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Oral carcinoma cuniculatum presenting with moth-eaten

destruction of the mandible
Chunye Zhang, DDS, MDS,a,b Yuhua Hu, DDS, MDS,a,b Zhen Tian, DDS, MDS, PhD,a,b Ling Zhu, DDS, PhD,c
Chenping Zhang, DDS, PhD,b,d and Jiang Li, DDS, MDS, PhDa,b

Objective. Carcinoma cuniculatum (CC) is a rare variant of squamous cell carcinoma. We describe the clinicopathologic find-
ings in a new case.
Study Design. This is a literature review and retrospective study of a case with CC.
Results. The clinical and imaging findings of CC are diverse; some cases might be challenging to diagnose accurately by biopsy.
This article reports a case of CC that occurred in the retromolar region with involvement of the mandible. The patient was a
39-year-old man. Clinically, the lesion manifested as an ulcerative mass in the mandibular molar region. Imaging results showed
that the lesion in the jaw exhibited moth-eaten destruction without obvious expansion of the jaw bone. The postoperative patho-
logic examinations were consistent with CC; additionally, metastases were present in 1 level II lymph node and 1 submandibular
lymph node. Left soft tissue metastasis and right cervical lymph node metastases were detected 10 and 27 months after surgery,
respectively.
Conclusions. CC is a rare epithelial malignant tumor and has variable clinical manifestations. The diagnosis of CC mainly depends
on pathologic features. Most patients with CC have a good prognosis; only a small percentage of patients might experience lymph
node metastasis. (Oral Surg Oral Med Oral Pathol Oral Radiol 2018;■■:■■–■■)

Carcinoma cuniculatum (CC) is a low-grade malignant
epithelial tumor derived from squamous epithelium. Mor-
phologically, CC exhibits a burrowing pattern formed by
branching arrangements of epithelial nests filled with
keratin; therefore, it is named for its similarity to rabbit
nests (cuniculatum is the Latin word for rabbit). CC is
a rare subtype of squamous cell carcinoma (SCC) and
was first reported in the foot in 19541; oral CC was first
reported in 1977.2 CC occurring in the oral cavity was
classified as a special subtype of SCC of the oral cavity
and mobile tongue in the 2017 World Health Organiza-
tion classification of head and neck tumors.3 Though CC
overlaps with verrucous carcinoma (VC) and well-
differentiated SCC according to microscopy, they have
different prognoses. For example, patients with CC are
particularly at risk for invasive growth along bone tissues
and the disease may metastasize to local lymph nodes
and the lung,4 whereas VC shows pushing border5 and
rarely metastasizes.
This work was supported by the Natural Science Fund of China (Nos.
81302360, 81372910) and Shanghai Science and Technology Com-
mission (No. 16140902200).
a
Department of Oral Pathology, Ninth People’s Hospital, Shanghai
JiaoTong University School of Medicine, Shanghai, China.
b
Shanghai Key Laboratory of Stomatology & Shanghai Research
Institute of Stomatology, National Clinical Research Center of
Stomatology, Shanghai, China.
c
Department of Radiology, Ninth People’s Hospital, Shanghai JiaoTong
University, Shanghai, China.
d
Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth
People’s Hospital, Shanghai JiaoTong University School of Medicine,
Shanghai, China.
Received for publication Jul 25, 2017; returned for revision Dec 28,
2017; accepted for publication Jan 8, 2018.
© 2018 Elsevier Inc. All rights reserved.
2212-4403/$ - see front matter
https://doi.org/10.1016/j.oooo.2018.01.008
CC was first reported in the skin1; the most common
location is the foot. It has also been reported in the penis,6
esophagus,7 larynx,8 and oral mucosa.4 To date, cases of
oral CC reported in the English literature are limited;
moreover, the clinical manifestations are diverse, and pre-
operative diagnosis is usually difficult. We present a case
of CC with moth-eaten destruction in imaging that was
derived from the molar region, with involvement of the
jawbone. We also review the English literature regard-
ing oral CC that is searchable in PubMed.
CASE REPORT
Clinical presentation and history
A 39-year-old male patient, with 15 years (10 cigarettes/
day) of smoking history and no history of alcohol abuse,
presented with a painful mass in his left lower gingiva
for 1 month. Two months before seeking treatment, the
patient underwent extraction of his lower left third molar
tooth because of the discomfort and looseness of the tooth.
A mass around the tooth extraction wound was discov-
ered approximately 1 month after the extraction, and the
mass displayed progressive enlargement. Incisional biopsy
results indicated SCC of the left lower gingiva. When
the patient was referred to our hospital, an intraoral ex-
amination revealed an ulcerated mass (2.5 × 2 cm) in the
left lower gingival and retromolar mucosal regions. A
2-cm lymph node was present in the left superior deep
cervical region.
Radiographic imaging studies
Cone bean computed tomography (CBCT) imaging re-
vealed that the body and ascending ramus of the left
mandible exhibited evidence moth-eaten resorption and
destruction. The range extended from the sigmoid notch
to the mental foramen, growing along the long axis of

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Fig. 1. Cone bean computed tomography imaging showed an extensive range of bone destruction in the body and ramus of the
left mandible (A). An area of bone destruction at the lower edge of the mandible corresponding to the left lower canine and pre-
molar areas was also observed; the destruction had a moth-eaten appearance (A, B). The lesion grew along the long axis of the
bone marrow cavity. The mental foramen on the ipsilateral side was significantly enlarged compared with that on the contralateral
side. The jaw did not show obvious expansion (C).

the jaw bone. No obvious buccolingual expansion was
identified (Figure 1). The imaging diagnosis consid-
ered a malignant lymphatic-hematopoietic system tumor.
Treatment
Under general anesthesia, the patient underwent partial
resection of the left mandibular body and ascending
ramus, along with left neck radical dissection. A pecto-
ralis major myocutaneous flap was designed to repair the
intraoral defect. The margins were verified as clear by
frozen examination during the surgery. Postoperative ra-
diotherapy and chemotherapy were administered.
tumor presented a penetrating growth pattern toward the
deep tissue, which resulted in burrowing growth along
the long axis of the mandible (Figure 3). Abundant keratin
pears were surrounded by well-differentiated squa-
mous epithelium, and microabscesses filled with
neutrophils were detected throughout. Marked inflam-
matory cell infiltration was identified in the stromal.
Twenty-eight lymph nodes from the neck dissection tissue
were examined, and tumor cells were found in 1 left sub-
mandibular lymph node and 1 level II lymph node
(Figure 4).

Pathologic examination Follow-up

Gross examination revealed an ulcerative, gray-white
tumor lesion in the mandibular retromolar region. The
cut surface revealed tumor invasion along the long axis
of the jaw. The lesion extended from the sigmoid notch
to the jaw below the left lower canine, and there was no
apparent grayish lesion tissue in the bone under the first
and second premolars (Figure 2). Microscopically, the
A strict follow-up was planned. After 10 months, a 2-cm
soft tissue masses was found by ultrasound scans in the
left neck. The expansion dissection confirmed the mass
to be tumor metastasis. Twenty-seven months after the
first surgery, lymph node enlargement of the right neck
was detected by computed tomography (CT), and the
largest lymph node was 2.5 cm. Lymph node metastases
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Fig. 2. The gross specimen had an ulcerative mass in the ret-
romolar region. Tumor tissues showed burrowing growth along
the long axis of the mandible. The inferior alveolar canal was
also destroyed. Destruction of bone cortex at the lower edge
of the mandible corresponding to the left lower canine (arrow)
and premolar region was identified.
of the right neck (level I: 1/2, level II: 1/4, and level III:1/
3) were verified after surgery.
DISCUSSION
Oral CC is a rare subtype of SCC. Because patients have
particular clinical and pathologic characteristics, the 2017
World Health Organization classification of head and neck
tumors classified oral CC as an independent subtype of
OSCC. Sun et al.4 retrospectively analyzed 540 cases of
OSCC and reported that CC accounted for 2.7% of OSCC.
There was no apparent gender predilection; the condi-
tion commonly occurred in middle-aged and elderly
people, and only 1 in young child was identified in that
report9 (Table I). The disease mainly occurs in the
gingiva,19 followed by the tongue.4 The patient in this
report was a 39-year-old man, and the disease occurred
in the mandibular gingiva.
CC derived from cutaneous tissue has a certain rela-
tionship with human papillomavirus infection infection,18,20
but the association between human papillomavirus and
oral CC has not been definitively identified10,11,14,16;
however, the same result has also been derived from
esophageal CC.21 Other possible etiologies include
smoking, alcohol consumption, trauma, chronic inflam-
mation, and radiotherapy.10 Currently, however, no direct
evidence has confirmed an association between tobacco
and alcohol consumption and oral CC.
ORIGINAL ARTICLE
Zhang et al. 3
Because CC is rare, making an accurate diagnosis
before surgery is usually very difficult. Commonly, CC
has been diagnosed as OSCC,11 VC,21 and leukoplakia.13
When the jaw is involved, CC is easily misdiagnosed as
jaw diseases, such as odontogenic keratocysts 12 or
osteomyelitis.22 In imaging, CC usually presents with jaw
destruction.12,13,17 The imaging results of this patient also
indicated bone destruction, which manifested as a moth-
eaten pattern. Although malignancy was considered, the
lesion did not have the typical presentation of epitheli-
al malignancies.
The histologic feature of CC is the invasive growth
of “nestlike” epithelium filled with keratinaceous mate-
rial that may destroy muscle and bone tissue. Epithelial
cells surrounding keratinaceous material have excellent
differentiation and might exhibit only mild atypia and
microabscess formation in epithelial nests.11 An obvious
inflammatory response in the tumor stroma with infil-
tration by lymphocytes, plasma cells, eosinophils, and
neutrophils was noted.23 The patient in this study had mor-
phologic findings typical of CC. The centers of the tumor
cell nests were filled with keratinaceous debris and were
surrounded by highly differentiated squamous epitheli-
um. The tumor nests penetrated along the bone trabecula,
with no obvious mandibular expansion identified.
Because of the possibility of different prognoses, CC
must be distinguished from other histologically overlap-
ping tumors, such as VC and well-differentiated SCC.
Specifically, the surface of VC is usually exophytic, and
the infiltrative front can be characterized as broad pushing,
which may typically involve only the lamina propria and
cause local damage. In contrast, CC is characterized by
the presence of deep and often complex branching keratin-
filled epithelial tunnels, which may deeply infiltrate into
the submucosal layers and bony tissues. VC may super-
ficially erode bone at its interface, but it does not deeply
invade it. Furthermore, mandibular invasion by CC may
result in a large radiolucent cavity. Both clinical descrip-
tion and imaging features need to be taken into
consideration in the accurate diagnosis of the 2 types of
tumor.
Well-differentiated SCC produces cytologic signs of
malignancy, a brisk mitotic rate, and even atypical mitotic
figures, with keratin pearls that are usually small, which
is totally different with CC. The cytologic atypia of CC
is minimal, and the mitoses are usually difficult to iden-
tify and usually contain more keratinaceous material in
tumor nests. Well-differentiated SCC tends to invade in
large islands, whereas a destructive deep burrowing pattern
also makes a differential point in the diagnosis of CC.
Total surgical excision is the preferred treatment mo-
dality for CC. Because lymph node metastasis is rare,
cervical lymph node dissection is performed only when
the CT results suggest metastasis.12 The patient in this
study already appeared to have cervical lymph node
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Fig. 3. Sections showed the destructive growth of tumor tissues along the long axis of the mandible (A). The lower edge of the
mandible bone corresponding to the left lower canine and first premolar regions had tumor involvement and destroyed bone cortex
(B). Some regions exhibited tumor tissue migration to the surface mucosa (C, D). A high-resolution version of this slide for use
with the Virtual Microscope is available as eSlide: VM04520, VM04521, VM04522, VM04528, VM04529.

enlargement when he first came to our hospital, and the
cervical lymph node dissection confirmed metastasis in
2 lymph nodes. Whether postoperative radiotherapy and
chemotherapy should be administered remains contro-
versial. Some patients received chemotherapy because
of tumor recurrence; however, no obvious efficacy was
noted.13 Although the patient in this study received ra-
diotherapy and chemotherapy after the first surgery, tumor
metastasis occurred rapidly after the surgery.
Patients with CC usually have a better prognosis after
undergoing primary total surgical resection. If the primary
resection is not performed according to definitive and
complete surgical resection principles for malignant
tumors because of an unclear diagnosis, there are risks
for tumor recurrence (10.8%, 4/37, Table I), lymph node
metastasis (5.4%, 2/37, Table I), and even death of the
patient (Table I). Two patients in the literature reports
had recurrences because the surgery was not extended
sufficiently to provide margins of safety as a result of
the lack of an accurate diagnosis at the time of the primary
surgery.13,15 The patient in this study underwent man-
dibular resection; however, metastases were detected in
the left neck 10 months postoperatively and in the right
neck 27 months postoperatively, perhaps because the
tumor had an advanced tumor-node-metastasis stage when
the patient first came to the hospital.
CC is a rare tumor that is difficult to definitively di-
agnose before surgery and the diagnosis of this tumor
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Table I. Review of the English literature regarding oral carcinoma cuniculatum
Alcohol
No. of Age/ and Preoperative Radiographic Follow-up
Authors (y) Cases Gender Location Clinical Features Tobacco Diagnosis Features Treatment (mo)
Allon et al. (2002)10 1 56/M Maxillary gingiva Mass, alveolar bone Tobacco Giant cell lesion/ Unilocular Excision NED (20)
destruction and periodontal disease/ radiolucent lesion
loosening of the teeth malignancy with irregular

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borders
Kruse et al. (2009)11 1 74/F Maxillary alveolus Intraoral ulceration No Squamous cell Bone destruction Excision NED (24)
carcinoma
Hutton et al. (2010)9 1 7/F Maxillary gingiva Swelling No Dental abscess Bone destruction Excision NED (24)
Pons et al. (2012)12 3 72/M Mandible Dental pain Not stated Mandibular abscess Osteolytic lesion Excision NED (24)
82/M Mandible Dental pain Not stated Not stated Cyst with marginal Excision DOOD (4)
cortical osteolysis
43/M Mandible Not stated Not stated Not stated Osseous destruction Excision NED (12)
Suzuki et al. (2012)13 1 68/M Mandibular gingiva Mandibular pain Alcohol and Osteomyelitis with Osteolytic lesion Excision LR (14), DOOD
tobacco leukoplakia (not stated)
Thavaraj et al. 1 61/M Tongue Painless dysphagia and Not stated Not stated Extensive mass Excision NED (24)
(2012)14 difficulty with
articulation
Fonseca et al. 2 62/F Mandibular gingiva Painful swelling with No Not stated Ill-defined osteolytic Excision LR (24)
(2013)15 cutaneous fistula area
47/F Maxillary gingiva Painful ulcers with 3 No Not stated Extensive destruction Excision NED (72)
cutaneous fistulas with ill-defined
borders
Sun et al. (2012)4 15 44-92/7 M 8 F Tongue (8), mandible Oral stomatitis (ache, Alcohol (6), Not stated Bone destruction (5) Excision 45 mo (mean), LR
(6), vestibule (1) ulcer, induration, tobacco (5) (3 cases), LM (1),
swelling, white DOD (1), DOOD
patches, bleeding, and (1 case)*
exudation)
Goh et al. (2014)16 1 62/M Tongue Ulcerated mass Tobacco Malignant tumor Tumorous lesion Excision NED (18)
(continued on next page)

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Zhang et al. 5
 6 Zhang et al.
ORAL AND MAXILLOFACIAL PATHOLOGY
Table I. Continued
Alcohol
No. of Age/ and Preoperative Radiographic Follow-up
Authors (y) Cases Gender Location Clinical Features Tobacco Diagnosis Features Treatment (mo)
Padilla et al. (2014)5 10 65/M Mandibular gingiva Erythroleukoplakia Not stated Malignant tumor Not stated Excision Not stated
38/F Mandibular gingiva Exophytic red and white Not stated Benign proliferation Not stated Excision NED (26)
lesion
72/M Maxillary gingiva Gingival enlargement Not stated Not stated Not stated Excision NED (96)

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81/F Palate Swollen, granulation Not stated Not stated Not stated Excision NED (30)
tissue–like lesion
67/F Mandibular gingiva Ulcerative, red and white, Not stated Lichen planus vs Not stated Excision Not stated
“pebbly” oral lesion carcinoma
76/M Mandibular gingiva Red and white pebbly Tobacco Not stated Erosion of the Excision NED (60)
lesion superficial cortical
bone
88/F Maxillary gingiva Red and white mass Not stated Not stated No evidence of Excision NED (10)
cortical bone
erosion
75/F Edentulous ridge of Fungating and ulcerated Tobacco Hyperkeratosis, Not stated Excision NED (9)
mandible lesion epithelial atrophy,
and dyskeratosis
69/F Mandibular gingiva “Spongy” lesion Not stated Not stated Not stated Excision NED (6)
85/F Maxillary gingiva Exophytic and Not stated Not stated Not stated Biopsy Not stated
hyperplastic-appearing
lesion
Shay et al. (2015)17 1 58/M Mandible Not stated No Oral and facial Large, destructive Excision NED (5)
abscesses mass in mandible
Datar et al. (2017)19 1 58/F Mandibular gingiva Nonhealing ulcer No Not stated Irregular radiolucent Excision NED (24)
lesion
Present case 1 39/M Mandibular gingiva Loose of the tooth and Tobacco Malignant tumor Moth-bitten Excision LM (10), CLNM
painful mass resorption and (27)
destruction
CLNM, contralateral lymph node metastasis; DOOD, died of other disease; F, female; LM, local metastasis; LR, local recurrence; M, male; NED, no evidence of disease.
*The average follow-up time was 45 months, and there was no specific time for every patient.

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Fig. 4. Tumor tissues invaded bone tissues in nested mass configurations (A, hematoxylin and eosin [HE] × 40). The center of
the epithelial mass had extensive keratinization. The surrounding cells were highly differentiated. The epithelial mass exhibited
microabscesses formed by neutrophilic infiltration (B, HE ×400). Continuity of the tumor tissues and surface mucosa was noted
in some areas (C, HE ×100). The superior deep cervical lymph node was involved via tumor metastasis (D, HE ×20). A high-
resolution version of this slide for use with the Virtual Microscope is available as eSlide: VM04520, VM04529, VM04530.

requires close correlations of clinical, pathologic, and
imaging findings to aid in an accurate diagnosis and to
provide the basis for clinical treatment. The current CC
treatment is mainly based on extensive surgical resec-
tion. Cervical lymph node dissection may be performed
based on whether cervical lymph node enlargement is
present.
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