INTRODUCTION

Extramedullary plasmacytoma is a rare malignant tumor of monoclonal plasma cells(1-3). The current classification of plasma cell dyscrasias require absence of multiple myeloma findings in order patients to be diagnosed with extramedullary plasmacytoma(1-4). Nevertheless, it has been well described that this tumor may either appear as a sequel of or convert to plasma cell myeloma(2,4).  Eighty to ninety percent of extramedullary plasmacytomas occur in the submucosal tissues of the head and neck, especially the aerodigestive tract(1-8,13,14), their incidence peaks earlier in life compared to multiple myeloma(3), and they are significantly more common in men than women(3,4).

CASE REPORT

A 74-year-old woman was referred to our department after presenting in the ophthalmology clinic of our hospital with headache and diplopia. Her previous medical and family history were unremarkable. The patient did not refer loss of weight or night sweats, fever or symptoms from the respiratory or digestive tract, but upon questioning she reported fatigue. On general physical examination there were no pathological findings. Ophthalmologic examination revealed right abducens nerve ophthalmoplegia and hypesthesia in the area of the right maxillary nerve distribution. The patient underwent blood test that revealed normocytic anemia with normal white blood cell count and increased erythrocyte sedimentation rate.

An MRI examination showed a lobulated mass in the sphenoid sinus that extended to the clivus and invaded the cavernous sinus on both sides, entrapping both internal carotid arteries (figures 1-3). Moreover, there were skull foci having pathological MR signal. Following the MRI exam, X-rays of the skull, the spine and the long bones of the extremities were performed, but they did not reveal any pathology. Subsequently, further serum biochemical tests were ordered that showed calcium levels within normal range and creatinine level of 126μmol/L. Serum protein electrophoresis demonstrated a monoclonal immunoglobulin spike. At that time all other laboratory examinations were normal. The patient underwent an endonasal biopsy of the tumor, which was histologically shown to be an extramedullary plasma cell tumor. She was treated with radiotherapy for the sphenoid sinus tumor focus and with systemic chemotherapy. 

DISCUSSION

Schridde Weitere first described plasmacytomas in 1905(15), over half a century after Otto Kahler defined multiple myeloma (also known as Kahler disease). Both plasmacytomas and multiple myeloma belong in the plasma cell dyscrasias, the classification of which has been revised in 2008 by the World Health Organization (WHO). Normal plasma cells are terminally differentiated cells originating from B lymphocytes (figure 4), they secrete immunoglobulins(3,8,9) and are situated in the red pulp of the spleen, the medullary cords of the lymph nodes and the bone marrow(9). Although older classification systems of plasma cell tumors grouped multiple myeloma as a type of plasmacytoma(4), the 2008 WHO classification of plasma cell dyscrasias categorize only solitary tumors under the plasmacytoma group (table 1)(3,9,12).

Multiple myeloma is the most common primary malignancy of skeletal tissue. It is the clinical syndrome of plasma cell myeloma(3) that is the neoplastic proliferation of plasma cells in the bone marrow, associated with production of monoclonal immunoglobulin in levels high enough to reach and be detectable in the serum or/and urine(3,11,12). Plasma cell myeloma originates from clonal plasma cells that in the bone marrow interact with the extracellular matrix, adhere to the stromal cells and trigger the plasma cell proliferation(11) and the production of monoclonal immunoglo-bulin(3). It occurs most often in males during their eighties and is more common in developed countries(3,11). Lytic bone lesions is the most common radiological finding, which explains the bone pain that is the presenting symptom in 70% of the patients with symptomatic plasma cell myeloma(3,11,12) (table 2).

Extramedullary plasmacytomas are isolated plasma cell neoplasms of soft tissues that need certain laboratory and imaging pre-requisites to be diagnosed(3).  They result from neoplastic proliferation of single clone plasma cells that, as a result, produce one type of immunoglobulin(8). Hence, a plasmacytoma is a single growth of proliferating plasma cells present either in bone as a solitary bone plasmacytoma or outside bone tissue, in which case it is called extramedullary or soft tissue plasmacytoma(3). For the diagnosis of skeletal or soft tissue plasmacytoma to be established, there are certain criteria that need to be met, which include i) normal skeletal X-ray, ii) normal humeri, spine, pelvis and proximal femurs MRI, iii) normal bone marrow biopsy, iv) no laboratory signs of anemia, hypercalcemia or compromise of renal function, and v) no or low levels of the involved monoclonal immunoglobulin with normal levels of the rest of the antibodies(3,12).  The incidence of extramedullary plasmacytomas is only 0.04-3 cases in 100,000(4), accounting for 1% of head and neck tumors(4). They most often (80%) occur in the aerodigestive soft tissues of the head and neck, and in particular in the nasal fossa, paranasal sinuses (especially the maxillary sinus), and the nasopharynx(1-8,13). Solitary plasmacytomas occur most often in males in their seventies(1-9,11-29) (table 2).      

Although there is no known agreement on whether extramedullary plasmacytoma and plasma cell myeloma are two different diseases or different stages of the same entity, there have been published cases of patients with multiple myeloma that have developed extramedullary plasmacytoma(24). It is generally accepted however, that it is more often, although still uncommon, extramedullary plasmacytoma to progress to plasma cell myeloma.  Rarely, it can also be the presenting form of plasma cell dyscrasia in a patient with multiple myeloma(4,16). Extramedullary plasmacytoma progresses in symptomatic plasma cell myeloma less frequently compared to its osseous counterpart(3,4), with one to three patients developing multiple myeloma within 10 years of being diagnosed with extramedullary plasmacytoma(17). The survival rate in these patients is very poor(4,24). Although extramedullary plasmacytoma most often appears in the aerodigestive tract of the head and neck(1-9,14, 16-18), involvement of the sphenoid sinus is rare, occurring only in 6.7% of the 175 patients that D'Aguillo et al reviewed(4) and recently described by Pagella et al to be only 2%(24).

The imaging examinations of patients with a suspected plasma cell dyscrasia include X-rays of the axial skeleton(3,11) and magnetic resonance imaging of the spine, humeri, pelvis and proximal femurs (3). Extramedullary plasmacytomas are detected in computed tomography scans and MRI imaging studies. CT demonstrates the tumor mass, which is often expansile and is always well-enhanced (27-31). However, CT is mainly useful for the imaging of bony lesions that may be present and occur due to plasma cell myeloma or/and due to the slow-growing extramedullary plasmacytoma that causes bone remodelling and that can extend to the neighbouring bone, leading to bone erosion(27-30). MRI is superior to CT for the imaging and the characterization of the soft tissue mass. The extramedullary plasmacytoma appears in T1 weighted MR images as a mass with intermediate signal intensity and in T2 weighted MR images as a moderate-to-high signal intensity mass(29). Because of the moderately to very high vascularity of the tumor(3), after the administration of contrast agent, the mass shows moderate to marked enhancement(29). Besides the role of imaging in the process of diagnosing multiple myeloma and/or extramedullary plasmacytoma, clinical symptomatology, blood examinations, biopsy and histopathology can only provide the definite diagnosis. Nevertheless, MRI is crucial in the follow-up of patients that have been treated for extramedullary plasmacytoma, permitting for the control of the tumor size(30). Regarding biopsy it should be noted that i) bone marrow involvement may be patchy, therefore a negative bone marrow biopsy in patients with clinical signs of disease should not be considered as absence of plasma cell myeloma(3,11), ii) biopsy of an extramedullary plasmacytoma should be undertaken only when feasible and when dissemination of malignant cells can be avoided(19), and iii) extramedullary plasmacytomas usually grow in the submucosa and therefore deep biopsy, open biopsy, or complete tumor excision is often required for histological confirmation of the diagnosis(2).

Although there are still controversies regarding the preferred treatment option of extramedullary plasma cell tumors, most authors suggest that depending on the tumor size and location, radiation therapy is the gold standard of therapy, with surgery being preferable only for tumors that can be safely removed(1,2,4,31-33).  Nevertheless, it should be kept in mind that radiotherapy in patients with extramedullary plasmacytoma increases the incidence of progression or conversion to multiple myeloma(2,4,23). Other prognostic factors related to increased risk of soft tissue plasmacytoma to multiple myeloma include tumor mass equal or greater than 5 cm, positive monoclonal protein, and β2 microglobulin levels in blood serum exam(23). Adjuvant chemotherapy is only considered for the treatment of patients with disseminated or recurrent disease(4). Since multiple myeloma is an incurable disease(11), patients with suspected extramedullary plasmacytoma require systematic clinical and diagnostic approach. Patients diagnosed and treated for extramedullary plasmacytoma need to be closely followed up with life-long observation.