Clinical Study | Open Access
Head and Neck Solitary Extramedullary Plasmacytoma
Introduction. This study aimed to report the characteristics and treatment outcome of 13 patients with solitary extramedullary plasmacytomas of the head and neck and analytical literature review. Materials and Methods. Nine patients (69%) were treated with gross surgical resection followed by radiotherapy, three (23%) were primarily treated with radiotherapy alone, and one (8%) was treated with surgery alone. Results. There were 3 women and 10 men with the median age of 52 years. Nasal cavity (46%) and paranasal sinuses (23%) were the most common primary sites. After a median follow-up of 28 months, 10 patients are alive and free of disease, one is alive with multiple myeloma, and two died of multiple myeloma. In the literature review the median age was 58 years and male/female ratio was 2.7. Sinonasal tract was the most common primary site. Ten-year local control and progression to multiple myeloma rates were 88% and 23%, respectively. The 5- and the 10-year overall survival rates were 71 and 69%, respectively. Conclusion. Radiation therapy with or without surgery is an effective treatment for patients with head and neck extramedullary plasmacytoma. However, long-term follow-up for detection of local recurrence and progression to multiple myeloma is essential.
Plasmacytoma is a rare malignant tumor of monoclonal proliferation of plasma cells. It includes multiple myeloma that is a generalized disease and solitary plasmacytoma that occurs in a localized site . Solitary plasmacytomas account for approximately 5–10% of all plasma cell neoplasms and are divided into medullary if developed in bone marrow and extramedullary if originated from soft tissue [1–6]. Solitary extramedullary plasmacytoma (EMP) is an uncommon tumor consisting of 1-2% of all plasma cell neoplasms [4, 7]. Eighty percent of EMP arises in head and neck, particularly in the submucosal tissue of the upper aerodigestive tract such as nasal cavity, paranasal sinuses, nasopharynx, pharynx, oropharynx, and larynx [7–9]. These neoplasms typically present in the fifth to seventh decades of life and are 3 times more common in males .
Diagnostic evaluation includes history, physical examination, complete blood count, whole skeletal radiographic survey, serum and urine protein electrophoresis and immunofixation, quantitative immunoglobulin levels, urinary protein excretion in 24 hours, in addition to bone marrow aspiration and biopsy. Radiotherapy with or without surgery gives the best local and regional control . However, approximately 50% of medullary plasmacytomas ultimately progress to multiple myeloma [6, 32]. The aim of this study was to report the characteristics and treatment outcome of 13 patients with solitary EMPs of the head and neck and a literature review with quantitative summary and analysis of 26 major related studies including 551 cases over the last 20 years.
2. Methods and Materials
Thirteen patients diagnosed with solitary EMP of head and neck that were treated and followed up at 2 academic tertiary referral hospitals since 1999–2011 were studied. The study was approved by the Clinical Research Ethics Committee of Shiraz University of Medical Sciences in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans. In this study, solitary EMP was defined as a biopsy-proven single area of extramedullary tumor due to clonal plasma cells, normal skeletal survey, normal bone marrow or less than 5% plasma cell infiltration in the bone marrow aspiration and a bone marrow biopsy specimen with no evidence of plasma cell nodules, the absence of M-protein in serum and/or urine, normal complete blood count, normal serum calcium level, and the absence of related organ or tissue impairment such as renal dysfunction. Patients with small serum M component and with posttherapy normalized serum levels were not excluded. In addition, Immunohistochemical staining was performed for kappa and lambda light chains in 7 cases. All patients were treated with curative intent. Nine patients (69%) were treated with gross surgical resection followed by radiotherapy, three (23%) were primarily treated with radiotherapy alone, and one (8%) was treated with surgery alone. The last patient received salvage radiotherapy for local failure one year after primary surgical resection. The median total radiation dose was 49 (range 40–50) GY. Furthermore, in this study we represent a quantitative summary and analysis of pooled data collection of 26 major related studies published between 1998 and 2012 in PubMed including 551 cases.
There were 3 women and 10 men with the median age of 52 (range 21–78) years. Nasal cavity (46%) and paranasal sinuses (23%) were the most common primary sites. The mean tumor size was 4.5 (range 3–7) cm. Nasal obstruction (46%), pain (23%), neck mass (15.5%), and nasal bleeding (15.5%) were the most common presentations. After a median follow-up of 39.2 (range 6–151) months for surviving patients, 10 patients are alive and free of disease, one is alive with multiple myeloma, and two died of multiple myeloma (Table 1).
|GTR: gross tumor resection, RTR: radical tumor resection, and RT: radiotherapy.|
The 10-year local control rate was 89%. The 2-, 5-, and 10-year disease free survival rates were 77.8%, 64.8%, and 64.8%, respectively. The 2-, 5-, and 10-year overall survival rates were 88.9%, 74.1%, and 74.1%, respectively.
The majority of cases with solitary EMP occur in the head and neck region, although these neoplasms account for less than 1% of all head and neck tumors . This neoplasm usually occurs in the sixth and seventh decades of life. In the literature review, the median age of 357 patients in 18 studies was 58 (range 47–68) years [3–5, 7, 10–23]. In the present study, the median age of our patients was 52 years, which is within the range reported in the literature. There is a significant sex-specific susceptibility differences to solitary EMP. In all reported series in the literature, men represent a higher proportion of solitary EMP sufferers than women, with a mean male/female ratio of 2.7 (range from 1.5 to 14) in 17 studies including 400 patients (Table 2) [3–5, 7, 10, 11, 13, 14, 16–22, 24, 25]. In the present study this ratio was 3.3 which is consistent with the average range of the literature review.
|Pts’ number: patients number, MCST: most common primary sites, M/F: male/female, LC: local recurrence, PTMM: progressed to multiple myeloma, OS: overall survival, SNT: sinonasal tract, NPX: nasopharynx, LRX: larynx, and NC: nasal cavity.|
Sinonasal tract (47%), nasopharynx (15%), and oral cavity (10%) were the most common primary sites for solitary EMP [3, 4, 6, 7, 11, 13–26]. Similarly, sinonasal tract consisted of 69% of primary sites in our series. Solitary EMP is a highly radiosensitive disease and most reports show excellent local disease control and long-term myeloma free survival following radiotherapy alone. A total dose of 40–50 Gy is recommended by most authors. Surgery may have role in selected cases [2, 3, 8, 10, 11, 15, 23, 24, 27, 28, 31, 33]. The average median total radiation dose used for 499 patients in 22 studies was 44.5 (range 35–52.6) Gy [3–7, 10, 11, 13–19, 21, 23–26, 28–30]. In the present study, the median total radiation dose was 49 (range 38–50) Gy which is in agreement with the literature.
The 10-year local control rate of our patients was 88.9%, which is consistent with 88% (range 73%–100%) for 435 patients in 21 reported series in the literature (Tables 2 and 3) [3–7, 10–16, 18, 19, 21, 23–28]. Patients with solitary EMP are at risk of progression and development of multiple myeloma at a rate of 15% in 10 years (Table 3). Therefore, these patients should be followed up for prolonged period for detecting local recurrence and multiple myeloma . In the literature review, we found an average rate of 23% progression to multiple myeloma in 10 years for 529 patients in 23 studies [3–7, 10–19, 21, 23–30]. The 10-year rate for progression to multiple myeloma in our study was 15% which is comparable to the literature. This difference may be due to lower follow-up in our cases compared to most reported series. The 5- and the 10-year overall survival rates of our patients were 74.1%. In the literature review, the 5-year overall survival rate was 71% for 230 patients in 8 studies [4, 7, 10, 16, 22, 23, 26, 28], and the 10-year overall survival rate was 69% for 240 patients in 12 studies [5, 6, 11–15, 18, 19, 21, 25, 29].
|LR: literature review; L.N.: lymph node; MM: multiple myeloma; OS: overall survival.|
a[6, 9, 14–22, 27, 28, 30, 31].
In a similar study, Alexiou et al. performed a comprehensive literature review and analysis. They searched more than 400 publications between 1905 and 1997 to find all cases with EMP of the head and neck published in the medical literature . In Table 3, we performed a comparison between the results of Alexiou et al. literature review (before 1998) and recent literature published (1998–2012) [6, 10, 11, 14–24, 28, 30]. In addition, we performed a quantitative summary and analysis of these pooled data collection. Figure 1 represents the distribution of primary sites in 1072 patients with EMP in the head and neck. Accordingly, we found a similar distribution of primary sites and overall survival rates between Alexiou’s literature review and recent literature published (1998–2012); however, the rates of local control and progression to multiple myeloma were higher in our review compared to Alexiou’s literature review [6, 10, 11, 14–24, 28, 30, 31].
According to the results of the present study and review of the literature and by analyzing the large data collection of recent major reported series, we found that radiation therapy with or without surgery is an effective treatment for patients with head and neck extramedullary plasmacytoma. However, long-term follow-up for detection of local recurrence and progression to multiple myeloma is essential.
Conflict of Interests
All authors have no conflict of interests to declare.
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