研究者詳細 - 榊原　綾子

論文 - 榊原　綾子

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Concurrent wild-type transthyretin amyloidosis and psoriasis vulgaris in an elderly man

Fujii, Y; Takeichi, T; Yamashita, Y; Okumura, T; Sakakibara, A; Muro, Y; Akiyama, M

JOURNAL OF DERMATOLOGY 2025年2月

Diagnostic approach for classic Hodgkin lymphoma in small samples with an emphasis on PD-L1 expression and EBV harboring in tumor cells: a brief review from morphology to biology 査読有り

Taishi Takahara, Ayako Sakakibara, Yuta Tsuyuki, Akira Satou, Seiichi Kato, and Shigeo Nakamura

J Clin Exp Hematop 63 巻 ( 2 ) 頁： 58 2023年6月

Which modality is better to diagnose high-grade transformation in retroperitoneal liposarcoma? Comparison of computed tomography, positron emission tomography, and magnetic resonance imaging 査読有り

Nakashima, Y; Yokoyama, Y; Ogawa, H; Sakakibara, A; Sunagawa, M; Nishida, Y; Mizuno, T; Yamaguchi, J; Onoe, S; Watanabe, N; Kawakatsu, S; Igami, T; Ebata, T

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 28 巻 ( 3 ) 頁： 482 - 490 2023年3月

記述言語：英語出版者・発行元：International Journal of Clinical Oncology

Background: Survival in patients with retroperitoneal liposarcoma (RPLS) depends on the surgical management of the dedifferentiated foci. The present study investigated the diagnostic yield of contrast-enhanced CT, 18F-fluorodeoxyglucose positron emission tomography (PET), and diffusion-weighted MRI in terms of dedifferentiated foci within the RPLS. Methods: Patients treated with primary or recurrent RPLS who underwent the above imaging between January 2010 and December 2021 were retrospectively reviewed. The diagnostic accuracy of the three modalities for histologic subtype of dedifferentiated liposarcoma (DDLS) and French Federation of Cancer Center (FNCLCC) grade 2/3 were compared using receiver operating characteristic curves and areas under the curves (AUCs). Results: The cohort involved 32 patients with 53 tumors; 30 of which exhibited DDLS and 31 of which did FNCLCC grades 2/3. The optimal thresholds for predicting DDLS were mean CT value of 31 Hounsfield Unit (HU) (AUC = 0.880, 95% CI 0.775–0.984; p < 0.001), maximum standardized uptake value (SUVmax) of 2.9 (AUC = 0.865 95% CI 0.792–0.980; p < 0.001), while MRI failed to differentiate DDLS. The cutoff values for distinguishing FNCLCC grades 1 and 2/3 were a mean CT value of 24 HU (AUC = 0.858, 95% CI 0.731–0.985; p < 0.001) and SUVmax of 2.9 (AUC = 0.885, 95% CI 0.792–0.978; p < 0.001). MRI had no sufficient power to separate these grades. Conclusions: Contrast-enhanced CT and PET were useful for predicting DDLS and FNCLCC grade 2/3, while MRI was inferior to these two modalities.

DOI： 10.1007/s10147-022-02287-6

SMALL INTESTINAL GANGLIONEUROMATOSIS IN A PATIENT WITH NEUROFIBROMATOSIS TYPE 1: A CASE REPORT 査読有り

Kida Y., Sawada T., Ishikawa E., Sakakibara A., Yamamura T., Maeda K., Esaki M., Hamazaki M., Murate K., Nakamura M.

Gastroenterological Endoscopy 65 巻 ( 7 ) 頁： 1232 - 1238 2023年

記述言語：日本語出版者・発行元：Gastroenterological Endoscopy

A 50-year-old woman with neurofibromatosis type 1 who hospitalized for chronic diarrhea was transferred to our hospital for evaluation of small intestinal dilatation and thickening. Transoral double-balloon enteroscopy revealed jejunal dilatation and suppressed peristalsis; however, mucosal inflammation, such as ulcers or erosions were not detected. Transanal double-balloon enteroscopy detected the intestinal stenosis with inflammatory polyps and a longitudinal ulcer. Histopathological evaluation of duodenal, jejunal, and ileal specimens by biopsy revealed ganglion cells and Schwannian cells; therefore, the patient was diagnosed with ganglioneuromatosis with neurofibromatosis type 1. Small intestinal dilatation was associated with suppressed peristalsis caused by ganglioneuromatosis and was diagnosed as secondary chronic intestinal pseudo-obstruction. Abdominal distention persisted despite conservative therapy. However, she remained asymptomatic, and oral intake remained unaffected. Ganglioneuromatosis is rare; however, clinicians should be mindful that ganglioneuromatosis is an abdominal complication associated with systemic disease such as neurofibromatosis type 1 and multiple endocrine neoplasia type 2B.

DOI： 10.11280/gee.65.1232

Laminectomy triggers symptomatic growth of spinal schwannoma in a patient with schwannomatosis. 査読有り

Oyama T, Nishimura Y, Nagashima Y, Nishii T, Hara M, Takayasu M, Sakakibara A, Saito R

Surgical neurology international 13 巻頁： 261 2022年

記述言語：英語出版者・発行元：Surgical Neurology International

Background: Schwannomatosis (SWN) is genetically similar to neurofibromatosis type 2 (NF2) and represents a NF2 gene mutation. Previous studies have shown that these mutations in both neurons and Schwann cells can lead to the development of schwannomas after nerve crush injuries. Here, we reviewed the potential pathoanatomical mechanisms for the development of a trauma-induced spinal schwannomas in a 55-year-old male with SWN. Case Description: A 49-year-old male had originally undergone a L3-L5 lumbar laminectomy for stenosis; the schwannomas seen on the preoperative magnetic resonance imaging (MRI) were not resected. Now at age 55, he newly presented with low back pain and numbness in the left L5 dermatome, and he was diagnosed with an L4 vertebral level cauda equina tumor on MRI. Following gross-total resection, the histopathological assessment revealed a Ki-67 labeling index 5-10% in hotspots (i.e., slightly higher than the normal range of schwannomas) and a 20% mosaic loss of SMARCB1. Based on these criteria, he was diagnosed as having SWN. Conclusion: In this patient with SWN, compression/physical trauma to nerves of the cauda equina during the L3-L5 laminectomy 6 years ago likely caused the progression of schwannoma.

DOI： 10.25259/SNI_453_2022

Clinicopathologic Analysis of Primary Adrenal Diffuse Large B-Cell Lymphoma A Reappraisal of 23 Japanese Patients Based on EBV Association and PD-L1 Expression in Tumor Cells 査読有り

Kawano, T; Tsuyuki, Y; Suzuki, Y; Shimada, K; Kato, S; Takahara, T; Mori, M; Nakaguro, M; Sakakibara, A; Nakamura, S; Satou, A

AMERICAN JOURNAL OF SURGICAL PATHOLOGY 45 巻 ( 12 ) 頁： 1606 - 1615 2021年12月

記述言語：英語出版者・発行元：American Journal of Surgical Pathology

Primary adrenal diffuse large B-cell lymphoma (PA-DLBCL) is rare. We investigate 23 Japanese patients with PA-DLBCL to understand the clinicopathologic features and biological behavior of this disease. The 17 males and 6 females had a median age of 74 years (range: 40 to 86 y). Tumor cells harbored Epstein-Barr virus-encoded small RNA (EBER) in 9 (39%) samples, including samples from the 2 patients with methotrexate-associated B-cell lymphoproliferative disorder. Programmed cell death ligand 1 (PD-L1) expression was detected in tumor cells of 6 (26%) samples, including 1 EBER+ and 5 EBER- samples. Four (17%) patients exhibited an intravascular proliferating pattern, and all 4 patient samples showed positive staining for PD-L1 in tumor cells. Among those patients, 3 showed intravascular proliferating pattern accompanied by a diffuse extravascular proliferation of tumor cells, and 1 patient was diagnosed with intravascular large B-cell lymphoma. We divided the 23 patients into 3 groups: EBER+ (n=9, 39%), EBER-PD-L1+ (n=5, 22%), and EBER-PD-L1- (n=9, 39%). A comparison of the outcomes among the 3 groups showed significant differences in overall survival (P=0.034). The EBER+ group had the worst prognosis, and the EBER-PD-L1- group had the best prognosis. We also compared the outcomes among the 3 groups that received rituximab-containing chemotherapies. Both the overall survival and progression-free survival were significantly different among these groups (P<0.001 and P=0.002, respectively). In conclusion, we evaluated 3 types of PA-DLBCL and found that each had unique clinical, pathologic, and prognostic features. Our results suggested that immune senescence, iatrogenic immunodeficiency, and immune evasion contribute to the development of PA-DLBCL.

DOI： 10.1097/PAS.0000000000001809

Two cases of solitary fibrous tumor/hemangiopericytoma with different clinical features according to the World Health Organization classification: case report and review of the literature.

Nishii T, Nagashima Y, Nishimura Y, Ito H, Oyama T, Matsuo M, Sakakibara A, Shimada S, Saito R

Journal of spine surgery (Hong Kong) 7 巻 ( 4 ) 頁： 532 - 539 2021年12月

記述言語：英語出版者・発行元：Journal of Spine Surgery

Solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) have been classified as one entity by the World Health Organization in 2016 due to gene fusion between NAB2 and STAT6. In the Central Nervous System (CNS), a hypocellular, collagenized tumor with a classic SFT phenotype is considered grade I, whereas more densely cellular tumors mostly corresponding to the HPC phenotype are classified as grade II or III (anaplastic) depending in mitotic count (<5 vs. >5 mitoses per 10 high-power fields). Herein, we report two cases of targeted SFT/HPC in which pathological differences and WHO grading affect clinical features. A 75-year-old woman presented with headache and had an intradural extramedullary tumor at the C1 to C2 level. The tumor was well-circumscribed and attached only to the dura mater. It was totally removed and diagnosed SFT/HPC grade I. In contrast, a 68-year-old woman presented with numbness in the right upper limb and had an intradural extramedullary tumor at the medulla to C3 levels The tumor was irregularly marginated and strongly adherent to the spinal cord and involved the vertebral artery. It was sub totally removed and diagnosed SFT/HPC grade II. To the best of our knowledge, there are only 12 cases of SFT/HPC at the craniocervical junction, including the present two cases, of which four that were adherent to the spinal cord or involved the vertebral artery were grade II or III. Although the location of the tumor was almost the same, there were significant differences in the intraoperative findings according to the WHO grading.

DOI： 10.21037/jss-21-83

Histiocytic and dendritic cell neoplasms: Reappraisal of a Japanese series based on t(14;18) and neoplastic PD-L1 expression 査読有り

Okada, K; Takahara, T; Suzuki, Y; Kohno, K; Sakakibara, A; Satou, A; Takahashi, E; Nakamura, S

PATHOLOGY INTERNATIONAL 71 巻 ( 1 ) 頁： 24 - 32 2021年1月

記述言語：英語出版者・発行元：Pathology International

Histiocytic and dendritic cell (H/DC) neoplasms are heterogeneous, originating from myeloid- or stromal-derived cells. Multiple reports describe the cross-lineage transdifferentiation of neoplastic B cells into H/DC neoplasms. Most such cases are from Western countries, and rarely from Japan or East Asia. Here we report 17 cases of H/DC neoplasms in Japanese patients, with analysis of t(14;18) by fluorescence in situ hybridization, and of neoplastic programmed death-ligand 1 (PD-L1) expression by immunostaining (clones SP142, E1J2J, and 28-8). These 17 cases were diagnosed according to the 2017 World Health Organization (WHO) classification, and included two histiocytic sarcomas (HS), two interdigitating cell (IDC) sarcomas, one Langerhans cell sarcoma, two dendritic cell sarcomas, and 10 follicular dendritic cell (FDC) sarcomas. No case had any past history of follicular lymphoma (FL). Two cases of HS and one IDC sarcoma, all of which were myeloid-driven, were found to exhibit t(14;18). In the latter case, at 30 months after IDC sarcoma diagnosis, FL development was detected. Three (30%) FDC sarcoma cases exhibited neoplastic PD-L1 expression with all the three PD-L1 antibody clones. This is the first report of t(14;18) and neoplastic PD-L1 expression on H/DC neoplasms among Japanese patients, each of which appeared to be associated with HS and FDC sarcoma, respectively.

DOI： 10.1111/pin.13044

Follicular T-cell lymphoma mimicking lymphocyte-rich classic Hodgkin lymphoma: a case report of a diagnostic pitfall

Sakakibara, A; Suzuki, Y; Kato, H; Yamamoto, K; Sakata-Yanagimoto, M; Ishikawa, Y; Furukawa, K; Shimada, K; Kohno, K; Nakamura, S; Satou, A; Kato, S

JOURNAL OF CLINICAL AND EXPERIMENTAL HEMATOPATHOLOGY 61 巻 ( 2 ) 頁： 97 - 101 2021年

記述言語：英語出版者・発行元：Journal of Clinical and Experimental Hematopathology

Follicular T-cell lymphoma (FTCL), one of the nodal T-cell lymphomas with T follicular helper (TFH) phenotype, is an uncom-mon disease. The diagnosis of FTCL is challenging on the distinction from the morphological mimics mostly exemplified by follicular lymphoma. Here, we described a case of FTCL that mimicked lymphocyte-rich classic Hodgkin lymphoma (LRCHL). A 47-year-old male presented with cervical lymphadenopathy. The biopsy specimen demonstrated nodular lym-phoid proliferation, which included scattered CD30+ CD15-CD20-PAX5 weakly+ Hodgkin and Reed-Sternberg (HRS)-like cells and a rich distribution of CD3+ CD4+ PD1+ T-cells. Epstein Barr virus was not detected in HRS-like cells, but it was detected in a small proportion of the scattered lymphocytes. The large cells were also negative for programmed cell death ligand 1, which appeared to be coincidental as described in our previous report of LRCHL. However, flow cytometry showed a CD3-CD4+ T-cell population that constituted 37.4% of all gated lymphocytes. A PCR analysis showed a clonal T-cell recep-tor-gamma gene rearrangement, but not a clonal immunoglobulin heavy chain gene rearrangement, and showed RHOA G17V mutation. The constellation of these findings led us to revise the diagnosis to FTCL. This result indicated that our case belonged to a relatively indolent subgroup of nodal peripheral T-cell lymphoma of TFH phenotype, which affects patients ≤60 years old, recently proposed by our group. This case report expands our understanding of the morphologic spectrum of FTCL and its clinicopathologic significance.

DOI： 10.3960/jslrt.20052

Lymphocyte-depleted classic Hodgkin lymphoma with primary extranodal disease: Two cases that highlight the combination of immunodeficiency and immune escape in the pathogenesis

Tsuyuki, Y; Kohno, K; Inagaki, Y; Sakai, Y; Kosugi, H; Takahashi, E; Suzuki, Y; Shimada, S; Kato, S; Takahara, T; Satou, A; Shimoyama, Y; Nakamura, S; Asano, N; Sakakibara, A

JOURNAL OF CLINICAL AND EXPERIMENTAL HEMATOPATHOLOGY 61 巻 ( 3 ) 頁： 173 - 179 2021年

記述言語：英語出版者・発行元：Journal of Clinical and Experimental Hematopathology

Neoplastic programmed cell death ligand 1 (PD-L1) expression, activated by PD-L1 gene alterations, is strongly associated with classic Hodgkin lymphoma (CHL). This association enabled a diagnostic consensus for lymphocyte-depleted CHL (LD-CHL), a previously enigmatic disease. We describe two patients with LD-CHL and primary extranodal disease. One patient was a 92-year-old female (Case #1) with a large mass that involved the uterus combined with swollen lymph nodes in the pelvic cavity. The second patient was a 76-year-old female (Case #2) with human T-cell leukemia virus type 1 (HTLV-1) who initially exhibited massive bone marrow involvement without peripheral lymphadenopathies. Biopsies of these tumors from the cervix uteri and bone marrow, respectively, revealed lesions rich in Hodgkin and Reed-Sternberg (H-RS) cells and diminished populations of other cell populations. Immunohistochemistry demonstrated that these H-RS cells expressed CD30, BOB1, and fascin, but not CD15, CD20, PAX5, or OCT2. They also expressed PD-L1, which led to our preferred diagnosis of LD-CHL in both patients. Epstein-Barr virus was associated with LD-CHL in Case #1, but not in Case #2. Both patients were deemed too frail for treatment. They died of disease at 1 (Case #1) and 15 months (Case #2) after the diagnosis. These find-ings highlight the abnormal biological behavior of this immune-escape-related lymphoid neoplasm in patients with immunode-ficiency due to immune senescence and HTLV1 infection.

DOI： 10.3960/jslrt.21008

Diagnostic utility of programmed cell death ligand 1 (clone SP142) immunohistochemistry for malignant lymphoma and lymphoproliferative disorders: A brief review 招待有り

Sakakibara, A; Kohno, K; Ishikawa, E; Suzuki, Y; Tsuyuki, Y; Shimada, S; Shimada, K; Satou, A; Takahara, T; Ohashi, A; Takahashi, E; Kato, S; Nakamura, S; Asano, N

JOURNAL OF CLINICAL AND EXPERIMENTAL HEMATOPATHOLOGY 61 巻 ( 4 ) 頁： 182 - 191 2021年

記述言語：英語出版者・発行元：Journal of Clinical and Experimental Hematopathology

The programmed cell death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important role in tumor cell escape from immune con-trol and has been most extensively investigated for therapeutic purposes. However, PD-L1 immunohistochemistry is still not used widely for diagnosis. We review the diagnostic utility of PD-L1 (by clone SP142) immunohistochemistry in large-cell lymphomas, mainly consisting of classic Hodgkin lymphoma (CHL) and diffuse large B-cell lymphoma (DLBCL). Neoplastic PD-L1 (nPD-L1) expression on Hodgkin and Reed-Sternberg cells is well-established among prototypic CHL. Of note, EBV+ CHL often poses a challenge for differential diagnosis from peripheral T-cell lymphoma with EBV+ non-malignant large B-cells; their distinction is based on the lack of PD-L1 expression on large B-cells in the latter. The nPD-L1 expression further provides a good diagnostic consensus for CHL with primary extranodal disease conceivably characterized by a combined pathogenesis of immune escape of tumor cells and immunodeficiency. Compared with CHL, the nPD-L1 expression rate is much lower in DLBCL, highlighting some specific subgroups of intravascular large B-cell lymphoma, primary mediastinal large B-cell lymphoma, and EBV+ DLBCL. They consist of nPD-L1-positive and-negative subgroups, but their clinicopatho-logical significance remains to be elucidated. Microenvironmental PD-L1 positivity on immune cells may be associated with a favorable prognosis in extranodal DLBCL. PD-L1 (by SP142) immunohistochemistry has helped us to understand the immune biology of lymphoid neoplasms possibly related by immune escape and/or immunodeficiency. However, knowledge of these issues remains limited and should be clarified for diagnostic consensus in the future.

DOI： 10.3960/jslrt.21003

Nodal diffuse large B-cell lymphoma with neoplastic PD-L1 positivity, but without EBV association: Three cases highlighting an aspect of gray zone lymphoma 査読有り

Kohno, K; Suzuki, Y; Harada, T; Sakai, A; Takeuchi, Y; Inagaki, Y; Megahed, NA; Takahara, T; Satou, A; Sakakibara, A; Nakamura, S

PATHOLOGY INTERNATIONAL 70 巻 ( 9 ) 頁： 695 - 697 2020年9月

Reappraisal of Primary Epstein-Barr Virus (EBV)-positive Diffuse Large B-Cell Lymphoma of the Gastrointestinal Tract Comparative Analysis Among Immunosuppressed and Nonimmunosuppressed Stage I and II-IV Patients 査読有り

Miyagi, S; Ishikawa, E; Nakamura, M; Shimada, K; Yamamura, T; Furukawa, K; Tanaka, T; Mabuchi, S; Tsuyuki, Y; Kohno, K; Sakakibara, A; Satou, A; Kato, S; Fujishiro, M; Nakamura, S

AMERICAN JOURNAL OF SURGICAL PATHOLOGY 44 巻 ( 9 ) 頁： 1173 - 1183 2020年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Journal of Surgical Pathology

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoproliferation encompasses a broad range of clinicopathologic findings, including specific subtypes, for example, EBV+ mucocutaneous ulcer. Here we reassessed 36 cases of primary EBV+ diffuse large B-cell lymphomas (16 men and 20 women; median age, 69.5 y; range, 35 to 84 y), including 8 immunosuppressed patients (Lugano stage II-IV; median age, 74 y), 7 nonimmunosuppressed patients with stage I disease (median age, 69 y), and 21 nonimmunosuppressed patients with stage II-IV disease (median age, 69 y). All immunosuppressed patients exhibited iatrogenic immunodeficiency and an ulcerative appearance, with ulcer sites including the stomach (1 patient), small intestine (6 patients), and rectum (1 patient). Four patients were in the setting of treated lymphoma-associated immunosuppression. Immunosuppressed patients had higher incidences of intestinal involvement (P=0.001) and perforation (n=2) compared with advanced stage nonimmunosuppressed patients. Among nonimmunosuppressed stage I patients, lesions were restricted to the stomach, none showed multiple lesions or elevated serum lactate dehydrogenase, and the overall survival curve plateaued, although it was not statistically significant (P=0.0581). One nonimmunosuppressed stage I patient with a polypoid lesion exhibited spontaneous regression within 2 months after diagnosis, while another with bulky disease pursued an aggressive clinical course. Nonimmunosuppressed stage I cases without bulky masses may be considered EBV mucocutaneous ulcer with local progression. Our results demonstrated that primary EBV+ gastrointestinal diffuse large B-cell lymphoma could be delineated into 3 groups based on immune status and clinical stage, revealing distinguishing features useful as a pragmatic guide for diagnostic and therapeutic approaches.

DOI： 10.1097/PAS.0000000000001499

Age-related EBV-associated B-cell lymphoproliferative disorders and other EBV plus lymphoproliferative diseases: New insights into immune escape and immunodeficiency through staining with anti-PD-L1 antibody clone SP142 査読有り

Sakakibara, A; Kohno, K; Ishikawa, E; Suzuki, Y; Shimada, S; Eladl, AE; Elsayed, AA; Daroontum, T; Satou, A; Takahara, T; Ohashi, A; Takahashi, E; Kato, S; Nakamura, S; Asano, N

PATHOLOGY INTERNATIONAL 70 巻 ( 8 ) 頁： 481 - 492 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Pathology International

Epstein–Barr virus (EBV) is prevalent among healthy individuals, and is implicated in numerous reactive and neoplastic processes in the immune system. The authors originally identified a series of senile or age-related EBV-associated B-cell lymphoproliferative disorders (LPD) bearing a resemblance to immunodeficiency-associated ones. These LPDs may be associated with immune senescence and are now incorporated into the revised 4th edition of 2017 WHO lymphoma classification as EBV-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS). These EBV+ B-cells often have a Hodgkin/Reed-Sternberg (HRS)-like appearance and are shared beyond the diagnostic categories of mature B-cell neoplasms, mature T-cell neoplasms, classic Hodgkin lymphoma, and immunodeficiency-associated LPD. In addition, peculiar new diseases, such as EBV+ mucocutaneous ulcer and EBV+ DLBCL affecting the young, were recognized. On the other hand, lymphoma classification is now evolving in accord with deeper understanding of the biology of programmed death ligand 1 (PD-L1). Assessing PD-L1 positivity by staining with the anti-PD-L1 monoclonal antibody SP142 provides new insight by discriminating between immune evasion and senescence or immunodeficiency. The aim of the present review is to briefly summarize the diagnostic use of immunostaining with SP142 in malignant lymphomas and/or LPDs that feature tumor and nonmalignant large B-cells harboring EBV.

DOI： 10.1111/pin.12946

PD-L1 expression on tumor or stromal cells of nodal cytotoxic T-cell lymphoma: A clinicopathological study of 50 cases 査読有り

Yamashita, D; Shimada, K; Kohno, K; Kogure, Y; Kataoka, K; Takahara, T; Suzuki, Y; Satou, A; Sakakibara, A; Nakamura, S; Asano, N; Kato, S

PATHOLOGY INTERNATIONAL 70 巻 ( 8 ) 頁： 513 - 522 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Pathology International

Inhibitors of programmed cell-death 1 (PD-1) and programmed cell-death ligand 1 (PD-L1) have revolutionized cancer therapy. Nodal cytotoxic T-cell lymphoma (CTL) is characterized by a poorer prognosis compared to nodal non-CTLs. Here we investigated PD-L1 expression in 50 nodal CTL patients, with and without EBV association (25 of each). We identified seven patients (14%) with neoplastic PD-L1 (nPD-L1) expression on tumor cells, including three males and four females, with a median age of 66 years. One of the seven cases was TCRαβ type, three were TCRγδ type and three were TCR-silent type. Six of the seven cases exhibited a lethal clinical course despite multi-agent chemotherapy, of whom four patients died within one year of diagnosis. Morphological findings were uniform, with six cases showing centroblastoid appearance. Among nPD-L1+ cases, two of three examined had structural variations of PD-L1 disrupting 3′-UTR region. Notably, all of the TCRγδ-type nodal CTL cases showed nPD-L1 or miPD-L1 positivity (3 and 10 cases, respectively). TCRγδ-type cases comprised 42% of nPD-L1+ cases (P = 0.043 vs. PD-L1−), and 35% of miPD-L1+ cases (P = 0.037 vs. PD-L1−). The results indicate that PD-L1+ nodal CTL cases, especially of the TCRγδ type, are potential candidates for anti-PD-1/PD-L1 therapies.

DOI： 10.1111/pin.12950

PD-L1 (SP142) expression in neoplastic cells predicts a poor prognosis for patients with intravascular large B-cell lymphoma treated with rituximab-based multi-agent chemotherapy 査読有り

Suzuki, Y; Kohno, K; Matsue, K; Sakakibara, A; Ishikawa, E; Shimada, S; Shimada, K; Mabuchi, S; Takahara, T; Kato, S; Nakamura, S; Satou, A

CANCER MEDICINE 9 巻 ( 13 ) 頁： 4768 - 4776 2020年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cancer Medicine

Background: Intravascular large B-cell lymphoma (IVLBCL) is a rare form of diffuse large B-cell lymphoma (DLBCL) arising in extranodal sites. PD-L1 expression of tumor cells has been reported in IVLBCL cells, but its clinicopathological relevance remains to be elucidated. Aims: This study was aimed to reveal the characteristics of PD-L1+ IVLBCL. Methods and results: Neoplastic PD-L1 expression was examined in 34 cases of IVLBCL and clinicopathological characteristics between patients with PD-L1+ and PD-L1− IVLBCL were compared. We assessed PD-L1 expression with SP142 antibody. Twelve (35%) of 34 cases showed positivity for PD-L1. The PD-L1+ group had significantly lower survival rates compared to the PD-L1− group. The PD-L1+ IVLBCL group also had a significantly lower age distribution and a lower frequency of patients older than 60 years compared to the PD-L1− group. Very recently, we speculate that there is possible link between PD-L1+ IVLBCL and PD-L1+ extranodal DLBCL-NOS (eDLBCL) because features of the two groups showed overlapping. Therefore, we compared the clinicopathological characteristics of the PD-L1+ IVLBCL and PD-L1+ eDLBCL. There were no significant differences in clinicopathological parameters and prognosis. Conclusion: The worse prognosis of the PD-L1+ group might be caused by immune evasion mechanisms, which are linked to PD-L1 expression. Therefore, PD-L1+ IVLBCL cases might be regarded as good candidates for targeted immunotherapy. We also highlighted the overlapping features of PD-L1+ IVLBCL and PD-L1+ eDLBCL. This result suggests that they should be regarded as one entity, immune evasion-related extranodal large B-cell lymphoma.

DOI： 10.1002/cam4.3104

Well-differentiated fetal adenocarcinoma of the lung: positron emission tomography features and diagnostic difficulties in frozen section analysis-a case report 査読有り

Hakiri, S; Fukui, T; Tsubouchi, H; Sakakibara, A; Iwano, S; Chen-Yoshikawa, TF

SURGICAL CASE REPORTS 6 巻 ( 1 ) 頁： 152 2020年6月

Immunohistochemical Assessment of the Diagnostic Utility of PD-L1 (Clone SP142) for Methotrexate-Associated Lymphoproliferative Disorders With an Emphasis of Neoplastic PD-L1 (Clone SP142)-Positive Classic Hodgkin Lymphoma Type 査読有り

Kohno, K; Suzuki, Y; Elsayed, AA; Sakakibara, A; Takahara, T; Satou, A; Kato, S; Nakamura, S; Asano, N

AMERICAN JOURNAL OF CLINICAL PATHOLOGY 153 巻 ( 5 ) 頁： 571 - 582 2020年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Journal of Clinical Pathology

Objectives: We describe results of programmed death ligand 1 (PD-L1) immunohistochemical assessment in methotrexate (MTX)-associated lymphoproliferative disorders (LPDs) and highlight the characteristics of classic Hodgkin lymphoma (CHL) type MTX-LPD. Methods: Fifty cases of MTX-LPD, including CHL type (n = 9), diffuse large B-cell lymphoma type (n = 15), and polymorphic B-cell LPD (n = 21), were investigated. Results: Staining with anti-PD-L1 clone SP142 was exclusively found in CHL type (89%) but not in the others. Cases of CHL type MTX-LPD involved nodal disease and were associated with Epstein-Barr virus. They were histopathologically characterized by a vaguely nodular pattern, predominance of mononuclear cells, and strong expression of at least one pan-B-cell marker. Their clinical course was variable, with spontaneous regression in 5 patients, relapse in 2, and a fatal course in 1. Conclusions: The PD-L1 (clone SP142) workup aids the diagnostic approach to patients with MTX-LPD. CHL type MTX-LPD appears to represent a unique morphologic variant of CHL.

DOI： 10.1093/ajcp/aqz198

Syncytial variant of classic Hodgkin lymphoma: Four cases diagnosed with the aid of CD274/programmed cell death ligand 1 immunohistochemistry 査読有り

Kohno, K; Sakakibara, A; Iwakoshi, A; Hasegawa, M; Adachi, S; Ishikawa, E; Suzuki, Y; Shimada, S; Nakaguro, M; Shimoyama, Y; Takahara, T; Takahashi, E; Ohashi, A; Satou, A; Kato, S; Asano, N; Nakamura, S

PATHOLOGY INTERNATIONAL 70 巻 ( 2 ) 頁： 108 - 115 2020年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Pathology International

Although several reports have highlighted neoplastic PD-L1 (nPD-L1) expression in classic Hodgkin lymphoma (CHL), some have addressed associations between its expression and detailed histopathologic features. Here we describe four cases of syncytial variant of CHL (SV-CHL), with and without Epstein–Barr virus (EBV) association, and highlight the diagnostic utility of PD-L1 (clone SP142) immunohistochemistry. The patients were a 61-year-old male, 45-year-old male, 85-year-old female, and 89-year-old female. All presented with cervical or axillary lymphadenopathy, which on biopsy had the established histopathologic features of SV-CHL with a biphasic pattern of cohesive sheets of large tumor cells and typically scattered distribution of Hodgkin and Reed–Stenberg (HRS) cells. These tumor cells showed identical immunophenotypic findings for CD15, CD30, Fascin, PAX5, OCT2, BOB1 and EBV harboring, regardless of location. The exception was absent or decreased expression of nPD-L1 from tumor cells in the confluent sheets, contrasting with HRS cell positivity in typical areas of CHL. These findings offer the first suggestion of possible downregulation of nPD-L1 expression in association with the histopathologic progression of CHL. The results may be relevant for recognizing ‘confluent’ sheets in the diagnostic workup for SV-CHL.

DOI： 10.1111/pin.12888

Diagnostic utility of programmed cell death ligand 1 (clone SP142) in mediastinal composite lymphoma: A report of two cases 査読有り

Sakakibara, A; Kohno, K; Iwakoshi, A; Moritani, S; Fujishiro, A; Kito, K; Suzuki, Y; Shimada, S; Nakaguro, M; Shimoyama, Y; Takahara, T; Takahashi, E; Ohashi, A; Satou, A; Kato, S; Asano, N; Nakamura, S

PATHOLOGY INTERNATIONAL 70 巻 ( 2 ) 頁： 116 - 122 2020年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Pathology International

Composite lymphoma is a well-known diagnostic entity exhibiting the synchronous occurrence of two or more distinct types of lymphomas in the same specimen. Here we report two patients, a 14-year-old female (Case 1) and a 45-year-old male (Case 2), with mediastinal composite lymphoma, comprising nodular sclerosis classic Hodgkin lymphoma (NSCHL) and primary mediastinal large B-cell lymphoma (PMBL). Both patients had a mediastinal mass, and manifested two different histologic components in the same biopsy, one characteristic of NSCHL and the other PMBL. The NSCHL areas included Hodgkin and Reed–Sternberg (HRS) cells with typical immunophenotypic features (CD30-positive and CD20-negative), whereas the sheets of large tumor cells characteristic of PMBL were strongly and uniformly CD20-positive. Interestingly, although both cases showed neoplastic PD-L1 (nPD-L1) positivity on the HRS cells of NSCHL, they differed regarding nPD-L1 expression on the PMBL tumor cells. In Case 1, the nPD-L1-negative PMBL component was anatomically situated outside the NSCHL lesion. On the other hand, in Case 2, the nPD-L1-positive PMBL component was characterized by transitional or continuous areas with the NSCHL component. These findings suggested that nPD-L1 expression may define two subtypes of PMBL that are more similar to or distinct from classic Hodgkin lymphoma.

DOI： 10.1111/pin.12891

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