Human pathology最新文献

{"title":"Salivary gland amyloidosis: Proteomic identification and clinicopathologic characterization of 57 cases","authors":"April Chiu ,&nbsp;Surendra Dasari ,&nbsp;Samih H. Nasr ,&nbsp;Angela Dispenzieri ,&nbsp;Linda N. Dao ,&nbsp;Joanna C. Dalland ,&nbsp;Matthew T. Howard ,&nbsp;Daniel P. Larson ,&nbsp;Karen L. Rech ,&nbsp;Jason D. Theis ,&nbsp;Julie A. Vrana ,&nbsp;Ellen D. McPhail","doi":"10.1016/j.humpath.2024.105628","DOIUrl":"10.1016/j.humpath.2024.105628","url":null,"abstract":"<div><p>Salivary gland amyloidosis is an uncommon diagnosis. Most studies have focused on minor salivary gland biopsies as a surrogate site for diagnosing systemic amyloidosis, while only few studies have investigated major salivary gland amyloidosis. We retrospectively identified 57 major and minor salivary gland amyloidosis cases typed using a proteomics-based method between 2010 and 2022. Frequency of amyloid types, clinicopathologic features, and distribution patterns of amyloid deposits were assessed. The indication for salivary gland biopsy/resection (known in 34 cases) included suspected amyloidosis (N = 14; 41.2%), lesion/mass (N = 12; 35.3%), swelling/enlargement (N = 5; 14.7%), and rule out Sjogren syndrome (N = 3; 8.8%). Concurrent pathology was reported in 16 cases, and included chronic sialadenitis (N = 11), extranodal marginal zone lymphoma (N = 3), plasma cell neoplasm (N = 1), and pleomorphic adenoma (N = 1). We identified 3 types of amyloidosis: immunoglobulin light chain/AL (N = 47; 82.5%); immunoglobulin heavy chain/AH (N = 1; 1.8%), and transthyretin/ATTR (N = 9; 15.8%). The patterns of amyloid deposits (assessed in 35 cases) included: 1) Perivascular and/or periductal distribution (N = 18; 51.4%); 2) Mass formation (N = 9; 25.7%); 3) Stromal micronodule formation (N = 7; 20.0%); and 4) Diffuse interstitial involvement (N = 1; 2.9%). We also identified one case of AL amyloidosis localized to the major salivary gland, where only 6 other cases with adequate staging workup to exclude systemic amyloidosis were previously reported. In conclusion, salivary gland amyloidosis is an uncommon diagnosis but may be underrecognized due to low index of suspicion. Most cases of salivary gland amyloidosis are AL type, but a minority are ATTR. Therefore, proteomics-based typing remains essential for treatment and prognosis.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"151 ","pages":"Article 105628"},"PeriodicalIF":2.7,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727133","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":"Small bowel pyloric metaplasia is associated with lower rates of earlier recurrence of Crohn's disease after resection","authors":"Jennifer Y. Ju ,&nbsp;David J. Escobar ,&nbsp;Yue Xue ,&nbsp;Adam L. Booth ,&nbsp;Jessica Nguyen ,&nbsp;Guang-Yu Yang","doi":"10.1016/j.humpath.2024.105629","DOIUrl":"10.1016/j.humpath.2024.105629","url":null,"abstract":"<div><p>Recurrence within one or two years is common after Crohn's disease (CD) resection. In this study, we seek to identify histologic features in CD resections that may predict earlier (≤18 months) recurrence to potentially guide post-operative management. A single-institution, retrospective review was performed on patients with first-time CD bowel resection specimens (2002–2007). Patient demographics and CD course were also documented. Slides were reviewed for inflammatory distribution and composition, small bowel (SB) pyloric metaplasia (PM), and presence and characteristics of submucosal fibrosis and granulomas. In our cohort, 14 of 41 patients experienced earlier clinical or endoscopic recurrence after initial resection. In the 38 patients who underwent SB resection (3 were colon only), PM was less common in those with earlier recurrence (6/12 [50%]) compared to those with later (&gt;18 months) or no known recurrence (22/26 [85%]) (<em>P</em> = 0.045). PM was present even in patients with &lt;1 year of known CD. Additionally, therapy with anti-tumor necrosis factor (TNF) prior to surgery was more common in earlier recurrence patients (7/14 [50%]) than later or no recurrence patients (4/27 [15%]) (<em>P</em> = 0.026). There was no significant difference in age, sex, smoking status, duration of CD, post-operative CD medication, distribution or features of inflammation, granulomas, or fibrosis. Overall, our results indicate that SB PM and pre-surgical anti-TNF therapy are possible helpful clinicopathologic features to evaluate for recurrence risk.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"151 ","pages":"Article 105629"},"PeriodicalIF":2.7,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727134","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":"The utility of the lineage specific immunohistochemical stains SATB2, CDX2, and villin, and the mucin glycoproteins MUC2, MUC5AC, and MUC6 to distinguish pulmonary invasive mucinous adenocarcinoma from metastatic colorectal carcinoma","authors":"Vilasinee Rerkpichaisuth ,&nbsp;Ryan P. Lau ,&nbsp;Cherise Meyerson ,&nbsp;Gregory A. Fishbein","doi":"10.1016/j.humpath.2024.105627","DOIUrl":"10.1016/j.humpath.2024.105627","url":null,"abstract":"<div><h3>Context</h3><p>The lungs are a common site of tumor metastasis. While morphology and immunophenotype can help differentiate primary from metastatic tumors, distinguishing pulmonary invasive mucinous adenocarcinoma (PIMA) from metastatic colorectal adenocarcinoma (CRC) may occasionally be challenging due to overlapping morphological and immunohistochemical features. Lineage-specific markers such as CDX2, TTF-1, and napsin A are helpful with pulmonary non-mucinous adenocarcinoma (PNMA), however they are non-specific and insensitive when applied to PIMA. SATB2 is a newer marker that distinguishes CRC from upper gastrointestinal and pancreaticobiliary tumors; its utility in distinguishing CRC from PIMA has not been fully elucidated.</p></div><div><h3>Objective</h3><p>To evaluate the performance of lineage-specific and mucin glycoprotein immunostains in distinguishing PIMA and CRC.</p></div><div><h3>Design</h3><p>We stained tissue microarrays comprising 34 PNMA, 31 PIMA, and 32 CRC with CK7, CK20, SATB2, CDX2, villin, TTF-1, napsin A, and gel-forming mucins MUC2, MUC5AC, and MUC6.</p></div><div><h3>Results</h3><p>PIMA showed significant (&gt;50% of cells) expression of SATB2 (6%), CDX2 (6%), villin (74%), TTF-1 (13%), and napsin A (23%). However, significant CK7 expression was seen in nearly all PIMA (30/31) and none of the metastatic CRC.</p></div><div><h3>Conclusion</h3><p>Our results suggest that CK7 remains one of the most useful markers for distinguishing primary PIMA from metastatic CRC. Expression of the mucin glycoproteins MUC5AC and MUC6 and lack of expression of MUC2 favored a diagnosis of PIMA, but expression of these markers was too heterogeneous to be of clinical utility. To our knowledge this is the only study comparing the immunohistochemical profile of PIMA and metastatic CRC in lung metastasectomy specimens.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"151 ","pages":"Article 105627"},"PeriodicalIF":2.7,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0046817724001291/pdfft?md5=72000903a7f481d57e2596f7d9b4d7b1&pid=1-s2.0-S0046817724001291-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727135","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}

{"title":"TPPP-BRD9 fusion-related gallbladder carcinomas are frequently associated with intracholecystic neoplasia, neuroendocrine carcinoma, and a distinctive small tubular-type adenocarcinoma commonly accompanied with a syringomatous pattern","authors":"Burcin Pehlivanoglu ,&nbsp;Juan Carlos Araya ,&nbsp;Scott Lawrence ,&nbsp;Juan Carlos Roa ,&nbsp;Serdar Balci ,&nbsp;Jesper B. Andersen ,&nbsp;Asif Rashid ,&nbsp;Ann W. Hsing ,&nbsp;Bin Zhu ,&nbsp;Yu-Tang Gao ,&nbsp;Jill Koshiol ,&nbsp;Volkan Adsay","doi":"10.1016/j.humpath.2024.07.001","DOIUrl":"10.1016/j.humpath.2024.07.001","url":null,"abstract":"<div><p>A fusion between tubulin polymerization-promoting protein (<em>TPPP</em>), a regulatory cytoskeletal gene, and the chromatin remodeling factor, bromodomain-containing protein 9 (<em>BRD9</em>), <em>TPPP-BRD9</em> fusion has been found in rare cancer cases, including lung and gallbladder cancers (GBC). In this study, we investigated the histopathological features of 16 GBCs previously shown by RNA sequencing to harbor the <em>TPPP-BRD9</em> fusion. Findings in the fusion-positive GBCs were compared with 645 GBC cases from the authors’ database. Among the 16 <em>TPPP-BRD9</em> fusion-positive GBC cases, most were females (F:M = 7:1) of Chinese ethnicity (12/16), whereas the remaining cases were from Chile. The histopathological examination showed the following findings: 1) Intracholecystic neoplasm (ICN) in 7/15 (47% vs. 7% 645 reference GBCs, p &lt; 0.001), all with gastro-pancreatobiliary phenotype, often with clear cell change, and in the background of pyloric gland metaplasia and extensive high-grade dysplasia. 2) Neuroendocrine carcinoma (NEC) morphology: 3 cases (27% vs. 4.6% in the reference database, p = 0.001) showed a sheet-like and nested/trabecular growth pattern of monotonous cells with salt-and-pepper chromatin characteristic of NECs. Two were large cell type, one had prominent clear cell features, a rare finding in GBNECs; the other one had relatively bland, well-differentiated morphology, and the remaining case was small cell type. 3) Adenocarcinoma identified in 8 cases had a distinctive pattern characterized by widely separated small, round tubular units with relatively uniform nuclei in a fashion seen in mesonephric adenocarcinomas, including hobnail-like arrangement and apical snouts, reminiscent of tubular carcinomas of the breast in many areas. In some foci, the epithelium was attenuated, and glands were elongated, some with comma shapes, which along with the mucinous/necrotic intraluminal debris created a “syringoid” appearance. 4) Other occasional patterns included the cribriform, glomeruloid patterns, and metaplastic tubular-spindle cell pattern accompanied by hemorrhage. In conclusion, <em>TPPP-BRD9</em> fusion-positive GBCs often develop through intracholecystic neoplasms (adenoma-carcinoma sequence) of gastro-pancreatobiliary lineage, appear more prone to form NEC morphology and have a propensity to display clear cell change. Invasive adenocarcinomas arising in this setting often seem to display a distinctive appearance that we tentatively propose as the <em>TPPP-BRD9</em> fusion-positive pattern of GBC.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 67-73"},"PeriodicalIF":2.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554642","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":"DUSP22-rearranged primary cutaneous CD30-positive T-cell lymphoproliferative disorders and adult T-cell leukemia/lymphoma frequently share the LEF1+/TIA1− immunophenotype","authors":"Bo-Jung Chen ,&nbsp;Shu-Min Hsieh ,&nbsp;Tsung-Han Hsieh ,&nbsp;Jie-Yang Jhuang ,&nbsp;Yu-Chien Kao","doi":"10.1016/j.humpath.2024.07.002","DOIUrl":"10.1016/j.humpath.2024.07.002","url":null,"abstract":"<div><p><em>DUSP22</em> rearrangements are genetic alterations observed in a subset of systemic anaplastic large cell lymphoma (S-ALCL), primary cutaneous anaplastic large cell lymphoma (C-ALCL), and lymphomatoid papulosis (LyP). Previous investigations have shown that the LEF1+/TIA1− immunoprofile and <em>MSC</em> E116K mutations are highly associated with <em>DUSP22</em> rearrangement in ALCL. However, the existing literature primarily focuses on S-ALCL. Our understanding of the LEF1/TIA1 immunoprofile and <em>MSC</em> mutation status in C-ALCL/LyP is still limited. In this study, we aimed to assess LEF1/TIA1 expression and <em>MSC</em> mutations in a cohort of 23 C-ALCL/LyP cases, along with a control group of histological mimickers. <em>DUSP22</em> rearrangements were detected by fluorescence in situ hybridization in eight cases (6/10 C-ALCL, 2/13 LyP). We found LEF1 expression in five out of eight (63%) <em>DUSP22-</em>rearranged cases (3/6 C-ALCL, 2/2 LyP), and none of the 15 cases lacking <em>DUSP22</em> rearrangements. Furthermore, we also found frequent LEF1 expression in adult T-cell leukemia/lymphoma (ATLL; 10 of 11, 91%) within the control group. TIA1 expression was consistently negative in all <em>DUSP22</em>-rearranged C-ALCL/LyP and ATLL cases tested. <em>MCS</em> E116K mutation was identified in one of five <em>DUSP22</em>-rearranged C-ALCL cases. RNA sequencing of a <em>DUSP22</em>-rearranged C-ALCL revealed a novel <em>DUSP22</em>::<em>SNHG</em> fusion coexisting with a <em>CD58</em>::<em>WNT2B</em> fusion. In conclusion, our findings demonstrated a lower rate of LEF1 expression in <em>DUSP22</em>-rearranged C-ALCL/LyP compared to previous reports that predominantly focused on S-ALCL. Moreover, we observed that the majority of ATLL cases also expressed LEF1, suggesting that the LEF1+/TIA1− immunoprofile does not differentiate <em>DUSP22</em>-rearranged C-ALCL/LyP from ATLL.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 58-66"},"PeriodicalIF":2.7,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544741","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":"Clinicopathologic features and outcomes of acute leukemia harboring PICALM::MLLT10 fusion","authors":"","doi":"10.1016/j.humpath.2024.07.003","DOIUrl":"10.1016/j.humpath.2024.07.003","url":null,"abstract":"<div><p>The <em>PICALM::MLLT10</em> fusion is a rare but recurrent cytogenetic abnormality in acute leukemia, with limited clinicopathologic and outcome data available. Herein, we analyzed 156 acute leukemia patients with <em>PICALM::MLLT10</em> fusion, including 12 patients from our institutions and 144 patients from the literature. The <em>PICALM::MLLT10</em> fusion preferentially manifested in pediatric and young adult patients, with a median age of 24 years. T-lymphoblastic leukemia/lymphoma (T-ALL) constituted 65% of cases, acute myeloid leukemia (AML) 27%, and acute leukemia of ambiguous lineage (ALAL) 8%. About half of T-ALL were classified as an early T-precursor (ETP)-ALL. In our institutions’ cohort, mediastinum was the most common extramedullary site of involvement. Eight of 12 patients were diagnosed with T-ALL exhibiting a pro-/pre-T stage phenotype (CD4/CD8-double negative, CD7-positive), and frequent CD79a expression. NGS revealed pathogenic mutations in 5 of 6 tested cases, including <em>NOTCH1,</em> and genes in RAS and JAK-STAT pathways and epigenetic modifiers. Of 138 cases with follow-up, pediatric patients (&lt;18 years) had 5-year overall survival (OS) of 71%, significantly better than adults at 33%. The 5-year OS for AML patients was 25%, notably shorter than T-ALL patients at 54%; this distinction was observed in both pediatric and adult populations. Furthermore, adult but not pediatric ETP-ALL patients demonstrated inferior survival compared to non-ETP-ALL patients. Neither karyotype complexity nor transplant status had a discernible impact on OS. In conclusion, <em>PICALM::MLLT10</em> fusion is most commonly seen in T-ALL patients, particularly those with an ETP phenotype. AML and adult ETP-ALL patients had adverse prognosis. <em>PICALM::MLTT10</em> fusion testing should be considered in T-ALL, AML, and ALAL patients.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"151 ","pages":"Article 105626"},"PeriodicalIF":2.7,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544740","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":"Corrigendum to “Plasma cells are essentially absent in the luminal gastrointestinal tract of patients with “complete” 22q11.2 Deletion Syndrome (DiGeorge Syndrome).” [Human Pathology (2021) 117, 1e8]","authors":"Avani A. Pendse ,&nbsp;Jake G. Maule ,&nbsp;Jadee L. Neff ,&nbsp;Shannon McCall","doi":"10.1016/j.humpath.2024.03.004","DOIUrl":"10.1016/j.humpath.2024.03.004","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"149 ","pages":"Page 80"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0046817724000479/pdfft?md5=c1bc0f845c4846bb4b6b9c6ed02cae9c&pid=1-s2.0-S0046817724000479-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331650","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}

{"title":"There are benefits of subtyping hepatocellular adenoma also in men – reply","authors":"Iván A. González,&nbsp;Michael Torbenson,&nbsp;Sanjay Kakar,&nbsp;Dhanpat Jain","doi":"10.1016/j.humpath.2024.05.004","DOIUrl":"10.1016/j.humpath.2024.05.004","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"149 ","pages":"Page 79"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087615","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":"Information for Authors","authors":"","doi":"10.1016/S0046-8177(24)00114-X","DOIUrl":"https://doi.org/10.1016/S0046-8177(24)00114-X","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"149 ","pages":"Page iv"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141483303","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":"Steatohepatitic hepatocellular Carcinoma:A new approach to classifying morphological subtypes of hepatocellular carcinoma","authors":"Gwyneth S.T. Soon ,&nbsp;Francesco Callea ,&nbsp;Alastair D. Burt ,&nbsp;Sam Cook ,&nbsp;Luigi Terracciano ,&nbsp;Caner Ercan ,&nbsp;Hans-Peter Dienes ,&nbsp;Zachary D. Goodman ,&nbsp;Eve A. Roberts ,&nbsp;Andrew D. Clouston ,&nbsp;Annette S.H. Gouw ,&nbsp;David E. Kleiner ,&nbsp;Young Nyun Park ,&nbsp;Taek Chung ,&nbsp;Peter Schirmacher ,&nbsp;Dina Tiniakos ,&nbsp;Konstantina Dimopoulou ,&nbsp;Achim Weber ,&nbsp;Katharina Endhardt ,&nbsp;Michael Torbenson","doi":"10.1016/j.humpath.2024.06.007","DOIUrl":"10.1016/j.humpath.2024.06.007","url":null,"abstract":"<div><p>Histological subtyping of hepatocellular carcinoma (HCC) is challenging in the presence of histological heterogeneity, where distinctly different morphological patterns are present within the same tumor. Current approaches rely on percent cut-offs. We hypothesized that morphologic intratumor heterogeneity is a non-random biological feature and that incorporating recurrent patterns would improve histological subtyping of HCC. Resected HCC were studied and the overall frequency of morphologic intratumor heterogeneity was 45% in 242 specimens. Steatohepatitic HCC (SH-HCC) had the highest frequency of morphologic intratumor heterogeneity (91%); this was confirmed in additional cohorts of SH-HCC from different medical centers (overall frequency of 78% in SH-HCC). Morphologic intratumor heterogeneity in SH-HCC showed distinct and recurrent patterns that could be classified as early, intermediate, and advanced. Incorporating these patterns into the definition of SH-HCC allowed successful resolution of several persistent challenges: the problem of the best cut-off for subtyping SH-HCC, the problem of the relationship between SH-HCC and scirrhous HCC, and the classification for HCC with abundant microvesicular steatosis. This approach also clarified the relationship between SH-HCC and <em>CTNNB1</em> mutations, showing that <em>CTNNB1</em> mutations occur late in a subset of SH-HCC. In summary, there is a high frequency of morphologic intratumor heterogeneity in HCC. Incorporating this finding into histological subtyping resolved several persistent problems with the SH-HCC subtype.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"149 ","pages":"Pages 55-65"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320757","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}