Yumiko Hori

Tumour-associated macrophages in diffuse large B-cell lymphoma: a study of the Osaka Lymphoma Study Group.

Wada N, Zaki M A A, Hori Y, Hashimoto K, Tsukaguchi M, Tatsumi Y, Ishikawa J, Tominaga N, Sakoda H, Take H, Tsudo M, Kuwayama M, Morii E & Aozasa K 
(2012) Histopathology 60, 313–319 
Tumour‐associated macrophages in diffuse large B‐cell lymphoma: a study of the Osaka Lymphoma Study Group

Epstein–barr virus in diffuse large B‐Cell lymphoma in immunocompetent patients in Japan is as low as in Western Countries

According to previous reports, the frequency of Epstein–Barr virus (EBV) positivity in diffuse large B‐cell lymphoma is higher in East Asia (approximately 9%) than in Western countries. The presence of the EBV genome was examined in diffuse large B‐cell lymphoma patients registered with the Osaka Lymphoma Study Group (OLSG) in Osaka, Japan, situated in East Asia. The EBV‐positive rate was examined with in situ hybridization (ISH) in 484 immunocompetent diffuse large B‐cell lymphoma patients registered with OLSG. The male‐to‐female ratio was 1.29, with ages ranging from 16 to 95 (median, 68) years. ISH with EBV‐encoded small RNAs (EBER) probes revealed positive signals in the nuclei of tumor cells: the frequency of positively stained cells among all tumor cells was almost none in 458 cases, 5–10% in 5, 10–20% in 5, 20–50% in 11, and >50% in 5. When the frequency was >20% or >50%, the EBV‐positive rate in the present series (3.3% or 1.0%) was rather similar to that reported in Western cases. Careful evaluation of patient backgrounds, including age distribution, type of lymphomas, exclusion of immunocompromised patients, and establishment of definite criteria for EBV positivity (>20%, >50%, or almost all tumor cells) are essential in comparing geographical differences. J. Med. Virol. 83:317–321, 2011.

Presence of B-cell clones in T-cell lymphoma

Objectives:  The presence of B‐cell clones in 76 cases with peripheral T‐cell lymphoma (PTCL) and precursor T‐lymphoblastic lymphoma (T‐LBL) and its correlation with Epstein–Barr virus (EBV) was studied.

Diffuse large B-cell lymphoma in the spinal epidural space: A study of the Osaka Lymphoma Study Group☆

Diffuse large B-cell lymphoma (DLBCL) involving spinal epidural space (SEDLBCL) is relatively rare, constituting 1.8% of DLBCLs in Osaka, Japan. The aim of this study was to analyze SEDLBCL cases for their clinical and histopathologic findings, including an association with Epstein-Barr virus (EBV) and immunohistochemical characteristics. We analyzed the clinicopathologic findings of 27 SEDLBCL cases. They consisted of 16 males and 11 females, their age ranging from 37-86 years (median 64 years). Eight patients had stage I disease, 3 had stage II, 5 had stage III, and 11 had stage IV. Based on the staining pattern for anti-CD10, bcl-6, and MUM-1, the cases were categorized into 17 cases of the germinal center B-cell (GCB) type and nine of the non-GCB type. There was a 4%-positive rate for EBV in the tumor cells. When compared to nodal DLBCL, the frequency of patients with a high performance status (PS) is higher in SEDLBCL. Compared to the DLBCL of the central nervous system (CNS), the frequency of cases with high stage, 2 or more extranodal lesions, high international prognostic index (IPI), and GCB-type is higher in SEDLBCL. There were no significant differences in the histologic features between SEDLBCL and nodal/CNS DLBCL. Univariate analysis revealed that advanced stage was an unfavorable factor for overall survival (P=0.060). SEDLBCL is different from nodal and CNS DLBCL, but an association with EBV is unlikely in every group.

Laparoscopic Excisional Surgery for Growing Teratoma Syndrome of the Ovary: Case Report and Literature Review

Growing teratoma syndrome (GTS) is rare clinical phenomenon occurring as a sequelae of a malignant germ cell tumor. We present the case of a 20-year-old woman who developed GTS after undergoing fertility-sparing surgery and chemotherapy for an immature teratoma. She underwent left salpingo-oophorectomy, right ovarian cystectomy, and disseminated tumor reduction during her primary surgery. The postsurgical histology report identified the tumor as an immature teratoma, grade 3, International Federation of Gynecology and Obstetrics (FIGO) stage IIIb. She subsequently received 3 cycles of chemotherapy consisting of bleomycin, etoposide, and cisplatin. At 17 months after the chemotherapy, follow-up computed tomography (CT) scan revealed an enlarged mass in her right paracolic gutter and a small peritoneal lesion in the pouch of Douglas. Her serum alpha-fetoprotein level was not elevated. These findings were compatible with GTS, but it was difficult to rule out a recurrent immature teratoma. Diagnostic exploratory laparoscopic surgery revealed the enlarged tumors that had been detected by the CT scan. Although there were multiple tumors in the pouch of Douglas, we were able to resect all of them laparoscopically. Histological diagnosis of the surgically resected specimens was of a mature teratoma, and so we concluded that this tumor was a GTS. Our experience suggests that laparoscopic surgery is an effective alternative diagnostic and therapeutic approach in cases suspicious of GTS where the disease is disseminated to the peritoneum.

Frequency of intravascular large B-cell lymphoma in Japan: Study of the Osaka Lymphoma Study Group

Intravascular large B-cell lymphomaB-IVLis listed as a distinct disease entity in the World Health Organization(WHO) classification for lymphoid neoplasms . The disease is rare, and information for its exact frequency among non-Hodgkin lymphomaNHLhas been extremely limited. There have been several reports mainly from Asian countries describing the different disease frequencies . In addition, population of the cases was variously described among these reports. Therefore it is difficult to know the geographical difference in disease frequency, which might be helpful for understanding pathogenesis of disease.

CUBIC pathology: three-dimensional imaging for pathological diagnosis

The examination of hematoxylin and eosin (H&E)-stained tissues on glass slides by conventional light microscopy is the foundation for histopathological diagnosis. However, this conventional method has some limitations in x-y axes due to its relatively narrow range of observation area and in z-axis due to its two-dimensionality. In this study, we applied a CUBIC pipeline, which is the most powerful tissue-clearing and three-dimensional (3D)-imaging technique, to clinical pathology. CUBIC was applicable to 3D imaging of both normal and abnormal patient-derived, human lung and lymph node tissues. Notably, the combination of deparaffinization and CUBIC enabled 3D imaging of specimens derived from paraffin-embedded tissue blocks, allowing quantitative evaluation of nuclear and structural atypia of an archival malignant lymphoma tissue. Furthermore, to examine whether CUBIC can be applied to practical use in pathological diagnosis, we performed a histopathological screening of a lymph node metastasis based on CUBIC, which successfully improved the sensitivity in detecting minor metastatic carcinoma nodules in lymph nodes. Collectively, our results indicate that CUBIC significantly contributes to retrospective and prospective clinicopathological diagnosis, which might lead to the establishment of a novel field of medical science based on 3D histopathology.

S100A4 accelerates the proliferation and invasion of endometrioid carcinoma and is associated with the “MELF” pattern

Endometrioid carcinoma (EC) is one of the most common malignancies of the female genital system. Although the behavior of EC ranges from an excellent prognosis to aggressive disease with a poor outcome, the factors that determine its diversity have not been determined. Here, we show that S100A4, a calcium‐binding protein of the EF‐hand type, is correlated with the proliferation and invasion ability of EC. We demonstrated previously that EC cells with high aldehyde dehydrogenase (ALDH) activity were more tumorigenic than ALDH‐lo cells. Screening by shotgun proteomics demonstrated that the expression level of S100A4 in ALDH‐hi EC cells was significantly higher than that in ALDH‐lo cells. S100A4‐knockout cells generated by the CRISPR/Cas9 system showed reduced proliferation and invasion. These cells showed impaired AKT phosphorylation and matrix metalloproteinase‐2 activation, accounting for their impaired proliferation and invasion, respectively. Furthermore, in clinical EC samples, elevated expression of S100A4 was highly related to myometrial and lymphatic invasion in well to moderately differentiated EC. Notably, strong and diffuse expression of S100A4 was observed in tumor tissues with a microcystic, elongated and fragmented (“MELF”) pattern, which is associated with a highly invasive EC phenotype. Collectively, our results demonstrate not only that high expression of S100A4 contributes to an aggressive phenotype of EC, but also that its elevated expression is closely related to the MELF histopathological pattern.

In Vivo Evaluation of Irinotecan-Loaded QuadraSphere Microspheres for Use in Chemoembolization of VX2 Liver Tumors

PURPOSE To investigate the pharmacokinetics and chemoembolization efficacy of irinotecan-loaded QuadraSphere microspheres (QSMs) in a rabbit VX2 liver tumor model. MATERIALS AND METHODS Fourteen rabbits with VX2 liver tumors were divided into two groups. In the irinotecan-loaded QSM group (n = 7), 3 mg of QSMs (30-60 μm) containing 12 mg of irinotecan (0.6 mL; 20 mg/mL) were injected into the left hepatic artery. In the control group (hepatic arterial infusion [HAI] and QSMs; n = 7), 3 mg of QSMs suspended in ioxaglic acid were injected following a bolus injection of 0.6 mL of irinotecan solution (20 mg/mL). Sequential irinotecan, SN-38, and SN-38G concentration changes were measured in plasma within 24 hours and at 1 week and in tissues at 1 week. The VX2 tumor growth rates at 1 and 2 weeks were calculated from computed tomographic images. RESULTS All rabbits underwent successful embolization. Plasma irinotecan, SN-38, and SN-38G concentrations in the irinotecan-loaded QSM group showed significantly sustained release compared with the control group (P = .01). Compared with the control group, the irinotecan-loaded QSM group had significantly higher irinotecan concentration in liver tumors (P = .03) and a tendency toward higher SN-38 concentration in liver tumors (P = .29). The SN-38G tissue concentrations were below the limits of quantification. The tumor growth rate was significantly lower and the tumor necrosis rate significantly higher in the irinotecan-loaded QSM group (P = .02 and P = .01, respectively). CONCLUSION Chemoembolization via irinotecan-loaded QSMs more effectively suppresses tumor growth than chemoembolization with unloaded QSMs after HAI. A clinical feasibility study is warranted.

Expression of FoxO3a in clinical cases of malignant lymphoma

Cancer-initiating cells (CICs) are a limited number of cells with tumorigenic activity. Few studies have been performed on CICs in malignant lymphoma. We recently demonstrated that a small number of FoxO3a-expressing cells possessed CIC-like potential in Hodgkins lymphoma (HL) cell lines. In the present study, FoxO3a expression was examined immunohistochemically in 137 patients with malignant lymphoma. Among patients with HL, FoxO3a-positive tumor cells were detected in 11 of 11 with nodular sclerosis classical HL, 8 of 15 with mixed cellularity classical HL, 0 of 1 with lymphocyte-rich classical HL, and 2 of 3 with nodular lymphocyte-predominant HL. Only limited numbers of patients with non-HL expressed FoxO3a: 4 of 66 with diffuse large B-cell lymphoma, 1 of 20 with follicular lymphoma, and 1 of 5 with peripheral T-cell lymphoma, not otherwise specified. No FoxO3a expression was detected in patients with mantle cell lymphoma (n=3), extranodal marginal zone B-cell lymphoma (n=3), mediastinal large B-cell lymphoma (n=1), NK/T cell lymphoma (n=5), anaplastic large cell lymphoma (n=2), or T-lymphoblastic lymphoma/leukemia (n=2). These results suggest that FoxO3a is expressed mostly in patients with HL, but not in patients with non-HL. FoxO3a expression was limited to a small number of Hodgkin cells in a quiescent state. FoxO3a may be a CIC marker of HL, but not of non-HL.