Solitary Mandibular Lesion as the Presenting Sign of Multiple Myeloma: A Rare Case Report
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1 CASE REPORT Solitary Mandibular Lesion as the Presenting Sign of Multiple Myeloma: A Rare Case Report Premalatha B R, 1 Lalitha R.M, 2 Roopa S Rao, 3 Jude J 4 ABOUT THE AUTHOR 1.Dr. Premalatha B R, Senior lecturer Karnataka, India prema.raaj@gmail.com, 2. Prof. Lalitha R.M, Professor & HOD Department of Oral Surgery lalitharm@gmail.com 3. Prof. Roopa S Rao, Professor & HOD drroopasrao1971@gmail.com 4.Dr. Jude J, Post graduate student jjudeib@gmail.com, Corresponding Author Dr. Premalatha B R, Senior lecturer M.S.Ramaiah Dental College Karnataka India prema.raaj@gmail.com Abstract Multiple myeloma (MM) is a rare hematological malignancy caused by monoclonal proliferation of plasma cells in the marrow of various bones. It is more common in men in the sixth and seventh decade of life. Patients usually present with bone pain, fatigue, recurrent infections, renal failure and nervous system dysfunction. Rarely, oral lesions may be the initial sign of multiple myeloma presenting with pain, jaw swelling, tooth mobility, multiple punched out radiolucencies and parasthesia. A case of multiple myeloma occurring in a 71 year old male patient who presented with a solitary lesion in the mandible is presented here. This paper highlights the importance of knowing oral manifestations of multiple myeloma and interdisciplinary approach required for early diagnosis. Key words: Elderly males, Multiple myeloma, solitary jaw lesion Introduction Multiple myeloma (MM) is a B-cell malignancy characterized by monoclonal proliferation of plasma cells in the bone marrow causing multifocal osteolytic lesions in the vertebrae, skull, ribs, pelvic bone and the jaw. The term Multiple myeloma was coined by Von Rustizky in It occurs more commonly in older men around years with mean age of 60 years. 2 Usually, MM manifests systemically as persistent bone pain, swelling and fracture, fever, fatigue, recurrent infections, kidney failure, hypercalcemia and temporal arteritis. Around 30% of the MM patients develop multiple osteolytic jaw lesions and other manifestations like tooth pain and mobility, gingival hemorrhage and parasthesia. 3 But, oral lesions may rarely present as the initial sign of MM in around 17% of the cases. 4 Here, we report a 71 year old male patient presenting with pain and solitary swelling in the posterior mandibular. CASE REPORT: A 71 year old male patient presented with a chief complaint of pain and swelling in the left mandibular posterior region since 20 days. Patient had undergone extraction of left mandibular molar tooth 1 month back, after which pain and swelling did not subside even after taking medication. His personal and family histories were non-contributory. On extraoral examination, patient had a swelling of size 4x4 cm with diffuse borders, firm consistency (Fig. 1). On intraoral examination, there was a swelling extending from 33 to 36 region, causing both buccal and lingual cortical expansion and unhealed sockets in relation to 33, 34 and 35.Orthopantamograph revealed solitary extensive radiolucent lesion with ill-defined margins perforating the lower border of mandible (Fig.2). CT scan of the mandible showed destructive lesion (Fig. 3). Routine blood examination revealed reduced RBC count and hemoglobin concentration. Microscopic evaluation of incisional biopsy revealed sheets of hyperchromatic round cells with few cells showing plasmacytoid features (Fig.4 A, B). An IHC panel for 1
2 Fig. 1: Small extra oral swelling in the left lower third of the face Fig. 2: OPG showing ill-defined radiolucency in left mandible molar region perforating the lower border. Fig. 3: CT scan showing destructive lesion with pathological fracture of left mandible. Fig. 5: Lateral skull radiograph showing characteristic multiple punched out radiolucencies. Fig. 4: A) Photomicrography shows replacement of bone by an infiltrative highly cellular lesion. (H&E, 4X). B) Pleomorphic round cells with few cells showing plasmacytoid differentiation. (H&E, 40X). C) IHC staining shows diffuse strong positivity for CD 138 2
3 Table 1: IHC panel- Round cell tumors Markers Cytokeratin CD 45 S 100 CD 99 CD 138 Desmin Results Table. 2: Diagnostic work-up for Multiple Myeloma Skeletal radiograph survey Complete hemogram Urine examination for Bence-Jones proteins and immunoelectrophoresis Serum protein electrophoresis Quantification of immunoglobulins Immunoelectrophoresis Bone marrow examination Biochemical assessment of renal function Calcium status round cell tumors was applied and strong positivity for CD 138 (Syndecan-1) was obtained. (Fig. 4 C, Table. 1). Hence, diagnosis of solitary plasmacytoma was made and further investigations were carried out to check for multiple lesions. On further evaluation, an x-ray of the hand revealed pathological fracture of the humerus, skull radiographs revealed multiple punched-out radiolucencies (Fig. 5). Considering the presence of multiple lesions in the skeleton, serum protein electrophoresis was done and it showed increase in M protein in the beta globulin region. Bone marrow examination revealed pleomorphic plasma cells confirming the diagnosis of Multiple myeloma. The patient was treated with combined chemotherapy and radiotherapy. The chemotherapy consisted of four cycles of thalidomide and corticosteroids. Radiotherapy consisted of 800 cgy to the right shoulder. The hand fracture was treated with placement of intramedullary nailing with an orthopaedic reference. Due to progressive bone pain, patient was given palliative treatment with pain killers. The patient responded to the treatment with a fifty percent decrease in the jaw tumor size after 4 months. But patient failed to report back and was lost for follow up. DISCUSSION: The plasma cell neoplasms of the head and neck can be classified into three types: 1) Solitary plasmacytoma affecting single site in bone 2) extramedullary plasmacytoma -affecting single site in soft tissues and 3) Multiple myeloma affecting multiple sites in the skeleton. 5 Most cases of plasmacytoma progresses to multiple myeloma involving multiple sites. The plasma cells in multiple myeloma are found to have profound genetic instability resulting in a complex set of numerical and structural chromosomal abnormalities like translocations involving 14q32and the immunoglobulin heavy-chain locus. 6 Bone involvement was thought to be due to tumour cell infiltration and proliferation. But, it is now believed that osteoclastic activating factor, a lymphokine, is responsible for the changes. 7,8 The incidence of multiple myeloma is 3:1,00,000 with a predilection for blacks when compared to whites. 9 Clinically, MM usually affects the vertebrae (66%), followed by the ribs (44%), skull (41%), and pelvis(28%). 6 The incidence of the oral lesions in multiple myeloma varies from 2% to 70%. 10 Jaws are affected usually at late stage of the disease, but rarely they may be the first presentation with an incidence of around 8-15 %. 11 Mandible is more commonly affected than maxilla and molar region is frequently involved than anterior region, as in our case. Oral manifestations of MM are jaw swelling, pain, tooth mobility, paresthesia, pathological fractures, gingival bleeding and soft tissue swelling with amyloid deposition. 3,8 Radiographically, MM usually presents as multiple radiolucent punched out lesions with distinct borders in the jaws. But, it can also occur as solitary radiolucent lesion with ill-defined borders as in our case. In these cases, further diagnostic work-up should be 3
4 done to rule out multiple myeloma (Table. 2). Rarely, MM can also present as diffuse osteosclerosis. 8 Bence Jones protein is a monoclonal globulin protein found in the blood or urine, with a molecular weight of kda. The proteins are immunoglobulin light chains (paraproteins) and are produced by neoplastic plasma cells. They are found in urine due to the kidneys' decreased filtration capabilities due to renal failure, sometimes induced by hypercalcemia from the calcium released as the bones are destroyed or from the light chains themselves. Bence Jones proteins are present only in 2/3 rd of multiple myeloma cases, hence their absence doesn t rule out the diagnosis. 12 A multidisciplinary approach is required to confirm the diagnosis when multiple myeloma is suspected (Table 2). 13 Diagnostic criteria for multiple myeloma are: 1) increased proliferation of plasma cells accompanied by an increase in their production of Monoclonal Ig proteins (M-protein)in the serum or urine (usually 30 g/l), 2) at least 10% plasma cells on a myelogram, 3) demonstration of monoclonal plasma cells on bone marrow biopsy and 4) end organ damage like hypercalcaemia, renal insufficiency, anemia, osteolytic bone lesions or extramedullary dissemination of myeloma tumour cells. Our case was confirmed by the increased serum M protein in electrophoresis and by bone marrow examination which revealed Grade III MM with plasmablastic type of cells with moderate to severe degree of pleomorphism and increased mitotic figures. Histologically, Multiple myeloma may be graded as: I) Low-grade -tumour cells indistinguishable from normal plasma cells. II) Intermediate grade -marked discrepancy of maturation between nucleus and cytoplasm. At least 50% of cells have enlarged nuclei with prominent nucleoli. III) High grade -plasmablastic type with large nuclei and very prominent centrally located nucleoli. The cytoplasm is restricted to a narrow rim. 14 Our case belonged to grade III with plasmablastic type of cells with moderate to severe degree of pleomorphism and increased mitotic figures. CD 138 or Syndecan is a useful specific IHC marker for plasma cells. The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. Syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. 15 Hematological examination with differential and total blood counts, biochemical assessment of renal function, calcium status, quantification of immunoglobulins, immunoelectrophoresis, urinalysis which includes immunofixation electrophoresis (IFE) and a radiographic skeleton survey should also be obtained for treatment planning and prognosis. Immunoelectrophoresis or immunofixation is used to identify the specific heavy (M, G, A, D, E) and light (κ or λ) Ig chain class. 16 Differential diagnosis of low grade multiple myeloma is plasmablastic lymphomas, where plasmacytoid cells can be seen, but they are negative for CD 138. In case of high grade multiple myeloma, differential diagnosis can be any round cell tumour like Ewing s family of tumours, rhabdomyosarcoma, lymphomas, small cell osteosarcoma and metastatic small cell tumour of lung. Multiple myeloma in younger adults can be a manifestation of HIV and should be investigated further. CONCLUSION: Although rare, oral manifestations can present as the initial sign of MM. Hence, clinicians should be aware of its manifestation in the oral cavity as a solitary jaw lesion. This can lead to an early diagnosis which is important for the better treatment and prognosis of multiple myeloma patients. BIBLIOGRAPHY: 1. Mandibular lesion presenting as the first sign of multiple myeloma a report of two cases. Merrin Jose, Anita Balan, Sharafuddeen K P, Nileena R Kumar, Haris P S.Int J Dent Case Reports 2011; 1(2): Pisano JJ, Coupland R, Chen SY, Miller AS. Plasmacytoma of the oral cavity and jaws: a clinicopathologic study of 13 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod Feb; 83(2): Epstein JB, Voss NJ, Stevenson-Moore P. Maxillofacial manifestations of multiple myeloma. An unusual case and review of the literature. Oral Surg Oral Med Oral Pathol 1984; 57: Witt C, Borges AC, Klein K, et al: Radiographic manifestations of multiple myeloma in the mandible: A retrospective of77 patients. J Oral MaxillofacSurg 1997; 53: John G. Batsakis, Jeffrey L. Medeiros, Mario A. Luna, and Adel K. El-Naggar. Plasma Cell Dyscrasias and the Head and Neck. Ann Diagn Pathol. 2002; 6: Drach J, Kaufmann H, Urbauer E, et al: The biology of multiple myeloma. J Cancer Res ClinOncol 2000; 126: Witt C, Adrian CB, Klein K, Neumann HJ. Radiographic manifestations of multiple myeloma in the mandible: A retrospective study of77 patients. J Oral MaxillofacSurg 1997; 55: T Baykul, U Aydin and MK O Carroll. Unusual combination of presenting features inmultiple myeloma. Dentomaxillofacial Radiology 2004; 33: Ryder C, Naclerio RM: Multiple myeloma presenting asproptosis. Ann OtolRhinolLaryngol 1999; 108: Lambertenghi-Deliliers G, Bruno E, Cortelezzi A, Fumagalli L, Morosini A. Incidence of jaw lesions in 193 patients with multiple myeloma. Oral Surg Oral Med Oral Pathol 1988; 65:
5 11. Zachriades N, Papanicolaou S, Papavassiliou D, Vairaktaris E, Triantafyllou D, Mezitus M. Plasma cell myeloma of the jaws. Int J Oral MaxillofacSurg 1987; 16: Hoffbrand V, Moss P, Pettit J (2006). Essential Haematology (Essential) (5th ed.). Blackwell Publishing Professional. p Greenberg MS, Glick M, Jonathan AS. Burket s Oral Medicine. 11th Edition. Ontario:BC Decker; 2008.p Sukpanichnant S, Cousar JB, Leelasiri A, et al: Diagnostic criteria and histologic grading in multiple myeloma: Histologic and immunohistologic analysis of 176 cases with clinical correlation.hum Pathol 1994; 25: Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J. "Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2". Somat. Cell Mol. Genet.1990; 16 (5): S.Vincent Rajkumar, Francis Buadi. Multiple myeloma: New staging systems for diagnosis, prognosis and response evaluation. Best Practice & Research Clinical Haematology 2007; 20(4):
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