Review Article Granulomatous conditions in the oral cavity – A review N. Vidulasri, M. P. Brundha* ABSTRACT Granulomatous diseases represent a unique form of the chronic inflammatory response with granulomatous diseases of the oral soft and hard tissues being an uncommon occurrence. When observed clinically, it presents a definite diagnostic dilemma due to the wide variety of possible etiologic diseases. Granulomatous diseases are also frequently observed due to a wide variety of infections. A granuloma is a distinct, compact microscopic structure composed of epithelioid-shaped macrophages typically surrounded by a rim of lymphocytes. Fibroblasts and collagen fibers are also seen immediately surrounding the lymphocytes. Granulomatous disorders comprise a large family of lesions that share a common histological feature: Granuloma formation. Therefore, an extensive clinical, microscopic, and laboratory evaluation is required to identify the source of the oral granulomatous disease. Therefore, the purpose of this article is to highlight the etiology, histopathological features, and differential diagnosis of various granulomatous diseases that affect the oral soft and hard tissues. KEY WORDS: Granuloma, Infectious disease, Inflammation, Macrophages, Oral lesions INTRODUCTION small, non-necrotizing or non-caseating granulomas with an aggregation of peripheral lymphocytes, A granuloma can be defined as a firm, tumor-like central epithelioid histiocytes, and presence of granulation with a compact collection of epithelioid multinucleated giant cells.[5,6] Granulomatous lesions cells and inflammatory cells formed as a reaction to present themselves as sessile, lobulated, moderately chronic inflammation due to foreign bodies, fungi, firm, and relatively non-tender nodules and papules [1] and bacteria. Oral granulomatous diseases are with normal coloration with little or no erythematous frequently observed due to a wide variety of infections. changes surrounding them.[7] The term granulomatous diseases include those conditions characterized by the histological presence Foreign substances such as endogenous and of granuloma resembling those of tuberculosis (TB) exogenous substances are the most common source of as well as condition without microscopic granuloma triggering localized granulomatous inflammation in formation but with the prominent proliferation of the oral cavity. These reactions present as non-descript granulation tissue.[2] Granulomas are normally the masses with the presence of erythema, localized or result of defensive mechanisms and form when generalized edema, pain, or even the presence of acute inflammatory processes are unable to destroy ulceration of the tissues.[8] On progression, some of invading agents and are believed to be the end the granulomas may ulcerate centrally and present result of a series of pathological events.[3] They as squamous cell carcinomas. The treatment of these possess a multifactorial etiology and may arise due conditions depends on the systemic cause. Localized to a reaction to environmental or genetic factors, lesions without systemic connection can be treated by infectious organisms, or may also be idiopathic, for conservative surgical removal.[9] The presence of signs which there is no trigger factor.[4] A wide variety of and symptoms may warrant additional clinical and granulomatous disorders can involve the orofacial laboratory testing to identify other possible sources of tissues. Such lesions of the oral cavity present as the inflammation, unless the foreign substance is not identified in microscopic sections, the granulomatous Access this article online inflammation generally presents a diagnostic dilemma for the clinicians. Often, the differential Website: jprsolutions.info ISSN: 0975-7619 diagnosis includes foreign body reactions, infection, Department of General Pathology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India *Corresponding author: Dr. M. P. Brundha, Department of General Pathology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, 162, Poonamallee High Road, Chennai - 600 077, Tamil Nadu, India. Phone: +91-9884421482. E-mail: [email protected] Received on: 12-08-2019; Revised on: 08-09-2019; Accepted on: 17-10-2019 172 Drug Invention Today | Vol 13 • Issue 1 • 2020 N. Vidulasri and M. P. Brundha Crohn’s disease (CD), sarcoidosis, and orofacial involve other organs as well which are, respectively, granulomatosis (OFG).[10] Knowledge of the clinical classified as pulmonary and extra-pulmonary TB.[16] and histologic patterns of granulomatous diseases will Primary pulmonary disease results from initial allow easier interpretation for practitioners to provide infection with M. tuberculosis. Most individuals are a useful differential diagnosis, thus facilitating asymptomatic with lesions that heal spontaneously appropriate clinical management.[11] Therefore, the but which later becomes evident with the presence of aim of this article is to provide information regarding small calcified nodules known as Ghon’s complex. the histology and oral manifestation of granulomatous Secondary pulmonary TB is a post-primary disease conditions that commonly affect the oral cavity. due to the endogenous reactivation of latent infection which may be primarily due to immunosuppression.[17] CLASSIFICATION OF GRANULOMATOUS Histopathology [12,13] Tuberculous granulomas are characterized by the CONDITIONS presence of central caseous necrosis. The site is As there is great variation among the possible encircled by epithelioid cells, lymphocytes, histiocytes, [18] etiological factors, the classification of granulomatous fibroblasts, and occasionally Langhans giant cells. disorders may include many conditions. These In some instances, caseating granulomas may not comprise infections, vascular irregularities, be present but may show non-caseating granulomas. immunological upsets, leucocyte oxidase defects, A biopsy exhibiting granulomatous inflammation and hypersensitivity reactions, and neoplasia. Broadly microscopic evidence of mycobacterial organisms are these causes may be categorized as: often suggestive of TB. 1. Bacterial • TB Oral manifestation • Leprosy Oral TB may occur at any location on the oral mucous • Syphilis membrane with the tongue and gingiva being most • Cat-scratch disease commonly involved. Other sites include the palate, 2. Fungal lips, buccal mucosa, gingiva, palatine tonsil, and • Histoplasmosis floor of the mouth.[19] Other manifestations include • Blastomycosis it presents as a single or multiple painless ulcers and • Paracoccidioidomycosis usually appear as irregular, well-circumscribed with • Aspergillosis surrounding erythema, which usually extends from the 3. Reactive lesions (Trauma, and hypersensitivity) gingival margin to the depths of the adjacent vestibule • Pyogenic granuloma and is often associated with enlargement of cervical • Peripheral giant cell granuloma lymph nodes, localized masses, and swellings. In • Periapical granuloma rare cases, there is the involvement of the maxilla 4. Foreign bodies and mandible which usually results in tuberculous • Oral foreign body reactions osteomyelitis as a result of the penetration of gingival 5. Other causes (Unknown, autoimmune, and/or lesions into jaw bones.[20] vascular origin) • Sarcoidosis Leprosy • CD Leprosy is a slowly progressive infectious disease caused • Cheilitis granulomatosa by Mycobacterium leprae. The disease is presented as • Eosinophilic granuloma either lepromatous leprosy – a low resistance form • Wegener’s granulomatosis or tuberculoid leprosy, the highly resistant form. The initial event is a chronic mycobacterial infection that TB elicits a range of cellular immune responses followed TB is a chronic granulomatous disease caused by by the second response is a peripheral neuropathy that various strains of mycobacteria, usually attributed is initiated by the infection, followed by immunologic to the bacteria Mycobacterium tuberculosis. Among events. The conditions affect the skin and peripheral all infectious diseases, TB remains to be among the nerves, resulting in disabling deformities.[21] Mild world’s most notorious, contributing to high morbidity to moderate effects on other organs which include and mortality rates.[14] Although, oral manifestations systems such as the liver, kidneys, eyes, oral mucosa, of TB have a rare occurrence, it has been considered lymph nodes, bones, and joints and gonads. to account for 0.1–5% of all TB infections.[15] These lesions are usually secondarily inoculated with infected Histology sputum or due to hematogenous spread. The most The typical granulomatous nodule shows collections commonly affected organs are the lungs, but may also of epithelioid cells and lymphocytes in a fibrous Drug Invention Today | Vol 13 • Issue 1 • 2020 173 N. Vidulasri and M. P. Brundha stroma. Langhans type giant cells are variably present An indurate ulceration of the dorsum of the tongue, with vacuolated macrophages called lepra cells these hyperplasic foliate papillae, is the only clinical signs are scattered throughout the lesions and often contain of the disease. Erythema, edema, and petechial the bacilli.[21] hemorrhage with or without the presence of a chancre may occur in the soft palate. The asymmetry of the Oral manifestation uvula or tonsillar pillar can be noticed in the initial The oral lesions in leprosy