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1612
Treatment, Patterns of Failure, and Survival of
Patients with Stage I Nodal and Extranodal NonHodgkin’s Lymphomas, According to Data in the
Population-Based Registry of the Comprehensive
Cancer Centre West
Augustinus D. Krol, M.D.1
Jo Hermans, Ph.D.2
Lilian Dawson, M.D.3
Simone Snijder, B.Sc.4
Pierre W. Wijermans, M.D., Ph.D.5
Hanneke C. Kluin-Nelemans, M.D.,
Philip M. Kluin, M.D., Ph.D.6
J. Han van Krieken, M.D., Ph.D.6
Evert M. Noordijk, M.D., Ph.D. 7
3
Ph.D.
1
Department of Radiotherapy, University Hospital
Rotterdam/Daniel den Hoed Cancer Center, Rotterdam, the Netherlands.
2
Department of Medical Statistics, University of
Leiden, Leiden, the Netherlands.
3
Department of Hematology, Leiden University
Hospital, Leiden, the Netherlands.
4
The Comprehensive Cancer Center West, Leiden,
the Netherlands.
5
Department of Hematology, Leyenburg Hospital,
Den Haag, the Netherlands.
6
Department of Pathology, Leiden University Hospital, Leiden, the Netherlands.
7
Department of Clinical Oncology, Leiden University Hospital, Leiden, the Netherlands.
BACKGROUND. Primary extranodal lymphomas (EN-NHLs) are a heterogeneous
category of tumors that are considered to be different from primary nodal nonHodgkin’s lymphomas (N-NHLs). To what extent these differences have clinical
implications is currently not very clear, because knowledge of EN-NHL as a
separate group is limited.
METHODS. Using data from the Comprehensive Cancer Centre West (CCCW) population-based NHL registry in the Netherlands, N-NHL and EN-NHL patients were
compared to determine differences in characteristics at diagnosis, responses to
treatment, patterns of failure, and survival.
RESULTS. At presentation, EN-NHL patients had poorer performance scores and
more often bulky tumors compared with N-NHL patients, resulting in poorer
responses to treatment (complete response rates were 72% and 84%, respectively;
P 5 0.04) and inferior 5-year overall survival (49% and 63%, respectively; P 5
0.003). Among EN-NHL patients, considerable variations in response, survival, and
relapse rates were observed, with gastric NHL patients having the best and central
nervous system NHL patients having the worst prognosis (66% and 7% 5-year
overall survival, respectively). Relapse rates for N-NHL and EN-NHL patients did
not differ (39% and 36% 5-year relapse rates, respectively), whereas among ENNHL patients considerable differences in relapse rates were noted. Relapses among
N-NHL patients were mainly found in nodal sites, whereas recurrent disease in
EN-NHL patients was mainly found in extranodal sites.
CONCLUSIONS. In this population-based study, Stage I EN-NHL patients as a group
had a poorer prognosis than N-NHL patients. However, among EN-NHL patients,
considerable differences in response, relapse risk, and survival were observed. The
failure analysis conducted in this study suggests that patterns of dissemination for
N-NHL and EN-NHL are different. Cancer 1998;83:1612–9.
© 1998 American Cancer Society.
KEYWORDS: non-Hodgkin’s lymphoma, nodal, extranodal, prognosis, patterns of
dissemination.
Address for reprints: Augustinus D. Krol, M.D.,
Department of Radiotherapy, University Hospital
Rotterdam/Daniel den Hoed Cancer Center, P.O.
Box 5201, 3008 AE Rotterdam, the Netherlands.
Received December 26, 1997; revision received
April 6, 1998; accepted April 6, 1998.
© 1998 American Cancer Society
U
p to 40% of non-Hodgkin’s lymphomas (NHLs) originate in sites
outside the lymph nodes.1– 4 These primary extranodal lymphomas (EN-NHL) are a heterogeneous category of tumors that are considered to be different from primary nodal non-Hodgkin’s lymphomas (N-NHL) with respect to patterns of dissemination and oncogene
expression.6 To what extent these differences have clinical implica-
Stage I Nodal and Extranodal NHL/Krol et al.
1613
TABLE 1
Disease Localization and Malignancy Grade (WF) of all Stage I NHL Patients (n 5 264) in the CCCW Population-Based Registry
No. of patients
Total
L
I
H
U
Nodal
Lymph node
Waldeyer’s tonsillar ring
Spleen
Extranodal
Head/necka
Stomach
Intestine
Bone
Connective tissue
Skin
Female breast
Testis
Bladder
Orbita/lacrimal gland
Brain
Spinal cord, epi-/extradural
Thyroid
114
96
17
1
150
19
47
17
7
6
11
5
7
1
6
14
5
5
37
35
1
1
14
2
4
2
–
–
1
–
–
–
1
2
–
2
59
45
14
–
99
12
38
9
5
4
7
4
6
1
2
5
3
3
11
10
1
–
18
–
3
5
2
–
1
–
–
–
1
6
–
–
7
6
1
–
19
5
2
1
–
2
2
1
1
–
2
1
2
–
Total
264
51
158
29
26
NHL: non-Hodgkin’s lymphoma; CCCW: Comprehensive Cancer Centre West; WF: Working Formulation; L: low grade; I: intermediate grade; H: high grade; U: unclassifiable.
a
Waldeyer’s tonsillar ring was excluded.
tions is currently not very clear because knowledge of
EN-NHL as a separate category is limited. Data on the
clinical behavior of EN-NHL have come mainly from
hospital-based series, in which bias due to patient
selection was unavoidable. Therefore, it remains unclear whether the picture of EN-NHL that has emerged
from these studies reflects its true nature. Populationbased information about clinical behavior of EN-NHL
is scarce.2,3
In the current study, we made a population-based
comparison of N-NHL and EN-NHL and analyzed
possible differences in patient characteristics at diagnosis, responses to treatment, and patterns of failure
and survival, with the aim of determining whether
extranodal lymphomas have specific clinical behavior.
To avoid uncertainties about primary nodal or extranodal origin of lymphomas, this study was limited to
patients with a single affected lymph node or extranodal organ (Ann Arbor Stages I and IE).
PATIENTS AND METHODS
All hospitals (15) and pathology laboratories (9) in
the western part of the Netherlands covered by the
Comprehensive Cancer Centre West (CCCW)(1.6
million inhabitants) cooperated in this study. From
June 1981 to December 1989, data on all newly
diagnosed NHL patients (n 5 1168) living in the
region were entered into a registry by the CCCW
Hemato-Oncology Group. Patients with primary cutaneus T-cell lymphoma, plasmacytoma, acute lymphoblastic leukemia, and chronic lymphocytic leukemia and all cases diagnosed at postmortem
examination were excluded. Diagnosis and classification by the local pathologist were reviewed by a
panel of pathologists. Lymphomas were classified
according to the original Kiel classification and
graded according to the malignancy grades of the
Working Formulation for Clinical Usage (WF).7
Cases included in the current study were reclassified
according to the revised European–American classification of lymphoid neoplasms (REAL)8 and
grouped into the categories “indolent,” “aggressive,” and “very aggressive” proposed by Hiddeman
et al.9 Complete clinical evaluation included history,
physical examination, performance status, leukocyte count and differential, lactate dehydrogenase
(LDH), chest radiograph, computed tomography
(CT) scan of the abdomen or lymphangiogram supplemented by isotope spleen and liver scan in the
early years of the registration, morphologic examination of bone marrow aspirate and biopsy, and
biopsy of involved tissues. Clinical parameters and
involved lymph nodes and extranodal sites were
documented. Patients were staged according to the
1614
CANCER October 15, 1998 / Volume 83 / Number 8
Ann Arbor classification.10 Disease localizations
in the lymph nodes, Waldeyer’s tonsillar ring, and
the spleen were considered to be N-NHL, and
other localizations were considered to be EN-NHL.
Patients were treated according to the preference
of the local physician. Response to treatment was
defined according to standard criteria, with complete response (CR) defined as the disappearance of
all clinical, radiologic, or other evidence of disease.
For patients who experienced disease recurrence
after any CR, involved sites and nodal and/or extranodal status of recurrence were recorded, using
the same definitions as for the primary disease localization. Recurrence was defined as local when the
initially affected organ or first-echelon lymph nodes
were involved and as distant if other sites were
involved. As some patients had both local and distant failures, the total number of recurrences was
greater than the number of patients with recurrent
disease. Overall survival (OS) was calculated from
diagnosis until death (of all causes) or last follow-up
(1996). Recurrence free survival (RFS) was calculated for patients in CR only, from the date of CR
until recurrence (failure) or last follow-up (including death in CR).
Statistical analysis was performed using chisquare tests to compare percentages in cross-tabulations and the log rank test to compare Kaplan–Meier
survival curves.
TABLE 2
Patient Characteristics of All Stage I NHL Patients (n 5 264) in the
CCCW Population-Based Registry
Characteristics
Gender
Male
Age (yrs)
$60
Performance (KPS)a
,80
LDHb
.Normal
Tumor bulkc
$5 cm
Complete staging
No
Grade (WF)
Low
Intermediate
High
Unclassifiable
REAL classification
Indolent
Aggressive
Very aggressive
Unclassifiable
Nodal
(n 5 114)
%
Extranodal
(n 5 150)
%
P value
50
46
ns
57
63
ns
7
32
,0.001
21
22
ns
28
46
0.009
27
31
ns
33
52
10
6
9
66
12
13
,0.001
37
52
3
8
19
72
3
6
0.005
NHL: non-Hodgkin’s lymphoma; CCCW: Comprehensive Cancer Centre West; KPS: Karnofsky performance status; LDH: lactate dehydrogenase; WF: Working Formulation; REAL: revised European–
American classification of lymphoid neoplasms; ns: not significant.
Missing: a 15%, b 16%, c 30%.
RESULTS
Patients
Of 1168 patients in the CCCW database, 264 (23%)
were considered Ann Arbor Stage I. Seventy-seven
patients (29%), most of them of advanced age and/or
with poor performance scores, were not completely
staged, usually because no bone marrow biopsy was
performed. As differences in response, OS, and RFS
between N-NHL and EN-NHL patients were not dependent on the completeness of staging, we decided
to include all 264 Stage I patients (completely and
incompletely staged) in our study.
One hundred fourteen patients (43%) presented
with N-NHL and 150 (57%) with EN-NHL. In patients
with N-NHL, the lymph nodes of the head and neck
were most frequently involved. The majority of ENNHLs were localized in the gastrointestinal tract, but
localizations in a wide diversity of organs were observed (Table 1). Patient characteristics are presented
in Table 2. EN-NHL patients more often presented
with bulky disease (especially patients with gastric and
intestinal localizations) and poor performance status
(especially patients with gastric and central nervous
system [CNS] localizations) than N-NHL patients. Ex-
tranodal lymphomas were more often of intermediate
and high grade malignancy (WF) than nodal lymphomas (Table 2, P , 0.001). Pathologic classification
(REAL) of all lymphomas is presented in Table 3. Most
EN-NHLs were classified as diffuse large B-cell and
mucosa-associated lymphoid tissue (MALT) high
grade lymphomas (according to Isaacson), whereas
the majority of N-NHLs were classified as follicular
lymphomas or diffuse large B-cell lymphomas. As the
relation between Helicobacter pylori infection and
MALT lymphomas was not known during the registration period, there were no data on test results for
Helicobacter pylori infection in patients with MALT
lymphomas. Information on the incidence of infection
with the human immunodeficiency virus (HIV) in this
series of patients would have given noteworthy additional information, because HIV infection is known to
be associated with high grade, often extranodal lymphomas. Due to the finding that HIV infections were
rare in the CCCW region during the registration period, tests for HIV antibodies were not performed on a
regular basis, but we expected the number of HIVrelated lymphomas in this cohort to be negligible.
Stage I Nodal and Extranodal NHL/Krol et al.
1615
TABLE 3
Histologic Classification (REAL) of All Stage I NHL Patients (n 5 264) in the CCCW Population-Based Registry
No. of patientsa
Nodal
Extranodal
Total
Indolent lymphomas (low risk)
B-cell chronic lymphocytic leukemia/lymphoma
Lymphoplasmacytoid lymphoma
Follicle center cell lymphoma, follicular
Follicle center cell lymphoma, diffuse
Marginal zone lymphoma, MALT low grade
Aggressive lymphomas (intermediate risk)
Mantle cell lymphoma
Follicle center cell lymphoma, large cell
Diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma, MALT high grade
peripheral T-cell lymphoma, unspecified
Very aggressive lymphomas (high risk)
Burkitt-like lymphoma
Precursor B-lymphoblastic lymphoma/leukemia
Unclassifiable
42 (29)
2 (1)
–
36 (25)
4 (3)
–
59 (46)
4 (4)
9 (8)
42 (31)
–
3 (3)
3 (3)
2 (2)
1 (1)
10 (5)
28 (17)
1 (1)
5 (3)
5 (3)
1 (1)
16 (9)
108 (76)
1 (1)
1 (1)
55 (40)
45 (33)
6 (2)
5 (4)
4 (3)
1 (1)
9 (7)
70 (46)
3 (2)
5 (3)
41 (28)
5 (4)
16 (9)
167 (122)
5 (5)
10 (8)
97 (71)
45 (33)
10 (5)
8 (7)
6 (5)
2 (2)
19 (11)
Total
114 (83)
150 (103)
264 (187)
NHL: non-Hodgkin’s lymphoma; CCCW: Comprehensive Cancer Centre West; REAL: revised European–American classification of lymphoid neoplasms; MALT: mucosa-associated lymphoid tissue.
a
Nos. in parentheses represent patients who were completely staged (n 5 187).
Treatment
Local treatment (surgery and/or radiotherapy) was
given to 180 patients (68%) and systemic treatment
(chemotherapy alone or in combination with surgery
and/or radiotherapy) to 59 (22%). Twenty-five patients
(10%) did not receive any treatment, in most cases
because of advanced age and/or poor performance
status. Surgery was performed twice as often on ENNHL patients (64%) than on N-NHL patients (32%).
No differences were observed between N-NHL and
EN-NHL patients regarding the application of chemotherapy and radiotherapy or the decision to refrain
from treatment.
Responses
One hundred eighty-seven (78%) of 239 patients
who received treatment achieved a CR during the
course of their disease. EN-NHL patients had a significantly lower CR rate (72%) than N-NHL patients
(84%) (P 5 0.04). For both N-NHL and EN-NHL
patients, age 60 years (P 5 0.05), Karnofsky performance status $80 (P , 0.001), normal lactate dehydrogenase (LDH) level (P , 0.001), and tumor bulk
, 5 cm (P 5 0.004) were of favorable prognostic
significance for CR, whereas malignancy grade (WF)
was not. EN-NHL patients younger than 60 years
with elevated LDH or bulky tumors had inferior CR
rates than N-NHL patients with similar characteristics (Table 4).
Response rates for the different nodal and extranodal primary sites are summarized in Table 5. The
inferior response rate for EN-NHL patients was mainly
a result of the poor CR rates of patients with intestinal
and CNS NHL.
Overall Survival
OS for the entire patient cohort, including patients
who did not receive any treatment, was 55% at 5 years.
The OS for EN-NHL patients was inferior to the OS for
N-NHL patients (49% and 63% at 5 years, respectively;
P 5 0.003). Age 60 years (P , 0.001), performance
status $80 (P , 0.001), normal LDH level (P , 0.001),
tumor bulk ,5 cm (P 5 0.006), and low grade malignancy (WF) (P 5 0.005) were of favorable prognostic
significance regarding OS for both N-NHL and ENNHL patients.
A comparison of the prognostic factors affecting
the OS of N-NHL and EN-NHL patients is presented
in Table 4. EN-NHL patients younger than 60 years
with elevated LDH or bulky tumors had lower OS at
5 years than N-NHL patients with similar characteristics. OS data in relation to involved site at diagnosis are presented in Table 5. The difference in the OS
for N-NHL and EN-NHL patients was mainly a resulted of the poor survival of patients with intestinal, brain, and female breast localizations. Patients
with a stomach localization fared better than other
1616
CANCER October 15, 1998 / Volume 83 / Number 8
TABLE 4
Prognostic Factors for Complete Response, Overall Survival, and Relapse Risk for Stage I Nodal and Extranodal NHL Patients in the CCCW
Population-based Registrya
% CR
Total
Completely staged patients
Age (yrs)
,60
$60
KPS
$80
,80
LDH
Normal
.Normal
Tumor bulk
,5 cm
$5 cm
Grade (WF)
Low
Intermediate
High
5-yr OS
5-yr RR
Nodal
EN
P value
Nodal
EN
P value
Nodal
EN
P value
84
86
72
75
0.04
0.007
63
68
49
52
0.003
0.009
39
27
36
33
ns
ns
91
78
75
70
0.02
ns
85
46
66
39
0.02
ns
30
48
32
39
ns
ns
84
67
81
51
ns
ns
67
29
57
31
ns
ns
39
62
40
38
ns
ns
87
81
86
44
ns
0.02
67
57
56
20
ns
,0.001
39
38
39
55
ns
ns
84
89
89
61
ns
0.01
64
62
63
40
ns
0.02
32
58
36
44
ns
ns
88
83
73
85
74
65
ns
ns
ns
75
56
54
71
52
33
ns
ns
ns
29
38
50
18
29
49
ns
ns
ns
NHL: non-Hodgkin’s lymphoma; CCCW: Comprehensive Cancer Centre West; CR: complete response; OS: overall survival; RR: relapse risk; EN: extranodal; KPS: Karnofsky performance status; LDH: lactate
dehydrogenase; WF: Working Formulation; ns: not significant.
a
OS data on all patients (n 5 264), CR data on patients who received treatment (n 5 239), RR data on patients in CR (n 5 187).
EN-NHL patients and had OS comparable to that of
N-NHL patients.
Relapse Risk
The 5-year relapse risk for all patients was 37%. Of
all factors tested, including completeness of staging,
only malignancy grade (WF) was of prognostic significance for relapse. Relapse rates for low, intermediate, and high grade lymphomas were 26%, 33%,
and 55% at 5 years, respectively (P 5 0.01). By comparison, N-NHL and EN-NHL patients had similar
relapse risks at 5 years, also when compared within
subgroups of the prognostic factors identified for CR
and OS (Table 4). Relapse risk within the group of
patients with extranodal lymphoma differed markedly (Table 5). Patients with gastric lymphomas had
a significantly lower relapse risk (16% at 5 years)
than patients with other extranodal or nodal lymphomas (36% and 39% relapse risk at 5 years, respectively; P 5 0.007).
Patterns of Failure
Risk for local and distant relapse at 5 years was 25%
and 22%, respectively. Elevated LDH level (P 5
0.002) and tumor bulk $5 cm (P 5 0.01) were prognostic for local relapse, and for distant relapse risk
the same trend was observed. Local and distant
relapse rates at 5 years for N-NHL and EN-NHL
patients did not differ. However, patients who presented with nodal disease experienced failure predominantly in nodal localizations, whereas the majority of those presenting with extranodal disease
had extranodal recurrences; this difference in preferential relapse sites between N-NHL and EN-NHL
patients was significant (P 5 0.04). We looked for
specific patterns of failure in subgroups of extranodal lymphomas, but the number of recurrences in
these groups was too small to permit conclusions.
Some noteworthy trends were observed, however. In
the group of MALT lymphoma patients, approximately half of the recurrences were localized in the
digestive and/or respiratory tract, whereas gastric
recurrence was observed in two patients with a
Waldeyer’s tonsillar ring localization. All recurrences of patients with cutaneous lymphomas occurred in the skin, and all patients with CNS NHL
experienced local failure. An analysis of patterns of
failure for individual nodal and extranodal primary
sites is presented in Table 6.
DISCUSSION
This study of Stage I NHL patients was performed to
investigate possible differences in the clinical picture for patients with primary nodal and extranodal
Stage I Nodal and Extranodal NHL/Krol et al.
TABLE 5
Complete Response, Overall Survival, and Relapse Risk for Stage I
NHL Patients in the CCCW Population-Based Registry, Analyzed by
Primary Disease Localizationa
Nodal (114)
Lymph node (96)
Waldeyer’s ring (17)
Extranodal (150)
Head/neck6 (19)
Stomach (47)
Intestine (17)
Bone/connective tissue (13)
Skin (11)
Female breast (5)
Testis (7)
Orbita/lacrimal gland (6)
Brain (14)
Spinal cord, epi-/extradural (5)
Thyroid (5)
CR
%
5-yr OS
(%)
5-yr RR
(%)
84
84
88
72
72
80
40
60
78
100
100
100
43
80
80
63
66
47
49
53
66
35
50
45
20
43
83
7
57
40
39
38
43
36
31
16
33
33
43
100
29
72
50
62
50
NHL: non-Hodgkin’s lymphoma; CCCW: Comprehensive Cancer Centre West; CR: complete response;
OS: overall survival; RR: relapse risk.
a
OS data on all patients (n 5 264), CR data on patients who received treatment (n 5 239), RR data on
patients in CR (n 5 187).
b
Waldeyer’s tonsillar ring was excluded.
disease. By analyzing patients from a populationbased registry, we circumvented the problem of bias
due to patient selection. The absence of selection is
reflected in the advanced age and poor performance
status of the patients in this study, which resulted in
a decision to refrain from treating 10% of the patients. When this is considered, it is not surprising
that these treatment results were inferior to those
for published hospital-based series, which usually
report on a younger selection of patients with aggressive NHL.11–15
The goal of this study was to compare primary
nodal and extranodal lymphoma patients with respect to their clinical situations at diagnosis, treatment, responses to treatment, relapse risk, patterns
of failure, and survival. The percentage of EN-NHL
patients in this series was high in comparison with
other population-based studies,1,3,4 probably due in
part to the fact that only Stage I patients were selected. The relative frequency of extranodal organs
affected, with gastrointestinal tract and localizations in the head and neck area the most commonly
involved sites, was in line with other populationbased data.1,3,4
EN-NHL patients had relatively low performance scores, bulky tumors, and more often lymphomas of intermediate or high grade malignancy at
diagnosis. Given the finding that the treatment of
1617
N-NHL and EN-NHL patients (including the decision to refrain from treatment) was not essentially
different, the reason for the observed inferior response rate and survival of EN-NHL patients must
be a result of the poor prognostic characteristics of
these patients at diagnosis. Patients with primary
EN-NHL and a considerable tumor load (elevated
LDH and bulky disease) or intermediate and high
grade lymphomas appeared to have especially poor
prognoses compared with N-NHL patients with the
same characteristics. The relatively poor prognostic
characteristics of EN-NHL patients became irrelevant, however, when CR was achieved following
treatment: in these cases, recurrence free survival
for N-NHL and EN-NHL patients was equal.
When the differences in prognostic factors between N-NHL and EN-NHL were analyzed in more
detail, the poor prognostic factors for EN-NHL patients were not characteristic of the entire group of
these patients; rather, they were observed in certain
subgroups of patients. Poor performance status was
mainly observed in patients with gastric and central
nervous system localizations. Bulky disease was
mainly found in patients with gastric, intestinal, and
bone or soft tissue localizations. As a consequence,
treatment results and survival for these patients were
inferior to those for other EN-NHL patients. However,
patients with a gastric localization were an exception
to this rule: despite poor performance and considerable tumor load at diagnosis, the survival of these
patients was superior to that of other EN-NHL patients and comparable to that of N-NHL patients. Our
analysis demonstrated that this was a result of the
relatively low relapse risk for gastric lymphoma patients. As 45 of 47 gastric lymphomas were classified as
MALT lymphomas of either low or high malignancy
grade, this observation supports the MALT concept
formulated by Isaacson.16 This concept postulated
that MALT lymphomas had restricted dissemination
due to “homing” receptors on the cell membranes of
MALT lymphoma cells, resulting in a favorable prognosis for patients with these lymphomas. In an analysis of all primary gastric lymphomas in the CCCW
database (disseminated cases included), the clinical
relevance of this concept was also illustrated.17
This study also focused on possible specific patterns of dissemination for extranodal lymphomas
other than MALT lymphomas. Although the relapse
risk for N-NHL and EN-NHL patients was similar, also
with respect to the distribution of local and distant
failures, a striking difference between these patients
was seen with respect to preferential sites for recurrence. N-NHL patients mainly experienced recurrence
in nodal sites, and EN-NHL patients in extranodal
1618
CANCER October 15, 1998 / Volume 83 / Number 8
TABLE 6
Patterns of Failure for Stage I NHL Patients in the CCCW Population-Based Registry, in Complete Response after Treatment (n 5 187)
No. of patients
CR
Failure free
Local failure
Distant failure
Local 1 distant failure
Nodal (114)
Lymph node (96)
Waldeyer’s tonsillar ring (17)
Spleen (1)
Extranodal (150)
Head/necka (19)
Stomach (47)
Intestine (17)
Bone/connective tissue (13)
Skin (11)
Female breast (5)
Testis (7)
Orbita/lacrimal gland (6)
Brain (14)
Spinal cord, epi-/extradural (5)
Thyroid (5)
88
73
14
1
99
13
32
6
9
7
5
7
6
6
4
4
55
46
9
–
64
10
27
3
5
4
–
6
2
3
2
2
13
9
3
1
13
–
1
1
1
1
2
–
3
3
–
1
9
9
–
–
14
2
3
2
3
–
1
1
1
–
1
–
11
9
2
–
8
1
1
–
–
2
2
–
–
–
1
1
Total
187
118
26
23
19
NHL: non-Hodgkin’s lymphoma; CCCW: Comprehensive Cancer Centre West; CR: patients in complete response after treatment.
a
Waldeyer’s tonsillar ring was excluded.
sites. This observation supports the concept of “directed migration” in the dissemination of NHL, regulated by adhesion molecules on the cellular membranes of lymphoma cells.5
In conclusion, this study demonstrated that primary
extranodal NHL patients as a group have a poorer response to treatment and consequently survival inferior
to that of patients with primary nodal NHL. However,
among EN-NHL patients, considerable variations in response to treatment and survival exist, with gastric lymphoma patients having the best and central nervous
system lymphoma patients having the worst prognosis.
Consequently, for clinical purposes, it seems more useful to make distinctions based on specific sites, tumor
grade, and histologic classification than to consider ENNHL a single entity. In cases of CR to treatment, differences between nodal and extranodal lymphoma patients
disappeared: no differences in relapse rates were observed. However, patterns of relapse for nodal and extranodal lymphomas were different, suggesting that sites
were preferential for recurrence depending on the primary site. In light of this, it also seems more important to
consider the primary site rather than the nodal or extranodal status of NHL.
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