British Journal of Radiology (2003) 76, 738-741
© 2003 British Institute of Radiology
doi: 10.1259/bjr/54563070
Definitive radiotherapy for extramedullary plasmacytomas of the head and neck
V J Michalaki, MD,
J Hall, MRCP,
J M Henk, FRCR,
C M Nutting, FRCR and
K J Harrington, FRCR
Head and Neck Unit, Royal Marsden Hospital NHS Trust, 207 Fulham Road, London SW3 6JJ, UK
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Abstract
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Extramedullary plasmacytoma of the head and neck region (EMPHN) is an uncommon malignant plasma cell neoplasm. In this study we conducted a retrospective analysis of our experience of EMPHN with particular emphasis on the role of definitive radiotherapy. From 1982 to 2001, 10 patients (6 males, 4 females) with EMPHN were treated in our institution. Of nine patients treated at initial diagnosis, all received definitive radiotherapy. One patient treated at relapse underwent surgical resection followed by post-operative radiotherapy. The median age at diagnosis was 55 years (range 35–84 years). The disease was most frequently localized in the paranasal sinuses (50%). All nine patients who received definitive radiotherapy at a dose of 40–50 Gy achieved a complete response. The median follow up period was 29 months (range 7–67 months). Four patients (40%) relapsed, three have died of their disease. Two patients (20%) with paranasal sinus disease subsequently relapsed with multiple myeloma at 10 months and 24 months, respectively. Our results indicate that treatment of EMPHN with radiotherapy achieves excellent rates of local control. The relapse rate in neck nodes of 10% does not justify elective irradiation of the uninvolved neck.
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Introduction
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Plasma cell malignancies include multiple myeloma, solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP). EMP is a rare tumour comprising approximately 3% of all plasma cell tumours. It typically arises in submucosal soft tissues and is destructive with a tendency to local recurrence. The disease is more common in males with a peak incidence in the sixth decade [1–4].
The head and neck region is the most common site of EMP. Tumours of the gastrointestinal tract and urogenital regions are also seen. For patients with extramedullary plasmacytoma of the head and neck (EMPHN), the most common subsites are the paranasal sinuses, nasal cavity and nasopharynx. Most patients with EMPHN present with local symptoms including obstruction, discharge, bleeding and pain, depending on the tumour subsite. The differential diagnosis includes benign reactive processes, carcinoma, lymphoma and esthesioneuroblastoma. The clinical behaviour of this tumour is not yet well defined and local recurrence, distant metastasis and transformation to multiple myeloma have all been reported [3–8].
Before making a diagnosis of EMPHN, it is mandatory to exclude multiple myeloma by performing serum protein electrophoresis, urinalysis for Bence-Jones protein, skeletal survey and bone marrow biopsy. For a diagnosis of EMP there should be less than 5% plasma cells in the bone marrow. As many as one-third of cases of EMP show a monoclonal band of serum protein at diagnosis and rarely Bence-Jones protein is seen in the urine. These markers usually disappear after successful treatment of the primary disease and subsequent elevation suggests recurrence or dissemination [5–10].
The optimal management of EMPHN is controversial. Surgery can achieve high rates of local control in certain situations. However, radical excision is often impossible due to the size of the tumour, the proximity of critical normal structures and the risk of a poor cosmetic result. EMP is a radiosensitive tumour and in most centres, radiotherapy is the mainstay of treatment. Adjuvant chemotherapy has not been shown to reduce relapse or improve survival rates and at present, has no place in the primary management of EMP [4, 9, 11].
The purpose of this article is to review our experience with these rare neoplasms, with particular emphasis on the role of radiotherapy as definitive treatment. A series of 10 patients with EMPHN is presented and their management and outcome are discussed.
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Patients and methods
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The Royal Marsden Hospital head and neck database (AHEAD) was searched for patients with a diagnosis of EMPHN between 1982 and 2001. This database contains information on all new patients referred to the Head and Neck Unit and is collected prospectively.
A comprehensive search was conducted using plasmacytoma, plasma cell neoplasm and plasma cell malignancy as search terms. The case notes of the patients who were identified in this way were analyzed for their demographic details, tumour description, management and outcome. In all cases it was confirmed that appropriate investigations (bone marrow biopsy, urine and plasma electrophoresis and skeletal survey) had been carried out to exclude a diagnosis of multiple myeloma.
Follow-up data were obtained for all patients. The response to treatment was defined as complete, partial or none according to RECIST criteria [12]. Disease-free (DFS) and overall survival (OS) times were calculated to the nearest month, taken from the time of presentation to the time of first relapse (for DFS) or death/last recorded follow-up (for OS). The relapse-free and OS curves were plotted and analyzed using the Kaplan Meier method.
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Results
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Clinical features
10 patients (6 males, 4 females) with EMPHN were identified. The median age was 55 years (range 35–84 years). In all cases, presentation was due to local symptoms. The subsites within the head and neck region that were involved are detailed in Table 1
. Nine patients were seen at their first presentation and one was referred at the time of relapse.
Treatment and response
In all cases the primary tumour was treated and no patient received elective cervical nodal irradiation or systemic chemotherapy. Radical radiotherapy was used as the definitive treatment in all nine patients who presented at first diagnosis. Radiation doses of 40–50 Gy in 15–25 fractions were delivered using megavoltage photons from a linear accelerator (or 60Co gamma rays in one early case). Another patient, referred at the time of disease relapse following previous chemotherapy, underwent maxillectomy and post-operative radiotherapy.
All nine patients who received radiotherapy as their primary treatment achieved a complete response. Seven patients (70%) were disease free at their most recent follow up (including one patient who achieved a complete response to cytotoxic chemotherapy following a diagnosis of multiple myeloma). Four patients (40%) relapsed, three have died of their disease. Two patients with paranasal sinus disease had locoregional relapses—one at the local site and one in bilateral cervical lymph nodes.
The patient who experienced failure at the local site as a result of a tumour resistant to radiotherapy, had previously received cytotoxic chemotherapy for an erroneous diagnosis of lymphoma. Two other patients with paranasal sinus disease subsequently relapsed with multiple myeloma at 10 months and 24 months, respectively. One patient remains disease-free 18 months after receiving combination VAD (vincristine, adriamycin, dexamethasone) chemotherapy and the other died 4 months after systemic relapse. The detailed follow-up of the 10 patients is described in Table 2.
Survival
The median follow-up for all patients was 29 months, ranging from 7 months to 67 months. At the time of analyzing these data 7 patients (70%) were alive and three (30%) have died of their disease. The disease progressed to multiple myeloma in two of the four patients who relapsed. There was no statistical difference in relapse rates when analyzed by age group (>60 years vs <60 years, p=0.93, log rank test), gender (male vs female, p=0.68, log rank test) or subsite (p=0.09, log rank test).
The OS and DFS estimates are shown in Figure 1.
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Figure 1. Kaplan-Meier curves showing overall survival (——) and relapse-free survival (----) for the 10 patients with extramedullary plasmacytoma of the head and neck.
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Discussion
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The optimal management of EMPHN is controversial with therapeutic choices resting between radiotherapy alone, surgery alone and surgery with post-operative radiotherapy. The rarity of EMPHN means that there have been no randomized controlled trials to define the best treatment, but there are several small retrospective case series (Table 3).
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Table 3. Previous series with results of five or more cases of extramedullary plasmacytoma of the head and neck (EMPHN)
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EMPHN is a radiosensitive tumour and in most centres, radiotherapy at a dose of 40–60 Gy over 4–6 weeks is the standard primary treatment [9]. The precise nature of the dose–response relationship is unclear. Mendenhall reported a threshold dose of 40 Gy for local control (69% for less than 40 Gy vs 94% for 40 Gy or more), but numbers were small [13].
In our series the doses used ranged from 40 Gy to 50 Gy with only a single (10%) local recurrence. If radiotherapy is to be used as primary treatment, it is clear that the primary tumour and involved lymph nodes should be irradiated, but controversy exists about the need to irradiate uninvolved locoregional nodes. Some authors have even advocated using a similar policy of nodal irradiation to that used for squamous cell carcinomas in the same site [14–18]. Our policy was to treat the primary tumour and involved nodes only. Despite this conservative approach, there was only one relapse in the cervical nodes.
The role of surgery is generally limited to open biopsy for diagnosis or for debulking a large tumour. Complete excision of EMPHN is often difficult due to the proximity to vital structures and frequent large size of the tumour. Surgery can often cause significant functional and cosmetic deformity. The rate of local control for EMPs following treatment with radiotherapy or surgery is good (75% to 95%). Persistence or recurrence of local disease does not often contribute to death, although a small number of those who die do so from local disease. Deaths from local disease tend to occur within 16 months of diagnosis [4, 19–21].
There does not appear to be a role for adjuvant chemotherapy. It has not been shown to reduce relapse or improve survival rates. However, it can be used at the time of recurrence or dissemination of disease [4, 23].
5-year survival rates for EMP are between 30% and 82% [1, 4, 9, 15–19, 21, 22, 25]. Most deaths occur from development of disseminated multiple myeloma. The rate of conversion of EMP to multiple myeloma has been shown to be from 10% to 36% in various series. Progression to multiple myeloma usually occurs within 2 years of diagnosis, but has occurred up to 15 years later indicating the need for long term follow-up [1, 4, 9, 15–19, 21, 22, 25, 26]. This biphasic nature of progression to multiple myeloma suggests that patients with early relapse probably had undetected myeloma present at the time of diagnosis. The more slowly progressing group may represent patients who developed new primaries in dysplastic marrow. This interpretation has important implications for more intensive screening to be carried out to exclude a diagnosis of multiple myeloma.
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Conclusion
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Treatment of EMPHN with radiotherapy achieves excellent rates for local control. The optimal dose is probably in the range of 40 Gy to 50 Gy although there are no randomized trials to confirm this. The low rate of relapse in regional nodes does not support a role for elective nodal irradiation. Intensive staging and long-term follow-up is essential to monitor local control and detect the development of multiple myeloma.
Received for publication February 20, 2003.
Revision received June 10, 2003.
Accepted for publication July 3, 2003.
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Abstract
Introduction
