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\begin{document}

\title{A chronic non-healing ulcer on the lower lip mimicking malignancy -- A
diagnostic dilemma.}



\author[1]{Rajlaxmi Mitra}%
\author[2]{Akhilanand Chaurasia}%
\author[1]{Ranjit Patil}%
\affil[1]{KGMU}%
\affil[2]{King George Medical University}%


\vspace{-1em}



  
  \date{May 23, 2024}


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\textbf{A Chronic Non-Healing Ulcer on the Lower Lip Mimicking
Malignancy --}

\textbf{A Diagnostic Dilemma.}

CLINICAL PRESENTATION

A 14-year-old male patient reported to the Department of Oral Medicine
and Radiology with a complaint of a chronic non-healing ulcer in the
lower lip. The patient reported that the lesion appeared 1 month back
and is slowly increasing in size since then. He was apparently healthy
and well-nourished without any Medical/ Dental history or parafunctional
habits. The patient did not recall any physical or chemical trauma to
the lip in the past before the appearance of this ulcer.

Clinical examination revealed a large, solitary ulcer on the right side
of the lower lip resulting in eversion of the lip. The ulcer was about
3.5cm\selectlanguage{ngerman}×2.5cm in greatest dimension. Clinically the non-healing ulcer had
presented with a grayish-pink base covered by a white slough and
indurated margins (Figure 1) however, sub-mental lymph nodes were
palpable. The ulceration was mostly asymptomatic, but the patient had
noticed occasional bleeding that would occur either spontaneously or as
a consequence of any minor agitation to the area.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Fig. 1. Clinical examination. A large solitary non-healing

ulcer on the right side of the lower lip.

DIFFERENTIAL DIAGNOSIS

Based on history, clinical presentation and location of the lesion
differential diagnoses of long-standing traumatic ulcer, malignancy,
eosinophilic ulcer, tuberculous ulcer, syphilitic ulcer,
herpes-associated erythema multiforme, and deep fungal infection has
been considered.

Single mucosal ulcers may result from direct physical, chemical,
thermal, or even vascular compromise, causing tissue damage and
ulceration. Acute bite injuries are a common example of direct physical
trauma and can be more severe if it occurs when the mucosa is numb after
local anesthesia has been given for a dental procedure. Malocclusion,
aggressive tooth brushing, and self-inflicted damage also cause
traumatic injuries. Inadvertent chewing of electrical wiring may induce
thermal injuries in children. Certain over-the-counter drugs for
treating aphthous ulcers contain high concentrations of silver nitrate,
phenol, or sulfuric acid and can cause solitary ulcerations. Vascular
compromise results in oral ulcerations such as necrotizing
sialometaplasia where there is local infarction of the salivary gland
tissue leading to overwhelming ulceration, exfoliation of the necrotic
tissue, and healing. The most common location for this condition is the
hard palate mucosa although any location that contains minor salivary
glands may be affected\textsuperscript{1}.

Oral ulcerations showing moderately rapid growth
rate\textsuperscript{2}and persisting for more than two weeks reflect
early signs of malignancy. The most common malignancy of epithelial
origin in the oral cavity is oral squamous cell carcinoma. Oral squamous
cell carcinoma most commonly affects the floor of the mouth, ventral and
lateral borders of the tongue, and lower lip. It can present as a white,
red, mixed red-white, exophytic or ulcerative lesion. The typical
clinical presentation of oral squamous cell carcinoma is a crater-like
solitary ulcer with indurated rolled border and velvety
base\textsuperscript{3}.

Eosinophilic ulceration (Traumatic ulcerative granuloma with stromal
eosinophilia) is a histopathologically distinct variety of chronic
traumatic ulceration of the oral mucosa. It presents with deep
pseudo-invasive inflammatory reactions causing very slow resolution. The
lesion can occur at any age with notably higher occurrence in
males\textsuperscript{4}. Although the anteroventral surface of the
tongue is the most common region for the lesion\textsuperscript{.} It
has also been reported on the gingiva, buccal mucosa, the floor of the
mouth, palate, and lip. Duration of the lesion may vary from 1 week to 8
months\textsuperscript{5}. The ulcerations are indistinguishable from
simple traumatic ulcers; however, occasionally the underlying
granulation tissue can proliferate and make a raised lesion matching the
clinical presentation of lobulated capillary
haemangioma\textsuperscript{6}.

Oral tuberculous lesions are usually secondary to pulmonary tuberculosis
(almost 3\% of patients with long-term active tuberculosis) but rarely
primary lesions may occur due to direct inoculation of the microbe into
oral mucosa. Of all the sites involved within the oral cavity, labial
involvement is extremely rare while the tongue is the most common region
affected. An ulceration with undermined edges and a granulating floor is
characteristic of such lesions\textsuperscript{7}.

Primary syphilitic chancres typically present as painless, sometimes
necrotic, ulcers with a rolled border and associated lymphadenopathy.
Common sites of occurrence are the lips, tongue, palate, and nostrils.
The lesions appear within 3 to 90 days of initial inoculation and may
heal spontaneously even without treatment\textsuperscript{6}.

Recurrent Aphthous Major (Sutton's disease) appears as ulcerations that
are larger than 1 cm in diameter and last for several weeks. The
extremely agonizing condition occurs when major portions of oral mucosa
get covered with extensive ulcerations that coalesce and result in
deeper and bigger lesions. Such conditions interfere with daily
activities like speaking and consuming food. The lesions may sometimes
be wrongly diagnosed as oral squamous cell carcinoma, granulomatous
disease, or a blistering disease such as pemphigus. Slow healing with
scarring causes reduced mobility of the uvula and
tongue\textsuperscript{6}.

Herpes-associated erythema multiforme is an acute disease caused by
herpes simplex virus. It results in exudative dermatic and mucosal
lesions. Oral lesions present as erythematous macules on the lips and
buccal mucosa that undergo epithelial necrosis, bullae formation, and
ulcerations with an irregular margin and strong inflammatory halo.
Bloody encrustations are visible on lips. The lip is the most common
site of preceding herpes simplex virus infection in cases of
herpes-associated erythema multiforme\textsuperscript{8}.

Deep fungal infections (histoplasmosis) are relatively rare in the oral
cavity and most commonly affect immunocompromised patients. Such lesions
typically manifest as chronic mucosal ulcerations or granular soft
tissue overgrowths that arise from either local inoculation or
dissemination by the hematogenous or lymphatic spread. These lesions are
non-specific and can mimic malignancy hence, it is crucial to obtain a
thorough clinical history and an adequate biopsy to confirm the
diagnosis.

Given the potential diagnoses mentioned earlier, it is important to
highlight that lesions of different aetiologies can have the same
clinical features and that histopathologic analysis is crucial for the
final diagnosis, treatment, and management of patients.

DIAGNOSIS AND MANAGEMENT.

Considering the rapid growth of the ulceration and its indurated margins
which provided high suspicion of malignancy we planned to have an
incisional biopsy. However, we decided to seek a second opinion from the
Department of Dermatology where he has been advised the same line of
treatment along with HSV serology and Mantoux test to rule out
hypertrophic herpes simplex and lupus vulgaris respectively.

The patient re-visited us with negative reports for HSV-serology and
Mantoux test. Routine blood investigations were within normal range. An
incisional biopsy was performed with informed consent. The
post-operative healing was uneventful.

The histopathological report illustrated hypertrophied and
hyperkeratinized stratified squamous epithelium with underlying
fibrocollagenous stroma infiltrated by dense mixed inflammatory
infiltrate comprising of predominantly lymphocyte, plasma cells,
neutrophils, and occasional histiocytes admixed with proliferating blood
vessels. There is no evidence of atypia or malignancy (Figure 2).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Fig. 2. (4\selectlanguage{ngerman}×Magnification) Hematoxylin-eosin staining showing

features suggestive of lobular capillary hemangioma.

The patient was then referred to the Department of Oral Surgery for
further management where the whole lesion was excised and sent for
biopsy. The second biopsy report was also suggestive of lobulated
capillary hemangioma.

DISCUSSION

Haemangiomas constitute about 7\% of all benign tumors in infancy and
childhood\textsuperscript{9}. An increase in the number of normal or
abnormal vessels engorged with blood is characteristic of these
entities. These lesions are broadly identified as (a) cavernous and (b)
capillary haemangioma. Cavernous haemangiomas are composed of large
dilated vascular channels that can infiltrate and involve deeper
structures making spontaneous regression a rare possibility. Capillary
haemangiomas are more common in comparison to cavernous type. These
occur in the skin, subcutaneous tissues, and mucous membranes of the
oral cavity, lips as well as in the liver, spleen, and
kidneys\textsuperscript{9}.

Lobular capillary haemangiomas are a benign proliferation of capillaries
that usually arise on the face, lips, or hands after episodes of minor
trauma\textsuperscript{10}.

They do not show age preponderance but are more common in children and
young adults, especially in men. It displays various clinical features
suggestive of reactive neovascularisation. It has a limited capacity to
grow, with a propensity for multiple eruptions that may be localized or
disseminated.

Lobular capillary haemangioma remains an etiopathological enigma.
Trauma, inflammatory and infectious agents are the suspected causative
factors. It is a relatively common benign mucocutaneous lesion occurring
intraorally or extra orally. It is a common lesion that presents with
varying clinical features that may sometimes mimic more serious lesions
such as malignancies.

Lobulated capillary haemangioma may resemble a squamous cell carcinoma
because it usually has an ulcerated patch on its surface. It is softer
on palpation and bleeds easily, and usually, its instigating irritant
can be found\textsuperscript{11}.

In a review of 639 vascular lesions of the oral cavity and upper
respiratory tract 73 cases presented with characteristic features of
Lobulated capillary haemangioma. Among the various sites, the lip was
the most common site involved (38\%). LCH presents as a spontaneous,
painless, bleeding mass. There is a predilection for males less than 18
years old, females in the reproductive years, and an equal sex
distribution beyond 40 years of age\textsuperscript{12}.

As an adage says, `Eyes cannot see what the mind does not know', a
clinician, not cognisant of the possibility of this lesion in its
unusual site mistakes it for the more serious ones and might jump to
conclusions which often leads to misleading results, uncertainty, and
mistrust. This is easily overcome by histopathology which confirms its
innocuous nature.

CONSENT STATEMENT: Written informed consent was obtained from the
patient's guardian as per guidelines to publish this report.

FUNDING: None

ACKNOWLEDGEMENT: None

CONFLICTS OF INTEREST: The authors have declared no conflict of
interest.

ETHICS STATEMENT: None

DETAILED AUTHOR'S CONTRIBUTION:

1. Rajlaxmi Mitra

Writing-Original draft

2. Akhilanand Chaurasia

Writing-Review and Editing

3. Ranjit Kumar Patil

Supervision and validation

DATA AVAILABILITY STATEMENT: None

REFERENCES

\begin{enumerate}
\tightlist
\item
  Glick M. Burket's oral medicine. PMPH USA; 2015.
\item
  Sivapathasundharam B. Shafer's Textbook of Oral Pathology-E Book.
  Elsevier Health Sciences; 2016 Jul 25.
\item
  Minhas S, Sajjad A, Kashif M, Taj F, Al Waddani H, Khurshid Z. Oral
  ulcers presentation in systemic diseases: An update. Open access
  Macedonian journal of medical sciences. 2019 Oct 10;7(19):3341.
\item
  Sarangarajan R, Vedam VV, Sivadas G, Sarangarajan A, Meera S.
  Traumatic ulcerative granuloma with stromal eosinophilia--Mystery of
  pathogenesis revisited. Journal of pharmacy \& bioallied sciences.
  2015 Aug;7(Suppl 2):S420.
\item
  Neville BW, Damm DD, Allen CM, Chi AC. Oral and maxillofacial
  pathology. Elsevier Health Sciences; 2015 May 13.
\item
  Glick M. Burket's oral medicine. PMPH USA; 2015.
\item
  Gupta A, Narwal A, Singh H. Case report: primary labial tuberculosis:
  a rare presentation. Annals of Medical and Health Sciences Research.
  2014;4(1):129-31.
\item
  Kamala KA, Ashok L, Annigeri RG. Herpes associated erythema
  multiforme. Contemporary clinical dentistry. 2011 Oct;2(4):372.
\item
  Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran pathologic
  basis of disease, professional edition e-book. Elsevier health
  sciences; 2014 Aug 27.
\item
  Sheehan DJ, Lesher JL. Pyogenic granuloma arising within a port-wine
  stain. CUTIS-NEW YORK-. 2004 Mar 1;73(3):175-80.
\item
  Wood NK, Goaz PW. Differential diagnosis of oral lesions. Mosby
  Elsevier Health Science; 1985.
\item
  Mills SE, Cooper PH, Fechner RE. Lobular capillary hemangioma: the
  underlying lesion of pyogenic granuloma. A study of 73 cases from the
  oral and nasal mucous membranes. The American Journal of surgical
  pathology. 1980 Oct 1;4(5):470-9.
\end{enumerate}

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