Mullerian adenosarcoma is a rare malignant biphasic tumor. The mesenchymal component may be low or high grade, with or without sarcomatous overgrowth (SO). Little is known about the molecular heterogeneity of these tumors. In this study, we aim to reclassify a large retrospective monocentric cohort of uterine adenosarcomas according to tumor grade and SO, to evaluate the clinical significance of pathological classification and to correlate with copy-number variations inferred from single nucleotide polymorphism array. Of the 67 uterine adenosarcomas, 18 (26.9%) were low grade without SO, 7 (10.4%) low grade with SO, 8 (11.9%) high grade without SO and 34 (50.7%) high grade with SO. SO, necrosis and RMS were more frequent in high grade than low grade adenosarcomas (p < 0.001). Low-rank test showed that recurrence-free survival was significantly shortened in high grade than low grade adenosarcomas (p = 0.035) and SO was associated with shortened overall and recurrence-free survival (p = 0.038 and p = 0.009, respectively). High-grade tumors displayed complex genomic profiles with multiple segmental losses including TP53, ATM and PTEN genes. The median genomic index was significantly higher in high grade than low grade tumors (27 [3–60] vs 5,3 [0–16], p < 0.0001) and was significantly higher in presence of SO in low grade tumors (12,8 [10–16] vs 2,6 [0–10], p = 0.0006). We propose to report sarcomatous overgrowth with the tumor grade for prognostication in adenosarcoma and representative sampling is crucial for evaluation of these histological criteria.
穆勒氏腺肉瘤是一种罕见的双相恶性肿瘤。间质成分可能是低级别或高级别,伴有或不伴有肉瘤过度生长(SO)。人们对这些肿瘤的分子异质性知之甚少。在这项研究中,我们旨在根据肿瘤分级和SO对一个大型回顾性单中心子宫腺肉瘤队列进行重新分类,评估病理分类的临床意义,并与单核苷酸多态性阵列推断出的拷贝数变异进行关联分析。在67例子宫腺肉瘤中,18例(26.9%)为无SO的低分级,7例(10.4%)为有SO的低分级,8例(11.9%)为无SO的高级别,34例(50.7%)为有SO的高级别。与低级别腺肉瘤相比,高级别腺肉瘤中SO、坏死和RMS的发生率更高(P <0.001)。低秩检验显示,高级别腺肉瘤的无复发生存期明显短于低级别腺肉瘤(p = 0.035),SO与总生存期和无复发生存期的缩短有关(分别为p = 0.038和p = 0.009)。高级别肿瘤显示出复杂的基因组图谱,存在多个节段性缺失,包括TP53、ATM和PTEN基因。高分级肿瘤的中位基因组指数明显高于低分级肿瘤(27 [3-60] vs 5,3 [0-16],p <0.0001),低分级肿瘤中出现 SO 的中位基因组指数明显高于高分级肿瘤(12,8 [10-16] vs 2,6 [0-10],p = 0.0006)。我们建议将肉瘤过度生长与肿瘤分级一起报告,用于腺肉瘤的预后评估,而代表性取样对于评估这些组织学标准至关重要。
{"title":"Uterine adenosarcoma: Clinical significance of histological classification and SNP array analysis","authors":"Carine Ngo , Sophie Cotteret , Imène Deneche , Maria Kfoury , Randa Chehab , Alicia Tran-Dien , Julien Vibert , Alexandra Leary , Sébastien Gouy , Amandine Maulard , Philippe Morice , Jean-Yves Scoazec , Patricia Pautier , Catherine Genestie","doi":"10.1016/j.humpath.2024.04.016","DOIUrl":"https://doi.org/10.1016/j.humpath.2024.04.016","url":null,"abstract":"<div><p>Mullerian adenosarcoma is a rare malignant biphasic tumor. The mesenchymal component may be low or high grade, with or without sarcomatous overgrowth (SO). Little is known about the molecular heterogeneity of these tumors. In this study, we aim to reclassify a large retrospective monocentric cohort of uterine adenosarcomas according to tumor grade and SO, to evaluate the clinical significance of pathological classification and to correlate with copy-number variations inferred from single nucleotide polymorphism array. Of the 67 uterine adenosarcomas, 18 (26.9%) were low grade without SO, 7 (10.4%) low grade with SO, 8 (11.9%) high grade without SO and 34 (50.7%) high grade with SO. SO, necrosis and RMS were more frequent in high grade than low grade adenosarcomas (p < 0.001). Low-rank test showed that recurrence-free survival was significantly shortened in high grade than low grade adenosarcomas (p = 0.035) and SO was associated with shortened overall and recurrence-free survival (p = 0.038 and p = 0.009, respectively). High-grade tumors displayed complex genomic profiles with multiple segmental losses including <em>TP53</em>, <em>ATM</em> and <em>PTEN</em> genes. The median genomic index was significantly higher in high grade than low grade tumors (27 [3–60] vs 5,3 [0–16], p < 0.0001) and was significantly higher in presence of SO in low grade tumors (12,8 [10–16] vs 2,6 [0–10], p = 0.0006). We propose to report sarcomatous overgrowth with the tumor grade for prognostication in adenosarcoma and representative sampling is crucial for evaluation of these histological criteria.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140824402","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}
Pub Date : 2024-04-27DOI: 10.1016/j.humpath.2024.04.008
{"title":"Expanding the spectrum of paratesticular mullerian-origin tumors: Adenocarcinoma with mixed serous and endometrioid features and clear cell carcinoma","authors":"","doi":"10.1016/j.humpath.2024.04.008","DOIUrl":"10.1016/j.humpath.2024.04.008","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848512","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}
Pub Date : 2024-04-26DOI: 10.1016/j.humpath.2024.04.012
Lan Zheng , Hui Chen , Jianping Zhao , Sinchita Roy-Chowdhuri , Ashish M. Kamat , Omar Alhalabi , Jianjun Gao , Arlene Siefker-Radtke , Donna E. Hansel , Bogdan Czerniak , Charles C. Guo
Plasmacytoid urothelial carcinoma (UC) is a rare histologic subtype of bladder cancer that is associated with an aggressive clinical behavior. We analyzed the clinicopathologic and molecular features of plasmacytoid UC in 52 patients from a single institute. The patients included 44 men and 8 women, with a mean age of 64 years (range, 41–91 years). All bladder cancers were high-grade UC, and plasmacytoid component accounted for a mean of 47% of bladder tumors (range, 5–100%). Distinct gene mutations were found in most plasmacytoid UCs (n = 49); the most common mutations were TP53 (n = 30), followed by TERT (n = 20), and CDH1 (n = 18). Copy number analysis was performed in 34 patients, and 13 of them showed copy number variations. Expression of HER2 was analyzed in 18 patients by immunohistochemistry, and 3 of them showed HER2 overexpression, which was confirmed by fluorescence in situ hybridization analysis. Thirty-two patients died of disease in a median of 15 months (range, 1–45 months). No individual gene mutations were significantly associated with clinical outcome, but mutations in the mammalian target of rapamycin (mTOR) pathway, including PICK3CA and PIK3R1 mutations, were associated with a significantly shorter survival duration (p < 0.05). Plasmacytoid UC is an aggressive histologic subtype that demonstrates frequent somatic gene mutations and CNVs, which may underlie its oncogenesis and progression. Gene mutations of the mTOR pathway are associated with poor outcome in a subset of patients with plasmacytoid UC.
{"title":"Plasmacytoid urothelial carcinoma of the urinary bladder–A clinicopathological and molecular analysis of 52 cases","authors":"Lan Zheng , Hui Chen , Jianping Zhao , Sinchita Roy-Chowdhuri , Ashish M. Kamat , Omar Alhalabi , Jianjun Gao , Arlene Siefker-Radtke , Donna E. Hansel , Bogdan Czerniak , Charles C. Guo","doi":"10.1016/j.humpath.2024.04.012","DOIUrl":"https://doi.org/10.1016/j.humpath.2024.04.012","url":null,"abstract":"<div><p>Plasmacytoid urothelial carcinoma (UC) is a rare histologic subtype of bladder cancer that is associated with an aggressive clinical behavior. We analyzed the clinicopathologic and molecular features of plasmacytoid UC in 52 patients from a single institute. The patients included 44 men and 8 women, with a mean age of 64 years (range, 41–91 years). All bladder cancers were high-grade UC, and plasmacytoid component accounted for a mean of 47% of bladder tumors (range, 5–100%). Distinct gene mutations were found in most plasmacytoid UCs (n = 49); the most common mutations were <em>TP53</em> (n = 30), followed by <em>TERT</em> (n = 20), and <em>CDH1</em> (n = 18). Copy number analysis was performed in 34 patients, and 13 of them showed copy number variations. Expression of <em>HER2</em> was analyzed in 18 patients by immunohistochemistry, and 3 of them showed <em>HER2</em> overexpression, which was confirmed by fluorescence in situ hybridization analysis. Thirty-two patients died of disease in a median of 15 months (range, 1–45 months). No individual gene mutations were significantly associated with clinical outcome, but mutations in the mammalian target of rapamycin (<em>mTOR</em>) pathway, including <em>PICK3CA</em> and <em>PIK3R1</em> mutations, were associated with a significantly shorter survival duration (p < 0.05). Plasmacytoid UC is an aggressive histologic subtype that demonstrates frequent somatic gene mutations and CNVs, which may underlie its oncogenesis and progression. Gene mutations of the <em>mTOR</em> pathway are associated with poor outcome in a subset of patients with plasmacytoid UC.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140815975","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}
Pub Date : 2024-04-25DOI: 10.1016/j.humpath.2024.04.010
Fengming Chen , Samuel E. Harvey , Eric D. Young , Tom Z. Liang , Tatianna Larman , Lysandra Voltaggio
Aims
Appendiceal mucinous neoplasms feature neoplastic mucinous epithelium with pushing borders and densely fibrotic walls. We have identified five examples of analogous colorectal tumours.
Methods and results
Slides, pathology reports, and clinical data were reviewed. Whole genome sequencing was performed in two cases. Three were women and the mean age was 70. Associated GI conditions included Crohn's disease [1], diverticulosis [2], and sarcoma of the terminal ileum [1]. Signs/symptoms included obstruction [2], nausea, vomiting, abdominal pain [1], and positive faecal immunohistochemical test [1]. Colonoscopic findings included narrowing [1], “fullness” [1], and caecal lesion concerning for GIST [1]. Tumours involved the rectosigmoid [2], sigmoid [1], transverse colon [1], and cecum [1] and ranged from 1.5 cm to 8.5 cm. All but one tumour arose in the setting of faecal stream abnormalities related to obstruction, diverticulosis, or bowel diversion. All cases showed columnar, variably mucinous epithelium associated with little-to-no lamina propria. All but one case showed fibrosis of the submucosa. Three cases had high-grade areas. Neoplastic glands and/or mucin dissected through the muscularis propria or subserosa in 3 examples. No extracolonic neoplastic cells/mucin, infiltrative invasion, or desmoplastic response were identified. Three patients with available follow-up [5.5–28 months] are alive. Whole genome sequencing identified pathogenic TP53 and ERBB2 variants, as well as ERBB2 copy number amplification in one high-grade example.
Conclusions
Though these tumours share clinicopathologic characteristics with their appendiceal counterparts, our cohort is too small to draw solid conclusions. We propose the term “extra-appendiceal mucinous neoplasm [EAMN]” for these rare lesions.
{"title":"Extra-appendiceal mucinous neoplasms: A tumour with clinicopathologic similarities to low- and high-grade appendiceal counterpart","authors":"Fengming Chen , Samuel E. Harvey , Eric D. Young , Tom Z. Liang , Tatianna Larman , Lysandra Voltaggio","doi":"10.1016/j.humpath.2024.04.010","DOIUrl":"10.1016/j.humpath.2024.04.010","url":null,"abstract":"<div><h3>Aims</h3><p>Appendiceal mucinous neoplasms feature neoplastic mucinous epithelium with pushing borders and densely fibrotic walls. We have identified five examples of analogous colorectal tumours.</p></div><div><h3>Methods and results</h3><p>Slides, pathology reports, and clinical data were reviewed. Whole genome sequencing was performed in two cases. Three were women and the mean age was 70. Associated GI conditions included Crohn's disease [1], diverticulosis [2], and sarcoma of the terminal ileum [1]. Signs/symptoms included obstruction [2], nausea, vomiting, abdominal pain [1], and positive faecal immunohistochemical test [1]. Colonoscopic findings included narrowing [1], “fullness” [1], and caecal lesion concerning for GIST [1]. Tumours involved the rectosigmoid [2], sigmoid [1], transverse colon [1], and cecum [1] and ranged from 1.5 cm to 8.5 cm. All but one tumour arose in the setting of faecal stream abnormalities related to obstruction, diverticulosis, or bowel diversion. All cases showed columnar, variably mucinous epithelium associated with little-to-no lamina propria. All but one case showed fibrosis of the submucosa. Three cases had high-grade areas. Neoplastic glands and/or mucin dissected through the muscularis propria or subserosa in 3 examples. No extracolonic neoplastic cells/mucin, infiltrative invasion, or desmoplastic response were identified. Three patients with available follow-up [5.5–28 months] are alive. Whole genome sequencing identified pathogenic <em>TP53</em> and <em>ERBB2</em> variants, as well as <em>ERBB2</em> copy number amplification in one high-grade example.</p></div><div><h3>Conclusions</h3><p>Though these tumours share clinicopathologic characteristics with their appendiceal counterparts, our cohort is too small to draw solid conclusions. We propose the term “extra-appendiceal mucinous neoplasm [EAMN]” for these rare lesions.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140777149","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}
Pub Date : 2024-04-25DOI: 10.1016/j.humpath.2024.04.013
Henriette L. Warm , Leonie D. Kandt , Nora Schaumann , Christopher Werlein , Malte Gronewold , Henriette Christgen , Malin Hellmann , Marcel Lafos , Bernd Auber , Peter Hillemanns , Hans Kreipe , Matthias Christgen
Collagenous spherulosis (CS) is a rare breast lesion of unknown histogenesis. Adenoid cystic carcinoma (ACC) is a rare basal-like breast carcinoma with low histological grade. CS is a benign lesion but resembles ACC. Both lesions show a similar histomorphology and feature bilineage differentiation. This study compared immunohistochemical markers in CS and ACC.
We compiled n = 13 CS cases and n = 18 mammary ACCs. Fourteen marker proteins (ER, PR, HER2, GATA3, CK7, E-cadherin, CD117, CK5/14, p40, p63, SMA, CD10, calponin, P-cadherin) were evaluated by immunohistochemistry (IHC). MYB rearrangement, a common alteration in ACC, was assessed by fluorescence in situ hybridization.
Patient age ranged between 40-60 years for CS lesions and 30–90 years for ACCs. 7/13 (54%) CS cases harbored a lobular carcinoma in situ (LCIS) in the luminal component. One CS/LCIS lesion occurred in a carrier of a pathogenic germline variant in CDH1/E-cadherin. MYB rearrangement was detected in 0/11 (0%) CS and 6/16 (37%) ACC cases (P = 0.054). CS was associated with expression of ER in the luminal component (P < 0.001), E-cadherin loss in the luminal component (P = 0.045), and expression of CD10 and calponin in the basal component (P < 0.001). Furthermore, CS was associated with GATA3 expression in the luminal component (12/13 [92%] versus 5/18 [27%], P < 0.001).
In summary, IHC for GATA3 and E-cadherin may contribute to the differential diagnosis between CS and ACC, although these markers are not exclusively expressed in either lesion. Histologic evaluation has to take into account that CS is frequently colonized by LCIS, requiring thorough correlation of histomorphology and immunohistochemical features.
{"title":"Immunohistochemical marker profiles for the differentiation of collagenous spherulosis from adenoid cystic carcinoma of the breast","authors":"Henriette L. Warm , Leonie D. Kandt , Nora Schaumann , Christopher Werlein , Malte Gronewold , Henriette Christgen , Malin Hellmann , Marcel Lafos , Bernd Auber , Peter Hillemanns , Hans Kreipe , Matthias Christgen","doi":"10.1016/j.humpath.2024.04.013","DOIUrl":"10.1016/j.humpath.2024.04.013","url":null,"abstract":"<div><p>Collagenous spherulosis (CS) is a rare breast lesion of unknown histogenesis. Adenoid cystic carcinoma (ACC) is a rare basal-like breast carcinoma with low histological grade. CS is a benign lesion but resembles ACC. Both lesions show a similar histomorphology and feature bilineage differentiation. This study compared immunohistochemical markers in CS and ACC.</p><p>We compiled n = 13 CS cases and n = 18 mammary ACCs. Fourteen marker proteins (ER, PR, HER2, GATA3, CK7, E-cadherin, CD117, CK5/14, p40, p63, SMA, CD10, calponin, P-cadherin) were evaluated by immunohistochemistry (IHC). <em>MYB</em> rearrangement, a common alteration in ACC, was assessed by fluorescence <em>in situ</em> hybridization.</p><p>Patient age ranged between 40-60 years for CS lesions and 30–90 years for ACCs. 7/13 (54%) CS cases harbored a lobular carcinoma <em>in situ</em> (LCIS) in the luminal component. One CS/LCIS lesion occurred in a carrier of a pathogenic germline variant in <em>CDH1/</em>E-cadherin. <em>MYB</em> rearrangement was detected in 0/11 (0%) CS and 6/16 (37%) ACC cases (P = 0.054). CS was associated with expression of ER in the luminal component (P < 0.001), E-cadherin loss in the luminal component (P = 0.045), and expression of CD10 and calponin in the basal component (P < 0.001). Furthermore, CS was associated with GATA3 expression in the luminal component (12/13 [92%] <em>versus</em> 5/18 [27%], P < 0.001).</p><p>In summary, IHC for GATA3 and E-cadherin may contribute to the differential diagnosis between CS and ACC, although these markers are not exclusively expressed in either lesion. Histologic evaluation has to take into account that CS is frequently colonized by LCIS, requiring thorough correlation of histomorphology and immunohistochemical features.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0046817724000650/pdfft?md5=2917c8de72e82928c136ed5761d7db78&pid=1-s2.0-S0046817724000650-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140780229","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}
Pub Date : 2024-04-25DOI: 10.1016/j.humpath.2024.04.014
Jiao-jie Lv , Qian-lan Yao , Xue-bing Jiang , Min Ren , Xu Cai , Bo Dai , Yun-yi Kong
This study investigated the clinicopathological, immunohistochemical, and molecular features of primary leptomeningeal melanocytic neoplasms (LMNs). Twelve LMN cases were retrospectively reviewed. We performed Fluorescence in-situ hybridization (including a 4-probe FISH assay with CDKN2A and MYC assay) and Next-Generation sequencing analyses on available cases. Histologically, 2 tumours were classified as melanocytomas (MC), 2 as intermediate-grade melanocytomas (IMC), and 8 as leptomeningeal melanomas (LMM). Two rare cases of LMM were associated with large plaque-like blue nevus. One MC case was associated with Ota. Ten cases (83.3%) showed melanocytic cells with benign features diffusely proliferating within the meninges. The Ki-67 in three categories differed (MC 0–1%, IMC 0–3%, LMM 3–10%). 57.1% of LMM cases (4/7) were positive for FISH. Nine of 10 tumours harboured activating hotspot mutations in GNAQ, GNA11, or PLCB4. Additional mutations of EIF1AX, SF3B1, or BAP1 were found in 40%, 30%, and 10% of tumours, respectively. During the follow-up (median = 43 months), 5 LMM patients experienced recurrence and/or metastasis, 3 of them died of the disease and the other 2 are alive with the tumour. Our study is by far the first cohort of LMN cases tested by FISH. In addition to morphological indicators including necrosis and mitotic figures, using a combination of Ki-67 and FISH helps to differentiate between IMC and LMM, especially in LMM cases with less pleomorphic features. SF3B1 mutation is first described in 2 cases of plaque-type blue nevus associated with LMM. Patients with SF3B1 mutation might be related to poor prognosis in LMN.
{"title":"Primary leptomeningeal melanocytic neoplasms: A clinicopathologic, immunohistochemical, and molecular study of 12 cases","authors":"Jiao-jie Lv , Qian-lan Yao , Xue-bing Jiang , Min Ren , Xu Cai , Bo Dai , Yun-yi Kong","doi":"10.1016/j.humpath.2024.04.014","DOIUrl":"10.1016/j.humpath.2024.04.014","url":null,"abstract":"<div><p>This study investigated the clinicopathological, immunohistochemical, and molecular features of primary leptomeningeal melanocytic neoplasms (LMNs). Twelve LMN cases were retrospectively reviewed. We performed Fluorescence <em>in-situ</em> hybridization (including a 4-probe FISH assay with <em>CDKN2A</em> and <em>MYC</em> assay) and Next-Generation sequencing analyses on available cases. Histologically, 2 tumours were classified as melanocytomas (MC), 2 as intermediate-grade melanocytomas (IMC), and 8 as leptomeningeal melanomas (LMM). Two rare cases of LMM were associated with large plaque-like blue nevus. One MC case was associated with Ota. Ten cases (83.3%) showed melanocytic cells with benign features diffusely proliferating within the meninges. The Ki-67 in three categories differed (MC 0–1%, IMC 0–3%, LMM 3–10%). 57.1% of LMM cases (4/7) were positive for FISH. Nine of 10 tumours harboured activating hotspot mutations in <em>GNAQ, GNA11,</em> or <em>PLCB4</em>. Additional mutations of <em>EIF1AX, SF3B1,</em> or <em>BAP1</em> were found in 40%, 30%, and 10% of tumours, respectively. During the follow-up (median = 43 months), 5 LMM patients experienced recurrence and/or metastasis, 3 of them died of the disease and the other 2 are alive with the tumour. Our study is by far the first cohort of LMN cases tested by FISH. In addition to morphological indicators including necrosis and mitotic figures, using a combination of Ki-67 and FISH helps to differentiate between IMC and LMM, especially in LMM cases with less pleomorphic features. <em>SF3B1</em> mutation is first described in 2 cases of plaque-type blue nevus associated with LMM. Patients with <em>SF3B1</em> mutation might be related to poor prognosis in LMN.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140776085","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}
Semi-quantitative scoring of various parameters in renal biopsy is accepted as an important tool to assess disease activity and prognostication. There are concerns on the impact of interobserver variability in its prognostic utility, generating a need for computerized quantification.
Methods
We studied 94 patients with renal biopsies, 45 with native diseases and 49 transplant patients with index biopsies for Polyomavirus nephropathy. Chronicity scores were evaluated using two methods. A standard definition diagram was agreed after international consultation and four renal pathologists scored each parameter in a double-blinded manner. Interstitial fibrosis (IF) score was assessed with five different computerized and AI-based algorithms on trichrome and PAS stains.
Results
There was strong prognostic correlation with renal function and graft outcome at a median follow-up ranging from 24 to 42 months respectively, independent of moderate concordance for pathologists scores. IF scores with two of the computerized algorithms showed significant correlation with estimated glomerular filtration rate (eGFR) at biopsy but not at the end of follow-up. There was poor concordance for AI based platforms.
Conclusion
Chronicity scores are robust prognostic tools despite interobserver reproducibility. AI-algorithms have absolute precision but are limited by significant variation when different hardware and software algorithms are used for quantification.
导言肾活检中各种参数的半定量评分被认为是评估疾病活动性和预后的重要工具。我们对 94 名肾活检患者进行了研究,其中 45 名患者患有原发性疾病,49 名移植患者接受了多瘤病毒肾病的指数活检。慢性化评分采用两种方法进行评估。经过国际磋商后商定了一个标准定义图,由四位肾脏病理学家以双盲方式对每个参数进行评分。结果在24至42个月的中位随访中,肾功能和移植物结果与预后密切相关,与病理学家评分的中度一致性无关。两种计算机算法的 IF 评分与活检时的估计肾小球滤过率(eGFR)有显著相关性,但与随访结束时的估计肾小球滤过率无显著相关性。结论 尽管观察者之间存在重复性,但chronicity评分是一种可靠的预后工具。人工智能算法具有绝对的精确性,但在使用不同的硬件和软件算法进行量化时,会受到显著差异的限制。
{"title":"Reproducibility and prognostic ability of chronicity parameters in kidney biopsy – Comprehensive evaluation comparing microscopy and artificial intelligence in digital pathology","authors":"Rajesh Nachiappa Ganesh MD, DNB (Professor) , Edward A. Graviss PhD (Professor) , Duc Nguyen PhD (Assistant Professor) , Ziad El-Zaatari MD (Assistant Professor) , Lillian Gaber MD (Professor) , Roberto Barrios MD (Professor) , Luan Truong MD (Professor) , Alton B. Farris MD (Professor)","doi":"10.1016/j.humpath.2024.04.006","DOIUrl":"https://doi.org/10.1016/j.humpath.2024.04.006","url":null,"abstract":"<div><h3>Introduction</h3><p>Semi-quantitative scoring of various parameters in renal biopsy is accepted as an important tool to assess disease activity and prognostication. There are concerns on the impact of interobserver variability in its prognostic utility, generating a need for computerized quantification.</p></div><div><h3>Methods</h3><p>We studied 94 patients with renal biopsies, 45 with native diseases and 49 transplant patients with index biopsies for Polyomavirus nephropathy. Chronicity scores were evaluated using two methods. A standard definition diagram was agreed after international consultation and four renal pathologists scored each parameter in a double-blinded manner. Interstitial fibrosis (IF) score was assessed with five different computerized and AI-based algorithms on trichrome and PAS stains.</p></div><div><h3>Results</h3><p>There was strong prognostic correlation with renal function and graft outcome at a median follow-up ranging from 24 to 42 months respectively, independent of moderate concordance for pathologists scores. IF scores with two of the computerized algorithms showed significant correlation with estimated glomerular filtration rate (eGFR) at biopsy but not at the end of follow-up. There was poor concordance for AI based platforms.</p></div><div><h3>Conclusion</h3><p>Chronicity scores are robust prognostic tools despite interobserver reproducibility. AI-algorithms have absolute precision but are limited by significant variation when different hardware and software algorithms are used for quantification.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140644459","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}
Pub Date : 2024-04-01DOI: 10.1016/j.humpath.2024.04.003
Kaitlyn J. Nielson , Ross Rowsey , Surendra Dasari , William R. Sukov , Benjamin R. Kipp , Aditya Raghunathan , Rumeal D. Whaley , Kingsley Ebare , Melissa L. Stanton , Jordan P. Reynolds , Vidit Sharma , R. Houston Thompson , Stephen A. Boorjian , Bradley C. Leibovich , Loren Herrera Hernandez , Rafael E. Jimenez , John C. Cheville , Sounak Gupta
Mucinous tubular and spindle cell carcinoma (MTSCC) shows significant overlap with papillary renal cell carcinoma (PRCC), and harbor recurrent copy-number alterations (CNA).
We evaluated 16 RCC with features suggestive of MTSCC using chromosomal microarrays.
The cohort was comprised of 8 females and males, each, with an age range of 33–79 years (median, 59), and a tumor size range of 3.4–15.5 cm (median, 5.0). Half the tumors were high-grade (8/16, 50%) with features such as necrosis, marked cytologic atypia, and sarcomatoid differentiation, and 5/16 (31%) were high stage (≥pT3a). Three (of 16, 19%) cases had a predominant (>95%) spindle cell component, whereas 5/16 (31%) were composed of a predominant (>95%) epithelial component. Most cases (12/16, 75%) exhibited a myxoid background and/or extravasated mucin, at least focally.
Twelve (of 16, 75%) cases demonstrated CNA diagnostic of MTSCC (losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22). In addition, 2 high-grade tumors showed loss of CDKN2A/B, and gain of 1q, respectively, both of which are associated with aggressive behavior. Three (of 16, 19%) cases, demonstrated nonspecific CNA, and did not meet diagnostic criteria for established RCC subtypes. One (of 16, 6%) low-grade epithelial predominant tumor (biopsy) demonstrated characteristic gains of 7, 17, and loss of Y, diagnostic of PRCC.
MTSCC can be a morphologically heterogenous tumor. Our study validates the detection of characteristic chromosomal CNA for diagnostic use that may be useful in challenging cases with unusual spindle cell or epithelial predominant features, as well as in high-grade tumors.
{"title":"Single nucleotide polymorphism (SNP) chromosomal microarray as a diagnostic tool for mucinous tubular and spindle cell carcinoma: A validation study","authors":"Kaitlyn J. Nielson , Ross Rowsey , Surendra Dasari , William R. Sukov , Benjamin R. Kipp , Aditya Raghunathan , Rumeal D. Whaley , Kingsley Ebare , Melissa L. Stanton , Jordan P. Reynolds , Vidit Sharma , R. Houston Thompson , Stephen A. Boorjian , Bradley C. Leibovich , Loren Herrera Hernandez , Rafael E. Jimenez , John C. Cheville , Sounak Gupta","doi":"10.1016/j.humpath.2024.04.003","DOIUrl":"https://doi.org/10.1016/j.humpath.2024.04.003","url":null,"abstract":"<div><p>Mucinous tubular and spindle cell carcinoma (MTSCC) shows significant overlap with papillary renal cell carcinoma (PRCC), and harbor recurrent copy-number alterations (CNA).</p><p>We evaluated 16 RCC with features suggestive of MTSCC using chromosomal microarrays.</p><p>The cohort was comprised of 8 females and males, each, with an age range of 33–79 years (median, 59), and a tumor size range of 3.4–15.5 cm (median, 5.0). Half the tumors were high-grade (8/16, 50%) with features such as necrosis, marked cytologic atypia, and sarcomatoid differentiation, and 5/16 (31%) were high stage (≥pT3a). Three (of 16, 19%) cases had a predominant (>95%) spindle cell component, whereas 5/16 (31%) were composed of a predominant (>95%) epithelial component. Most cases (12/16, 75%) exhibited a myxoid background and/or extravasated mucin, at least focally.</p><p>Twelve (of 16, 75%) cases demonstrated CNA diagnostic of MTSCC (losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22). In addition, 2 high-grade tumors showed loss of <em>CDKN2A/B</em>, and gain of 1q, respectively, both of which are associated with aggressive behavior. Three (of 16, 19%) cases, demonstrated nonspecific CNA, and did not meet diagnostic criteria for established RCC subtypes. One (of 16, 6%) low-grade epithelial predominant tumor (biopsy) demonstrated characteristic gains of 7, 17, and loss of Y, diagnostic of PRCC.</p><p>MTSCC can be a morphologically heterogenous tumor. Our study validates the detection of characteristic chromosomal CNA for diagnostic use that may be useful in challenging cases with unusual spindle cell or epithelial predominant features, as well as in high-grade tumors.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140606813","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}
Pub Date : 2024-04-01DOI: 10.1016/S0046-8177(24)00078-9
{"title":"Information for Authors","authors":"","doi":"10.1016/S0046-8177(24)00078-9","DOIUrl":"https://doi.org/10.1016/S0046-8177(24)00078-9","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825110","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}
Pub Date : 2024-04-01DOI: 10.1016/j.humpath.2024.04.005
Yasuni Nakanuma , Yuko Kakuda , Yasunori Sato , Mana Fukushima , Takashi Sugino
Aims
Significance of peribiliary capillary plexus (PCP) in gallbladder neoplasms remains unclear. Aims are to characterize high-grade biliary intraepithelial neoplasm (BilIN), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN), precursors of gallbladder carcinoma, and to differentiate invasive carcinoma from pseudo-invasive lesions in gallbladder walls, referring to PCP.
Materials and methods
High-grade BilIN (38 cases), PGA (5 cases), and ICPN (25 cases) were examined using capillary immunostaining. Non-neoplastic gallbladders were used as controls.
Results
In non-neoplastic gallbladders, a single layer of regularly dotted capillaries (PCP) was located beneath lining epithelia and around non-neoplastic glands (NNGs), including Rokitansky-Aschoff sinus (RAS), presenting a two-layer of lining epithelia and PCP. Intra-luminal components of all cases of high-grade BilIN and PGA and one-third of ICPNs presented a two-layer pattern. In the remaining ICPNs, capillaries were irregular and sparse in intraluminal neoplastic components presenting irregular and complicated lesions. Neoplastic glands in gallbladder walls of high-grade BilIN and ICPN were classifiable into 2 types: glands that were underlain by densely dotted capillaries and those that were not, with the latter suggestive of invasive carcinoma, while the former suggestive of non-invasive neoplasms involving NNGs intraepithelially and/or showing an expanding growth into gallbladder wall (pseudo-invasion).
Conclusion
A two-layer pattern of lining epithelia and underlining capillaries were preserved in all cases of high-grade BilIN and PGA and one-third of ICPN cases. Presence or absence of dotted capillaries around neoplastic glands may be able to be added as a new pathologic feature to differentiate invasive carcinomas from pseudo-invasion in gallbladder wall.
{"title":"Pathologic significance of peribiliary capillary plexus in gallbladder neoplasm","authors":"Yasuni Nakanuma , Yuko Kakuda , Yasunori Sato , Mana Fukushima , Takashi Sugino","doi":"10.1016/j.humpath.2024.04.005","DOIUrl":"https://doi.org/10.1016/j.humpath.2024.04.005","url":null,"abstract":"<div><h3>Aims</h3><p>Significance of peribiliary capillary plexus (PCP) in gallbladder neoplasms remains unclear. Aims are to characterize high-grade biliary intraepithelial neoplasm (BilIN), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN), precursors of gallbladder carcinoma, and to differentiate invasive carcinoma from pseudo-invasive lesions in gallbladder walls, referring to PCP.</p></div><div><h3>Materials and methods</h3><p>High-grade BilIN (38 cases), PGA (5 cases), and ICPN (25 cases) were examined using capillary immunostaining. Non-neoplastic gallbladders were used as controls.</p></div><div><h3>Results</h3><p>In non-neoplastic gallbladders, a single layer of regularly dotted capillaries (PCP) was located beneath lining epithelia and around non-neoplastic glands (NNGs), including Rokitansky-Aschoff sinus (RAS), presenting a two-layer of lining epithelia and PCP. Intra-luminal components of all cases of high-grade BilIN and PGA and one-third of ICPNs presented a two-layer pattern. In the remaining ICPNs, capillaries were irregular and sparse in intraluminal neoplastic components presenting irregular and complicated lesions. Neoplastic glands in gallbladder walls of high-grade BilIN and ICPN were classifiable into 2 types: glands that were underlain by densely dotted capillaries and those that were not, with the latter suggestive of invasive carcinoma, while the former suggestive of non-invasive neoplasms involving NNGs intraepithelially and/or showing an expanding growth into gallbladder wall (pseudo-invasion).</p></div><div><h3>Conclusion</h3><p>A two-layer pattern of lining epithelia and underlining capillaries were preserved in all cases of high-grade BilIN and PGA and one-third of ICPN cases. Presence or absence of dotted capillaries around neoplastic glands may be able to be added as a new pathologic feature to differentiate invasive carcinomas from pseudo-invasion in gallbladder wall.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140644460","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}