drug - induced gingival overgrowth ( digo ) remains a significant problem for the dental clinicians .
amlodipine is a third - generation dihydropyridine calcium channel blockers ( ccb ) that is used in the management of both hypertension and angina .
ellis et al . , first reported gingival sequestration of amlodipine and amlodipine - induced gingival overgrowth ( aigo ) .
since then , very few isolated cases of aigo have appeared in the dental literature although there are numerous reports of nifedipine induced gingival overgrowth until date .
the incidence of gingival hypertrophy with nifedipine therapy has been reported to be as high as 20% .
other synonyms have been used to describe similar lesions , such as inflammatory pseudotumor , histiocytoma , xanthomatous granuloma , inflammatory myofibroblastic tumor , and spindle cell pseudotumor .
it occurs primarily in the lungs , but has occurred in other extra - pulmonary sites .
this lesion is not a neoplastic process , nor is it associated with a monoclonal expansion of a single plasma cell instead ; this is a reactive , inflammatory lesion which usually involves the mobile tissues of the oro - nasopharyngeal region , such as paranasal sinuses , buccal mucosa , tongue , and lip .
they are even rarer on the gingiva and very few case reports have been documented .
there are no reports of amlodipine - related plasma cell granuloma of gingiva existing in the extant literature .
the present case report describes an unusual case of amlodipine induced massive plasma cell granuloma on the gingiva .
a 54-year - old female patient reported to the multispecialty private dental clinic ( latur , india ) with the chief complaint of diffuse swelling in the right maxillary anterior region .
patient was not aware of such growth until 8 months back when she noticed a small slowly growing bead - like nodular enlargement of the gums that gradually progressed to the present size covering almost the entire front teeth .
her past medical history revealed that the patient was hypertensive for last 2 years and was under medication ( amlodipine 10 mg , once daily ) .
the lesion was asymptomatic , but the patient complained it to be severely interfering with mastication , speech , and oral hygiene practice resulting in functional and aesthetic problem .
on intraoral examination , the lesion was a well - circumscribed exophytic sessile spherical mass of 1.5 inches diameter with color same as that of the surrounding oral mucosa with the scattered erythema [ figure 1 ] .
the lesion was extended from distal surface of upper right canine to distal surface of upper left central incisor crossing the midline .
poor oral hygiene status of the patient was assessed from the presence of local irritating factors contributing to the mild inflammatory component of the gingival enlargement .
pre - operative clinical presentation of amlodipine induced plasma cell granuloma of gingiva complete hemogram showed all blood counts to be within the normal limits .
intraoral periapical radiograph and orthopantomogram in the region of aigo showed generalized advanced horizontal bone loss around all teeth resulting in pathologic migration the lesion was biopsied under local anesthesia .
the area was sutured and the specimen submitted for histopathological examination . as the extraction of all the remaining teeth with poor prognosis was planned substitution of amlodipine was not considered . planned extraction of remaining mandibular teeth was carried out in subsequent appointment . following healing period of 2 months complete denture prosthesis
histopathological examination using hematoxylin and eosin stain , revealed proliferative parakeratinized stratified squamous epithelium , connective tissue with sheets of plasma cells intermixed with scattered small lymphocytes .
high power microscopy : h and e staining shows sheets of plasma cells intermixed with scattered small lymphocytes immunohistochemical study of the biopsy material revealed the polyclonal plasma cell infiltrate uniformly positive for cd138 , a marker for plasmacytoid cells [ figure 3 ] and kappa light chain [ figure 4 ] and weak expression was noted for the lambda light chain .
absence of findings from common tetrad of multiple myeloma ( crab : c = calcium ( elevated ) , r = renal failure , a = anemia , b = bone lesions ) ruled out its possibility .
positive staining for d138 positive staining for kappa light chain on the basis of clinicohistopathologic examination and immunohistochemistry , a confirmative diagnosis of plasma cell granuloma was made .
healing was uneventful and the patient is presently under follow - up since 5 months .
gingival overgrowth is an often overlooked , but potentially harmful side - effect of treatment with amlodipine and other ccb .
the reason for this adverse event is not absolutely known , but two main inflammatory and non - inflammatory pathways have already been suggested .
the proposed non - inflammatory mechanisms include defective collagenase activity due to decreased uptake of folic acid , blockage of aldosterone synthesis in the adrenal cortex and consequent feedback increase in adrenocorticotropic hormone level , and up - regulation of keratinocyte growth factor .
alternatively , inflammation may develop as a result of direct toxic effects of concentrated drug in gingival crevicular fluid and/or bacterial plaques .
this inflammation could lead to the up - regulation of several cytokine factors such as transforming growth factor beta . in a series of 150 cardiac patients
, it was found that amlodipine at a dose of 5 mg / day can not induce gingival hyperplasia even if taken more than 6 months .
plasma cells are terminally differentiated b lymphocytes , which are typically found in the red pulp of the spleen , medulla of the lymph nodes , tonsils , lamina propria of the entire gastrointestinal tract , mucosa of the nose and upper airway , and sites of inflammation . a plasma cell 's main function is to produce immunoglobulins or antibodies
. periodontal lesions with a predominance of plasma cells were reported initially by during late 1960s and only very few case reports have been documented since then .
these cases reported a similar reactive gingival growth with similar histological and clinical appearance , which was treated by excisional biopsy , as in the present case .
gingival plasma cell granulomas have been reported in patients with cyclosporine - induced gingival overgrowth .
it was suggested that interleukin-6 and phospholipase c-1 may induce heavy plasma cell infiltration in cyclosporine - induced gingival overgrowth .
it is important to differentiate plasma cell granulomas from tumors of bone such as multiple myeloma , solitary myeloma , and soft - tissue myeloma ( extramedullary plasmacytoma ) considering the poor prognosis of these neoplasms .
differentiating the type of soft - tissue tumor is mandatory , as plasma cell granuloma may be benign , extramedullary plasmacytoma may be malignant or a precursor to malignancy .
histologically , extramedullary plasmacytoma consists of mixture of typical and atypical plasma cells while plasma cell granuloma consists of normal plasma cells and small lymphocytes that are surrounded by connective tissue septa .
the immunohistochemical analysis have shown that in the case of malignancy ratio of the kappa to lambda light chain may be greater than 10:1 or 1:10 , whereas in a reactive lesion the ratio is 2:1 .
plasma cell lesions with the predominance of plasma cells may represent an autoimmune reaction or an alteration of blood - flow imposing congestive vasodilatation or lesions occurring due to parasitic infiltration .
recent studies have reported that a gingival plasma cell granuloma shows variable gene expression for cell - mediated immunity and stromal tissue degeneration , undergoing sclerotic fibrosis with a persistent inflammatory reaction . in conclusion ,
amlodipine induced plasma cell granuloma of gingiva is a distinct pathological entity characterized by the presence of mature polyclonal plasma cell sheets and fibrovascular connective tissue stroma .
while the mechanism of amlodipine - induced gingival plasma cell granuloma of gingiva is considered to be multi - factorial , the drug / cellular interaction may play an important role in the pathogenesis of this entity .
this case highlights the need to biopsy unusual lesions to rule out potential neoplasms and also emphasizes the need to submit the excised tissue for histopathological examination regardless of clinical notion and/or perceived surgical success .
 drug - induced gingival overgrowth ( digo ) can be a serious concern for both patients and clinicians . 
 digo is a well - documented side - effect of some pharmacologic agents , including , but not limited to , calcium channel blockers , phenytoin , and cyclosporine . 
 plasma cell granulomas ( pseudotumors ) are exceedingly rare , non - neoplastic , reactive tumor - like proliferation , primarily composed of plasma cells that manifest primarily in the lungs , but may occur in various anatomic locations . 
 intraoral plasma cell granulomas involving the lip , oral mucosa , tongue , and gingiva have been reported in the past . 
 this is the first case report of amlodipine induced plasma cell granuloma of the gingiva in the medical literature presenting a 54 year - old female patient with hypertension , who received amlodipine ( 10 mg / day , single dose orally ) for 2 years , sought medical attention because of developing maxillary anterior massive gingival overgrowth causing functional and esthetic problem , which was treated by excisional biopsy . 
 histologically , these lesions were composed of mature plasma cells , showing polyclonality for both lambda and kappa light chains and fibrovascular connective tissue stroma confirming a diagnosis of plasma cell granuloma 
 . this case also highlights the need to biopsy for unusual lesions to rule out potential neoplasms . 
INTRODUCTION
CASE REPORT
DISCUSSION