A L Paterson, R Gaurav, L Swift, R Webster, C Fear, A J Butler, C J E Watson
Aims: There is a shortage of livers for transplantation in the United Kingdom; despite this, more than a fifth of those retrieved are not transplanted. Normothermic machine perfusion (NMP) allows a functional assessment of marginal organs using biochemical parameters. This study describes the histological changes in livers undergoing NMP.
Methods and results: A total of 170 biopsies taken pre-NMP, after 4 h of NMP, end-NMP and at implantation from 50 livers undergoing NMP as part of standard local transplant practice were retrospectively reviewed. Thirty-eight per cent had large droplet macrovesicular steatosis pre-NMP, which was associated with reduced organ utilisation, P = 0.096, subsequent extracellular fat and a neutrophilic reaction; 32% had small droplet macrovesicular steatosis pre-NMP suggestive of acute cellular stress, the severity of which was unchanged in 64% during the perfusion period. Those showing at least moderate hepatocellular necrosis at end-NMP were less likely to be transplanted (55 versus 24%, P = 0.0505). Variation in the extent of hepatocyte necrosis was seen between biopsies, with 43% of transplanted cases showing less hepatocyte necrosis at implantation compared to end-NMP and 21% more severe necrosis. Patchy portal inflammation was present in 96% of pre-NMP biopsies, although identifiable duct injury was rare and portal thrombi were not identified. Sinusoidal dilation pre-NMP was more frequent in donation after circulatory death donors, typically persisted during NMP although had improved by implantation in most and had resolved in cases with an early post-transplant biopsy.
Conclusions: Histological changes in NMP livers predominantly comprise donor-derived steatosis, stress-associated small droplet steatosis, retrieval- and procedure-associated sinusoidal dilation and ischaemic injury.
{"title":"Evolution of morphological changes in donor livers undergoing normothermic machine perfusion.","authors":"A L Paterson, R Gaurav, L Swift, R Webster, C Fear, A J Butler, C J E Watson","doi":"10.1111/his.15371","DOIUrl":"https://doi.org/10.1111/his.15371","url":null,"abstract":"<p><strong>Aims: </strong>There is a shortage of livers for transplantation in the United Kingdom; despite this, more than a fifth of those retrieved are not transplanted. Normothermic machine perfusion (NMP) allows a functional assessment of marginal organs using biochemical parameters. This study describes the histological changes in livers undergoing NMP.</p><p><strong>Methods and results: </strong>A total of 170 biopsies taken pre-NMP, after 4 h of NMP, end-NMP and at implantation from 50 livers undergoing NMP as part of standard local transplant practice were retrospectively reviewed. Thirty-eight per cent had large droplet macrovesicular steatosis pre-NMP, which was associated with reduced organ utilisation, P = 0.096, subsequent extracellular fat and a neutrophilic reaction; 32% had small droplet macrovesicular steatosis pre-NMP suggestive of acute cellular stress, the severity of which was unchanged in 64% during the perfusion period. Those showing at least moderate hepatocellular necrosis at end-NMP were less likely to be transplanted (55 versus 24%, P = 0.0505). Variation in the extent of hepatocyte necrosis was seen between biopsies, with 43% of transplanted cases showing less hepatocyte necrosis at implantation compared to end-NMP and 21% more severe necrosis. Patchy portal inflammation was present in 96% of pre-NMP biopsies, although identifiable duct injury was rare and portal thrombi were not identified. Sinusoidal dilation pre-NMP was more frequent in donation after circulatory death donors, typically persisted during NMP although had improved by implantation in most and had resolved in cases with an early post-transplant biopsy.</p><p><strong>Conclusions: </strong>Histological changes in NMP livers predominantly comprise donor-derived steatosis, stress-associated small droplet steatosis, retrieval- and procedure-associated sinusoidal dilation and ischaemic injury.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675700","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}
Mélanie Legrand, Baptiste Louveau, Nicolas Macagno, Maxence Mancini, Dmitry V Kazakov, Daniel Pissaloux, Franck Tirode, Anne Tallet, Samia Mourah, Quentin Lepiller, Arnaud de la Fouchardière, Pierre Sohier, Eric Frouin, Andreas von Deimling, Keisuke Goto, Bernard Cribier, Eduardo Calonje, Saleem Taibjee, Maxime Battistella, Thibault Kervarrec
Aims: Sebaceous neoplasms constitute a group of adnexal tumours, including sebaceous adenoma, sebaceoma and sebaceous carcinoma. Although mismatch repair deficiency may be observed, the nature of the genetic alterations contributing to the development of most of these tumours is still unknown. In the present study, we describe the clinical, microscopic, and molecular features of eight sebaceomas with GRHL gene rearrangement.
Methods and results: Among these sebaceomas, four occurred in women and four in men; the median age was 63 years (range = 29-89). The tumours were located in the head and neck area in all cases. Microscopic examination revealed a well-demarcated lesion located in the dermis with focal extension into the subcutaneous tissue (three cases). The neoplasms displayed macronodular (eight cases), cribriform (seven cases) and organoid (six cases) growth patterns, occurring in combination. The tumours were mainly composed of immature basophilic cells associated with scattered mature sebocytes. Numerous small infundibular cysts were present in seven cases. Mitotic activity was low (none/one to four mitoses/mm2). Immunohistochemistry showed positivity for androgen receptor and p63. Preserved expression of MLH1, PMS2, MSH2 and MSH6 was observed in all cases. RNA-sequencing revealed RCOR1::GRHL2 (three cases), BCL6::GRHL1 (two cases), a BCOR::GRHL2 (one case), RCOR1::GRHL1 (one case) and TLE1::GRHL1 (one case) fusion transcript. Methylation analysis demonstrated that GRHL-fused sebaceomas form an independent cluster and highlight the proximity of such tumours with poromas with folliculo-sebaceous differentiation.
Conclusions: In conclusion, we report recurrent fusions of the GRHL genes in a distinctive subset of sebaceomas harbouring infundibulocystic differentiation, a frequent organoid growth pattern and lack of mismatch repair deficiency.
{"title":"Recurrent GRHL fusions in a subset of sebaceoma: microscopic and molecular characterisation of eight cases.","authors":"Mélanie Legrand, Baptiste Louveau, Nicolas Macagno, Maxence Mancini, Dmitry V Kazakov, Daniel Pissaloux, Franck Tirode, Anne Tallet, Samia Mourah, Quentin Lepiller, Arnaud de la Fouchardière, Pierre Sohier, Eric Frouin, Andreas von Deimling, Keisuke Goto, Bernard Cribier, Eduardo Calonje, Saleem Taibjee, Maxime Battistella, Thibault Kervarrec","doi":"10.1111/his.15361","DOIUrl":"https://doi.org/10.1111/his.15361","url":null,"abstract":"<p><strong>Aims: </strong>Sebaceous neoplasms constitute a group of adnexal tumours, including sebaceous adenoma, sebaceoma and sebaceous carcinoma. Although mismatch repair deficiency may be observed, the nature of the genetic alterations contributing to the development of most of these tumours is still unknown. In the present study, we describe the clinical, microscopic, and molecular features of eight sebaceomas with GRHL gene rearrangement.</p><p><strong>Methods and results: </strong>Among these sebaceomas, four occurred in women and four in men; the median age was 63 years (range = 29-89). The tumours were located in the head and neck area in all cases. Microscopic examination revealed a well-demarcated lesion located in the dermis with focal extension into the subcutaneous tissue (three cases). The neoplasms displayed macronodular (eight cases), cribriform (seven cases) and organoid (six cases) growth patterns, occurring in combination. The tumours were mainly composed of immature basophilic cells associated with scattered mature sebocytes. Numerous small infundibular cysts were present in seven cases. Mitotic activity was low (none/one to four mitoses/mm<sup>2</sup>). Immunohistochemistry showed positivity for androgen receptor and p63. Preserved expression of MLH1, PMS2, MSH2 and MSH6 was observed in all cases. RNA-sequencing revealed RCOR1::GRHL2 (three cases), BCL6::GRHL1 (two cases), a BCOR::GRHL2 (one case), RCOR1::GRHL1 (one case) and TLE1::GRHL1 (one case) fusion transcript. Methylation analysis demonstrated that GRHL-fused sebaceomas form an independent cluster and highlight the proximity of such tumours with poromas with folliculo-sebaceous differentiation.</p><p><strong>Conclusions: </strong>In conclusion, we report recurrent fusions of the GRHL genes in a distinctive subset of sebaceomas harbouring infundibulocystic differentiation, a frequent organoid growth pattern and lack of mismatch repair deficiency.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675740","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}
Stephan Schwarz-Furlan, Carole Gengler, Ayami Yoshimi-Noellke, Guido Piontek, Yuki Schneider-Kimoto, Markus Schmugge, Christian Thiede, Charlotte M Niemeyer, Miriam Erlacher, Martina Rudelius
Aim: Tandem-duplications of the UBTF gene (UBTF-TDs) have recently been identified as a new genetic driver in young individuals with acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). Disease in these newly defined subgroups is characterized by poor response to standard intensive chemotherapy and inferior survival of the affected patients. However, a thorough analysis of bone marrow histomorphology of UBTF-mutated neoplasia has not been undertaken thus far.
Methods and results: In this retrospective study, we investigated the characteristic histopathological features of a cohort comprising 14 paediatric MDS patients with an excess of blasts (MDS-EB) and UBTF-TD. Bone marrow biopsies from these patients revealed hypercellularity and severe dysplasia across all three haematopoietic lineages. In particular, a marked hyperplastic megakaryopoiesis characterized by the presence of frequent micromegakaryocytes and a high number of monolobulated cells forming small clusters was observed. Additionally, erythropoiesis was left-shifted, with numerous blastoid precursors. The granulopoietic precursors displayed prominent UBTF-positive nucleoli.
Conclusion: The unique combination of these histomorphological features strongly suggests a possible UBTF aberration. It will allow initiating the appropriate genetic testing to confirm the presence of UBTF-TD and identify potential additional genetic alterations. Such molecular profiling will not only contribute to a better understanding of the disease mechanism, but also facilitate more rational treatment approaches for these high-risk paediatric MDS patients.
{"title":"Diagnostic features in paediatric MDS-EB with UBTF-internal tandem duplication: defining a unique subgroup.","authors":"Stephan Schwarz-Furlan, Carole Gengler, Ayami Yoshimi-Noellke, Guido Piontek, Yuki Schneider-Kimoto, Markus Schmugge, Christian Thiede, Charlotte M Niemeyer, Miriam Erlacher, Martina Rudelius","doi":"10.1111/his.15378","DOIUrl":"https://doi.org/10.1111/his.15378","url":null,"abstract":"<p><strong>Aim: </strong>Tandem-duplications of the UBTF gene (UBTF-TDs) have recently been identified as a new genetic driver in young individuals with acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). Disease in these newly defined subgroups is characterized by poor response to standard intensive chemotherapy and inferior survival of the affected patients. However, a thorough analysis of bone marrow histomorphology of UBTF-mutated neoplasia has not been undertaken thus far.</p><p><strong>Methods and results: </strong>In this retrospective study, we investigated the characteristic histopathological features of a cohort comprising 14 paediatric MDS patients with an excess of blasts (MDS-EB) and UBTF-TD. Bone marrow biopsies from these patients revealed hypercellularity and severe dysplasia across all three haematopoietic lineages. In particular, a marked hyperplastic megakaryopoiesis characterized by the presence of frequent micromegakaryocytes and a high number of monolobulated cells forming small clusters was observed. Additionally, erythropoiesis was left-shifted, with numerous blastoid precursors. The granulopoietic precursors displayed prominent UBTF-positive nucleoli.</p><p><strong>Conclusion: </strong>The unique combination of these histomorphological features strongly suggests a possible UBTF aberration. It will allow initiating the appropriate genetic testing to confirm the presence of UBTF-TD and identify potential additional genetic alterations. Such molecular profiling will not only contribute to a better understanding of the disease mechanism, but also facilitate more rational treatment approaches for these high-risk paediatric MDS patients.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675771","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}
Ana C Xavier, Andishe Attarbaschi, Dita Gratzinger, Olga Balagué
Non-Hodgkin lymphoma (NHL) represents the fourth most common malignant disease among children and adolescents. Current disease classifications, including the most recent World Health Organization (WHO) classification and the International Consensus Classification (ICC), rely on a combination of clinical, epidemiological, histologic, immunophenotypic, and molecular data to define discrete clinicopathologic entities. There is growing evidence that children, adolescents, and young adults (CAYA) with B-cell NHL display unique clinical and epidemiologic characteristics. This may be explained by distinct age-related developmental plasticity, immune and haematopoietic repertoires, environmental exposures and social determinants of health, and germline or acquired genetic and molecular features, including those associated with inborn errors of immunity (IEI). Here, we discuss the unique clinical and biological characteristics of several distinct paediatric B-cell NHL types to indicate a path forward in classification of these CAYA NHL to optimally support multidisciplinary patient care and personalized treatment. We propose a potential "arising in CAYA" classification qualifier to denote the distinct clinicopathologic characteristics of B-cell NHLs that, otherwise, histologically and immunophenotypically resemble those arising in middle-aged and older adults. We also discuss how haemopathology diagnoses are evolving to incorporate the most current scientific knowledge into future classification systems of CAYA B-cell NHL.
非霍奇金淋巴瘤(NHL)是儿童和青少年中第四大常见恶性疾病。目前的疾病分类,包括最新的世界卫生组织(WHO)分类和国际共识分类(ICC),都依赖于临床、流行病学、组织学、免疫表型和分子数据的组合来定义不同的临床病理实体。越来越多的证据表明,患有 B 细胞 NHL 的儿童、青少年和年轻成人(CAYA)显示出独特的临床和流行病学特征。这可能是由于与年龄相关的发育可塑性、免疫和造血系统、环境暴露和健康的社会决定因素以及种系或获得性遗传和分子特征(包括与先天性免疫错误(IEI)相关的特征)所造成的。在此,我们将讨论几种不同类型的儿科 B 细胞 NHL 的独特临床和生物学特征,为这些 CAYA NHL 的分类指明方向,以便为多学科患者护理和个性化治疗提供最佳支持。我们提出了一个潜在的 "产生于 CAYA "分类限定词,以表示 B 细胞 NHL 的独特临床病理特征,除此之外,这些 B 细胞 NHL 在组织学和免疫表型上与产生于中老年人的 B 细胞 NHL 相似。我们还讨论了血液病理学诊断如何发展,以便将最新的科学知识纳入未来的 CAYA B 细胞 NHL 分类系统。
{"title":"Dedicated diagnostic approaches for mature B-cell non-Hodgkin lymphomas occurring in children, adolescents, and young adults.","authors":"Ana C Xavier, Andishe Attarbaschi, Dita Gratzinger, Olga Balagué","doi":"10.1111/his.15362","DOIUrl":"https://doi.org/10.1111/his.15362","url":null,"abstract":"<p><p>Non-Hodgkin lymphoma (NHL) represents the fourth most common malignant disease among children and adolescents. Current disease classifications, including the most recent World Health Organization (WHO) classification and the International Consensus Classification (ICC), rely on a combination of clinical, epidemiological, histologic, immunophenotypic, and molecular data to define discrete clinicopathologic entities. There is growing evidence that children, adolescents, and young adults (CAYA) with B-cell NHL display unique clinical and epidemiologic characteristics. This may be explained by distinct age-related developmental plasticity, immune and haematopoietic repertoires, environmental exposures and social determinants of health, and germline or acquired genetic and molecular features, including those associated with inborn errors of immunity (IEI). Here, we discuss the unique clinical and biological characteristics of several distinct paediatric B-cell NHL types to indicate a path forward in classification of these CAYA NHL to optimally support multidisciplinary patient care and personalized treatment. We propose a potential \"arising in CAYA\" classification qualifier to denote the distinct clinicopathologic characteristics of B-cell NHLs that, otherwise, histologically and immunophenotypically resemble those arising in middle-aged and older adults. We also discuss how haemopathology diagnoses are evolving to incorporate the most current scientific knowledge into future classification systems of CAYA B-cell NHL.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675758","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}
Martina Bradová, Valerie Costes-Martineau, Jan Laco, Tomáš Vaněček, Petr Grossmann, Jana Němcová, Zdeněk Pavlovský, Alena Skálová, Michal Michal
Aims: Sinonasal adenosquamous carcinoma (ASC) is a rare tumour classified as a variant of squamous cell carcinoma, exhibiting both squamous and glandular differentiation. ASC has a poorer prognosis compared to sinonasal mucoepidermoid carcinoma (MEC), another uncommon tumour in this region. ASC is believed to originate from metaplastic squamous epithelium, though it may also arise from respiratory epithelium in respiratory epithelial adenomatoid hamartoma (REAH) or seromucinous glands in seromucinous hamartoma (SH).
Methods and results: Five cases of sinonasal ASC were retrieved from our registry. Initially, they were classified as sinonasal MEC (n = 3), ASC (n = 2), and carcinoma ex REAH (n = 1). All cases showed adenosquamous malignant proliferation beneath the surface respiratory epithelium with occasional squamous metaplasia, except for one case that showed dysplasia. The respiratory epithelium exhibited an inverted growth pattern consistent with REAH/SH, and displayed atypical sinonasal glands (ASGSH) arising within seromucinous hamartoma. Next-generation sequencing (NGS) revealed multiple pathogenic mutations in two cases, and in case 4 GGA2::PRKCB and EYA2::SERINC3 gene fusions. One case was positive for high-risk HPV. None of the cases exhibited CRTC1/3::MAML2 gene fusion.
Conclusion: The connection between ASGSH and ASC has not been described in the literature. There is a growing need for additional studies on the morphological, immunohistochemical, and genetic aspects of these tumours. SH/REAH may serve as precursor lesions in the progression of atypical sinonasal glands to malignancy, and their role in tumour development deserves further investigation.
{"title":"Sinonasal adenosquamous carcinomas arising in seromucinous hamartoma or respiratory epithelial adenomatoid hamartoma with atypical features: Report of five detailed clinicopathological and molecular characterisation of rare entity.","authors":"Martina Bradová, Valerie Costes-Martineau, Jan Laco, Tomáš Vaněček, Petr Grossmann, Jana Němcová, Zdeněk Pavlovský, Alena Skálová, Michal Michal","doi":"10.1111/his.15369","DOIUrl":"https://doi.org/10.1111/his.15369","url":null,"abstract":"<p><strong>Aims: </strong>Sinonasal adenosquamous carcinoma (ASC) is a rare tumour classified as a variant of squamous cell carcinoma, exhibiting both squamous and glandular differentiation. ASC has a poorer prognosis compared to sinonasal mucoepidermoid carcinoma (MEC), another uncommon tumour in this region. ASC is believed to originate from metaplastic squamous epithelium, though it may also arise from respiratory epithelium in respiratory epithelial adenomatoid hamartoma (REAH) or seromucinous glands in seromucinous hamartoma (SH).</p><p><strong>Methods and results: </strong>Five cases of sinonasal ASC were retrieved from our registry. Initially, they were classified as sinonasal MEC (n = 3), ASC (n = 2), and carcinoma ex REAH (n = 1). All cases showed adenosquamous malignant proliferation beneath the surface respiratory epithelium with occasional squamous metaplasia, except for one case that showed dysplasia. The respiratory epithelium exhibited an inverted growth pattern consistent with REAH/SH, and displayed atypical sinonasal glands (ASGSH) arising within seromucinous hamartoma. Next-generation sequencing (NGS) revealed multiple pathogenic mutations in two cases, and in case 4 GGA2::PRKCB and EYA2::SERINC3 gene fusions. One case was positive for high-risk HPV. None of the cases exhibited CRTC1/3::MAML2 gene fusion.</p><p><strong>Conclusion: </strong>The connection between ASGSH and ASC has not been described in the literature. There is a growing need for additional studies on the morphological, immunohistochemical, and genetic aspects of these tumours. SH/REAH may serve as precursor lesions in the progression of atypical sinonasal glands to malignancy, and their role in tumour development deserves further investigation.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675743","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}
Zlatko Marusic, Louise van der Weyden, Dimas Suárez Vilela, Faustino Suárez Sánchez, Jose Ramón Méndez Álvarez, Martin Del Castillo Velasco-Herrera, Ingrid Ferreira, David J Adams, Eduardo Calonje
{"title":"Shared immunohistochemical and genomic features of the low- and high-grade components of a cutaneous secretory carcinoma with epidermotrophism and lymph node involvement.","authors":"Zlatko Marusic, Louise van der Weyden, Dimas Suárez Vilela, Faustino Suárez Sánchez, Jose Ramón Méndez Álvarez, Martin Del Castillo Velasco-Herrera, Ingrid Ferreira, David J Adams, Eduardo Calonje","doi":"10.1111/his.15351","DOIUrl":"10.1111/his.15351","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667603","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}
Stefan K Alig, Björn Chapuy, Daisuke Ennishi, Kieron Dunleavy, Daniel J Hodson
This review aims to provide an overview of the latest developments in the classification and molecular understanding of aggressive B-cell lymphomas, specifically focusing on diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL). Advances in molecular techniques have led to novel ways to classify these lymphomas based on clinical, histological, transcriptional, and genetic properties. While these methods have predominantly focused on the malignant compartment, recent studies emphasize the value of profiling the tumour microenvironment for a more comprehensive disease classification. Additionally, the integration of liquid biopsies represents a promising advancement, offering less invasive and dynamic insights into tumour characteristics and treatment response. Although molecular profiles are not yet routinely used to guide therapy, emerging data highlight their potential to predict responses to novel treatments. It is our belief that integrating molecular profiling and liquid biopsies into clinical practice and research now will pave the way for more personalized and effective therapies in the future.
{"title":"Evolving molecular classification of aggressive B-cell lymphoma.","authors":"Stefan K Alig, Björn Chapuy, Daisuke Ennishi, Kieron Dunleavy, Daniel J Hodson","doi":"10.1111/his.15350","DOIUrl":"10.1111/his.15350","url":null,"abstract":"<p><p>This review aims to provide an overview of the latest developments in the classification and molecular understanding of aggressive B-cell lymphomas, specifically focusing on diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL). Advances in molecular techniques have led to novel ways to classify these lymphomas based on clinical, histological, transcriptional, and genetic properties. While these methods have predominantly focused on the malignant compartment, recent studies emphasize the value of profiling the tumour microenvironment for a more comprehensive disease classification. Additionally, the integration of liquid biopsies represents a promising advancement, offering less invasive and dynamic insights into tumour characteristics and treatment response. Although molecular profiles are not yet routinely used to guide therapy, emerging data highlight their potential to predict responses to novel treatments. It is our belief that integrating molecular profiling and liquid biopsies into clinical practice and research now will pave the way for more personalized and effective therapies in the future.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619330","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}
Yoon Jung Hwang, Yangkyu Lee, Su Jong Yu, Suk Kyun Hong, Nam-Joon Yi, YoungRok Choi, Hyejung Lee, Wonju Chung, Haeryoung Kim
Aims: The frequency of CTNNB1 mutation, one of the most frequent genetic events in hepatocellular carcinoma (HCC), is lower in Asian countries and in hepatitis B virus (HBV)-related HCCs. In this study, we evaluated the prevalence and types of CTNNB1-mutation in HBV-related HCC and correlated the molecular status with the histomorphological and immunohistochemical features.
Methods and results: A total of 108 consecutive cases of treatment-naïve, surgically resected HBV-related HCCs were selected. Targeted sequencing for CTNNB1 exons 3, 7 and 8 was performed, and the results were correlated with the expression pattern of glutamine synthetase (GS), nuclear β-catenin expression status and the histomorphological characteristics of the tumour. CTNNB1 mutations were identified in 13% of HBV-related HCCs; of these cases, mutations were found in D32-S37 (7%), T41 (4%) and S45 (2%) of exon 3. None of the HCCs demonstrated alterations in exons 7 and 8. CTNNB1 mutation was strongly associated with diffuse strong GS expression (P < 0.001), nuclear β-catenin expression (P < 0.001) and the classic CTNNB1 morphology (P = 0.038). Diffuse strong GS expression was observed in 78.6% of the CTNNB1-mutated HCCs, and nuclear β-catenin expression was identified in 64.3% of these cases. The classic CTNNB1 morphology was observed in 57% of all CTNNB1-mutated HCCs. Furthermore, programmed death-ligand 1 (PD-L1) was less frequently expressed in HCCs with classic CTNNB1 morphology.
Conclusions: CTNNB1 mutation was observed in 13% of HBV-related HCCs in this Korean cohort, and was associated with diffuse strong GS expression, nuclear β-catenin expression and classic CTNNB1 morphology.
{"title":"Correlation between CTNNB1 mutation status and tumour phenotype in hepatitis B virus-related hepatocellular carcinoma.","authors":"Yoon Jung Hwang, Yangkyu Lee, Su Jong Yu, Suk Kyun Hong, Nam-Joon Yi, YoungRok Choi, Hyejung Lee, Wonju Chung, Haeryoung Kim","doi":"10.1111/his.15363","DOIUrl":"https://doi.org/10.1111/his.15363","url":null,"abstract":"<p><strong>Aims: </strong>The frequency of CTNNB1 mutation, one of the most frequent genetic events in hepatocellular carcinoma (HCC), is lower in Asian countries and in hepatitis B virus (HBV)-related HCCs. In this study, we evaluated the prevalence and types of CTNNB1-mutation in HBV-related HCC and correlated the molecular status with the histomorphological and immunohistochemical features.</p><p><strong>Methods and results: </strong>A total of 108 consecutive cases of treatment-naïve, surgically resected HBV-related HCCs were selected. Targeted sequencing for CTNNB1 exons 3, 7 and 8 was performed, and the results were correlated with the expression pattern of glutamine synthetase (GS), nuclear β-catenin expression status and the histomorphological characteristics of the tumour. CTNNB1 mutations were identified in 13% of HBV-related HCCs; of these cases, mutations were found in D32-S37 (7%), T41 (4%) and S45 (2%) of exon 3. None of the HCCs demonstrated alterations in exons 7 and 8. CTNNB1 mutation was strongly associated with diffuse strong GS expression (P < 0.001), nuclear β-catenin expression (P < 0.001) and the classic CTNNB1 morphology (P = 0.038). Diffuse strong GS expression was observed in 78.6% of the CTNNB1-mutated HCCs, and nuclear β-catenin expression was identified in 64.3% of these cases. The classic CTNNB1 morphology was observed in 57% of all CTNNB1-mutated HCCs. Furthermore, programmed death-ligand 1 (PD-L1) was less frequently expressed in HCCs with classic CTNNB1 morphology.</p><p><strong>Conclusions: </strong>CTNNB1 mutation was observed in 13% of HBV-related HCCs in this Korean cohort, and was associated with diffuse strong GS expression, nuclear β-catenin expression and classic CTNNB1 morphology.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619329","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}