Extramedullary plasmacytoma presenting as a nasal mass in an immunosuppressed patient: treatment after failed primary radiotherapy.

Abstract

Most of the recent evidence suggests that extramedullary plasmacytoma should be treated initially with radiation, as response rates have exceeded 90% in many studies. Surgery is not considered a primary treatment modality for such tumors. We report the case of a chronically immunosuppressed 43-year-old man with bilateral extramedullary plasmacytomas of the nasal cavities. The right-sided mass was surgically excised, while the left-sided mass was initially treated with radiation. However, the left mass proved to be radioresistant, and it was subsequently excised surgically. The patient showed no evidence of recurrence of either mass at 42 months of follow-up. We believe that the particulars of this case, combined with the results of some recent studies, provide good evidence that surgery should be considered in the treatment of certain cases of extramedullary plasmacytoma.

Introduction

In view of the excellent outcomes, localized primary radiation therapy has become the treatment of choice for extramedullary plasmacytoma. (1,2) However, the optimal treatment for radiation failures has not been delineated. (3,4) Extramedullary plasmacytoma presenting in the setting of chronic immunosuppression may have unique characteristics and might require its own treatment strategy. In this article, we describe our treatment of a chronically immunosuppressed patient with a nasal extramedullary plasmacytoma that failed to respond to multiple administrations of primary radiotherapy.

Case report

A 43-year-old man was referred to our department by an allergist for evaluation of a 9-month history of progressive unilateral nasal obstruction. His medical history was significant for rheumatoid arthritis, for which he had been taking long-term immunosuppression therapy. He also had a history of gout and obstructive sleep apnea.

Nasal endoscopy detected a pink polypoid mass in each of the patient's nasal cavities. On computed tomography (CT), the mass in the left naris was situated just anterior to the inferior turbinate, and the smaller mass in the right cavity had originated in the nasal floor (figure 1). No evidence of bone invasion was seen in either naris.

The patient underwent endoscopic excisional biopsy of the right mass for diagnosis. The pathologic analysis identified the lesion as a plasmacytoma (figure 2). The specimen stained positive for IgA and lambda light chains, and it was also positive for Epstein-Barr virus (EBV).

During the immediate postoperative period, the patient underwent hematologic and oncologic evaluations. The results of a bone marrow biopsy and a bone survey were both normal. Protein electrophoresis revealed that the IgA and IgG levels were normal, but the IgM kappa monoclonal immunoglobulin level was elevated. Urinalysis showed the kappa light chain Bence Jones protein.

In this patient, two separate entities were present simultaneously--an extramedullary IgA-secreting plasmacytoma and a monoclonal gammopathy of undetermined significance that had occurred as a result of the immunosuppression therapy for his rheumatoid arthritis. After our multidisciplinary tumor board reviewed this case, the patient was counseled to undergo treatment for the left-sided extramedullary plasmacytoma with stereotactic radiotherapy (54 Gy in 30 fractions). However, despite delivery of the full course of radiotherapy, the size of the left nasal plasmacytoma did not change. Three months after the completion of radiotherapy, it was removed endoscopically. Pathology confirmed the mass as a persistent plasmacytoma. Despite a prolonged healing time, the patient exhibited no evidence of persistence or recurrence following surgical excision at 42 months of follow-up.

[FIGURE 1 OMITTED]

Discussion

Extramedullary plasmacytomas are monoclonal B-cell tumors that present as localized masses but do not meet the criteria for multiple myeloma because they do not involve the bone marrow. They account for approximately 3% of all plasma cell malignancies and less than 1% of all head and neck cancers. (1-3,5) More than 85% of extramedullary plasmacytomas are found in the upper aerodigestive tract. (2,5)

The most common symptoms at presentation are nasal discharge, nasal obstruction, and epistaxis. (2,5) The clinical features of extramedullary plasmacytoma include a median age at diagnosis of 55 years, a 3:1 male preponderance, and the presence of multiple lesions in about 10% of cases. (2) Progression to multiple myeloma occurs in less than 30% of cases. (2-4) When progression does occur, it is more common in patients with high-grade tumors. (1,5) Reported 5- and 10-year survival rates are approximately 80 and 67%, respectively. (2,5,6)

Treatment options for the potential cure of extramedullary plasmacytoma include surgery and radiation therapy. Radiation therapy is the more popular treatment because it is associated with excellent response rates (>90%) and low morbidity. (1,2) The British Society for Haematology has issued a set of guidelines for the diagnosis and treatment of extramedullary plasmacytoma. (2) The Society recommends initial radiation treatment with 40 Gy in 20 fractions with a 2-cm margin for tumors smaller than 5 cm, and 50 Gy in 25 fractions for larger tumors. Regional cervical lymph nodes should be irradiated only if they are directly involved or if there is a high risk of spread.

Overall, local recurrence rates following adequate radiation are less than 7%. (7) Most treatment failures are attributable to large tumor size (>5 cm) at the initiation of radiotherapy. (2,4,7) Surgery is an option when widely clear surgical margins can be obtained without causing surgical morbidity. (2,5) When clear margins are obtained, the probability of local control with surgery is similar to that with radiation therapy. (5,6)

Several investigators have suggested that the treatment of extramedullary plasmacytoma with adjuvant chemotherapy improves neither local control nor survival. (3,4,7) Current thought is that chemotherapy should be used for most cases of disseminated disease or conversion to multiple myeloma and in some cases of recurrence. The most significant tumor characteristic that may favor the addition of chemotherapy is histologic grade; high-grade tumors are associated with a higher risk of eventual disease dissemination or conversion to multiple myeloma. (1,3,5) Systemic chemotherapy can delay the development of multiple myeloma, and it may prolong survival in patients who eventually develop it. (7)

[FIGURE 2 OMITTED]

In addition to extramedullary plasmacytoma, our patient had rheumatoid arthritis. Prior to the diagnosis of extramedullary plasmacytoma, his arthritis had been treated for several years with the immunosuppressants methotrexate and cyclosporine and occasionally with prednisone. An increased risk of transplantation-related malignancies has been documented in patients who have undergone long-term immunosuppression. (8) The most common of these malignancies are the nonmelanoma skin cancers and non-Hodgkin lymphoma. It is interesting that transplant-associated non-Hodgkin lymphomas are usually associated with EBV infection in extranodal sites; our patient also had an EBV infection. (8) Also, an association between cyclosporine treatment and the development of malignancy has been known for years. (8)

In conclusion, the currently published guidelines on the treatment of extramedullary plasmacytoma suggest that radiotherapy is the best initial treatment for the vast majority of cases. (2) Surgical excision is an option when negative margins can be obtained without causing significant surgical morbidity; it is also an option for patients with persistent disease. Recent evidence suggests that complete surgical resection with clear margins and close follow-up is a legitimate primary treatment option. (3,5,6) Additional radiotherapy should be given when margins are not clear. Surgery also spares the patient the long-term complications of radiation.

The addition of chemotherapy should be considered in cases of high-grade tumors and if systemic dissemination or conversion to multiple myeloma occurs. After resolution, a strict follow-up plan should be maintained for the first several years because the risk of conversion to multiple myeloma is greatest during the first 3 years after treatment. (1,2,5,6)

References

(1.) Majumdar S, Raghavan U, Jones NS. Solitary plasmacytoma and extramedullary plasmacytoma of the paranasal sinuses and soft palate. J Laryngol Otol 2002;116(11):962-5.

(2.) Soutar R, Lucraft H, Jackson G, et al; Guidelines Working Group of the UK Myeloma Forum; British Committee for Standards in Haematology; British Society for Haematology. Guidelines on the diagnosis and management of solitary plasmacytoma of bone and solitary extramedullary plasmacytoma. Br J Haematol 2004;124(6):717-26.

(3.) Susnerwala SS, Shanks JH, Banerjee SS, et al. Extramedullary plasmacytoma of the head and neck region: Clinicopathological correlation in 25 cases. Br J Cancer 1997;75(6):921-7.

(4.) Tsang RW, Gospodarowicz MK, Pintilie M, et al. Solitary plasmacytoma treated with radiotherapy: Impact of tumor size on outcome. Int J Radiat Oncol Biol Phys 2001;50(1): 113-20.

(5.) Strojan P, Soba E, Lamovec J, Munda A. Extramedullary plasmacytoma: Clinical and histopathologic study. Int J Radiat Oncol Biol Plays 2002;53(3):692-701.

(6.) Liebross RH, Ha SH, Cox JD, et al. Clinical course of solitary extramedullary plasmacytoma. Radiother Oncol 1999;52(3):245-9.

(7.) Holland J, Trenkner DA, Wasserman TH, Fineberg B. Plasmacytoma. Treatment results and conversion to myeloma. Cancer 1992;69(6):1513-17.

(8.) Pacheco TR, Hinther L, Fitzpatrick J. Extramedullary plasmacytoma in cardiac transplant recipients. J Am Acad Dermatol 2003;49(5 Suppl):S255-8.

From the Department of Otolaryngology--Head and Neck Surgery, University of Iowa Hospital and Clinics, Iowa City.

Corresponding author: John H. Lee, MD, Department of Otolaryngology--Head and Neck Surgery, 200 Hawkins Dr., 21201 PFD, Iowa City, IA 52242-1093. Phone: [phone]; fax: [phone]; e-mail: [e-mail]

Ryan Dempewolf, MD; John H. Lee, MD