Jpn J Clin OncoI1998;28(4)245-249

Diagnosis and Treatment of Malignant Lymphoma of the Parotid

Gland
Naoki Hirokawa1, Masato Hareyama1, Hidenari Akiba1, Masaaki Satoh
2
, Atsushi Oouchi1,
Mitsuharu Tamakawa
1
, Koh-ichi Sakata1, Hisayasu Nagakura1, Kazumitsu Koito1, Kazuo Morita1,
Yasuaki Harabuchi
3
, Akikatsu Kataura
3
and Yuji Hinoda
4
Departments of 1Radiology, 2Clinical Pathology, 30tolaryngology and4First Internal Medicine, Sapporo Medical
University, School of Medicine, Sapporo, Japan
Background: To correlate the imaging and pathological features and to discuss therapeutic
modalities and the prognosis of malignant lymphoma originating in the parotid gland, which is
relatively rare.
Methods: The subjects were five patients with malignant lymphoma originating in the parotid
gland. Three andtwopatients were stage I andstage II, respectively. CTexamination wasapplied
to all, whereas onlyonecase wasexamined by MRI. All weretreated with radiotherapy following
surgery or chemotherapy. Three patients underwent combination chemotherapy, such as with
MACOP-P or VEPA, following surgery.
Results: Although malignant lymphoma originating intheparotid gland ishistologically described
as low-grade non-Hodgkin's lymphoma, twoandoneof thecases were classified asintermediate
andhigh grade inthepresent series, respectively. These three exhibited atendency for infiltration
intotheadjacent tissue andtumorinhomogeneity intheimaging findings, suggesting acorrelation
with histologically intermediate or high-grade non-Hodgkin's lymphoma. It was successfully
controlled byradiotherapy, with dosages ranging from 40 to 44 Gy. Thepatients werefollowed for
2-8 years. Norelapse wasfound inthethree patients with stage I. However, bothstage II patients
hadrelapses andwere subjected to additional radiotherapy combined withchemotherapy. Since
then, no tumor relapse hasbeen noted at either thisor othersites.
Conclusions: Malignant lymphoma including intermediate or highgrade originating intheparotid
gland indicated satisfactory prognosis following radiotherapy andchemotherapy.
Key words: malignant lymphoma - parotid tumor - radiotherapy - chemotherapy - CT - MR
INTRODUCTION
It has been reported that primary tumors of the parotid gland show
no characteristic features in diagnostic imaging, reflecting none
of their histological findings (1). Therefore, it is difficult to
differentiate benign conditions from malignant tumors and most
patients are subjected to surgical procedures before a definitive
diagnosis has been made. The head and neck region is the most
common site where malignant lymphomas occur, but malignant
lymphoma of the parotid gland is relatively rare (2). As stated
before, the imaging features are non-contributory to a diagnosis
Received August 27, 1997; accepted December 17, 1997
For reprints and all correspondence, Naoki Hirokawa, Department of
Radiology, Sapporo Medical University, School of Medicine, South-l ,
West-16, Chuo-ku, Sapporo 060, Japan
Abbreviations: MACOP-P, cyclophosphamide, doxorubicin, vincristine,
methotrexate, pepleomycin, predonisolone; VEPA, vincristine,
cyclophosphamide, doxorubicin, prednisolone
and the majority of patients are surgically treated. However,
radiotherapy and chemotherapy are also effective, often with a
favorable prognosis, so it is desirable to differentiate malignant
lymphoma of the parotid gland from other tumors prior to surgery.
We recently encountered five cases of malignant lymphoma of
the parotid gland. The purpose of this paper is to present the CT
and MRI fmdings, therapeutic modalities and the prognosis of
malignant lymphoma of the parotid gland.
MATERIALS AND METHODS
The subjects were five patients with malignant lymphoma
originating in the parotid gland. They had been treated at the
Department of Radiology, Sapporo Medical University, between
September 1985 and January 1995. The patients (one male and
four females) ranged from 44 to 74 years of age (mean 55.4
years). No patients suffered complication of facial nerve palsy or
Sjogren's syndrome. Patients were staged according to the Ann
Arbor criteria. All specimens were stained with hematoxylin-
eosin and monoclonal antibodies (CD20, CD45RO) and classi-

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246 Malignant lymphoma of the parotid gland
fied according to the working formulation (WF). The characteris-
tics seen at CT and MRI imaging of the parotid gland, such as
tumor size, tumor margins, signal intensity, tumor homogeneity
and tumor infiltration into adjacent tissues, correlated with
malignant lymphoma. The CT examination was applied to all,
whereas only one case was examined by MRI. As a therapeutic
policy, all were first subjected to surgical procedure, which
included total parotidectomy for one, superficial parotidectomy
for two and biopsy for two cases. Of the two patients who
underwent superficial parotidectomy, the procedure was com-
bined with cervical lymph node dissection in one. Three and two
patients were stage I and stage II, respectively. Bilateral cervical
lymph node involvement was noted in both stage II patients. In
three cases the surgical procedure was followed by chemother-
apy. All were treated with radiotherapy following surgery or
Table 1. Patients' characteristics
chemotherapy. The radiation dosage applied to the tumor ranged
from 40 to 44 Gy.
RESULTS
PATHOLOGICAL FINDINGS
According to the WF classification, two patients had diffuse large
cells as intermediate grade, one had diffuse small cleaved
immunoblastic type cells as high grade and one had follicular
mixed cell type as low grade. The remaining patient had MALT
lymphoma (Table 1). When classified by surface markers, all five
cases belonged to the B-cell type. When the primary site was
classified by the location, the tumor was situated in the superficial
lobe in three cases, deep lobe in one case and both in one case.
Case
2
3
4
5
Age Sex Histopathological Cell type Stage Lobe
classification
47 Male F. Mixed B II L-superficial
61 Female D. Large B II L-deep
44 Female D. Small cleaved, B
immunoblastic
51 Female MALToma B L-superficial
74 Female D. Large B R-both
R, right; L, left.
Table 2. CT or MR imaging of the parotid tumor
Case
2
3
4
5
Size (mm)
22 x 8 x 30
55 x 38 x 83
34 x 24 x 58
18x 12x 28
41 x 36 x 55
Homogeneity
Homogeneous
Inhomogeneous
Inhomogeneous
Homogeneous
Inhomogeneous
Margin
Well
III
III
III
III
Edema
+
+
+
Infiltration
v+
v+
Cystic change
+
+
+
Growth
Moderate
Rapid
Rapid
Moderate
Rapid
Well, well defined; ill, ill defined; s, subcutaneous tissue; m, muscle; v, vessel.

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Figure 1. MR image of case 3. The tumor in the superficial layer of the parotid
gland infiltrates into the adjacent tissues. vessels and subcutaneous tissue. This
tumor has a cystic lesion which is regarded as necrosis.
IMAGING FINDINGS
In the imaging examination, emphasis was placed on the manner
of infiltration into the adjacent tissue and the internal homogene-
ity of the tumor. Cases 1 and 4 exhibited homogeneity with
absence of infiltration. The tumor margin was well defined in case
1 and case 4 showed an ill-defined tumor margin with multiple
projections (Table 2). The tumors had rapidly increased in size
within 2 months in cases 2, 3 and 5. All exhibited infiltration into
the adjacent vasculature, muscles and subcutaneous tissue and
necrosis or cystic changes of the internal structures, suspected to
be retention cysts (Figs I and 2).
TREATMENT
All subjects underwent surgical procedure. According to the
specific locations of the foci, superficial parotidectomy (two
cases) or total parotidectomy (one case) was done. More recently,
biopsies have been performed in two cases for intraoperative
rapid pathological diagnosis (the frozen section) when malignant
lymphoma was suspected. Cases 2, 3 and 5 underwent combina-
tion chemotherapy, such as with MACOpP or VEPA, following
surgery. For radiotherapy, cobalt y-irradiation was employed for
all subjects. Cases 3 and 4 were irradiated on the parotid gland
Jpn J Clin OncoI1998;28(4) 247
Figure 2. CT image of case 5. The tumor infiltrates into adjacent tissues and
vessels. This tumor has a cystic lesion which is regarded as necrosis or a
retention cyst.
where the lesion was located and on the ipsilateral neck through
the lateral portal. Case 1 was irradiated on the parotid gland,
oropharynx and whole neck including through the parallel
opposed lateral portals and antero-posterior portals. Cases 2 and
5 were irradiated on both the parotid glands and oropharynx and
on the neck from upper to middle through the parallel opposed
lateral portals. The radiation dosage ranged from 40 to 44 Gy
delivered at 1.8-2.0 Gy per fraction over 4-5 weeks (Table 3).
CLINICAL COURSE
The patients have been followed for 2-8 years. No relapses have
occurred and clinical courses were satisfactory for those in stage
I (cases 3-5). After 8 months, a biopsy specimen showed relapse
of the inguinal lymph nodes in case I, which was treated with
chemotherapy. Since then, he has been alive and well for more
than 7 years. It should be noted that this patient did not initially
undergo chemotherapy. MRI suggested a tumor relapse in the
lymph node of the upper cervical region which had been treated
with radiotherapy in case 2. The patient was subjected to
additional radiotherapy with 24 Gy of cobalt y-irradiation
combined with MACOP-P. Since then, no tumor relapse has been
noted at either this or other sites (Table 4).

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248 Malignant lymphoma of the parotid gland
Table 3. Modalities of treatment
SPD +LND 60Co
Case
2
3
4
5
Surgical procedure
Biopsy
Biopsy
SPD
Total resection
Source
60CO
60Co
Radiation dose (Gy) Treatment method Field
30 Opposed Primary lesion
antero-posterior whole neck
14 Opposed lateral
44 Opposed lateral Primary lesion
whole neck
40 Lateral Primary lesion
upper neck
40 Lateral Primary lesion
upper neck
40 Opposed lateral Primary lesion
whole neck
Chemotherapy
MACOP-P
VEPA
MACOP-P
MACOP-P
SPD, superficial parotidectomy; LND, lymph node dissection.
Table 4. Outcome after treatment
Case Period of observation (months) Site of relapse Time of relapse
95 Lt. inguinal lymph node After 8 months
2 83 Cervical lymph node After 2 months
3 55 None
4 25 None
5 66 None
NED, no evidence of disease.
Treatment
VEPA
24 Gy,MACOP
Present state
NED
NED
NED
NED
NED
DISCUSSION
It has been reported that 80-85% of parotid gland tumors are
benign and 15-20% are malignant (3). It is common knowledge
that tumors originating in the parotid gland are without character-
istic features in their various imaging presentations and that
differentiation between benign and malignant tumors is difficult.
However, some workers have reported that these tumors can be
differentiated by tumor margins, tumor homogeneity, infiltration
into the adjacent tissue and signal intensity in MRI. There are also
some correlations between the malignancy seen in histopatho-
logical examinations and the fmdings from imaging studies
(1,4-7). Malignant lymphoma originating in the parotid gland is
relatively rare and occurs in 1-5% of tumors where the parotid
gland is the original site of the tumor (2). It is commonly believed
that the differentiation of malignant lymphoma originating in the
parotid gland from other tumors, including benign tumors, is
difficult; however, some authors have reported that malignant
lymphomas showed tumor homogeneity surrounded by well
defmed margins and were rarely associated with necrosis (8,9).
The observations of the present cases indicated that it is necessary
to consider the possibility of malignant lymphoma even when the
lesion rapidly increases in size and exhibits necrosis or an
infiltrative tendency in the imaging presentations, strongly
suggesting epithelial tumors.
In general, malignant lymphoma originating in the parotid
gland is histologically described as low-grade non-Hodgkin's
lymphoma, frequently belongs to the B-cell type and rarely
relapses into other sites (7,10-16). However, in the present series,
two and one of the cases were classified as diffuse large cell type
and diffuse small cleaved immunoblastic type, respectively.
These three exhibited a tendency to infiltrate the adjacent tissue
and tumor inhomogeneity in the imaging findings, suggesting a
correlation with a histologically intermediate or high grade of
non-Hodgkin's lymphoma. In the present series, it was success-
fully controlled by radiotherapy, with dosages ranging from 40 to
44 Gy. The patients were followed for 2-8 years and no relapse
was found in the three patients with stage 1. However, both stage
II patients had relapses and were subjected to additional
radiotherapy combined with chemotherapy. Since then, no tumor
relapse has been noted at either this or other sites.
Generally, most patients experience xerostomia if a substantial
part of the parotid glands is included within the radiation portal.
Only one patient (case 1), who received 44 Gy in the bilateral
parotid glands, developed mild dry mouth. However, the
remaining four patients did not suffer from xerostomia. The low
incidence of xerostomia at the time of the last follow-up was
thought to be due to the fact that the dosage of less than 44 Gy on
the parotid glands did not cause irreversible depression of the

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parotid function. Franzen et al. (17) reported that most patients
who received less than 52 Gy showed a recovery of secretion
beginning after 2 months with a continuous improvement of the
salivary flow up to 18 months. Also, Valdes Olmos et al. (18)
reported that excretion was almost invariably impaired at doses
higher than 45 Gy, regardless of the time interval after radiother-
apy.
Two patients underwent superficial parotidectomy and and one
total parotidectomy. However, more recently, biopsies have been
performed in two cases for intraoperative rapid pathological
diagnosis (frozen section), as malignant lymphoma was sus-
pected.
In conclusion, malignant lymphoma including intermediate or
high grade originating in the parotid gland indicated satisfactory
prognosis following radiotherapy and chemotherapy.
Acknowledgments
The authors thank Mr Robert Holmes (Sapporo Medical Univer-
sity, Sapporo, Japan) for assistance with the manuscript and Ms
E. Sudou for secretarial assistance. This work was supported by
grants for Cancer Research from the Ministry of Education,
Science and Culture (M.H.), Japan.
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