Extranodal Non-Hodgkin 's Lymphoma

of the Head and Neck

A Clinicopathologic Study
in the Kyoto-Nara Area of Japan
Nobuko Shima, MD,*,t Yoichiro Kobashi, MD,$
Kazushige Tsutsui, MD,§ Katsuhiko Ogawa, MD,"
Shunzo Maetani, MD, 1) Yasuaki Nakashima, MD,T
Kunio Ichijima, MD,$ and Hirohiko Yamabe, MDt

The clinicopathologic features of 114 Japanese patients with extranodal non-

Hodgkin's lymphoma of the head and neck region were analyzed. The median age
was 60.5 years and the ma1e:female ratio was 1.5:l. The most common site of
involvement was Waldeyer's ring, followed by the oral cavity, thyroid gland,
paranasal sinuses, nasal cavity, and larynx. Seventy-five percent of the patients
were in Stage I or Stage I1 at admission. Histologically, diffuse lymphoma accounted
for 94% and follicular lymphoma for 6% of cases. The histologic grade according to
the Working Formulation System of the National Cancer Institute was low in 11%,
intermediate in and high in 14% of cases. Immunohistochemical study showed
that the majority of the cases were of B-cell type and only 13 cases (11%) were of
the T-cell type. Peripheral T-cell lymphomas (eight cases) mainly occurred in the
nasopharynx and nasal cavity, whereas four of five thymic T-cell lymphomas were
found in the palatine tonsil. The over-all !&yearsurvival rate was 54%, and the
factors affecting survival were sex, histologic grade, T/B phenotype, clinical stage,
and the site of initial presentation. Five-year survival with nasal cavity and
Waldeyer's ring lymphoma was 24% and 46%, respectively. The poor prognosis of
lymphomas at these sites might result from the predominance of T-cell lymphoma,
the paucity of low grade lymphoma, and the relatively high incidence of cases that
were in an advanced stage at presentation. In Stage 11, patients treated with
combined therapy tended to have a better 5-year survival rate than those treated
with radiotherapy alone. Cancer 66:1190-1197,1990.

T HE HEAD AND NECK REGION is One of the most COm-

mon sites of extranodal non-Hodgkin's lymphoma,
and there have been several previous reports on this sub-
ject.'-' The most common site of involvement is Wal-
deyer's and more than half the patients are in an
early stage at p r e s e n t a t i ~ n . ~Diffuse
, ~ . ~ , ~lymphoma is pre-
From the Departments of *Pathology, $Radiology, and 11 Surgery,
Kyoto University, Kyoto, the ?Laboratory of Anatomic Pathology and
the lICentral Clinical Laboratory, Kyoto University Hospital, Kyoto,
and the $Department of Pathology, Tenri Hospital, Nara, Japan.
Address for reprints: Hirohiko Yamabe, MD, Laboratory of Anatomic
Pathology, Kyoto University Hospital, 54 Shogoin Kawahara-cho, Sakyo-
ku. Kyoto 606, Japan.
Accepted for publication February 20, 1990.
dominant (82% to 94%),2-5with the diffuse large cell (dif-
fuse histiocytic) type being the most common.'-5 Most of
the lymphomas are of B-cell origin but T-cell lymphomas
are also found in the nasal cavity or nasopharyn~.~,'~For
patients in Stages I and 11, radiotherapy alone has been
the usual mode of treatment. However, the initial treat-
ment of these patients with localized disease remains a
matter of controversy.' '-I7
This study describes the clinicopathologic characteris-
tics of 114 patients with extranodal head and neck lym-
phoma. The subjects presented to Kyoto University Hos-
pital in Kyoto and to Tenri Hospital in Nara, which are
located in the central part of Japan and are outside the
endemic area for adult T-cell leukemia/lymphoma.

1190
No. 6 EXTRANODAL LYMPHOMA
NON-HODGKIN’S OF THE HEADAND NECK * Shima et d. 1191

Materials and Methods TABLEI . Site of Primary Tumor

We reviewed 1 14 cases of primary extranodal non- Waldeyer’s ring 72 (63%)

Palatine tonsil 45
Hodgkin’s lymphoma of the head and neck that were di- Nasopharynx 24
agnosed and treated at Kyoto University Hospital and Base of tongue 3
Tenri Hospital between 1966 and 1986. Lymphomas of Oral cavity 14 (12%)
Palate 6
Waldeyer’s ring were included, but lymphomas of the Gingiva 4
brain, orbit, and skin, lymphoepithelial lesions of the sal- Buccal mucosa 3
ivary gland, and polymorphic reticulosis of the nasal cavity Unknown 1
Thyroid gland 10 (9%)
were excluded from this study. Paranasal sinus I(6Yo)
Hematoxylin and eosin-stained slides and paraffin Ethmoid sinus 4
blocks were available in all cases. All histologic specimens Maxillary sinus 3
Nasal cavity 1(6%)
were fixed in buffered formalin or buffered 4% parafor- Larynx 4 (4%)
maldehyde and processed in the usual way for paraffin
Total 114(100%)
embedding. Four-micrometer thick sections were cut and
stained with hematoxylin and eosin for routine histologic
studies. Lymphomas were classified according to the
Working Formulation System of the National Cancer In- scintigram, computed tomography, upper gastrointestinal
stitute.” Immunohistochemical studies were performed series, barium enema, blood count, biochemical profile,
on paraffin sections by the avidin-biotin-peroxidase com- and bone marrow aspiration. Staging laparotomy was not
plex technique” using a panel of monoclonal antibodies. performed. Since it is sometimes difficult to decide the
Antibodies employed in the present study and their di- primary site in Stages 111 and IV, we regarded a case as
lutions were as follows: ( 1 ) L26 (X 100, Dakopatts, Den- having a primary tumor in the head or neck if the largest
mark),*’ (2) MB 1 (X80, Bio-Science Products, Switzer- tumor was located in the head and neck region and/or
land),21( 3 )LN 1 (prediluted, Techniclone Int. Co., USA),22 the initial presentation was mainly due to involvement
(4) LN2 (prediluted, Techniclone Int. C O . ) , (5) ~ ~ MT1 at this site. Follow-up data were available in 110 cases
(X25, Bio-Science Products),21 and (6) UCHLl (X25, (96%). The duration of follow-up ranged from 1 to 258
D a k o p a t t ~ )The
. ~ ~ L26, MB1, LN1, and LN2 antibodies months, with an average of 45 months. Lymphoma-spe-
were used as B-cell markers while the MT1 and UCHLl cific survival was calculated using the method of Kaplan
antibodies were as T-cell markers. and Meier.25 The statistical significance of differences be-
Pertinent clinical information and follow-up data were tween the survival curves was assessed using the Mantel-
obtained from hospital charts for all cases, and staging Haensel test.26
was performed according to the Ann Arbor system24using
the following parameters where available: physical ex- Results
amination, chest X-ray, lymphangiogram, 67Gaand 9 9 m T ~
Age and Sex
As shown in Figure 1, the age at the presentation ranged
cn from 1 to 85 years with a mean of 56.7 years and a median

.
5 30
c,

I
Female (N=45)
Male (N=69)
of 60.5 years, the peak age being in the seventh decade.
There were 69 males and 45 females, giving a ma1e:female
c,
(P
ratio of 1.5:1.
P
20 Site of Primary Tumor
L
Q, The sites of the primary tumors are shown in Table 1.
P The most common site was Waldeyer’s ring (63%), fol-
E 10
lowed by the oral cavity (12%),thyroid gland (9%), para-
3
z nasal sinuses (6%), nasal cavity (6%), and larynx (4%).

10 20 30 40 50 60 70 80 90 Presenting Symptom
Age The major presenting symptoms varied with the site,
FIG. 1. Age and sex distribution of the 114 patients with extranodal as shown in Table 2. The most frequent symptom was
non-Hodgkin’s lymphoma. local swelling.
1192 September 15 1990
CANCER Vol. 66

2. Presenting Svmutoms for Each Primam Site

TABLE TABLE4. Histologic Classification According to Primary Site

Waldeyer's ring Cervical tumor (30%) Low Intermediate High

Tonsillar swelling (2 1%) grade grade grade
Pain or foreign body sensation in throat (1 8%)
Oral cavity Local swelling (79%) A B C D E F G H I J
Pain or discomfort in throat (1 4%)
Ulcer ( 14%) Waldeyer's ring (72) I 2 1 0 8 13 35 8 4 0
Thyroid gland Struma (8070) Oral cavity ( 1 4 ) 4 0 1 1 0 2 3 2 0 1
Hoarseness (20%) Thyroid gland (10) I 1 1 0 I 1 5 0 0 0
Fever (20%) Paranasal sinus (7) 0 0 0 0 0 4 3 0 0 0
Paranasal sinus Exophthalmus (86%) Nasal cavity ( 7 ) O O O O 1 3 2 1 0 0
Buccal swelling (29%) Larynx ( 4 ) l O O O 0 0 3 0 0 0
Visual disturbance (29%)
Nasal cavity Nasal obstruction (86%) Total (114) 7 3 3 1 10 23 51 I1 4 1
Rhinorrhea (29%) 13 (11%) 85 (75%) 16 (14%)
Tinnitus (14%)
Larynx Hoarseness (7570) Working Formulation: A: Small lymphocytic. B: Follicular, predom-
Dyspnea (50%) inantly small cleaved cell. C : Follicular, mixed, small cleaved and large
Dysphagia (25%) cell. D: Follicular, predominantly large cell. E: Diffuse, small cleaved
cell. F: Diffuse, mixed, small and large cell. G: Diffuse, large cell. H:
Large cell, immunoblastic. I: Lymphoblastic. J: Small noncleaved cell.

Stage
The stage at presentation is shown in Table 3. More tions (Table 5). The phenotype of the remaining two cases
than seventy-five percent of patients were diagnosed at remained undefined by this method. Ninety-nine cases
an early stage (I or 11). Three out of seven patients with (87%)were shown to have B-cell lymphoma, and 13 cases
nasal cavity lymphoma, however, were at Stage 111 or IV. (palatine tonsil, five; nasopharynx, four; nasal cavity,
three; and oral cavity, one) ( 1 1%) had T-cell lymphoma.
Histologic Classificarion and Grade Among T-cell lymphomas, four of five palatine tonsil
lymphomas and one of four nasopharyngeal lymphomas
Table 4 shows the histologic classification of tumors were of the lymphoblastic type (i.e., thymic T-cell lym-
according to the Working Formulation.'' The most fre- phomas), whereas three of four nasopharyngeal and all
quent histologic type was diffuse large cell lymphoma ( 5 1 the nasal and oral T-cell lymphomas were of the diffuse
cases, 45%), followed by diffuse mixed lymphoma (23 mixed or diffuse immunoblastic types, which indicate pe-
cases, 20%). Follicular lymphoma comprised only 6% of ripheral T-cell lymphoma. Of the eight peripheral T-cell
the cases (seven cases). Grading according to the Working lymphomas, six (75%) presented with lesions in the na-
Formulation revealed 11% low grade, 75% intermediate sopharynx or nasal cavity.
grade, and 14%high grade lesions. Tumors of Waldeyer's
ring and the nasal cavity were predominantly of inter- Treatment
mediate or high grade.
The method of treatment is summarized in Table 6
Irnm unohistochemical Findings according to the initial staging. Thirty-nine patients (34%)
had radiotherapy, 13 (1 1%) had chemotherapy, 50 (44%)
The T/B phenotype of 1 12 cases (98%)was determined
using a panel of monoclonal antibodies on paraffin sec-
TABLE5. T/B Phenotype According to Primary Site
TABLE3. Stage According to Primary Site T-cell
Stage B-cell Peripheral Thymic Undefined
1 I1 Ill IV U Waldeyer's ring
Palatine tonsil 38 1 4 2
Waldeyer's ring 15 35 11 8 3 Nasopharynx 20 3 1 0
Oral cavity 6 5 3 0 0 Base of tongue 3 0 0 0
Thyroid gland 4 5 1 0 0 Oral cavity 13 1 0 0
Paranasal sinus 3 4 0 0 0 Thyroid gland 10 0 0 0
Nasal cavity 2 2 1 2 0 Paranasal sinus 7 0 0 0
Larynx 3 1 0 0 0
Nasal cavity 4 3 0 0
Total 33 52 16 10 3 Larynx 4 0 0 0
(29%) (46%) (14%) (9%) (2%) 99 8
Total 5 2
(87%) (7%) (4%) (290)
U: unknown
 No. 6 EXTRANODAL LYMPHOMA
NON-HODGKIN’S OF THE HEADAND NECK Shima et al. 1193

6 . Treatment According to Stage of Disease

TABLE -
ae
Y
lOOn1--7----1

Radio- Cherno- Combined

Stage therapy therapy therapy Untreated Unknown

I 16 3 10 4 0
I1 18 5 25 2 2
111 4 1 11 0 0
IV I 4 4 1 0
40 -
i
Unknown 0 0 0 0 3 I
I
Total 39 13 50 7 5
I
I -F
(34%) (11%) (44%) (6%) (5%) 20-

had combined chemotherapy and radiotherapy, seven

01
0 1 2 3 4 s
Years
(6%) were untreated, and the method of treatment was
unknown in five (5%). Even with Stage 111 and IV patients, FIG. 3. Survival according to site. (A) Paranasal sinuses, n = 7. (B)
Thyroid gland, n = 10. ( C )Larynx, n = 4. (D) Oral cavity, n = 14. (E)
more than half were treated by local radiotherapy with Waldeyer’s ring, n = 72. (F) Nasal cavity, n = 7.
or without chemotherapy to diminish tumor bulk and
alleviate local symptoms.
there was a significant difference between any two groups
of patients at each stage except between Stages I and 11.
Prognostic Factors and the Survival of the Patient When the patients were classified according to the
Working Formulation, the 5-year survival of those with
The overall 5-year survival rate was 54% (Fig. 2), and
low grade, intermediate grade, and high grade histologic
the median survival was 99 months. The difference in 5-
types was 91%, 54%, and 14%,respectively (Fig. 5). There
year survival between males (42%)and females (72%)was
was a significant difference in 5-year survival between low
statistically significant ( P < 0.025) (Fig. 2). With respect
and intermediate grade (P< 0.005),and between low and
to age, there was no significant difference in 5-year survival
high grade (P< 0.005). However, there was no statistically
between any two decades. However, patients younger than
significant difference between patients with intermediate
20 had a worse 5-year survival (28%) than patients older
and high grade lymphoma ( P = 0.1). Five-year survival
than 20 ( 5 5 % ) ( P < 0.25). The 5-year survival of patients
of patients with B-cell lymphoma (6 1%) was significantly
with lymphoma of the paranasal sinuses, thyroid gland,
better than with T-cell lymphoma (12%) ( P < 0.005)
or larynx was greater than 75%, whereas with Waldeyer’s
(Fig. 6).
ring or nasal cavity lymphoma survival was less than 50%
With regard to treatment, in both Stages I and I1 there
(Fig. 3). The difference in 5-year survival between patients
was no significant difference in 5-year survival between
with paranasal sinus and nasal cavity lesions was statis-
patients treated with radiotherapy (Stage I, 7 I %; Stage 11,
tically significant ( P < 0.005). Five-year survival became
5 I %), combined chemotherapy and radiotherapy (Stage
poorer as the stage of the patients advanced (Fig. 4), and
I, 75%; Stage 11, 63%), or chemotherapy (Stage I, 50%;
Stage 11, 75%) (Figs. 7 and 8).
;;;: l0OL

80 - m
Stage I (N=33)
L
60 - 3

.-
0
v) 60 I_____ Stage II (N=52)
’c I____________________I
0

Years
FIG. 2. Overall survival of patients with extranodal non-Hodgkin’s
lymphoma. FIG.4. Survival according to stage.
1194 September 15 1990
CANCER Vol. 66

CI n 100-
dz 8
-Q
Y
-
Y

> .-Q> 80-

>
L
3
fn hermediate grade (N=85) 5
03 Combined therapy (N = 10)
.-o 60-
L-
I
I
.-v 60-
'c 'c
0
Q) Q)
chemotherapy @J=3)
$ 40-
L._.___

2 40-

s
A 01 1 f 01 I
0 1 2 3 4 5 0 1 2 3 4 5
Years Years
FIG.5 . Survival according to histologic grade. FIG.7. Survival of Stage I patients according to mode of treatment.

Association With Other Malignancies
Four patients (3.5%)developed other malignancies after
initial treatment for the lymphoma: two gastric carcino-
mas, one laryngeal carcinoma, and one bile duct carci-
noma.
Discussion
In the current study, we have examined retrospectively
the clinicopathologic characteristics of 1 14 extranodal
non-Hodgkin's lymphomas occurring in the head and
neck region. The patients were from Kyoto and Nara in
Japan, where adult T-cell leukemia/lymphoma is not en-
demic.
The mean age at diagnosis was 56.7 years; the male:
female ratio was 1.5: 1, and the most common primary
site was Waldeyer's ring, where palatine tonsil was mainly
involved. Most of the presenting symptoms were attrib-
utable to a local mass, and "B" symptoms (unexplained
weight loss of more than 10% of the body weight in the
6 months before admission, unexplained fever of above
38°C and night sweats) were uncommon. Seventy-five
percent of the patients were in Stages I or I1 at admission.
These results are in accordance with those reported by
Conley et af.,2 Jacobs and H ~ p p e Jacobs
,~ et al.,' and
Wong et aL5 from the United States, Wulfrank et aL6
from Belgium, and Horiuchi et a1.' from Japan.
It is well known that the incidence of follicular lym-
phoma in general is higher in the United States than in
Japan.27The incidence of follicular lymphoma occurring
in lymph nodes is, in our preliminary study of the patients
from Kyoto and Nara area between 1966 and 1986, 16%
in Japan, and is reported to be 17.1% in Hong Kong2X
and 37% in the United States.2 In the current series, 94%
of the patients had diffuse lymphoma and only 6% had
follicular lymphoma. The incidence of extranodal follic-
ular lymphoma in this series is comparable to that reported
by Horiuchi et al.' in Japan (6%) and Ho et d2* in Hong
Kong (5.3%), but it is lower than that reported by inves-
tigators in the United state^,^.^.^ where the incidence
ranges from 10% to 18%, except for the report of Mill et

.-> 80-
II lymphoma (N=99)

Radiotherapy (N = 18)
40 tI

2
*
I
I

5
A
q , ,
0 A 0
0 1 2
,
3 4
, ,
5
Years Years
FIG. 6. Survival according to T/B phenotype FIG.8. Survival of Stage I1 patients according to mode o f treatment.
No. 6 EXTRANODAL
NON-HODGKIN’S
LYMPHOMA
OF THE HEADAND NECK
al. (6%).4It appears that follicular lymphomas are less
frequent in Asia than the United States, although in both
regions they more commonly involve lymph nodes than
extranodal sites. The reported lower incidence of follicular
lymphoma in extranodal sites, however, may be partly
due to technical factors, because biopsy specimens from
these sites are often small and show artifacts.
There was some correlation between histologic grade
and the primary site of involvement in our series. The
majority of non-Hodgkin’s lymphomas in the Waldeyer’s
ring and the nasal cavity were intermediate or high grade
lesions. This result is in agreement with the reports by
Yamanaka et u I . , ~ Shimm et and Saul and Ka~a d ia .~ ’
Saul and Kapadia3’ stated that high grade lesions were
most commonly found in the nasopharynx. Lymphomas
of the thyroid gland were exclusively low or intermediate
grade lesions in our study. Chak et aL3‘ and Aozasa et
al.32have also reported that the majority of thyroid lym-
phomas comprised low or intermediate grade tumors.
Most of the lymphomas in the current series were of
the B-cell type (87%). There were, however, 13 cases ( 1 1%)
of T-cell lymphoma, including eight peripheral T-cell
lymphomas (nasopharynx, three; nasal cavity, three; pal-
atine tonsil, one; oral cavity, one) and five thymic T-cell
lymphomas (palatine tonsil, four; nasopharynx, one).
Despite the lack of serologic data, none of the peripheral
T-cell lymphomas was considered to be of the adult T-
cell leukemia/lymphoma type (ATL/L), judging from the
demographic and clinical data and from the tumor mor-
phology. This is in contrast to the high incidence of T-
cell lymphoma/leukemia of the ATL type in Kagoshima
Prefecture, which is one of the endemic areas in Japan.33
Chan et al.” reported that all 1 1 of their cases of nasal/
nasopharyngeal lymphomas were of the peripheral T-cell
type, including five cases of polymorphic reticulosis. They
also studied 20 cases of primary Waldeyer’s ring lym-
phoma occurring outside the nasopharynx and found that
all had the B-cell phenotype.34In the report of Yamanaka
et ~ l .19, of~ 22 cases (86%) of Waldeyer’s ring lymphoma
expressed B-cell markers and three (14%) had T-cell
markers (peripheral, two; thymic, one). However, all six
cases of nasal cavity lymphoma were peripheral T-cell
lymphomas consistent with the so-called “lethal midline
granuloma” or “rhinitis gangrenosa progressiva.” Weis et
ai.35and Horning et al.36have also described the presence
of peripheral T-cell lymphomas in the nasal cavity or na-
sopharynx. Thus, our data are in agreement with the pre-
vious studies, except for the fact that all paranasal sinus
lymphomas (seven cases) were of the B-cell type in our
series. It is appears that peripheral T-cell lymphomas in
the head and neck region occur almost exclusively in the
nasopharynx and nasal cavity, but rarely in Waldeyer’s
ring outside the nasopharynx or in other extranodal sites.
In our series, five cases of T-lymphoblastic lymphoma
* Shima et UI. 1195
involved in Waldeyer’s ring at presentation, showing that
lymphoblastic lymphoma may also involve this site al-
though the incidence is not high.
Wulfrank et aL6 have reported that sex did not affect
the prognosis. Conley et a1.* used the Working Formu-
lation for histologic classification and showed that the
survival of patients with low grade lymphoma was better
than that of patients with intermediate or high grade lym-
phoma. Jacobs and Hoppe3 and Mill et aL4used the Rap-
paport classification and found that 5-year survival for
favorable histologies was significantly better than for un-
favorable histologies. In our current series, sex was shown
to have prognostic significance and patients with low grade
lymphoma had a better outcome than intermediate or
high grade cases.
Recently, there have been some reports on the rela-
tionship between T/B phenotype and survival. Lippman
et al.37 stated that disease-free survival was shorter in T-
cell lymphoma than in B-cell lymphoma and that B-cell
lymphoma patients had a twofold advantage in median
survival. On the other hand, several studies have shown
no significant difference in median survival or complete
remission rate between B-cell and T-cell lymphoma in
aggressive case^.^^,^^ Yamanaka et aL9 reported that the
median survival of a T-cell lymphoma group was greatly
inferior to that of a B-cell lymphoma group. Also, in our
series the 5-year survival in T-cell lymphoma was poorer
than in B-cell lymphoma. It appears that the poor prog-
nosis in T-cell lymphoma is due to the high proportion
of histologically aggressive lymphomas.
In our series, Stage 1 and I1 patients had a good prog-
nosis and advanced stage patients had a poor prognosis,
which is in accordance with previous report^.^-^
In a study of 156 cases of extranodal head and neck
lymphoma, Jacobs and Hoppe reported that 5-year sur-
vival was influenced by the primary site and stated that
lymphoma of the paranasal sinuses had the poorest prog-
nosis (5-year survival, 12%).3They suggested that this was
due to very bulky local disease and unfavorable histology.
In their series, despite good local control with radiother-
apy, the majority of patients developed extranodal re-
lapses. In our series, however, the prognosis of patients
with paranasal lymphoma was the best for the head and
neck region (5-year survival, 86%). Our cases were all in-
termediate grade B-cell lymphomas in the early stages and
all but one were treated with combined chemotherapy
and radiotherapy. Thus, the difference in prognosis be-
tween the two series may be due to differences in histology,
phenotype, and/or mode of treatment. The poor prognosis
for nasal cavity or Waldeyer’s ring lymphoma demon-
strated in our current study as well as other ~ t u d i e s ~ ~ ~ ’
may be due to the prominence of T-cell lesions, the paucity
of low grade lymphoma, and the relatively high incidence
of advanced cases.
1196 CANCER
September 15 1990
Traditionally, Stage I and I1 patients have been treated
with radiotherapy alone, but the initial treatment of this
type of localized disease is yet a matter of controversy.
Some authors have stated that combined therapy was sig-
nificantly superior to radiotherapy alone in Stage I and
I1 patients, with respect to overall survival, I disease-free
survival,’ relapse-free survival,I 2 , I 3 and the relapse
rate.I1,l2 We found that Stage I1 patients treated with
combined therapy tended to have a better 5-year survival
(63%)than those treated with radiotherapy alone (50%),
although the difference was not statistically significant.
There was little difference in 5-year survival between ra-
diotherapy and combined therapy in Stage I. Teshima et
al. l4 demonstrated the superiority of combined therapy
over radiotherapy alone for Stage I1 patients and the in-
effectiveness of chemotherapy for Stage I patients. On the
other hand, Cabanillas et al.,I5 Cabanillas,16and Miller
and JonesI7 found that chemotherapy alone was effective
for patients with Stage I and I1 disease, although
CabanillasI6 recommended radiotherapy following the
chemotherapy in Stage I1 patients with bulky disease. We
found that the 5-year survival of five Stage I1 patients
treated by chemotherapy alone was excellent (75%).
Four patients (3.5%) in our series were found to have
second malignancies. In contrast to Hodgkin’s disease,
there are far fewer reports on second malignancies, es-
pecially on solid malignancies complicating non-Hodg-
kin’s l y m p h ~ m a . ~ ’ Zarrabi4’
-~~ reported the occurrence
of second solid malignancies in 16 of 438 patients with
non-Hodglun’s lymphoma (3.7%).They indicated that the
incidence of these tumors did not differ significantly from
the predicted values for a normal population. However,
there are some reports of a selective increase in the inci-
dence of skin ~ a n c e r ,lung
~ ’ cancer,42and colon cancer4’
in patients with malignant lymphoma.
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