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 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.
Figure 1.
Imaging findings: X-ray (A, B), computed tomography (CT) images (C-G), bone scintigraphy (H), and 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (PDG-PET/CT) (I-L). (A) 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). 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.
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 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 = 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 iron-deficiency 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.
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 κ 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 CD5-negative, CD23-negative, CD10-negative, weakly CD20-positive, CD19-positive, and CD22-positive.
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: CD25-negative 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 κ-chain-negative B-cell clonality. This B-cell tumor was CD10-negative. 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.
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, CD79a-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 spindle-shaped DLBCL (Sp-DLBCL) with a storiform pattern (germinal center (GC) -type) was made.
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 (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.
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.
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. 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.
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 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 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.
Table 1.
Clinical features of spindle-shaped diffuse large B-cell lymphoma
| Case no. | Age (yr) | Sex | Lesions | LN involvement | Extranodal lesions | BM | Stage | Therapy | 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.
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.
Table 2.
Immunophenotypic analysis of spindle-shaped diffuse large B-cell lymphoma
| Case no. | CD20 | PAX5 | CD10 | BCL6 | MUM1 | CD30 | ALK | CD68 | EBER | Desmin | Vimentin | MIB1 | Authors |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | [8] |
| 2 | ++ | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | [8] |
| 3 | ++ | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | [8] |
| 4 | ++ | NA | NA | NA | NA | - | NA | NA | NA | - | - | NA | [14] |
| 5 | + | NA | NA | NA | NA | - | NA | - | NA | NA | NA | + | [15] |
| 6 | + | NA | NA | NA | NA | - | NA | - | NA | NA | NA | + | [15] |
| 7 | + | NA | NA | NA | NA | - | NA | NA | NA | NA | NA | NA | [15] |
| 8 | + | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | [15] |
| 9 | + | NA | NA | NA | NA | - | NA | NA | NA | NA | NA | NA | [15] |
| 10 | + | NA | NA | NA | NA | - | NA | - | NA | - | NA | NA | [16] |
| 11 | + | NA | NA | NA | NA | - | NA | - | NA | - | NA | NA | [16] |
| 12 | + | NA | NA | NA | NA | - | NA | - | NA | - | NA | NA | [16] |
| 13 | + | NA | NA | NA | NA | - | NA | - | NA | - | NA | NA | [16] |
| 14 | + | NA | NA | NA | NA | - | NA | - | NA | NA | NA | + (many) | [17] |
| 15 | ++ | NA | ++ | ++ | NA | - | NA | - | NA | NA | NA | NA | [18] |
| 16 | ++ | NA | +/- | ++ | NA | - | NA | NA | NA | - | NA | NA | [19] |
| 17 | + | NA | - | + | - | - | NA | NA | NA | NA | - | + (60%) | [20] |
| 18 | + | NA | - | + | - | + | NA | NA | NA | NA | - | + (70%) | [20] |
| 19 | + | NA | - | + | - | - | NA | NA | NA | NA | - | + (60%) | [20] |
| 20 | + | NA | - | + | - | - | NA | NA | NA | NA | - | + (40%) | [20] |
| 21 | + | NA | - | + | - | +/- | NA | NA | NA | NA | - | + (40%) | [20] |
| 22 | + | NA | - | NA | NA | - | - | NA | NA | NA | NA | + (40%) | [21] |
| 23 | ++ | NA | NA | - | NA | NA | NA | - | NA | NA | - | NA | [22] |
| 24 | ++ | NA | - | + | - | NA | NA | - | NA | - | NA | NA | [23] |
| 25 | + | NA | + (focally) | + | - | - | NA | - | NA | - | NA | + | [24] |
| 26 | + | + | + | + | - | - | - | - | - | -* | -* | NA | [10] |
| 27 | + | + | + | + | - | - | - | - | - | -* | -* | NA | [10] |
| 28 | + | + | + | + | + | - | - | - | - | -* | -* | NA | [10] |
| 29 | + | + | - | + | - | + | - | - | - | -* | -* | NA | [10] |
| 30 | + | + | - | + | + | - | - | - | - | -* | -* | NA | [10] |
| 31 | + | + | + | + | + | - | - | - | - | -* | -* | NA | [10] |
| 32 | + | + | + | + | + | - | - | - | - | -* | -* | NA | [10] |
| 33 | + | + | + | + | - | - | NA | - | NA | -* | -* | NA | [10] |
| 34 | + | + | + | + | + | - | - | - | - | -* | -* | NA | [10] |
| 35 | + | + | + | + | - | - | - | - | - | -* | -* | NA | [10] |
| 36 | + | + | - | + | - | - | - | - | - | - | + | + (30%) | present case |
Notes: ++ strongly positive; + positive; +/- weakly positive; - negative; NA, not available;
Double-immunohistochemistry with PAX5.
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 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.
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