The American Journal of Surgical Pathology最新文献

{"title":"Primary Female Urethral Carcinoma: Proposed Staging Modifications Based on Assessment of Female Urethral Histology and Analysis of a Large Series of Female Urethral Carcinomas.","authors":"Manju Aron,&nbsp;Sanghui Park,&nbsp;Brett M Lowenthal,&nbsp;Sounak Gupta,&nbsp;Debashis Sahoo,&nbsp;John C Cheville,&nbsp;Donna E Hansel","doi":"10.1097/PAS.0000000000001569","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001569","url":null,"abstract":"<p><p>Primary female urethral carcinoma is rare. Limited clinicopathologic information has hindered development of staging criteria in this disease. We analyzed 29 primary female urethral carcinoma resections from 3 academic medical centers to characterize histopathologic features, clinical outcomes, and applicability of current and a novel modified staging criteria. We complemented this analysis with review of fully embedded female autopsy urethras to detail anterior and posterior urethral wall histology. Primary female urethral carcinoma subtypes included urothelial carcinoma in situ (3/29, 10%), adenocarcinoma in situ (1/29; 3%), invasive urothelial carcinoma (13/29, 45%), clear cell carcinoma (5/29, 17%), adenocarcinoma not otherwise specified (4/29, 14%) and squamous cell carcinoma (3/29, 10%). Only 6/29 cases (21%) were originally assigned a stage at diagnosis. Using histologic landmarks specific to the female urethra, we modified existing eighth edition American Joint Committee on Cancer urethral staging to a histology-based female urethral carcinoma staging (UCS) system. UCS stages were defined as pTa/pTisUCS (noninvasive carcinoma), pT1UCS (subepithelial tissue invasion), pT2UCS (periurethral muscle invasion), pT3UCS (vaginal adventitia or surrounding fibrovascular tissue), and pT4UCS (anterior wall fibroadipose tissue or posterior vaginal wall). UCS staging was applicable to all cases and showed stepwise changes in disease recurrence with increasing stage and was statistically significant for disease-specific and overall survival in contrast to the American Joint Committee on Cancer staging system. This study of one of the largest cohort of primary female urethral carcinomas provides a modified histology-based staging system specific to female urethral anatomy that provides outcomes-related information, which may be further validated by larger multi-institutional studies.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1591-1601"},"PeriodicalIF":5.6,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315296/pdf/nihms-1694876.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38328876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent YAP1 and MAML2 Gene Rearrangements in Retiform and Composite Hemangioendothelioma.","authors":"Cristina R Antonescu,&nbsp;Brendan C Dickson,&nbsp;Yun-Shao Sung,&nbsp;Lei Zhang,&nbsp;Albert J H Suurmeijer,&nbsp;Albrecht Stenzinger,&nbsp;Gunhild Mechtersheimer,&nbsp;Christopher D M Fletcher","doi":"10.1097/PAS.0000000000001575","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001575","url":null,"abstract":"<p><p>Retiform and composite hemangioendotheliomas (CHEs) are both locally aggressive, rarely metastasizing vascular neoplasms characterized by arborizing vascular channels lined by endothelial cells with a hobnail morphology. CHE displays additional cytologic and architectural components, including often vacuolated epithelioid cells, solid areas, or features reminiscent of well-differentiated angiosarcoma. Triggered by an index case of a soft tissue retiform hemangioendothelioma (RHE) which revealed a YAP1-MAML2 gene fusion by targeted RNA sequencing, we sought to investigate additional cases in this morphologic spectrum for this genetic abnormality. A total of 24 cases, 13 RHE and 11 CHE involving skin and soft tissue were tested by fluorescence in situ hybridization using custom BAC probes for rearrangements involving these genes. An additional visceral CHE with neuroendocrine differentiation was tested by targeted RNA sequencing. Among the soft tissue cohort, 5/13 (38%) RHE and 3/11 (27%) CHE showed YAP1 gene rearrangements, with 5 cases showing a YAP1-MAML2 fusion, including all 3 CHE. The single neuroendocrine CHE showed the presence of a PTBP1-MAML2 fusion. All YAP1-positive CHE lesions occurred in female children at acral sites, compared with fusion-negative cases which occurred in adults, with a wide anatomic distribution. YAP1-positive RHE occurred preferentially in males and lower limb, compared with negative cases. These results suggest that RHE and CHE represent a morphologic continuum, sharing abnormalities in YAP1 and MAML2 genes. In contrast, the neuroendocrine CHE occurring in a 37-year-old male harbored a distinct PTBP1-MAML2 fusion and showed aggressive clinical behavior (pancreatic mass with multiple liver and lung metastases). These preliminary findings raise the possibility that neuroendocrine CHE may be genetically distinct from the conventional RHE/CHE spectrum. Further studies are needed to investigate the pathogenetic relationship of fusion-negative cases with this subset and, less likely, with other members of the HE family of tumors.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1677-1684"},"PeriodicalIF":5.6,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773139/pdf/nihms-1626302.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38432518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FUS-NFATC2 or EWSR1-NFATC2 Fusions Are Present in a Large Proportion of Simple Bone Cysts.","authors":"Jože Pižem,&nbsp;Daja Šekoranja,&nbsp;Andrej Zupan,&nbsp;Emanuela Boštjančič,&nbsp;Alenka Matjašič,&nbsp;Blaž Mavčič,&nbsp;Juan A Contreras,&nbsp;Barbara Gazič,&nbsp;David Martinčič,&nbsp;Žiga Snoj,&nbsp;Katarina A Limpel Novak,&nbsp;Vladka Salapura","doi":"10.1097/PAS.0000000000001584","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001584","url":null,"abstract":"<p><p>A simple bone cyst (SBC) is a benign bone lesion of unknown etiology. It can be differentiated from an aneurysmal bone cyst (ABC) by radiologic and histopathologic features, as well as by the absence of fusions of the USP6 gene characteristic of an ABC. In an attempt to differentiate between ABC and SBC in a recurrent bone cyst, we performed targeted RNA sequencing and found an EWSR1-NFATC2 fusion and no fusion of the USP6 gene. We subsequently analyzed additional 10 cysts, consistent with SBCs after radiologic-pathologic correlation, for the presence of an NFATC2 gene fusion, by targeted RNA sequencing, reverse-transcription polymerase chain reaction (RT-PCR) and Sanger sequencing, and fluorescent in situ hybridization. Targeted RNA sequencing showed a FUS-NFATC2 fusion in 4 of 11 SBCs and an EWSR1-NFATC2 fusion in 2 of 11 SBCs. No fusion was identified in 3 SBCs and the analysis was not successful in 2 SBCs because of the low quantity or poor quality of isolated RNA. All the 6 fusions detected by targeted RNA sequencing were confirmed by RT-PCR and Sanger sequencing, and 5 of the 6 fusions by fluorescent in situ hybridization. An additional FUS-NFATC2 fusion was identified by RT-PCR, Sanger sequencing, and fluorescent in situ hybridization in 1 of the 3 cases negative for fusions by targeted RNA sequencing. At least a large subset of SBCs represents cystic neoplasms characterized by FUS-NFATC2 or EWSR1-NFATC2 fusions, which also define a group of distinct, rare \"Ewing-like\" sarcomas that predominantly arise in long bones. Our results provide additional evidence of the existence of benign lesions with FUS-NFATC2 or EWSR1-NFATC2 fusions. Although they can recur locally in a nondestructive manner, their clinical course and possible relation to sarcoma with EWSR1-NFATC2 or FUS-NFATC2 fusion remains to be elucidated.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1623-1634"},"PeriodicalIF":5.6,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/PAS.0000000000001584","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38435134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic Study of Gleason Pattern 5 Prostatic Adenocarcinoma With \"Single-cell\" Growth Reveals 2 Distinct Types, One With \"Plasmacytoid\" Features.","authors":"Jane K Nguyen,&nbsp;Yunn-Yi Chen,&nbsp;Cristina Magi-Galluzzi,&nbsp;Jesse K McKenney","doi":"10.1097/PAS.0000000000001550","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001550","url":null,"abstract":"<p><p>Each Gleason score category of prostatic adenocarcinoma (or Grade Group) may encompass a diverse group of architectural patterns such as well-formed glands, poorly formed glands, cribriform structures, single cells, and/or solid sheets. We have noted heterogeneity within the single-cell subtype of Gleason pattern 5 prostatic adenocarcinoma that has not been fully addressed. Therefore, we retrospectively reviewed a series of radical prostatectomies with high-grade prostatic adenocarcinoma (Grade Group 4 or 5), identifying tumors with a component of single-cell infiltration. Additional cases identified prospectively were also included. TNM status, association with other histologic patterns, and clinical follow-up status were determined. Immunohistochemistry for NKX3.1, E-cadherin, p120 catenin, and prostate-specific antigen (PSA) were performed in each case. Eighteen cases with a component of well-developed Gleason pattern 5 characterized by single infiltrative cells that comprised ≥5% of the tumor were identified (15/202 retrospective radical prostatectomies with the high-grade disease [7.5%]). The single-cell pattern ranged from 5% to 50% of the tumor volume, with 5 cases containing ≥40%, and variable secondary architecture included diffuse infiltrating single cells with targetoid growth pattern around benign glands, solid expansive nests of noncohesive cells, and corded/single file growth pattern. Further morphologic analysis demonstrated 2 distinct histologic subtypes: (1) (subtype 1; n=9) monomorphic \"plasmacytoid\" tumor cells with eccentrically placed nuclei and variable intracytoplasmic vacuoles with bland cytology and discohesion and (2) (subtype 2; n=9) more cohesive tumor cells with greater cytologic atypia characterized by prominent nucleoli, greater variability in nuclear size/shape, occasional mitotic figures, and more irregular infiltration. By immunohistochemistry, NKX3.1 nuclear expression and PSA cytoplasmic expression was retained in all cases. Concomitant membranous E-cadherin loss and strong cytoplasmic p120 catenin expression were present in 5 of the 18 (28%) cases, all in subtype 1 (5/9, 56%). Overall, 56% (10/18) of patients had advanced-stage disease (≥pT3b), and 70% (7/10) of these patients had associated lymphovascular invasion. All patients had concomitant cribriform patterns of carcinoma. The outcome was available for 14 patients: 4 died of unknown cause; 6 had biochemical recurrence with distant bone metastasis in 5 of the 6; and 4 patients with <3 years of follow-up currently have undetectable serum PSA levels (2 patients received salvage radiotherapy with androgen deprivation and 2 remain on routine follow-up). In summary, the single-cell pattern of Gleason pattern 5 prostatic adenocarcinoma is uniformly associated with other high-risk histologic patterns (eg, cribriform growth), and high-stage disease with distant metastasis is not uncommon. Our data suggest that the \"single-cell\" Gleason pattern 5 prostatic ad","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1635-1642"},"PeriodicalIF":5.6,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38435135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chondroblastoma Expresses RANKL by RNA In Situ Hybridization and May Respond to Denosumab Therapy.","authors":"David I Suster,&nbsp;Pawel Kurzawa,&nbsp;Azfar Neyaz,&nbsp;Jason A Jarzembowski,&nbsp;Santiago Lozano-Calderon,&nbsp;Kevin Raskin,&nbsp;Joseph Schwab,&nbsp;Edwin Choy,&nbsp;Ivan Chebib,&nbsp;Vikram Deshpande","doi":"10.1097/PAS.0000000000001568","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001568","url":null,"abstract":"<p><p>Lesions of bone featuring osteoclast-like giant cells comprise a diverse group of entities, including giant cell tumor (GCT) of bone, chondroblastoma, and aneurysmal bone cyst, among others. The receptor activator of nuclear factor-κB ligand (RANKL) has been implicated in the pathogenesis of GCT of bone and may play a role in the pathogenesis of other giant cell-rich lesions as well. In addition, RANKL inhibitors (denosumab) have also been shown to have some efficacy in treating some giant cell-rich lesions. Herein, we examine RANKL expression by RNA in situ hybridization in a total of 84 osseous lesions with a focus on chondroblastoma, GCT, fibrous dysplasia, and aneurysmal bone cyst. The lesions were tested for RANKL expression using a chromogenic RNA in situ hybridization assay. RANKL expression was identified in 24/25 (96%) GCT, 24/26 (92%) chondroblastomas, 6/7 (86%) aneurysmal bone cysts, and 3/16 (19%) patients with fibrous dysplasia. RANKL expression was statistically lower in chondroblastoma and aneurysmal bone cyst compared with GCT. RANKL reactivity in fibrous dysplasia was exclusively seen in the 3 cases with osteoclast-type giant cells. Our results indicate a high proportion of chondroblastomas, GCTs, and aneurysmal bone cysts express RANKL while reactivity in fibrous dysplasia is dependent on the presence of osteoclast-type giant cells. On the basis of the success of denosumab therapy for GCTs, our results indicate that it may be a potential therapeutic option in other primary osseous tumors.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1581-1590"},"PeriodicalIF":5.6,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38289066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SRF Fusions Other Than With RELA Expand the Molecular Definition of SRF-fused Perivascular Tumors.","authors":"Marie Karanian,&nbsp;Anna Kelsey,&nbsp;Sandrine Paindavoine,&nbsp;Adeline Duc,&nbsp;Helene Vanacker,&nbsp;Liz Hook,&nbsp;Nicolas Weinbreck,&nbsp;Christophe Delfour,&nbsp;Veronique Minard,&nbsp;Pauline Baillard,&nbsp;Jean-Yves Blay,&nbsp;Daniel Pissaloux,&nbsp;Franck Tirode","doi":"10.1097/PAS.0000000000001546","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001546","url":null,"abstract":"<p><p>Pericytic tumors encompass several entities sharing morphologic and immunohistochemical features. A subset of perivascular myoid tumors associated with the SRF-RELA fusion gene was previously described. Herein, we report a series of 13 tumors belonging to this group, in which we have identified new fusion genes by RNA-sequencing, thus expanding the molecular spectrum of this entity. All patients except 1 were children and infants. The tumors, frequently located in the head (n=8), had a mean size of 38 mm (range 10 to 150 mm) and were mostly (n=9) well-circumscribed. Exploration of the follow-up data (ranging from 3 to 68 mo) confirmed the benign behavior of these tumors. These neoplasms presented a spectrum of morphologies, ranging from perivascular patterns to myoid appearance. Tumor cells presented mitotic figures but without marked atypia. Some of these tumors could mimic sarcoma. The immunohistochemical profiles confirmed a pericytic differentiation with the expression of the smooth muscle actin and the h-caldesmon, as well as the frequent positivity for pan-cytokeratin. The molecular analysis identified the expected SRF-RELA fusion gene, in addition to other genetic alterations, all involving SRF fused to CITED1, CITED2, NFKBIE, or NCOA2. The detection of SRF-NCOA2 fusions in spindle cell rhabdomyosarcoma of the infant has previously been described, representing a risk of misdiagnosis, although the cases reported herein did not express MyoD1. Finally, clustering analyses confirmed that this group of SRF-fused perivascular myoid tumors forms a distinct entity, different from other perivascular tumors, spindle cell rhabdomyosarcomas of the infant, and smooth muscle tumors.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1725-1735"},"PeriodicalIF":5.6,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38459920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-grade B-Cell Lymphoma With MYC, BCL2, and/or BCL6 Translocations/Rearrangements: Clinicopathologic Features of 51 Cases in a Single Institution of South China.","authors":"Jijun Zhang,&nbsp;Zeping Weng,&nbsp;Yuhua Huang,&nbsp;Min Li,&nbsp;Fang Wang,&nbsp;Yu Wang,&nbsp;Huilan Rao","doi":"10.1097/PAS.0000000000001577","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001577","url":null,"abstract":"<p><p>Double-hit/triple-hit lymphomas (DH/THLs) are high-grade B-cell lymphomas with MYC and BCL2 rearrangements and/or BCL6 rearrangements, which have poor outcomes after standard chemoimmunotherapy. This retrospective study analyzed 51 patients (range, 19 to 82 y) diagnosed from 2016 to 2019 and treated for DH/THL (n=34 MYC/BCL6 DHL, n=14 MYC/BCL2 DHL, n=3 THL) at one institution in South China. Extranodal lesions occurred in 32 patients (62.7%), more frequently in MYC/BCL6 DHL (22/34, 64.7%) than in MYC/BCL2 DHL (7/14, 50%). The most common extranodal sites were the stomach (8/32, 25.0%) and intestine (5/32, 15.6%). Most patients (33/45, 73.3%) presented with Ann Arbor stage III/IV. Interestingly, 14.3% (4/28) of MYC/BCL6 DHL tumors showed diffuse, medium-intensity CD30 expression. Epstein-Barr virus-encoded RNA was positive in 3 cases, all MYC/BCL6 DHL. Among 48 patients (94.1%) with follow-up data, 18 (37.5%) died owing to the disease, and the median survival was 5.5 months. Germinal center B cells were observed more frequently in MYC/BCL2 DHL (14/14, 100.0%) than in MYC/BCL6 DHL (15/34, 44.1%; P<0.001). Bone marrow involvement tended to lower overall survival (OS) (P=0.033). No association was observed between stage, B symptoms, lactate dehydrogenase levels, and central nervous system involvement and OS. A total of 25 patients (25/47, 53.2%) with previous hepatitis B virus (HBV) infections had significantly poorer OS (P=0.014). Chronic HBV infection was positively correlated with MYC/BCL6 DHL (r=0.317, P=0.030). Compared with DH/THL in western countries, the disease in South China has distinct characteristics with a higher prevalence of MYC/BCL6 DHL. We speculate that HBV is important in DH/THL tumorigenesis. These findings might provide clues for novel treatment strategies.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1602-1611"},"PeriodicalIF":5.6,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38435133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endometrial Gastric-type Carcinoma: An Aggressive and Morphologically Heterogenous New Histotype Arising From Gastric Metaplasia of the Endometrium.","authors":"Richard Wing-Cheuk Wong,&nbsp;Karen L Talia,&nbsp;W Glenn McCluggage","doi":"10.1097/PAS.0000000000001473","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001473","url":null,"abstract":"In Reply: We thank Travaglino and colleagues for their comments on our study and their description of an additional case of endometrial gastric-type carcinoma.1 We read with interest the points raised by Travaglino and colleagues regarding the morphologic heterogeneity of this tumor type and the possible precursor lesions and would like to supplement their correspondence by reporting another case, which similarly demonstrates the broad morphologic spectrum that may be encountered. With the scarcity of published cases, it is important to document further examples of endometrial gastric-type adenocarcinomas, especially those with previously unpublished features. Our case was recently encountered in consultation by one of us (W.G.M.). The patient was a 48-year-old woman who underwent hysterectomy, bilateral salpingectomy, and left oophorectomy 4 years earlier. The uterine corpus contained a deeply myoinvasive tumor with prominent lymphovascular invasion and no cervical involvement in the section sampled (the cervix was not completely submitted). No adnexal involvement was seen; the tumor was FIGO stage IB. The tumor contained “well-differentiated” areas featuring widely spaced glands with abundant clear or eosinophilic cytoplasm, as well as solid, poorly differentiated areas. There were foci","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1736-1737"},"PeriodicalIF":5.6,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38585885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRG1, INI1, and ARID1B Deficiency in Endometrial Carcinoma: A Clinicopathologic and Immunohistochemical Analysis of a Large Series From a Single Institution.","authors":"Atsushi Kihara,&nbsp;Yusuke Amano,&nbsp;Daisuke Matsubara,&nbsp;Noriyoshi Fukushima,&nbsp;Hiroyuki Fujiwara,&nbsp;Toshiro Niki","doi":"10.1097/PAS.0000000000001581","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001581","url":null,"abstract":"<p><p>Switch/sucrose nonfermenting complex subunits, such as BRG1, INI1, and ARID1B, are inactivated in a subset of endometrial undifferentiated carcinoma and dedifferentiated carcinoma (DC). Limited information is currently available on their prevalence in other subtypes or the nosological status of endometrial carcinoma with their deficiencies. This study immunohistochemically examined the expression status of BRG1, INI1, and ARID1B using 570 archived cases of endometrial carcinoma and carcinosarcoma resected at a single institution. We identified 1 BRG1-deficient undifferentiated carcinoma, 8 BRG1/INI1/ARID1B-deficient DC, and 3 BRG1-deficient clear-cell carcinomas. None of the cases of endometrioid and serous carcinomas or carcinosarcoma showed deficiencies of these subunits. We then compared 8 BRG1/INI1/ARID1B-deficient DC with 6 BRG1/INI1/ARID1B-intact DC and 28 carcinosarcomas, the latter of which was often confused with DC. Histologically, BRG1/INI1/ARID1B-intact and BRG1/INI1/ARID1B-deficient DC shared a monotonous solid appearance with rhabdoid and epithelioid cells and a myxoid stroma; however, abrupt keratinization and cell spindling was absent in BRG1/INI1/ARID1B-deficient tumors. The median overall survival of patients with BRG1/INI1/ARID1B-deficient DC was 3.8 months, which was worse than those with BRG1/INI1/ARID1B-intact DC (P=0.008) and with carcinosarcoma (P=0.004). BRG1/INI1/ARID1B-deficient DC may be a separate entity with an aggressive behavior to be distinguished from BRG1/INI1/ARID1B-intact DC and carcinosarcoma. Regarding clear-cell carcinoma (n=12), BRG1 deficiency appeared to be mutually exclusive with abnormal ARID1A, BRM, and p53 expression. Further studies are needed to clarify whether BRG1 deficiency plays a role in the pathogenesis of clear-cell carcinoma.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1712-1724"},"PeriodicalIF":5.6,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38365181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathologic Characterization of Mogamulizumab-associated Rash.","authors":"Jennifer Y Wang,&nbsp;Kelsey E Hirotsu,&nbsp;Tatiana M Neal,&nbsp;Shyam S Raghavan,&nbsp;Bernice Y Kwong,&nbsp;Michael S Khodadoust,&nbsp;Ryanne A Brown,&nbsp;Roberto A Novoa,&nbsp;Youn H Kim,&nbsp;Kerri E Rieger","doi":"10.1097/PAS.0000000000001587","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001587","url":null,"abstract":"<p><p>Rash is one of the most common adverse events observed with mogamulizumab, an anti-C-C chemokine receptor 4 monoclonal antibody approved for previously treated mycosis fungoides (MF) and Sezary syndrome (SS). Given the nonspecific clinical presentations of this rash, histopathologic distinction from MF/SS is critical for informing clinical management. We performed a comprehensive characterization of the histopathologic findings in mogamulizumab-associated rash (MAR) with the integration of high-throughput sequencing of T-cell receptor (TCR) genes. Fifty-two biopsy specimens from 19 patients were evaluated retrospectively. Three major histologic reaction patterns were identified: spongiotic/psoriasiform dermatitis (33/52), interface dermatitis (11/52), and granulomatous dermatitis (8/52). Almost half of the specimens (21/52) showed at least 2 of these reaction patterns concurrently. Dermal eosinophils were not a consistent feature, being present in only half (27/52) of specimens and prominent in only 3. Features mimicking MF/SS, including lymphocyte exocytosis, lamellar fibroplasia, and adnexal involvement, were commonly seen but tended to be focal and mild. In 38/43 specimens with available immunohistochemistry, intraepidermal lymphocytes demonstrated a CD4:CD8 ratio ≤1 : 1. Low background levels of the patient's previously identified MF/SS-associated TCR sequence(s) were demonstrated in 20/46 specimens analyzed by high-throughput sequencing of TCR. We conclude that MAR may demonstrate diverse histologic features. Findings that may distinguish MAR from MF/SS include the inverted or normalized CD4:CD8 ratio within intraepidermal lymphocytes and demonstration of absent or nondominant levels of disease-associated TCR sequences. Correlation with the clinical findings and immunohistochemical and molecular characterization of the patient's MF/SS before mogamulizumab, when possible, may facilitate recognition of MAR.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1666-1676"},"PeriodicalIF":5.6,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38418915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}