Journal of Indian Society of Periodontology
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Year : 2017  |  Volume : 21  |  Issue : 5  |  Page : 409-411  

Drug-induced atypical hyperplasia enveloping salivary gland malignancy

1 Department of Oral Pathology, Postgraduate Institute of Dental Sciences, Rohtak, Haryana, India
2 Department of Oral Surgery, Postgraduate Institute of Dental Sciences, Rohtak, Haryana, India
3 Department of Periodontics, Postgraduate Institute of Dental Sciences, Rohtak, Haryana, India

Date of Submission19-Dec-2015
Date of Acceptance26-Sep-2017
Date of Web Publication9-Feb-2018

Correspondence Address:
Anjali Narwal
Department of Oral Pathology, Pt. B. D Sharma University of Health Sciences, Postgraduate Institute of Dental Sciences, Rohtak, Haryana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jisp.jisp_456_15

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Gingival enlargement is a very common side effect associated with the administration of several drugs, mainly anticonvulsants, calcium channel blockers (CCBs), and immunosuppressants. Amlodipine (a CCB) is a safe antihypertensive drug with a longer duration of action. Gingival enlargement induced by amlodipine is less prevalent among CCBs. Since the pathogenesis is not well understood, it is still a challenge for clinicians to diagnose and manage cases effectively. This case presents an atypical unilateral palatal gingival enlargement in a 61-year-old hypertensive female taking amlodipine. Difficulty for a pathologist in diagnosing in spite of repeated sample submission from the lesion and repeated failure for the operator to reach the underlying pathology due to amlodipine-induced hyperplasia have also been discussed in this case report.

Keywords: Amlodipine, calcium channel blocker, mucoepidermoid carcinoma

How to cite this article:
Narwal A, Singh V, Bala S. Drug-induced atypical hyperplasia enveloping salivary gland malignancy. J Indian Soc Periodontol 2017;21:409-11

How to cite this URL:
Narwal A, Singh V, Bala S. Drug-induced atypical hyperplasia enveloping salivary gland malignancy. J Indian Soc Periodontol [serial online] 2017 [cited 2020 Sep 25];21:409-11. Available from:

   Introduction Top

Drug-induced gingival enlargement is a well-documented side effect of phenytoin, cyclosporine, and calcium channel blockers (CCBs). The prevalence of gingival enlargement induced by CCBs ranges from 20% to 83%.[1] Several factors, namely, age, genetic predisposition, presence of preexisting plaque, and gingival inflammation influence the relationship between the drugs and gingival tissue.[2] Great variability in the extent and severity of the changes in gingival tissues has been reported in literature.[3] Although different mechanisms of action for these drugs have been postulated, the most accepted is their action at cellular level by inhibiting intracellular Ca 2+ ion influx.[4]

Among calcium antagonists, nifedipine-induced gingival hyperplasia has been the most frequently encountered gingival enlargement in clinical practice. Lederman et al. in 1984 were the first to report negative oral effects of nifedipine.[5] Numerous reports on gingival enlargement with newer generation of CCBs, such as felodipine, nicardipine, manidipine, and diltiazem, have been documented. The prevalence of verapamil- and amlodipine-induced gingival hyperplasia is significantly lower (4.2% and 3.3%, respectively) than that of nifedipine.[6]

We report an interesting case of a 61-year-old female patient who presented with amlodipine-induced atypical palatal hyperplasia.

   Case Report Top

A 61-year-old female reported to the department of oral and maxillofacial surgery with a swelling in the left posterior part of the palate for 2 years. The swelling was nonpainful, gradually increasing in size, and firm in consistency, with few areas of superficial ulceration. It was extending from tooth 24 to 28 with no mobility of associated teeth. The swelling was approximately 5 cm × 3 cm and partially crossing the midline [Figure 1]. On palpation, the margins of the swelling did not seem to be fixed to the underlying bone rather it appeared to be attached to the palate by a peduncle. The undersurface of the swelling bled upon palpation. Mucosa covering cheek, tongue, and floor of the mouth appeared to be healthy and no gingival hyperplasia was observed in the areas where teeth were present, though they were periodontally compromised. Generalized gingival recession was present along with multiple root stumps in upper and lower jaws. The patient lost multiple teeth due to her ignorance and access to tooth-saving modalities.
Figure 1: Pedunculated unilateral swelling (5 cm × 3 cm) partially crossing the midline

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Family history did not reveal any significant finding. Her past medical history revealed that the patient was hypertensive for the last 15 years and was under medication (amlodipine 5 mg, once daily). Hematological investigations were noncontributory to the diagnosis. Radiological examination showed no remarkable bone loss in the palate but significant bone loss due to chronic periodontitis in the areas, where teeth were present.

A provisional diagnosis of pyogenic granuloma or pleomorphic adenoma was made on the basis of clinical and radiological findings.

An incisional biopsy was done in the department of oral surgery and biopsied tissue was sent to the department of oral pathology for histopathological examination. The tissue submitted showed overlying stratified squamous epithelium with abundant collagen bundles in the connective tissue stroma. The whole architecture of the underlying connective tissue was obliterated by haphazardly arranged collagen bundles in the stroma. No salivary gland was identified and not many blood vessels or endothelial proliferation were seen [Figure 2]. The biopsied tissue appeared to be taken very superficially from the lesion, and a request of repeat biopsy was made to the operator.
Figure 2: (a and b) Overlying stratified squamous epithelium with haphazardly arranged collagen bundles in the connective tissue stroma (H and E, ×10)

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After a week, repeat biopsy was performed at a different site of the swelling and again the tissue was sent to us for confirmatory diagnosis. Histopathological findings were similar to the initial one, but the only difference this time was the presence of few atypical cells in the deeper connective tissue of the biopsied material [Figure 3]. An impression of again not reaching into the deep-seated pathology was made.
Figure 3: (a) Dense collagen bundles with presence of salivary gland tumor at greater depth (H and E, ×10). (b) Dense collagen bundles with the presence of salivary gland tumor at greater depth (PAS, ×10)

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Again, a humble request of repeat biopsy was made, and this time, the surgeon did an excisional biopsy under general anesthesia. To our surprise, it came out to be low-grade mucoepidermoid carcinoma. The tissue showed areas of cystic degeneration, atypical mucous cells, and pooling of mucin into these cystic spaces. Tumor cells showed hyperchromatism and enlarged nucleoli. Few islands of epidermoid cells were also seen [Figure 4]. The excised tumor appeared to be well cradled by the proliferative collagen mass all around the tumor cells. Another very important finding which the operating surgeon gave every time while conducting biopsy was the excessive bleeding and uncontrolled high blood pressure during biopsy procedures. This finding along with the drug history of the patient was absent in the requisition form every time and we could not correlate collagen hyperplasia with drug use. And finally, when we kept all pieces of jigsaw puzzle together, the picture came out to be low-grade malignancy in the cradle of amlodipine-induced unilateral atypical palatal hyperplasia.
Figure 4: (a and b) Abundant atypical mucous cells with pooling of mucin into cystic spaces (×10)

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   Discussion Top

Antihypertensive drugs in the CCB group are used extensively in elderly patients who have angina or peripheral vascular disease. The total number of annual prescriptions for this class of agents has continued to rise in the recent years.[7] Amlodipine is a third-generation dihydropyridine calcium antagonist. It has a unique physiochemical profile, which is characterized by near-complete absorption, late-peak plasma concentrations, high bioavailability, and slow hepatic biodegradation. The associated slow elimination of amlodipine with resulting long duration of its action means that only a single daily dose is required. This in turn results in better patient compliance and has until now been associated with similar or reduced severity of side effects compared with nifedipine.[8]

In the present case, no gingival overgrowth was seen in dentulous areas. Only palatal swelling masquerading pleomorphic adenoma or pyogenic granuloma was present. The patient also denied any history of gingival overgrowth at any period of time after taking amlodipine. Giving a diagnosis of fibrous hyperplasia every time after two consecutive repeat incisional biopsies was frustrating for the pathologist as well as for the operator. The posterior part of palate is a site wherein, on routine incisional biopsy, we see minor salivary glands and not much difficulty arises to identify such structure even in tumors. However, in the present case, even after repeated biopsies, no salivary gland on the first biopsy and very few tumor cells on the second biopsy that too only in few areas of deeper connective tissue were identified. Overall impression of all biopsies was that extensive collagen deposition around the tumor cells.

Extensive collagen deposition only in areas where low-grade mucoepidermoid carcinoma is present makes it an interesting case to report as we are not sure how drug-induced hyperplasia has targeted only collagen bundles around pathology. The interaction between the tumor-secreted cytokines and drug-induced stromal changes could be one of the hypotheses for such presentation.

   Conclusion Top

Drug-induced enlargements are not only seen in normal gingiva or palate, but also pathologic tissues secrete certain molecules which might interact with drug molecules and give an enhanced reaction of proliferation as seen in this case. Detailed history whether associated with pathology or not should be taken as findings from the patient which can only help to keep all building blocks correctly to diagnosis and management.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that her name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.


Sincere thanks to my laboratory technicians: Mr. Sanjeev and Mrs. Manjeet.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Pradhan S, Mishra P. Gingival enlargement in antihypertensive medication. JNMA J Nepal Med Assoc 2009;48:149-52.  Back to cited text no. 1
Seymour RA, Thomason JM, Ellis JS. The pathogenesis of drug-induced gingival overgrowth. J Clin Periodontol 1996;23:165-75.  Back to cited text no. 2
Seymour RA, Ellis JS, Thomason JM. Risk factors for drug-induced gingival overgrowth. J Clin Periodontol 2000;27:217-23.  Back to cited text no. 3
Dongari A, McDonnell HT, Langlais RP. Drug-induced gingival overgrowth. Oral Surg Oral Med Oral Pathol 1993;76:543-8.  Back to cited text no. 4
Lederman D, Lumerman H, Reuben S, Freedman PD. Gingival hyperplasia associated with nifedipine therapy. Report of a case. Oral Surg Oral Med Oral Pathol 1984;57:620-2.  Back to cited text no. 5
Livada R, Shiloah J. Calcium channel blocker-induced gingival enlargement. J Hum Hypertens 2014;28:10-4.  Back to cited text no. 6
Marshall RI, Bartold PM. A clinical review of drug-induced gingival overgrowths. Aust Dent J 1999;44:219-32.  Back to cited text no. 7
Jorgensen MG. Prevalence of amlodipine-related gingival hyperplasia. J Periodontol 1997;68:676-8.  Back to cited text no. 8


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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