Type of the Paper (Article Journal of Baghdad College of Dentistry, Vol. 34, No. 2 (2022), ISSN (P): 1817-1869, ISSN (E): 2311-5270 17 Research Article Clinicopathological analysis of 80 cases of oral lobular and non lobular capillary hemangioma (pyogenic granuloma): A Retrospective study Karrar N.Shareef(1), Bashar H. Abdullah(2) 1 Ph.D. Student, Department of Oral and Maxillofacial Pathology, College of Dentistry, University of Baghdad. 2 Professor, Department of Oral and Maxillofacial Pathology, College of Dentistry, University of Bagh- dad. *Correspondence: Karrarnajeh33@gmail.com Abstract: Background: Oral pyogenic granuloma (PG) is a clinicopathological entity that could develop due to the reaction to a variety of stimuli, such as low-grade local irritation, traumatic damage, and hormonal stimulation. There are two histopathological types of py- ogenic granuloma; lobular type -capillary hemangioma (LCH) and non-lobular type; with PG,LCH has highly vascular, diffuse capillary growth while non- lobular variant mimicking granulation tissue with heavily inflammated stroma. The study aims were to review the clinical and histopathological spectrum of an oral pyogenic granuloma from different in- traoral sites in order to avoid diagnostic pitfalls associated with similar morphological le- sions and to determine whether lobular and non-lobular histopathological subtypes being distinct entities. Materials and Methods: A retrospective review of eighty formalin-fixed paraffin-embedded tissue blocks (40 cases each of males and females) were retrieved from the archives of Oral & Maxillofacial Pathology at the University of Baghdad, from 1979 to 2017. According to Mills et al., criteria for lobular capillary hemangioma description, the diagnosis of each case was confirmed by the examination of Hematoxylin and Eosin stained sections by an expert pathologists. Results:The present result revealed that patients with oral pyogenic granuloma were with age range from 12 to 59 years, with a mean of 30.57 years. Fourty nine cases (61.25%) out of eighty were of lobular pattern and 31 cases (38.7%) of non-lobular pattern type PG. The most common site of LCH was in the buccal mucosa, 12 cases (75%), while higher case numbers were observed in the 21-30 year age group. There were non-significant differences between lobular and non-lobular pattern prevalence re- garding age groups and between other studied variables. Conclusio: It has been proposed that LCH and non-LCH subtypes reflect distinct phases in the development of a single lesion, which exhibits variable degrees of proliferative, angiogenic, and inflammatory activities. Keywords: Lobular capillary hemangioma, pyogenic granuloma, Oral cavi- ty,histopathological differences. Introduction Pyogenic granuloma (PG) is a relatively frequent type of vascular growth on the mucosal surface epithelium and skin. For the first time in 1904, Hartzell used the word “pyogenic granuloma” which is a misleading phrase since the lesion does not contain pus, as the name suggests (1,2). The oral Pyogenic granuloma is a clinicopathological entity that could result from the tissues reaction to a variety of stimuli such as low-grade local irritation, traumatic damage, and sex hormones. It is a painless growth comonly occurs in maxillary gingival area, particularly on the gingiva's labial side as well as; the prefe ence inci- dence for the pregnant female, tumor that sometimes grows at an accelerating rate. Lesions are more prevalent intra-orally in the anterior and younger age groups, are believed to be due to a hormonal im- pact on the vasculature. However, a few infections, such as Bartonella henselae, have been linked to recur- ring pyogenic granuloma(3). Oral PG is described clinically as a solitary soft mass that may be smooth or lobulated, sessile or nodule-like, or it can be a pedunculated growth. The color of the lesion varies from Received date: 9-9-2021 Accepted date: 10-11-2021 Published date: 15-6-2022 Copyright: © 2022 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licens es/by/4.0/). https://doi.org/10.26477/jbcd .v34i2.3142 https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://doi.org/10.26477/jbcd.v34i2.3142 https://doi.org/10.26477/jbcd.v34i2.3142 J. Bagh. Coll. Dent. Vol. 34, No. 2. 2022 Shareef and Abdullah 18 pink to red that changes according to its vascularity and tumor progression. There may be some blood flowing spontaneously or as a result of a trauma(2,4). Two common histopathological variants of PG were reported in previous studies. The first variant consists of lobular architecture including several small-sized capillaries lined by plump endothelial sep- arated by fibrous septa with a paucity of the inflammatory stromal cells called lobular-capillary heman- gioma (LCH). Non-lobular type PG (non-LCH) is the second histopathologic type characterized by highly vascular, diffusely arranged capillary proliferation resembling granulation tissue with heavy in- flammatory stroma(5,6). Numerous studies have previously investigated the clinicopathologic and im- munohistochemical characteristics of PG, but distinctions between PG's two histological variants are uncommon. To avoid diagnostic pitfalls associated with similar morphological lesions and to determine whether lobular and non-lobular histopathological subtypes are two distinct entities, the study aims were to re- view the clinical histopathological spectrum of an oral pyogenic granuloma from different intraoral sites. Materials and Methods A retrospective review of eighty formalin-fixed, paraffin-embedded tissue blocks reported as pyo- genic granuloma of the oral cavity were retrieved from the archives of the department of Oral & Maxil- lofacial Pathology/College of the Dentistry/University of Baghdad; from 1979 to 2017. Clinical and De- mographic data, including the patient's age, gender, and intraoral site of occurrence of PG, were ob- tained from the relevant histopathological reports that were available with the tissue specimens. Ac- cording to Mills, et al., 1980 criteria for lobular capillary hemangioma description, the diagnosis of each case was confirmed by the examination of H & E sections by an expert pathologists. The statistical anal- ysis was performed as follows: SPSS Version 23 was used to perform statistical analysis. A chi-squared test was applied to test statistical differences. Differences between studied variables were set as not sig- nificant P>0.05,significant P≤0.05, or highly significant (P≤0.01). Results A total of eighty cases (40 cases of males and 40 cases of females) of oral pyogenic granuloma were evaluated. The age ranges of patients with oral PG were from 12 to 59 years, with a mean age of 30.57year. There were no significant differences in the mean age of patients with PG between males (29.77 years) and females (31.37); Figure (1). Regarding the site, in the present study, equal numbers were collected in both males and females (16 cases from each: gingiva, buccal mucosa, tongue, palate, lips). Histopathological study of oral pyogenic granuloma cases revealed that 49 cases (61.25%) out of 80 were of lobular pattern, and 31 cases (38.7%) out of the 80 were of non-lobular pattern type PG. The higher number of cases and percentage of lobular pyogenic granuloma cases were detected in females, 25 cases (62.25%), at a young age (less than 15 years old and age (30-40) receptively, 10 cases (83.33%), and the most common cases were in the buccal mucosa12 cases (75%) While the number and of cases percentage of non-lobular pyogenic granuloma cases showed higher case numbers in the 21-30 years of age group, 12 cases (66.67%), and higher cases of non-LCH occurred in the palate, 9 cases (56.25%) J. Bagh. Coll. Dent. Vol. 34, No. 2. 2022 Shareef and Abdullah 19 There were non-significant differences between lobular and non-lobular pattern prevalence regarding age groups, gender; Table (1). Microscopically, both groups had two distinct components: an ulcerated surface and a deep section. In both groups, the ulcerated surface was equivalent, consisting of inflam- matory granulation tissue covered by a fibrinopurulent membrane. The deep part of the LCH group had lobular zones of tiny capillaries lined by plump endothelial cells separated by fibrous stroma with little or no inflammatory cell infiltration; Figures (2,3). The non-LCH type pyogenic granuloma in the deep part showed many dilated capillaries with a dispersed pattern comparable to that of the granulation tis- sue, which was more infiltrated by chronic inflammatory cells than the LCH type figures (4, 5). Table (1): Demographic description of studied cases (lobular and non-lobular pyogenic granulomas)concerining gender,age,and intraoral sites . Parameters Lobular Non-lobular Total P-value Gender 24(60%) 25(62.5%) 16(40%) 15(37.5%) 40 40 0.818 ns Males Females Age groups ≤15 16-20 21-30 31-40 41-50 >50 10(83.33%) 10(66.67%) 6(33.33%) 10(71.43%) 7(58.33%) 6(66.67%) 2(16.67%) 5(33.33%) 12(66.67%) 4(28.57%) 5(41.67%) 3(33.33) 12 15 18 14 12 9 0.097ns Site Gingiva Palate Lip Tongue Buccal muccosa 9(56.25%) 7(43.75%) 11(68.75%) 10(62.5) 12(75%) 7(43.75%) 9(56.25%) 5(31.25%) 6(37.5%) 4(25%) 16 16 16 16 16 0.477ns Total 49(61.25) 31(38.75) 80 χ 2 test, P<0.05 was selected to improve significant differences J. Bagh. Coll. Dent. Vol. 34, No. 2. 2022 Shareef and Abdullah 20 Figure (1): mean age of studied patients Independent t-test, ns =non-significant Figure (3-B): Photomicrograph lobular PG 40x B Figure (2-A): Photomicrograph lobular PG 10x A Figure (3-A): Photomicrograph lobular PG 40x Figure (2-B): Photomicrograph lobular PG 10x B A J. Bagh. Coll. Dent. Vol. 34, No. 2. 2022 Shareef and Abdullah 21 Discussion Because the oral mucosa is continuously being influenced by external and internal factors, which could be lead to developmental disorders, irritants, inflammatory responses, as well as benign and\or malignancies. These lesions mimic benign and /or malignant clinically. Early identification and treat- ment of such lesions by clinicians may minimize dentoalveolar consequences. This better understanding could help practitioners improve diagnoses and provide appropriate management (7). Pyogenic granuloma is a vascular growth that occurs quite often on the mucosal surface epithelium and subcutaneous tissue. The term granuloma pyogenicum (pyogenic granuloma) was coined by Hartzell in 1904; while in 1980, the name "lobular capillary hemangioma" (LCH) was pub- lished as the synonym for pyogenic granuloma according to histological characteristics (5,8). The prevalence of oral PG varied across investigations, ranging from 1.85 percent to 37 percent of reported oral lesions in previous research (9). The clinicopathological findings of the present study re- vealed that the mean age for the occurrence of pyogenic granuloma was 30.57 years, and a higher num- ber of cases and percentage of lobular pyogenic granuloma cases were detected in females, 25 cases (62.25%). These findings concur with previous studies (10,11). This may reflect a hormonal impact on mu- cosal lesions (10,12,13). The gingiva was found to be the most often seen intraoral site of PG incidence. Fol- lowing common sites intraorally were the lips, tongue, buccal mucosa, and palate (13). A Figure (4-A): Photomicrograph non-lobular PG 10x Figure (5-A): Photomicrograph non-lobular PG 40x A B Figure (4-B): Photomicrograph non-lobular PG 10x B Figure (5-B): Photomicrograph non-lobular PG 40x J. Bagh. Coll. Dent. Vol. 34, No. 2. 2022 Shareef and Abdullah 22 Although our study involved 16 cases from the gingiva, buccal mucosa, lips, tongue, and palate equally. As well as for both genders. The most striking histopathological feature was detected in all examined oral PG cases was the presence of significant capillary development inside the hyperplastic granulation tissue, indicating the presence of robust angiogenic activity in both histological subtypes (lobular and non-lobular). The histological types of PG have been studied in many prior clinicopatho- logical investigations, some of which included both LCH and non-LCH histopathological subtypes. Some of these studies have shown clinical, histological, and immunohistochemical distinctions between LCH and non-LCH PG. (2,6); which agrees partially with our study findings that showed statistically clinicopathological differences between lobular and non-lobular subtypes. However, this study did not include immunohistochemical (IHC) makers to support our results. Even though immunohistochemistry may help exclude some alternative diagnoses and identify growth features, no immunohistochemical marker was specific for LCH, and diagnosis is often made using morphologic criteria. (14). In addition, it is still not obvious how the many etiological factors contribute to the various histo- logical types of PG. Accordingly, The oral PG may appear differently, creating a diagnostic challenge for the treating surgeon. As a consequence of an overactive tissue repair reaction, it's a begin vascular tumor. The diagnosis is confirmed by a histopathological assessment, which also excludes out other soft tissue lesions that seem similar. The most significant differential diagnoses are as follows: Hemangioma, pe- ripheral giant cell granuloma, peripheral ossifying fibroma, Hodgkin’s lymphoma, and conventional granulation as well as, for capillary-type vascular tumors. The presence of giant cells or scattered ossifications inside the tumor stroma assists in ruling out peripheral giant cell granuloma, peripheral ossifying fibroma, or both to rule out are Kaposi sarcoma and low-grade angiosarcoma. lobular capillary hemangioma endothelial cells may be somewhat spin- dled. However, in Kaposi sarcoma, the spindle cells are elongated and organized in a slit-like pattern, forming pseudo-vascular blood-filled areas. Unlike capillary hemangioma and its variations, Kaposi sarcoma lacks conspicuous endothelial cells. Human herpesvirus type 8 (HHV8) has been detected in Kaposi sarcoma and, if present, may help confirm the diagnosis, Additionally, nuclear atypia and pleo- morphism are required for the diagnosis of angiosarcoma. While mitotic figures may be observed throughout the proliferative phase of lobular-capillary hemangioma in children and adults, the mitotic index is much increased in angiosarcoma, and the mitoses often take on unusual configurations. Neither angiosarcoma nor Kaposi sarcoma has an overall lobular architecture; rather, they develop infiltrating. The preferred method of cure is surgical excision. After surgical excision, recurrence is very uncommon (11,15,16). According to the results, this study proposed that LCH and non-LCH subtypes reflect distinct phases in the development of a single lesion (PG), which exhibits variable degrees of proliferative, angi- ogenic, and inflammatory activities. Our suggestion is the usage of the descriptive term "lobular capil- lary hemangioma" as a suitable alternative term (PG) in the oral cavity. Further research with larger sample size and molecular methods is suggested to confirm or refute this study assumption. Conflict of interest: None. J. Bagh. Coll. Dent. Vol. 34, No. 2. 2022 Shareef and Abdullah 23 References 1. Kapadia SB, Heffner DK. Pitfalls in the histopathologic diagnosis of pyogenic granuloma. Eur Arch Oto-Rhino-Laryngology. 1992;249(4):195–200. 2. Epivatianos A, Antoniades D, Zaraboukas T, et al. Pyogenic granuloma of the oral cavity: Comparative study of its clinicopathological and immunohistochemical features. Pathol Int. 2005;55(7):391–7. 3. Krishnapillai R, Punnoose K, Angadi P V, et al. Oral pyogenic granuloma-a review of 215 cases in a South Indian Teaching Hospital, Karnataka, over a period of 20 years. Oral Maxillofac Surg. 2012;16(3):305–9. 4. Vázquez‐Martínez OT, González‐Betancourt A, Barboza‐Cerda MC, et al. Human papillomavirus type 2 associated with pyogenic granuloma in patients without clinical evidence of warts. Int J Dermatol. 2016;55(7):745–50. 5. 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(5):470–9. 6. Rezvani G, Azarpira N, Bita G, et al. Proliferative activity in oral pyogenic granuloma: a comparative immunohistochemical study. Indian J Pathol Microbiol. 2010;53(3):403. 7. Kadeh H, Saravani S, Tajik M. Reactive hyperplastic lesions of the oral cavity. Iran J Otorhinolaryngol. 2015;27(79):137–44. 8. Graham RM. Pyogenic granuloma: an unusual presentation. Dent Update. 1996;23(6):240–1. 9. Agel M, Ahluwalia M. Unusual Presentation of a Pyogenic Granuloma in a 6-Year-Old Child. Dent Update. 2020;47(2):149–52. 10. Toida M, Hasegawa T, Watanabe F, et al. Lobular capillary hemangioma of the oral mucosa: Clinicopathological study of 43 cases with a special reference to the immunohistochemical characterization of the vascular elements. Pathol Int. 2003;53(1):1–7. 11. Al-Noaman AS. Pyogenic granuloma: Clinicopathological and treatment scenario. J Indian Soc Periodontol. 2020;24(3):233. 12. Harris MN, Desai R, Chuang TY, et al. Lobular capillary hemangiomas: An epidemiologic report, with emphasis on cutaneous lesions. J Am Acad Dermatol. 2000;42(6):1012–6. 13. Isaza-Guzmán DM, Teller-Carrero CB, Laberry-Bermúdez MP,et al. Assessment of clinicopathological characteristics and immunoexpression of COX-2 and IL-10 in oral pyogenic granuloma. Arch Oral Biol [Internet]. 2012 May;57(5):503–12. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0003996911003827 14. Fortna RR, Junkins-Hopkins JM. A case of lobular capillary hemangioma (pyogenic granuloma), localized to the subcutaneous tissue, and a review of the literature. Am J Dermatopathol. 2007;29(4):408–11. 15. Stagner AM, Jakobiec FA. A Critical Analysis of Eleven Periocular Lobular Capillary Hemangiomas in Adults. Am J Ophthalmol [Internet]. 2016;165:164–73. Available from: http://dx.doi.org/10.1016/j.ajo.2016.03.010 16. Parajuli R, Maharjan S. Unusual presentation of oral pyogenic granulomas: a review of two cases. Clin Case Reports. 2018;6(4):690–3. J. Bagh. Coll. Dent. Vol. 34, No. 2. 2022 Shareef and Abdullah 24 لـ المرضي السريري ال 80التحليل الفموية الدموية الشعيرات من الصفصمحالة وغير حبيبي ةصصفمة )ورم وعائي ورم رجعيقيحي(: دراسة بأثر (2) عبدهللا حامد، بشار (1) شريف ناجح كرار المستخلص: حالة من الورم الوعائي الحبيبي الشعري المفصص في الفم )ورم حبيبي قيحي(: دراسة بأثر 80التحليل النسيجي المرضي اإلكلينيكي لـ يتطور بسبب تفاعل األنسجة مع مجموعة متنوعة من المحفزات مثل التهيج ( هو كيان إكلينيكي يمكن أن PGالخلفية: الورم الحبيبي القيحي الفموي ) رجعي الورم الوعائي -النوع الفصيصي -الموضعي منخفض الدرجة والضرر الناتج عن الصدمات وتحفيز الهرمونات. هناك نوعان من الورم الحبيبي القيحي نتشر للغاية بينما يحاكي البديل غير الفصيص األنسجة الحبيبية ذات السدى لديه نمو شعري وعائي م PG.LCH( والنوع غير الفصيصي LCHالشعري ) حالة لكل من الذكور واإلناث( من 40االلتهابي الثقيل.المواد وطرق العمل : تمت مراجعة ثمانين عينة نسيجية مثبتة بالفورمالين و مضمنة بالبارافين ) . بالنسبة لمعايير ميلز وآخرون لوصف الورم الوعائي الشعري 2017إلى 1979اد. مؤرخة في الفترة من أرشيف أمراض الفم والوجه والفكين في جامعة بغد راض. الفصيصي ، تم تأكيد تشخيص كل حالة من خالل فحص المقاطع المصبوغة بالهيماتوكسيلين واأليوزين من قبل اثنين من المتخصصين في علم األم ٪( من أصل 61.25حالة ) 49سنة. 30.57سنة ، بمتوسط 59إلى 12( تراوحت أعمارهم من P.Gورم الحبيبي القيحي )النتائج: المرضى الذين يعانون من ال حالة 12في الغشاء المخاطي الشدق ، LCH. كان الموقع األكثر شيوًعا لـ p.G٪( من النمط غير الفصيصي 38.7حالة ) 31كانت من النمط الفصيصي و 80 عاًما. ال توجد فروق ذات داللة إحصائية بين انتشار النمط الفصيصي وغير الفصيصي 30-21رتفاع أعداد الحاالت في الفئة العمرية ٪( ، بينما لوحظ ا75) فيما يتعلق بالفئات العمرية باالضافة الى عدم وجود فروق احصائية المتغيرات المدروسة األخرى. تعكس مراحل متميزة في تطور آفة واحدة ، والتي تظهر درجات متغيرة LCHوغير LCHألنواع الفرعية االستنتاجات: يستنتج من البحث اعاله هو أن ا من األنشطة التكاثرية ، وتولد األوعية ، وانتشار كثيف للخاليا االلتهابية في الورم.