HistopathologyPub Date : 2025-10-02DOI: 10.1111/his.70017
Amy Llewellyn, Adam Brown, Juliet Morel, Kalnisha Naidoo
{"title":"To VAE or not to VAE: outcomes of radial scars/complex sclerosing lesions and papillary lesions without atypia in the King's College Hospital breast service (2017-2023).","authors":"Amy Llewellyn, Adam Brown, Juliet Morel, Kalnisha Naidoo","doi":"10.1111/his.70017","DOIUrl":"https://doi.org/10.1111/his.70017","url":null,"abstract":"<p><strong>Aims: </strong>Since there is currently limited data regarding the risk of malignancy that radial scars/complex sclerosing lesions (RS/CSL) or papillary lesions without atypia carry, we reviewed all such cases treated at King's College Hospital between January 2017 and June 2023 to determine the upgrade rates following immediate excision and longer follow-up.</p><p><strong>Methods and results: </strong>Patients were identified using electronic database searches. An 'upgrade' was defined as the presence of ductal carcinoma in situ (DCIS) or invasive breast carcinoma (IBC) on excision at the biopsy site. One hundred and two patients had RS/CSL (85% screen-detected; 15% symptomatic). Only one (1%) of the 90 patients who underwent excision was upgraded to DCIS; none to IBC. On longer follow-up, four patients (4%) developed ipsilateral DCIS/IBC, while one patient developed contralateral DCIS with microinvasion. Two hundred and twenty-six patients had papillary lesions without atypia (42% screen-detected; 58% symptomatic). Eight (4%) of the 179 patients who underwent excision were upgraded to DCIS; none to IBC. On longer follow-up, one patient developed ipsilateral DCIS; another patient developed contralateral IBC. For both lesions, radiological size was not significantly associated with atypia/upgrade (P > 0.05; Mann-Whitney U-test).</p><p><strong>Conclusion: </strong>Since RS/CSL without atypia carry a low upgrade risk (1%), these patients could avoid excision and be followed up with mammographic surveillance. However, further data are needed for this change in practice to be considered. Papillary lesions without atypia appear to be more heterogeneous in behaviour, carrying an upgrade risk of 4%. Current treatment guidelines should not change until we better understand the biology of these lesions.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"TRPS1 expression in neuroendocrine neoplasms of breast and other organs.","authors":"Qiqi Ye, Jeannelyn Estrella, Neda Kalhor, Audrey Liu, Cody Han, Hongxia Sun, Lavinia P Middleton, Hui Chen, Constance Albarracin, Aysegul Sahin, Yun Wu, Qingqing Ding","doi":"10.1111/his.70013","DOIUrl":"https://doi.org/10.1111/his.70013","url":null,"abstract":"<p><strong>Background: </strong>Primary neuroendocrine (NE) neoplasms of the breast are rare. In the absence of in situ carcinoma, metastasis from other organs needs to be ruled out first. TRPS1 is a recently identified marker for breast origin. In the current study, we investigated TRPS1 expression in breast neuroendocrine neoplasms, including well-differentiated neuroendocrine tumour (NET) and poorly differentiated neuroendocrine carcinoma (NEC), and compared its expression with neuroendocrine neoplasms from other organs, such as lung, gastrointestinal tract and pancreas.</p><p><strong>Methods and results: </strong>A total of 105 cases of NE neoplasms were included in our study cohort, including 56 from breast (39 NETs and 17 NECs), 18 from lung (12 typical and atypical carcinoids, and 6 NECs), 19 from gastrointestinal tract (10 NETs, 3 NECs, 6 NETs metastases to breast) and 12 from pancreas (9 NETs, 3 NECs). TRPS1 exhibited moderate to strong expression in 38 of 39 breast NETs (97.4%). Four of 17 (23.5%) breast NECs showed weak to moderate staining. By contrast, no TRPS1 staining was observed in any of the 18 lung and 12 pancreatic NE neoplasms. Among 19 gastrointestinal NE neoplasms, only 1 NEC displayed scattered low TRPS1 positivity.</p><p><strong>Conclusions: </strong>Our study demonstrated that TRPS1 is universally expressed in mammary NET, and it is a valuable marker to distinguish primary mammary NET from metastatic NET of other organs, including lung, gastrointestinal tract and pancreas. TRPS1 has limited utility in differentiating mammary NEC from NEC of other organs. Clinical radiographic correlation is paramount in diagnosing primary NEC of the breast.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2025-09-30DOI: 10.1111/his.70016
Azfar Neyaz, Dale Davis, David J Papke, Ivy John
{"title":"S100 expression in molecularly confirmed dermatofibrosarcoma protuberans, including fibrosarcomatous variants.","authors":"Azfar Neyaz, Dale Davis, David J Papke, Ivy John","doi":"10.1111/his.70016","DOIUrl":"https://doi.org/10.1111/his.70016","url":null,"abstract":"<p><strong>Aims: </strong>Dermatofibrosarcoma protuberans (DFSP) is a superficial, locally aggressive spindle cell neoplasm, characterised by diffuse CD34 expression and the presence of COL1A1::PDGFB or related fusions. S100 expression is not a feature of DFSP. Prompted by a recent case of classic DFSP with significant S100 expression, we sought to explore the prevalence of S100 expression in DFSP, including its fibrosarcomatous variants.</p><p><strong>Methods and results: </strong>We reviewed our institutional and consultation archives for cases of DFSP that had undergone S100 immunohistochemical staining. A total of 176 cases were identified. Pigmented DFSP (Bednar tumour) cases were excluded from this study. S100 positivity expression was observed in 9 of 176 cases (5.1%), all of which lacked SOX10 expression. The mean patient age was 46.2 years, and there was a male predominance (M:F 3.5:1). The majority of tumours were located in the head and neck region (6/9), with the scalp being the most common location (n = 4). Pan-TRK staining was variably positive in 5 of the 7 cases tested. Fibrosarcomatous transformation was present in 7 of the 9 cases. Molecular confirmation was achieved in all 9 cases.</p><p><strong>Conclusion: </strong>S100 expression occurs in a small subset of DFSP, with a notable association with fibrosarcomatous transformation and head and neck location. The co-expression of CD34 and S100, in the absence of SOX10, mirrors the immunoprofile of emerging 'NTRK-rearranged spindle cell tumours'. Awareness of this unexpected immunophenotypic finding is essential to avoid misdiagnosis and to ensure appropriate molecular workup, which carries important prognostic and therapeutic implications.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2025-09-23DOI: 10.1111/his.70003
Xuan Tao, Xiao-Tong Wang, Peng-Cheng Wang, Yu-Peng Chen, Yi-Juan Wu, Qiu-Yuan Xia, Qiu Rao, Xiao-Ming Qiu, Ni Chen, Hong Chen
{"title":"Clinicopathological and molecular characterization of seven rare cases of renal cell carcinoma with hemangioblastoma-like features: Expanding the morphological spectrum of renal tumours with tuberous sclerosis complex/mammalian target of rapamycin mutations.","authors":"Xuan Tao, Xiao-Tong Wang, Peng-Cheng Wang, Yu-Peng Chen, Yi-Juan Wu, Qiu-Yuan Xia, Qiu Rao, Xiao-Ming Qiu, Ni Chen, Hong Chen","doi":"10.1111/his.70003","DOIUrl":"https://doi.org/10.1111/his.70003","url":null,"abstract":"<p><strong>Aims: </strong>Renal cell carcinoma with hemangioblastoma-like features (RCC-HB) is a rare renal cell carcinoma (RCC) subtype. It consists of renal cell carcinoma with fibromyomatous stroma (RCC FMS)-like and hemangioblastoma (HB)-like components. However, its molecular characteristics and whether it is a subtype of clear cell renal cell carcinoma (CCRCC), a part of the morphologic spectrum of RCC FMS, or a distinct entity remain unclear.</p><p><strong>Methods and results: </strong>We conducted clinicopathological evaluation, immunohistochemistry testing, and next-generation sequencing (NGS) on seven RCC-HB cases of tumour tissue, non-tumour tissue, and blood samples. The cohort included five female and two male patients, aged 33-68 years, with no personal or family history of syndromic disease. Six cases were unifocal, and one was multifocal. Tumours measured 1.2-6.0 cm and were well-circumscribed by a thick fibrous capsule, with fibromuscular bundles extending into and dividing the lesions. RCC FMS-like regions resembled CCRCC, RCC FMS, or clear cell papillary renal cell tumour (CCPRCT) and showed CK7 positivity. HB-like regions featured polygonal or short spindle-shaped neoplastic stromal cells interspersed with rich capillary networks and were highlighted by S100, α-inhibin, and GPNMB. DNA sequencing revealed pathogenic variants in MTOR, TSC1, and TSC2 in six cases, while one case did not detect these gene mutations. All patients were alive without recurrence or metastasis after surgery, with a mean follow-up of 47.7 months (range: 4-111 months) and a median of 46 months.</p><p><strong>Conclusion: </strong>This is the largest clinicopathological study to date on RCC-HB. Our findings support that the vast majority of RCC-HB harboured TSC/MTOR mutations, different from CCRCC, expanding the morphological spectrum of TSC/MTOR-mutated renal tumours.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Colorectal carcinoma with sarcomatoid component: isolated SMARCA2 loss and high PD-L1 expression as a potential therapeutic target.","authors":"Furkan Aknar, Tuce Soylemez-Akkurt, Huseyin Karatay","doi":"10.1111/his.70012","DOIUrl":"https://doi.org/10.1111/his.70012","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2025-09-22DOI: 10.1111/his.70007
João Lobo, Nuno Tiago Tavares, Fernanda Fernandes-Pontes, Carmen Jerónimo, Rui Henrique, Yiying Yang, Matija Snuderl, Melissa Hruby, Muhammad T Idrees, Thomas M Ulbright, Andres M Acosta
{"title":"Low-grade glial neoplasms of germ cell origin may represent maturation of embryonic-type neuroectodermal elements.","authors":"João Lobo, Nuno Tiago Tavares, Fernanda Fernandes-Pontes, Carmen Jerónimo, Rui Henrique, Yiying Yang, Matija Snuderl, Melissa Hruby, Muhammad T Idrees, Thomas M Ulbright, Andres M Acosta","doi":"10.1111/his.70007","DOIUrl":"https://doi.org/10.1111/his.70007","url":null,"abstract":"<p><strong>Aims: </strong>Glial tumours of germ cell origin are relatively rare in men, occurring predominantly after chemotherapy. Many exhibit low-grade histological features within a spectrum that includes teratomas with mature glial/ganglioglial elements and pure low-grade tumours with glial/ganglioglial phenotype (LGGT) that resemble gliomas/gangliogliomas of the central nervous system. Because foci of glial differentiation are very often seen in association with embryonic-type neuroectodermal tumour (ENT), we hypothesise that LGGTs may represent differentiation of embryonic-type neuroectodermal elements of teratoma and/or ENT.</p><p><strong>Methods and results: </strong>To address this hypothesis, we compared LGGTs, ENT, non-teratomas, and teratomas using microRNA and DNA methylation analyses. Seven LGGTs underwent microRNA-371~373 analysis and genomic methylation profiling. Evidence of a prior or concurrent germ cell tumour component containing embryonic neuroectoderm (including overt ENT) was present in 4 LGGTs. None of the tested LGGTs were positive for miR-371a-3p, with three cases demonstrating low levels of expression within the so-called \"grey zone\". Unsupervised clustering based on microRNA-371~373 showed two clusters, one comprising non-teratomas and another including teratomas, ENTs, and LGGTs. Clustering according to top-differentially methylated probes did not demonstrate a clear separation according to histology. Genome-wide assessment of mean methylation levels using violin plots demonstrated that LGGT show a methylation profile \"intermediate\" between ENT and teratoma.</p><p><strong>Conclusions: </strong>These results suggest that LGGTs of germ cell origin result from the maturation of ENT components.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2025-09-19DOI: 10.1111/his.70002
Astrid De Boeck, Eun Young Kang, Nicola S Meagher, Kylie L Gorringe, Cheng Han Lee, Parham Minoo, Martin Köbel
{"title":"A 5-marker immunohistochemical panel of CK17, MEP1A, PAX8, SMAD4, and CDX2 to distinguish ovarian mucinous carcinoma from metastatic pancreatic ductal adenocarcinoma.","authors":"Astrid De Boeck, Eun Young Kang, Nicola S Meagher, Kylie L Gorringe, Cheng Han Lee, Parham Minoo, Martin Köbel","doi":"10.1111/his.70002","DOIUrl":"https://doi.org/10.1111/his.70002","url":null,"abstract":"<p><strong>Aims: </strong>Metastatic pancreatic adenocarcinoma (PDAC), albeit uncommon, may involve the ovary, and distinction from primary ovarian mucinous tumours (OMT) poses a diagnostic challenge. Our aim was to develop an ancillary immunohistochemical (IHC) panel to aid in diagnosis and to validate the morphological features of metastatic PDAC.</p><p><strong>Methods and results: </strong>Six IHC markers (CDX2, CK17, MEP1A, MUC2, PAX8, SMAD4) selected based on a literature review were stained on tissue microarrays containing 256 PDAC, 102 mucinous ovarian carcinomas (MC) and 58 mucinous borderline ovarian tumours (MBOT). Detailed morphological features were reviewed in 16 ovarian metastases from PDAC, 25 MC, and 9 MBOT. We confirmed that tumours with a size less than 13 cm, bilaterality, ovarian surface involvement, low-power nodularity, infiltrative invasion, pseudomyxoma ovarii despite cystadenoma or borderline areas, and moderate nuclear atypia should raise suspicion for metastatic PDAC and prompt evaluation with the recommended IHC panel. A 5-marker panel consisting of CK17, MEP1A, PAX8, SMAD4, and CDX2 had an overall accuracy of 91.8% (95% CI 88.8%-94.3%) using recursive partitioning, with the highest weight resting on CK17. CK17 was expressed in 80.9% of PDAC compared to 18.6% of MC and 1.7% of MBOT, respectively.</p><p><strong>Conclusions: </strong>This is the first ancillary IHC panel to distinguish between PDAC and OMT with high accuracy. These results inform further studies on diagnostic workflows tailored to the complexity of metastatic presentations of tumours at the ovary.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2025-09-18DOI: 10.1111/his.15561
Emma L Kaderly Rasmussen, Susanne K Kjær, Lise G Larsen, Else Mejlgaard, Maria B Franzmann, Alexander K Kjær, Nadia V Salinas, Doris Schledermann, Kirsten Frederiksen, Tatiana Hansen, Birgitte H Winberg, Marianne Waldstrøm, Louise Baandrup
{"title":"Six-pattern p53 interpretation in 1293 vulvar squamous cell carcinomas: inter-pathologist variation and pattern distribution according to p16 status.","authors":"Emma L Kaderly Rasmussen, Susanne K Kjær, Lise G Larsen, Else Mejlgaard, Maria B Franzmann, Alexander K Kjær, Nadia V Salinas, Doris Schledermann, Kirsten Frederiksen, Tatiana Hansen, Birgitte H Winberg, Marianne Waldstrøm, Louise Baandrup","doi":"10.1111/his.15561","DOIUrl":"https://doi.org/10.1111/his.15561","url":null,"abstract":"<p><strong>Aims: </strong>Vulvar squamous cell carcinoma (VSCC) is classified into human papillomavirus (HPV)-associated and HPV-independent types, primarily using p16 immunohistochemistry, with p53 staining playing a complementary role since a subset of HPV-independent VSCC is driven by TP53 mutations. We aimed to assess the robustness of the six-pattern p53 classification by evaluating interobserver agreement and mapping pattern distribution in relation to p16 status.</p><p><strong>Methods: </strong>We performed p53 immunohistochemistry on 1293 VSCC cases, comprising 832 p16-negative and 461 p16-positive cases. Eight pathologists independently evaluated p53, with each case assessed by two pathologists. Expression was classified as wild-type (scattered or mid-epithelial) or mutated (basal overexpression, parabasal/diffuse overexpression, absent or cytoplasmic). Interobserver agreement was measured using kappa statistics.</p><p><strong>Results: </strong>Overall concordance across the six p53 patterns was 66.7%, increasing to 86.9% when dichotomized as wild-type versus mutated. In the p16-negative cases, concordance was 68.8% across all six patterns and 82.6% when dichotomized. Corresponding rates in the p16-positive cases were 62.9% and 94.6%. Kappa values for pairwise assessments ranged from 0.44 to 0.73 (six-pattern) and from 0.60 to 0.88 (dichotomized). After resolving discordant cases, 79.9% of p16-negative cases showed a mutated pattern, and 20.1% were wild type (scattered). Among the p16-positive cases, 93.1% exhibited a wild-type pattern.</p><p><strong>Conclusions: </strong>Findings support the clinical robustness of the six-pattern p53 framework, as interobserver agreement was high and most discrepancies were unlikely to impact tumour classification. While p16 proved helpful in p53 interpretation, certain cases remained challenging due to p53 heterogeneity or ambiguous p16/p53 combinations indicating a need for additional molecular testing in such instances.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2025-09-18DOI: 10.1111/his.15563
Rofyda Elhalaby, Priyadharshini Sivasubramaniam, Benjamin J Van Treeck, Lindsey Smith, Nadarra Stokes, Won-Tak Choi, Huaibin Mabel Ko, Roger K Moreira, Christopher P Hartley, Catherine E Hagen
{"title":"Featured Cover","authors":"Rofyda Elhalaby, Priyadharshini Sivasubramaniam, Benjamin J Van Treeck, Lindsey Smith, Nadarra Stokes, Won-Tak Choi, Huaibin Mabel Ko, Roger K Moreira, Christopher P Hartley, Catherine E Hagen","doi":"10.1111/his.15563","DOIUrl":"https://doi.org/10.1111/his.15563","url":null,"abstract":"<p>The cover image is based on the article <i>Mycophenolate mofetil-induced colitis versus colonic graft-versus-host disease: a comparative histologic study with artificial intelligence model development</i> by Catherine Hagen et al., https://doi.org/10.1111/his.15521\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"87 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.15563","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}