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Labial pyogenic granuloma related to trauma: A case report and mini-review

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Running title: Labial pyogenic granuloma related to trauma

Authors:
Assim Banjar1, Abrar Abdrabuh2, Manaf Al-Habshi3, Mohamed Parambil3, Pedro
Bastos4,5, Hassan Abed1,4,5

Affiliations:
1 Faculty of Dentistry, Umm Al-Qura University, Makkah, Saudi Arabia
2 College of Dentistry, Al-Farabi Colleges, Jeddah, Saudi Arabia
3 King Faisal Hospital and Research Centre, Makkah, Saudi Arabia
4 Faculty of Dentistry, Oral and Craniofacial Sciences, King’s College London,
London, United Kingdom
5 Guy’s Hospital, London, United Kingdom

Correspondence author: Dr.Hassan Abed, Department of Basic and Clinical Oral


Sciences, Faculty of Dentistry, Umm AL-Qura University, P.O.BOX 14405, Post Code
21955, Tel: +966 12 5270000, Makkah, Saudi Arabia, E-mail: hhabed@uqu.edu.sa

Ethics: No ethical approval was required.

Conflict of interest statement: The authors declare no conflict of interest.

Funding statement: No funding was required.

This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process, which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1111/EDT.12537
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Acknowledgments: Authors would like to thanks Ayoub Al-Thobaiti (a lab specialist)
and Dr.Nasir Al-Noor (a histopathology consultant) at King Faisal Hospital and
Research Centre, Makkah, Saudi Arabia, for preparing and reporting the histopathology
slides. Also, the authors would like to thanks Dr. Hussam Abualola (a general dentist)
and Dr.Jaber Al-Zaed (an endodontist) at King Faisal Hospital and Research Centre,
Makkah, Saudi Arabia, for dental treatment that was provided for the patient.

Contributions: AB, AA and MP wrote the introduction and focused on the clinical
aspects of the case report. MA and HH developed the searching protocol process,
search strategy keywords and wrote the remaining parts of the manuscript (i.e.,
materials and methods, results, discussion, and conclusions). PB revised the
manuscript. All authors read and approved the final manuscript.

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Accepted Article
DR HASSAN ABED (Orcid ID : 0000-0003-3817-3938)

Article type : Mini Review

Labial pyogenic granuloma related to trauma: A case report and


mini-review

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Accepted Article

Abstract

This paper reports a case of a labial pyogenic granuloma in the lower lip of a 15-
year-old male due to chronic trauma from the maxillary left central incisor. The
case report is based on the CARE (CAse REport) Checklist developed by the
Joanna Briggs Institute. A further aim is to present a mini-review about the link
between labial pyogenic granuloma and trauma, through searching in three
databases (MEDLINE, EMBASE and Global Health) using a predefined search
strategy and keywords. The Cochrane library and PROSPERO were also searched
for published and ongoing systematic reviews, respectively. Only five case reports
were found that discussed the link between labial pyogenic granuloma and trauma.
Chronic trauma was found to be the most common cause of pyogenic granuloma
affecting the lip. Excisional biopsy was the preferable treatment due to the

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advantage of allowing histopathologic assessment, which is necessary to establish
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a definitive diagnosis. Dentists advise to include labial pyogenic granuloma in their
differential diagnosis (i.e., mucocele, cyst, abscess, hematoma, minor salivary
gland trauma or tumor) when assessing lesions in the upper and lower lips, in
particular when related to a history of trauma.
Keywords
Labial pyogenic granuloma, extra-gingival lesion, trauma, pediatric patients

Introduction

Pyogenic granuloma (PG) is a benign lesion that occurs in the skin and mucous
membrane as inflammatory hyperplasia.1 Predominantly, the gingiva is the affected
site, whereas PG rarely occurs extra-gingivally.2 It is also called vascular epulis,
hemangiomatous granuloma and when it occurs during the gestation period,
pregnancy granuloma.3 Although Hartzell in 1904 gave the name of granuloma
pyogenicum, it was first described by Hullihen in 1844.4 Clinically, it presents as a
sessile or pedunculated lesion with a smooth or lobulated surface; it is
erythematous, can bleed easily and is non-painful to palpation.5 PG usually
resembles the gingival color unless the vascularity decreases due to aging. 6 It more
commonly appears in females than males, with a ratio of 2:1.6 It is usually
asymptomatic. In a review study, PG developed in 22% of young patients.7 The
peak age incidence of PG is in the second decade and it is not very prevalent in
children.8 There is a controversy around the etiology of PG.7 Local irritation and
chronic trauma are the more common factors, such as poor oral hygiene,
parafunctional habits, history of dental extraction, overhanging dental restorations
and toothbrush trauma.7, 9 Others have suggested that it is an infective process or a

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result of hormonal changes.10 The diagnosis of PG is based on biopsy and
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histopathologic assessment. This case report presents a labial pyogenic granuloma
(LPG) affecting the vermilion border of the lower lip in a 15-year-old male patient
due to chronic trauma. A mini-review about the link between LPG and trauma in
pediatric patients is also presented.

Materials and methods

The case report was based on the CARE (CAse REport) Checklist developed by
the Joanna Briggs Institute at the University of Adelaide, South Australia.11 Three
databases (i.e., Ovid MEDLINE (1946 to May 21, 2019), Embase (1974 to 2019
Week 20) and Global Health (1973 to 2019 Week 19)) using a predefined search
strategy and keywords were considered during the searching process (Table 1).
The Cochrane library and PROSPERO were also searched for published and
ongoing systematic reviews, respectively, about the link between LPG and trauma
in pediatric patients.

Results

The selection process for the articles included in this paper is shown in Figure 1.
Forty-seven articles were identified through EMBASE, 7 articles were identified
through MEDLINE and one was identified through Global Health databases. One
article was found in the Cochrane library but was related to PG that developed in
the skin (the anatomical site was not reported by the authors).12 No ongoing
systematic review was found in PROSPERO. Thirty-eight articles remained after
duplicates were removed. After the screening stage, 31 articles were excluded and
7 articles were assessed for eligibility. Only five case reports were found that

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investigated the link between the LPG and trauma in pediatric patients and
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included in the mini-review (Table 2).13-17 These case reports were published from
2009 to 2016.

Case report

A 15-year-old male was referred to the oral and maxillofacial surgery clinic at
King Fahad Hospital in Makkah, Saudi Arabia, presenting with an asymptomatic
lesion in the left side of the vermilion border of the lower lip. It had been presented
for three months and had started as a small blister lesion, which was associated
with fluid discharge. The patient’s medical history was unremarkable. Upon extra-
oral examination, no abnormalities were detected. Intra-oral examination revealed
poor oral hygiene, with plaque accumulation and moderate deposits of calculus.
There was a small (size 1.2x0.8x0.6 cm), pedunculated, lobulated swelling on the
left side of the vermilion border of the lower lip (Figure 2). It was pink in color and
partially covered by a pseudomembrane. It had a soft consistency and bled on
touch. Figure 3 shows the lesion interfering with the occlusion and it also shows a
scar/healing lesion in the upper lip (right side) related to a fractured upper right
central incisor. The upper right central incisor was fractured two months after the
lesion in the left side of the lower lip developed while the patient was playing
football. Ethyl chloride was applied to the fractured upper right central incisor. The
responses indicated that the tooth was a pulpless, infected root canal system with
chronic apical periodontitis associated with an uncomplicated crown fracture
(Figure 4).

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The treatment plan was discussed with the patient and his parents. He was advised
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to have an excisional biopsy of the lesion. This followed by root canal treatment
and dental restoration of the upper right central incisor. He was also referred to a
dental hygienist to improve his oral health status. Lastly, the patient was advised to
see an orthodontist to have his occlusion assessed.

An excisional biopsy was performed under local anesthesia in the oral and
maxillofacial surgery clinic at King Fahad Hospital and it was sent to the
histopathology laboratory. Figure 5 shows the lower lip vermillion border
immediately after the excisional biopsy. The histopathologic assessment revealed a
polypoid lesion covered by non-keratinized stratified squamous epithelium, with
irregular acanthosis, extensive ulceration and underlying inflamed granulation
tissue. The underlying stroma was edematous with foci of lymphoplasmacytic
inflammatory cells infiltrate. There was diffuse proliferation of dilated thin-walled
and congested vascular spaces in the stroma. The blood vessels were lined by a
single layer of bland endothelial cells. No microorganisms, granulomas, atypia, or
malignancy were seen. Figure 6 shows the microscopic findings of the lesion.

One week post-operatively there was no complaint from the patient. Once the
surgical site healed, the sutures were removed (Figure 7). After 6 months, the
clinical review showed complete healing of the surgical site with no signs of
recurrence lesion (Figure 8). The upper right central incisor was treated with root
canal treatment and restored with composite filling (i.e., Universal compsite,
Dentsply Sirona®) (Figure 9).

Discussion

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The search process in the three databases found only five case reports that
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discussed the link between LPG and trauma in pediatric patients. All reported the
vermilion border of the upper lip to be the site of the PG, which contrasts with this
case as it occurred in the vermilion border of the lower lip. Asha et al.18 reported a
case of LPG that affected the vermilion border of the lower lip, but in a 54-year-
old male rather than in a child.

Trauma was found to be the most common factor for the development of LPG in
the reported cases. Low-grade trauma or chronic irritation combined with poor oral
hygiene was found to contribute to the development of LPG.18

In regards to management, surgical excision was the most common treatment


modality for LPG reported in three case reports.14,16,17 One case report proposed a
non-surgical approach with the use of 0.5% of Timolol gel.13 Timolol gel is a beta-
blocker that has anti-angiogenic and vasoconstrictive effects, which could help to
reduce the size of LPG.13 Treatment with Timolol gel may be used selectively to
avoid surgery and scar formation. Despite these benefits, there is no consensus
regarding the treatment dose and it has the disadvantage of not allowing
histopathology assessment. Lastly, Asnaashari et al.15 in their case report used a
diode laser to treat the LPG, but the lesion recurred five days post-operatively and
conventional surgical excision had to be performed.

Recurrence of PG is possible in some cases (16%) as a result of deficient excision


or failure to eliminate the cause.19 However, it is important to highlight that the
recurrence rate of PG in gingival cases is higher than PG that affects other parts of
the oral cavity. Therefore, the recurrence of LPG after surgical excision is very
rare.4,15,20,21

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Conclusions
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Chronic trauma was found to be the most reported etiology of LPG. Excisional
biopsy was the most common treatment modality of LPG and this has the
advantages of eliminating the lesion and providing a definitive diagnosis based on
histopathological assessment. Dentists should include LPG in their differential
diagnosis when assessing lesions in the upper and lower lips, in particular when
related to a history of chronic trauma. Clinically, LPG resembles other lesions
affecting the lips that should be included in the differential diagnosis, such as
mucocele, cyst, abscess, hematoma, minor salivary gland trauma or tumor.

References
1. Mighell AJ, Robinson PA, Hume WJ. Immunolocalisation of tenascin‐C in
focal reactive overgrowths of oral mucosa. J Oral Pathol Med. 1996;25:163-9.
2. Akyol MU, Yalçiner EG, Doğan AI. Pyogenic granuloma (lobular capillary
hemangioma) of the tongue. Int J Pediatr Otorhinolaryngol. 2001;58:239-41.
3. Graham R. Pyogenic granuloma: an unusual presentation. Dent Update.
1996;23:240-1.

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4. Jafarzadeh H, Sanatkhani M, Mohtasham N. Oral pyogenic granuloma: a
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review. J Oral Sci. 2006;48:167-75.
5. Neville BW, Damm DD, Allen CM, Chi AC. Oral and maxillofacial
patholology. 2nd Edn. New Delhi, India: Elsevier Health Sciences; 2015; 447-449.
6. Sachdeva SK. Extragingival pyogenic granuloma: an unusual clinical
presentation. J Dent. 2015;16:282-5.
7. Krishnapillai R, Punnoose K, Angadi PV, Koneru A. Oral pyogenic
granuloma—a review of 215 cases in a south indian teaching hospital, karnataka,
over a period of 20 years. J Oral Maxillofac Surg. 2012;16:305-9.
8. Al-Khateeb T, Ababneh K. Oral pyogenic granuloma in jordanians: a
retrospective analysis of 108 cases. J Oral Maxillofac Surg. 2003;61:1285-8.
9. Patil K, Mahima V, Lahari K. Extragingival pyogenic granuloma. Indian J
Dent Res. 2006;17:199-202.
10. 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. Am J Surg Pathol. 1980;4:470-9.
11. Joanna Briggs Institute (JBI). Critical Appraisal Tools. Available at: URL:
'https://joannabriggs.org/sites/default/files/2019-05/JBI_Critical_Appraisal-
Checklist_for_Case_Reports2017_0.pdf'. Accessed November 2019.
12. El‐Khateeb EA, Lotfi RA, Abdel‐Aziz KM, El‐Shiekh SE. Prevalences of
skin diseases among primary schoolchildren in D amietta, E gypt. Int J Dermatol.
2014;53:609-16.
13. Atakan M, Atakan T, Ulusoy M, Ayanoğlu B. Pyogenıc granuloma treated
with topical timolol in a 7-month-old child. Eur J Pediat Dermatol. 2016;26:213-5.
14. de Carvalho FK, Pinheiro TN, Arid J, de Queiroz AM, De Rossi A, Nelson-
Filho P. Trauma-induced giant pyogenic granuloma in the upper lip. J Dent Child.
2015;82:168-70.

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15. Asnaashari M, Bigom-Taheri J, Mehdipoor M, Bakhshi M, Azari-Marhabi
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S. Posthaste outgrow of lip pyogenic granuloma after diode laser removal. Lasers
Med Sci. 2014;5:92-5.
16. Gonçales ES, Damante JH, Rubira CMF, Taveira LAdA. Pyogenic
granuloma on the upper lip: an unusual location. J Appl Oral Sci. 2010;18:538-41.
17. das Chagas MS, Pinheiro RdS, Janini ME, Maia LC. Pyogenic granuloma:
lobular capillary hemangioma in the upper lip of a 24-month-old child: case report.
J Dent Child. 2009;76:237-40.
18. Asha V, Dhanya M, Patil BA, Revanna G. An unusual presentation of
pyogenic granuloma of the lower lip. Contemp Clin Dent. 2014;5:524-6.
19. Erbasar GNH, Senguven B, Gultekin SE, Cetiner S. Management of a
recurrent pyogenic granuloma of the hard palate with diode laser: a case report.
Lasers Med Sci. 2016;7:56-61.
20. Gomes SR, Shakir QJ, Thaker PV, Tavadia JK. Pyogenic granuloma of the
gingiva: A misnomer? A case report and review of literature. J Indian Soc
Peridontol. 2013;17:514-9.
21. Kamal R, Dahiya P, Puri A. Oral pyogenic granuloma: Various concepts of
etiopathogenesis. J Oral Maxillofac Pathol. 2012;16:79-82.

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Legends

Figure 1. The flow diagram of the selection process.


Figure 2. There is a small (size 1.2x0.8x0.6 cm), pedunculated, painless, soft
lobulated growth on left side of the lower lip covered by a yellow fibrin membrane.
Figure 3. The lesion interferes with the occlusion.
Figure 4. The Fractured upper right central incisor.
Figure 5. The lower lip vermilion border after excisional biopsy.
Figure 6. The microscopic findings of the lesion revealed a polypoid lesion
covered by non-keratinized stratified squamous epithelium, with irregular
acanthosis, extensive ulceration and underlying inflamed granulation tissue.
Figure 7. Healing of the lip one-week post-surgical excisional biopsy.
Figure 8. Complete healing of the surgical site after 6 months with no signs of
recurrence lesion.
Figure 9. The upper right central incisor after the dental restoration.

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Table 1: Keywords used during the searching process.†
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1. pyogenic granuloma.mp. or exp Granuloma, Pyogenic/
2. Trauma.mp. or exp "Wounds and Injuries"/
3. lip.mp. or exp Lip/ or exp Lip Neoplasms/ or exp Lip Diseases/
4. 1 and 2 and 3


Ovid MEDLINE (1946 to May 21, 2019), Embase (1974 to 2019 Week 20) and Global Health (1973 to 2019
Week 19).

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Table 2: Summary of articles being included in the mini-review.

Author name Country Type of study Summary of the case Site of lesion Management Conclusion

Topical Timolol 0.5% Treatment with topical Timolol provided


13
A 7-month-old infant with a pyogenic
Atakan et al. Turkey gel twice daily for four complete regression of the extra-gingival
granuloma
months pyogenic granuloma

Large pyogenic granuloma measuring


A large pyogenic granuloma in an 11-year-
4.5cm could be the result of acute intense
14
Brazil old boy resulting from small laceration and Surgical excision
De Carvalho et al. trauma and should be included in the
injury
differential diagnosis
Case report Upper lip
Lesion removed by laser
followed by surgical Removal of the lesion and surgical
15
A case of 15-year-old male with
Asnaashari et al. Iran excision at the second excision was the treatment of choice to
immediate recurrence of pyogenic
visit due to recurrence ensure no recurrence
granuloma after first removal by laser

Extra-gingival pyogenic granuloma is not


16
A pyogenic granuloma in a 12-year-old
Gonçales et al. Brazil Surgical excision unusual in the lip and should be included
girl with a four-year follow-up
in the differential diagnosis

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A rare case of a two-year-old child with a Surgical excision Extra-gingival pyogenic granuloma in the
Das Chagas et al.17 Brazil
pyogenic granuloma after trauma lip could lead to eating difficulties

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