Q U I N T E S S E N C E I N T E R N AT I O N A L
RADIOLOGY/IMAGING
Rujuta A. Katkar
Multiple myeloma in bisphosphonate-affected jaws – a diagnostic challenge: Case report Rujuta A. Katkar, BDS, MDS, MS1/Joseph Katz, DMD2/Jan S. Moreb, MD3/Madhu K. Nair, DMD, MS, Lic Odont, PhD4 Objective: To discuss the challenges in diagnosis and appropriate management of critical underlying pathoses if a patient presents with signs and symptoms indicative of different conditions that may coexist. Summary: This case features clinical and radiographic challenges in reaching a diagnosis in a middle-aged man undergoing bisphosphonate therapy for multiple myeloma. The patient had history of bisphosphonaterelated osteonecrosis of the jaw (BRONJ) in the mandible. The patient presented with pain and swelling in the anterior maxilla, associated with paresthesia of upper lip. The radiographic
features were suggestive of BRONJ and invasive fungal sinusitis. MRI appearance was suggestive of malignant involvement by plasmacytoma or lymphoma. Although biopsy is usually not advocated in bisphosphonate-affected jaws, it was advised in this case and was positive for multiple myeloma. Vigilance is required to correlate clinical and radiologic findings and further investigations must be considered if malignancy is suspected. (Quintessence Int 2014;45:613–617; doi: 10.3290/j.qi. a31962)
Key words: bisphosphonate-related osteonecrosis of jaw, invasive fungal sinusitis, multiple myeloma
Recent advances in the development of new and effective anti-resorptive agents such as bisphosphonates (BPs) have brought a significant increase in the use of these drugs for osteoporosis, and primary and metastatic bone cancer including multiple myeloma (MM). It is not uncommon, therefore, for the general dental practitioner to encounter a patient affected by osteo-
1
Assistant Professor and Division Director, Oral and Maxillofacial Radiology, Department of Oral and Maxillofacial Diagnostic Sciences, Radiology, Colleges of Dentistry and Medicine, University of Florida, Gainesville, USA.
2
Professor, Oral & Maxillofacial Diagnostic Sciences, College of Dentistry, University of Florida, Gainesville, USA.
3
Professor and Clinical Director, Hematologic Malignancies, Division of Hematology/Oncology, College of Medicine, University of Florida, Gainesville.
4
Professor and Chairman, Oral & Maxillofacial Diagnostic Sciences, Radiology, Colleges of Dentistry and Medicine, University of Florida, Gainesville, USA.
Correspondence: Dr Rujuta Katkar, Oral and Maxillofacial Radiology, Department of Oral and Maxillofacial Diagnostic Sciences, Radiology, Colleges of Dentistry and Medicine, University of Florida, Gainesville, USA. Email: [email protected]
VOLUME 45 • NUMBER 7 • JULY / AUGUST 2014
necrosis of the jaw (ONJ), a complication of anti-resorptive agents that may affect 1% to 15% of the treated patients. It is imperative that the dental practitioner is familiar with different clinical and radiologic manifestations of ONJ for proper diagnosis and management of these patients. Specifically, detection of underlying malignancy can be challenging in the presence of changes associated with BP therapy. MM is a malignant plasma cell disorder that accounts for 15% of all plasma cell dyscrasias and 10% of all hematologic malignancies. It is more frequent in developed countries. The American Cancer Society (ACS) estimates that in 2012, about 21,700 new MM cases will be diagnosed in the United States, while 10,710 deaths are expected to occur.1 MM is characterized by a wide heterogeneity in clinical presentation and course. Recent advances have led to better understanding of the makeup of the disease and its micro-
613
Q U I N T E S S E N C E I N T E R N AT I O N A L Katkar et al
Fig 1
Exposed bone on the mylohyoid ridge of left mandible
environment, leading to new and novel therapies that have resulted in significant improvement in overall survival of patients with MM. The 2012 ACS’s statistics estimate that the 5-year relative overall survival rate for MM patients is around 40%. Intravenous BPs have been very instrumental in prevention of MM bone complications such as compression of the vertebra and pathologic bone fractures;2,3 however, 10% to 15% of patients receiving BP will develop BP-related osteonecrosis of the jaw (BRONJ), characterized by exposed bone that may become infected and may result in significant effects on the patient’s quality of life.4 Since the onset of BRONJ might be without symptomatology, a prompt and accurate diagnosis is essential to prevent further complication. Although the diagnosis of BRONJ is clinical, imaging has a significant role in supporting the diagnosis. Interestingly, the jaws are frequently affected by MM and as they are an exclusive site for the presence of BRONJ, the differential diagnosis of these two conditions may sometimes be challenging.4
CASE REPORT A 55-year-old man was referred to the oral medicine clinic due to sores on the left dorsum of the tongue and roughness on the lingual aspect of the posterior mandible. The patient’s medical history was significant for stage IIIA IgG lambda MM. He was on bortezomib and dexamethasone as well as monthly zoledronic acid intravenously. He was approximately 1-year post-autologous peripheral blood stem cell transplant (ASCT).
614
On examination, a 3 × 1 cm area of exposed bone with brownish color and rough edges was seen on the mylohyoid ridge of the left mandible (Fig 1). The appearance was consistent with BRONJ. There was also corresponding ulceration along the tip of the left side of the tongue. The patient was prescribed chlorhexidine rinses till the ulcer healed and the exposed bone resolved to some extent. The patient was taken off zoledronic acid and 3 months later had extractions of bilateral maxillary canines that were very mobile and painful, in preparation for a complete maxillary denture. Three months following the extraction, the patient was admitted complaining of significant pain in the left maxilla. On examination, bony expansion and tenderness on palpation of the left maxillary sinus and infraorbital area were noted. Partial paresthesia of the left upper lip was also reported. Non-contrast cone beam volumetric computed tomography (CBCT) study was performed (Figs 2 to 4). Multiplanar reconstructions demonstrated a mixeddensity appearance in the anterior maxilla. There was increased sclerosis with multiple areas of osteolysis and destruction of the buccal and palatal cortical plates. The inferior anterolateral wall of the left maxillary sinus was disrupted, resulting in oro-antral communication. These findings were compatible with BRONJ. However, clinically, there was no evidence of exposed bone in these regions. Mucoperiosteal thickening was present in both maxillary sinuses. There was no frank evidence of sequestration or periosteal reaction, which is usually seen in advanced cases of BRONJ. Because of frank bone destruction in the anterior wall of the left maxillary sinus with swelling and paresthesia in the affected region, malignancy was suspected. Non-contrast medical grade CT demonstrated mass lesions involving the pre-antral fat with erosive changes in both maxillary canine alveolar sockets, left side greater than right (Fig 3). Infiltration of the fat in the left buccal space and the left side of the face, and subtle infiltration in the right retro-antral fat was also present. Mucoperiosteal thickening was present in both maxillary sinuses. The appearance on CT was suspicious for invasive fungal sinusitis. Magnetic reso-
VOLUME 45 • NUMBER 7 • JULY / AUGUST 2014
Q U I N T E S S E N C E I N T E R N AT I O N A L Katkar et al
a
b
c
Figs 2a to 2c Pretreatment CBCT scan. (a) Axial view demonstrating destruction of the anterior wall of the left maxillary sinus, nonhealing extraction socket in the left maxillary canine region and increased sclerosis of the anterior maxilla. (b) Sagittal view demonstrating a soft tissue mass with destruction of the bone in maxillary left canine region. (c) Coronal view demonstrating non-healing extraction sockets in the maxillary canine regions bilaterally with disruption of the cortical plates and increased sclerosis of the bone. Fig 3 (left) Pretreatment CT axial view soft tissue window demonstrating mucoperiosteal thickening in the left maxillary sinus, erosion of the anterior wall with a soft tissue mass obliterating pre-antral fat. Fig 4 (right) Pretreatment MRI axial T2-weighted turbo-spin echo (TSE) postcontrast image demonstrating soft tissue masses in the anterior maxilla and mucoperiosteal thickening in the maxillary sinuses, left more than right
Fig 5 (left) Histopathologic section showing large plasmacytoid cells exhibiting pleomorphic hyperchromatic round to ovoid nuclei exhibiting a stippled chromatin pattern. Also noted in some areas are cells with abundant eosinophilic cytoplasm pushing the nuclei to an eccentric position. Foci of anaplastic cells, abnormal and increased mitoses, and cellular and nuclear pleomorphism are noted throughout this framework (hematoxylin-eosin; magnification 20×) Fig 6 (right) Photomicrograph showing florid positive cytoplasmic staining of neoplastic cells for lambda light chain stain thereby confirming a diagnosis of lambdarestricted multiple myeloma (magnification 10×).
nance imaging (MRI) evaluation was advised for further investigation. MRI evaluation showed mucoperiosteal thickening in both maxillary sinuses. Mass lesions involving the preantral fat pads and maxillary canine alveolar sockets, left greater than right, were noted as well (Fig 4). These lesions demonstrated enhancement on contrast imaging. The appearance was suggestive of plasmacytoma or lymphoma. Possibility of fungal sinusitis was ruled out.
VOLUME 45 • NUMBER 7 • JULY / AUGUST 2014
An incisional biopsy from the submucosa from the left maxilla revealed a malignant plasmacytic neoplasm consistent with lambda-restricted MM (Figs 5 and 6). The patient had palliative radiation treatment of the left maxillary region, left maxillary sinus, and bilateral maxillary alveolar ridges for 2 weeks. A CT scan taken 10 days later showed increased bone destruction involving the anterolateral and posterolateral walls of bilateral maxillary sinuses, increased mucoperiosteal
615
Q U I N T E S S E N C E I N T E R N AT I O N A L Katkar et al
a
a
b
Figs 7a and 7b CT scan after palliative radiation. Axial view bone windows demonstrate increased bone destruction involving the anterolateral and posterolateral walls of bilateral maxillary sinuses, increased mucoperiosteal thickening, and enlarged soft tissue mass on the left.
b
Figs 8a and 8b CT scan after chemotherapy. Axial CT bone windows demonstrate significant interval regression of the mucoperiosteal thickening, bony erosion, and soft tissue swelling.
thickening, and enlarged soft tissue mass on the left (Fig 7). The patient was put on a chemotherapy regimen followed by salvage ASCT with busulfan, cyclophosphamide, and etoposide conditioning. CT study about 1 month later showed significant improvement in the condition, with interval regression of the mucoperiosteal thickening, bony erosion, and soft tissue swelling (Fig 8).
DISCUSSION The radiographic findings in patients with BRONJ include ill-defined areas of osteolysis, osteosclerosis, dense woven bone, thickened lamina dura, and persistent alveolar sockets with failure of postsurgical remodeling.5-7 More severe osseous destruction with a mixed density appearance, sequestration, and resulting periosteal reaction may be evident in advanced cases on CT.5,8,9 CBCT examinations of patients on bisphosphonates may show early bone alterations associated with the treatment, such as increased sclerosis and pronounced
616
crestal cortication. Even areas where there is no bone exposure show differences in bone structure that could be detected by fractal dimension evaluation.10 The radiographic features of BRONJ can be listed as: • thickening of cortical plate and lamina dura • increased crestal cortication • loss of distinction between the cortical and trabecular bone • focal areas of sclerosis • persistent extraction sockets • mixed sclerotic and lytic areas involving alveolar bone and basal bone • sequestra formation • periosteal reaction. Osteolytic punched out lesions without marginal sclerosis and generalized osteopenia are the most common radiographic manifestations of MM.11 Osteosclerotic manifestations such as diffuse or focal osteosclerosis, sunray appearance, and mixed radiolucent-radiopaque appearance are rare and have been reported in the literature.11-13
VOLUME 45 • NUMBER 7 • JULY / AUGUST 2014
Q U I N T E S S E N C E I N T E R N AT I O N A L Katkar et al
Although changes associated with BRONJ are apparent with various imaging modalities, including conventional radiographs, CT, MRI, positron emission tomography (PET), and nuclear medicine studies, the findings are typically nonspecific. Malignancy, usually metastatic, is often the differential diagnosis of greatest concern. If the changes are purely osteolytic and there is an associated destructive soft tissue mass, it merits further investigation. Sequestra and periosteal new bone formation are often seen in advanced cases of BRONJ and could help to rule out metastasis. However, when new malignant lesions develop in the preexisting BRONJ lesions, it is very difficult to differentiate based on panoramic radiographs or CBCT studies alone, which happen to be the commonly used diagnostic imaging modalities for evaluating such lesions. The CT findings in the present case were also suggestive of invasive fungal sinusitis. Invasive fungal sinusitis classically presents in immune-compromised patients with hematologic malignancies, diabetes mellitus, chronic steroid use, and acquired immune deficiency syndrome, as well as solid organ transplantation.14,15 CT has been found to be effective at isolating late-stage bone destruction while MRI is more sensitive for soft-tissue contrast and early-stage detection of extra-sinus involvement.16 Post-transplantation lymphoproliferative disorder can mimic invasive fungal sinusitis.16 Unusual coexistence of sinonasal myeloid sarcoma and acute fulminant invasive fungal sinusitis in a patient with relapsed acute myeloid leukemia has been reported recently.17 This case reflects how the clinical course of the patient can confound diagnosis and thus affect intervention. Imaging is one of the tools to assist in diagnosis, and multiple imaging techniques may be required for establishment of correct diagnosis. The patient had an established BRONJ lesion in the mandible. The maxillary CBCT was suggestive of BRONJ. However, the lack of exposed bone, and history of paresthesia warranted a soft tissue biopsy which was positive for MM. Biopsy is usually not advocated in cases of BRONJ to avoid further damage to already compromised osseous tissue. Vigilance is required to correlate clinical and radio-
VOLUME 45 • NUMBER 7 • JULY / AUGUST 2014
logic findings and further investigations must be considered if malignancy is suspected. Diagnoses and appropriate management of critical underlying pathoses can be challenging if the patient presents with signs and symptoms indicative of different conditions that may coexist.
REFERENCES 1. American Cancer Society. Cancer Facts & Figures 2012. Atlanta: American Cancer Society, 2012. 2. Fonseca R, Bergsagel PL, Drach J, et al. International myeloma working group molecular classification of multiple myeloma: Spotlight review. Leukemia 2009;23:2210–2221. 3. Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol 2005;23:3412–3420. 4. Katz J, George T, Sandow P, Machado M, Dickerson L, Moreb JS. Bisphosphonate-induced osteonecrosis of the jaw: Long-term outcomes. J Support Oncol 2009;7:9–10. 5. Arce K, Assael LA, Weissman JL, Markiewicz MR. Imaging findings in bisphosphonate-related osteonecrosis of jaws. J Oral Maxillofac Surg 2009;67(5 Suppl):75–84. 6. Khosla S, Burr D, Cauley J, et al. Bisphosphonate-associated osteonecrosis of the jaw: Report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007;22:1479–1491. 7. Morag Y, Morag-Hezroni M, Jamadar DA, et al. Bisphosphonate-related osteonecrosis of the jaw: A pictorial review. Radiographics 2009;29:1971–1984. 8. Bianchi SD, Scoletta M, Cassione FB, Migliaretti G, Mozzati M. Computerized tomographic findings in bisphosphonate-associated osteonecrosis of the jaw in patients with cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:249–258. 9. Bisdas S, Chambron Pinho N, Smolarz A, Sader R, Vogl TJ, Mack MG. Biphosphonate-induced osteonecrosis of the jaws: CT and MRI spectrum of findings in 32 patients. Clin Radiol 2008;63:71–77. 10. Torres SR, Chen CS, Leroux BG, Lee PP, Hollender LG, Schubert MM. Fractal dimension evaluation of cone beam computed tomography in patients with bisphosphonate-associated osteonecrosis. Dentomaxillofac Radiol 2011;40:501–505. 11. Witt C, Borges AC, Klein K, Neumann HJ. Radiographic manifestations of multiple myeloma in the mandible: A retrospective study of 77 patients. J Oral Maxillofac Surg 1997;55:450–453; discussion 454–455. 12. Ramon Y, Oberman M, Horowitz I, Freedman A, Tadmor R. A large mandibular tumor with a distinct radiological “sun-ray effect” as the primary manifestation of multiple myeloma. J Oral Surg 1978;36:52–54. 13. Ghosh S, Wadhwa P, Kumar A, Pai K, Seshadri S, Manohar C. Abnormal radiological features in a multiple myeloma patient: A case report and radiological review of myelomas. Dentomaxillofac Radiol 2011;40:513–518. 14. Gillespie MB, O’Malley BW Jr, Francis HW. An approach to fulminant invasive fungal rhinosinusitis in the immunocompromised host. Arch Otolaryngol Head Neck Surg 1998;124:520–526. 15. Parikh SL, Venkatraman G, DelGaudio JM. Invasive fungal sinusitis: A 15-year review from a single institution. Am J Rhinol 2004;18:75–81. 16. Hatten KM, Loevner LA, Palmer JN, Adappa ND. Isolated sinonasal posttransplantation lymphoproliferative disorder: A clinical and radiographic invasive fungal sinusitis look-a-like. ORL J Otorhinolaryngol Relat Spec 2012;74:339–342. 17. Kuo CL, Yu YB, Li WY, Lee YL. Unusual coexistence of sinonasal myeloid sarcoma and acute fulminant invasive fungal sinusitis: A diagnostic dilemma. J Laryngol Otol 2013;127:415–418.
617
RADIOLOGY/IMAGING
Rujuta A. Katkar
Multiple myeloma in bisphosphonate-affected jaws – a diagnostic challenge: Case report Rujuta A. Katkar, BDS, MDS, MS1/Joseph Katz, DMD2/Jan S. Moreb, MD3/Madhu K. Nair, DMD, MS, Lic Odont, PhD4 Objective: To discuss the challenges in diagnosis and appropriate management of critical underlying pathoses if a patient presents with signs and symptoms indicative of different conditions that may coexist. Summary: This case features clinical and radiographic challenges in reaching a diagnosis in a middle-aged man undergoing bisphosphonate therapy for multiple myeloma. The patient had history of bisphosphonaterelated osteonecrosis of the jaw (BRONJ) in the mandible. The patient presented with pain and swelling in the anterior maxilla, associated with paresthesia of upper lip. The radiographic
features were suggestive of BRONJ and invasive fungal sinusitis. MRI appearance was suggestive of malignant involvement by plasmacytoma or lymphoma. Although biopsy is usually not advocated in bisphosphonate-affected jaws, it was advised in this case and was positive for multiple myeloma. Vigilance is required to correlate clinical and radiologic findings and further investigations must be considered if malignancy is suspected. (Quintessence Int 2014;45:613–617; doi: 10.3290/j.qi. a31962)
Key words: bisphosphonate-related osteonecrosis of jaw, invasive fungal sinusitis, multiple myeloma
Recent advances in the development of new and effective anti-resorptive agents such as bisphosphonates (BPs) have brought a significant increase in the use of these drugs for osteoporosis, and primary and metastatic bone cancer including multiple myeloma (MM). It is not uncommon, therefore, for the general dental practitioner to encounter a patient affected by osteo-
1
Assistant Professor and Division Director, Oral and Maxillofacial Radiology, Department of Oral and Maxillofacial Diagnostic Sciences, Radiology, Colleges of Dentistry and Medicine, University of Florida, Gainesville, USA.
2
Professor, Oral & Maxillofacial Diagnostic Sciences, College of Dentistry, University of Florida, Gainesville, USA.
3
Professor and Clinical Director, Hematologic Malignancies, Division of Hematology/Oncology, College of Medicine, University of Florida, Gainesville.
4
Professor and Chairman, Oral & Maxillofacial Diagnostic Sciences, Radiology, Colleges of Dentistry and Medicine, University of Florida, Gainesville, USA.
Correspondence: Dr Rujuta Katkar, Oral and Maxillofacial Radiology, Department of Oral and Maxillofacial Diagnostic Sciences, Radiology, Colleges of Dentistry and Medicine, University of Florida, Gainesville, USA. Email: [email protected]
VOLUME 45 • NUMBER 7 • JULY / AUGUST 2014
necrosis of the jaw (ONJ), a complication of anti-resorptive agents that may affect 1% to 15% of the treated patients. It is imperative that the dental practitioner is familiar with different clinical and radiologic manifestations of ONJ for proper diagnosis and management of these patients. Specifically, detection of underlying malignancy can be challenging in the presence of changes associated with BP therapy. MM is a malignant plasma cell disorder that accounts for 15% of all plasma cell dyscrasias and 10% of all hematologic malignancies. It is more frequent in developed countries. The American Cancer Society (ACS) estimates that in 2012, about 21,700 new MM cases will be diagnosed in the United States, while 10,710 deaths are expected to occur.1 MM is characterized by a wide heterogeneity in clinical presentation and course. Recent advances have led to better understanding of the makeup of the disease and its micro-
613
Q U I N T E S S E N C E I N T E R N AT I O N A L Katkar et al
Fig 1
Exposed bone on the mylohyoid ridge of left mandible
environment, leading to new and novel therapies that have resulted in significant improvement in overall survival of patients with MM. The 2012 ACS’s statistics estimate that the 5-year relative overall survival rate for MM patients is around 40%. Intravenous BPs have been very instrumental in prevention of MM bone complications such as compression of the vertebra and pathologic bone fractures;2,3 however, 10% to 15% of patients receiving BP will develop BP-related osteonecrosis of the jaw (BRONJ), characterized by exposed bone that may become infected and may result in significant effects on the patient’s quality of life.4 Since the onset of BRONJ might be without symptomatology, a prompt and accurate diagnosis is essential to prevent further complication. Although the diagnosis of BRONJ is clinical, imaging has a significant role in supporting the diagnosis. Interestingly, the jaws are frequently affected by MM and as they are an exclusive site for the presence of BRONJ, the differential diagnosis of these two conditions may sometimes be challenging.4
CASE REPORT A 55-year-old man was referred to the oral medicine clinic due to sores on the left dorsum of the tongue and roughness on the lingual aspect of the posterior mandible. The patient’s medical history was significant for stage IIIA IgG lambda MM. He was on bortezomib and dexamethasone as well as monthly zoledronic acid intravenously. He was approximately 1-year post-autologous peripheral blood stem cell transplant (ASCT).
614
On examination, a 3 × 1 cm area of exposed bone with brownish color and rough edges was seen on the mylohyoid ridge of the left mandible (Fig 1). The appearance was consistent with BRONJ. There was also corresponding ulceration along the tip of the left side of the tongue. The patient was prescribed chlorhexidine rinses till the ulcer healed and the exposed bone resolved to some extent. The patient was taken off zoledronic acid and 3 months later had extractions of bilateral maxillary canines that were very mobile and painful, in preparation for a complete maxillary denture. Three months following the extraction, the patient was admitted complaining of significant pain in the left maxilla. On examination, bony expansion and tenderness on palpation of the left maxillary sinus and infraorbital area were noted. Partial paresthesia of the left upper lip was also reported. Non-contrast cone beam volumetric computed tomography (CBCT) study was performed (Figs 2 to 4). Multiplanar reconstructions demonstrated a mixeddensity appearance in the anterior maxilla. There was increased sclerosis with multiple areas of osteolysis and destruction of the buccal and palatal cortical plates. The inferior anterolateral wall of the left maxillary sinus was disrupted, resulting in oro-antral communication. These findings were compatible with BRONJ. However, clinically, there was no evidence of exposed bone in these regions. Mucoperiosteal thickening was present in both maxillary sinuses. There was no frank evidence of sequestration or periosteal reaction, which is usually seen in advanced cases of BRONJ. Because of frank bone destruction in the anterior wall of the left maxillary sinus with swelling and paresthesia in the affected region, malignancy was suspected. Non-contrast medical grade CT demonstrated mass lesions involving the pre-antral fat with erosive changes in both maxillary canine alveolar sockets, left side greater than right (Fig 3). Infiltration of the fat in the left buccal space and the left side of the face, and subtle infiltration in the right retro-antral fat was also present. Mucoperiosteal thickening was present in both maxillary sinuses. The appearance on CT was suspicious for invasive fungal sinusitis. Magnetic reso-
VOLUME 45 • NUMBER 7 • JULY / AUGUST 2014
Q U I N T E S S E N C E I N T E R N AT I O N A L Katkar et al
a
b
c
Figs 2a to 2c Pretreatment CBCT scan. (a) Axial view demonstrating destruction of the anterior wall of the left maxillary sinus, nonhealing extraction socket in the left maxillary canine region and increased sclerosis of the anterior maxilla. (b) Sagittal view demonstrating a soft tissue mass with destruction of the bone in maxillary left canine region. (c) Coronal view demonstrating non-healing extraction sockets in the maxillary canine regions bilaterally with disruption of the cortical plates and increased sclerosis of the bone. Fig 3 (left) Pretreatment CT axial view soft tissue window demonstrating mucoperiosteal thickening in the left maxillary sinus, erosion of the anterior wall with a soft tissue mass obliterating pre-antral fat. Fig 4 (right) Pretreatment MRI axial T2-weighted turbo-spin echo (TSE) postcontrast image demonstrating soft tissue masses in the anterior maxilla and mucoperiosteal thickening in the maxillary sinuses, left more than right
Fig 5 (left) Histopathologic section showing large plasmacytoid cells exhibiting pleomorphic hyperchromatic round to ovoid nuclei exhibiting a stippled chromatin pattern. Also noted in some areas are cells with abundant eosinophilic cytoplasm pushing the nuclei to an eccentric position. Foci of anaplastic cells, abnormal and increased mitoses, and cellular and nuclear pleomorphism are noted throughout this framework (hematoxylin-eosin; magnification 20×) Fig 6 (right) Photomicrograph showing florid positive cytoplasmic staining of neoplastic cells for lambda light chain stain thereby confirming a diagnosis of lambdarestricted multiple myeloma (magnification 10×).
nance imaging (MRI) evaluation was advised for further investigation. MRI evaluation showed mucoperiosteal thickening in both maxillary sinuses. Mass lesions involving the preantral fat pads and maxillary canine alveolar sockets, left greater than right, were noted as well (Fig 4). These lesions demonstrated enhancement on contrast imaging. The appearance was suggestive of plasmacytoma or lymphoma. Possibility of fungal sinusitis was ruled out.
VOLUME 45 • NUMBER 7 • JULY / AUGUST 2014
An incisional biopsy from the submucosa from the left maxilla revealed a malignant plasmacytic neoplasm consistent with lambda-restricted MM (Figs 5 and 6). The patient had palliative radiation treatment of the left maxillary region, left maxillary sinus, and bilateral maxillary alveolar ridges for 2 weeks. A CT scan taken 10 days later showed increased bone destruction involving the anterolateral and posterolateral walls of bilateral maxillary sinuses, increased mucoperiosteal
615
Q U I N T E S S E N C E I N T E R N AT I O N A L Katkar et al
a
a
b
Figs 7a and 7b CT scan after palliative radiation. Axial view bone windows demonstrate increased bone destruction involving the anterolateral and posterolateral walls of bilateral maxillary sinuses, increased mucoperiosteal thickening, and enlarged soft tissue mass on the left.
b
Figs 8a and 8b CT scan after chemotherapy. Axial CT bone windows demonstrate significant interval regression of the mucoperiosteal thickening, bony erosion, and soft tissue swelling.
thickening, and enlarged soft tissue mass on the left (Fig 7). The patient was put on a chemotherapy regimen followed by salvage ASCT with busulfan, cyclophosphamide, and etoposide conditioning. CT study about 1 month later showed significant improvement in the condition, with interval regression of the mucoperiosteal thickening, bony erosion, and soft tissue swelling (Fig 8).
DISCUSSION The radiographic findings in patients with BRONJ include ill-defined areas of osteolysis, osteosclerosis, dense woven bone, thickened lamina dura, and persistent alveolar sockets with failure of postsurgical remodeling.5-7 More severe osseous destruction with a mixed density appearance, sequestration, and resulting periosteal reaction may be evident in advanced cases on CT.5,8,9 CBCT examinations of patients on bisphosphonates may show early bone alterations associated with the treatment, such as increased sclerosis and pronounced
616
crestal cortication. Even areas where there is no bone exposure show differences in bone structure that could be detected by fractal dimension evaluation.10 The radiographic features of BRONJ can be listed as: • thickening of cortical plate and lamina dura • increased crestal cortication • loss of distinction between the cortical and trabecular bone • focal areas of sclerosis • persistent extraction sockets • mixed sclerotic and lytic areas involving alveolar bone and basal bone • sequestra formation • periosteal reaction. Osteolytic punched out lesions without marginal sclerosis and generalized osteopenia are the most common radiographic manifestations of MM.11 Osteosclerotic manifestations such as diffuse or focal osteosclerosis, sunray appearance, and mixed radiolucent-radiopaque appearance are rare and have been reported in the literature.11-13
VOLUME 45 • NUMBER 7 • JULY / AUGUST 2014
Q U I N T E S S E N C E I N T E R N AT I O N A L Katkar et al
Although changes associated with BRONJ are apparent with various imaging modalities, including conventional radiographs, CT, MRI, positron emission tomography (PET), and nuclear medicine studies, the findings are typically nonspecific. Malignancy, usually metastatic, is often the differential diagnosis of greatest concern. If the changes are purely osteolytic and there is an associated destructive soft tissue mass, it merits further investigation. Sequestra and periosteal new bone formation are often seen in advanced cases of BRONJ and could help to rule out metastasis. However, when new malignant lesions develop in the preexisting BRONJ lesions, it is very difficult to differentiate based on panoramic radiographs or CBCT studies alone, which happen to be the commonly used diagnostic imaging modalities for evaluating such lesions. The CT findings in the present case were also suggestive of invasive fungal sinusitis. Invasive fungal sinusitis classically presents in immune-compromised patients with hematologic malignancies, diabetes mellitus, chronic steroid use, and acquired immune deficiency syndrome, as well as solid organ transplantation.14,15 CT has been found to be effective at isolating late-stage bone destruction while MRI is more sensitive for soft-tissue contrast and early-stage detection of extra-sinus involvement.16 Post-transplantation lymphoproliferative disorder can mimic invasive fungal sinusitis.16 Unusual coexistence of sinonasal myeloid sarcoma and acute fulminant invasive fungal sinusitis in a patient with relapsed acute myeloid leukemia has been reported recently.17 This case reflects how the clinical course of the patient can confound diagnosis and thus affect intervention. Imaging is one of the tools to assist in diagnosis, and multiple imaging techniques may be required for establishment of correct diagnosis. The patient had an established BRONJ lesion in the mandible. The maxillary CBCT was suggestive of BRONJ. However, the lack of exposed bone, and history of paresthesia warranted a soft tissue biopsy which was positive for MM. Biopsy is usually not advocated in cases of BRONJ to avoid further damage to already compromised osseous tissue. Vigilance is required to correlate clinical and radio-
VOLUME 45 • NUMBER 7 • JULY / AUGUST 2014
logic findings and further investigations must be considered if malignancy is suspected. Diagnoses and appropriate management of critical underlying pathoses can be challenging if the patient presents with signs and symptoms indicative of different conditions that may coexist.
REFERENCES 1. American Cancer Society. Cancer Facts & Figures 2012. Atlanta: American Cancer Society, 2012. 2. Fonseca R, Bergsagel PL, Drach J, et al. International myeloma working group molecular classification of multiple myeloma: Spotlight review. Leukemia 2009;23:2210–2221. 3. Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol 2005;23:3412–3420. 4. Katz J, George T, Sandow P, Machado M, Dickerson L, Moreb JS. Bisphosphonate-induced osteonecrosis of the jaw: Long-term outcomes. J Support Oncol 2009;7:9–10. 5. Arce K, Assael LA, Weissman JL, Markiewicz MR. Imaging findings in bisphosphonate-related osteonecrosis of jaws. J Oral Maxillofac Surg 2009;67(5 Suppl):75–84. 6. Khosla S, Burr D, Cauley J, et al. Bisphosphonate-associated osteonecrosis of the jaw: Report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007;22:1479–1491. 7. Morag Y, Morag-Hezroni M, Jamadar DA, et al. Bisphosphonate-related osteonecrosis of the jaw: A pictorial review. Radiographics 2009;29:1971–1984. 8. Bianchi SD, Scoletta M, Cassione FB, Migliaretti G, Mozzati M. Computerized tomographic findings in bisphosphonate-associated osteonecrosis of the jaw in patients with cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:249–258. 9. Bisdas S, Chambron Pinho N, Smolarz A, Sader R, Vogl TJ, Mack MG. Biphosphonate-induced osteonecrosis of the jaws: CT and MRI spectrum of findings in 32 patients. Clin Radiol 2008;63:71–77. 10. Torres SR, Chen CS, Leroux BG, Lee PP, Hollender LG, Schubert MM. Fractal dimension evaluation of cone beam computed tomography in patients with bisphosphonate-associated osteonecrosis. Dentomaxillofac Radiol 2011;40:501–505. 11. Witt C, Borges AC, Klein K, Neumann HJ. Radiographic manifestations of multiple myeloma in the mandible: A retrospective study of 77 patients. J Oral Maxillofac Surg 1997;55:450–453; discussion 454–455. 12. Ramon Y, Oberman M, Horowitz I, Freedman A, Tadmor R. A large mandibular tumor with a distinct radiological “sun-ray effect” as the primary manifestation of multiple myeloma. J Oral Surg 1978;36:52–54. 13. Ghosh S, Wadhwa P, Kumar A, Pai K, Seshadri S, Manohar C. Abnormal radiological features in a multiple myeloma patient: A case report and radiological review of myelomas. Dentomaxillofac Radiol 2011;40:513–518. 14. Gillespie MB, O’Malley BW Jr, Francis HW. An approach to fulminant invasive fungal rhinosinusitis in the immunocompromised host. Arch Otolaryngol Head Neck Surg 1998;124:520–526. 15. Parikh SL, Venkatraman G, DelGaudio JM. Invasive fungal sinusitis: A 15-year review from a single institution. Am J Rhinol 2004;18:75–81. 16. Hatten KM, Loevner LA, Palmer JN, Adappa ND. Isolated sinonasal posttransplantation lymphoproliferative disorder: A clinical and radiographic invasive fungal sinusitis look-a-like. ORL J Otorhinolaryngol Relat Spec 2012;74:339–342. 17. Kuo CL, Yu YB, Li WY, Lee YL. Unusual coexistence of sinonasal myeloid sarcoma and acute fulminant invasive fungal sinusitis: A diagnostic dilemma. J Laryngol Otol 2013;127:415–418.
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