American Journal of Surgical Pathology最新文献

{"title":"Papillary Intralymphatic Angioendothelioma Versus Splenic Lymphatic Malformation With Papillary Endothelial Proliferation: Different Terms for the Same Entity.","authors":"Jonathan C Slack, Antonio R Perez-Atayde","doi":"10.1097/PAS.0000000000002309","DOIUrl":"10.1097/PAS.0000000000002309","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1473-1475"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRKC Fusion Melanocytic Tumors, a Subgroup of Melanocytic Tumors More Closely Aligned to Blue Nevi Than to PRKAR1A-inactivated Pigmented Epithelioid Melanocytomas.","authors":"Pragi Patel, Alice Chen, Natasha Sharma, Yongzhan Zhang, Victor L Quan, Shantel Olivares, Pedram Gerami","doi":"10.1097/PAS.0000000000002262","DOIUrl":"10.1097/PAS.0000000000002262","url":null,"abstract":"<p><p>Tumors morphologically classified as pigmented epithelioid melanocytomas (PEMs) are genomically diverse, with the 2 most common genomic subtypes being PRKC fusions or PRKAR1A inactivating mutations. PRKC fusions activate the Gα q/11 pathway similar to blue nevi. Conversely, inactivating mutations in PRKAR1A activate the Gα s pathway. We hypothesize that PRKC fusions have greater genomic overlap with blue nevi compared with PRKAR1A-inactivated PEMs. We characterized the clinical and morphologic features of 21 PRKC and PRKACB fusion melanocytic tumors and compared this to PRKAR1A mutated PEMs. To test our hypothesis regarding greater genomic overlap between PRKC fusions and blue nevi relative to PRKAR1A mutated PEMs, we performed a principal component analysis (PCA) using mRNA expression data. Lastly, we performed a meta-analysis focusing on the outcome data of PRKC fusions. PRKC fusions occur at a younger median age than PRKAR1A mutated PEMs (16 vs. 27). Histologically, PRKC fusions have solid aggregates of epithelioid melanocytes not typical of PRKAR1A mutated PEMs. The PCA plot showed no overlap between the PRKC fusion group and the PRKAR1A-mutated PEMs. There was a significant overlap between PRKC fusions and blue nevi. A meta-analysis of PRKC fusion cases in the literature suggests melanoma is uncommon, but the loss of BAP-1 nuclear expression may be associated with an adverse prognosis as in tumors from the blue nevus family. PRKC fusion melanocytic tumors have greater genomic overlap with blue nevi compared with PRKAR1A mutated PEMs. We recommend categorizing benign PRKC fusion melanocytic tumors as blue fusion nevi/tumors.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1349-1358"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sinonasal Squamous Cell Carcinoma with DEK::AFF2 Rearrangement : An Aggressive Cancer with Bland Morphology.","authors":"Aude Trinquet, Marick Laé, Charles Lépine, Marie-Delphine Lanic, Vanessa Lacheretz-Szablewski, Caroline Shaar Chneker, Jean-Michel Goujon, Valentin Favier, Valérie Costes-Martineau","doi":"10.1097/PAS.0000000000002281","DOIUrl":"10.1097/PAS.0000000000002281","url":null,"abstract":"<p><strong>Aims: </strong>DEK::AFF2 squamous cell carcinoma is a recently described cancer entity, with 29 cases reported to date. Occasionally, these carcinomas appear deceptively indistinguishable; however, specific morphological and phenotypic features suggest the presence of this rearrangement. However, the prognostic value of this diagnosis remains unclear. We aimed to report a new case series with histological, molecular, and clinical features.</p><p><strong>Methods: </strong>We collected data from 15 patients and investigated their phenotypes, including the expression profiles of CK7, P63/P40, PDL1, AFF2, and P16, morphological features, and associated prognostic data. We analyzed these data along with the previously published data.</p><p><strong>Results: </strong>Most of these cases exhibited indicative morphological features, such as exophytic and endophytic papillary growth, nuclear monomorphism, and abundant neutrophil-rich inflammatory infiltrates. Immunohistochemical analysis revealed the expression of AFF2 and squamous cell markers in all the patients. Overexpression of P16 was not detected, whereas CK7 and PDL1 were expressed variably. In our study cohort, a 50% progression or recurrence rate, 25% lymph node metastasis, 17% distant metastasis, and 18% disease-related death were identified, with a short follow-up time.</p><p><strong>Conclusion: </strong>DEK::AFF2 squamous cell carcinoma incidence is probably underestimated. The low-grade appearance of these tumors sometimes limits their detection. The rates of recurrence and metastasis seem to be high despite an often bland morphology. We propose AFF2 immunohistochemistry as an effective tool, and a diagnostic algorithm has been established to support accurate diagnosis of these tumors.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1408-1416"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Papillary Intralymphatic Angioendothelioma Versus Splenic Lymphatic Malformation With Papillary Endothelial Proliferation: Different Terms for the Same Entity.","authors":"Larisa Debelenko, Fabrizio Remotti","doi":"10.1097/PAS.0000000000002212","DOIUrl":"10.1097/PAS.0000000000002212","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1472-1473"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarker Testing in Microinvasive Carcinoma of the Breast.","authors":"Olivier Michaud, Muhammad Ahmad, Syed A Hoda","doi":"10.1097/PAS.0000000000002252","DOIUrl":"10.1097/PAS.0000000000002252","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1475-1479"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PEComa With MITF Overexpression: Clinicopathologic and Molecular Analysis of a Series of 36 Cases.","authors":"John Hanna, Eleanor Russell-Goldman, Esther Baranov, Daniel Pissaloux, Yvonne Y Li, Franck Tirode, Arnaud de la Fouchardiere, Christopher D M Fletcher","doi":"10.1097/PAS.0000000000002276","DOIUrl":"10.1097/PAS.0000000000002276","url":null,"abstract":"<p><p>Perivascular epithelioid cell neoplasms (PEComas) are tumors of uncertain cell lineage that occur across a wide age range, at a variety of anatomic sites, and with a female predominance. Most PEComas are associated with dysregulation of the mTOR pathway, most commonly through inactivating mutations of TSC2 or TSC1 . However, a small subset of PEComas are instead associated with TFE3 gene fusions. MITF is closely related to TFE3 and is frequently overexpressed in PEComas, often in a mutually exclusive manner with TFE3. Here we report the clinical, histopathologic, and molecular features of MITF-overexpressing PEComas in a series of 36 cases. The clinical and morphologic features were comparable to conventional PEComa, although the immunohistochemical profile was notable for the relatively limited expression of melanocytic markers, a surprising finding given that MITF is the master regulator of melanocytic differentiation. At the molecular level, 20 cases (56%) showed supernumerary copies of the MITF gene, suggesting a potential explanation for MITF overexpression. A putative genetic driver event within the mTOR pathway was identified in 11 of 15 cases (73%) analyzed by DNA or RNA sequencing. Interestingly, the malignant PEComas showed 2 distinguishing molecular features: they were associated with a complex chromosomal copy number profile, and they tended to show additional genetic changes, most commonly inactivating events involving TP53 , RB1 , and ATRX . These results elucidate key features of PEComas showing MITF overexpression, begin to explain the molecular basis for MITF overexpression in some PEComas and identify potential molecular correlates for malignancy that may be applicable to the broader PEComa family.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1381-1388"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraductal Implantation of Biliary Neoplasms: A Potential Cause of \"Multifocal\" Tumors.","authors":"Yoh Zen, Masayuki Akita, Evangelia Florou, Takumi Fukumoto, Tomoo Itoh, Evangelos Prassas, Krishna Menon, Parthi Srinivasan","doi":"10.1097/PAS.0000000000002279","DOIUrl":"10.1097/PAS.0000000000002279","url":null,"abstract":"<p><p>Multiple biliary tumors rarely develop in patients without underlying chronic hepatobiliary disease. Those lesions are regarded as multifocal neoplasms if there is no interconnecting dysplasia. This study aimed to determine whether 2 separate tumors in the biliary tract represent true multifocal independent tumorigenesis or intraluminal implantation of a single neoplasm. Two separate biliary tumors without intervening dysplasia were identified in 9 cases: biliary intraductal papillary neoplasm (IPNB; n=5) and extrahepatic cholangiocarcinoma (n=4). The 2 tumors were histologically similar in all cases. In 5 metachronous cases, the second tumor developed 2 to 13 years after the complete resection of the first tumor. In 4 synchronous cases, 2 separate neoplasms were identified in a surgical specimen. The metachronous presentation was more common in IPNB cases, whereas the synchronous development was more frequent in cholangiocarcinoma cases. The second tumors in 4 metachronous cases (4/5; 80%) and smaller lesions in all synchronous cases (4/4; 100%) were located in a lower part of the biliary. Immunophenotypes of cytokeratins and mucin core proteins were almost identical between the 2 lesions. Next-generation sequencing also confirmed that the 2 neoplasms shared gene mutations involving KRAS , GNAS , APC , BRAF , CTNNB1 , SMAD4 , TP53 , or ARID1A in all cases. In conclusion, multiple biliary tumors without underlying chronic biliary disease are most likely due to intraductal implantation of a single neoplasm. Thick mucinous bile in IPNB and increasing use of trans-ampullary biliary interventions may contribute to this unique form of tumor extension.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1464-1471"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifocal Papillary Thyroid Carcinomas With Discordant Molecular Drivers: Emphasizing the Morphology and Collision Tumors.","authors":"Jonathan P Rivera, Yi-Chen Yeh, Paul Chih-Hsueh Chen, Jen-Fan Hang","doi":"10.1097/PAS.0000000000002256","DOIUrl":"10.1097/PAS.0000000000002256","url":null,"abstract":"<p><p>Multifocal papillary thyroid carcinomas (PTCs) are common and the majority of the tumors harbor mutual BRAF p.V600E mutation. This study aimed to investigate a contemporary series of multifocal PTCs with discordant molecular drivers. Consecutive thyroidectomies diagnosed with multifocal PTCs ≥0.5 cm between 2019 and 2023 were reviewed. Immunohistochemistry (IHC) for BRAF VE1 was performed for all tumors. Cases with discordant BRAF IHC results or morphologic discrepancy were identified, and BRAF IHC-negative tumors were subjected to RAS Q61R IHC and/or targeted RNA next-generation sequencing. A total of 770 patients with a main PTC ≥0.5 cm were identified; 255 (33.1%) had multifocal disease, and 142 (18.4%) had at least another PTC ≥0.5 cm. Among them, 13 cases (9.2%, 13/142) had discordant molecular drivers. Twelve cases had one or more BRAF -positive PTCs accompanied by a BRAF -negative PTC (3 with CCDC6::RET fusion, 1 with NCOA4::RET fusion, 1 with ACBD5::RET fusion, 2 with ETV6::NTRK3 fusion, 1 with TG::FGFR1 fusion, 1 with LMTK2::BRAF fusion, 1 with AGK::BRAF fusion and RAS p.Q61R mutation, 1 with RAS p.Q61R mutation, and 1 without detectable molecular drivers). The last case had tumors with discordant fusion drivers ( VIM::NTRK3 and TNS1::BRAF ). Most cases showed tumors that were morphologically distinct (92.3%, 12/13) and occurred in the contralateral lobes (76.9%, 10/13). Notably, we identified 4 cases (30.8%) that presented as collision tumors and 6 cases (46.2%) that showed lymph node metastases, including 2 with simultaneous involvement by tumors with discordant molecular drivers, as novel findings. In summary, a subset (9.2%) of multifocal PTCs had discordant molecular drivers and 84.6% of them were a combination of BRAF -positive and kinase gene fusion-associated PTCs, most with distinct morphologies. Almost half of the cases had nodal metastasis and a third of them showed simultaneous involvement by tumors with discordant molecular drivers. The results highlight the clinical importance of identifying such cases, given the potentially different treatments.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1359-1371"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reporting of Incidental Thrombotic Arteriopathy in Lung Resection Specimens: Examination of Clinical Impact.","authors":"Andréanne Gagné, Robert F Padera, Rachel K Putman, Lynette M Sholl","doi":"10.1097/PAS.0000000000002292","DOIUrl":"10.1097/PAS.0000000000002292","url":null,"abstract":"<p><p>Pulmonary thrombotic arteriopathy (PTA) can be an incidental finding in lung resections performed for various indications. Historic studies largely examined PTA in autopsies. Thus, the prevalence in surgical samples, particularly in the modern era of lung cancer screening, is poorly defined. Detection of PTA in surgical samples may provide an opportunity for therapeutic intervention, but the impact of this finding on clinical management is unknown. We retrospectively examined consecutive lung surgical resections containing a report of incidental PTA between 2019 and 2022 in our institution. A retrospective chart review was performed to determine the history of systemic thromboembolism and clinical and radiographic follow-up. All slides were reviewed to morphologically characterize the vascular changes. Among 2930 pulmonary resections, 66 (2.3%) reportedly contained PTA. Twenty-four (36.4%) patients had a clinically recognized thromboembolic event either before or after surgical resection. Patients with clinically recognized thromboembolic disease were significantly more likely to have both acute and organized thrombi affecting large arteries. The presence of infarct, chronic hypertensive vasculopathy, or number of vessels with thrombi were not significantly associated with a clinically detected event. Reporting of incidental PTA led to clinical intervention in six patients and confirmed systemic thromboembolic disease in 2. Moreover, 2 patients with no further workup based on the incidental pathology findings subsequently developed pulmonary embolism. PTA is incidentally detected in 2.3% of surgical lung resections, and in two-thirds of cases, there is no clinical suspicion of thromboembolic disease. Pathologic reporting of PTA rarely led to clinical intervention, suggesting a need for improved communication of incidental pathology findings.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1448-1454"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological and Molecular Characteristics of Rare EBV-associated Diffuse Large B-cell Lymphoma With IRF4 Rearrangement.","authors":"Yuxiu Zhang, Anqi Li, Yimin Li, Binshen Ouyang, Xuan Wang, Lei Zhang, Haimin Xu, Yijin Gu, Xinyuan Lu, Lei Dong, Hongmei Yi, Chaofu Wang","doi":"10.1097/PAS.0000000000002301","DOIUrl":"10.1097/PAS.0000000000002301","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a rare form of aggressive B-cell lymphoma with limited molecular information reported regarding interferon regulatory factor 4 ( IRF4 ) status. Here, we presented 3 EBV-positive DLBCL cases with IRF4 rearrangement (EBV+DLBCL- IRF4 -R) verified by fluorescence in situ hybridization (FISH). Three patients, including 1 male and 2 females (median age: 64 y; range: 45 to 68 y), had normal immune function. During a median follow-up of 12 months (range: 0 to 24 mo), 2 patients succumbed to the disease, and 1 patient achieved complete response. Three tumors were present in the mediastinum, stomach, and thalamus, respectively. All three tumors exhibited DLBCL morphology and were identified as the non-germinal center B-cell subtype, with EBV-encoded small RNA positivity ranging from 70% to 80%. RNA sequencing was able to identify RHOH and IGH as fusion partners of IRF4 in two cases. No MYC and BCL2 rearrangements were detected in 3 cases by FISH and RNA sequencing. Next-generation sequencing revealed a low mutation burden, and only IRF4 was recurrently mutated in two EBV+DLBCL- IRF4 -R cases. Using the LymphGen 2.0 classifier, 1 case was classified as the MCD (including MYD88L265P and CD79B mutations) subtype. We report rare EBV+DLBCL- IRF4 -R that may enhance our understanding of the diverse spectrum of large B-cell lymphoma.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1341-1348"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}