Head and Neck Solitary Extramedullary Plasmacytoma

1 Shiraz Institute for Cancer Research, Department of Otolaryngology and Head and Neck Surgery, Khalili Hospital, Shiraz University of Medical Sciences, Shiraz 71936-13511, Iran 2 Student Research Committee, Department of Otolaryngology and Head and Neck Surgery, Khalili Hospital Shiraz University of Medical Sciences, Shiraz 71936-13511, Iran 3 Colorectal Research Center, Department of Radiation Oncology, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz 71936-13511, Iran 4 Student Research Committee, Department of Radiation Oncology, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz 71936-13511, Iran 5 Student Research Committee, School of Dentistry, Shiraz University of Medical Sciences, Shiraz 71447-16699, Iran


Introduction
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 [1].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][2][3][4][5][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][8][9].These neoplasms typically present in the fifth to seventh decades of life and are 3 times more common in males [7].
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 [10].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.

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.

Discussion
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 [31].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.
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 [31].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.[31] with the present study [6, 9, 14-22, 27, 28, 30, 31].

Variables
Alexiou's LR (before 1998) [31] Present  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].

Conclusion
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.

Table 1 :
Patient and tumor characteristics and treatment outcome of 13 patients with solitary EMP of the head and neck.

Table 3 :
Comparison of the results of patients with extramedullary solitary plasmacytoma of the head and neck in Aliexiou's et al. 's literature review