Oral Pyogenic Granuloma: a Review

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Journal of Oral Science, Vol. 48, No. 4, 167-175, 2006 Review Oral pyogenic granuloma: a review

Hamid Jafarzadeh1), Majid Sanatkhani2) and Nooshin Mohtasham3)

1)Department of Endodontics, Faculty of Dentistry, Mashad University of Medical Sciences, Mashad, Iran 2)Department of Oral Medicine, Faculty of Dentistry, Mashad University of Medical Sciences, Mashad, Iran 3)Department of Oral Pathology, Faculty of Dentistry, Mashad University of Medical Sciences, Mashad, Iran

(Received 29 June and accepted 11 August 2006)

Abstract: Pyogenic granuloma is one of the inflammatory hyperplasias seen in the oral cavity. This Introduction term is a misnomer because the lesion is unrelated to Pyogenic granuloma (PG) is a kind of inflammatory infection and in reality arises in response to various hyperplasia. The term “inflammatory hyperplasia” is used stimuli such as low-grade local irritation, traumatic to describe a large range of nodular growths of the oral injury or hormonal factors. It predominantly occurs mucosa that histologically represent inflamed fibrous and in the second decade of life in young females, possibly granulation tissues (1,2). It includes fibrous inflammatory because of the vascular effects of female hormones. hyperplasia (clinical fibroma, epulis fissuratum, and pulp Clinically, oral pyogenic granuloma is a smooth or polyp), palatal papillary hyperplasia, giant cell granuloma, lobulated exophytic lesion manifesting as small, red pregnancy epulis and PG (2). erythematous papules on a pedunculated or sometimes PG is a common tumor-like growth of the oral cavity sessile base, which is usually hemorrhagic. The surface or skin that is considered to be non-neoplastic in nature ranges from pink to red to purple, depending on the (3,4). Hullihen’s description (5) in 1844 was most likely age of the lesion. Although excisional surgery is the the first PG reported in English literature, but the term treatment of choice for it, some other treatment “pyogenic granuloma” or “granuloma pyogenicum” was protocols such as the use of Nd:YAG laser, flash lamp introduced by Hartzell (6) in 1904. Although it is a common pulsed dye laser, cryosurgery, intralesional injection of disease in the skin, it is extremely rare in the gastrointestinal ethanol or corticosteroid and sodium tetradecyl sulfate tract, except for the oral cavity (7) where it is often found sclerotherapy have been proposed. Because of the high on keratinized tissue (8). There are two kinds of PG namely frequency of pyogenic granuloma in the oral cavity, lobular capillary hemangioma (LCH type) and non-LCH especially during pregnancy, and necessity for proper type, which differ in their histological features (9). diagnosis and treatment, a complete review of published Because of the high incidence of oral PG, especially in information and investigations about this lesion, in pregnant women, and the critical need for its proper addition to knowledge about new approaches for its diagnosis, management and treatment, this review will treatment is presented. (J. Oral Sci. 48, 167-175, 2006) address the etiology, clinical and histopathologic features and its correlation with pregnancy. This paper will also Keywords: inflammatory hyperplasia; oral cavity; review the differential diagnosis as well as new treatment pregnancy; pyogenic granuloma. approaches for PG.

Etiology and Epidemiology Correspondence to Dr. Hamid Jafarzadeh, Mashad Dental School, While some investigators (10) regard PG as a benign P.O. Box: 91735-984, Vakilabad Blv, Mashad, Iran neoplasm, it is usually considered to be a reactive tumor- Tel: +98-511-8829501 Fax: +98-511-7626058 like lesion which arises in response to various stimuli E-mail: [email protected] such as a chronic low-grade local irritation (3,11), traumatic 168 injury, hormonal factors (12) or certain kinds of drugs (13). activity of the tumor cells but also on the rate of cell death. Although it was originally thought to be caused by pyogenic Nakamura (28) suggested that the low apoptotic rate in PG organisms, it is now believed to be unrelated to infection is closely related to its rapid growth and is regulated by (2,3). So the term “pyogenic granuloma” is a misnomer Bcl-2 family proteins. because the lesion does not contain pus and is not strictly Although PG may occur in all ages (29,30), it is speaking a granuloma (1,3,11,14). It should be emphasized predominant in the second decade of life in young adult that as infective organisms such as Bartonella henselaea females, possibly because of the vascular effects of female (peliosis hepatis), B. henselae and B. quintana (bacillary hormones (1,3,11). Studies done in Jordanian (29) and angiomatosis), and human herpes virus type 8 (Kaposi’s Singaporean (31) populations were in agreement with this sarcoma and angiolymphoid hyperplasia) have been finding. In contrast, a recent study reported that the average identified in other vascular tumors, some authors have patient age was 52 years with a peak incidence of postulated that infective agents may play a part in recurrent occurrence in the sixth decade of life (9). Some authors PG. However, there is no evidence confirming the presence believe that patients are mostly males under 18 years of of infectious organisms in larger groups of PGs (15). age, females in the age range 18 to 39, and older patients Approximately one third of the lesions occur after with an equal gender distribution (16). Epivatianos et al. trauma (16), so the history of trauma before development (9) reported predominance in women (1:1.5) and the of this lesion is not unusual, especially for extragingival presence of etiological factors in 16% of cases, whereas, PGs (3,17). Poor oral hygiene may be a precipitating non-LCH PG was associated more frequently (86%) with factor in many of these patients (1,3,11). Aguilo (18) etiological factors. reported the formation of PG as a result of an injury to a Oral PG, which in reality is the most common gingival primary tooth and Milano et al. (19) reported a case of PG tumor (32), shows a striking predilection for the gingiva associated with aberrant tooth development. accounting for 75% of all cases, where they are presumably Some factors such as inducible nitric oxide synthase (20), caused by calculus or foreign material within the gingival vascular endothelial growth factor (21), basic fibroblast crevice. The lips, tongue, and buccal mucosa are the next growth factor (22) or connective tissue growth factor (23) most common sites (1,3,11). Lesions are slightly more are known to be involved in angiogenesis and rapid growth common on the maxillary gingiva than the mandibular of PG. gingiva; anterior areas are more frequently affected than Additionally, some drugs such as cyclosporine have an posterior areas. Also, these lesions are much more common important role in the genesis of PG. Bachmeyer et al. (24) on the facial aspect of the gingiva than the lingual aspect; and Lee et al. (25) reported four cases of oral PG in chronic some extend between the teeth and involve both the facial graft-versus-host disease in patients who were under and lingual gingiva (3). According to Vilmann et al. (4), cyclosporine. Also, some iatrogenic stimulations in dental majority of PGs are found on the marginal gingiva with practice may cause PG. Fowler et al. (8) first reported a only 15% of the tumors on the alveolar part. case in which PG was found associated with guided tissue regeneration. The lesion arose after demineralized freeze Clinical Features dried bone allograft with an expanded polytetra- Clinically, PG is a smooth or lobulated exophytic lesion fluoroethylene membrane were utilized to repair osseous manifesting as small, red erythematous papules on a defects. Oral complications occur after bone marrow pedunculated or sometimes sessile base, which is usually transplantation (BMT) due to regimen-related toxicity of hemorrhagic and compressible (1,3,11) and may develop the preparative regimen, and others by infections. Although as dumb-bell-shaped masses (14). However, Epivatianos oral granulomatous lesions are not common after BMT, et al. (9) reported that the two types of PG were clinically Kanda et al. (26) presented a patient who developed PG different. They found that LCH PG occurred more of the tongue early after allogenic BMT done for multiple frequently (66%) as a sessile lesion, whereas non-LCH PG myeloma. mostly occurred as pedunculated (77%). In 1980, Davies et al. (27) found inclusion bodies in the The size varies in diameter from a few millimeters to fibroblasts suggestive of disordered protein metabolism. several centimeters (3,11). Rarely does PG exceed 2.5 cm They suggested that PG constitutes a lesion produced by in size and it usually reaches its full size within weeks or a primitive tissue organizer resulting from gene de- months, remaining indefinitely thereafter (14). Clinical repression in the papillary fibroblasts, perhaps the result development of the lesion is slow, asymptomatic and of a C-type virus infection. It should be noted that the painless (3, 11) but it may also grow rapidly (33). The growth rate of tumors depends not only on the proliferative surface is characteristically ulcerated and friable (2) which 169 may be covered by a yellow, fibrinous membrane (11) and Factor (bFGF) and Transforming Growth Factor beta1 its color ranges from pink to red to purple, depending on (TGF-β1) production in fibroblasts, leading to granulation the age of the lesion. Young PGs are highly vascular in tissue formation. Estrogen enhances Vascular Endothelial appearance (3) because they are composed predominantly Growth Factor (VEGF) production in macrophages, an of hyperplastic granulation tissue in which capillaries are effect that is antagonized by androgens and which may be prominent. Thus minor trauma to the lesion may cause related to the development of PG during pregnancy. These considerable bleeding, due to its pronounced vascularity regulatory effects of sex steroids may be manipulated as (3,11), whereas older lesions tend to become more therapeutic or prophylactic measures in PG (40). Ojanotko- collagenized and pink (3). Rarely, PG may cause significant Harri et al. (41) suggested that progesterone functions as bone loss, as reported by Goodman-Topper and Bimstein an immunosuppressant in the gingival tissues of pregnant (34). women, preventing a rapid acute inflammatory reaction against plaque, but allowing an increased chronic tissue Correlation with Pregnancy reaction, resulting clinically in an exaggerated appearance PG of the gingiva develops in up to 5% of pregnancies of inflammation. Yuan et al. (42) proposed that PG (35), hence the terms “pregnancy tumor” and “granuloma expressed significantly more VEGF and bFGF than healthy gravidarum” are often used (3). The hormonal imbalance gingiva and periodontium. Also, angiostatin was expressed coincident with pregnancy heightens the organism’s significantly less in PG than in healthy gingiva and response to irritation (1), however, bacterial plaque and periodontally involved gingiva. gingival inflammation are necessary for subclinical It should be noted that the molecular mechanism for hormone alterations leading to gingivitis (36). The regression of pregnancy PG after parturition remains development of this particular kind of gingivitis, typical unclear. It has been proposed that, in the absence of VEGF, in pregnancy, not different from that appearing in non- Angiopoietin-2 (Ang-2) causes blood vessels to regress. pregnant women, suggests the existence of a relationship Yuan and Lin (43) proposed that Tumor Necrosis Factor- between the gingival lesion and the hormonal condition α (TNF-α) upregulated the expression of Ang-2 in all observed in pregnancy. Sometimes pregnancy gingivitis endothelial cell types tested. The protein level of Ang-2 can show a tendency towards localized hyperplasia, which was highest in the granulomas in pregnancy, followed by is called pregnancy granuloma. Generally it appears in the those after parturition and normal gingiva. The amount of 2nd - 3rd month of pregnancy, with a tendency to bleed VEGF was high in the granulomas in pregnancy and and a possible interference with mastication (37). During almost undetectable after parturition. After parturition, the first months of pregnancy, the persistent influence of there are more apoptotic cells and less Ang-2 than in plaque induces catarrhal inflammation of the gingiva that pregnancy, so VEGF alone or in combination with Ang- serves as a base for development of hyperplastic gingivitis 2 could protect microvessels from apoptosis, while Ang- during the last months, modulated by the cumulating 2 alone had no effect. hormonal stimuli. In uncontrolled cases, PG may arise. This Characteristic oral manifestations of hormonal oral lesion is rarely observed in women with poor oral hygiene contraceptive intake are similar to oral changes associated in areas with local irritating factors such as improperly with pregnancy, such as the pronounced vascularity of fitting restorations or dental calculus. During pregnancy, the gingiva, hyperplastic gingivitis, and PG. How oral PG when treated by surgical excision may reappear due contraceptives influence vascular changes in the to incomplete excision or inadequate oral hygiene (38). periodontium is unclear; prostaglandin E2 may be The molecular mechanisms behind the development implicated as a possible mediator of the inflammatory and regression of PG during pregnancy have been process (44). On the other hand, Nichols et al. (45) indicated extensively studied. The profound endocrine upheaval of that despite the PG relationship to pregnancy and oral pregnancy is frequently associated with changes in the contraceptive pills, the periodontium lacks steroid hormone function and structure of the blood and lymph receptors which suggests that estrogen or progesterone are microvasculature of the skin and mucosa. (39) Recent not directly involved in formation of this lesion. studies have revealed that sex hormones manifest a variety of biological and immunological effects. Estrogen Histopathology accelerates wound healing by stimulating Nerve Growth Microscopic examination of PG shows a highly vascular Factor (NGF) production in macrophages, Granulocyte- proliferation that resembles granulation tissue (3). Macrophage-Colony Stimulating Factor (GM-CSF) Numerous small and large channels are formed which are production in keratinocytes and basic Fibroblast Growth engorged with red blood cells (1,3) and lined by banal flat 170 or plump endothelial cells that may be mitotically active capillary phase, the lobules become frankly vascular with (16). The blood vessels often show a clustered or medullary abundant intra-luminal red blood cells. One or more central pattern separated by less vascular fibrotic septa, leading vessels develop a large lumen with a thick muscular layer some authorities to consider PG as a polypoid form of resembling a vein. In the involutionary phase, there is a capillary hemangioma or nothing more than an inflamed tendency for intra- and perilobular fibrosis with increased lobular hemangioma; others prefer to use the term venular differentiation (32). granulation tissue-type hemangioma (14). Some There are two histological types of PG. The first type pathologists require these vessels, which are sometimes is characterized by proliferating blood vessels that are organized in lobular aggregates, for diagnosis (lobular organized in lobular aggregates although superficially the capillary hemangioma) (3,11,46). lesion frequently undergoes no specific change, including At low magnification, particularly at the lateral edges, edema, capillary dilation or inflammatory granulation a lobular arrangement is noted wherein groups of capillaries tissue reaction. This histological type of PG was called proliferate but abruptly stop. Each lobule is surrounded by lobular capillary hemangioma (LCH type) (10), whereas a thin collagen layer. This arrangement is disrupted at the the second type (non-LCH type) consists of highly vascular base, where irregularly shaped larger vascular channels proliferation that resembles granulation tissue (3, 14). reside and presumably communicate with the proliferation. The lobular area of the LCH PG contains a greater number It is here that some anastomosing channels (resembling of blood vessels with small luminal diameter than does the angiosarcoma) can occasionally be identified, but they central area of non-LCH PG. In the central area of non- are focal rather than an integral part of the lesion. At LCH PG, a significantly greater number of vessels with higher magnification, another discriminating feature of perivascular mesenchymal cells non-reactive for α-smooth benign vascular lesion is found: the small capillary muscle actin and muscle-specific actin is present than in endothelial-lined spaces are themselves surrounded by a the lobular area of LCH PG. These differences suggest that perithelial or pericytic layer of cells. This double layer of two histological types of PG represent distinct entities cells, also seen in intramuscular angiomatosis, is not seen (9). Toida et al. (49) found that the presence of blood in the clonal angiosarcoma (32). vessels with different luminal diameter in the lobular area Polymorphs, as well as chronic inflammatory cells, are of LCH PG and in the central area of non-LCH PG may consistently present throughout the edematous stroma, be because different pathogenic factors influence their with micro-abscess formation (2). The fibroblasts are development. Epivatianos et al. (9) observed that foci of typically plump and mitotic activity may be noted in the fibrous maturation were present in 15% of non-LCH PG stromal cells. Older lesions demonstrate fewer and more but were totally absent in LCH PG. Although it is possible mature cells, which are fibrocytes. Occasional lesions that PG can undergo fibrous maturation, they showed that demonstrate an extreme predominance of plasma cells, this happened only in non-LCH PG which suggests that prompting some pathologists to call them plasma cell the two types of PG have different pathways of evolution. granuloma, a term that is best avoided because of the potential confusion with mucosal solitary plasmacytoma Differential Diagnosis or multiple myeloma. Rare examples of intravenous PG When a mass is found in the oral cavity, it is important have been reported (47). to formulate a differential diagnosis since this would help Some scarring may be noted in some of these lesions, further evaluation of the condition and management of the suggesting that occasionally there may be maturation of patient (48). Biopsy findings have an important role and the connective tissue repair process (11). The surface of are definitive in establishing the diagnosis. (11) Differential the lesion may undergo secondary, nonspecific changes that diagnosis of PG includes peripheral giant cell granuloma, include stromal edema, capillary dilation, inflammation, peripheral ossifying fibroma, metastatic cancer (1,11), and granulation tissue reaction (48). The surface is usually hemangioma (1,11,16,47,50), pregnancy tumor (37), ulcerated and replaced by a thick fibrin purulent membrane conventional granulation tissue, hyperplastic gingival (3). A mixed inflammatory cell infiltrate of neutrophils is inflammation (47,50), Kaposi’s sarcoma, bacillary mostly prevalent near the ulcerated surface; chronic angiomatosis (16,47,50), angiosarcoma (16), and Non- inflammatory cells are found deeper in the specimen (3, Hodgkin’s lymphoma (51). 11). Peripheral giant cell granuloma (PGCG) is an exophytic In brief, the natural history of the lesion follows three lesion that is seen exclusively in the gingiva (2) and is distinct phases. In the cellular phase, the lobules are clinically similar to PG (11), but PGCG is often more compact and cellular with little lumen formation. In the bluish-purple compared to the bright red of a typical PG 171

(3). Although PGCG is more likely to cause bone resorption the validity of the clinical term “pregnancy tumor”. On the than a PG, the differences are otherwise minimal. Generally, basis of its clinical presentation and histologic appearance, this lesion is clinically indistinguishable from a PG but the some authors believe that it simply represents a PG, features that set PGCG apart from other reactive whereas others believe that the lesion is unique because hyperplasias are the appearance of multinucleated giant of the apparent influence of female sex hormones (56). cells (11) and lack of infectious source (1). Increased prevalence of pregnancy epulis toward the end Depending on its duration, PG will vary in texture from of pregnancy and the tendency for this lesion to shrink after soft to firm, and can be suggestive of a fibroma (1,11) so delivery indicate a definitive role for hormones in the peripheral odontogenic or ossifying fibroma may be another etiology of the lesion. (2,57) According to Ojanotko-Harri consideration, although these tend to be much lighter in et al. (41), there is no clinical and histological difference color (11). Also, it is usually about 1.5 cm in diameter, between pregnancy tumor and PG that occurs in non- although some have reached 6 cm in diameter (52). Like pregnant patients but some authors believe that unlike PG, it is commonly encountered among pregnant women PG, pregnancy tumor is usually confined to the interdental but unlike PG, this lesion is found exclusively on the papilla (57). Daley et al. (56) indicated that diagnosis of gingiva (2), and has a minimal vascular component (11). pregnancy tumor is valid clinically in describing a PG Although metastatic tumors to the oral region are occurring in pregnancy, because it describes a distinct uncommon, the attached gingiva is the most common lesion not on the basis of histologic features but on etiology, affected soft tissue site followed by the tongue. In nearly biologic behavior, and treatment protocol. 30% of cases, the metastatic lesion in the oral region is Conventional granulation tissue is another differential the first indication of an undiscovered malignancy at a diagnosis that should be considered. Despite the close distant site (53) so the microscopic appearance should relationship between PG and conventional granulation resemble the tumor of origin (3). Hirshberg et al. (54) tissue, PG shows clinically different behavior, such as analyzing 157 cases, reported that most cases (64%) were rapid growth, multiple occurrence and frequent recurrence, diagnosed in patients in their fifth to seventh decade which from those in granulation tissue (47,50,58,59). is different from PG. The clinical appearance of the Hyperplastic gingival inflammation should also be metastatic oral lesion in most cases resembled hyperplastic considered. The histopathologic differentiation of PG or reactive lesions such as PG. from hyperplastic gingival inflammation is sometimes One important differential diagnosis of PG is impossible, and the pathologist must depend on the hemangioma which is a developmental disorder (1,2), but surgeon’s description of a distinct clinical mass to diagnose small lesions may be clinically indistinguishable from the granuloma (14). Kaposi’s sarcoma of Acquired PG. Diascopy, the technique of applying pressure to a Immuno-Deficiency Syndrome (AIDS) shows proliferation suspected vascular lesion to visualize the evacuation of of dysplastic spindle cells, vascular clefts, extravasated coloration, supports the fact that patent blood-filled spaces erythrocytes and intracellular hyaline globules, none of constitute the lesion. Most oral hemangiomas are located which are features of PG (14). The initial diagnosis of on the tongue, where they are multinodular and bluish red Kaposi’s sarcoma requires microscopic evaluation of (2). In comparison with PG, hemangioma has more plump, biopsy material because this disease can mimic a number histiocytoid, endothelial cell proliferation without an acute of intraoral lesions such as PG, bacillary angiomatosis, inflammatory cell infiltrate (47,50). Freitas et al. (55) hemangioma, and lymphoma (60). evaluated the immuno-histochemical expression of VEGF- Bacillary angiomatosis, also AIDS-related, shows dense, C1 and showed that there was no statistically significant extracellular deposits of pale hematoxyphilic granular difference in the angiogenesis index between PG and material representing masses of bacilli that stain positive hemangioma. There was no statistically significant with Warthin-Ostarry stain (14). difference between the lesions in the number of cells PG can be distinguishable from angiosarcoma by its highlighted by staining for VEGF-C1. The VEGF-positive lobular growth pattern, well-formed vessels, and cells in PG were macrophages and fibroblasts. These cytologically bland endothelial cells (16). Another results affirm the role of angiogenic factors in the consideration is Non-Hodgkin’s lymphoma (NHL) of etiopathogenesis of hemangioma and PG, however, it which primary sites in the head and neck are Waldeyer’s showed that microvessel quantification is not useful in the ring, paranasal sinuses, salivary glands, the oral cavity, and differential diagnosis of these lesions. the larynx. Clinical appearance of gingival NHL varies but Another differential diagnosis is pregnancy tumor is usually found to be an asymptomatic gingival (pregnancy epulis) (37). There is some disagreement about enlargement or mass resembling a PG (51). 172

Treatment by both the specific and the nonspecific actions of STS, Although many treatment techniques have been described which specifically causes endothelial cell damage and for PG, when it is large or occurs in a surgically difficult obliterates vessel lumina. Moreover, infiltrations of STS area, choosing an appropriate treatment modality can be into stromal tissues can cause nonspecific necrotic changes. difficult (35). Excisional biopsy is indicated for treatment Also, Parisi et al. (33) used a series of intralesional of PG, except when the procedure would produce marked corticosteroid injections for treatment of PG, particularly deformity; in such a case, incisional biopsy is mandatory for highly recurrent lesions. (2). So, management of PG depends on the severity of Treatment considerations during pregnancy are very symptoms. If the lesion is small, painless and free of important. During this period, careful oral hygiene, removal bleeding, clinical observation and follow up are advised of dental plaque, and use of soft toothbrushes are important (35). Although conservative surgical excision and removal to avoid occurrence of a pregnancy tumor. If uncontrolled of causative irritants (plaque, calculus, foreign materials, bleeding occurs, management should be based on the source of trauma) are the usual treatments (1,3,11,61) for individual condition and should range from supportive gingival lesions, the excision should extend down to the therapy such as desiccation of bleeders; local, firm periosteum and the adjacent teeth should be thoroughly compression and oral hygiene to blood transfusion, as scaled to remove the source of continuing irritation (3). well as medication to accelerate fetal lung maturity or even Recently, some other treatment protocols, instead of termination of pregnancy to save the patient's life, as with excisional surgery, have been proposed. Powell et al. (62) treatment of uncontrollable eclampsia (68). Steelman and reported the use of Nd:YAG laser for excision of this Holmes (69) believed that maintenance of oral hygiene and lesion because of the lower risk of bleeding compared to regular follow up appointments should be recommended other surgical techniques. They chose the Nd:YAG laser while pregnant. Surgical and periodontal treatment should over the CO2 laser, because of its superior coagulation be completed, when possible, during the second trimester, characteristics. White et al. (63) proposed that laser excision with continued surveillance of home care until after delivery is well tolerated by patients with no adverse effects. They (2) but some authors believe that in the gravid patient, also stated that CO2 and Nd:YAG laser irradiation is recurrence is likely and treatment, to be successful, should successful in surgical treatment. await parturition (1). In pregnant women, lesional shrinkage Meffert et al. (64) used the flash lamp pulsed dye laser after the birth may make surgery unnecessary (14). on a mass of granulation tissue which did not respond to After excision, recurrence occurs in up to 16% of the the usual treatment methods and concluded that previously lesions (70) so in some cases re-excision is necessary resolute tissue responded well to a series of treatments with (1,3,11). Recurrence is believed to result from incomplete the pulsed dye laser. Ishida and Ramos-e-Silva (65) believed excision, failure to remove etiologic factors, or re-injury that cryosurgery is a very useful technique for treatment of the area (11). Some recurrences manifest as multiple of PG. They stated that oral mucosa, because of its humidity deep satellite nodules that surround the site of the original and smoothness is an ideal site for this technique. It shows lesion (Warner-Wilson Jones syndrome) (70). It should be a very good esthetic result and it may be either the first emphasized that gingival cases show a much higher choice or an alternative option to conventional surgery. recurrence rate than lesions from other oral mucosal sites Although conservative treatment by techniques such as (4). cryosurgery, laser surgery, and electrodessication are usually adequate, excisional treatment can often result in Conclusion scars, so Ichimiya et al. (66) attempted a different approach Although pyogenic granuloma is a non-neoplastic growth using an injection of absolute “ethanol” in patients with in the oral cavity, proper diagnosis, prevention, management recurrence due to inadequate cryosurgery and concluded and treatment of the lesion are very important. Pyogenic that this therapy was less invasive than surgical excision granuloma arises in response to various stimuli such as low- and appeared to be an alternative therapy for PG. grade local irritation, traumatic injury, sex hormones or Moon et al. (67) reported that sodium tetradecyl sulfate certain kinds of drugs, so removal of causative irritants (STS) sclerotherapy successfully cleared the lesions in most (plaque, calculus, foreign materials, and source of trauma) patients, without major complications. They believe that is the major line of treatment. Excisional surgery is the this technique offers a better alternative than excision treatment of choice for pyogenic granuloma, but some new because of its simplicity and lack of scarring, even though approaches for treatment such as cryosurgery, excision by multiple treatment sessions are required. The mechanism Nd:YAG laser, flash lamp pulsed dye laser, injection of of the therapeutic effects of their technique may be mediated ethanol or corticosteroid and sodium tetradecyl sulfate 173 sclerotherapy have been reported as alternative therapies. pyogenic granuloma as a complication of pregnancy In spite of these treatments, recurrence is not infrequent and the use of hormonal contraceptives. Int J so in some cases re-excision may be necessary. It should Gynaecol Obstet 14, 187-191 be emphasized that one important point about pyogenic 13. Miller RA, Ross JB, Martin J (1985) Multiple granuloma is the effect of sex hormonal imbalances during granulation tissue lesions occurring in isotretinoin pregnancy which is one of the most common causes of treatment of acne vulgaris – successful response to pyogenic granuloma. During pregnancy, careful oral topical corticosteroid therapy. 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