Int J Clin Exp Pathol 2014;7(7):4381-4390
www.ijcep.com /ISSN:1936-2625/IJCEP0000700
Case Report
Primary platelet-derived growth factor-producing,
spindle-shaped diffuse large B-cell lymphoma of
the skull: a case report and literature review
Kei-Ji Sugimoto1, Asami Shimada1, Kunimoto Ichikawa1, Mutsumi Wakabayashi1, Yasunobu Sekiguchi1,
Hiroshi Izumi3, Yasunori Ota4, Norio Komatsu2, Masaaki Noguchi1
Department of Hematology, Juntendo University Urayasu Hospital, Urayasu, Japan; 2Department of Hematology,
Juntendo University School of Medicine, Tokyo, Japan; 3Department of Pathology, Juntendo University Urayasu
Hospital, Urayasu, Japan; 4Department of Pathology, Research Hospital, The Institute of Medical Science, The
University of Tokyo, Japan
1
Received May 3, 2014; Accepted June 24, 2014; Epub June 15, 2014; Published July 1, 2014
Abstract: A 39-year-old woman with a right frontal mass underwent a cranial bone tumor biopsy. Histopathologic
examination of hematoxylin and eosin–stained slides showed spindle-shaped tumor cells in a storiform pattern, appearing somewhat like a sarcoma. However, the tumor cells were CD20-positive by immunohistochemical staining.
Therefore, a diagnosis of spindle-shaped diffuse large B-cell lymphoma (Sp-DLBCL) was made. There have been
at least 35 cases of Sp-DLBCL documented in the literature, and most were of the germinal center type, while the
present case is the first report of a vimentin-positive primary Sp-DLBCL of the skull. The DLBCL in this case was
immunohistochemically stained for six representative cytokines that might give rise to fibrosis, due to the evidence
of fibroblastic proliferation. The DLBCL cells were positive for platelet-derived growth factor (PDGF), and some cells
were also positive for tumor necrosis factor (TNF) α. Based on these findings, it was inferred that the PDGF and TNFα
produced by DLBCL cells induced fibroblastic proliferation. The resultant conspicuous fibrosis caused interfibrous
impingement on the DLBCL cells, which deformed them into a spindle shape. The present case is the first reported
case of a PDGF-producing Sp-DLBCL.
Keywords: Spindle cell, storiform, diffuse large B-cell lymphoma, skull, platelet-derived growth factor, vimentin
Introduction
Spindle-shaped diffuse large B-cell lymphoma
(Sp-DLBCL) is an atypical variant of DLBCL, not
otherwise specified. It is generally recognized
that lymphomatous cells may assume a spindle
shape upon entry into osseous or soft tissues.
In our case, however, the findings seemed to
indicate that in the case of DLBCL, fibroblastic
proliferation in the soft tissues caused impingement and deformation of the cells. Furthermore,
in our case, the DLBCL tumor cells per se were
found to produce platelet-derived growth factor
(PDGF), and occasionally, tumor necrosis factor
(TNF) α, which are cytokines that stimulate
fibroblastic proliferation. Thus, it is inferred that
fibroblasts stimulated by factors such as PDGF
and TNFα proliferate to cause interfibrous
impingement in DLBCL, resulting in spindle-
shaped deformation of the cells in the neoplasm.
Case report
The patient was a 39-year-old woman who presented with the chief complaint of painful swelling in the right side of her forehead. She had a
past history of panic disorder and depression
diagnosed when she was 23 years of age. She
was allergic to alcohol and iodine. She had
started to experience pain in the right frontal
region in the summer of 2011. Subsequently,
she developed stiff shoulders, a tense feeling in
her head, and pain in the occipital and frontal
regions as well as in the right retroauricular
region and molar teeth. She sought medical
advice at a neighborhood medical clinic in
March 2012. As seen in Figure 1, she was
Spindle-shaped diffuse large B-cell lymphoma
Figure 1. Imaging findings: X-ray (A, B), computed tomography (CT) images (C-G), bone scintigraphy (H), and 18Ffluorodeoxyglucose positron emission tomography combined with computed tomography (PDG-PET/CT) (I-L). (A)
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Int J Clin Exp Pathol 2014;7(7):4381-4390
Spindle-shaped diffuse large B-cell lymphoma
Plain radiograph of the skull, frontal view. (B) Plain radiograph of the skull, lateral view. (C) 3-Dimensional CT of the
cranium. (D) Axial-section CT image. (E) Coronal-section CT image. (F) Sagittal-section CT image. (G) CT of the femur.
Images (A to G) show multiple punched-out osteolytic lesions. (H) Bone scintigraphy showing a markedly hot area in
the right parietal region of the cranium and a weak hot spot in the left femoral diaphysis. (I, K) FDG-PET/CT images
showing FDG uptake in and around the right parietal bone (SUVmax = 13.5). A hot spot (SUVmax = 9.1) was also noted
in the left femoral diaphysis in (J, L); in (G), an osteomatoid was suspected on CT, however, there was no finding
suggestive of malignant neoplasm. (I) FDG uptake (SUVmax = 8.6), possibly physiological, was noted in the tonsils.
(I) FDG uptake (SUVmax = 6.3), possibly physiological, was noted in the ileocecal to the ascending colon region. (I)
FDG uptake (SUVmax = 12.0) was noted in the left lower abdomen, where colonoscopic examination did not reveal
any lesion.
Figure 2. Flow cytometry of skull bone tumor in mononuclear round cells. A: Negative control. B: CD5-positive T
cells accounted for about 55%. C: CD10-negative B-cells. D: CD20-positive B-cells, which accounted for about 9%.
E: CD19-positive B-cells, accounting for about 12%. F: CD22-positive B-cells, accounting for about 11%. G: CD25negative B-cells. H: CD34-negative B-cells. I: CD56-positive NK cells, accounting for about 30%. J: Light-chain restriction was evident; predominantly λ-chain-positive and ĸ-chain-negative B-cell clonality. This B-cell tumor was CD10negative. The proportion of gates for the round cell region of flow cytometry was considerably reduced, probably due
to the B-cells being largely deformed into a spindle shape.
noted at this clinic to have a cranial bone tumor
by a plain X-ray of the skull and computed
tomography (CT), with evidence of osteolytic
bone destruction (Figure 1A-F). Bone scintigraphy revealed hot areas in the cranial bone and
left femur (Figure 1H). The CT findings of the
left femur led to a suspicion of osteoid osteoma, but not of any malignant neoplasm (Figure
1G). A biopsy of the cranial bone tumor was performed under local anesthesia at a local clinic
in April 2012.
Histopathologic examination of hematoxylin
and eosin (H&E)-stained biopsy specimens at
the clinic revealed proliferation of spindle cells
and fibers, somewhat consistent with sarcomatous features. On immunohistochemical staining, however, the spindle cells were found to be
extensively positive for CD45 and CD20, so
that the diagnosis of B-cell lymphoma was also
considered. In May 2012, the patient was
4383
referred to us for treatment. We secured the
biopsied tissue block specimens from the previous clinic and re-examined them, including an
immunohistochemical study. Unfortunately,
however, the tissue sections scarcely reacted
to immunostains for clusters of differentiation
other than CD45 and CD20 due to the effect of
a bone acid decalcification procedure employed
at the previous clinic, and a definitive diagnosis
proved impossible. A bone marrow examination
revealed no evidence of infiltration into the
bone marrow. Cerebrospinal fluid examination
showed no obvious lymphomatous infiltration
(data not shown). In June 2012, 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (PDG-PET/
CT) was performed (Figure 1I-L). This examination revealed FDG uptake (SUVmax = 13.5) in the
right parietal bone (Figure 1I, 1K), the left femoral diaphysis (SUVmax = 9.1; Figure 1J, 1L), and
the lower quadrant of the abdomen (SUVmax =
Int J Clin Exp Pathol 2014;7(7):4381-4390
Spindle-shaped diffuse large B-cell lymphoma
Figure 3. Histopathology of the skull bone tumor. A: Hematoxylin and eosin (H&E)-stained section under low power
magnification (x 600) showing slenderly elongated spindle cells, somewhat reminiscent of a sarcoma, predominating along the stream of spaces between the periosteum and the underlying fibrous connective tissue. B: Fibers
occurring around spindle cells were positive on silver stain (x 600). C to Z: Immunostaining of spindle cells (x 600).
C: LCA-positive. D: CD3-negative (the CD3-positive round cells are T cells). E: CD5-negative (the CD5-positive round
cells are T cells). F: CD10-negative. G: CD20-positive. H: CD56-negative. I: CD68-negative. J: CD79a-positive. K:
CyclinD1-negative. L: BCL2-positive. M: In part, BCL6-positive. N: PAX5-positive. O: MUM1-negative. P: The Ki-67
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Int J Clin Exp Pathol 2014;7(7):4381-4390
Spindle-shaped diffuse large B-cell lymphoma
(MIB-1)-positive rate was 40%-50%. Q: ALK-negative. R: LMP-1-negative. S: Vimentin-positive. T: Desmin-negative.
U: PDGF-positive. V: TGFβ1-negative. W: The spindle cells and round cells were also occasionally weakly positive for
TNFα. X: FGF2-negative. Y: IL-1β-negative. Z: IL-6-negative.
A: Intense reaction to CD20 was noted at PDGF-positive sites. B: The tissues were positive for CD79a at
PDGF-positive sites. C: There was no reaction to CD3
in PDGF-positive areas.
12.0; Figure 1I). The patient was admitted to
the hospital for a lower gastrointestinal endoscopy to explore the cause of the increased FDG
uptake in the left lower abdomen, a re-biopsy of
the cranial bone tumor, medical work-up, and
treatment.
At admission, the patient’s body temperature
was 36.5°C, and there were no palpable superficial lymph nodes or hepatosplenomegaly. The
incision biopsy wound was noted in the right
frontal region. No overt elevated lesion was palpable. Laboratory examinations on admission
revealed hematologic evidence of mild irondeficiency anemia; however, the blood biochemical data, including the serum LDH and
ALP levels, revealed no abnormalities. Serum
soluble IL-2R was within normal limits. Virologic
tests showed evidence of past Epstein-Barr
virus infection. Tests for HIV and HTLV-1 antibodies were negative. Serum immunoglobulin
levels were within normal limits, and no M protein was demonstrable on immunoelectrophoresis.
Figure 4. Double-immunofluorescence staining of
the skull tumor cells. Tissues were subjected to fluorescence microscopic examination by using BIOREVO BZ-9000 after double-immunofluorescence staining. For the detection of PDGF, an SB Filter GFP-BP
(dynamic mirror wavelength: 495 nm, green fluorescence) was used, while the SB Filter TexasRed (dynamic mirror wavelength: 593 nm, red fluorescence)
was employed for the detection of PAX5, CD20,
CD79a, and CD3. Images obtained with the use of
the respective filters were synthesized by means of
an analysis software into multiple stained photographs. A: PDGF/CD20. B: PDGF/CD79a. C: PDGF/
CD3. The tissues were positive for PDGF on all slides.
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Lower gastrointestinal endoscopy failed to
reveal any obvious lesions. A cranial bone
tumor excision biopsy was performed at the
Department of Neurosurgery of this hospital at
our request. The bone lesion containing neoplastic tissues was excised en bloc under navigation guidance. Intraoperative exploration disclosed subcutaneous and epidural tumor
progression. A re-biopsy specimen was obtained solely from the soft tissues of the tumor.
Flow-cytometric analysis revealed that the cranial bone tumor cells were immunoglobulin λ
chain–positive and ĸ chain-negative, as shown
in Figure 2, and were hence light chain- restricted; therefore, B-cell lymphoma was tentatively
diagnosed. The B-cell lymphoma was CD5negative, CD23-negative, CD10-negative, weakly CD20-positive, CD19-positive, and CD22positive.
Int J Clin Exp Pathol 2014;7(7):4381-4390
Spindle-shaped diffuse large B-cell lymphoma
Table 1. Clinical features of spindle-shaped diffuse large B-cell lymphoma
Case Age
Sex Lesions
no.
(yr)
LN involvement
Extranodal
lesions
BM
StaTherapy
ge
Outcome
Authors
1
52
F
Cervical LN, maxilla, palatum, nasopharynx, tonsill, parapharynx,
sinus, skull
(+)
Bone
NA
IVA
CHOP
ACR/NA
[8]
2
58
F
Alveolar Bone
(-)
Bone
(-)*
IE
Radiotherapy
ACR/NA
[8]
3
38
F
Maxilla
(-)
Bone
(-)*
IE
CHOP
ACR/NA
[8]
4
64
M
Inguinal LN, Anterior Chest Wall
(+)
Chest Wall
(-)
IVA* MVP
DOU/3Mo
[14]
5
59
F
Back near the right shoulder
(-)
Skin
(-)*
IEA
completely excised + Radiotherapy
ACR/53Mo
[15]
6
89
F
Large ulcerated tumor on her scalp
(-)
Skin
(-)*
IEA
none
DOD/8Mo
[15]
7
30
F
Nodule on her forehead
NA
Skin
NA
NA
NA
NA
[15]
8
69
M
Right ear
NA
Skin
NA
NA
NA
NA
[15]
9
54
M
Plaque on the skin of his aternum
NA
Skin
NA
NA
Excised, Promace-cytabom + ICE
NA
[15]
10
78
F
Right upper arm mass
NA
Skin
NA
NA
NA
NA
[16]
11
48
M
Right submandibular skin nodule
NA
Skin
NA
NA
NA
AWD
[16]
12
51
M
Left orbital mass, nasal mucosa, paranasal sinuses
NA
Orbit
NA
NA
NA
Alive
[16]
13
24
F
Left antierior upper chest wall, mediastinal mass
NA
Chest wall
NA
NA
NA
Alive
[16]
14
48
M
Right submandibular subcutaneous nodule
NA
Skin
NA
NA
NA
NA
[17]
15
73
F
Lump on the scalp
(-)*
Skin
NA
NA
Radiotherapy
DOU/7Mo
[18]
16
32
F
Uterine cervix, right parametrium
(-)
Uterus
(-)
IEA
CHOP + Radiotherapy
ACR/10Mo
[19]
17
21
F
Vagina, uterus
(-)
Vagina, uterus
(-)
IV
CHOP + Radiotherapy
ACR/20Mo
[20]
18
67
F
Vagina
(-)
Vagina
(-)
I
Rituximab-CHOP
ACR/7Mo
[20]
19
48
M
Salivary bland, liver
(+)
Liver
(-)
IV
Rituximab-VACOP-B
ACR/4Mo
[20]
20
70
F
Liver
(+)
Liver
(-)
IV
Rituximab-CHOP
ACR/6Mo
[20]
21
71
F
Soft tissue, skin
(+)
Skin
(-)
IV
CIEP + Radiotherapy
ACR/57Mo
[20]
22
70
M
Liver
(-)
Liver
(-)
IEA
Operation + Rituximab-CHOP + Radiotherapy
ACR/24Mo
[21]
23
48
M
Scalp
NA
Skin
NA
IES
Radiotherapy
ACR/NA
[22]
24
68
M
Polycyclic annular plaques and papulonodular lesions on his back
(-)
Skin
(-)
IEA
Rituximab-CHOP
ACR/NA
[23]
25
69
F
Giant tumor on her left back
(-)
Skin
NA
IEA
completely excised
ACR/4Y
[24]
26
79
F
Neck, Axilla, Para-aorta LN
(+)
(-)
(-)*
III
Modified Rituximab-THP-COP
ACR/40Mo
[10]
27
92
M
Neck LN
(+)
(-)
(-)*
II
Not done
NA
[10]
28
73
M
Axilla, Inguen LN
(+)
(-)
(-)*
III
Rituximab-CHOP
ACR/36Mo
[10]
29
63
M
Para-aorta, Inguen LN, Spleen
(+)
Spleen
(-)*
III
Modified Rituximab-CHOP + Radiotherapy
DOD/13Mo
[10]
30
42
F
Axilla LN, Iliac, bone
(+)
Iliac, Bone
(-)*
IV
Rituximab-CHOP
ACR/34Mo
[10]
31
73
F
Para-aorta LN
(+)
(-)
(-)*
IIx
Rituximab-CHOP + Radiotherapy
ACR/29Mo
[10]
32
61
M
Mesenterium, Para-aorta LN, Small intestine
(+)
Small Intestine
(-)*
IV
Rituximab-CHOP
ACR/29Mo
[10]
33
49
M
Neck, Axilla, Para-aorta,Inguen LN, Cecum, Spleen, Bone marrow
(+)
Cecum, Spleen
(+)
IV
Rituximab-CHOP
ACR/23Mo
[10]
34
78
M
Mesenterium LN
(+)
(-)
(-)*
II
Rituximab-THP-COP
DOD/10Mo
[10]
35
78
M
Neck LN
(+)
(-)
(-)*
I
Rituximab-CHOP + Radiotherapy
ACR/23Mo
[10]
36
39
F
Cranial bone, femoral bone, bone marrow
(-)
Bone
(+)
IVA
Operation + Rituximab-CHOP
ACR/3Mo
Present case
Abbreviations: ACR, alive in complete response; AWD, alive with disease; CHOP, cyclophosphamide, doxorubicin, vincristine, prednisone; CIEP cyclophosphamide, idarubicin, epirubicin, prednisone; DOD, died of disease; DOU, died of unknown
cause; F, female; LN, lymph node; M, male; Mo, months; MVP, methotrexate, vincristine, prednisone; NA, not available; VACOP-B, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin; Y, years; *, suspicious.
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Int J Clin Exp Pathol 2014;7(7):4381-4390
Spindle-shaped diffuse large B-cell lymphoma
There was fibrous proliferation surrounding the
Sp-DLBCL (Figure 3B). This cranial bone lymphoma tissue was examined by immunohistochemical staining for six fibroblast-stimulating
cytokines. As shown in Figure 3U-Z, the DLBCL
tumor cells were positive for PDGF, negative for
TGFβ1, occasionally weakly positive for TNFα,
negative for fibroblast growth factor (FGF) 2,
and negative for interleukin (IL)-1β and for IL-6.
Furthermore, the cranial bone lymphoma tissue was assessed by double-immunofluorescence staining to ascertain that the Sp-DLBCL
was positive for PDGF (Figure 4). As a result,
the Sp-DLBCL proved to be positive for CD20,
as well as for PDGF.
Beginning in July 2012, the patient received
four intrathecal injections of methotrexate and
cytarabine and six cycles of CHOP chemotherapy with concomitant rituximab administration.
The patient has remained in complete remission for about 2 years.
Discussion
In DLBCL, fine reticulin fibers occur in intercellular spaces among individual tumor cells; at
times, these fibers form thick fibrous bands.
The abundance of fibrosis may in rare instances cause Sp-DLBCL to exhibit a storiform pattern of lymphoma cells, which often leads to a
mistaken diagnosis of sarcoma [1]. A problem
inherent in diagnosing lymphoma in cases of
Sp-DLBCL is that the cells are often depressed,
making it difficult to identify individual tumor
cells. Therefore, as in the case reported herein,
vimentin-positive Sp-DLBCL is liable to be misdiagnosed as sarcoma. There have been several previous reports of vimentin-positive
Sp-DLBCL [2-6]. However, the present case is
the first case report of primary Sp-DLBCL of the
cranial bone. According to the WHO classification, Sp-DLBCL is recognized as a rare morphologic variant of DLBCL, not otherwise specified
[7]. In 1984, Kluin et al. were the first to report
three cases of primary B-cell lymphoma of the
maxilla exhibiting a sarcomatoid pattern [8]. It
has not been clearly verified, nevertheless, why
the lymphoma cells show a spindle shape.
To examine the cause of this feature of the
cells, we conducted an immunohistochemical
study for six cytokines that induce fibrotic
growth, on account of the fibrous proliferation
4387
noted around the GC-type Sp-DLBCL tumor in
this case. As shown in Figure 3, the DLBCL
tumor cells were PDGF-positive and occasionally weakly positive for TNFα. However, the cells
were negative for fibroblast growth factor-2
(FGF2), interleukin-1beta (IL-1β), and interleukin-6 (IL-6). Furthermore, we evaluated these
tissues by double-immunofluorescence staining for PDGF and CD20, PDGF and CD79a, and
PDGF and CD3 (Figure 4). The cells were positive for PDGF on all of the slides tested. There
was no reaction for CD3 in the PDGF-positive
areas; however, these areas showed strong
reactions for CD20 and CD79a. These results
suggest the possibility in our case that the
CD20-positive, CD79a-positive GC-type DLBCL
tumor cells per se produced PDGF, which
induced fibrosis and the subsequent impingement of the tumor cells, and this tumor cell
impingement imparted a spindle shape to the
tumor cells.
Oshima et al. have described that the phenotype of spindle-shaped lymphoma may be T-cell
type or B-cell type, and that those cells may be
actin-positive [9]. As another mechanism operating in Sp-DLBCL, it has been postulated that
cells such as macrophages produce TGFβ1 and
TNFα, and consequent changes in the T cells
and myofibrohistio-rich stroma may play a role
in the lymphoma cells exhibiting a spindle
shape [10]. In the present case, however, our
findings suggest that the GC-type DLBCL tumor
cells per se were probably producing the PDGF,
and, in part, TNFα, which induced fibrosis. Our
previous reports described the production of
PDGF and TGFβ by the malignant lymphoma
itself, which was presumed to be involved in the
fibrous proliferation in cases of myelofibrosis
secondary to bone marrow metastasis of angioimmunoblastic T-cell lymphoma (AITL) [11, 12].
Cells deformed into fusiform cells were sparse,
presumably because of the modest fibrous proliferation and small tumor bulk. It is of profound
interest that AITL can be regarded as GC-type
peripheral T-cell lymphoma, as both have features characteristic of follicle-derived lymphomas.
There have been at least 36 cases of Sp-DLBCL
reported to date (Table 1). Of the 36 cases,
lesions arising from the skin were the most frequent (13 pts., 36%), followed by lesions arising
from the bone (5 pts., 14%). The bone lesions
were all practically confined to the perimaxillary
Int J Clin Exp Pathol 2014;7(7):4381-4390
Spindle-shaped diffuse large B-cell lymphoma
Table 2. Immunophenotypic analysis of spindle-shaped diffuse large B-cell lymphoma
Case
CD20 PAX5
no.
1
NA
NA
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
++
++
++
+
+
+
+
+
+
+
+
+
+
++
++
+
+
+
+
+
+
++
++
+
+
+
+
+
+
+
+
+
+
+
+
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
+
+
+
+
+
+
+
+
+
+
+
NA
NA
NA
NA
NA
NA
EB- Des- VimenER min
tin
NA NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
++
+/NA
+ (focally)
+
+
+
+
+
+
+
+
-
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
++
++
+
+
+
+
+
NA
+
+
+
+
+
+
+
+
+
+
+
+
+
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
+
+
+
+
+
-
NA
NA
NA
+
+/NA
NA
+
-
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
-
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
-
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
-
CD10
BCL6 MUM1 CD30 ALK CD68
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
-*
-*
-*
-*
-*
-*
-*
-*
-*
-*
-
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
-*
-*
-*
-*
-*
-*
-*
-*
-*
-*
+
MIB1
Authors
NA
[8]
NA
[8]
NA
[8]
NA
[14]
+
[15]
+
[15]
NA
[15]
NA
[15]
NA
[15]
NA
[16]
NA
[16]
NA
[16]
NA
[16]
+ (many)
[17]
NA
[18]
NA
[19]
+ (60%)
[20]
+ (70%)
[20]
+ (60%)
[20]
+ (40%)
[20]
+ (40%)
[20]
+ (40%)
[21]
NA
[22]
NA
[23]
+
[24]
NA
[10]
NA
[10]
NA
[10]
NA
[10]
NA
[10]
NA
[10]
NA
[10]
NA
[10]
NA
[10]
NA
[10]
+ (30%) present case
Notes: ++ strongly positive; + positive; +/- weakly positive; - negative; NA, not available; *Double-immunohistochemistry with
PAX5.
On H&E-stained sections of the soft tissue
tumor of the skull, the nuclei and cytoplasm of
the tumor cells appeared slenderly elongated
along interfibrous spaces, somewhat akin to
spindle cells, reminiscent of a sarcoma (Figure
3A). On immunohistochemical staining, the
spindle cells were CD20-positive, CD79a4388
positive, CD5-negative, CD10-negative, occasionally BCL6-positive, MUM1-negative, cyclinD1-negative, LMP-1-negative, and PAX5-positive, and the Ki-67-positive rate was 40%-50%
(Figure 3C-T). Thus, the diagnosis of spindleshaped DLBCL (Sp-DLBCL) with a storiform pattern (germinal center (GC) -type) was made.
Int J Clin Exp Pathol 2014;7(7):4381-4390
Spindle-shaped diffuse large B-cell lymphoma
regions, whereas ours is the first reported case
of the tumor involving the skull and the femur.
Bone marrow was examined in 23 cases, and
Case 33 was the only case in which bone marrow infiltration was noted and in which there
was no bone marrow fibrosis or spindle-shaped
cells in the tumor. This may indicate the importance of fibrotic proliferation in the formation of
spindle-shaped/fusiform cells. Although the
duration of follow-up is unknown, there were as
few as five cases of death, suggestive of the
possibility of a favorable prognosis of Sp-DLBCL.
As shown in Table 2, Sp-DLBCLs were checked
in 18 cases for the expression of CD10, BCL6,
and MUM1, and 17 cases (all cases except
Case 30) were the GC-type (94%). The favorable prognosis in the case described herein
might be ascribed to her tumor being the
GC-type. However, it is yet to be ascertained
why the GC-type is common among cases of
Sp-DLBCL. It is probable that follicle-derived
lymphomas, like AITL mentioned above, are
more likely to produce cytokines involved in
fibrosis, such as PDGF and TNFα.
According to a report by El Asri et al., of 39
cases of primary lymphoma of the cranial vault
[13], the mean age of the patients was about
60 years; our present case was relatively young
(39 years old). As for the histologic type, cases
of DLBCL accounted for more than half of the
cases in that report. There were 16 patients
who were followed-up for 12 months or longer,
of whom 13 survived for 1 year or longer, suggesting a favorable prognosis. Our patient
reported herein continues to remain in complete remission at the present time, about 2
years after the treatment.
To summarize, we recently encountered a case
of Sp-DLBCL diagnosed by bone biopsy. Bone
biopsies for Sp-DLBCL, although rare, pose difficulty in terms of obtaining a definitive diagnosis due to acid decalcification. This variant of
lymphoma is composed of spindle-shaped cells
and is occasionally found to be vimentin-positive, so that caution should be exercised in
diagnostic differentiation from sarcoma. As a
cause of the spindle-shaped cell pattern, our
findings of the present case suggest for the first
time that DLBCL per se produces cytokines
such as PDGF and TGFβ, which induce the proliferation of fibroblasts; the cellular deformation caused by impingement of the cells as a
4389
result of fibrosis results in the cells adopting a
spindle shape. Sp-DLBCL is of the GC-type in
almost all cases, and it is yet to be clarified why
GC-type DLBCL produces PDGF and TNFα,
which give rise to fibrosis.
Disclosure of conflict of interest
None.
Address correspondence to: Dr. Kei-Ji Sugimoto, Department of Hematology, Juntendo University
Urayasu Hospital, 2-1-1 Tomioka, Urayasu 2790021, Japan. Tel: +81-47-353-3111; Fax: +81-47381-5054; E-mail: [email protected]
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