Independent Researcher, Paterson, NJ 07533, USAUnited States
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Background: This study reviews the published literature related to nasopharyngeal plasmacy-toma. Clinical presentation, demographics, treatment, and outcomes of this uncommon disease have been reported. Methods: A systematic review of studies on nasopharyngeal plasmacytoma from 1935 to 2016 was conducted. A PubMed database search was performed for articles related to this condition along with the bibliographies of those selected articles. Articles were examined for patient data that reported the disease outcome. Results: Fifty-eight journal articles were included in this analysis, comprising of a total of 114 studies indicative of a predilection for cases particularly in men with a mean age of 55 years (sixth decade of life) characterized with symptoms such as nasal obstruction, epistaxis and neck lymphadenopathy. Radiotherapy was the most common treatment modality, followed by a combination of surgery and radiotherapy. Most of the patients were alive with no evidence of the disease after the median follow-up of 59 months. Of the 3 most common treatment modalities, a combination of radiotherapy and surgery had the most favorable outcome for a majority of patients. The existing condition for 8 patients (7%) deteriorated leading to the development of multiple myeloma. Conclusion: This review contains a large pool of information about nasopharyngeal plasma-cytoma patients examined to date suggesting that aggressive radiotherapy is the most common treatment modality for this condition. Of the 3 most common treatment modalities, a combination of surgery and radiotherapy was shown to have the best survival outcomes.
Keywords: Pharyngeal plasmacytoma; Extramedullary plasmacytoma; Nasopharyngeal tumor; plasmacytoma; Radiotherapy; Chemotherapy; Surgical management; Nasopharyngeal tu- mor
Extramedullary plasmacytoma (EMP) is an uncommon tumor, constituting only 3% of all
plasma cell neoplasms and less than 1% of all head and neck tumors. Nasopharyngeal plasma-
cytomas are very rare tumors with very few cases reported in the literature. Thus, there is little
evidence regarding the epidemiology, optimal management, and long-term prognosis for these
types of cancers. Because it is an uncommon tumor, it is difficult to perform a randomized con-
trolled trial to determine the optimal management of nasopharyngeal EMPs.Therefore, in this
article; we perform a systematic review of 114 cases of nasopharyngeal EMPs, representing the
largest unified collection of nasopharyngeal EMPs investigated to date.
of tumor.
A systematic review was conducted for all cases of nasopha-
ryngeal plasmacytoma reported from 1935 to 2016 using the
PubMed database. The search criteria were set as “nasopharyn-
geal plasmacytoma,” “head and neck plasmacytoma,” “upper
airways plasmacytoma,” and “sinonasalplasmacytoma”. Four
hundred eighty-one articles were initially analyzed. Articles
were then filtered to exclude studies conducted in non-human
subjects and non-English articles.
Abstracts were first reviewed to search for articles that
discussed cases of plasmacytoma occurring in the nasopharynx
and full-text articles were subsequently selected and reviewed
for data extraction. References of the included studies were ex-
amined for additional cases (Figure 1).
All studies conducted on human subjects and published in Eng-
lish language that reported individual data for nasopharyngeal
plasmocytoma were included if they reported diagnosis, treat-
ment, follow-up, and outcome. Non-human, radiologic, cadav-
eric, anatomical, and histological studies were excluded, on ac-
count of being sources with insufficient or unextractable data.
Articles with unobtainable full text were also excluded from the
study. Outcome measures extracted included: demographic data,
presenting symptoms, primary treatment modality, recurrence,
MM development and metastasis.
Two-year overall survival (OS), disease-specific sur-
vival (DSS), locoregional recurrence and MM development
Figure 1. Flowchart of the Study Selection Process.
Additional 3 articles from
other resources
rates were calculated using the Kaplan-Meier method. Differ-
ences in the survival rates were assessed by the log-rank test. All
the recorded p-values were two-sided, and a p-value <0.05 was
adopted as the threshold for statistical significance.
The final PubMed searches using the selected keywords yielded
58 studies from a total of 114 patients which were left for sta-
tistical analysis. All 58 studies included individual patient data
that was extractable and fit the minimum criteria for inclusion
(Table 1).
Patient demographics for 113 patients included in this review are
summarized in Table 2.
The mean age of patients was 55 years, ranging from 3
to 85 years. Males constituted nearly 69.4% of the cases, where-
as females constituted nearly 30.6% of the cases. The mean
follow-up for patients was 59 months. Information about his-
tological grade was reported in only 19 articles. The most com-
mon presenting symptom was nasal obstruction (29.8% of cas-
es). Further demographic information is summarized in Table 2.
A majority of patients nearly 56% were treated with radiother-
apy alone (n=63) and nearly 21% were treated in combination
with surgery, or in combination with surgery and chemotherapy
(n=3), or in combination with chemotherapy (n=4). The remain-
ing patients received surgery alone (n=13) or chemotherapy
alone (n=1). Further information regarding treatment modality
• 4 PubMed searches
• Non-full text
• No individual data
• Non-human
• Irrelevant
• Duplicate
• Histologic or radiologic articles
Table 1. Patients Data.
Fu et al 68/M S Nasal obstruction N/A
35/M S Nasal obstruction N/A
Poole et al 51/M M foreign body N/A
41/M M Epistaxis N/A
78/M S N/A
59/F S N/A
3 Nasal obstruction Lindberg et al 65/M S N/A
Bush et al 41/M S N/A N/A
56/M S N/A N/A
Kapedia et al 45/M S N/A N/A
78/M S N/A N/A
52/M S N/A N/A
Du et al 63/M S epistaxis N/A
Stout et al 61/F s Nasal obstruction N/A
38/M s Post nasal discharge N/A
Figi et al 48/M s N/A N/A
47/F s N/V
Scuderi et al 39/M s N/A N/A
Mattick et al 61/M M N/A N/A
Ewing et al 61/M S N/A N/V
48/F S Hearing loss N/A
Webb et al 48/M S Accidentally N/A
83/F S Epistaxis N/A
49/M S N/A
76/M S N/A
13 Nasal obstruction Waltner et al 39/M S N/A
61/F S N/V N/A
14 Nasal obstruction Anderson et al 39/M S N/A
72/M S N/A
77/F S N/A
- S - - NED 3 M
- S - - NED 1 M
Nasal obstruction
- S+RT - - Dead 4 Y
sensation
- S+RT - - Dead 5 Y
Nasal obstruction - S+RT - - NED 7 Y epistaxis
Nasal obstruction RT - - - NED 8 Y epistaxis
RT - - NED 10 Y epistaxis
Another AWD RT + solitary - On chemotherapy local mylonatibia 7.5 year 18 months
MM 2 Y Dead 9 Y
- RT - - N/A
- RT - - N/A
Other MM 2 M - RT+ CH back of tibia Dead MM 14 M
Nasal obstruction RT - - NED 18 M - 6 cranial nerve palsy
Dead from
RT - + femur metastasis
3.5 Y
S+RT - - NED 2 Y
- S+RT - - NED 3 Y
N/A - S+RT - - AWD 20 Invasive
- S+RT - - NED 6 M
- S - - NED 3 M
- RT - - N/A
Dead of
- RT - - stomach
cancer 3 Y
- S - - NED 22 Y
Another Dead 1 Y - RT - Solitary metastasis Ankle
Lymph node Nasal obstruction - RT 7 year - NED 7 Y
removed s+RT
Nasal obstruction + RT - - Dead 6 M
- RT - - NED 2 Y
Dead 6 Y metas- - RT - + tasis
Dead 1 YEAR + RT Local 1 year + 1 Y metastasis
Nasal obstruction - S+RT - - NED 5 Y
Nasal obstruction + RT - - Dead 7 M
57/M S N/A
Fuerste et al M/56 M N/A N/A
Dolin et al M/66 S N/A N/A
M/65 S N/A N/A
Mann et al M/3 S N/A N/A
M/3 S N/A N/A
Tan et al F/12 S N/A N/A
Rutherford et al F/13 S N/A N/A
Strojan et al M/43 MM N/A N/A
M/38 S N/A K
M/56 S N/A L
M/43 M N/A K
M/85 S N/A L
Kayrouz et al M/71 S N/A N/V
Corwin et al 54/M S N/A N/A
57/M S N/A N/A
Wiltshaw et al F/21 S N/A N/A
Ching et al F/66 S Headache N/A
F/43 S Epistaxis N/A
Zou et al M/45 S N/A N/A
F/66 S N/A N/A
26 Nasal obstruction Khademi et al F/60 S N/A
Susnerwala et al M/72 S N/A k
M/48 S N/A
M/73 S N/A k
M/74 S N/A L
Wein et al M/48 S epistaxis k
Manganaris et al F/41 S Epistaxis N/A
30 Epistaxis Chang et al M/15 S N/A
31 Epistaxis Abdullah et al 64/F S N/A
Lin et al 42/M S Nasal Obstruction N/V
33 Epistaxis Azman et al M56 S l
Natt et al M75 S Epistaxis N/A
Sulzner et al M/56 S Epistaxis N/A
Foreign body - RT - - NED 2 Y sensation
Dead 2 Y metas- - none - + tasis
Local
- S+RT recurrent - AWD 2 Y
2 year
Local
- S+RT recurrent - AWD 1 Y
1 year
- S - - NED 4 Y
- S - - NED 1 Y
- S+RT - - NED 1 Y
- none - - N/A
- RT - - NED 19.5 Y
S+RT - - NED 14.4 Y
- S+RT - - NED 4.2 Y
- S+RT - - NED 3.7 Y
- RT NED 2 M
Recurrent
2 years - RT - NED 10 Y treated with
radiotherapy
RT - - - NED 320 M
RT - - - NED 116 M
- RT+Ch - - NED 8 Y
- RT - - NED I Y
Recurrent
- RT local - AWD 1 Y
1 year
- S - - N/A
- S+RT - - NED 65 M
- S - - NED 32 M
- RT - - Dead 48 M from MI
k MM 120 M Amyloidosis Dead 180 M
- RT - - NED 40 M
- RT - - NED 44 M
Recurrent Nasal obstruction 6 months - RT - NED 1 Y retreated anosmia stereotactically
- S - - NED 2 Y
+ S+RT - - NED 3 M nasal obstruction
- S+RT - - NED 6 M nasal obstruction
- RT - - N/A
- RT - - NED 7 Y nasal obstruction
- RT - - NED 6 M
+ RT - - Dead 6 Y of MI
Knowlin et al M/79 S N/A N/A
37 Epistaxis Sadek et al M/48 S K
38 N/A Woodruff et al M/20 S N/A
M/77 S N/A N/A
M/56 S N/A
Chao et al M/69 S E N/A
M/74 S Nasal obstruction N/A
40 Hearing loss Nikolidakis et al F/72 S K
Hotz et al 63 M N/A N/A
77 M N/A N/A
59 S N/A N/A
44 S N/A N/A
45 M N/A N/A
63 S N/A N/A
Kotner et al 59 S N/A N/A
49 S N/A N/A
60 S N/A N/A
64 S N/A
78 S N/A N/A
72 S N/A
Miller et al M/76 S Nasal obstruction k
M/64 S Nasal obstruction l
M/49 S N/V
F/20 S Nasal obstruction N/A
M/47 S Hearing Loss K
M/63 S Nasal obstruction K
44 M Isri et al F/49 Nasal obstruction N/A
Widziszowska et al M/63 S epistaxis N/A
Satomi et al M/72 S Epistaxis L
47 Hearing loss Lorusso et al M/71 S K
Shih et al M/49 S N/V N/A
M/28 S Mass N/A
M/62 S Mass N/V
M/64 S Mass N/V
Dead 100 M of COPD
+ - RT+ S+ Ch - NED 12 Y nasal obstruction
RE DEAD 6 Y of - RT+CH - Invasive 3 M disease
DEAD 3 M MI
N/A DEAD + RT - - Invasive 16 Y
MM 9 M DEAD 11M
- RT - - NED 68 M
- RT+S - - NED 2 Y nasal obstruction
- RT+S - - NED 108 M
- RT+S - - AWD 18 M
- RT+S - - NED 157 M
- S - - N/A
- RT+S - - AWD 108 M
- RT+S - - AWD MM 116 M
Recurrent
- RT 1 year - NED 8 Y
then RT
Recurrent - RT - NED 9 Y then RT
- RT - - NED 1 M
N/A MM 6 M Invasive Dead 6 M
Dead 6 M - S - - MI
Nasal obstruction - none - - Dead 6 M invasive
- RT 56 - - NED 26 M
- RT 64 - - NED 36 M
Nasal obstruction - RT 48 GY - - NED 131 M headache
- RT 46 Gy - - NED 120 M
Local
recurrence
- RT 60 Gy 1 year - NED 28 M
Treated with
surgery
- RT 25 - - NED 27 M
- RT+ch+ S - - NED 2 Y
Nasal obstruction Recurrent - RT+ch+ S - AWD 6 M 6 month invasive
- RT+ch+ S - - NED 2 Y
- S - - NED 4 M epistaxis
Recurrent - RT - AWD 131 M 9 years
Recurrent 1
+ RT+CH year - NED 2 Y
then RT+ CH
+ RT - - NED 95 M
MM 64 M + CH CH - AWD 97 M
49 N O Yavas et al F/43 M k
Mayar et al M/73 S N/A N/A
M/47 S N/A
M/36 S N/A N/A
Petrovich et al M/52 S Epistaxis N/A
M/68 S Nasal obstruction N/A
M/63 S Nasal obstruction N/A
M/68 S N/A
M/50 S N/A
Abemayor et al M/34 S N/A N/A
53 N/A Wax et al M/65 S N/A
The overall annual incidence of plasma cell tumors is 3:100,000.
Plasma cell tumors are classified into three subtypes. Multiple
myeloma is the most common type, bone solitary plasmacyto-
ma, and soft tissue EMP being considerably less common (Table
4).30
Genetic factors, smoking, chronic antigenic stimulation
such as osteomyelitis, radiation exposure, and occupational ex-
posures have also been reported as possible etiologic agents in
the literature.32
Wiltshaw et al23 reported that 80% of extramedullary
plasmacytomas occur in the head and neck region, and 40% of
them occur in the nasal cavity and paranasal sinus, 20% in the
nasopharynx, and 18% in the oropharynx. Cervical lymph node metastasis is reported as initial presentation in 12-26% of the
cases, and about 20% of the EMP cases have multiple lesions.
The EMP stages can be identified according to the spread of the
disease (Table 5).24
Table 2. Characteristics.
Cases, n 114
Age, years, mean (range) 55 (3-85)
Male 79 (69%)
Female 23 (20%)
Unknown 12 (11%)
Obstruction 36 (64%)
Epistaxis 19 (33%)
Hearing loss 4 (7%)
Nasal discharge 1 (2%)
CN VI palsy 1 (2%)
Headache 2 (3%)
Foreign body sensation 4 (6%)
neck mass 10 (18%)
Dysphagia, anosmia 3 (5%)
Kappa 13/19
Lambda 6/19
Follow-up, months, mean; median (range) only 106 article 59.6 (1-336)
NED 67 (59%)
AWD 11 (10%)
DOD 15 (13%)
D 13 (11%)
N/A 8 (7%)
Loco-regional recurrence 20 (17%)
Multiple myeloma 8 (7%)
Metastasis 109%
NED: No evidence of disease; AWD: Alive with disease; DOD: Dead of the disease;
D: Dead of other causes; N/A: Non-Available.
Table 3. Treatment Modalities.
Radiotherapy alone 64 (56%)
Surgery alone 13 (11%)
Chemotherapy alone 1 (1%)
Surgery and radiotherapy 25 ( 21%)
Radiotherapy and chemotherapy 5 (3%)
Radiotherapy, surgery, and chemotherapy 3 (2%)
None 3 (2%)
Head and neck plasmacytoma tend to occur more fre-
th th quently in males (male: female ratio, 3:1) during the 5th and 7th
decades of life, however, it is rarely diagnosed in younger pa-
tients.60
Table 4. The EMP Diagnostic Criteria of EMP.
(a) Pathological monoclonal plasma cells neoplasm involving a single extramedullary site
(b) No bone marrow involvement
(c) Negative skeletal survey results
d) No anemia, hypercalcemia or renal impairment caused by plasma cell dyscrasia
(e) Low serum or urinary levels of monoclonal
Nasopharyngeal EMP was first reported by Kusunoki
in 1915, of which about 20% of the head and neck plasmacyto-
mas occur in the nasopharynx. (Table 4). Patel et al58 identified
778 patients with EMP in the head and neck region, 137 of them
reportedly have plasmacytoma in the nasopharynx. D’Aguillo et
al59 reported 176 cases of sinonasal extramedullary plasmacy-
toma, of which 36 cases were associated with the nasopharynx
(Table 6).
The common symptoms of nasopharyngeal EMP in-
clude nasal obstruction, epistaxis, and conductive hearing loss.
On performing nasal endoscopic examination, the lesions usu-
ally grow sub-mucosally as soft gray sessile or pedunculated
masses, which can rarely be ulcerated. The diagnosis of EMP is
done by tissue biopsy. Deep biopsies must be performed since
the tumor is located in the submucosal layer and the mucosa
may be thickened due to an inflammatory reaction. Once the di-
agnosis has been confirmed, further investigations are required
to exclude multiple myeloma. Three histological subtypes of
plasmacytoma have been reported including plasmacytic, plas-
mablastic and anaplastic subtypes. However, these subtypes are
not indicative of prognosis or increased risk of recurrence. Local
immunoglobulin
Table 5. EMP Stage.
Stage I is disease confined to one site
Stage II includes tumors with local extension of lymph node involvement.
Stage III has metastatic spread.
amyloid deposits may be found in 11-38% of the cases reported
but systemic amyloidosis is a rare occurrence. Immunohisto-
chemical techniques may indicate a monoclonal staining pattern
for heavy chain class, light chain class tumor or both, CD 138
30,32 has been reported as a gold marker for plasma cell tumor.
Complete surgical resection (if possible) with postop-
erative radiotherapy is the treatment of choice for solitary EMP.
In general, EMPs are considered radiosensitive, with a local
control rate of 90-100%. A radiation dose of 4050 Gy delivered
to the primary site of the EMP in the nasopharynx is usually
recommended. Since EMP is highly radio-sensitive with a local
control rate of 90%, there is no evidence as to whether radio-
therapy should also be targeted against cervical lymph nodes, in
order to decrease the risk of local and regional recurrence. Che-
motherapy is generally recommended for recurrent, advanced,
or disseminated disease.30
Nasopharyngeal extramedullary plasmacytoma has a
good prognosis but also requires a long-term follow-up to de-
tect any local recurrence or progression towards multiple my-
58,59 eloma.
Liebross et al 22 2
Tsang et al 76 3
Tournier et al 17 7
Creach et al 18 2
Alexiou et al 713 131
Saski et al 67 7
Stout et al 104 20
Ewing et al 21 2
This review contains the largest pool of data collected from na-
sopharyngeal EMP patients examined till date. Our data suggests
that radiotherapy alone is the most common type of treatment
used, followed by a combination of radiotherapy and surgery,
then surgery alone. A combination of radiotherapy and surgery
showed the best outcomes in patients in terms of survival and
eradication of the disease; however, this subgroup consisted of
only 25 patients. MM developments occurred in 7% of the pa-
tients.
Most of the data included in this study was collected
from case reports and case series. Further research on the opti-
mal treatment modality, should be done using randomized con-
trolled clinical trials to ensure less bias and better accuracy of
results.
The author declared no conflict of interest.