Download Verruciform xanthoma of the oral mucosa－cases report(J Dent Sci

Verruciform xanthoma of the oral mucosa
－cases report
CHIUNG-FANG HUANG1
JING-MING HUNG2
CHENG-YUE SUNG1
YI-JUNG LU1
KUANG-HSUN LIN3
YUN-HO LIN4
1
Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan, ROC.
School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan, ROC.
3
Department of Dentistry, Taipei Medical University – Municipal Wan Fang Hospital, Taipei, Taiwan, ROC.
4
Department of Pathology, Taipei Medical University, Taipei, Taiwan, ROC.
2
A verruciform xanthoma (VX) is an uncommon lesion confined mainly to the oral mucosa. The
diagnosis is almost always made during a histologic examination. Histologically, it is characterized by
papillomatosis, parakeratosis, and aggregates of foam cells in the connective tissue papillae. The
histogenetic origin of the lipid-laden foam cells is controversial. Three cases of oral mucosal VX are
reported. The immunohistochemical study showed that the foam cells were positive for CD68 and
vimentin and negative for S-100. Based on our findings, we suggest that foam cells, as a histological
hallmark of the lesion, are most likely derived from the monocyte-macrophage lineage. We failed to
detect human papillomavirus in all 3 cases. Differentiating a verrucous carcinoma from VX is
important, especially in small superficial lesions, which could lead to an inappropriate and excessive
surgical intervention. Treatment of VX consists of a simple surgical excision and the prognosis is
excellent. （J Dent Sci, 2(4)：226-229 , 2007）
Key words: verruciform xanthoma, monocyte-macrophage.
A verruciform xanthoma (VX) is an uncommon
lesion confined mainly to the oral mucosa1. The
most common site of involvement is the gingival
margin, followed by the palate and floor of the
mouth2,3. Lesions that may occur elsewhere usually
arise on the perineum or skin. Clinically, a VX is a
single lesion with a verruciform appearance, but it
may appear as polypoid, papillomatous, or sessile. A
few authors have reported the rare occurrence of
multiple lesions4-6. The color of such lesions may be
red or pink, but may occasionally be yellowish-red or
grayish. The clinical appearance of a VX is not
diagnostic; the diagnosis is almost always made
during histologic examination. Histologically, it is
characterized by papillomatosis, parakeratosis, and
aggregates of foam cells in the submucosal stroma
without epidermal atypia1,2,7. It was reported that the
most often affected sites were in epithelia subjected to
trauma or irritation. Most patients with a VX do not
have hyperlipidemia. The histogenetic origin of the
lipid-laden foam cells is controversial, but they are
known to be cells of the monocyte / macrophage
lineage 8-12 . The pathogenesis of VX remains
unknown, although an inflammatory, immuneassociated response and possibly human papillomavirus (HPV) infection have been proposed. We
present 3 cases of oral mucosal VX and results of
the immunohistochemical studies.
CASE PRESENTATION
Received: October 2, 2007
Accepted: November 27, 2007
Reprint requests to: Dr. Yun-Ho Lin, Department of Pathology, Taipei
Medical University, No.250, Wu-Hsing Street, Taipei,
Taiwan 11042, ROC.
226
The 3 cases diagnosed with a VX were taken
from the pathology files of the Dental Department of
Taipei Medical University Hospital in 2004~2006.
J Dent Sci 2007‧Vol 2‧No 4
Verruciform xanthoma of the oral mucosa
Case 1
Histopathology
A 66-year-old Asian female requested for a
routine oral examination, and a pink soft mass in the
area of the right mandibular buccal gingivae of the
central and lateral incisor was found. The patient
said that the mass had existed for a long time and
was painless. The patient has cardiomegaly and
hypertension which is well controlled by medications.
On physical examination, we observed a 0.3 ×
0.2 cm, pink, well-demarcated papillomatous mass.
There was no other lymphadenopathy. Under the
impression of a papilloma as a clinical diagnosis, it
was excised.
Histopathologically, these 3 sections were similar
on microscopic examination. The lesions showed
papillomatosis with parakeratotic squamous epithelium and a hyperplastic epidermis without atypia.
Exocytosis of leukocytes of the epidermis was seen.
Simultaneously, there was abundance of pale foamy
histiocytes in the elongated dermal papillae (Figures 1,
2). Below the benign epithelium, a focal interface
and interstitial infiltrate of lymphocytes, plasma cells,
and neutrophils were observed.
Serial 5-µm-thick, formalin-fixed, paraffinembedded specimens were immunohistochemically
stained with monoclonal antibodies against CD68,
Case 2
A 33-year-old Asian male was referred to our
hospital from a local dentist on account of a mass over
the right mandibular buccal gingivae of the first and
second premolars for 1 year. The lesion was neither
painful nor ulcerated. The patient had a social
history of smoking, alcohol consumption, and betel
nut chewing for over 10 years, but denied any
systemic disease.
On physical examination, a 1.5 × 1.0 cm, sessile,
pink, exophytic papilloma-like mass distinctly delineated from the adjacent tissue was found. In the
bilateral buccal areas, submucosal fibrosis and
leukoplakia were also noted. Our impression was a
papilloma and the mass was excised under local
anesthesia.
Case 3
A 76-year-old Asian male was referred to our
hospital from a local dentist on account of an
inconspicuous mass growing in the area of the left
mandibular lingual gingivae between the first and
second premolars. The lesion was painless and
moderately inflamed.
On physical examination, a 0.5 × 0.5 cm, pink to
red, non-tender verruciform projection was found.
The patient had periodontitis with poor oral hygiene.
There was no other lymphadenopathy. Laboratory
results revealed mildly elevated levels of creatinine
(2.3 mg/dl), uric acid (8.7 mg/dl), cholesterol (249
mg/dl), and blood urea nitrogen (26 mg/dl). Under
local anesthesia, the verrucous hyperplastic mass was
excised.
J Dent Sci 2007‧Vol 2‧No 4
Figure 1. Microscopically, the lesion showed papillary epithelium
with parakeratosis. There was an abundance of xanthoma foam cells
which had infiltrated the dermal papillae. Inflammatory infiltrates of
lymphocytes and neutrophils were also noted. (H&E stain, 100×)
Figure 2. Higher magnification of Figure 1 showing xanthoma
cells with small nuclei in the dermal papillae. (H&E stain, 200×)
227
C.F. Huang, J.M. Hung, K.H. Lin, et al.
Figure 3. Foam cells showing strong cytoplasmic CD68
immunostaining. The epithelial cells
(immunohistochemical staining, 200×)
were
negative.
vimentin, and S-100 protein. The sections were also
subjected to detect of HPV using genechips
(EasychipHPV Blot, King Car Food Industrial, Ilan,
Taiwan). Easychip HPV Blot genechips are capable
of identifying the genotypes of HPV via a polymerase
chain reaction-based method. The results were as
follows: the foam cells showed strong cytoplasmic
CD68 immunostaining (Figure 3). The mesodermal
and foam cells in the interstitial tissue showed strong
immunoreactivity to vimentin. S-100 protein staining highlighted Langerhans' cells, while epithelial
cells and xanthoma cells showed almost no
immunostaining. The xanthoma foam cells were
positive for CD68 and vimentin and negative for
S-100. Therefore, the xanthoma foam cells were
confirmed to be macrophages.
HPV was not
detected in any of the specimens.
DISCUSSION
A VX was first reported by Shafer in 1971, and
this rare lesion is mainly confined to the oral cavity1.
The gingiva is the most commonly affected site
(57.4%) as reported by Philipsen et al.2, which was
also found in our 3 cases. Many authors consider it
to be a reactive process rather than a true neoplasm.
Mild trauma or irritation has been proposed as playing
a role in the etiopathogenesis because lesions are often
found in the masticatory mucosa yet there is usually
no direct evidence of local irritants, including our
3 cases. A VX is characterized by a squamous
epithelial surface of varying morphologies covered
with parakeratin and a hyperplastic epidermis without
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atypia1,2,7. The outstanding feature of this lesion is
the presence of foam cells, which fill the elongated
dermal papillae but the relationship between these
features has not been defined. The histogenetic
origin of the lipid-laden foam cells is controversial.
Foam cells have been regarded as fibroblasts,
melanoytes13,14, or macrophages. Most authors believe that foam cells are lipid-laden macrophages8-11.
Mostafa et al.12 were the first to demonstrate the origin
of VX foam cells as cells of the monocyte/macrophage
lineage. In our 3 cases, the foam cells showed strong
CD68 immunoreactivity. CD68 is a monocytichistiocytic cell marker, confirming the possible role of
macrophages in the formation of typical foam cells.
Another proof of their mesodermal origin is that foam
cells are strongly stained by vimentin. S-100 proteinpositive dendritic cells (Langerhans' cells) were not
observed in previous reports11,12,15 and our results were
also in accordance.
The etiology and pathogenesis of oral VXs are
still far from being clarified. Zegarelli et al. and
others2,13,16-18 introduced the concept that lipidcontaining macrophages accumulate due to epithelial
degeneration. The products of epithelial breakdown
elicit an inflammatory response and a subsequent
release of lipid material through epithelial degeneration, which is finally scavenged by macrophages.
Travis et al.6 suggested that xanthoma cells are
macrophages responsible for removing lipids that
accumulate in the submucosal tissues, and that the
epithelial hyperplasia is a secondary event. VXs
were suggested to be a local immunologic disorder by
Mostafa et al.12 Mohsin et al.19 considered that the
possible viral infection of the oral cavity and genital
skin was similar to an HPV infection. Khaskhely et
al.20 reported a case of a VX associated with HPV type
6, but this is not consistent with the research of many
other workers or our own3,11,21-23. The HPV is a fairly
ubiquitous organism and can be isolated from
apparently normal tissue24,25 even in up to 55% of
people in Zhang’s report26. Further studies are
needed to determine whether HPV plays a role in the
pathogenesis of VX or is merely coincidental.
The clinical features of VXs are non-specific.
The papillary or verrucous outer appearance often
leads to a clinical misdiagnosis of a papilloma (cases 1
and 2) or verrucous hyperplasia (case 3). A correct
diagnosis is almost always made during the histologic
examination.
Histopathologically, VXs can be
misdiagnosed as verruca vulgaris, a granular cell
J Dent Sci 2007‧Vol 2‧No 4
Verruciform xanthoma of the oral mucosa
tumor, condyloma accuminatum, or verrucous
carcinoma2,20. Differentiating verrucous carcinoma
from a VX is important, especially in small superficial
lesions, which could lead to an inappropriate and
excessive surgical intervention. VXs show papillomatosis with parakeratotic squamous epithelium and a
hyperplastic epidermis without atypia. In verrucous
carcinoma, the characteristic xanthoma cells are
absent; furthermore, the epidermal downgrowth takes
the form of bulbous processes rather than relatively
narrow ridges2. Treatment of a VX consists of
simple surgical excision. The prognosis for VXs is
excellent.
ACKNOWLEDGEMENTS
The authors thank the Yuan-Shan Research
Institute, King Car Food Industrial Co., Ilan, Taiwan
and Mr. Lee Bor-Heng for the detection of HPV in the
study.
11.
12.
13.
14.
15.
16.
17.
18.
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