Faculty Profiles - NAKAGURO Masato

Salivary Gland Polymorphous Adenocarcinoma: Clinicopathological Features and Gene Alterations in 36 Japanese Patients Reviewed International journal

Masahiro Fukumura, Kenichiro Ishibashi, Masato Nakaguro, Toshitaka Nagao, Kosuke Saida, Makoto Urano, Maki Tanigawa, Hideaki Hirai, Takahiro Yagyuu, Kentaro Kikuchi, Naomi Yada, Yoshihiko Sugita, Megumi Miyabe, Shogo Hasegawa, Mitsuo Goto, Hidetaka Yamamoto, Tomoyuki Ohuchi, Kimihide Kusafuka, Ikuko Ogawa, Hiroaki Suzuki, Kenji Notohara, Masayuki Shimoda, Yuichiro Tada, Tadaaki Kirita, Takashi Takata, Shojiroh Morinaga, Hatsuhiko Maeda, Saman Warnakulasuriya, Satoru Miyabe, Toru Nagao

Journal of Oral Pathology & Medicine Vol. 51 ( 8 ) page： 710 - 720 2022.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley

OBJECTIVES: Polymorphous adenocarcinoma (PAC) is a common intraoral minor salivary gland carcinoma in Western countries but is extremely rare in Japan. The current study aimed to characterize the clinicopathological features and status of molecular alterations of PAC-associated genes, such as (e.g., PRKD1/2/3, ARID1A, and DDX3X) in a large cohort of Japanese patients with PAC. MATERIALS AND METHODS: We examined the cases of 36 Japanese patients with salivary gland PAC and 26 cases involving histopathological mimics. To detect gene splits, fluorescence in situ hybridization was carried out for PAC-associated genes. Additionally, we applied a SNaPshot multiplex assay to identify PRKD1 hotspot mutations. RESULTS: This study revealed the indolent clinical course of PAC with a high 10-year overall survival rate (92.9%), accompanied by occasional local recurrences and cervical lymph node metastasis (both 23.3%). Twenty cases (55.6%) of PAC (but none of the mimics) exhibited alterations in at least one PAC-associated gene. Rearrangement of PAC-associated genes and PRKD1 E710D were identified in 17 (47.2%) and 4 (11.1%) cases, respectively; one case showed coexisting PRKD3 split and PRKD1 E710D. In the multivariate analysis, high clinical stage (P=0.0005), the presence of prominent nucleoli (P=0.0003), and ARID1A split positivity (P=0.004) were independent risk factors for disease-free survival. CONCLUSION: Japanese patients with PAC showed clinicopathological features similar to those reported in Western countries. This study disclosed that PAC-associated genetic alterations were common and specific findings in PACs. The diagnostic role and possible prognostic significance of PAC-associated genetic alterations in PACs were suggested.

DOI： 10.1111/jop.13336

Survival benefit of HER2-targeted or androgen deprivation therapy in salivary duct carcinoma. Reviewed International journal

Daisuke Kawakita, Toshitaka Nagao, Hideaki Takahashi, Satoshi Kano, Yoshitaka Honma, Hideaki Hirai, Natsuki Saigusa, Kohei Akazawa, Kaori Tani, Hiroya Ojiri, Kiyoaki Tsukahara, Hiroyuki Ozawa, Kenji Okami, Takahito Kondo, Takafumi Togashi, Chihiro Fushimi, Tomotaka Shimura, Akira Shimizu, Isaku Okamoto, Takuro Okada, Yorihisa Imanishi, Yoshihiro Watanabe, Kuninori Otsuka, Akihiro Sakai, Koji Ebisumoto, Yuichiro Sato, Keisuke Yamazaki, Yushi Ueki, Toyoyuki Hanazawa, Yuki Saito, Mizuo Ando, Takashi Matsuki, Masato Nakaguro, Yukiko Sato, Makoto Urano, Yoshitaka Utsumi, Shinji Kohsaka, Takashi Saotome, Yuichiro Tada

Therapeutic advances in medical oncology Vol. 14 page： 17588359221119538 - 17588359221119538 2022.9

Language：English Publishing type：Research paper (scientific journal)

Background: The efficacy and safety of human epidermal growth factor receptor 2 (HER2)-targeted therapy and androgen deprivation therapy (ADT) for locally advanced or recurrent or metastatic (LA/RM) salivary duct carcinoma (SDC) have been reported in prospective studies. However, the survival benefit of these therapies to conventional therapy remains controversial, and whether HER2-targeted therapy or ADT should be chosen in HER2- and androgen receptor (AR)-positive SDC patients remains unknown. Methods: Overall, 323 LA/RM SDC patients treated at seven institutions between August 1992 and June 2020 were retrospectively enrolled. The primary aim was to analyze the effect of HER2-targeted therapy and ADT on overall survival from the diagnosis of LA/RM disease to death from any cause (OS1). The secondary indicators included the overall response rate (ORR), clinical benefit rate (CBR), overall survival from therapy initiation for LA/RM disease (OS2), progression-free survival (PFS), time to second progression (PFS2), duration of response (DoR), and duration of clinical benefit (DoCB) of HER2-targeted therapy or ADT as first-line therapy for HER2-positive/AR-positive SDC. Results: Patients treated with HER2-targeted therapy or ADT had longer OS1 than those treated without these therapies (Median OS1: historical control, 21.6 months; HER2-targeted therapy, 50.6 months; ADT, 32.8 months; HER2-targeted therapy followed by ADT, 42.4 months; and ADT followed by HER2-targeted therapy, 45.2 months, p < 0.001). Among HER2-positive/AR-positive SDC patients, although HER2-targeted therapy had better ORR, CBR, and PFS than those of ADT as first-line therapy, we found no significant differences between HER2-targeted therapy and ADT regarding OS2, PFS2, DoR, and DoCB. Conclusion: Patients treated with HER2-targeted therapy and ADT showed longer survival in LA/RM SDC. HER2-targeted therapy can be recommended prior to ADT for HER2-positive/AR-positive SDC. It is warranted to establish a biomarker that could predict the efficacy of clinical benefit or better response in ADT.

DOI： 10.1177/17588359221119538

今月の話題唾液腺腫瘍の病理診断における遺伝子異常の代替的免疫染色マーカー

中黒匡人, 長尾俊孝

病理と臨床 Vol. 40 ( 9 ) page： 0940 - 0944 2022.9

Microsatellite instability-high is rare events in refractory pediatric solid tumors. Reviewed International journal

Taro Yoshida, Hideki Muramatsu, Manabu Wakamatsu, Rieko Taniguchi, Daisuke Ichikawa, Masato Nakaguro, Atsushi Natsume, Yoshiyuki Takahashi

Pediatric hematology and oncology Vol. 39 ( 5 ) page： 468 - 474 2022.8

Language：English Publishing type：Research paper (scientific journal)

Microsatellite instability (MSI)-high status is associated with good responsiveness to immune checkpoint inhibitors. Although MSI-high status has been actively investigated in pediatric brain tumors, studies of other pediatric solid tumors are lacking. Among 334 consecutive pediatric patients with solid tumors, we retrospectively analyzed formalin-fixed paraffin-embedded tumor tissues of 36 of 74 patients (49%) who died of disease. We assessed the MSI status in these tissues using five multiplexed markers. The results revealed that none of the patients had an MSI-high status. These results indicate that MSI-high status is a rare event in pediatric patients with refractory/relapsed solid tumors.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1998266.

DOI： 10.1080/08880018.2021.1998266

Non-sebaceous lymphadenoma-like mucoepidermoid carcinoma: A case report. Reviewed International journal

Shinnichi Sakamoto, Mutsumi Miyauchi, Toshinori Ando, Megumu Fujihara, Masato Nakaguro, Toshitaka Nagao, Ikuko Ogawa

Pathology international Vol. 72 ( 7 ) page： 371 - 375 2022.7

Language：English Publishing type：Research paper (scientific journal)

Non-sebaceous lymphadenoma is a rare benign salivary gland tumor comprised of non-sebaceous epithelial cells and lymphoid tissue. Although its clinicopathological features have been described, its histogenesis and genetic background have not yet been elucidated. MAML2 rearrangement and the resultant CRTC1/3-MAML2 fusion gene are well-known specific genetic changes in mucoepidermoid carcinoma. Here, we present a case of lymphoepithelial tumor characterized by histomorphology of the non-sebaceous lymphadenoma and CRTC1-MAML2 fusion gene. The patient was an 83-year-old woman with an 8-year history of a solid, well-circumscribed tumor in the parotid gland. Histologically, the tumor was surrounded by thin fibrous connective tissue and was composed of tubular-cystic and solid nests of epithelial cells equally distributed in the lymphoid tissue. The histological features were suggestive of non-sebaceous lymphadenoma. Although the histomorphology was not consistent with mucoepidermoid carcinoma, a diagnosis of non-sebaceous lymphadenoma-like mucoepidermoid carcinoma was made based on the presence of the CRTC1-MAML2 fusion gene. The histological features alone could not establish the diagnosis, and ancillary molecular analysis was required.

DOI： 10.1111/pin.13236

Subtype classification of malignant lymphoma using immunohistochemical staining pattern Reviewed International journal

Noriaki Hashimoto, Kaho Ko, Tatsuya Yokota, Kei Kohno, Masato Nakaguro, Shigeo Nakamura, Ichiro Takeuchi, Hidekata Hontani

International Journal of Computer Assisted Radiology and Surgery Vol. 17 ( 7 ) page： 1379 - 1389 2022.7

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Abstract

Purpose

For the image classification problem, the construction of appropriate training data is important for improving the generalization ability of the classifier in particular when the size of the training data is small. We propose a method that quantitatively evaluates the typicality of a hematoxylin-and-eosin (H&E)-stained tissue slide from a set of immunohistochemical (IHC) stains and applies the typicality to instance selection for the construction of classifiers that predict the subtype of malignant lymphoma to improve the generalization ability.

Methods

We define the typicality of the H&E-stained tissue slides by the ratio of the probability density of the IHC staining patterns on low-dimensional embedded space. Employing a multiple-instance-learning-based convolutional neural network for the construction of the subtype classifier without the annotations indicating cancerous regions in whole slide images, we select the training data by referring to the evaluated typicality to improve the generalization ability. We demonstrate the effectiveness of the instance selection based on the proposed typicality in a three-class subtype classification of 262 malignant lymphoma cases.

Results

In the experiment, we confirmed that the subtypes of typical instances could be predicted more accurately than those of atypical instances. Furthermore, it was confirmed that instance selection for the training data based on the proposed typicality improved the generalization ability of the classifier, wherein the classification accuracy was improved from 0.664 to 0.683 compared with the baseline method when the training data was constructed focusing on typical instances.

Conclusion

The experimental results showed that the typicality of the H&E-stained tissue slides computed from IHC staining patterns is useful as a criterion for instance selection to enhance the generalization ability, and this typicality could be employed for instance selection under some practical limitations.

DOI： 10.1007/s11548-021-02549-0

Other Link： https://link.springer.com/article/10.1007/s11548-021-02549-0/fulltext.html

増刊号結果の読み方がよくわかる!　耳鼻咽喉科検査ガイド Ⅵ.頭頸部腫瘍の検査融合遺伝子

中黒匡人

耳鼻咽喉科・頭頸部外科 Vol. 94 ( 5 ) page： 218 - 223 2022.4

Predictors of Failure of Mitral Valve Repair Using Artificial Chordae. Reviewed International journal

Masato Mutsuga, Yuji Narita, Yoshiyuki Tokuda, Wataru Uchida, Hideki Ito, Sachie Terazawa, Masato Nakaguro, Akihiko Usui

The Annals of thoracic surgery Vol. 113 ( 4 ) page： 1136 - 1143 2022.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: We investigated predictors of failure of mitral valve repair (MVr) using expanded polytetrafluoroethylene (ePTFE) and its durability in the long term in a single institution. METHODS: Four hundred twenty-one consecutive patients with primary mitral valve disease underwent MVr using artificial chordae (group A, n = 304) and suture repair (group S, n = 117) at our institution from January 2002 to April 2020. A comparison study was performed to examine the long-term outcomes, reoperation rate, and risk factors for reoperation. RESULTS: One hospital death and 5 late deaths occurred in group S, and 20 late deaths occurred in group A. The reoperation rates were similar: group A, n = 8 (2.6%); and group S, n = 6 (5%). The major cause of reoperation was ruptured ePTFE (CV-4, n = 1; CV-5, n = 6) in group A, and suture rupture in group S. Reoperation was performed after a median of 88 months for ruptured ePTFE, and 26 months for group S. The rate of ePTFE rupture was 1.8% with CV-5 and 0.2% with CV-4. Risk factors for reoperation included postoperative arrhythmia, urgent operation, no annular ring, ruptured ePTFE, and suture rupture. The rates of freedom from reoperation and actuarial mitral valve survival rates at 5, 10, and 15 years were 99%, 95%, and 93% and 96%, 91%, and 89%, respectively, in group A; and 96%, 91%, and 91% and 95%, 94%, and 94%, respectively, in group S. CONCLUSIONS: The long-term surgical outcomes of MVr using both techniques were feasible. Over the long term, the ePTFE rupture rate of CV-5 was higher than that of CV-4.

DOI： 10.1016/j.athoracsur.2021.04.084

CDKN2A/B Loss in High-Grade Transformation of Salivary Gland Carcinoma: High-Grade Malignant Potential in Histologically Low-Grade Component Reviewed

Nakaguro, M; Faquin, W; Snuderl, M; Baloch, Z; Cantley, R; Compton, M; Ely, K; Holmes, B; Hu, R; Kerr, D; Montone, K; Nishino, M; Pantanowitz, L; Rossi, E; Nagao, T; Sadow, P

MODERN PATHOLOGY Vol. 35 ( SUPPL 2 ) page： 894 - 895 2022.3

CDKN2A/B Loss in High-Grade Transformation of Salivary Gland Carcinoma: High-Grade Malignant Potential in Histologically Low-Grade Component Reviewed

Nakaguro, M; Faquin, W; Snuderl, M; Baloch, Z; Cantley, R; Compton, M; Ely, K; Holmes, B; Hu, R; Kerr, D; Montone, K; Nishino, M; Pantanowitz, L; Rossi, E; Nagao, T; Sadow, P

LABORATORY INVESTIGATION Vol. 102 ( SUPPL 1 ) page： 894 - 895 2022.3

The Role of the EZH2 and H3K27me3 Expression as a Predictor of Clinical Outcomes in Salivary Duct Carcinoma Patients: A Large-Series Study With Emphasis on the Relevance to the Combined Androgen Blockade and HER2-Targeted Therapy Reviewed International journal

Natsuki Saigusa, Hideaki Hirai, Yuichiro Tada, Daisuke Kawakita, Masato Nakaguro, Kiyoaki Tsukahara, Satoshi Kano, Hiroyuki Ozawa, Takahito Kondo, Kenji Okami, Takafumi Togashi, Yukiko Sato, Makoto Urano, Manami Kajiwara, Tomotaka Shimura, Chihiro Fushimi, Akira Shimizu, Isaku Okamoto, Takuro Okada, Takayoshi Suzuki, Yorihisa Imanishi, Yoshihiro Watanabe, Akihiro Sakai, Koji Ebisumoto, Yuichiro Sato, Yoshitaka Honma, Keisuke Yamazaki, Yushi Ueki, Toyoyuki Hanazawa, Yuki Saito, Hideaki Takahashi, Mizuo Ando, Shinji Kohsaka, Takashi Matsuki, Toshitaka Nagao

Frontiers in Oncology Vol. 11 page： 779882 - 779882 2022.2

Language：English Publishing type：Research paper (scientific journal) Publisher：Frontiers Media SA

<sec><title>Objective</title>Salivary duct carcinoma (SDC) is a highly aggressive and uncommon tumor arising not only <italic>de novo</italic> but also in pleomorphic adenoma. Androgen receptor (AR)- and HER2-targeted therapy have recently been introduced for SDC as promising treatment options; however, no predictive biomarkers have yet been established. EZH2 and H3K27me3 are closely linked to the development and progression of various cancers, and EZH2 is also expected to be a desirable therapeutic target. We therefore explored the clinicopathological and prognostic implications of EZH2 and H3K27me3 in a large cohort of SDC patients, focusing on their impact on the therapeutic efficacy of AR- or HER2-targeted therapy.

</sec><sec><title>Materials and Methods</title>The EZH2 and H3K27me3 immunohistochemical expression and <italic>EZH2</italic> Y646 gain-of-function mutation status were examined in 226 SDCs, and the relationship with the clinicopathological factors as well as clinical outcomes were evaluated within the three groups depending on the treatment: AR-targeted (combined androgen blockade with leuprorelin acetate and bicalutamide; 89 cases), HER2-targeted (trastuzumab and docetaxel; 42 cases), and conventional therapy (112 cases).

</sec><sec><title>Results</title>EZH2 and H3K27me3 were variably immunoreactive in most SDCs. A positive correlation was found between the expression of EZH2 and H3K27me3. The EZH2 expression in the SDC component was significantly higher than that in the pre-existing pleomorphic adenoma component. <italic>EZH2</italic> Y646 was not identified in any cases. EZH2-high cases more frequently had an advanced clinical stage and aggressive histological features than EZH2-low cases. An EZH2-high status in patients treated with AR-targeted therapy was associated with a significantly shorter progression-free and overall survival as well as a lower objective response rate and clinical benefit rate. In addition, a H3K27me3-high status in patients treated with AR-targeted therapy was related to a shorter overall survival. Conversely, there was no association between the EZH2 and H3K27me3 expression and the clinical outcomes in the conventional or HER2-targeted therapy groups.

</sec><sec><title>Conclusions</title>A high expression of EZH2 and H3K27me3 in SDC might be a predictor of a poor efficacy of AR-targeted therapy. Our data provide new insights into the role of EZH2 and H3K27me3 in therapeutic strategies for SDC.

</sec>

DOI： 10.3389/fonc.2021.779882

NR4A3 Immunostain Is a Highly Sensitive and Specific Marker for Acinic Cell Carcinoma in Cytologic and Surgical Specimens. Reviewed International journal

Kartik Viswanathan, Shaham Beg, Bing He, Taotao Zhang, Richard Cantley, Daniel J Lubin, Qiuying Shi, Zahra Maleki, Saeed Asiry, Rema Rao, Nora Katabi, Masato Nakaguro, William C Faquin, Peter M Sadow, Momin T Siddiqui, Theresa Scognamiglio

American journal of clinical pathology Vol. 157 ( 1 ) page： 98 - 108 2022.1

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Salivary gland acinic cell carcinoma (AciCC) has recognizable cytomorphologic features that can overlap with benign and malignant entities, creating a diagnostic challenge. AciCC harbors a t(4;9) translocation increasing nuclear receptor subfamily 4 group A member 3 (NR4A3) expression, detectable by immunohistochemistry (IHC) on surgical resection (SR). NR4A3 IHC cytology data are limited. Here, we examine NR4A3 IHC on smears, cell blocks (CBs), and SRs of AciCC and its mimickers. METHODS: Our cohort comprised AciCC (including high-grade transformation), secretory carcinoma, mucoepidermoid carcinoma (MEC), Warthin tumor, pleomorphic adenoma (PA), cellular PA, carcinoma ex-PA, oncocytic carcinoma, oncocytoma, and nodular oncocytosis. NR4A3 IHC (Santa Cruz Biotechnology and Origene antibodies) was positive if more than 5% tumor cells showed nuclear staining. RESULTS: Among CBs, 90% of AciCC cases and none of the mimickers expressed NR4A3. Among SRs, 100% of AciCC cases showed diffuse NR4A3, whereas one high-grade MEC expressed focal NR4A3. Concordance was 95% with two antibody clones. Sensitivity, specificity, positive predictive value, and negative predictive value were 90%, 100%, 100%, and 94.7% for CBs and 100%, 98.8%, 92.3%, and 100% for SRs, respectively. NR4A3 immunostaining was demonstrable on smears from an AciCC case. CONCLUSIONS: NR4A3 IHC can be a robust diagnostic tool to identify AciCC, especially for cytology specimens.

DOI： 10.1093/ajcp/aqab099

A multi‐institutional study of salivary gland cytopathology: Application of the Milan System for Reporting Salivary Gland Cytopathology in Japan Reviewed International journal

Kayoko Higuchi, Makoto Urano, Jun Akiba, Miwako Nogami, Yukiya Hirata, Yoko Zukeran, Koki Moriyoshi, Yuichiro Tada, Mana Fukushima, Mariko Obayashi, Shinnichi Sakamoto, Kazuya Kuraoka, Kana Kira, Akihiko Kawahara, Taku Kato, Maki Tanigawa, Masato Nakaguro, Hidetaka Yamamoto, Toshitaka Nagao

Cancer Cytopathology Vol. 130 ( 1 ) page： 30 - 40 2022.1

Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a risk-stratification reporting system that was introduced in 2018. The objective of this multi-institutional study was to evaluate the utility of the MSRSGC in Japan. METHODS: In total, 1608 fine-needle aspiration samples with matching histologic diagnoses were retrieved from 12 large institutions in Japan. The diagnostic categories of the MSRSGC were assigned prospectively or retrospectively, and the results were compared with the histologic diagnoses. RESULTS: The cases were classified as follows: nondiagnostic, 18.1%; non-neoplastic, 4.1%; atypia of undetermined significance, 11.5%; neoplasm-benign, 43.7%; salivary gland neoplasm of uncertain malignant potential, 9.6%; suspicious for malignancy, 3.6%; and malignant, 9.4%. The risk of neoplasm and the risk of malignancy in each MSRSGC category were as follows: nondiagnostic, 72.9% and 13.4%, respectively; non-neoplastic, 15.2% and 9.1%, respectively; atypia of undetermined significance, 77.9% and 24.9%, respectively; neoplasm-benign, 99% and 1.8%, respectively; salivary gland neoplasm of uncertain malignant potential, 94.8% and 37%, respectively; suspicious for malignancy, 100% and 89.7%, respectively; and malignant, 100% and 99.3%, respectively. The accuracy of the MSRSGC for diagnosing neoplasms was 97.8%, and its accuracy for diagnosing malignancy was 97.3%. Institutions that used Romanowsky-stained preparations had lower nondiagnostic rates and lower risks of neoplasm and malignancy in the non-neoplastic category. CONCLUSIONS: The MSRSGC is useful for risk stratification and quality control. Widespread use of the MSRSGC would improve the accuracy of salivary gland cytology and lead to better patient care in Japan.

DOI： 10.1002/cncy.22505

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cncy.22505

Microsecretory Adenocarcinoma of Salivary Glands: An Expanded Series of 24 Cases. Reviewed International journal

Justin A Bishop, Dipti P Sajed, Ilan Weinreb, Brendan C Dickson, Elizabeth A Bilodeau, Abbas Agaimy, Alessandro Franchi, Syed Ali Khurram, Philip Da Forno, Juliana Robledo, John R Kalmar, Sarah Aguirre, Jeffrey F Krane, Jose Luis Tapia, Katalin Kiss, Kitrina Cordell, Molly Rosebush, A William Barrett, Dolphine Oda, Adel Assaad, Toshitaka Nagao, Fumi Kawakami, Masato Nakaguro, Ismail Zahir, Kristina Wakeman, Stephan Ihrler, Jacinthe Chenevert, Yi-Ling Lin, William H Westra, Jeffrey Gagan, Lisa M Rooper

Head and neck pathology Vol. 15 ( 4 ) page： 1192 - 1201 2021.12

Language：English Publishing type：Research paper (scientific journal)

Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor with a characteristic histologic and immunophenotypic profile and recurrent MEF2C-SS18 fusions. Because only six cases of MSA have been published, its complete clinicopathologic spectrum is unclear, and its biologic behavior has not been documented. Here, we present an updated and expanded experience of 24 MSA cases. All cases of MSA were obtained from the authors' files. Immunohistochemistry for S100, SOX10, p63, p40, SMA, calponin, and mammaglobin was performed. Molecular analysis was performed by targeted RNA sequencing, SS18 break apart fluorescence in situ hybridization, and/or reverse transcriptase polymerase chain reaction for MEF2C-SS18 fusion. Clinical follow-up was obtained from medical records. A total of 24 MSA cases were collected, from 13 women and 11 men, ranging from 17 to 83 years (mean 49.5 years). The vast majority (23 of 24) arose in the oral cavity, with the palate (n = 14) and buccal mucosa (n = 6) as the most frequent subsites. Tumors showed consistent histologic features including: (1) microcystic tubules, (2) flattened intercalated duct-like cells, (3) monotonous oval hyperchromatic nuclei, (4) abundant basophilic luminal secretions, (5) fibromyxoid stroma, and (6) circumscribed borders with subtle infiltration. The tumors were very consistently positive for S100 (24 of 24), p63 (24 of 24), and SOX10 (14 of 14) and negative for p40 (0 of 21), calponin (0 of 12) and mammaglobin (0 of 16), while SMA (4 of 20) was variable. MEF2C-SS18 fusion was demonstrated in 21 of 24 cases; in the remaining 3 cases with insufficient RNA, SS18 break apart FISH was positive. Treatment information was available in 17 cases, all of which were managed with surgery only. In 14 cases with follow-up (1-216 months, mean 30), no cases recurred or metastasized. MSA is a distinct salivary gland neoplasm with remarkably consistent clinical, histologic, immunophenotypic, and genetic features that generally behaves in an indolent manner following surgery alone. These observations solidify MSA as a unique, low-grade salivary gland carcinoma that warrants inclusion in the next version of the WHO classification of head and neck tumors.

DOI： 10.1007/s12105-021-01331-7

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. Reviewed International journal

Tasuku Kawano, Yuta Tsuyuki, Yuka Suzuki, Kazuyuki Shimada, Seiichi Kato, Taishi Takahara, Mayuko Mori, Masato Nakaguro, Ayako Sakakibara, Shigeo Nakamura, Akira Satou

The American journal of surgical pathology Vol. 45 ( 12 ) page： 1606 - 1615 2021.12

Language：English Publishing type：Research paper (scientific journal)

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