Modern Pathology最新文献

{"title":"Proposing New Criteria for Classification of Benign Fibroepithelial Lesions Based on Clinicopathologic Evaluations of 507 Cases with Clinical Outcome","authors":"Thi Truc Anh Nguyen ,&nbsp;Jilun Zhang ,&nbsp;Jabed Iqbal ,&nbsp;Syed Salahuddin Ahmed ,&nbsp;Yi Liu ,&nbsp;Linlin Yang ,&nbsp;Gloria Zhang ,&nbsp;Bohan Ning ,&nbsp;Hua Guo ,&nbsp;Shi Wei ,&nbsp;Yanjun Hou ,&nbsp;Indu Agarwal ,&nbsp;Sayeeda Yasmeen ,&nbsp;Thaer Khoury ,&nbsp;Di Ai ,&nbsp;Huiyan Deng ,&nbsp;Yueping Liu ,&nbsp;Limin Peng ,&nbsp;Yunn-Yi Chen ,&nbsp;Kalliopi P. Siziopikou ,&nbsp;Xiaoxian Li","doi":"10.1016/j.modpat.2025.100812","DOIUrl":"10.1016/j.modpat.2025.100812","url":null,"abstract":"<div><div>Cellular fibroadenoma (cFA), benign phyllodes tumor (BePT), and borderline phyllodes tumor (BoPT) demonstrate overlapping clinicopathologic features. We evaluated 507 cases including 91 cFAs, 230 BePTs, and 186 BoPTs. The World Health Organization–recommended morphologic criteria were used to classify cFA and BePT. BoPT was diagnosed when a tumor presented at least 1 of the 5 morphologic features (permeative border, markedly increased stromal cellularity, marked stromal atypia, ≥5 mitoses/10 high-power fields, and the presence of stromal overgrowth) but did not meet our recently proposed refined diagnostic criteria for malignant phyllodes tumor. The median follow-up time was 79 months. Overall, 23 (4.5%) of the 507 cases developed recurrence. None had distant metastasis or recurred as malignant phyllodes tumor. The recurrence rates were 7.7%, 2.2%, and 5.9% in cFA, BePT, and BoPT, respectively. Of the 507 cases, younger age, larger tumor size, the presence of myxoid stroma, and stromal overgrowth were significantly associated with higher recurrence rate in univariate analysis (all <em>P</em> &lt; .05); in multivariate analysis, younger age (years) and larger tumor size were significantly associated with recurrence, whereas the other 2 variables were marginally associated with recurrence. Tumors &gt; 6.5 cm had a recurrence rate of 13.5% vs 3.5% in tumors ≤ 6.5 cm; tumors with stromal overgrowth had a recurrence rate of 15% vs 4.1% in tumors without stromal overgrowth. In cFA, being of Hispanic race and the presence of myxoid stroma were significantly associated with recurrence; in BePT, increased number of leaf-like structure and the presence of myxoid stroma were significantly associated with recurrence; and in BoPT, younger age (years) and large tumor size were significantly associated with recurrence. Surgical margin status (positive vs negative) was not associated with recurrence in cFAs, BePTs, or BoPTs. The recurrence rate in benign fibroepithelial lesions was low. No metastasis or recurrence as malignant phyllodes tumor was observed. Surgical margin status was not associated with recurrence rate. These results indicate that the current classification does not correlate with clinical outcomes. We propose to use tumor size of 6.5 cm and/or the presence of stromal overgrowth as the diagnostic criteria to classify these lesions as benign and borderline fibroepithelial lesions because they best correlate with clinical outcome. The significance of myxoid stroma warrants further investigation.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 10","pages":"Article 100812"},"PeriodicalIF":7.1,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294105","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":"Contemporary Approach to the Diagnosis and Classification of Myelodysplastic Neoplasms/Syndromes: Authors’ Response to “Concerns and Issues”","authors":"Fnu Aakash ,&nbsp;Sanam Loghavi","doi":"10.1016/j.modpat.2025.100795","DOIUrl":"10.1016/j.modpat.2025.100795","url":null,"abstract":"","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 7","pages":"Article 100795"},"PeriodicalIF":7.1,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144262185","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 Features of Untreated Colorectal Cancer with Acellular Mucin–Only Lymph Nodes","authors":"Wenyi Luo ,&nbsp;Shaomin Hu ,&nbsp;Irene Rana Riahi ,&nbsp;Hanlin L. Wang ,&nbsp;Nuha Shaker ,&nbsp;Ibrahim Abukhiran ,&nbsp;Tiffany Wang ,&nbsp;Alexandros D. Polydorides ,&nbsp;Adeyinka Akinsanya ,&nbsp;Iván A. González ,&nbsp;Catherine Hagen ,&nbsp;Rondell P. Graham ,&nbsp;Mikhail Lisovsky ,&nbsp;Teri A. Longacre ,&nbsp;Bindu Challa ,&nbsp;Wei Chen ,&nbsp;Daniel Harter ,&nbsp;Cameron Beech ,&nbsp;Mehran Najibi ,&nbsp;Wenqing Cao ,&nbsp;Xuchen Zhang","doi":"10.1016/j.modpat.2025.100811","DOIUrl":"10.1016/j.modpat.2025.100811","url":null,"abstract":"<div><div>Lymph nodes (LNs) containing only acellular mucin are considered negative for metastasis in treated colorectal cancers (CRCs). However, no data exist on how to stage these LNs in untreated CRCs. We collected 63 untreated CRC cases with LNs containing only acellular mucin from 27 US institutions and 23 additional cases from the Dutch Nationwide Pathology Databank. The practice patterns of pathologists in handling such cases, as well as the clinicopathological features of these cases, were analyzed. The survival of the study group was compared with 2 control groups: 102 pN0 and 76 pN1 untreated CRC cases. US and Dutch pathologists demonstrated similar practice patterns in assigning the pN stage and in the use of additional studies. Tumors in the study group were more likely to be located in the right colon, exhibit mucinous features, and be mismatch repair deficient compared with tumors in the pN0 and pN1 control groups. Compared with the pN1 control group, the study group showed significantly lower frequencies of lymphovascular invasion, local recurrence, and distant metastasis. No patient in the study group died of CRC, similar to the pN0 group. In contrast, the pN1 group had a significantly higher risk of CRC-related death. These findings suggest that LNs containing only acellular mucin in untreated CRCs should be interpreted as negative and staged as pN0, in line with current practice in neoadjuvant-treated CRCs.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 10","pages":"Article 100811"},"PeriodicalIF":7.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294096","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":"Deciphering Pseudoendocrine Sarcoma: A Clinicopathological, Molecular, and Epigenetic Study Suggesting Biological Links With Solid Pseudopapillary Neoplasm of the Pancreas","authors":"Juan Fernández-Pérez ,&nbsp;Isabelle Pommepuy ,&nbsp;Michael Michal ,&nbsp;Michal Michal ,&nbsp;Arjen H.G. Cleven ,&nbsp;Corinne Bouvier ,&nbsp;Anne Gomez-Brouchet ,&nbsp;Noelle Weingertner ,&nbsp;David J. Papke ,&nbsp;Vickie Y. Jo ,&nbsp;Jeremy Garcia ,&nbsp;Abbas Agaimy ,&nbsp;Rihab Azmani ,&nbsp;Aurelien Bourdon ,&nbsp;Isabelle Hostein ,&nbsp;Isabelle Soubeyran ,&nbsp;Melissa Alame ,&nbsp;Valérie Velasco ,&nbsp;Jean-Michel Coindre ,&nbsp;François Le Loarer ,&nbsp;Raul Ezequiel Perret","doi":"10.1016/j.modpat.2025.100810","DOIUrl":"10.1016/j.modpat.2025.100810","url":null,"abstract":"<div><div>Pseudoendocrine sarcoma (PS) is a recently described neoplasm of uncertain differentiation, characterized by recurrent <em>CTNNB1</em> mutations, frequent paravertebral location, and a neuroendocrine-like histomorphology. In this study, we report the clinicopathologic, immunohistochemical, transcriptomic, and epigenetic findings of 12 PS cases. The tumors affected 7 men and 5 women with a median age of 66 years and were located in the paraspinal/paravertebral region (n = 11) and the thigh (n = 1). Median tumor size was 82 mm (range, 32-170 mm). Histologically, the tumors comprised sheets and nests of epithelioid-to-ovoid cells with uniform nuclei and speckled chromatin, frequently associated with extracellular hyaline globules and fibrovascular cords/septa. Uncommon findings included microcalcifications, myxoid stroma, pseudopapillary, pseudoglandular, microcystic or corded architecture, and lumen and rosette-like structures. Necrosis was absent, and mitotic activity was low. On immunohistochemistry, the tumors showed aberrant nuclear staining for beta-catenin (8/8) and expression of CD56 (7/7), S100 (8/8), desmin (2/6), and androgen receptor (1/4). Pankeratin (AE1/AE3), progesterone receptor, synaptophysin, chromogranin, and INSM1 were negative. All tested cases harbored <em>CTNNB1</em> mutations. Using a customized cohort, methylation profiling revealed that PS formed a common cluster with solid pseudopapillary neoplasm of the pancreas (SPNP), distinct from all methylation classes from the Heidelberg sarcoma classifier and a subset of paragangliomas. Transcriptomic analysis showed that PS formed an independent cluster from a control group of tumors (including SPNP). Differential gene expression analysis showed enrichment in genes of the Wnt signaling pathway (HALLMARK gene sets) and biological processes related to sensory perception, among others (gene ontology - biological process [GO-BP]). Additionally, upregulated genes were related to various fetal cell types from the cell type signature data set (MSigDB), particularly of neuronal and epithelial lineage. Immunohistochemical assessment of potential markers identified through gene expression analysis revealed focal-to-diffuse expression of GLUT1 (6/6) and focal/multifocal expression of Brachyury (4/9) and HuD (3/7). Follow-up information, available for 10 cases (median duration of 18 months; range, 7-69 months), showed local recurrences and metastatic spread in 2 patients each. Evidence of response to radiotherapy was documented in one tumor. Altogether, this study expands knowledge on PS and suggests biological links with SPNP, including a potential shared cell of origin.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 10","pages":"Article 100810"},"PeriodicalIF":7.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294097","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":"Prognostic Value of an Integrated Human Papillomavirus and Immunoscore Model to Predict Survival in Vulva Squamous Cell Carcinoma","authors":"Rammah Elnour ,&nbsp;Ingjerd Helstrup Hindenes ,&nbsp;Malene Færevaag ,&nbsp;Ingrid Benedicte Moss Kolseth ,&nbsp;Liv Cecilie Vestrheim Thomsen ,&nbsp;Anne Christine Johannessen ,&nbsp;Daniela Elena Costea ,&nbsp;Line Bjørge ,&nbsp;Harsh Nitin Dongre","doi":"10.1016/j.modpat.2025.100809","DOIUrl":"10.1016/j.modpat.2025.100809","url":null,"abstract":"<div><div>Although the prognostic value of immune-related biomarkers is well characterized in many solid tumors, their significance in vulva squamous cell carcinoma (VSCC) remains unclear. In this study, we report a comprehensive analysis of programmed death ligand protein 1 (PD-L1) and immune cell infiltration in VSCC and establish immunoscore models for classification of the disease. Tissue microarrays, immunohistochemistry, and digital quantification were used to investigate the number of CD4+, CD8+, CD68+, CD14+, FoxP3+, and PD-L1+ cells in epithelial and stromal compartments of VSCC (<em>n</em> = 117). Immunoscores were developed using these parameters and applying the least absolute shrinkage and selection operator to identify predictors of survival. Immunoscores were then integrated with human papillomavirus (HPV) status, as determined using messenger RNA in situ hybridization, to construct internally validated nomograms. The prognostic models were subsequently applied in whole tissue sections (<em>n</em> = 25) to investigate agreement. Advanced VSCC (International Federation of Gynecology and Obstetrics stage III/IV) was characterized by high densities of CD68+ macrophages and PD-L1+ cells (Spearman correlation, ρ = 0.80) in the epithelium. PD-L1 status independently predicted poor progression-free survival (PFS) (hazard ratio = 1.828; 95% CI, 1.039-3.215; <em>P</em> = .036). Immunoscore^PFS and immunoscore^DSS were developed and found to be independent prognosticators of PFS (<em>P</em> = .003) and disease-specific survival (DSS) (<em>P</em> = .007), respectively. Integrating immunoscores with HPV status (IS-HPV index) improved model performance. The concordance index of IS-HPV index^PFS was 0.750 for prediction of PFS compared with 0.666 for HPV status and 0.667 for immunoscore^PFS. The concordance index of IS-HPV index^DSS was 0.752 for predicting DSS compared with 0.631 for HPV status and 0.715 for immunoscore^DSS. Strong agreement (phi coefficient [ϕ] = 0.76-0.8) was observed when the IS-HPV index models developed using tissue microarrays were applied to whole tissue sections. In summary, an index based on HPV status and an immunoscore built on PD-L1 expression and immune cell infiltrates could potentially serve as prognostic tools to refine risk stratification in VSCC. Further validation is warranted to demonstrate clinical use.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 10","pages":"Article 100809"},"PeriodicalIF":7.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285501","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":"Beyond Hybrid Morphology: A Large Series of Fusion-Driven Benign Peripheral Nerve Sheath Tumors Including 5 Tumors With Novel Fusions","authors":"Carina A. Dehner ,&nbsp;Tania Platero-Portillo ,&nbsp;George Jour ,&nbsp;Carla Saoud ,&nbsp;Yanming Zhang ,&nbsp;Darya Buehler ,&nbsp;Meera Hameed ,&nbsp;Michael Michal ,&nbsp;Darcy Kerr ,&nbsp;Klaus J. Busam ,&nbsp;Abbas Agaimy ,&nbsp;Jorge Torres-Mora ,&nbsp;Cristina R. Antonescu ,&nbsp;Konstantinos Linos","doi":"10.1016/j.modpat.2025.100806","DOIUrl":"10.1016/j.modpat.2025.100806","url":null,"abstract":"<div><div>Benign peripheral nerve sheath tumors (PNSTs) represent a heterogeneous group of neoplasms with varying histologic and molecular characteristics. Although traditional classifications categorize these tumors based on predominant cell types, recent advances in molecular pathology have revealed the presence of hybrid tumors featuring elements from at least 2 nerve sheath tumors (hybrid peripheral nerve sheath tumor [hPNST]). We herein studied 20 cases of hPNST involving 15 female and 5 male patients (median age, 29.5 years; range, 3 weeks-71 years). Tumors occurred on the upper extremity (6), scalp (3), trunk (3), face (3), lower extremity (2), right lateral neck (1), nasal sinus (1), and retroperitoneum (1). Follow-up information was available in 9 of 20 cases (45%; median, 10 months; range, 2 weeks-144 months) and documented local recurrence in 2 of 9 patients (22%) at 10 and 144 months after incomplete excision. Next-generation sequencing demonstrated vestigial-like family member 3 (<em>VGLL3</em>) fusions in 14 cases, fused with <em>CHD7</em> (10 tumors), <em>CHD9</em> (3 tumors), and <em>MAMLD1</em> (1 tumor), an alternative <em>TEAD1::NCOA2</em> (1 tumor) fusion and several novel fusions including <em>TOX::TEAD1</em> (2 tumors), <em>RREB1::LPP</em> (1 tumor), <em>SRF::MYOCD</em> (1 tumor), and <em>KANK1::CDK5RAP2</em> (1 tumor). Most tumors with <em>VGLL3</em> fusions showed morphologically and immunophenotypically classic features of hybrid schwannoma-perineurioma, whereas rare cases showed unusual microscopic features, such as prominent myxoid stroma, pseudolipoblasts, prominent Schwannian nodules, or solely schwannomatous morphology. The <em>RREB1::LPP</em>-driven tumor showed features of hybrid schwannoma-neurofibroma. Lastly, 1 tumor with a novel <em>SRF::MYOCD</em> fusion displayed morphologic features reminiscent of desmoplastic melanoma although exhibiting a combined neural and smooth muscle phenotype. Our data expand on the morphologic and molecular spectrum of fusion-driven hPNSTs, including 5 previously undescribed fusions, and further expand on noncentral nervous system schwannomas with <em>VGLL3</em> fusions.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 10","pages":"Article 100806"},"PeriodicalIF":7.1,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248771","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":"The Spectrum of Placental Findings of First-Trimester Cytomegalovirus Infection Related to the Presence of Symptoms in the Newborns and Stillbirths","authors":"Eva Manuela Pena-Burgos ,&nbsp;Rita María Regojo-Zapata ,&nbsp;Ángela Caballero-Ferrero ,&nbsp;Cristina Martínez-Payo ,&nbsp;María del Carmen Viñuela-Benéitez ,&nbsp;Dolores Montero ,&nbsp;María De La Calle","doi":"10.1016/j.modpat.2025.100808","DOIUrl":"10.1016/j.modpat.2025.100808","url":null,"abstract":"<div><div>Cytomegalovirus (CMV) is one of the most common congenital infections worldwide and a leading cause of prenatal neurological disorders, sensorineural hearing loss, and stillbirth. The placental factors involved in CMV transmission from mother to fetus remain poorly understood. We aimed to evaluate the histopathological placental findings associated with first-trimester CMV infection in relation to stillbirth and symptomatic presentation in newborns. This retrospective case-control study analyzed pregnancies with confirmed first-trimester CMV infection followed at 2 tertiary referral hospitals between 2012 and 2024. Symptomatic newborns were compared with asymptomatic newborns and stillbirths. Univariate statistical analyses were performed. A total of 40 placentas were included: 23 from asymptomatic newborns, 11 from symptomatic newborns, and 6 from stillbirths. Compared with asymptomatic cases, placentas from symptomatic newborns were smaller and showed increased chronic plasma cell deciduitis, chronic villitis (without avascular villi, breakdown villi, necrosis, or hemosiderin deposits), more CMV inclusions in fibroblasts, and higher rates of positive CMV immunostaining. Stillbirth placentas exhibited more severe chronic villitis (with avascular villi, breakdown villi, necrosis, and hemosiderin deposits), more extensive intervillous fibrin deposition, CMV inclusions in endothelial and trophoblastic cells, and higher frequencies of maternal and fetal vascular malperfusion compared with placentas from symptomatic newborns. Ultrasound screening did not appear to be a reliable predictor of placental involvement in first-trimester CMV infection. Greater involvement of the villous and vascular barriers—both direct and indirect—was associated with more severe fetal outcomes, likely facilitating viral transmission to the fetus. Adjunctive treatments aimed at reducing villous and vascular damage may help prevent symptomatic infection and stillbirth in first-trimester CMV cases.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 9","pages":"Article 100808"},"PeriodicalIF":7.1,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248773","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":"Phenotypic and Molecular Features of Somatically Derived “Yolk Sac Tumors”: Similarities and Differences With Counterparts of Germ Cell Origin","authors":"João Lobo ,&nbsp;Nuno Tiago Tavares ,&nbsp;Fernanda Fernandes-Pontes ,&nbsp;Diana Fonseca ,&nbsp;Carmen Jerónimo ,&nbsp;Rui Henrique ,&nbsp;Costantino Ricci ,&nbsp;Antonio de Leo ,&nbsp;Katrina Collins ,&nbsp;Muhammad T. Idrees ,&nbsp;Thomas M. Ulbright ,&nbsp;Sounak Gupta ,&nbsp;Andres M. Acosta","doi":"10.1016/j.modpat.2025.100807","DOIUrl":"10.1016/j.modpat.2025.100807","url":null,"abstract":"<div><div>A subset of somatic carcinomas shows morphologic and immunophenotypic similarities to yolk sac tumor (YST) of germ cell origin, including fetal adenocarcinomas of the lung and somatic carcinomas with “YST”/enteroblastic differentiation. At least some of these tumors may result from reprogramming somatic cancer cells, leading to the acquisition of a “pluripotent” phenotype. Although these somatic tumors express markers such as SALL4, glypican 3, and alpha-fetoprotein, which are positive in germ cell-derived YST, it is currently uncertain to what degree their molecular features overlap with those of germ cell tumors (GCTs). We assessed i(12p) (fluorescence in situ hybridization) and levels of micro-RNA-371-373 (real-time PCR), hallmarks of germ cell neoplasia in situ (GCNIS)-derived GCTs, in a cohort of 11 somatically derived neoplasms with YST/enteroblastic phenotype (designated as “YST-like” tumors hereafter). In addition, we used immunohistochemistry to assess expression of FOXA2, a critical regulator of induction and maintenance of YST phenotype in GCTs. All YST-like tumors showed expression of FOXA2 and were negative for i(12p). Expression of miR-371a-3p (the most specific member of the miR-371-373 cluster) was detectable in 6 of 10 (60%) of YST-like tumors. Four samples showed levels in the gray zone of detection (ie, expression of uncertain clinical significance), and 2 samples (separate tumors from a single patient) showed positive levels similar to those found in nonteratoma GCNIS-derived GCTs. The remaining members of the micro-RNA cluster (miRs 372 and 373) followed the same patterns. Our results show that the overlap of somatically derived YST-like tumors and YSTs of germ cell origin goes beyond morphology, including expression of one of the master regulators of the YST phenotype and, in some cases, miR-371a-3p. However, these neoplasms lack a hallmark finding of GCNIS-derived GCTs (i[12p]) and show significant biologic and clinical differences with GCTs.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 9","pages":"Article 100807"},"PeriodicalIF":7.1,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248772","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":"Observer Variation in the Diagnosis of Testicular Sex Cord-Stromal Tumors by a Genitourinary Pathology Society and International Society of Urological Pathology Panel: Paving the Way for a New Classification","authors":"Daniel M. Berney ,&nbsp;Maurizio Colecchia ,&nbsp;Eva Comperat ,&nbsp;Kristine M. Cornejo ,&nbsp;Anthony J. Gill ,&nbsp;Sounak Gupta ,&nbsp;John C. Cheville ,&nbsp;Muhammad T. Idrees ,&nbsp;Chia-Sui Kao ,&nbsp;Fiona Maclean ,&nbsp;Andres Matoso ,&nbsp;Kvetoslava Michalova ,&nbsp;Maria Rosaria Raspollini ,&nbsp;Miguel Reyes Múgica ,&nbsp;Satish K. Tickoo ,&nbsp;Toyonori Tsuzuki ,&nbsp;Thomas M. Ulbright ,&nbsp;Sean R. Williamson ,&nbsp;Stephanie Siegmund ,&nbsp;Lynette M. Sholl ,&nbsp;Andres M. Acosta","doi":"10.1016/j.modpat.2025.100804","DOIUrl":"10.1016/j.modpat.2025.100804","url":null,"abstract":"<div><div>The diagnosis of sex cord-stromal tumors is challenging. They show a wide spectrum of behaviors and associations with clinically important pathogenic germline variants. In view of recent advances in molecular subtyping and risk factors, we wished to investigate the differences in diagnosis for a range of these tumors using expert genitourinary pathologists with an interest in this area. Forty-four tumors were selected, and 18 pathologists (members of TEsticular Sex cord-Stromal Tumor group) were invited to view the cases online and give a diagnosis. Consensus was taken as 70% agreement. Consensus was achieved in 59% (26/44) cases. However, there were many areas of disagreement, which included variability in the diagnosis of Sertoli cell and Leydig cell tumors, particularly in malignant lesions, and difficulty in the assignation of fibrothecomas or myoid gonadal stromal tumors, as well as variability in the diagnosis of granulosa cell tumors and in the diagnosis of rarer pediatric tumors. Pathologists placed different weights on positivity with some markers, particularly beta-catenin, S100, and SMA. Some pathologists diagnosed novel diagnostic entities, such as inflammatory and nested testicular sex cord tumors, not currently in the World Health Organization classification. Recommendations to assist in the construction of a new classification to achieve more concordance and better treatment of these rare tumors are included.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 9","pages":"Article 100804"},"PeriodicalIF":7.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234547","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":"Colorectal Liver Metastasis Pathomics Model: Integrating Single-Cell and Spatial Transcriptome Analysis With Pathomics for Predicting Liver Metastasis in Colorectal Cancer","authors":"Tianyu Zeng ,&nbsp;Yang Wang ,&nbsp;Bo Tang ,&nbsp;Haipeng Cui ,&nbsp;Deqin Tang ,&nbsp;Hong Ding ,&nbsp;Yutong Zhang ,&nbsp;Peiling Cai ,&nbsp;Yamei Luo ,&nbsp;Hao Lin ,&nbsp;Qingxi Guo ,&nbsp;Hua Tang","doi":"10.1016/j.modpat.2025.100805","DOIUrl":"10.1016/j.modpat.2025.100805","url":null,"abstract":"<div><div>The liver is the primary target organ for hematologic metastasis of colorectal cancer (CRC), and CRC liver metastasis (CRLM) often precludes radical resection, making it the leading cause of death in patients with CRC. To improve the identification and prediction of liver metastasis risk, we identified a cell type of liver metastasis--triggering malignant cells (LMTMCs) through integrating single-cell RNA sequencing and spatial transcriptome analysis. Multiomics cell communication analysis indicated that the interaction between fibroblasts and LMTMCs through the COL1A1-CD44/SDC4 and LAMA4-CD44 signaling axes could promote CRLM. By applying the one-class logistic regression algorithm, we developed a CRLM scoring system in the bulk RNA-sequencing data according to the abundance of LMTMCs in each individual. Using the grouping labels derived from the CRLM scoring system in the bulk data and the corresponding whole-slide images without any manual annotations at the region or pixel level, processed via slide-level weakly supervised learning, a deep-learning model based on the ResNet18 architecture, called Colorectal Liver Metastasis Pathomics Model, was developed to predict the risk of liver metastasis in patients with CRC. The Colorectal Liver Metastasis Pathomics Model achieved an area under the curve of 0.84 at the internal test set of The Cancer Genome Atlas-CRC histology images. In the external independent validation sets, namely the Affiliated Hospital of Southwest Medical University and the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University cohorts, the areas under the curve were 0.89 and 0.72, respectively, indicating effective classification performances. This study provided new insights and tools for the early identification of CRLM and demonstrated the potential of combining multiomics with deep learning–based pathomics in cancer research.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 9","pages":"Article 100805"},"PeriodicalIF":7.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234546","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}