Open Journal of Stomatology, 2011, 1, 109-113 OJST
doi:10.4236/ojst.2011.13017 Published Online September 2011 (
Published Online September 2011 in SciRes.
Glycogen-rich adenoca rcin oma in the lo wer lip: report of a
case with particular emphasis on differential diagnosis
Kazumasa Mori*, Jun Shimada, Nozomi Tamura, Nobuaki Tamura
Division of First Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics Sciences,
Meikai University School of Dentistry, Saitama, Japan.
Email: *
Received 22 June 2011; revised 25 July 2011; accepted 9 August 2011.
We herein report a glycogen-rich adenocarcinoma
occurring in the lower lip of a 44-year-old female.
The lesion appeared as painless slowly growing mass
in the right side of the lower lip. Histologically, infil-
trative tumor nests with duct-like or pseudocyst
structure into the mucosa and/or dermis were ob-
served. The basaloid neoplastic cells had granular
but occasionally vacuolated cytoplasm with salient
reaction of diastase-digestible periodic acid-Schiff,
thus indicating that they were glyc ogen-rich in nature.
The tumor cells were positive for CEA, cytokeratin,
and S-100 protein, and negative for SMA, alpha-1
antitrypsin, and amylase by immunohistochemistry.
The origin of the tumor with infiltrative nests was
indistinguishable from salivary gland and skin ap-
pendage malignancy. A differential diagnosis of this
peculiar neoplasm was discussed.
Keywords: Adenocarcinoma; Glycogen; Differntial
Diagnosis; Lower L i p
A 44-year-old female was referred to the 1st Department
of Oral and Maxillofacial Surgery by a dentist for diag-
nosis and management of a painless “lump” on the right
side of her lower lip. The mass had been noticed 8 years
before the current consultation. According to the patient,
the mass has recently enlarged, interfering with her mas-
tication, but caused no difficulty in speech. No changes
of size or growth of the mass during meal times were
reported. The patient was in apparent good health and
her medical history was noncontributory.
Clinical examination showed a 2.5 × 2.5 cm swelling
with induration on the right side of the lower lip (Figure
1). It was covered by skin that was normal in both tex-
ture and color. Intraorally, a whitish lesion with a papil-
lary outgrowth (Figure 2), in which there was a partial
ulcerated surface, was observed. No induration or pain
was detected in the regional lymph node. A computer-
ized tomography (CT) scan confirmed a tumor-like mass
with an unclear border in the lower lip (Figure 3). Mag-
netic resonance imaging (MRI) showed a high signal in
the tumor-like mass in a T2 weight image (Figure 4).
The lower lip may be affected by several pathologic
conditions, including inflammatory, obstructive, trau-
matic, or neoplastic causes [1,2]. Lesions in this area
may be present for a prolonged period of time before the
patient seeks a medico-dental consultation, usually as a
result of spee c h or co smetic insuff ici e ncy .
Inflammatory disorders of the minor salivary gland
were considered f or the differential diagnosis of the pre-
sent lesion. An acute sialadenitis of the lower lip usually
represents as a swelling associated with pain and redness,
and chronic sialadenitis runs a prolonged course of
pos t- i n flamma to ry scleros i s .
Mucous retention phenomenon or a mucous retention
cyst can affect any minor salivary gland site intraorally,
but is most frequently encountered in the lower lip of
young individuals. They are characterized by a soft fluc-
tuant swelling that may present bluish dome-like nodules.
The lesion is usually treated by conservative surgical
excision. Because of its benign nature, the lesion does
not have any tendency to recur.
Dermoid and/or epidermoid cyst was an other possible
lesion that may occur in the lower lip as well. Dermoid
cysts are most commonly seen in the midline of the floor
of the mouth, while epidermoid cysts are common in
acne-prone areas of skin on the face, neck and back.
However these cystic lesions are classified as a devel-
opmental cyst, and young adults are more likely to be
Salivary gland tumors including monomorphic ade-
noma and benign mixed tumors (MT), commonly present
in the third to sixth decades, should be differentiated,
K. Mori et al. / Open Journal of Stomatology 1 (2011) 109-113
Copyright © 2011 SciRes. OJST
Figure 1. Extra oral view at first visited, showing swelling on
the right s ide of the lower lip.
Figure 2. A whitish lesion with papillary outgrowth on the
inn er s id e o f th e lip.
Figure 3. The CT findings revealed a tumor with an unclear
border in the lower lip.
Figure 4. MRI findings revealed a high signal in the tumor
mass in a T2 weighted image (T2 weighted MRI image).
as they may rarely arise in the lower li p [3]. Monom orphic
adenomas are usually encapsulated or well circumscribed.
MTs are partially circumscribed, exhibiting the character-
istic histologic featurers with myxoid and chondroid areas.
They generally have more varied growth pattern consist-
ing mostly of m yoepitheli al cell prol iferati on.
Because of its frequency among the salivary gland
tumors, a diagnosis of MT should be approached with
caution to exclude other salivary gland neoplasms with
malignant features, mucoepidermoid and adenoid cystic
(ACC) carcinomas. Although these tumors do not al-
ways show a rapid growth pattern or even cytologic
atypia, their microscopic characteristics can readily be
Cutaneous skin appendage tumors [4-6], including
microcystic adnexal carcinoma, porocarcinoma, and
adenoid cystic carcinoma of the skin (DACC) were also
considered. Among of these skin malignancies, DACCs
are morphologically similar to those arising in salivary
glands, and are composed of a somewhat uniform popula-
tion of basaloid tumor cells. However, malignant tumors
of the skin genellary appear as a pedunculated mass or
nodule on the skin with a rapid growth patte rn.
Before the diagnosis of a primary submucosal or cu-
taneous malignant tumor is made, the possibility of a
metastasis from other organs, such as from the breast [7],
should be ruled out based on the clinico-pathological
background. It should be emphasized, therefore, that
careful examination of the breasts and other organs, in
combination with meticulous history-taking, are neces-
sary to make an accurate differential diagnosis.
Light microscopic examination of hematoxylin-eosin-
K. Mori et al. / Open Journal of Stomatology 1 (2011) 109-113
Copyright © 2011 SciRes. OJST
stained sections of the tumor revealed closely apposed
neoplastic nests in the submucosal and/or subcutaneous
region with an infiltrative growth pattern . The tumor was
composed of basaloid cells forming small duct-like
spaces (or pseudocysts) within the tumor nests (Figure
5). Nuclear hyperchromatisum and nuclear disarrange-
ment were subtle, and only rare mitotic figures were
Routine hematoxylin and eosin histologic features
were insufficient to make a definitive diagnosis. There-
fore, we performed periodic acid-Schiff (PAS) and PAS
after diastase digestion (D-PAS). The D-PAS revealed
an apparent disappearance of the conventional PAS re-
active material (Figures 6 (a) and (b)). These results
indicated an accumulation of glycogen in their cyto-
plasm, possibly derived either from the minor salivary
gland or skin appendage organs. However, these results
alone did not provide enough evidence to distinguish
between a salivary gland tumor and a skin appendage
tumor, since glycogen-rich characteristics can be seen
both in salivary gland tumors and in some skin append-
age tumors [4].
Immunohistochemically, the tumor cells showed a
positive reaction for cytokeratin (Figure 7), S-100 pro-
tein (not shown), CEA in part (Figure 8), but a negativ e
reaction for smooth muscle actin (SMA), alpha-1 anti-
trypsin, and amylase. The positive result for the S-100
protein indicated a possibility of myoepithelial origin.
However, the negative reaction for SMA excluded the
possibility that the tumor was myoepithelial in nature.
As described, the possibility of skin appendage ma-
lignancy, such as microcystic adnexal carcinoma or ec-
crine porocarcinoma [5], was considered in the differen-
tial diagnosis of the present tumor. However, in consid-
eration of the histologic, histochemical, and immuno-
histochemical findings, the final diagnosis was tentative-
ly made as a glycogen-rich adenocarcinoma of undeter-
mined origin.
After the diagnosis of the lower lip malignancy was
made by the biopsy specimen, the patient was trans-
ferred to the Saitama Prefectural Cancer Institute where
the lesion was surgically removed. Seven months after
the primary surgery, a swelling was observed in the
right submental lymph node, and lymphectomy was
performed. Post-surgical lymph node specimens exhib-
ited a metastatic focus of the tumor, with extra-capsular
During the follow-up period (approximately ten months)
after the lymphectomy, further swelling was noted in the
right submandibular lymph nodes, and radical neck dis-
section was performed. A metastatic tumor focus was
again observed in the histlogical sections. However, nei-
ther recurrence nor metastatic signs have been present
since the neck surgery. The patient’s post-surgical status
has been uneventful during the past five years.
Figure 5. A small duct-like or pseudo cystic structures were
detected in tumor nests (hematoxylin and eosin, original mag-
nification, ×200).
Figure 6. (a) Positive reaction to PAS stain in the tumor nests
and pseudocysts (PAS stain, original magnification, ×200); (b)
Disappearance of PAS-positive material after diastase digestion
seen in the tumor nests (PAS stain after diastase digestion,
original magnification, ×200).
K. Mori et al. / Open Journal of Stomatology 1 (2011) 109-113
Copyright © 2011 SciRes. OJST
Figure 7. Immunohistochemical detection of cytokeratin in the
tumor nests (original magnification, ×200).
Figure 8. Immunohistochemical detection of CEA the tumor
nests (original mag nification, ×200).
Intraoral glycogen-rich adenocarcinoma is a rare neo-
plasm particulary in the lower lip. The accurate charac-
teristics of the cells of origin have not yet been fully
clarified. In the head and neck region, tumors of salivary
gland origin [1-3], dermal appendage derivation [4-6],
and metastatic tumors from a distant organ (such as the
breast) [7] should be included in the differential diagno-
sis. In our case, metastatic malignancy was ruled out by
careful systemic examinations, using conventional X-ray,
CT, MRI , a nd even by blo od biochemistry.
Before considering these other diseases, the first
thought should be that the tumors is a primary salivary
gland malignancy, such as an ACC or mucoepidermoid
carcinoma. In particular, the cribriform of ACC, which is
composed of sheets of basaloid cells forming “cribri-
form” pseudocysts within the tumor nests, may show a
similar cytopathology to the present case. However, the
possibility of ACC and mucoepidermoid carcinoma was
excluded by the abundant accumulation of glycogen
within the tumor nests in the present case.
The published literature about glycogen-rich or clear
cell carcinoma of the salivary gland have described it as
epith eli al -myoep it h elial car cin oma [3 ]. T his t umor mani -
fests a biphasic growth pattern consisting of the small
ductal cells that are surrounded by the proliferating
myoepithelial clear cells. Immunohistochemically, the
ductal cells show cytokeratin, while the clear cells dem-
onstrate strongly positive immunoreactions for S-100
protein and SMA, and a variable degree of staining for
cytokeratin. Again, although some amount of glycogen
can be seen in clear cells, epithelial-myoepithelial carci-
noma could be excluded by the large amount of glycogen
accumulation s een in the pre s e nt case.
The accumulation of glycogen suggests the possibility
of a malignant tumor of a cutaneous skin appendage. The
presence of glycogen in most of the tumor cells in the
present case could be consistent with their being imma-
ture cells of the intraepidermal eccrine sweat gland duct,
since these cells are rich in glycogen in the human em-
bryo [4]. Therefore, skin appendage tumors shoud be
differentiated from primary salivary gland tumors, and
skin lesions arising near the salivary gland may provide
diagnostic difficulty. A more real concern is the distinc-
tion between glycogen-rich adenocarcinoma and eccrine
adenocarcinoma, both of which are rich in cytoplasmic
accum ulat ion of glycog en.
The treatment of choice for the lower lip malignancy
is surgical excision, together with some kind of chemo-
therapy. Our patient was treated with surgical excision
with a 10 mm safety margin. Seven months after the
surgery, a suspicious metastatic focus was found in her
regional cervical lymph nodes. The regional lymph
nodes were removed, and the focus was diagnosed as a
metastatic tumor of the primary carcinoma. A relatively
good prognosis was obtained, and she has been recur-
rence and metastasis-free for about five years after the
radical neck surgery. However, since local recurrence
and distant metastasis are possible because of the malig-
nant nature of the tumor, long-term careful follow-up is
The authors express their gratitude to Drs. S. Okabe and K. Yagihara,
Saitama Prefectural Institute of Cancer, for their helpful discussion and
management of the patient in due of follow-up course, and Dr. Y. Ta-
jima, Department of Oral Pathology, Meikai University School of
De nt is try , fo r pre pa ri ng this m anusc rip t.
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