The analysis of case reports in this article also

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The analysis of case reports in this article also revealed the importance of histopathological examination of the DIGO lesions. Kim et al . in 2002 [69] reported two cases of cyclosporine‑induced gingival overgrowth. However, the histopathological examination of the excised gingival tissues was suggestive of plasma cell granuloma composed of mature plasma cells. Thus, a careful differential diagnosis from malignant plasmacytoma had to be made in those cases. Another report by Rolland et al . in 2004 [64] presented two cases of gingival overgrowth in heart transplant patients under cyclosporine therapy. The histologic picture of the excised tissue showed diffuse lamina propria infiltration by large malignant‑appearing lymphoid cells. Subsequently, a diagnosis of posttransplant lympho‑proliferative disorders was suggested. In yet another report, Yoon et al . in 2006 [22] presented a case of gingival enlargement in a patient who had been under long‑term amlodipine therapy. Histopathological examination of an incisional gingival biopsy of the lesion revealed neoplastic cells. Further immunohistochemical study yielded a diagnosis of myeloid sarcoma. Later, a bone marrow biopsy was performed and the diagnosis was changed to acute myeloid leukemia. Unfortunately, the patient never showed remission and died 4 months after initial diagnosis. da Silveira et al . in 2007 [90] reported a case of gingival enlargement in a patient under long‑term phenytoin and phenobarbital therapy who also presented a peripheral calcifying epithelial odontogenic tumor which could be confused with fibrous hyperplasia. Vishnudas et al . in 2014 [28] reported a gingival enlargement after amlodipine use, which on histopathological examination was identified as plasma cell granuloma. These above reported cases clearly signify the importance of histopathological examination of gingival tissues in the diagnosis and management of DIGO. Significant findings of the review 1. Besides gingiva, drug‑induced hyperplasias of edentulous mucosa and peri‑implant mucosa have also been reported (although rare) 2. Azithromycin therapy for cyclosporine‑induced gingival enlargement is not a definitive management module 3. Tacrolimus is the best alternative substitute (available till date) for cyclosporine as an immunosuppressant to avoid/treat gingival hyperplasia 4. Meticulous oral hygiene maintenance is a critical factor in regression of DIGO 5. Persisting enlargement after drug cessation/substitution and meticulous oral hygiene maintenance might require surgical excision 6. Histopathological examination of all persisting enlargements is mandatory to evaluate malignant changes 7. Incidence of DIGO is believed to be influenced by genotype of the individual. This signifies the need for transformation to the concept of personalized medicine to prevent DIGO. Further research is, however, needed for such transformation in medicine to be practiced 8. Treatment recommendations as in Figures 2 and 3.
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