American Journal of Surgical Pathology最新文献

{"title":"High FCGR2B Expression Can Identify Low-tumor-burden Follicular Lymphoma Patients Who Do Not Require Any Antilymphoma Therapy for a Long Term.","authors":"Shotaro Watanabe, Hiroki Kato, Tohru Fujiwara, Shunsuke Hatta, Yasuo Tomiya, Koichi Onodera, Satoshi Ichikawa, Yasushi Onishi, Hisayuki Yokoyama, Fumiyoshi Fujishima, Ryo Ichinohasama, Hideo Harigae, Noriko Fukuhara","doi":"10.1097/PAS.0000000000002397","DOIUrl":"10.1097/PAS.0000000000002397","url":null,"abstract":"<p><p>Spontaneous regression or a long-term lack of obvious progression is often observed in patients with low-tumor-burden (LTB) follicular lymphoma (FL). However, conventional prognostic risk models are unable to precisely identify the patients who will not require any antilymphoma treatment for a long term, especially at diagnosis. In this study, we identified genes whose expression levels were associated with the clinical outcome of LTB FL and verified their prognostic value using immunohistochemistry. Because the tumor microenvironment may influence FL pathogenesis, we used digital expression profiling to quantify the expression of 730 immune-related genes extracted from tumor tissue specimens collected from 55 untreated patients with LTB FL. Five genes were identified as potential transcriptomic predictive markers. Among these, FCGR2B , an inhibitory FC gamma receptor, was immunohistochemically stainable and identified as a reliable immunohistochemical prognostic marker mainly expressed in tumor cells but not in the surrounding reactive cells. Our findings could help identify patients with LTB FL who do not require any antilymphoma treatment for the long term.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"740-747"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794456","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":"NTRK Fusions in Xanthogranuloma, a Clinicopathologic and Molecular Analysis of 23 Cases.","authors":"Brandon Umphress, Aofei Li, Matthew Kuhar, Rachel Kowal, Ahmed K Alomari, LeeAnn Baldridge, Anthony J Ross, Simon J Warren","doi":"10.1097/PAS.0000000000002394","DOIUrl":"10.1097/PAS.0000000000002394","url":null,"abstract":"<p><p>Xanthogranuloma is the most common category of histiocytic neoplasia, with a range of clinical behaviors from solitary cutaneous lesions to multiple cutaneous lesions and less frequent cases with evolution to disseminated disease. Solitary lesions make up 78% to 81% of total cases. We encountered 2 consecutive index patients with solitary cutaneous xanthogranuloma with NTRK overexpression by immunostaining and confirmed the presence of an NTRK1 fusion with both RNA and DNA sequencing. We screened 55 additional patients by pan-TRK immunostain, and found that 26 of 48 (54%) with solitary xanthogranulomas had TRK overexpression, whereas 0 of 7 (0%) multifocal or disseminated xanthogranulomas had TRK overexpression. We sequenced a subset of 23 patients with solitary xanthogranuloma. In all 16 patients with a positive pan-TRK immunostain, we confirmed the presence of an NTRK1 fusion using RNA and DNA sequencing. In all 7 patients that were negative by immunostain we identified no NTRK fusion by sequencing. All patients with a fusion identified by sequencing had overexpression of the NTRK1 RNA transcript relative to wild-type tumors with a mean 58-fold increase over wild-type tumors ( P =8.77e-15). Further, all cases with fusions had a loss of the extracellular portion of NTRK1 , and fusion partners were limited to TPM3, PRDX1, IRF2BP2, LRRIP1 , and SQSTM1 . DNA sequencing identified additional recurrent loss of function mutations in DNA methylation genes DNMT3A, KDM5D , and SETD2, as well as the MTOR-PI3K pathway gene FLCN . Recurrent copy number gains were detected in MTOR-PI3K pathway genes PIK3CG , IL10Ra , as well as transcriptional regulator PAX8 . The frequency of NTRK1 fusions appears markedly higher in solitary compared with multifocal and disseminated xanthogranuloma (54% vs. 0%). The reduced proportion of NTRK1 fusions in disseminated cases relative to solitary cases suggests that NTRK1 fusions are less efficient than MAP kinase pathway point mutations at driving tumor evolution towards disseminated disease. As NTRK1 fusions are uncommon in other histiocytoses, pan-TRK immunostain may have utility to confirm the diagnosis of xanthogranuloma in a histiocytic lineage tumor and to screen for low-risk xanthogranuloma.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"639-645"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750687","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":"Commentary: Insights From H3-Wild-Type Diffuse Midline Glioma With EZHIP Overexpression.","authors":"Linmao Zheng, Ni Chen","doi":"10.1097/PAS.0000000000002422","DOIUrl":"10.1097/PAS.0000000000002422","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"750-751"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101320","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":"A Clinical, Morphologic, and Molecular Comparison of Bonafide Spitz Melanomas and Atypical Spitz Tumors in the Pediatric Population.","authors":"Haya Mary Beydoun, Julia Edwin Jeyakumar, Afua Addo, Shantel Olivares, Lili Zhao, Yangruijue Ma, Jennifer Ko, Armita Bahrami, Scott Florell, Larissa V Furtado, Klaus Busam, Pedram Gerami","doi":"10.1097/PAS.0000000000002381","DOIUrl":"10.1097/PAS.0000000000002381","url":null,"abstract":"<p><p>Pediatric Spitz melanoma (SM) with bonafide metastatic disease is rare. In this study, we assembled the largest cohort to date of pediatric SM with a verified Spitz-associated genomic driver and clinical follow-up demonstrating bonafide metastasis. We compared the clinical, morphologic, and molecular features of these SMs to a control cohort of 57 pediatric atypical Spitz tumors (ASTs). Pediatric SM patients were significantly older than AST patients (12 vs 8 years of age). While not statistically significant, SMs were more likely to be heavily pigmented (5/7 SMs vs 11/57 ASTs), to have a sheet-like growth pattern (3/7 SMs vs 8/57 ASTs), and have severe nuclear atypia (6/7 SMs vs 20/57 ASTs). SMs had significantly greater mitotic activity (avg of 4.3/mm 2 in SMs and 2.7/mm 2 in ASTs, P =0.008) and more frequent larger cell size ( P =0.006). However, none of these features were specific and could also be seen in ASTs. The presence of homozygous deletions of 9p21 in conjunction with TERT promoter hot spot mutations or PTEN deletions (n=2), as well as MYC overexpression or amplification (n=2) were only seen in the SMs and none of the ASTs. These findings were mutually exclusive in the SM group and mutually exclusive with the presence of complex chromosomal copy number aberrations, which were seen in the remaining 3 pediatric SMs. This study demonstrates that there are multiple pathways to malignancy for pediatric SMs and none of our commonly used biomarkers have a particularly high sensitivity. Hence, the optimal distinction of pediatric SM from ASTs will continue to require the integration of clinical, histologic, and molecular data.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"663-673"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603595","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":"Clinicopathologic and Molecular Analysis of Malignant Neoplasms With Yolk Sac Tumor Differentiation in Women 40 Years of Age and Older.","authors":"Tricia A Numan, Brigitte M Ronnett, Lisa Haley, Aparna Pallavajjala, Jaclyn B Murry, Jaden Kohn, Phillip M Galbo, Russell Vang, Fausto J Rodriguez, Harsimar Kaur, Kimberly Levinson, Jeffrey Lin, Doreen N Palsgrove","doi":"10.1097/PAS.0000000000002389","DOIUrl":"10.1097/PAS.0000000000002389","url":null,"abstract":"<p><p>Gynecologic yolk sac tumors (YSTs) are more commonly encountered in children and young women as pure or mixed germ cell tumors and are rarely observed in older women. YSTs in older women are sometimes accompanied by a Müllerian-type carcinoma component, indicating a likely somatic rather than germ-cell origin. Studies of YSTs of germ cell and somatic types in this age group are limited. Analysis of additional pure and mixed tumors with YST differentiation could elucidate differences between these tumor subtypes and the relationship between components in mixed tumors. Clinicopathologic features of 32 malignant neoplasms with YST differentiation in women aged 40+ were analyzed. There were 11 pure YSTs, 7 mixed germ cell tumors, and 14 YSTs with a malignant non-germ cell tumor component (somatically derived yolk sac tumor [SDYST]). Targeted next-generation sequencing (NGS) was performed in 4/11 pure YSTs, 0/7 mixed germ cell tumors, and 4/14 SDYSTs. For the pure YSTs, alterations in DICER1 (1/4), PIK3R1 and PTPRT (1/4), PMS1 (1/4) , and TP53 (2/4) were identified. One other pure YST had alterations in PTEN , ARID1A , ARID1B , FGFR2 , and CTNNB1 (alterations common in endometrioid carcinoma). SDYSTs demonstrated shared alterations between both components including TP53 , KRAS , FBXW7, and KMT2C , suggesting a common origin. The findings in the pure YSTs in older women suggest that for some, the origin could be germ cell as they harbor similar alterations as those described in pure YSTs in young women, whereas in other \"pure\" YSTs, the molecular profile aligns with previously described SDYSTs, which suggests a SDYST with an unsampled Müllerian carcinoma component rather than a germ cell origin. In SDYSTs, shared alterations are consistent with prior studies and suggest a somatic rather than germ-cell origin.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"686-700"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810329","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":"International Society of Urological Pathology Consensus Meeting 2024: Working Group 2 Preneoplastic and Precursor Lesions of the Urinary Bladder.","authors":"Michelle R Downes, Antonio Lopez-Beltran, Roberto Contieri, Donna E Hansel, Gladell P Paner, Steven Shen, Bas W G van Rhijn, Hikmat Al-Ahmadie, Mahul B Amin, Matteo Brunelli, Eva Comperat, Michael S Cookson, Bishoy M Faltas, Charles C Guo, Arndt Hartmann, Ashish M Kamat, Laura S Mertens, Jeffrey S Ross, Theodorus H van der Kwast, Joshua Warrick, Glen Kristiansen, Liang Cheng, Maria R Raspollini","doi":"10.1097/PAS.0000000000002440","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002440","url":null,"abstract":"<p><p>Preneoplastic and precursor lesions are important to recognize and report, as they can influence clinical management decisions. The International Society of Urological Pathology (ISUP) organized a consensus meeting in Florence, Italy, in September 2024 focused on preneoplastic and precursor lesions of the genitourinary organs. Working group 2 was assigned the topic of bladder and a group of pathologists and clinicians was convened. They developed a 46 question premeeting survey for the ISUP membership assessing flat, papillary, squamous, and glandular entities and clinical issues to determine use of terminology, reporting practices, and areas that needed to be addressed at the consensus meeting. The premeeting survey results showed consistency in the terminology used by pathologists, similarities in reporting practices, and highlighted areas of uncertainty with respect to whether certain entities could be classified as precursors/preneoplastic. The results enabled the working group to conduct focused literature reviews and to develop a presentation and set of in-meeting polling questions to address the problematic topics from the survey results. Overall, 14/18 in-meeting polling questions achieved consensus. The surveys and in-person voting demonstrated a strong preference to use existing terminology such as dysplasia, verrucous squamous, and papillary hyperplasia, to grade glandular and squamous dysplasia and to judiciously use immunohistochemistry to classify lesions. Pathologists expressed highly variable opinions with respect to questions about quantification, management recommendations, and inclusion of newer entities as precursors/preneoplastic lesions.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537790","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":"Clinical Significance of Different Histology and High-Risk HPV Types in Neuroendocrine Carcinomas of the Cervix.","authors":"Seung Jun Lee, Seokhyun Lee, Ilias P Nikas, Misong Kim, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Jae-Weon Kim, Haeryoung Kim, Sumi Yun, Kyung-Ah Hwang, Se Ik Kim, Cheol Lee","doi":"10.1097/PAS.0000000000002391","DOIUrl":"10.1097/PAS.0000000000002391","url":null,"abstract":"<p><p>This study aimed to investigate the impact of different histologic and high-risk (HR) human papillomavirus (HPV) types on the clinicopathologic characteristics and survival of patients with neuroendocrine carcinoma of the cervix (NEC). We retrospectively reviewed the medical records of patients with NEC diagnosed and treated at the Seoul National University Hospital between January 2000 and December 2021. Two pathologists specializing in gynecologic oncology thoroughly examined the slides. To determine the type of HPV infection, microarray analysis and next-generation sequencing were conducted. In addition, the impact of several variables on progressoin-free survival (PFS) and overall survival (OS) was investigated. In total, 47 patients with NEC were included in this analysis. Small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC) were identified in 36 (76.6%) and 11 (23.4%) patients, respectively. Whereas 31 (66.0%) patients had a pure NEC, 16 (34.0%) were diagnosed with a mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN). Of the 32 NEC patients whose HPV infection status was confirmed, HR-HPV infection was found in 30 of them (93.8%). Nineteen patients were infected with HPV 18. Between patients infected with HPV 16 or 18 and HR-HPV other than 16 or 18, there was no significant difference in most clinicopathologic characteristics such as histology ( P =0.311). However, HR-HPV type other than 16 or 18 was associated with pelvic lymph node metastasis ( P =0.044) and advanced stage ( P =0.035). In the Kaplan-Meier analysis and the Cox regression analyses, no significant difference in PFS and OS was observed between LCNEC and SCNEC, pure NEC and MiNEN, and HPV 16 or 18 and HR-HPV other than 16 or 18. High-risk HPV infection, especially from HPV 18, might play a role and impact on NEC pathogenesis. In this study, we did not find evidence that diverse histology and HR-HPV types affect PFS and OS.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"701-710"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707962","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":"CDKN2A Chromogenic In Situ Hybridization for Separating Benign From Malignant Mesothelial Proliferations.","authors":"Andrew Churg, Tara Spence, Karina C Martin, Janine Senz, Stephen Yip, Julia R Naso","doi":"10.1097/PAS.0000000000002395","DOIUrl":"10.1097/PAS.0000000000002395","url":null,"abstract":"<p><p>CDKN2A FISH is a standard method for separating mesotheliomas from reactive mesothelial proliferations, but FISH requires specialized equipment and technical expertise for interpretation. Here, we show that a commercially available CDKN2A CISH probe provides equivalent information but can be easily scored using an ordinary light microscope and does not require specialized training.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"646-649"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750684","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":"Biphasic Myoepithelial Carcinoma With 5p/5q Loss: Morphomolecular Characterization and Provisional Designation of a Proposed Novel Salivary Tumor Entity.","authors":"Philipp Jurmeister, Maximilian Leitheiser, Linda Bergmayr, Emma Payá Capilla, Liliana H Mochmann, Yauheniya Zhdanovich, Fabian Engelhardt-Schott, Konstanze Schleich, Doreen Klingler, Edgar Chimal, Cornelia M Focke, Gerben E Breimer, Ilse van Engen van Grunsven, Andreas von Deimling, David Capper, Frederick Klauschen, Stephan Ihrler","doi":"10.1097/PAS.0000000000002450","DOIUrl":"10.1097/PAS.0000000000002450","url":null,"abstract":"<p><p>Salivary gland tumors are diagnostically challenging due to major diversity of benign and malignant tumors with enormous intra-tumorous and inter-tumorous heterogeneity and, hence, frequently overlapping histologic features. DNA methylation has greatly enhanced tumor classification in several organs and led to the identification of previously unrecognized entities. In a recent study on DNA methylation of salivary gland tumors, we had identified a group of unclassifiable tumors. In this study, we characterize this group through an integrated analysis of clinical, histomorphologic, immunohistochemical, and molecular features. This group of 12 tumors is characterized by small, clinically benign appearing tumors with striking female predominance (91.7%), the latter not paralleled in other salivary tumor types. In addition to distinct DNA methylation profiling, copy number analysis revealed unique alterations with highly recurrent chromosome 5p/5q loss and frequent amplification of the MDM2 locus on chromosome 12q. Whole-exome and transcriptome sequencing detected no recurrent mutations or fusions. The histomorphologic features were only moderately distinct, comprising an obligate, thereby variable admixture of biphasic-tubular and monophasic-myoepithelial areas, low or absent nuclear atypia, and minimal proliferation. Frequent invasive behavior, a solitary lymph node metastasis, and the molecular alterations, altogether, strongly support classification as a, presumably low-grade, carcinoma. Altogether, these findings clearly distinguish this tumor group from histomorphologically similar tumor entities, in particular myoepithelial carcinoma, epithelial-myoepithelial carcinoma, and adenoid cystic carcinoma. We present thorough arguments that this tumor group represents a distinct salivary carcinoma entity rather than a variant of an existing one. We propose the provisional designation \"Biphasic myoepithelial carcinoma with 5p/5q loss\" for discussion.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"890-900"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537789","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":"Insights From H3-Wildtype Diffuse Midline Glioma With EZHIP Overexpression.","authors":"Minjun Yan, Bo Wang, Bo Han, Zhuo Li, Xing Liu, Pinan Liu","doi":"10.1097/PAS.0000000000002388","DOIUrl":"10.1097/PAS.0000000000002388","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"748-750"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646797","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}