postoperative Size II and preoperative Size II.
mBCC, mucosal basal cell carcinoma; ML, mucosal lip; MMS, Mohs micrographic surgery; SD, standard deviation; UCSD, University of
California, San Diego; VL, vermilion lip.

For the 35 cases from the literature, the average lesion
diameter was 10.8 mm. Of these cases, 22 (62%) were
treated with MMS, and the average number of stages
required for removal was 2.63 stages. Most of the
remaining cases were treated with excision, with a few
undergoing radiation. At UCSD, the average lesion
size at presentation was 7.9 · 9.6 mm. All 8 cases were
treated with MMS, and the average number of stages
required to obtain clear margins was 2.0. The average
final surgical margin was 7.8 · 13.4 mm (Table 2).
Histopathology
In the early literature, some authors reasoned that
mBCCs should be classified with peripheral amelo-
blastomas, due to similarities in their clinical and
histopathological presentations.16,42,43 However,
throughout time, histological analyses have demon-
strated that mBCCs do display classic features of
cutaneous BCCs (cBCCs) that distinguish them from
odontogenic tumors.

In some instances, mBCCs of the lip have been found
to infiltrate deeper into underlying structures.
Silapunt and colleagues reported that of 18 cases
of BCCs on the VL, 6 showed perineural, peri-
vascular, or muscular infiltration, and Mlika and
colleagues also reported muscular invasion from
a BCC tumor of the upper VL.22,27
For example, Shumway and colleagues24 demon-
strated that like classic cBCCs, mBCCs show strong
reactivity to Ber-EP4, a monoclonal antiepithelial
antibody that binds to epithelial membrane glyco-
proteins in humans. Ber-EP4 is not taken up by
normal keratinocytes of the stratum basale, but it
shows high reactivity in BCC tumors.45 Shumway

1316 DERMATOLOGIC SURGERY

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and colleagues24 reported a case of BCC on the
buccal mucosa with diffuse, strong uptake for
Ber-EP4, similar to cases of other non-mBCCs. In
contrast, most ameloblastomas were found to be
negative for Ber-EP4.24,46
In addition, histologic features of mBCCs, such as
the uniform arrangement of pale-staining
polygonal cells throughout tumor islands, the
absence of stellate reticulum-like areas, and the
observation of frequent mitoses and apoptotic
bodies24 are more consistent with a diagnosis of
BCC rather than ameloblastoma, further suggesting
that these 2 tumors should be considered distinct.
Treatment, Prognosis, and Follow-up
Treatment of mBCCs has historically been achieved
with wide excision or MMS. Of the 35 mBCC cases
from the literature, 22 were treated with MMS, 8
with wide excision, and 5 with radiation or other
techniques. There have been no reported cases of
metastasis, and prognosis is generally good. In the
reviewed cases, follow-up period after treatment
ranged from 8 months to 10 years, and only 1 case of
recurrence was observed (the tumor presented at the
same site 8 times over 20 years and was treated with
curettage, excision, and laser ablation, but the patient
was lost to follow-up30).
Thus, it seems that surgical removal through either
excision or MMS is effective for clearing the malignancy.
Conclusion
Mucosal basal cell carcinomas have a very low inci-
dence, and data on these types of tumors are limited.
With this updated review, the authors present 8 more
cases of mBCCs on the lip that will help elucidate the
clinical presentation and characteristics of these lesions.
When the cases and those from the literature are
combined, the male to female ratio is roughly 1:1, with
a slightly higher incidence in males (23 males, 20
females). This gender ratio differs in other BCC sub-
types and NMSCs. In general, NMSCs, especially
those in the central facial areas, occur more commonly
© 2016 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
LOH ET AL
in females47,48; Lee and colleagues47 found that of 281
cases of lip BCCs (including cutaneous cases), 55%
occurred in women. This may be due to facial hair
masking cutaneous lip tumors in males, making
lesions less noticeable and leading to lower rates of
presentation in clinic. However, VL tumors are not
obscured by facial hair, and may be more easily
noticed, prompting patients to seek care and evening
the gender ratio in mBCC cases.
Interestingly, most cases from the literature and UCSD
occurred on the upper VL/ML. The lower lip receives
more intense sun exposure than the upper lip, and
because UV-B is the primary predisposing factor for
BCCs, the predominance of upper lip mBCCs is
surprising. Previous studies have noted that
approximately one third of BCCs occur on relatively
sun-protected areas, whereas squamous cell carcino-
mas develop more commonly in areas of significant
sun exposure, such as the lower lip.22,49,50 It seems
that BCC occurrence on mucosal surfaces may not
depend as heavily on UV-B exposure and that other
factors may contribute to their development.22
Both wide excision and MMS seem to be effective
treatments for mBCCs. A comparison of the average
preoperative and postoperative sizes of the 8 cases to
previously collected data (Table 2) indicates that
lesion sizes in the VZ are comparable with those on
various cutaneous locations. However, the VL is
important both cosmetically and functionally, and
BCC invasion into deeper structures of the lips has
been noted in several instances.22,27 In addition, the
mean final surgical margin required to clear these
mBCCs in the authors’ institution was much greater
than the standard recommended 4 mm excision
margins; therefore, MMS may be a preferable
treatment technique for tumors involving this zone.
Overall, the updated review of the literature highlights
crucial aspects of the clinical presentation and
possible risk factors for mBCCs. Because current data
on these tumors are limited, this study is important
for establishing a more complete characterization of
mBCCs. These findings may contribute toward
developing better management methods for these
malignancies in the future.
42:12:DECEMBER 2016 1317
 MUCOSAL BCC REVIEW
There are limitations to this study because it was per-
formed in a single center, academic setting. Because
this center specializes in MMS procedures, many of the
cases are severe lesions that may not reflect charac-
teristics of less advanced disease states. In addition,
the patients presenting in the authors’ clinic may not
be representative of ethnic distribution and socio-
economic statuses seen across the United States.
Finally, as mBCCs occur infrequently, the data are
based on a small sample size. Future large, multi-
center studies focusing on mBCC tumor character-
istics and risk factors are necessary to further
elucidate these results.
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Address correspondence and reprint requests to: Shang I
Brian Jiang, MD, Department of Dermatology, University
of California San Diego, 8899 University Center Lane,
#350, San Diego, CA 92122, or e-mail: s2jiang@ucsd.edu
42:12:DECEMBER 2016 1319