|Year : 2015 | Volume
| Issue : 3 | Page : 423-427
Non-exposed variant of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with a plasmacytoma: A rare case report
Arvind Muthukrishnan1, Gowri Shankar Sekar2
1 Department of Oral Medicine and Radiology, Saveetha Dental College and Hospital, Saveetha University, Chennai, Tamil Nadu, India
2 Department of Oral Medicine and Radiology, SRM Kaatankulathur Dental College and Hospital, SRM University, Chennai, Tamil Nadu, India
|Date of Submission||29-May-2015|
|Date of Acceptance||26-Oct-2015|
|Date of Web Publication||25-Nov-2015|
Department of Oral Medicine and Radiology, Saveetha Dental College and Hospital, Saveetha University, Chennai - 600 077, Tamil Nadu
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Bisphoshonate-related osteonecrosis of the jaw (BRONJ) is an avascular osteo-chemonecrosis of the jaw which results after administration of the group of drugs called as bisphosphonates. Bisphosphonates are given to prevent bone resorption in osteolytic diseases such as Paget's, osteoporosis, osteogenic carcinoma, and other carcinomas where there could be metastasis and bone resorption. Incidence of BRONJ is reported to be high in western literature and is found to be more after intravenous route compared to oral route of administration. There are various clinical stages of BRONJ as per the American Association of Oral and Maxillofacial Surgeons (AAOMS). Here, we present a rare case of a 60-year-old lady who presented with a complaint of a painless swelling in the alveolus and gingiva in the left maxillary posterior region. This patient was on intravenous Zolendronate for more than 4 years. Thorough examination with detailed investigations revealed BRONJ along with a coexisting second primary tumor, plasmacytoma. Metastasis to distant site is a common feature of malignancy. A metastatic lesion usually occurs within 6 months to 1 year after treatment of a primary lesion. Any fresh neoplasm beyond 1 or 2 years after detection of a primary can be regarded as a second primary tumor. Solitary bone plasmacytoma is a localized form of plasma cell tumor. Diagnosis is based on the presence of the following: Malignant proliferation of plasma cells in biopsy, absence of osteolytic bone lesion, absence of Bence Jones proteins, low concentration of monoclonal proteins, elevated IgG and gamma globulin levels.
Keywords: Bisphosphonates, osteonecrosis, jaw, plasmacytoma, second primary tumor, Zolendronate
|How to cite this article:|
Muthukrishnan A, Sekar GS. Non-exposed variant of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with a plasmacytoma: A rare case report. J Indian Acad Oral Med Radiol 2015;27:423-7
|How to cite this URL:|
Muthukrishnan A, Sekar GS. Non-exposed variant of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with a plasmacytoma: A rare case report. J Indian Acad Oral Med Radiol [serial online] 2015 [cited 2020 Jun 2];27:423-7. Available from: http://www.jiaomr.in/text.asp?2015/27/3/423/170484
| Introduction|| |
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) adversely affects the quality of life, producing significant morbidity in afflicted patients. Intravenous (IV) bisphosphonates (BPs) are effective and primarily used in the treatment and management of cancer-related conditions including hypercalcemia of malignancy, skeletal-related events associated with bone metastasis in the context of solid tumors such as breast cancer, prostate cancer, and lung cancer, and in the management of lytic lesions in the setting of multiple myeloma.  They bind to the mineralized bone matrix and by acting upon the osteoclasts, inhibit bone resorption. In addition, they inhibit formation of new osteoclasts, subsequently creating an unfavorable environment for bone metastasis development. 
An association between BPs and osteonecrosis of the jaws was first described in 2003 followed by successive modifications of its classification by the American Association of Oral and Maxillofacial Surgeons (AAOMS) [Table 1]. Nitrogen-containing BPs administered intravenously have become the standard of care to reduce skeletal-related complications, including bone pain, pathologic fracture, spinal cord compression, and hypercalcemia, in patients with multiple myeloma, and in bone metastasis secondary to prostate cancer, lung cancer, and renal cell carcinoma. Diagnosis may be delayed because BRONJ is not initially radiographically detectable and has no specific radiographic characteristics, though it may exhibit numerous late nonspecific radiographic changes, including osteolysis, osteosclerosis, widening of the periodontal ligament (PDL), and persisting alveolar bone sockets.  The exact incidence of BRONJ is unknown, but reports show the incidence to range from 1% to 11% for patients receiving intravenously administered BPs and as 1% for oral BPs. Preclinical and clinical studies suggest that BPs are able to prevent bone metastasis in a variety of cancers such as breast, lung, and prostate. Although their value in clinical practice has been proven, patients taking BPs are at risk of developing BRONJ. 
|Table 1: Clinical classifi cation of BRONJ by Ruggiero (2006) and successive modifications by AAOMS 2009|
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| Case Report|| |
A 60-year-old female patient came to the oral medicine clinic of Saveetha Dental College with a complaint of painful swelling in the left upper jaw region for the past 6 months [Figure 1]. History revealed that she had carcinoma of right breast (Grade 2) in 2003. She was surgically treated with mastectomy and subsequent chemotherapy. In 2009, she was diagnosed with metastatic deposits in the right pelvis region, for which she was treated with chemotherapy and radiotherapy. Following resolution of the metastatic lesion, she was on a weekly IV injection of 4 mg of Zolendronic acid (Zometa; Novartis Pharma, Stein AG, Stein, Switzerland) since 2010. Subsequently, in March 2013, she developed a swelling in the left maxillary gingival and alveolar region. She was treated for this gingival swelling by her primary dentist, who extracted the root stump (26) in the region of the swelling. As the swelling did not subside even after extraction, she was referred to the oral medicine clinic [Figure 2].
|Figure 2: OPG showing the presence of root stumps in 26 region which was subsequently extracted|
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Clinical examination revealed a well-defined swelling in the left maxillary alveolar region, with missing 26 and 27. Mucosa over the swelling showed areas of ulceration and a sinus opening which on probing led to pus discharge. We subjected the patient to an orthopantomogram (OPG), which revealed areas of altered bone pattern and erosions. Cone-beam computed tomography (CBCT) revealed osteomylitic (necrosed bone) like changes and areas of bone destruction in the left maxillary alveolar region [Figure 3]. Based on the chief complaint and by reviewing the medical history, radiographic and imaging findings, a provisional diagnosis of BRONJ Stage 1 or a possible metastasis was made. We then referred the patient back to the oncology department with our opinion. Our provisional diagnosis was endorsed by the oncologist and the patient was discontinued from BP therapy for 6 weeks and clearance for biopsy was given.
After 6 weeks of stoppage of BPs, an excisional biopsy was done under general anesthesia (GA) [Figure 4] and [Figure 5]. Biopsy specimen revealed the tissue showing fragmented islands of bone tissue with amorphous calcification and absence of osteoid, suggestive of BRONJ [Figure 6]. Deeper sections revealed lining of acanthotic squamous epithelium of the buccal mucosa. Tissue surrounding these islands showed dense sheets of plasma cells, atypical plasma cells, binucleated plasma cells, and sparse lymphocytes, suggestive of a plasma cell disorder [Figure 7].
|Figure 6: Tissue showing fragmented islands of bone tissue with amorphous calcification and absence of osteoid and abundance of plasma cells|
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|Figure 7: Section shows a lining of acanthotic squamous epithelium of the buccal mucosa. Tissue surrounding these islands shows dense sheets of plasma cells, atypical plasma cells, binucleated plasma cells, and sparse lymphocytes|
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We then subjected the patient to whole-body X-ray; however, X-rays of the skull and long bones did not reveal any osteolytic bone lesions [Figure 8]. The biochemical investigations [Table 2] revealed that the patient was anemic (Hb- 10.3%), had a decreased hematocrit (33.7%), decreased mean corpuscular volume (MCV; 72 fl), and decreased mean corpuscular hemoglobin (MCH; 22 pg) values. However, the red cell distribution width (RDW) was elevated (21.9%) and erythrocyte sedimentation rate (ESR) was abundantly increased (102 mm). Specific protein analysis showed elevated IgG (20.00 g/l). Spot urine studies showed that Bence Jones protein test was negative. Serum protein electrophoresis showed increase in total protein count (8.1 g/dl), decreased albumin (37.80%), elevated alpha-1 globulin (4.1%) and alpha-2 globulin (15.90%), and exceedingly high gamma globulin level (26.40%), which are diagnostic of a plasmacytoma. Based on clinical findings, imaging, histopathological and biochemical values, a final diagnosis of Stage I osteonecrosis due to BPs with a second primary tumor, i.e. plasmacytoma (or) monoclonal gammopathy of undetermined significance (MGUS), was made. The patient was subsequently referred to the medical oncologist. The BPs have been permanently stopped and the patient is under observation.
| Discussion|| |
Metastasis to distant site is a common feature of malignancy. A metastatic lesion usually occurs within 6 months to 1 year after treatment of a primary lesion. Any fresh neoplasm beyond 1 or 2 years after detection of a primary can be regarded as a second primary tumor. Here, a case of osteonecrosis of the jaw due to BPs (Stage 1) and a solitary plasmacytoma of the maxilla has been presented.
BRONJ is defined as the presence of exposed necrotic bone for more than 8 weeks following administration of BPs and no history of radiation therapy to the jaws. The clinical presentation is variable; some patients may be asymptomatic, whereas others may present with mobile teeth, soft tissue inflammation, and neurosensory changes of the lip, sinus tracts, and a foul-tasting discharge. Although early manifestations of BRONJ are not easily identified, prompt recognition is important to avoid misdiagnosis and facilitate management. Solitary bone plasmacytoma is a localized form of plasma cell tumor. Maxillofacial area is rarely affected. It is associated with bone swelling, localized bone and teeth pain, bleeding, and mobility. Diagnosis is based on the following: Presence of malignant proliferation of plasma cells in biopsy, absence of osteolytic bone lesion, absence of Bence Jones proteins, low concentration of monoclonal proteins, and elevated IgG and gamma globulin levels as seen in our case.
Our case showed radiographic and histologic evidence of necrotic bone, which validates the possibility of BRONJ. Even though metastasis to the jaw from a primary breast carcinoma is a possibility, in our case, histologically, there were no features of carcinomatous infiltration. The presence of atypical plasma cells which are binucleated, increased protein count, elevated alpha-1, alpha-2 globulin, and exceedingly high gamma globulin level confirmed the diagnosis of a plasmacytoma or MGUS. The patient under the supervision of an oncologist has to be constantly reviewed, the investigations repeated after regular intervals, and appropriate treatment has to be done. Based on the clinical course of the disease, these patients should be weaned off IV BPs. There is always a possibility that over a period of time, there could be a transformation from a solitary plasmacytoma to a multiple myeloma.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
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Weinstein RS, Roberson PK, Manolagas SC. Giant osteoclast formation and long-term oral bisphosphonate therapy. N Engl J Med 2009;360:53-62.
Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B; Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws, American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaw-2009 update. Aust Endod J 2009;35:119-30.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
[Table 1], [Table 2]