Journal of Oral Oncology

Volume 2014 (2014), Article ID 238698, 5 pages

http://dx.doi.org/10.1155/2014/238698

Clinical Study

Head and Neck Solitary Extramedullary Plasmacytoma

Bijan Khademi,¹ Zohreh Zandifar,² Mohammad Mohammadianpanah,³ Sayed Hasan Hamedi,⁴ Samira Razzaghi,⁴ Sareh Mahdavi,⁵ and Leila Moaddabshoar⁴

¹Shiraz Institute for Cancer Research, Department of Otolaryngology and Head and Neck Surgery, Khalili Hospital, Shiraz University of Medical Sciences, Shiraz 71936-13511, Iran

²Student Research Committee, Department of Otolaryngology and Head and Neck Surgery, Khalili Hospital Shiraz University of Medical Sciences, Shiraz 71936-13511, Iran

³Colorectal Research Center, Department of Radiation Oncology, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz 71936-13511, Iran

⁴Student Research Committee, Department of Radiation Oncology, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz 71936-13511, Iran

⁵Student Research Committee, School of Dentistry, Shiraz University of Medical Sciences, Shiraz 71447-16699, Iran

Received 3 April 2013; Accepted 19 December 2013; Published 4 February 2014

Academic Editor: Enver Ozer

Copyright © 2014 Bijan Khademi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

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.

1. 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 [1–6]. 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 [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.

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.

3. Results

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).

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

Case
Age (yr)/sex
Tumor location
Tumor size (cm)
Symptom
Follow-up (month)
Treatment
Dose of RT (Gy)

1
21/F
Nasal cavity
3.5
Nasal obstruction
36
GTR + RT
49

2
73/M
Nasal cavity
3
Nasal obstruction
40
GTR + RT
50

3
29/F
Nasal cavity
4
Nasal obstruction
39
GTR + RT
50

4
78/M
Nasal cavity
3
Nasal bleeding
14
GTR + RT
50

5
42/M
Nasal cavity
5.5
Nasal obstruction
151
RT alone
49

6
52/M
Nasal cavity
7
Nasal obstruction
15
GTR + RT
50

7
60/F
Nasopharynx
4
Nasal obstruction
32
RTR
40

8
63/M
Maxillary sinus
4.5
Pain
33
RT alone
50

9
36/M
Maxillary sinus
5
Pain
26
RTR + RT
48

10
21/M
Maxillary sinus
3.5
Nasal bleeding
6
GTR + RT
50

11
70/M
Neck soft tissue
6
Pain
28
RT alone
40

12
45/M
Neck L.N.
5
Neck mass
28
GTR + RT
45

13
73/M
Neck L.N.
4
Neck mass
16
GTR + RT
38

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.

4. 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.

Table 2: Characteristics and treatment outcomes of 565 patients with extramedullary solitary plasmacytoma of the head and neck in 26 reported series and the present study [3–7, 10–30].

Authors (references)
Pts’ number
MCPS
M/F
Median age
RT dose (Gy)
LC (%)
PTMM (%)
OS rate

Bachar et al. [24]
68
SNT
41/27
—
35
—
23
76% (5 yr)

Bolek et al. [29]
10
—
—
—
43.2
100
54
80% (15 yr)

Chao et al. [11]
14
SNT, NPX
14/0
59
45
100
31
54% (10 yr)

Creach et al. [10]
18
—
16/2
64
50.4
100
11
31–82% (5 yr)

Galieni et al. [12]
16
—
—
54
—
92
15
78% (15 yr)

Hotz et al. [27]
14
—
—
—
—
86
14
—

Jyothirmayi et al. [3]
7
SNT
6/1
58
40
85
42
57%

Kapadia et al. [13]
20
SNT, NPX
16/5
59
40–45
85
20
85% (10 yr)

Kilciksiz et al. [14]
23
Oral cavity
14/9
47
50
95
17.4
89% (10 yr)

Krause et al. [15]
8
NPX
—
61
48
100
25
100 (10 yr)

Liebross et al. [28]
19
—
—
—
50
95
44
50% (5 yr)

Mendenhall et al. [4]
20
SNT, NPX
17/3
62
40–50
100
30
80% (5 yr)

Michalaki et al. [16]
10
SNT
6/4
55
40–50
100
20
50% (5 yr)

Miller et al. [17]
18
SNT, NPX
12/6
50.4
45–50
—
11
—

Ozsahin et al. [26]
52
SNT
—
—
40
74
36
72% (5 yr)

Reed et al. [23]
23
SNT
—
56
45
92
30
85% (5 yr)

Sasaki et al. [18]
67
SNT
43/24
64
50
87
12
56% (10 yr)

Shih et al. [5]
10
—
9/1
63
54
70
20
100% (10 yr)

Strojan et al. [25]
22
Oropharynx
17/5
—
54
100
8
61% (10 yr)

Suh et al. [19]
13
SNT
8/5
52
50
77
15
87% (10 yr)

Susnerwala et al. [7]
25
SNT
23/2
68
38.9
79
8
59% (5 yr)

Tournier-Rangeard et al. [21]
17
SNT, NPX
14/3
62
52.6
73
31
63.4% (10 yr)

Tsang et al. [6]
14
SNT, NPX
—
—
35
93
84
65% (10 yr)

Yang et al. [20]
23
SNT
17/6
49
—
—
—
—

Yang et al. [30]
8
—
—
—
35
—
12.5
—

Zhou et al. [22]
12
SNT
10/2
57
—
—
—
53% (5 yr)

Present study
13
SNT, NPX
10/3
52
49
89
15
74.1% (10 yr)

Total
564
SNT
293/108
58
44.5
88
23
70

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 [31]. 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].

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

Variables
Alexiou’s LR (before 1998) [31]
Present LR (1998–2012)a
Present study
Overall

Patients’ number
714
345
13
1072

Primary sites

    Sinonasal tract
313 (44%)
163 (47%)
9 (69%)
485 (45%)

    Nasopharynx
131 (18%)
51 (15%)
1 (8%)
183 (17%)

    Oral cavity
22 (3%)
35 (10%)
0 (0.0%)
57 (6%)

    Oropharynx
103 (15%)
26 (7.5%)
0 (0.0%)
129 (12%)

    Larynx
79 (11%)
26 (7.5%)
0 (0.0%)
105 (10%)

    Hypopharynx
4 (0.5%)
2 (0.5%)
0 (0.0%)
6 (0.5%)

    Salivary glands
29 (4%)
4 (1%)
0 (0.0%)
33 (3%)

    Cervical L.N.
12 (1.5%)
13 (4%)
2 (15%)
27 (2.5%)

    Orbit
0 (0.0%)
13 (4%)
0 (0.0%)
13 (2%)

    Miscellaneous
16 (2%)
12 (3.5%)
1 (8%)
29 (3%)

Local control rate
78%
87%
89%
81%

Progression to MM rate
16.1%
21%
15%
17.7%

5-year OS
73.3%
72.5%
74.1%
73%

10-year OS
68.5%
69%
74.1%
69%

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 [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. 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].

Figure 1: The distribution of primary sites in 1072 patients with EMP in the head and neck in the literature [6, 9, 13–22, 27–29, 31].

5. 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.

Conflict of Interests

All authors have no conflict of interests to declare.

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