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970
Hodgkin Disease with Subsequent Transformation to
CD30 Positive Non-Hodgkin Lymphoma in Six Patients
Naoyoshi Mori1
Kazuko Watanabe1
Yoriko Yamashita1
Atsuo Nakayama1
Yasushi Yatabe2
Michihiko Narita3
Toshitaka Kobayashi4
Yuuichi Hasegawa5
Hiroshi Kojima5
Toshiro Nagasawa5
1
First Department of Pathology, Nagoya University
School of Medicine, Nagoya, Japan.
2
Department of Pathology and Clinical Laboratories, Aichi Cancer Center Hospital, Nagoya, Japan.
3
Department of Pathology, Koseiren Kamo Hospital, Toyota, Japan.
4
Department of Internal Medicine, Tsuchiura
Kyodo Hospital, Tsuchiura, Japan.
5
Department of Internal Medicine, Tsukuba University, Tsukuba, Japan.
Supported in part by a grant-in-aid from the Ministry of Education (09670183)
The authors thank Mr. Nobuaki Misawa and Yoshie
Ieda for their excellent technical assistance.
Address for reprints: Dr. Naoyoshi Mori, Department of Pathology, Nagoya University School of
Medicine, Tsuruma-cho 65, Nagoya, showa-ku,
Nagoya, 466-8550, Japan.
Received January 9, 1998; revision received April
13, 1998; accepted July 31, 1998.
© 1999 American Cancer Society
BACKGROUND. Previous studies have indicated that some patients with Hodgkin
disease have an aggressive clinical course. However, their characteristics have not
been elucidated.
METHODS. Six patients initially diagnosed as having Hodgkin disease with subsequent transformation to CD30 positive non-Hodgkin lymphoma were clinically
and immunohistochemically studied. Ten patients with classic anaplastic large cell
lymphoma (ALCL) and 19 patients with classic Hodgkin disease were studied for
comparison by immunohistochemistry.
RESULTS. Five patients, excluding one whom the authors recently encountered,
had an aggressive clinical course and died within approximately 1 year after
diagnosis; four of them were autopsied. Common histologic findings in the six
patients included sheets of atypical mononuclear cells and sinusoidal infiltration of
small numbers of these cells, as well as Reed–Sternberg cells or lacunar cells.
Follow-up biopsies revealed histologic progression to ALCL in which sheets of
atypical mononuclear or multinucleated cells spread throughout the lymph nodes.
Immunohistochemically, epithelial membrane antigen, granzyme B, perforin, and
pancadherin were expressed frequently in the six patients and in ALCL but were
not expressed in Hodgkin disease. Latent membrane protein-1 (LMP-1) and Epstein–Barr virus-encoded RNA (EBER-1) were totally negative in the six patients
and in ALCL but were expressed frequently in Hodgkin disease. In contrast, LeuM1
(CD15) was expressed frequently in the six patients and in Hodgkin disease,
whereas it was not expressed in ALCL. MT1 (CD43), UCHL-1 (CD45RO), and P80
were totally negative in the six patients and in Hodgkin disease, whereas they were
expressed variably in ALCL.
CONCLUSIONS. These results suggest that the six patients studied had intermediate
phenotypes between ALCL and Hodgkin disease. The authors also suggest that
patients with sheets of atypical mononuclear cells and sinusoidal infiltration of
atypical mononuclear and multinucleated cells have an aggressive clinical course
and should be treated with intensive chemotherapy. Cancer 1999;85:970 –9.
© 1999 American Cancer Society.
KEYWORDS: Hodgkin disease, anaplastic large cell lymphoma, granzyme B, perforin,
Epstein–Barr virus-encoded RNA, latent membrane protein-1 (LMP-1), pancadherin,
p80.
R
ecent studies have revealed that Hodgkin disease and anaplastic
large cell lymphoma (ALCL)1–5 have various features, such as the
presence of t(2;5)(p23;q35) translocation6 –14 in ALCL and its absence
of Hodgkin disease. Furthermore, ALCL may have null-cell or T-cell
phenotypes, whereas Hodgkin disease occasionally has B-cell phenotypes.15–18 However, there are some patients in which the disease is
quite difficult to differentiate.19,20 In addition, some reports indicate
that some patients with Hodgkin disease progressed to ALCL.21,22
Transformation of Hodgkin Disease to ALCL/Mori et al.
971
TABLE 1
Histologic and Immunohistochemical Characteristics of the Initial Lymph Node Biopsy Specimens from the
Six Patients
Patient
Characteristics
1
2
3
4
5
6
Histologic subtype
Fibrosis
Sheets of atypical cells
Sinus involvement
RS cells
Lacunar cells
Main immunophenotypes
BerH2
LeuM1
EMA
LCA
L26
CD3
LD
2
111
11
1
2
LD
2
111
1
1
2
MC
2
111
1
1
2
MC
2
11
1
1
2
NS syn
11
11
1
1
1
NS syn
11
11
1
1
11
11
1
1
2
2
2
11
2
2
2
2
2
11
1
2
2
2
2
1
11
2
2
2
2
11
11
1
2
2
2
1
11
2
2
2
2
LD: Hodgkin disease, lymphocytic depletion; MC: Hodgkin disease, mixed cellularity; NS syn: Hodgkin disease, nodular sclerosis, syncytial variant; RS cells:
Reed-Sternberg cells; EMA: epithelial membrane antigen; LCA: leukocyte common antigen; 2: negative; 1: positive; 11: strongly positive.
Based on these results, the Revised European and
American Lymphoma (REAL) classification23 has proposed a provisional entity of Hodgkin-like ALCL.24
However, this entity has ambiguous features along
with its morphology. The authors had experience with
six patients who were diagnosed with Hodgkin disease
on initial biopsies but who had subsequent biopsies
that revealed ALCL and had an aggressive clinical
course. Further studies of such patients may elucidate
the correlation between Hodgkin disease and ALCL.
MATERIALS AND METHODS
Paraffin Tissue
Lymph node samples were obtained, fixed in a 10%
formaldehyde solution, and embedded in paraffin.
Sections were cut 2– 4 mm thick and were stained with
hematoxylin and eosin. An avidin-biotin-peroxidase
complex (Nichirei Corp., Tokyo, Japan) method25 was
used for all immunohistochemical studies [BerH2
(CD30), LCA (CD45), epithelial membrane antigen
(EMA), L26 (CD20), polyclonal CD3, CD8, and LMP-1
from DAKO (Copenhagen, Denmark); UCHL-1
(CD45RO) from Nichirei Corp.; LeuM1 (CD15) from
Beckton Dickinson Monoclonal Center (Mountain
View, CA); MT1 (CD43) from Bioscience (Emmerbruecke, Switzerland); granzyme B (GrzB) from
Monozan (Ueden, Netherlands); pancadherin (p-cadherin) from Sigma Biosciences (St. Louis, MO); and
p80NPM/ALK from Nichirei Corp.].
Frozen Tissue
Fresh tissue samples were first fixed in periodatelysine-paraformaldehyde,26 frozen, sectioned 6-8 m
thick with a cryostat, postfixed in acetone for 10 minutes, and then incubated with the primary antibodies
[Leu1 (CD5), Leu2 (CD8), Leu3 (CD4), Leu4 (CD3),
Leu19 (CD56), and Ki-1 (CD30), from DAKO; B1
(CD20) and B4 (CD19) from Coulter Immunology (Hialeah, FL); bF1 and TCRd1 from T Cell Sciences (Cambridge, MA); and perforin from T Cell Diagnostics, Inc.
(Cambridge, MA)]. The avidin-biotin-peroxidase complex method25 was also used.
In Situ Hybridization
After deparaffinization and digestion with proteinase
K (Sigma Chemical Co., St. Louis, MO), the tissue
sections were hybridized with fluorescein-conjugated
oligonucleotide probes for Epstein–Barr virus (EBV)encoded RNA (EBER-1; 30 bp; EBV probe in situ hybridization kit; Novocastra Laboratories Ltd., Newcastle, United Kingdom). Stringently washed sections
were reacted with an antifluorescein antibody, and the
reactions were visualized with 5-bromo-4-chloroindolylphosphatase and nitroblue tetrazolium salt. Details of the in situ hybridization procedure have been
described elsewhere.27–31
Southern Blot Hybridization
Ten micrograms of high-molecular-weight DNA extracted from each sample were digested with EcoRI,
BamHI, and HindIII (Nippon-Gene Corp., Tokyo, Japan) restriction enzymes. Electrophoresis of the resulting fragments was performed by using 0.7% agarose gel slabs, followed by Southern blotting32 with JH,
CTb, and Jr probes labeled with 32phosphorus. After
972
CANCER February 15, 1999 / Volume 85 / Number 4
FIGURE 1.
Hematoxylin and eosin (H&E) staining of an initial lymph node
biopsy reveals a few Reed–Sternberg cells with prominent nucleoli (patient 4;
3600).
appropriate washing, autoradiography was performed
at 280°C for 4 days.
RESULTS
All of the patients were diagnosed with Hodgkin disease on initial biopsies but then underwent a rapid
clinical course with the exception of one patient. The
histologic characteristics of the six patients are shown
in Table 1. Of these, four patients were characterized
by scant fibrosis, revealing histologic features of mixed
cellularity (Fig. 1) or of a lymphocyte-depleted type of
Hodgkin disease. In these patients, typical, isolated
Reed–Sternberg cells with large cytoplasms and eosinophilic, prominent nucleoli were observed surrounded by nonneoplastic lymphocytes in the entire
lymph nodes. In addition, these lymph nodes also
contained small clusters of atypical mononuclear or
multinucleated cells (Fig. 2) and small numbers of
these cells in sinuses (Fig. 3). An admixed inflammatory cell infiltrate composed of eosinophils and epithelioid cells was variably noted. The remaining two
FIGURE 2. H&E
staining of an initial lymph node biopsy reveals sheets of
atypical mononuclear and multinucleated cells (patient 2; 3300).
patients, who were considered to have Hodgkin disease, nodular syncytial variant, had biopsies that were
characterized by thick, fibrous connective tissue that
encircled lymphoid tissue, which contained Reed–
Sternberg cells and lacunar cells (Fig. 4), as well as
sheets of atypical mononuclear cells. Plasma cells,
neutrophils, eosinophils, and necrosis were also observed.
Main immunophenotypic findings of the initial
lymph node biopsies from the six patients showed that
Reed–Sternberg cells or their variants were positive for
BerH2 in 6 of 6 patients, for LeuM1 (Fig. 5) in 5 of 6, for
EMA in 2 of 6, for LCA in 1 of 6, for L26 in 0 of 6, and
for CD3 in 0 of 6 (Table 1). Based on these histologic
and immunohistochemical findings, we diagnosed
these patients with Hodgkin disease on initial biopsies.
All of the patients were treated after initial diagnosis (Table 2). Of these, one patient (6) responded
well to chemotherapy, and complete remission was
achieved. Two patients (1 and 2) responded relatively
well to chemotherapy, with significant decrease of
lymphadenopathy. However, lymph node enlarge-
Transformation of Hodgkin Disease to ALCL/Mori et al.
FIGURE 3. H&E staining of an initial lymph node biopsy reveals sinusoidal
infiltration of a small number of atypical mononuclear cells (patient 1; 3600).
ment recurred shortly after chemotherapy, and the
patients underwent a progressive clinical course with
systemic lymphadenopathy and bone marrow involvement. The remaining three patients responded
poorly to chemotherapy, with partial reduction of
lymphadenopathy, and underwent an aggressive clinical course. Follow-up biopsies were obtained from
patients with recurrent lymph nodes after successful
treatment or after partial response to chemotherapy.
Follow-up biopsies revealed histologic progression to ALCL in which sheets of atypical mononuclear
or multinucleated cells spread throughout the lymph
nodes. In addition, biopsies of the skin, liver, spleen,
and bone marrow often revealed lymphomatous involvement in many of the patients. Subsequent biopsies of various organs and tissues did not show significant change of the phenotypes of neoplastic cells
(Table 3). However, some of the neoplastic cells became positive for EMA in two additional patients (2
and 3).
Ten patients with classic ALCL and 19 patients
with Hodgkin disease were studied for comparison by
immunohistochemistry (Table 4). Cytotoxic mole-
973
cules, GrzB (Fig. 6) and perforin, were expressed in 4
of 6 patients. Either one or both of the cytotoxic molecules were expressed in 8 of 10 patients with classic
ALCL. In contrast, only one of the patients with
Hodgkin disease expressed perforin. Pan-cadherin
was expressed in all our patients (Fig. 7) and in patients with classic ALCL but was expressed only in 10
of 19 patients with Hodgkin disease. Latent membrane
protein-1 and EBER-1 were not expressed in any of the
current patients or in patients with classic ALCL. Latent membrane protein-1 and EBER-1 were expressed
in 11 patients and 13 patients, respectively, with
Hodgkin disease. MT1 (CD43) and UCHL1 (CD45RO)
staining were absent both in our patients and in those
with Hodgkin disease but were identified in 6 patients
and 5 patients, respectively, with classic ALCL. Leu19
(CD56) was positive in two samples from our patients
and in three samples from patients with classic ALCL.
P80NPM/ALK was totally negative in our patients and in
patients with Hodgkin disease but was positive in 7
patients with classic ALCL.
Southern blot hybridization studies revealed that
none of the patients studied possessed a clonal rearrangement band of T-cell receptor b chain (Cb1). All
but one patient died within approximately 1 year after
diagnosis. Autopsies performed on four patients revealed lymphomatous infiltration of various organs.
The involved organs contained lymphomatous cells
that tended to form clusters (Fig. 8). Variable fibrosis
was noted, and occasional nodules larger than 1 cm in
greatest dimension were formed. Skin involvement
was observed in four patients, liver involvement was
observed in four patients, lung involvement was observed in four patients, spleen involvement was observed in three patients, and bone marrow involvement was observed in two patients. Systemic lymph
node involvement was seen in all patients.
DISCUSSION
Strickler et al.33 reported on 18 patients with Hodgkin
disease with sheets and cohesive clusters of numerous
Reed–Sternberg cell variants and called them a syncytial variant of nodular sclerosing (NS) Hodgkin disease. MacLennan et al.34 studied 1659 patients who
were treated for Hodgkin disease and found that NS
Hodgkin disease with extensive lymphocyte depletion
or numerous anaplastic Hodgkin cells (Grade II NS) is
resistant to initial therapy, frequently recurs, and has a
worse prognosis than Grade I NS. They concluded that
patients with Grade II NS require more aggressive
initial therapy. This work formed the basis for the
ALCL Hodgkin-like subtype in the REAL classification.23 However, a great deal remains to be elucidated
about the nature of Hodgkin-like ALCL. Two of our
974
CANCER February 15, 1999 / Volume 85 / Number 4
FIGURE 4. (a) H&E staining of an initial lymph node biopsy reveals thick, fibrous connective tissue encircling lymphoid nodules (patient 5; 330). (b) Higher
magnification reveals numerous lacunar cells (3300).
patients were consistent with Grade II NS, and the
remaining four patients were considered to have the
mixed cellularity or lymphocyte depleted types on initial biopsies.
We studied six patients retrospectively who were
diagnosed initially with Hodgkin disease, but their
subsequent biopsies revealed ALCL features, and their
disease underwent a rapid, aggressive clinical course.
This is the first precise report to reveal the histologic
progression of Hodgkin disease to ALCL in sequential
biopsies. Some previous reports have indicated a close
correlation between Hodgkin disease and nonHodgkin lymphoma. Sundeen et al.35 reported lymphocyte predominant Hodgkin disease, nodular subtype, with coexistent large cell lymphoma. Others have
reported that some patients had Hodgkin disease that
progressed to non-Hodgkin lymphoma, including
ALCL,21,22 and some patients had ALCL that changed
into Hodgkin disease.20 Our patients belong to the
second type. These patients with secondary ALCL reportedly have worse prognoses than those with primary ALCL.36
Pileri et al.22 reported on five patients with
Hodgkin disease associated with ALCL and suggest
that ALCL lymphoma with previous or simultaneous
Hodgkin disease should be regarded as the blastic
transformation of Hodgkin disease because of the occurrence of both neoplasms in one patient and the
onset of ALCL lymphoma in the same anatomical sites
as those of Hodgkin disease and because of the short
interval between Hodgkin disease and ALCL in three
of five of their patients. Those authors also argued in
favor of the blastic transformation of previous
Hodgkin disease by the absence of any significant
variation in the phenotype of the neoplastic cells at
presentation and at the time of second biopsy. Our
current study also had similar results. Immunophenotypic studies of our patients did not reveal any significant change in the phenotypes of the neoplastic cells
between the initial biopsies and subsequent biopsies.
Our patients showed the morphology of Hodgkin disease on initial biopsy with foci of ALCL that progressed subsequently to ALCL with an aggressive clinical course and was accompanied frequently by early
skin, liver, spleen, bone marrow, and systemic lymph
node involvement.
Transformation of Hodgkin Disease to ALCL/Mori et al.
975
TABLE 2
Clinical and Autopsy Findings from the Six Patients
Patient
Sex/age (yrs)
Involved sites clinical (biopsies)
Stage
Therapy
Clinical course
Involved sites at autopsy
1
M/45
Cervical,a aortic, inguinal LN,a spleen, skin,a bone
marrowa
IIIB
C-MOPP
7.9 mo (dead)
2
M/31
Mediastinal,a paraaortic LN, bone marrow,a livera
IVB
C-MOPP
6.8 mo (dead)
3
4
M/69
F/38
Cervical,a aortic, inguinal LN, skina
Cervical,a paraaortic LN,a bone marrow,a spleen,a skina
IVB
IVB
COP
C-MOPP
7.8 mo (dead)
13 mo (dead)
5
M/77
IVB
C-MOPP
11 mo (dead)
6
M/23
Cervical,a mediastinal, paraaortic,a LN, liver, spleen,
lung, skina
Cervical,a mediastinal,a supraclavicular LNa
Liver, spleen, bone marrow, skin,
lung, pericardium, kidneys, lymph
nodes
Liver, spleen, bone marrow, lung
adrenals, dura mater, intestines,
ureters, lymph nodes
—
Liver, bone marrow, lung, stomach
pharynx, lymph nodes
Liver, spleen, skin, lung, lymph nodes
IIB
CDDP 1 CHOP
5 mo (CR)
—
M: male; F: female; MOPP: mechlorethamine, vincristine, procarbazine, and prednisone; COP: cyclophosphamide, vincristine, and prednisone; CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone;
CDDP: cisplatin; CR: complete remission; mo: month; LN: lymph node.
a
Biopsied tissues or organs.
TABLE 3
Immunohistochemical and Immunogenetic Findings of Lymph Node
Biopsies with Anaplastic Large Cell Lymphoma Features from the Six
Patients
Patient
FIGURE 5. LeuM1 staining of an initial lymph node biopsy reveals positive
reactivity in many atypical cells (Patient 4) (3300).
Initial biopsies from all of our patients contained
small numbers of atypical BerH2 (or LeuM1) positive
mononuclear, or multinucleated atypical sinusoidal
cellular infiltrates along with sheets of atypical mononuclear cells. This finding is in marked contrast to the
Antibody (or probe)
1
2
3
4
5
6
BerH2 (CD30)
LeuM1 (CD15)
LCA (CD45)
EMA
L26 (CD20)
CD3
CD8
MT1 (CD43)
UCHL1 (CD45RO)
P-cad
Leu1 (CD5)
Leu2 (CD8)
Leu3 (CD4)
Leu4 (CD3)
bF1
TCRd1
B1 (CD20)
B4 (CD19)
GrzB
PF
Leu19 (CD56)
LMP1
EBER1
P80
Cb1
111
2
1
1
2
2
2
2
2
11
2
2
11
2
2
2
2
2
1
1
2
2
2
2
2
111
2
2
1
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
1
2
2
2
2
11
1
2
1
2
2
2
2
2
11
2
2
11
2
2
2
2
2
1
1
11
2
2
2
2
1
11
2
2
2
2
2
2
2
1
2
2
2
2
2
2
2
2
1
1
2
2
2
2
2
11
11
2
1
2
2
2
2
2
1
2
2
1
2
2
2
2
2
11
1
2
2
2
2
2
1
11
2
2
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
LCA: leukocyte common antigen; EMA: epithelial membrane antigen; P-cad: pancadherin; GrzB: granzyme B; PF: perforin; LMP1: latent membrane protein 1; EBER1: EBV-encoded RNA; p80: p80NPM/ALK;
Cb1: T cell receptor gene Cb1; 2: positive neoplastic cells , 10%; 1: positive neoplastic cells ^ 10–50%;
11: positive neoplastic cells . 50–80%; 111: positive neoplastic cells . 80%.
976
CANCER February 15, 1999 / Volume 85 / Number 4
TABLE 4
Comparison of Immunohistochemical and In Situ Hybridization
Findings among the Six Patients, Anaplastic Large Cell Lymphoma,
and Hodgkin Disease
Antibody
(or probe)
The six
patients
ALCL
(n 5 10)
Hodgkin’s disease
(n 5 19)
EMA
GrzB
PF
P-cad
LMP1
EBER1
LeuM1(CD15)
LCA(CD45)
MT1(CD43)
UCHL1(CD45RO)
P80
4a
4
4
6
0
0
4
1
0
0
0
8
5
8
10
0
0
0
8
6
5
7
1
0
1
10
11
12
14
0
0
0
0
ALCL: anaplastic large cell lymphoma; EMA: epithelial membrane antigen; GrzB: granzyme B; PF:
perforin; P-cad: pancadherin; LMP1: latent membrane protein 1; LCA: leukocyte common antigen; p80:
p80NPM/ALK.
a
Number of positive cases.
FIGURE 7. Pancadherin staining of an initial lymph node biopsy reveals
positive reactivity in many atypical cells (patient 5; 3300).
FIGURE 6.
Granzyme B staining of an initial lymph node biopsy reveals
positive reactivity in most of the atypical cells (patient 4; 3300).
biopsies from patients with Hodgkin disease in which
sinus infiltration of a few Reed–Sternberg cells was
rarely observed. Therefore, we must emphasize the
need to examine extensively for sinus involvement in
patients with sheets of atypical cells.
All of the our patients were positive for BerH2
(CD30). Previous study has indicated that most ALCLs
are positive for EMA37 and LCA but are negative for
LeuM1. In contrast, most patients with Hodgkin disease are negative for EMA and LCA but are positive for
LeuM1. Although immunohistochemical findings of
the initial biopsies were mostly consistent with
Hodgkin disease phenotypes, subsequent biopsies revealed some change in the phenotypes, namely, EMA
positivity in two additional patients.
Some patients with ALCL have been reported to
be positive for the p80 antibody, which is raised
against the NPM/ALK gene.14,38 All of the samples from
our patients were negative for this antibody, whereas 7
of 10 samples from patients with classic ALCL were
positive.
Foss et al.39 reported that almost all T/null ALCLs
express perforin40 transcripts and GrzB41– 44 and that
Transformation of Hodgkin Disease to ALCL/Mori et al.
FIGURE 8. H&E staining of an autopsied lymph node reveals sheets of
atypical mononuclear and multinucleated cells (patient 5; 3300).
clonal gene rearrangements of the TCR-b chain are
observed in 10 of 11 patients with null cell ALCL and in
9 of 10 patients with T-cell ALCL.
The current study indicate GrzB expression in
four of our six patients and perforin expression in
three patients. GrzB and perforin expression was
demonstrated in six patients and seven patients
with classic ALCL, respectively. Krenacs et al.45 also
reported that 76% of patients with ALCL expressed
cytotoxic molecules. Oudejans et al.46 found GrzB
expression in a portion of the Reed–Sternberg cells
found in 11 of 61 patients with Hodgkin disease
(18%). However, only one of our patients with
Hodgkin disease expressed GrzB or perforin. Therefore, these markers may be useful in differentiating
our patients from those with Hodgkin disease, because these molecules are expressed infrequently in
Hodgkin disease. The lack of MT1 reactivity9 in our
patients sharply contrasts with the frequent reactivity in patients with classic ALCL.
Ashton-Key et al.47 reported essentially invariable
expression of p-cadherin, a family of cell-to-cell adhesion molecules, in ALCL but less frequent expression
977
in Hodgkin disease. The current study revealed that
p-cadherin was expressed in all patients with ALCL
and in our patients, but it was absent in 9 of 19
patients with Hodgkin disease.
EBER-130,48,49 and/or LMP-150,51 are expressed
frequently in Hodgkin disease and are mostly absent
in ALCL.52,53 Similarly, EBER-1 positivity was seen in
13 of 19 of our patients with Hodgkin disease. Several
previous studies54,55 have indicated that ALCLs may
occasionally express EBER-1. However, EBER-1 could
not be demonstrated in our set of patients with ALCL
or in our current six patients. Therefore, these markers, in addition to their clinical features, may help to
distinguish our patients from those with Hodgkin disease.56 –58
In conclusion, our six patients were diagnosed
with Hodgkin disease on initial biopsies but subsequently developed ALCL associated with an aggressive clinical course. The disease in our patients appears to be related more closely to ALCL than to
Hodgkin disease clinically but showed intermediate
phenotypes between ALCL and Hodgkin disease.59
We suggest that patients who have disease with the
features of Hodgkin disease with sheets of atypical
mononuclear or multinucleated giant cells should
be examined extensively for sinus involvement as
well as multiparameter analysis, because our patients had worse prognoses than those with Hodgkin
disease. Therefore, more aggressive chemotherapy
is necessary.
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