|Year : 2010 | Volume
| Issue : 1 | Page : 49-54
Multiple myeloma: Periapical location can challenge diagnostic skills
MB Radhika, Lalita J Thambiah, K Paremala, M Sudhakara
Department of Oral Pathology, Krishnadevaraya College of Dental Sciences, Bangalore, Karnataka, India
|Date of Web Publication||18-Nov-2011|
M B Radhika
Department of Oral Pathology, Krishnadevaraya College of Dental Sciences, Bangalore - 562157, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Multiple myeloma is a relatively rare malignant hematological disease, which is characterized by multicentric proliferation of plasma cells in the bone marrow and radiographically by osteolytic bone lesions and detectable presence of monoclonal immunoglobulins in serum and/or urine. Diagnosis of multiple myeloma can sometimes be challenging because of its plethora of clinical signs and symptoms. The product of the malignant plasma cells causes the different types of unusual clinical manifestations. We present the case of a 55-year-old female who presented with a periapical swelling in anterior maxilla in relation with 11 as the first sign of the disease.
Keywords: Multiple myeloma, Osteolytic lesion in maxilla, Periapical radiolucencies, Plasmacytoma
|How to cite this article:|
Radhika M B, Thambiah LJ, Paremala K, Sudhakara M. Multiple myeloma: Periapical location can challenge diagnostic skills. J Int Clin Dent Res Organ 2010;2:49-54
|How to cite this URL:|
Radhika M B, Thambiah LJ, Paremala K, Sudhakara M. Multiple myeloma: Periapical location can challenge diagnostic skills. J Int Clin Dent Res Organ [serial online] 2010 [cited 2020 Oct 21];2:49-54. Available from: https://www.jicdro.org/text.asp?2010/2/1/49/89997
| Introduction|| |
Multiple myeloma is a debilitating malignancy of the plasma cells. The disease was first described in 1844 as a disease characterized by proliferation of malignant plasma cells and a subsequent abundant production of monoclonal paraprotein. , An intriguing feature of multiple myeloma is that the antibody-forming cells (i.e., plasma cells) are malignant, and therefore may cause unusual manifestations.
We present a case of multiple myeloma presenting as a periapical lesion in the anterior maxilla of a 55-year-old female as the first sign of the disease. Jaw lesions are rarely the first sign of the disease, the incidence of which varies from 8 to 15%.  Multiple myeloma represents 1% of all cancers and 10% of all hematological neoplasms. 
| Case Report|| |
A 55-year-old female patient reported to a dental clinic in Bangalore with the complaint of swelling in the right side of the face near the nostril for the past 6 months, which was slow growing and not painful. Earlier, she had consulted an endodontist with the complaint of pain and tenderness in relation with 11 and was diagnosed as having non-vital 11 with periapical radiolucency. The endodontist had carried out endodontic therapy in 11 and had attempted incision and drainage. Later, she was referred for apicoectomy. On examination, the patient was well built. There was no history of any systemic disease. Extraorally, the patient had a diffuse swelling in the right ala region, measuring 1.0 cm × 1.5 cm; the skin over the swelling was normal in color and no pain was elicited on palpation. Intraorally, the patient had a restored 11 tooth and a periapical swelling in relation to it. The lesion was measuring 2.5 × 3.0 cm, firm in consistency, and the overlying mucosa was reddish in color with a break in the continuity of the mucosa.
Intraoral periapical radiograph revealed an ill-defined periapical radiolucency measuring 1.5 × 1 cm in relation to 11. The orthopantomograph was noncontributory [Figure 1].
|Figure 1: Intraoral periapical radiograph showing ill-defined periapical radiolucency in relation to 11|
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Routine blood examination was carried out and was within normal limits. Under local anesthesia with intravenous sedation, the lesion was surgically enucleated in toto. The enucleated mass was soft and fleshy in consistency, creamish brown in color with an irregular surface. The mass was sent for histological examination with a clinical provisional diagnosis of periapical granuloma.
The Hematoxylin and Eosin stained sections showed an extremely cellular lesional tissue showing diffuse sheets of neoplastic variably differentiated plasmacytoid cells in the connective tissue stroma [Figure 2]. These cells showed a round and eccentric nucleus with fine granular chromatin and evident nucleolus. Mitotic activity was evident. These features were characteristic of solid malignant hemopoietic neoplasm, and hence the given lesional tissue was suggestive of plasmacytoma.
|Figure 2: Photomicrograph showing different stages of differentiation and plasmacytoid appearance of the tumor cells (H&E, ×200)|
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The patient was advised to undergo urine analysis for Bence Jones protein examination, serum electrophoresis, computerized axial tomography (CT) of the head and neck, followed by a full body positron emission tomography (PET) scan.
The urine examination did not reveal Bence Jones protein. CT scan (paranasal with axial and coronal) performed with axial plane showed small destructive lesion in maxillary alveolar process in right paramedian region extending to the hard palate. Associated small soft tissue mass was seen. Small destructive lesions were seen in the frontal bone, left frontal sinus in the midline and left paramedian extending to the left ethmoidal sinus. Associated mild enhancing soft tissue mass was seen extending intracranially in the epidural plane. Small soft tissue mass was seen in the right frontal sinus.
The electrophoresis revealed increase in the serum free kappa light chains (392 mg/L), urine free kappa light chain (146 mg/L) and the urine kappa lambda ratio (130.4).
A detailed immunohistochemistry (IHC) workup was done for the following markers on the lesional tissue and the following were observed : kappa light chain showed strong cytoplasmic positivity [Figure 3], CD138 showed strong membranous and cytoplasmic positivity [Figure 4] and Ki67 showed 70% proliferation rate [Figure 5].
|Figure 3: Photomicrograph showing strong positivity (+++) for immunomarker kappa light chain, ×200|
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|Figure 4: Photomicrograph showing strong positivity (+++) for immunomarker CD138, ×200|
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|Figure 5: Photomicrograph showing 70% proliferation for immunomarker Ki67, ×200|
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The patient was referred to the regional oncology unit and was lost for follow-up.
| Discussion|| |
Multiple myeloma is a debilitating malignancy that is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance to plasma cell leukemia. Plasma cell tumors are lymphoid neoplastic proliferations that have been grouped among B-cell peripheral lymphomas, according to the classification of the European-American International Lymphoma Study Group.  They can affect a single bone, a condition called solitary plasmacytoma, or may involve only soft tissues, an extramedullary plasmacytoma. However, in approximately 95% of the cases, they involve several bones, and hence the condition is called as multiple myeloma. , The signs and symptoms of the disease were first documented by Samuel Solley in 1844, though the name multiple myeloma was given in 1873 by Jvon Rustizky. , It is also known by other names such as Kahlers disease, myelomatosis and medullary plasmacytoma.  The disease occurs frequently in patients of 50-80 years of age with a mean age of 60 years.  Rarely, the lesion is seen in patients younger than 40 years.  It is more frequently seen in men, and in all races, but more commonly seen in African-Americans and less commonly in the Asian population. , Bone invasion secondary to bone marrow infection is the most common. The frequently affected sites are vertebra, ribs, skull, femur, clavicle, pelvis and scapula. Jaw lesions in multiple myeloma may vary from 5 to 39% of the cases and represent the first sign of disease in 17% of the patients approximately. Though its occurrence in the maxilla and mandible is very common, oral lesions rarely appear as a primary manifestation of the disease. More than 30% of patients with multiple myeloma develop osteolytic lesions in posterior mandible.  Oral manifestations such as gingival hemorrhage, odontalgia, paraesthesia, dental mobility, and ulcerations may be the first presenting symptom. ,
Multiple myeloma lesions are more common in the mandibular posterior region, but in our case it presented itself as an anterior maxillary swelling.  Hence, it is a prudent to keep the diagnosis of multiple myeloma when single or widespread skeletal involvement is seen in the jaw bones.
A plain radiograph remains the golden standard for imaging procedure for diagnosis and staging of multiple myeloma.  A soap bubble appearance of osteolytic lesion can be frequently seen. PET scanning and magnetic resonance imaging (MRI) can add great value in diagnosis/prognosis and prediction. MRI has a higher sensitivity and specificity in diagnosis and treatment. 
Fine needle aspiration of the jaw swellings can yield useful results. Aspiration of bone/bone marrow can also be used. The microscopic appearance of biopsy of the lesion and bone marrow of multiple myeloma characteristically shows a monoclonal population of proliferating plasma cells with variable maturity. ,
Differential diagnosis on the jaw swellings can be exhaustive clinically but the main histopathological differential diagnoses are lymphomas (lymphoplasmacytic), granulomatosis (Langerhans cell) and metastatic tumors. 
IHC proves to be a useful tool in differentiating the lymphomas and multiple myelomas and gives an insight into the molecular basis of the disease. Myeloma cells express Syndecan-1 (CD 138) surface antigen that is limited to terminally differentiated plasma cells originating from the B-cell lineage. 
Light chain restriction for kappa or lambda is usually observed, and nearly 70% of plasma cell neoplasms are kappa positive. , AE1/AE3, HMB45 and S100 immunoreactivity in plasmacytomas is generally considered rare and these are done to exclude other pathologies. 
The monoclonal precursors of myeloma cells in the bone marrow originate in the lymph nodes. The mechanisms that enable these precursor cells to selectively lodge in the bone marrow where the particular microenvironment is conducive to their differentiation, proliferation and survival are not well understood. However, it is probable that the bone marrow microenvironment provides the specific chemotactic signals, and the monoclonal myeloma precursor cells express the necessary cell surface receptors for the bone marrow lodgement. There is adhesion to and transmigration of the endothelium that lines the bone marrow sinuses by the monoclonal precursors, which contribute to the preferential trafficking of these cells in the bone marrow. The interaction between tumor cells and the bone marrow stromal cells promotes neoangiogenesis that is essential for myeloma growth and facilitates the lodging of new tumor cells in the bone marrow and their subsequent uncontrolled proliferation. This leads to the osteolytic activity responsible for the development of the bone lesions characteristic to myeloma. ,
In the case presented here, the histological picture followed by subsequent IHC diagnosis and diagnostic workup clinched the diagnosis.
Plasmacytomas, lymphomas, leukemias and central giant cell granulomas can cause periapical bone destruction which can mimic periapical pathologies. ,,,
| Conclusion|| |
Multiple myeloma is a disseminated plasma cell neoplasm. Multiple myeloma is a systemic B-cell lymphoproliferative disease with varied head and neck and systemic manifestations. The diagnosis of multiple myeloma can be established by hematologic and biochemical findings, urine analysis and a skeletal radiographic survey. Cystic lesions in the jaw bones reinforce the fundamental role of dentist in recognition and early diagnosis of the systemic condition. Unfortunately, the disease carries an unfavorable or poor prognosis. Ongoing research in the field of molecular biology and phenotyping can improve diagnosis, classification, management and prognostic protocols of multiple myeloma.
| Acknowledgments|| |
We, the authors, would like to thank Mr. Samuel Rathna Raju and Mrs. Sunita. S, lab technicians, Krishnadevaraya College of Dental Sciences, Bangalore, for their technical work.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]