Oral pyogenic granuloma: An unusual presentation in tongue – Case report and comprehensive review

P Deena; Chithra Sivakumar; Darshana Jawahar; P Boobalan; Bhavadha Mohanadhass; V Vasanthi

doi:10.4103/srmjrds.srmjrds_116_20

CASE REPORT

Year : 2020 | Volume : 11 | Issue : 4 | Page : 212-215

Oral pyogenic granuloma: An unusual presentation in tongue – Case report and comprehensive review

P Deena¹, Chithra Sivakumar², Darshana Jawahar², P Boobalan², Bhavadha Mohanadhass², V Vasanthi³
¹ PG Student, Department of Oral Pathology &Microbiology, SRM Dental College, SRMIST, Chennai, India
² CRRI, Department of Oral Pathology &Microbiology, SRM Dental College, SRMIST, Chennai, India
³ Senior Lecturer, Department of Oral Pathology &Microbiology, SRM Dental College, SRMIST, Chennai, India

Date of Submission	16-Nov-2020
Date of Acceptance	19-Nov-2020
Date of Web Publication	05-Feb-2021

Correspondence Address:
Dr. V Vasanthi
Department of Oral Pathology and Microbiology, SRM Dental College, SRMIST, Ramapuram, Chennai - 600 089, Tamil Nadu
India

Check

DOI: 10.4103/srmjrds.srmjrds_116_20

Abstract

Pyogenic granuloma (PG) is a reactive, hyperplastic lesion of the skin and mucosa in response to chronic irritation. It clinically presents as sessile or pedunculated growth, most commonly in the gingiva. The clinical and histopathological spectrum of PG depends on the phase of the lesion. Healing lesions are pinkish white compared to reddish lesions in the established phase. Long-standing lesions show features of fibrosis and calcification. We report a case of PG extra gingival in location, on the left lateral surface of tongue in a 45-year-old male with an insight into etiopathogenesis, clinical presentation, histopathological, molecular, and immunohistochemical features. Novel concept of isolation of stem cells from pathological tissues such as PG might help future research in regenerative dentistry.

Keywords: Pyogenic granuloma, regenerative dentistry, stem cell, tongue

How to cite this article:
Deena P, Sivakumar C, Jawahar D, Boobalan P, Mohanadhass B, Vasanthi V. Oral pyogenic granuloma: An unusual presentation in tongue – Case report and comprehensive review. SRM J Res Dent Sci 2020;11:212-5

How to cite this URL:
Deena P, Sivakumar C, Jawahar D, Boobalan P, Mohanadhass B, Vasanthi V. Oral pyogenic granuloma: An unusual presentation in tongue – Case report and comprehensive review. SRM J Res Dent Sci [serial online] 2020 [cited 2021 Feb 26];11:212-5. Available from: https://www.srmjrds.in/text.asp?2020/11/4/212/308779

Introduction

The first case of pyogenic granuloma (PG) was described by Poncet and Dor in 1897. Hartzell coined the term PG in 1904. The term is believed to be a misnomer as the lesion is neither related to pus formation nor resembles a granuloma histologically.^[1],[2],[3] The histological presentation was described by Angelopoulos as “hemangiomatous granuloma.” Granuloma pyogenicum, botryomycoma, human botryomycosis, pseudobotryomycosis, fibroangioma, benign pedunculated granuloma, lobular hemangioma, eruption hemangioma, pregnancy tumor, Crocker and Hartzell's disease, and granuloma telangiectacticum are few of the eponyms of the lesion. Lobular capillary hemangioma (LCH) and the non-LCH are the two forms of the lesion.^[4],[5],[6]

Here, we present a case of PG in a 45-year-old male on the left lateral aspect of the tongue. Etiopathogenesis, clinical presentation, histopathological, molecular, immunohistochemical, and recent concept of expression stem cell markers in tissue of PG are being discussed.

Case Report

A 45-year-old male reported to our department with the complaint of difficulty in feeding due to the growth on the left lateral side of the tongue. The patient gave a history that he noticed the growth 5 months ago, which gradually increased in size to attain the present form. The patient also gave a history of bleeding from the growth at times. Intraoral examination revealed a reddish, lobular, pedunculated growth of 7 mm × 4 mm in size over the left lateral aspect of the anterior two-thirds of the tongue in relation to 34.35 [Figure 1]. The growth was soft-firm, nontender and did not bleed on palpation. Lymph nodes were not palpable. The lesion was provisionally diagnosed as PG. Oral squamous cell carcinoma was also considered owing to the site of the lesion and associated tooth. Irritational fibroma, fibroepithelial polyp, and peripheral giant cell granuloma were considered in the differential diagnosis. The lesion was excised under local anesthesia. Macroscopically, the specimen was brownish in color, firm in consistency, and measured 7 mm × 5 mm in size [Figure 2]. Histopathology revealed parakeratinized stratified squamous epithelium showing hyperplasia and atrophy. The underlying connective tissue showed proliferating endothelial cells, numerous capillaries of various sizes engorged with red blood cells, and mild-to-moderate inflammatory cell infiltrate [Figure 3]. The histopathological features were suggestive of PG. Postoperative follow-up was found to be uneventful.

Figure 1: Intraoral photograph of exophytic lesion on the lateral tongue

Click here to view

Figure 2: Macroscopic image of the biopsied specimen

Click here to view

Figure 3: Photomicrograph showing hyperplastic epithelium, proliferating endothelial cells, budding capillaries, and inflammatory infiltrate

Click here to view

Discussion

PG is a nonneoplastic, reactive, inflammatory, hyperplastic lesion of skin or mucosa in response to chronic irritation. Chronic irritation from dental plaque, calculus, or overhanging restorations activates the host defense mechanism to elicit inflammatory response through chemokines. Expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 promotes adhesion and migration of the inflammatory cells.^[7] Vascular endothelial growth factor (VEGF) induces angiogenesis and results in exuberant mass of tissue. Mast cells also contribute to the neoangiogenesis through potent mediators such as heparin, histamine, tryptase, interleukin-8, tumor necrosis factor-alpha, basic fibroblast growth factor (bFGF), and VEGF.^[8],[9] Female hormones are also reported to synergistically increase the production of bFGF and VEGF.^[10] Long-standing cases of PG exhibit a desmoplastic response characterized by transformation of fibroblast to myofibroblast phenotype.^[5]

PG is most commonly reported in females in the age group of 20–59 years. Gingiva is the most common site, followed by tongue, hard palate, buccal mucosa, lip, and floor of the mouth. It clinically presents as nontender, sessile, or pedunculated mass of few millimeter to centimeters in size. The color depends on the clinical course and vascularity. Early lesions resemble normal mucosa, established lesions are reddish to purplish, and healing lesions are pinkish to white.^{[11],[12],[13]} Clinically, LCH is usually sessile and non-LCH is usually pedunculated.^[14]

Histologically, three phases have been reported, namely, the cellular, capillary/vascular, and involutionary phase. The early cellular phase exhibits a cellular stroma with little lumen. The vascular phase shows dilated, capillaries engorged with red blood cells and proliferating endothelial cells. The involutionary phase shows fibrosis inducing reparative action.^{[2],[15],[16],[17]}

Histologically, based on the vascularity and proliferation, subforms of PG include LCH and non-LCH. LCH type presents with lobular aggregates of proliferating blood vessels and non-LCH type resembles granulation tissue with vascular proliferation. The lobular type has small luminal diameter compared to non-LCH type. The perivascular mesenchymal cells of LCH type are positive for α-smooth-muscle actin (α-SMA) whereas of non-LCH type are negative for α-SMA. Considering all the above facts, Epivatianos et al. reported that there might be different evolutionary pathways for both types of PG.^{[1],[6],[14],[18]}

On a molecular level, reactive nature and vascular growth in PG are reported to be driven by FLT4, a tyrosine kinase receptor, and the nitric oxide pathway.^[19]

Immunohistochemically, PG was reported to show positive expression of bFGF, VEGF, anti-CD3, Tie-2, factor VIII-related antigen, anti-alpha SMA antibodies, angiopoietin-1, angiopoietin-2, ephrinB2, and ephrinB4. The expression of VEGF is found to decrease during the course of the lesion as the budding capillaries mature and form well-organized vessels. The decreased expression of VEGF in established lesions may also be attributed due to the expression of angiogenesis inhibitors, namely, TSP-1 and angiostatin.^{[20],[21],[22],[23]}

Recent studies revealed that stem cells can be isolated from pathological tissue such as PG. PG has properties of stemness as it is positive for embryonic stem cell markers such as pSTAT3, OCT4, SOX2, and NANOG.^[24],[25] Dehghani Nazhvani et al. reported osteogenic and adipogenic differentiation from single cell cultures of PG.^[24] Blackwell et al. reported that expression of embryonic stem cell markers by endothelial cells of microvessels suggested primitive origin and by the interstitial cells represented downstream derivative of primitive endothelium.^[25] Dehghani Nazhvani et al. reported the expression of STRO-1+cells, a mesenchymal stem cell marker in PG.^[26] Novel insights into research may be implicated into the histopathological and immunohistochemical aspects of PG to prove the biology of stemness.

Being a reactive lesion, surgical excision is the mode of treatment. Proper oral hygiene measures and withdrawal of the source of irritation are recommended as a preventive measure.

Conclusion

The histopathological spectrum of Pyogenic granuloma depends on the phase of the lesion. Long-standing lesions may possess feature of fibrous lesions. Stem cells can also be isolated from pathological lesions such as PG. Being the most commonly reported reactive oral lesion, expression of stem cell markers in PG might contribute to tissue regeneration in dentistry.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Jafarzadeh H, Sanatkhani M, Mohtasham N. Oral pyogenic granuloma: A review. J Oral Sci 2006;48:167-75.
2.	Marla V, Shrestha A, Goel K, Shrestha S. The histopathological spectrum of pyogenic granuloma: A case series. Case Rep Dent 2016;1323798.
3.	Sapp JP, Eversole LR, Wysocki GP. Contemporary Oral and Maxillofacial Pathology. 2^nd ed. St. Louis, Missouri: Mosby; 2004.
4.	Saravana GH. Oral pyogenic granuloma: A review of 137 cases. Br J Oral Maxillofac Surg 2009;47:318-9.
5.	Al-Shiaty RA, Ottoman BA. Recurrent pyogenic granuloma: An update. Int J Sci Rep 2015;1:22-31.
6.	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 Periodontol 2013;17:514-9. [PUBMED] [Full text]
7.	Seyedmajidi M, Shafaee S, Hashemipour G, Bijani A, Ehsani H. Immunohistochemical evaluation of angiogenesis related markers in pyogenic granuloma of gingiva. Asian Pac J Cancer Prev 2015;16:7513-6.
8.	Sheethal HS, Kn H, Smitha T, Chauhan K. Role of mast cells in inflammatory and reactive pathologies of pulp, periapical area and periodontium. J Oral Maxillofac Pathol 2018;22:92-7. [PUBMED] [Full text]
9.	Shekar S, Angadi PV. Quantification of mast cells in reactive oral lesions – A clue to the morphologic diversity. Indian J Health Sci Biomed Res 2019;12:123-6. [Full text]
10.	Andrikopoulou M, Chatzistamou I, Gkilas H, Vilaras G, Sklavounou A. Assessment of angiogenic markers and female sex hormone receptors in pregnancy tumor of the gingiva. J Oral Maxillofac Surg 2013;71:1376-81.
11.	Parajuli R, Maharjan S. Unusual presentation of oral pyogenic granulomas: A review of two cases. Clin Case Rep 2018;6:690-3.
12.	Sachdeva SK. Extragingival pyogenic granuloma: An unusual clinical presentation. J Dent (Shiraz) 2015;16:282-5.
13.	Ravi V, Jacob M, Sivakumar A, Saravanan S, Priya K. Pyogenic granuloma of labial mucosa: A misnomer in an anomolous site. J Pharm Bioallied Sci 2012;4:S194-6.
14.	Epivatianos A, Antoniades D, Zaraboukas T, Zairi E, Poulopoulos A, Kiziridou A, et al. Pyogenic granuloma of the oral cavity: Comparative study of its clinicopathological and immunohistochemical features. Pathol Int 2005;55:391-7.
15.	Sheth SN, Gomez C, Josephson GD. Pathological case of the month. Diagnosis and discussion: Pyogenic granuloma of the tongue. Arch Pediatr Adolesc Med 2001;155:1065-6.
16.	Gonçales ES, Damante JH, Fischer Rubira CM, Taveira LA. Pyogenic granuloma on the upper lip: An unusual location. J Appl Oral Sci 2010;18:538-41.
17.	Deshmukh J, Kulkarni VK, Katti G, Deshpande S. Pyogenic granuloma, an unusual presentation in pediatric patient-a case report. Indian J Dent Sci 2013;1:90-3.
18.	Mastammanavar D, Hunasgi S, Koneru A, Vanishree M, Surekha R, Vardendra M. Aggressive pyogenic granuloma: A case report. Int J Oral Maxillofac Pathol 2014;5:29-32.
19.	Godfraind C, Calicchio ML, Kozakewich H. Pyogenic granuloma, an impaired wound healing process, linked to vascular growth driven by FLT4 and the nitric oxide pathway. Mod Pathol 2013;26:247-55.
20.	Sato H, Takeda Y, Satoh M. Expression of the endothelial receptor tyrosine kinase Tie2 in lobular capillary hemangioma of the oral mucosa: An immunohistochemical study. J Oral Pathol Med 2002;31:432-8.
21.	Yuan K, Jin YT, Lin MT. The detection and comparison of angiogenesis-associated factors in pyogenic granuloma by immunohistochemistry. J Periodontol 2000;71:701-9.
22.	Vara JT, Gurudu VS, Ananthaneni A, Bagalad BS, Kuberappa PH, Ponnapalli HP. Correlation of vascular and inflammatory index in oral pyogenic granuloma and periapical granuloma-An insight into pathogenesis. J Clin Diagn Res 2017;11:ZC25-8.
23.	Yuan K, Jin YT, Lin MT. Expression of Tie-2, angiopoietin-1, angiopoietin-2, ephrin B2 and ephrinB4 in pyogenic granuloma of human gingiva implicates their roles in inflammatory angiogenesis. J Periodontal Res 2000;35:165-71.
24.	Dehghani Nazhvani A, Ahzan S, Hosseini SM, Attar A, Monabati A, Tavangar MS. Purification of stem cells from oral pyogenic granuloma tissue. Open Dent J 2018;12:560-6.
25.	Blackwell MG, Itinteang T, Chibnall AM, Davis PF, Tan ST. Expression of embryonic stem cell markers in pyogenic granuloma. Journal of Cutaneous Pathology. 2016;43(12):1096-101.
26.	Dehghani Nazhvani A, Hosseini SM, Tahoori B, Tavangar MS, Attar A. Identification of mesenchymal stem cell marker STRO-1 in oral reactive lesions by immunofluorescence method. J Dent (Shiraz) 2015;16:246-50.