Cytological diagnosis of multiple myeloma presenting as a jaw swelling.

Multiple myeloma is a systemic B-cell lymphoproliferative disease with varied manifestations. Its diagnosis can therefore pose difficulties for both the clinicians and pathologists. Jaw lesions, though not uncommon, rarely present as the first sign in multiple myeloma. We present here the case of a 45 year-old female who presented with a swelling of the jaw and on subsequent work-up, was diagnosed with multiple myeloma. Recent research regarding this disease has also been highlighted.

Introduction

Multiple myeloma is also known as Kahler's disease, myelomatosis, and medullary plasmacytoma.[1] It is considered to be the most common hematological malignancy after lymphoma, constituting about 10% of blood cancers.[2] The incidence of this disease is quite variable. In the USA, it varies from 1/100,000/year among Asians to 8–10/100,000/year among Afro–Americans.[2]

Bone involvement secondary to bone marrow infiltration is the most common manifestation and results in osteolytic lesions, bone pains, and pathological fractures. The resorption of bone is attributed to increased osteoclastic activity with increased proliferation and survival of osteoclasts.[2] It is now known that myeloma cells also cause inhibition of osteoblastic differentiation through the production of the dickkopf-1 protein.[23] Frequently affected sites include the vertebrae, ribs, skull, femur, clavicles, pelvis, and scapulae.[4]

Jaw lesions are rarely the first sign of the disease and the incidence varies from 8 to 15%.[56]

We present here the case of a patient whose initial presentation of multiple myeloma was a mandibular swelling.

Case Report

A 45 year-old female presented with swelling of the left jaw of two months′ duration that was associated with difficulty in swallowing. Local examination revealed a swelling in the left mandibular region, 2 × 3 cm in size, firm, fixed, and nontender with normal overlying skin. The margins were well defined and the surface was smooth; local temperature was not raised. Radiographic investigation revealed a destructive, radiolucent lesion in the posterior part of the body and ascending ramus of the left mandible.

The patient's hemoglobin was 5.1 g/dL and erythrocyte sedimentation rate was markedly raised (75 mm in the first two hours). The patient's urine was positive for Bence – Jones proteins. Other supportive investigations were subsequently conducted.

Radiological examination revealed the presence of punched-out lesions in the skull with generalized osteopenia. Mild splenomegaly was noted on ultrasonography of the abdomen.

Fine needle aspiration of the jaw swelling yielded a highly cellular aspirate with uniformly dispersed populations of abnormal plasma cells having abundant basophilic cytoplasm, eccentric, hyperchromatic nuclei with prominent nucleoli, and reticular chromatin [Figures 1 and 2]. The cells could be easily identified as plasma cells with their characteristic morphological appearance and therefore, the need for immunohistochemical analysis did not arise. Based on the pathological picture and reports of ancillary investigations, a diagnosis of multiple myeloma was established.

Figure 1

Numerous plasma cells in varying stages of maturation (Pap, ×500)

Figure 2

Dispersed population of myeloma cells with atypical nuclei, binucleation, prominent nucleoli, and loss of normal ‘clockwork’ chromatin pattern (H and E, ×500)

Discussion

Plasma cell myeloma of the jaw involves the mandible more frequently than the maxilla.[7] It is prudent to keep in mind that jaw involvement can also be asymptomatic and the jawbones are usually involved in patients with widespread skeletal involvement.[7] Therefore, radiographic assessment of the jaw is essential, especially in advanced cases.[7] Such an examination can yield three different types of presentations: generalised rarefaction, multiple radiolucent areas or, on occasion, there may be absence of bony abnormality.[8]

Fine needle aspiration is now a standard technique for the initial assessment of tumorous masses. Aspiration of bone frequently results in hemorrhagic aspirates with poor cellularity, but, in general, sufficient diagnostic material can be obtained from a malignant lesion.

The microscopic appearance of multiple myeloma is highly characteristic, with a monoclonal proliferation of plasma cells of variable maturity.[9]

The differential diagnosis of a jaw swelling can be exhaustive. Relevant conditions include osteomyelitis of the jaw, osteosarcoma, and lymphoplasmacytic lymphoma. Other conditions that should be kept in mind are Langerhans cell granulomatosis and metastatic disease.[10]

Osteosarcoma of the jaw is relatively uncommon.[11] The microscopic picture is usually characteristic with pleomorphic cells and osteoid in the background.

Lymphoplasmacytic lymphoma is characterised by a neoplastic proliferation of malignant lymphoid cells with plasmacytoid features.[9] However, the nuclei of the cells in lymphoplasmacytic lymphoma resemble the nuclei of lymphocytes rather than plasma cells. Immunochemistry is also helpful in differentiating it from plasma cell myeloma. The cells in lymphoplasmacytic lymphoma show positivity for surface immunoglobulin, CD19, and CD20 whereas myeloma cells are strongly positive for CD138 and negative for surface immunoglobulin and CD20.[1] Other lymphomas that can show plasmacytoid features include B-cell chronic lymphocytic lymphoma and follicular lymphoma.[1]

Langerhans cell granulomatosis can be identified without difficulty in presence of the characteristic Langerhans cells with a polymorphous mixture of inflammatory cells in the background.[9] Metastasis to the mandible or the maxilla is rare but the possibility must not be overlooked. Common sources of metastasis to the jawbone are the breast, lungs, kidney, and prostate.[12]

Ongoing research has provided insight into the molecular basis of multiple myeloma. These findings have an impact on prognosis and may possibly alter current treatment protocols of this disease.

Multiple myeloma can be subclassified into four types: hyperdiploid, hypodiploid, pseudodiploid, and near-tetraploid.[13] The latter three are collectively designated as ′non-hyperdiploid multiple myeloma′.[13] The non-hyperdiplioid (NH-MM) variant is characterised by primary translocation of the IgH locus on chromosome 14q32, whereas there is infrequent translocation of the IgH locus in hyperdiploid multiple myeloma.[13] It has thus been proposed that the evolution of multiple myeloma can proceed along two different or dichotomous paths.[14]

In addition, based on the pattern of IgH translocation and expression of cyclin D, multiple myeloma has been divided into different categories, providing a format for a molecular classification. This has been designated as the translocation/cyclin D expression (TC) classification.[14] The groups are identified as IIqB (16%), 6p21 (3%), MAF, 4p16, D1 (34%), D1 + D2 (6%) D2 (17%), and none (2%).[14]

Specific translocations of IgH have a bearing on prognosis. For example, patients with 4p16 have shortened survival, whereas D1 and 11q13 have better prognosis.[1516] Again, lytic bone lesions are very prevalent in categories 6p21, 11q13, D1, and D1 + D2.[14]

The molecular classification of multiple myeloma may thus provide a model for predicting response to therapy and survival. However, a composite standardised format will have to be developed and brought into widespread use. Novel therapeutic targets have also been identified, such as the dickkopf-1 protein[3] and CS-1,[17] a cell surface glycoprotein which is expressed in multiple myeloma.

Exciting developments in myeloma research promise a better opportunity for survival for patients and may help to reduce morbidity and mortality. However, since the clinical presentation of the disease does not seem to be influenced to any major extent by the molecular changes, an in-depth knowledge of the varied forms of presentation is unquestionably necessary for the clinician.