Human pathology最新文献_第5页

Hepatic adenomas in males: Is molecular characterization helpful in guiding its management? 男性肝腺瘤：分子特征是否有助于指导其治疗？

IF 2.7 2区医学

Human pathology Pub Date : 2025-05-01 DOI: 10.1016/j.humpath.2025.105795

Ekta Jain , Sarah A. Anderson , Eric Ollila , D. Bryan Johnson , Darshan Shimoga Chandrashekar , Abdullah Osme , Behiye Goksel , Goo Lee , Sameer Al Diffalha , Sanjay Kakar , Shuko Harada , Deepti Dhall

{"title":"Hepatic adenomas in males: Is molecular characterization helpful in guiding its management?","authors":"Ekta Jain , Sarah A. Anderson , Eric Ollila , D. Bryan Johnson , Darshan Shimoga Chandrashekar , Abdullah Osme , Behiye Goksel , Goo Lee , Sameer Al Diffalha , Sanjay Kakar , Shuko Harada , Deepti Dhall","doi":"10.1016/j.humpath.2025.105795","DOIUrl":"10.1016/j.humpath.2025.105795","url":null,"abstract":"<div><h3>Background and aims</h3><div>Hepatocellular adenomas (HCAs) in males are very rare. We performed detailed clinicopathologic, immunohistochemical and molecular characterization of HCAs in males, to understand their pathogenesis and malignant potential.</div></div><div><h3>Methods</h3><div>Seven cases of HCA in males formed our study cohort. The histologic slides, clinical and follow-up information were reviewed and immunohistochemical stains were performed. DNA was extracted and targeted sequencing was performed using Ion Torrent chemistry. Filtered variants were annotated to identify pathogenic mutations.</div></div><div><h3>Results</h3><div>Six (86 %) patients were morbidly obese. All showed at least focal cytologic atypia. Three lesions were markedly steatotic and 2 were hemorrhagic. One lesion showed focal reticulin loss, diffuse glutamine synthetase (GS) positivity and beta-catenin (β-catenin) nuclear staining, suggestive of atypical hepatocellular neoplasm. Three (42.8 %) cases were inflammatory-type, showing diffuse serum amyloid-associated protein/C-reactive protein. One other inflammatory-type HCA showed peripheral accentuation with GS and another non-inflammatory HCA showed patchy staining with GS; both revealed <em>CTNBB1</em> mutations but no β-catenin nuclear staining. None showed <em>TP53</em>, <em>TERT</em> promotor mutations, or significant copy number alterations.</div></div><div><h3>Conclusion</h3><div>A significant proportion of HCAs in males occurred in obese patients and were inflammatory-type. While some are beta-catenin mutated and need to be resected, a subset of HCAs in males appears to be low-risk by molecular features and may be treated conservatively.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"159 ","pages":"Article 105795"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144072396","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}

引用次数: 0

Adaptive immune response and PD-1/ PD-L1 status in chemotherapy treated high grade serous carcinoma is dependent on chemotherapy response score 化疗治疗的高级别浆液性癌的适应性免疫反应和PD-1/ PD-L1状态依赖于化疗反应评分

IF 2.7 2区医学

Human pathology Pub Date : 2025-05-01 DOI: 10.1016/j.humpath.2025.105800

Christine H. Miller , Anusha Vemuri , Ernst Lengyel , Ricardo R. Lastra

{"title":"Adaptive immune response and PD-1/ PD-L1 status in chemotherapy treated high grade serous carcinoma is dependent on chemotherapy response score","authors":"Christine H. Miller , Anusha Vemuri , Ernst Lengyel , Ricardo R. Lastra","doi":"10.1016/j.humpath.2025.105800","DOIUrl":"10.1016/j.humpath.2025.105800","url":null,"abstract":"<div><h3>Background</h3><div>Platinum-based chemotherapy and debulking surgery is the standard of care for patients with advanced tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response scoring (CRS) system is a histopathologic scoring system developed to measure response to neoadjuvant chemotherapy with prognostic implications. Omental samples with high CRS have greater inflammatory cell infiltrates, but the immunophenotype of infiltrating immune cells and PD-L1 expression of the residual tumor has not been well-defined.</div></div><div><h3>Design</h3><div>Twenty cases of patients with FIGO stage IIIA to IIIC HGSC undergoing interval debulking after receiving 3–4 rounds of chemotherapy were selected. 6/20 cases of omental samples were graded as CRS 1, 7/20 were graded CRS 2, and 7/20 were graded CRS 3. The following immunohistochemical stains were performed: CD8, CD4, Foxp3, PD1, and PD-L1. The total number of tumor-infiltrating lymphocytes was recorded, and each case was given a PD-L1 combined positive score (CPS) and tumor proportion score (TPS).</div></div><div><h3>Results</h3><div>There was a significantly greater number of CD8<sup>+</sup> T cells, PD-1+ T cells, CD4<sup>+</sup> T cells, and Foxp3+ T cells in CRS 3-scored cases compared to CRS 1 scored cases (p-values: 0.0018, 0.0224, 0.0071, and 0.0136, respectively). CRS 3-scored cases had a greater PD-L1 CPS (CRS 3 CPS 13 ± 8.2 versus CRS 1 CPS 0 ± 0; p-value: 0.0485).</div></div><div><h3>Conclusions</h3><div>Tubo-ovarian high-grade serous carcinoma with greater response to neoadjuvant treatment have significantly greater T cell infiltrate and greater PD-L1 combined positive score, highlighting a potential role of the CRS as a predictive biomarker for immune checkpoint blockade therapy.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"159 ","pages":"Article 105800"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101656","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}

引用次数: 0

Information for Authors 作者信息

IF 2.7 2区医学

Human pathology Pub Date : 2025-05-01 DOI: 10.1016/S0046-8177(25)00119-4

引用次数: 0

Chimeric antigen receptor (CAR) T-cell therapy-related gastrointestinal toxicity: Histologic features and morphologic mimics 嵌合抗原受体（CAR） t细胞治疗相关的胃肠道毒性：组织学特征和形态模拟

IF 2.7 2区医学

Human pathology Pub Date : 2025-04-01 DOI: 10.1016/j.humpath.2025.105791

Saman S. Karimi , Tatianna C. Larman , Tania Jain , Lysandra Voltaggio , Jacqueline E. Birkness-Gartman

{"title":"Chimeric antigen receptor (CAR) T-cell therapy-related gastrointestinal toxicity: Histologic features and morphologic mimics","authors":"Saman S. Karimi , Tatianna C. Larman , Tania Jain , Lysandra Voltaggio , Jacqueline E. Birkness-Gartman","doi":"10.1016/j.humpath.2025.105791","DOIUrl":"10.1016/j.humpath.2025.105791","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR) T-cell therapy is a contemporary treatment modality for hematologic malignancies, with potential future applications in solid tumors. While the clinical side effects of CAR T-cell therapy are well-documented, histologic correlations of gastrointestinal (GI) toxicity remain underreported. This study prospectively identified 5 sets of GI biopsies from 3 patients presenting with CAR T-cell therapy-associated GI toxicity. Patients exhibited symptoms such as abdominal pain, hematochezia, non-bloody diarrhea, weight loss, and fever/chills, occurring 1.5–8 months post-therapy. Histologic examination revealed a graft versus host disease (GVHD)-like pattern of injury in colon biopsies, characterized by epithelial apoptosis, crypt dropout, and neuroendocrine cell nests. One duodenal biopsy showed intraepithelial lymphocytosis and villous blunting, mimicking celiac disease. A notable paucity of CD20-positive B-cells and CD38-positive plasma cells was observed in both colonic and small intestinal biopsies. Two patients required biologic agents for treatment, while one patient improved with corticosteroids but succumbed to an upper respiratory infection. The findings underscore the necessity of correlating symptom onset with therapy timing to achieve accurate diagnosis of CAR T-cell therapy-associated GI toxicity.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"158 ","pages":"Article 105791"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936520","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}

引用次数: 0

Intestinal and liver involvement by endometrial stromal sarcoma: Expanding the differential diagnosis of mesenchymal tumors involving the GI tract 子宫内膜间质肉瘤累及肠道和肝脏：扩大累及胃肠道间充质肿瘤的鉴别诊断

IF 2.7 2区医学

Human pathology Pub Date : 2025-04-01 DOI: 10.1016/j.humpath.2025.105784

Yujie Zhang , Saman S. Karimi , Domenika Ortiz Requena , Armen Khararjian , Tom Z. Liang , Chen Mayer , Jacqueline Birkness-Gartman , Tatianna Larman , Elizabeth Anne Montgomery , Lysandra Voltaggio

{"title":"Intestinal and liver involvement by endometrial stromal sarcoma: Expanding the differential diagnosis of mesenchymal tumors involving the GI tract","authors":"Yujie Zhang , Saman S. Karimi , Domenika Ortiz Requena , Armen Khararjian , Tom Z. Liang , Chen Mayer , Jacqueline Birkness-Gartman , Tatianna Larman , Elizabeth Anne Montgomery , Lysandra Voltaggio","doi":"10.1016/j.humpath.2025.105784","DOIUrl":"10.1016/j.humpath.2025.105784","url":null,"abstract":"<div><div>Endometrial stromal sarcoma (ESS) is a mesenchymal tumor known for infiltrative growth and lymphovascular invasion. Most examples arise in the endometrium, but some occur in the abdominal cavity without a primary uterine lesion, likely originating from endometriosis. ESS involving the gastrointestinal (GI) tract and liver is rare. We reviewed 15 examples from 13 women between 2010 and 2023. The mean age was 51 (range 16–81); just over half of the patients (7/13, 54 %) had a history of uterine ESS. Twelve tumors involved the intestines and three the liver; rectosigmoid colon was the most affected site. Tumors averaged 4.6 cm (range 0.3–10 cm) and involved all bowel layers with two showing transmural involvement. Predominantly low-grade features were observed, including uniform round to spindle cells in fibrous or myxoid stroma, permeative growth, hyaline plaques, and spiral arterioles. Endometriosis was seen in 4 (27 %) cases. Immunohistochemical analysis revealed positivity for ER (93 %), PR (92 %), CD10 (91 %), and focal cyclin D1 (80 %). A minority of cases showed staining with smooth muscle markers, CD117, DOG1, and keratins. High-grade features were suggested but not diagnostic in three cases. Follow-up data for three patients showed one death at 16 months, one patient disease-free at 94 months, and another alive at 16 months. ESS involving the GI tract is rare, may lack a uterine primary, and can mimic other neoplasms due to keratin, smooth muscle, and CD117/DOG1 expression. Recognizing ESS-associated features—such as a permeative pattern, hyaline plaques, and spiral arterioles—is key to avoiding misdiagnosis.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"158 ","pages":"Article 105784"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918024","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}

引用次数: 0

Plasmacytoid urothelial carcinoma of the urinary bladder: A single institution experience with focus on next-generation sequencing (NGS) and PD-L1 immunohistochemistry 膀胱浆细胞样尿路上皮癌：一个专注于下一代测序（NGS）和PD-L1免疫组织化学的单一机构经验

IF 2.7 2区医学

Human pathology Pub Date : 2025-04-01 DOI: 10.1016/j.humpath.2025.105788

Dimitrios Korentzelos , Leonidas Diamantopoulos , Maedeh Mohebnasab , Rajiv Dhir , Gabriela M. Quiroga-Garza

{"title":"Plasmacytoid urothelial carcinoma of the urinary bladder: A single institution experience with focus on next-generation sequencing (NGS) and PD-L1 immunohistochemistry","authors":"Dimitrios Korentzelos , Leonidas Diamantopoulos , Maedeh Mohebnasab , Rajiv Dhir , Gabriela M. Quiroga-Garza","doi":"10.1016/j.humpath.2025.105788","DOIUrl":"10.1016/j.humpath.2025.105788","url":null,"abstract":"<div><div>Plasmacytoid urothelial carcinoma (PUC) of the urinary bladder is an aggressive UC subtype characterized by infiltrating cells with plasmacytoid appearance, and somatic <em>CDH1</em> mutations leading to E-cadherin loss. 32 PUC cases were found in our pathology archives from 2018 to 2024; next-generation sequencing (NGS) was available in 18 cases, and PD-L1 immunohistochemistry in all 32 cases. PD-L1 tumor proportion score (TPS) and combined positive score (CPS) were calculated. Kaplan-Meier method and log-rank test were used for survival analysis. Median patient age was 72.5 years (IQR: 64.3–78.8 years). The cohort consisted predominantly of males (29/32, 91%). 25 patients (78%) underwent radical cystectomy/cystoprostatectomy (RC), while 7 (22%) transurethral resection. Median tumor size was 5.2 cm (IQR of 3.6–8.0 cm). Most RCs (22/25, 88 %) were high-stage (pT3-4). Lymphovascular invasion was identified in 22/25 RCs (88%) and 12/23 RCs (52%) were pN1-2. 17/32 cases (53%) showed a PD-L1 TPS≥1% (6/17 received immune-checkpoint inhibitors – ICIs), while 21/32 (66%) exhibited a CPS≥1% (8/21 received ICIs). Recurrently mutated genes included <em>TP53</em>, <em>TERT</em>, <em>RB1</em>, <em>CREBBP</em>, and <em>ERBB2</em>, among others; our NGS panel does not cover <em>CDH1</em>. Most frequent copy number alterations were <em>RB1</em>, <em>CDKN2A</em>, and <em>CDKN1B</em> losses. Median tumor mutational burden (TMB) was 10.3 mut/Mb (IQR 5.4–15.73 mut/Mb). Median overall survival (OS) was 13.0 months (95% CI 4.2–21.8 months) with some evidence for superior OS among patients with PD-L1 expression. Overall, PUCs frequently exhibit high TMB and/or PD-L1 expression, suggesting a potential for intervention with ICIs. Finally, NGS is recommended to identify actionable alterations, including <em>ERBB2</em> mutations.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"158 ","pages":"Article 105788"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937814","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}

引用次数: 0

Significance of mucin-suspended tumor bud-like structures in colorectal cancer 黏液悬浮肿瘤芽状结构在结直肠癌中的意义

IF 2.7 2区医学

Human pathology Pub Date : 2025-04-01 DOI: 10.1016/j.humpath.2025.105772

Ville K. Äijälä , Päivi Sirniö , Hanna Elomaa , Henna Karjalainen , Meeri Kastinen , Vilja V. Tapiainen , Maarit Ahtiainen , Olli Helminen , Erkki-Ville Wirta , Jukka Rintala , Sanna Meriläinen , Juha Saarnio , Tero Rautio , Toni T. Seppälä , Jan Böhm , Jukka-Pekka Mecklin , Anne Tuomisto , Markus J. Mäkinen , Juha P. Väyrynen

{"title":"Significance of mucin-suspended tumor bud-like structures in colorectal cancer","authors":"Ville K. Äijälä , Päivi Sirniö , Hanna Elomaa , Henna Karjalainen , Meeri Kastinen , Vilja V. Tapiainen , Maarit Ahtiainen , Olli Helminen , Erkki-Ville Wirta , Jukka Rintala , Sanna Meriläinen , Juha Saarnio , Tero Rautio , Toni T. Seppälä , Jan Böhm , Jukka-Pekka Mecklin , Anne Tuomisto , Markus J. Mäkinen , Juha P. Väyrynen","doi":"10.1016/j.humpath.2025.105772","DOIUrl":"10.1016/j.humpath.2025.105772","url":null,"abstract":"<div><div>Tumor budding (TB) is an independent predictor of adverse prognosis in colorectal cancer (CRC), defined as clusters of fewer than 5 tumor cells at the invasive margin of cancer. According to the international consensus criteria (ITBCC), TB should be evaluated from the non-mucinous regions. However, some tumors also contain tumor bud-like structures within extracellular mucin pools, and the prognostic impact of these structures remains unclear. To assess this, we defined a modified tumor budding variable (TB-Muc), representing the highest number of tumor buds/bud-like structures observed in a hotspot (0.785 mm<sup>2</sup>) at the invasive margin, including extracellular mucin regions. We analyzed the prognostic significance of TB (ITBCC criteria) and TB-Muc in two CRC cohorts (N = 1876). TB-ITBCC was associated with advanced stage and lymphovascular invasion (p < 0.001) but also with shorter cancer-specific survival independent of other prognostic factors (Cohort 1: HR for high vs. low 1.99, 95 % CI 1.32–3.01, p<sub>trend</sub> = 0.0007; Cohort 2: HR 1.35, 95 % CI 0.98–1.85, p<sub>trend</sub> = 0.037). TB-Muc had a comparable independent association with shorter cancer-specific survival (Cohort 1: HR for high vs. low 1.77, 95 % CI 1.18–2.65, p<sub>trend</sub> = 0.006; Cohort 2: HR 1.39, 95 % CI 1.02–1.89, p<sub>trend</sub> = 0.019). Our results indicate that tumor bud-like structures in mucin do not provide additional prognostic value and should not be included in TB evaluation.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"158 ","pages":"Article 105772"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838189","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}

引用次数: 0

Epstein-Barr virus–positive small cell neuroendocrine carcinoma of the nasopharynx: A clinicopathologic study of 7 cases and literature review eb病毒阳性鼻咽部小细胞神经内分泌癌7例临床病理分析及文献复习

IF 2.7 2区医学

Human pathology Pub Date : 2025-04-01 DOI: 10.1016/j.humpath.2025.105787

Yuan Zhan , Fei Zheng , Shousheng Liao , Xiangtong Lu , Fang Cao , Tao Huang , Xuan Yang , Yue Han , Lei Zeng , Lixiang Li , Wenyong Huang

{"title":"Epstein-Barr virus–positive small cell neuroendocrine carcinoma of the nasopharynx: A clinicopathologic study of 7 cases and literature review","authors":"Yuan Zhan , Fei Zheng , Shousheng Liao , Xiangtong Lu , Fang Cao , Tao Huang , Xuan Yang , Yue Han , Lei Zeng , Lixiang Li , Wenyong Huang","doi":"10.1016/j.humpath.2025.105787","DOIUrl":"10.1016/j.humpath.2025.105787","url":null,"abstract":"<div><div>Epstein-Barr virus (EBV)-positive small cell neuroendocrine carcinoma (NEC) of the nasopharynx is a rare entity with poorly characterized clinicopathological and prognostic features. In this study, seven cases of EBV-positive nasopharyngeal small cell NEC will be compared to 6 EBV-negative cases of nasopharyngeal small cell NEC. The overall EBV-positive rate, defined by EBV-encoded small RNAs (EBERs) in situ hybridization of nasopharyngeal small cell NEC, was 53.8 % (7/13). The patients’ age ranged from 38 to 73 years, with a median age of 56 years. There was a large preponderance of males, with a male-to-female ratio of 6:1. In the present study, EBV-positive nasopharyngeal small cell NEC had a significantly higher expression of POU2F3 (85.7 %, 6/7) than EBV-negative nasopharyngeal small cell NEC (16.7 %, 1/6). RNA sequencing revealed that EBV-positive nasopharyngeal small cell NEC was distinct from EBV-negative nasopharyngeal small cell NEC in the control group. There was no statistically significant difference in overall survival between patients with EBV-positive and EBV-negative nasopharyngeal small cell NEC in the present cohort. These findings suggest that EBV-positive nasopharyngeal small cell NEC may be closely associated with POU2F3. In addition, POU2F3 and ASCL1 may play important roles in the tumorigenesis of EBV-positive nasopharyngeal small cell NEC.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"158 ","pages":"Article 105787"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941539","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}

引用次数: 0

Hydroa vacciniforme lymphoproliferative disorder, a clinicopathologic and genetic analysis 疫苗样水疱性淋巴增生性疾病的临床病理和遗传分析

IF 2.7 2区医学

Human pathology Pub Date : 2025-04-01 DOI: 10.1016/j.humpath.2025.105770

Weiwei Zhang , George Pupwe , Liliana Vasquez , Yasodha Nakunam , Atif Saleem , Hernan Molina-Kirsch , Brady Beltran , Ivan Maza Medina , Mauricio Postigo , Joo Y. Song , Wing C. Chan

{"title":"Hydroa vacciniforme lymphoproliferative disorder, a clinicopathologic and genetic analysis","authors":"Weiwei Zhang , George Pupwe , Liliana Vasquez , Yasodha Nakunam , Atif Saleem , Hernan Molina-Kirsch , Brady Beltran , Ivan Maza Medina , Mauricio Postigo , Joo Y. Song , Wing C. Chan","doi":"10.1016/j.humpath.2025.105770","DOIUrl":"10.1016/j.humpath.2025.105770","url":null,"abstract":"<div><div>Hydroa vacciniforme lymphoproliferative disorder (HV-LPD) is a rare Epstein–Barr virus (EBV)-associated disease and the systemic form shows a propensity to progress and some cases may eventually develop a disease simulating NK/T-cell lymphoma or even aggressive NK-cell leukemia. We report 12 patients with systemic HV-LPD of median age 15.8 years with dermatosis involving the face, trunk, extremities and serous membranes. Ten of 12 patients (83 %) had systemic symptoms including 9 with prominent facial edema and 2 with bone marrow involvement. All cases were positive for EBER and CD3 and lacked CD20. Additional positive markers included CD8 in 11 of 12 (91.6 %), CD56 in 1 of 12 (8.3 %), granzyme B in 6 of 7 (85.7 %), TIA1 in 2 of 2 (100 %) and CD30 in 1 of 3 (33.3 %). Two cases studied demonstrated monoclonal TCR-γ and one also had TCR-β rearrangements. Five cases were sequenced and showed recurrent mutations in <em>ALMS1, ALPK2, BCORL1</em>, KANK2, <em>KMT2D</em>, <em>NCOR1</em>, <em>PTPRD,</em> RHOA, TNIK, <em>TP53</em> and <em>ZFHX3</em>, and single cases showed a variety of mutations including <em>BCOR, CREBBP, DDX3X, DMXL2, IRF4, IRF8, KDM6A, MGA, NCOR2, PLCG1, PRDM1, RNF213, SMARCA4, STAT5B and TET2</em> mutation<em>.</em> Most patients were treated with immunomodulating therapy, two received methotrexate, three received multiagent chemotherapy and one underwent hematopoietic stem cell transplant. Follow-up was available in 10 patients of whom 6 died of disease and one was alive without disease. Our results showed that patients with persistent/progressive systemic HV-LPD have a poor prognosis and did not respond well to chemotherapy. The mutation spectrum bore some resemblance to extranodal NK/T lymphomas but also had notable differences.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"158 ","pages":"Article 105770"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870833","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}

引用次数: 0

Molecular and clinicopathological characteristics of invasive breast cancers with HER2-ultralow expression 侵袭性乳腺癌her2超低表达的分子和临床病理特征

IF 2.7 2区医学

Human pathology Pub Date : 2025-04-01 DOI: 10.1016/j.humpath.2025.105796

Yike Gao , Ruping Hong , Jun Wang, Junyi Pang, Shafei Wu, Zhiyong Liang

{"title":"Molecular and clinicopathological characteristics of invasive breast cancers with HER2-ultralow expression","authors":"Yike Gao , Ruping Hong , Jun Wang, Junyi Pang, Shafei Wu, Zhiyong Liang","doi":"10.1016/j.humpath.2025.105796","DOIUrl":"10.1016/j.humpath.2025.105796","url":null,"abstract":"<div><div>The identification of HER2-low and HER2-ultralow breast cancer (BC) subgroups has garnered considerable attention following the demonstrated clinical efficacy of HER2-targeted antibody-drug conjugates (ADCs). This study investigated whether these subgroups represent distinct biological subtypes compared to HER2-undetected tumors. Analyzing 297 HER2-negative BCs stratified by immunohistochemistry (50.2 % HER2-low, 35.7 % HER2-ultralow, 14.1 % HER2-undetected), we systematically compared clinicopathological and molecular profiles (AmoyDx® HANDLE Classic Panel). HER2-detected tumors (combined low/ultralow cohort) showed significant differences in hormone receptor (HR) positivity versus HER2-undetected tumors (<em>p</em> = 0.001). The mutation frequencies of the three most frequently altered genes (<em>TP53</em>, <em>PIK3CA</em>, and <em>PTEN</em>) in HER2-ultralow tumors did not significantly differ from those in the two other subgroups. However, HER2-detected tumors exhibited different molecular alterations compared to HER2-undetected tumors, with increased <em>PIK3CA</em> mutations in the former (<em>p</em> = 0.024) and <em>TP53</em> mutation enrichment in the latter (<em>p</em> = 0.007). These differences attenuated when tumors were stratified by HR status. In addition, HER2 expression positively correlated with <em>ERBB2</em> copy number, showing higher mean values in HER2-detected subgroups versus undetected counterparts (2.01 ± 0.31 vs 1.88 ± 0.23; <em>p</em> = 0.011). While no significant survival differences emerged across subgroups, most mortality events occurred in HER2-low (6/12, 50.0 %) and HER2-ultralow (5/12, 41.7 %) cases. Our findings indicate that while HER2-low and HER2-ultralow breast cancers may not represent independent biological subtypes, their clinical distinction from HER2-undetected tumors remains crucial due to potential ADC therapeutic implications.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"158 ","pages":"Article 105796"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071156","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}

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