Pub Date : 2025-01-14DOI: 10.1016/j.anndiagpath.2025.152440
Aysha Mubeen , Richard Pacheco , Mahmut Akgul , Sean R. Williamson , Katrina Collins , Emily Chan , Ankur R. Sangoi
Gamna-Gandy (GG) bodies are sclerosiderotic nodules composed of iron pigment and calcium, that have been described predominantly in the spleens of patients with sickle cell disease. Their formal depiction in the kidney is mainly limited to case reports and small series. We aimed to investigate the incidence of GG bodies and associated clinicopathologic features in consecutive nephrectomies performed for renal tumors. Slides of consecutive nephrectomies for renal neoplasms at 3 institutions were reviewed by genitourinary pathologists, with detailed clinicopathologic features recorded. The incidence of GG bodies in our nephrectomy cohort was 13% (44/350). The most common tumor exhibiting GG bodies was clear cell renal cell carcinoma (RCC) (40/44), followed by papillary RCC (2/44), chromophobe RCC (1/44), and epithelioid angiomyolipoma (1/44). Most RCCs were pathologic stage pT3a (46%). GG bodies were intratumoral in 77%, peritumoral in 5%, and both in 18% of patients. They were focal in 43% and multifocal in 57%, with the largest focus ranging from 0.2 to 7 mm (mean 1.7 mm). Background fibrosis and hemosiderin laden macrophages were commonly associated (93% for both). All tumors demonstrated cystic elements. In 2 renal tumor specimens, an extensive fungal workup was performed and was negative; the “structures” were not formally recognized as GG bodies in either specimen. GG bodies are not an uncommon finding in renal tumors, particularly in clear cell RCC. Awareness of the morphologic appearance is crucial to avoid mistaking them for fungal structures or other organisms.
{"title":"Gamna-Gandy bodies in renal neoplasms: A multi-institutional clinicopathologic study of 350 consecutive nephrectomies","authors":"Aysha Mubeen , Richard Pacheco , Mahmut Akgul , Sean R. Williamson , Katrina Collins , Emily Chan , Ankur R. Sangoi","doi":"10.1016/j.anndiagpath.2025.152440","DOIUrl":"10.1016/j.anndiagpath.2025.152440","url":null,"abstract":"<div><div>Gamna-Gandy (GG) bodies are sclerosiderotic nodules composed of iron pigment and calcium, that have been described predominantly in the spleens of patients with sickle cell disease. Their formal depiction in the kidney is mainly limited to case reports and small series. We aimed to investigate the incidence of GG bodies and associated clinicopathologic features in consecutive nephrectomies performed for renal tumors. Slides of consecutive nephrectomies for renal neoplasms at 3 institutions were reviewed by genitourinary pathologists, with detailed clinicopathologic features recorded. The incidence of GG bodies in our nephrectomy cohort was 13% (44/350). The most common tumor exhibiting GG bodies was clear cell renal cell carcinoma (RCC) (40/44), followed by papillary RCC (2/44), chromophobe RCC (1/44), and epithelioid angiomyolipoma (1/44). Most RCCs were pathologic stage pT3a (46%). GG bodies were intratumoral in 77%, peritumoral in 5%, and both in 18% of patients. They were focal in 43% and multifocal in 57%, with the largest focus ranging from 0.2 to 7 mm (mean 1.7 mm). Background fibrosis and hemosiderin laden macrophages were commonly associated (93% for both). All tumors demonstrated cystic elements. In 2 renal tumor specimens, an extensive fungal workup was performed and was negative; the “structures” were not formally recognized as GG bodies in either specimen. GG bodies are not an uncommon finding in renal tumors, particularly in clear cell RCC. Awareness of the morphologic appearance is crucial to avoid mistaking them for fungal structures or other organisms.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"75 ","pages":"Article 152440"},"PeriodicalIF":1.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-13DOI: 10.1016/j.anndiagpath.2025.152438
F. Yilmaz , K. Atay
The correlation between clinical, serological, and endoscopic findings and histological response after a gluten-free diet (GFD) is limited in adult celiac (CD) patients. This study aims to evaluate the effects of GFD on intraepithelial lymphocyte (IEL) localization by comparing the histopathological, clinical, serological, and endoscopic findings of adult CD patients. The patients (n = 131) were divided into three groups: those with good (CDgc) (n = 23) and poor (CDpc) (n = 21) GFD compliance and newly diagnosed ones (nCD) (n = 87). Total and supranuclear IELs were counted per 100 enterocytes and divided into three groups: apical, mixed, and basal, according to ROC (Receiver operating characteristic) analysis. The roles of clinicopathological parameters in predicting good dietary compliance were calculated using the multivariable logistic regression model. CDgc group predominantly (78.3 %) exhibited a basal pattern, and none exhibited an apical. Conversely, most CDpc and nCD patients showed mixed (66.7 % and 73.6 %, respectively) and apical (9.5 % and 25.3 %) patterns. Non-atrophic Marsh types (p = 0.040) and basal pattern (p = 0.043) were independent parameters predicting good dietary compliance. This study first showed that IEL localizations can indicate GFD compliance in samples from CD patients. Localization-based examination of IELs can be an additional histological indicator in monitoring GFD compliance and signs of recovery, especially in adult CD patients.
{"title":"A new histomorphological finding in the follow-up of celiac disease: Intraepithelial lymphocyte localization is a reliable indicator of dietary compliance","authors":"F. Yilmaz , K. Atay","doi":"10.1016/j.anndiagpath.2025.152438","DOIUrl":"10.1016/j.anndiagpath.2025.152438","url":null,"abstract":"<div><div>The correlation between clinical, serological, and endoscopic findings and histological response after a gluten-free diet (GFD) is limited in adult celiac (CD) patients. This study aims to evaluate the effects of GFD on intraepithelial lymphocyte (IEL) localization by comparing the histopathological, clinical, serological, and endoscopic findings of adult CD patients. The patients (<em>n</em> = 131) were divided into three groups: those with good (CDgc) (<em>n</em> = 23) and poor (CDpc) (<em>n</em> = 21) GFD compliance and newly diagnosed ones (nCD) (<em>n</em> = 87). Total and supranuclear IELs were counted per 100 enterocytes and divided into three groups: apical, mixed, and basal, according to ROC (Receiver operating characteristic) analysis. The roles of clinicopathological parameters in predicting good dietary compliance were calculated using the multivariable logistic regression model. CDgc group predominantly (78.3 %) exhibited a basal pattern, and none exhibited an apical. Conversely, most CDpc and nCD patients showed mixed (66.7 % and 73.6 %, respectively) and apical (9.5 % and 25.3 %) patterns. Non-atrophic Marsh types (<em>p</em> = 0.040) and basal pattern (<em>p</em> = 0.043) were independent parameters predicting good dietary compliance. This study first showed that IEL localizations can indicate GFD compliance in samples from CD patients. Localization-based examination of IELs can be an additional histological indicator in monitoring GFD compliance and signs of recovery, especially in adult CD patients.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"75 ","pages":"Article 152438"},"PeriodicalIF":1.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10DOI: 10.1016/j.anndiagpath.2025.152437
Raymond Gong , Zongming E. Chen , Karen Matsukuma
Two morphologic subtypes of intrahepatic cholangiocarcinoma (iCCA), small duct and large duct, are now recognized, and importantly, these subtypes are associated with distinct molecular pathways and therapeutic options. Initial studies demonstrated the feasibility of morphologic subclassification and helped characterize the immunoprofile of the subtypes. However, few studies have been undertaken in Western countries where incidence of the subtypes is likely distinct from that in the East. To address this, 48 tumors from a North American cohort, consisting of 29 iCCAs, 18 extrahepatic CCAs (eCCAs), and 1 tumor of unclear origin (liver vs. gallbladder growing into liver) were classified by morphologic criteria as large duct (19 tumors), small duct (13 tumors), or indeterminate (13 tumors; all iCCAs). Notably, only 3 iCCAs were classified as large duct. Additionally, we evaluated the utility of common biomarkers to aid in subclassification, given that a significant portion of iCCAs were challenging to classify (e.g., indeterminate morphology). Tumors were screened for expression of mucicarmine, epithelial membrane antigen (EMA), monoclonal (mCEA), polyclonal CEA (pCEA), N-cadherin, CD56, and albumin by in situ hybridization (ALB-ISH). Of these, pCEA, CRP, N-cadherin, and ALB-ISH showed statistically significant differences between large and small duct types (P < 0.0028), with high specificity (≥88 %) and at least moderate sensitivity (≥60 %). Eleven of the 13 morphologically indeterminate tumors could be classified based on their expression of these 4 markers. Four additional large duct iCCAs were subsequently obtained from a second North American institution and assessed for pCEA, N-cadherin, and albumin expression. Combining these data with the initial cohort of large duct iCCAs (total of 7 large duct iCCAs) showed similar biomarker associations. In conclusion, in this Western cohort, 55 % of iCCAs (16 of 29) could be subclassified as large or small duct type based on morphology alone. With the aid of the 4-marker panel, 93 % of iCCAs (27 of 29) could be classified. Unlike in East Asian cohorts, the vast majority of iCCAs (88 %) was small duct type, and hepatolithiasis was not observed. CRP, N-cadherin, and ALB-ISH were found to be specific for small duct iCCA, whereas diffuse, strong expression of pCEA showed specificity for large duct tumors. This is the first report to highlight the utility of pCEA to subclassify iCCAs. Additionally, in cases in which the primary site (within the biliary tract) was unclear, CRP, ALB-ISH, N-cadherin, and pCEA were helpful in distinguishing iCCA from eCCA.
{"title":"Morphologic and immunohistochemical characterization of small and large duct cholangiocarcinomas in a Western cohort: A panel of pCEA, CRP, N-cadherin, and albumin in situ hybridization aids in subclassification","authors":"Raymond Gong , Zongming E. Chen , Karen Matsukuma","doi":"10.1016/j.anndiagpath.2025.152437","DOIUrl":"10.1016/j.anndiagpath.2025.152437","url":null,"abstract":"<div><div>Two morphologic subtypes of intrahepatic cholangiocarcinoma (iCCA), small duct and large duct, are now recognized, and importantly, these subtypes are associated with distinct molecular pathways and therapeutic options. Initial studies demonstrated the feasibility of morphologic subclassification and helped characterize the immunoprofile of the subtypes. However, few studies have been undertaken in Western countries where incidence of the subtypes is likely distinct from that in the East. To address this, 48 tumors from a North American cohort, consisting of 29 iCCAs, 18 extrahepatic CCAs (eCCAs), and 1 tumor of unclear origin (liver vs. gallbladder growing into liver) were classified by morphologic criteria as large duct (19 tumors), small duct (13 tumors), or indeterminate (13 tumors; all iCCAs). Notably, only 3 iCCAs were classified as large duct. Additionally, we evaluated the utility of common biomarkers to aid in subclassification, given that a significant portion of iCCAs were challenging to classify (e.g., indeterminate morphology). Tumors were screened for expression of mucicarmine, epithelial membrane antigen (EMA), monoclonal (mCEA), polyclonal CEA (pCEA), N-cadherin, CD56, and albumin by in situ hybridization (ALB-ISH). Of these, pCEA, CRP, N-cadherin, and ALB-ISH showed statistically significant differences between large and small duct types (<em>P</em> < 0.0028), with high specificity (≥88 %) and at least moderate sensitivity (≥60 %). Eleven of the 13 morphologically indeterminate tumors could be classified based on their expression of these 4 markers. Four additional large duct iCCAs were subsequently obtained from a second North American institution and assessed for pCEA, N-cadherin, and albumin expression. Combining these data with the initial cohort of large duct iCCAs (total of 7 large duct iCCAs) showed similar biomarker associations. In conclusion, in this Western cohort, 55 % of iCCAs (16 of 29) could be subclassified as large or small duct type based on morphology alone. With the aid of the 4-marker panel, 93 % of iCCAs (27 of 29) could be classified. Unlike in East Asian cohorts, the vast majority of iCCAs (88 %) was small duct type, and hepatolithiasis was not observed. CRP, N-cadherin, and ALB-ISH were found to be specific for small duct iCCA, whereas diffuse, strong expression of pCEA showed specificity for large duct tumors. This is the first report to highlight the utility of pCEA to subclassify iCCAs. Additionally, in cases in which the primary site (within the biliary tract) was unclear, CRP, ALB-ISH, N-cadherin, and pCEA were helpful in distinguishing iCCA from eCCA.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"75 ","pages":"Article 152437"},"PeriodicalIF":1.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-07DOI: 10.1016/j.anndiagpath.2025.152436
Maria Faraz , Andrew Rosenzweig , Angel Panizo , Sabina Hajiyeva , Nusret B. Subasi , Mohammed A. Alghamdi , Andrea A. Lightle , Levente Kuthi , Dora Kelemen , Ankur R. Sangoi , Luiz M. Nova-Camacho , María Garcia Martos , Mehrnaz Movassaghi , Anandi Lobo , Shilpy Jha , Kutsal Yörükoğlu , Busra Yaprak Bayrak , Sean R. Williamson , Swati Bhardwaj , Shivani Kandukuri , Mahmut Akgul
Intrarenal hemangiomas lack concise clinicopathologic information, due to the predominance of single case reports and inclusion of other vascular neoplasms and hemangiomas of perirenal, hilar, and renal vein origin. Herein, in this multi-institutional study we evaluate clinicopathologic features of 39 intrarenal hemangiomas. The median age was 62 years (range = 27–94 years; 2:1 male to female ratio), with left-sided predominance (left = 21, right = 13; one case was bilateral). The median tumor size was 1.5 cm (0.2-10 cm). Two cases arose from transplanted kidneys. Most were asymptomatic (n = 30, 86 %), even though most surgical interventions (19 partial, 19 radical, 1 biopsy) were due to hemangiomas (n = 24, 62 %). Synchronous renal neoplasms were present in 9 (23 %) patients, including clear cell renal cell carcinoma (RCC) (n = 4), angiomyolipoma (n = 2), oncocytoma (n = 2), and chromophobe RCC (n = 1). Multifocal hemangiomas (n = 5) were seen in cases with end stage renal disease. Intrarenal hemangiomas were mostly anastomosing (n = 18; 46 %), followed by capillary (n = 15; 38 %), and cavernous (n = 6; 16 %) subtypes. Fibrin thrombus (n = 9; 23 %) and extramedullary hematopoiesis (n = 4; 10 %) were occasionally present, the latter being only in the anastomosing subtype. Immunohistochemistry was performed on a majority (n = 33, 84 %) of hemangiomas, with vascular markers CD31 and CD34 and lack of PAX8 were most used for diagnosis. 30 patients had follow-up (median 48 months, range 1–241 months), none showed disease progression/recurrence. This study provides comprehensive observation of the largest intrarenal hemangioma cohort, highlighting their frequent cause of surgical intervention when present, predominance of anastomosing subtype, multifocality in end stage kidney disease, and occasional concurrent ipsilateral neoplasms.
{"title":"Primary intrarenal hemangioma – A series of 39 cases","authors":"Maria Faraz , Andrew Rosenzweig , Angel Panizo , Sabina Hajiyeva , Nusret B. Subasi , Mohammed A. Alghamdi , Andrea A. Lightle , Levente Kuthi , Dora Kelemen , Ankur R. Sangoi , Luiz M. Nova-Camacho , María Garcia Martos , Mehrnaz Movassaghi , Anandi Lobo , Shilpy Jha , Kutsal Yörükoğlu , Busra Yaprak Bayrak , Sean R. Williamson , Swati Bhardwaj , Shivani Kandukuri , Mahmut Akgul","doi":"10.1016/j.anndiagpath.2025.152436","DOIUrl":"10.1016/j.anndiagpath.2025.152436","url":null,"abstract":"<div><div>Intrarenal hemangiomas lack concise clinicopathologic information, due to the predominance of single case reports and inclusion of other vascular neoplasms and hemangiomas of perirenal, hilar, and renal vein origin. Herein, in this multi-institutional study we evaluate clinicopathologic features of 39 intrarenal hemangiomas. The median age was 62 years (range = 27–94 years; 2:1 male to female ratio), with left-sided predominance (left = 21, right = 13; one case was bilateral). The median tumor size was 1.5 cm (0.2-10 cm). Two cases arose from transplanted kidneys. Most were asymptomatic (<em>n</em> = 30, 86 %), even though most surgical interventions (19 partial, 19 radical, 1 biopsy) were due to hemangiomas (<em>n</em> = 24, 62 %). Synchronous renal neoplasms were present in 9 (23 %) patients, including clear cell renal cell carcinoma (RCC) (<em>n</em> = 4), angiomyolipoma (n = 2), oncocytoma (n = 2), and chromophobe RCC (<em>n</em> = 1). Multifocal hemangiomas (<em>n</em> = 5) were seen in cases with end stage renal disease. Intrarenal hemangiomas were mostly anastomosing (<em>n</em> = 18; 46 %), followed by capillary (<em>n</em> = 15; 38 %), and cavernous (<em>n</em> = 6; 16 %) subtypes. Fibrin thrombus (<em>n</em> = 9; 23 %) and extramedullary hematopoiesis (<em>n</em> = 4; 10 %) were occasionally present, the latter being only in the anastomosing subtype. Immunohistochemistry was performed on a majority (<em>n</em> = 33, 84 %) of hemangiomas, with vascular markers CD31 and CD34 and lack of PAX8 were most used for diagnosis. 30 patients had follow-up (median 48 months, range 1–241 months), none showed disease progression/recurrence. This study provides comprehensive observation of the largest intrarenal hemangioma cohort, highlighting their frequent cause of surgical intervention when present, predominance of anastomosing subtype, multifocality in end stage kidney disease, and occasional concurrent ipsilateral neoplasms.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"75 ","pages":"Article 152436"},"PeriodicalIF":1.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
POLE status determination is necessary for the molecular classification of endometrial carcinomas (EC). However, this determination is only achievable by molecular techniques, which are not available in many practice settings. A previously published study reported elevated AMF/GPI and AMFR/gp78 levels in POLE-mutant EC. We examined the relationship between POLE status and AMF and AMFR expression. Our study included 55 molecularly classified EC, assessed for AMF and AMFR immunohistochemically. Staining intensity was scored 0 (negative), 1 (weak), 2 (medium), 3 (strong), extent was scored 0 (0 %), 1 (1–25 %), 2 (26–50 %), 3 (51–75 %), 4 (76–100 %), with those parameters summed for the final score for each case. The molecular subtypes POLE mutant, mismatch repair-deficient, no specific molecular profile, p53 abnormal had mean AMF scores of 5.909, 4.643, 5.000, 4.667, respectively. The POLE-mutant subtype had a significantly higher average AMF score than POLE wild-type (POLEwt) group (p = 0.003). Using POLE mutant status as an end-point, ROC analysis showed that an AMF immunohistochemical score of 6 and above had an 81.8 % sensitivity, 61.4 % specificity, AUC of 0.708 (95 % CI, 0.565–0.851). POLE-mutant subtype had higher prevalence of a score of 6 and above than the POLEwt group (9/11 vs 17/44 cases, p = 0.010). An AMF score 6 and above increased the likelihood of being POLE-mutant by a factor of 10.496 (95 % CI, 1.592–69.212). Similarly, the POLE-mutant subtype had higher prevalence of AMFR scores of 5 and above than the POLEwt group (p = 0.023). AMF may offer some promise in identifying POLE-mutant EC with relatively high sensitivity, but suboptimal specificity indicates that it cannot be applied alone in practice. Additional studies are required to determine whether AMF can be combined with other markers to more optimally identify POLE mutant EC.
子宫内膜癌（EC）的分子分类需要确定POLE状态。然而，这种测定只能通过分子技术来实现，这在许多实践环境中是不可用的。先前发表的一项研究报告了pole突变EC中AMF/GPI和AMFR/gp78水平升高。我们研究了极点状态与AMF和AMFR表达之间的关系。我们的研究包括55个分子分类的EC，对AMF和AMFR进行免疫组织化学评估。染色强度评分为0（阴性）、1（弱）、2（中）、3（强），程度评分为0（0%）、1（1- 25%）、2（26- 50%）、3（51- 75%）、4(76- 100%)，并将这些参数相加作为每个病例的最终评分。分子亚型POLE突变、错配修复缺陷、无特异性分子谱、p53异常的平均AMF评分分别为5.909、4.643、5.000、4.667。POLE突变亚型的平均AMF评分显著高于POLE野生型（POLEwt）组（p = 0.003）。以POLE突变状态为终点，ROC分析显示，AMF免疫组织化学评分6分及以上敏感性81.8%，特异性61.4%，AUC为0.708 （95% CI, 0.565-0.851）。POLE-mutant亚型在6分及以上的患病率高于POLEwt组（9/11 vs 17/44, p = 0.010）。AMF评分在6分及以上，极突变的可能性增加10.496倍（95% CI, 1.592-69.212）。同样，pole突变亚型的AMFR评分在5分及以上的患病率高于POLEwt组（p = 0.023）。AMF可能以相对较高的灵敏度为鉴定极突变EC提供了一些希望，但不理想的特异性表明它不能单独应用于实践。需要进一步的研究来确定AMF是否可以与其他标记物结合以更优化地识别POLE突变体EC。
{"title":"Immunohistochemical markers of potential utility in identifying POLE-mutant endometrial carcinomas: An assessment of autocrine motility factor (AMF) and autocrine motility factor receptor (AMFR)","authors":"Anıl Alpsoy , Gözde Koca Yılmaz , Ceyda Karadağ , Özer Birge , Tayup Şimşek , Gülgün Erdoğan , Hadice Elif Peştereli","doi":"10.1016/j.anndiagpath.2024.152433","DOIUrl":"10.1016/j.anndiagpath.2024.152433","url":null,"abstract":"<div><div><em>POLE</em> status determination is necessary for the molecular classification of endometrial carcinomas (EC). However, this determination is only achievable by molecular techniques, which are not available in many practice settings. A previously published study reported elevated AMF/GPI and AMFR/gp78 levels in <em>POLE</em>-mutant EC. We examined the relationship between <em>POLE</em> status and AMF and AMFR expression. Our study included 55 molecularly classified EC, assessed for AMF and AMFR immunohistochemically. Staining intensity was scored 0 (negative), 1 (weak), 2 (medium), 3 (strong), extent was scored 0 (0 %), 1 (1–25 %), 2 (26–50 %), 3 (51–75 %), 4 (76–100 %), with those parameters summed for the final score for each case. The molecular subtypes <em>POLE</em> mutant, mismatch repair-deficient, no specific molecular profile, p53 abnormal had mean AMF scores of 5.909, 4.643, 5.000, 4.667, respectively. The <em>POLE</em>-mutant subtype had a significantly higher average AMF score than <em>POLE</em> wild-type (<em>POLEwt</em>) group (<em>p</em> = 0.003). Using <em>POLE</em> mutant status as an end-point, ROC analysis showed that an AMF immunohistochemical score of 6 and above had an 81.8 % sensitivity, 61.4 % specificity, AUC of 0.708 (95 % CI, 0.565–0.851). <em>POLE</em>-mutant subtype had higher prevalence of a score of 6 and above than the <em>POLEwt</em> group (9/11 vs 17/44 cases, <em>p</em> = 0.010). An AMF score 6 and above increased the likelihood of being <em>POLE</em>-mutant by a factor of 10.496 (95 % CI, 1.592–69.212). Similarly, the <em>POLE</em>-mutant subtype had higher prevalence of AMFR scores of 5 and above than the <em>POLEwt</em> group (<em>p</em> = 0.023). AMF may offer some promise in identifying <em>POLE</em>-mutant EC with relatively high sensitivity, but suboptimal specificity indicates that it cannot be applied alone in practice. Additional studies are required to determine whether AMF can be combined with other markers to more optimally identify <em>POLE</em> mutant EC.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"75 ","pages":"Article 152433"},"PeriodicalIF":1.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06DOI: 10.1016/j.anndiagpath.2024.152434
Agnes Stephanie Harahap , Dina Khoirunnisa , Salinah , Maria Francisca Ham
Papillary thyroid carcinoma (PTC) is the most prevalent thyroid neoplasm, classified into BRAF-like and RAS-like subtypes. Nuclear alterations serve as a diagnostic criterion of PTC and are fully manifested in BRAF-like. This single-center retrospective study aimed to assess the different presentation of nuclear features in 40 samples of BRAFV600E- and 40 samples of RAS-mutated PTCs using both bivariate and multivariate analytic approaches. Nuclear features are evaluated histologically using the 3-point and 8-point scoring systems established by the World Health Organization and the Asian Thyroid Working Group, respectively. We found the presence of membrane irregularities, nuclear elongation, nuclear groove, sickle-shaped nuclei, nuclear pseudoinclusion, and higher nuclear scores are significantly associated with BRAFV600E. Multivariate analysis showed that nuclear pseudoinclusion is predictive for the presence of BRAFV600E mutation (OR = 10.97, 95%CI = 2.81–42.96, p = 0.001) and has sensitivity of 55 %, specificity of 92.5 %, positive predictive value of 88 %, negative predictive value of 67.3 %, and accuracy of 73.8 %. There are various pathways and protooncogenes associated with the development of thyroid neoplasm. This study found significant differences in nuclear features between BRAFV600E and RAS-mutated PTC. BRAFV600E tend to display florid nuclear features, whereas the RAS- mutation is associated with subtle nuclear features. These findings emphasize the distinct cytological profiles of BL and RL PTC, reinforcing the need for precise subtyping to guide tailored management.
{"title":"Nuclear pseudoinclusion is associated with BRAFV600E mutation: Analysis of nuclear features in papillary thyroid carcinoma","authors":"Agnes Stephanie Harahap , Dina Khoirunnisa , Salinah , Maria Francisca Ham","doi":"10.1016/j.anndiagpath.2024.152434","DOIUrl":"10.1016/j.anndiagpath.2024.152434","url":null,"abstract":"<div><div>Papillary thyroid carcinoma (PTC) is the most prevalent thyroid neoplasm, classified into BRAF-like and RAS-like subtypes. Nuclear alterations serve as a diagnostic criterion of PTC and are fully manifested in BRAF-like. This single-center retrospective study aimed to assess the different presentation of nuclear features in 40 samples of <em>BRAF</em>V600E- and 40 samples of <em>RAS</em>-mutated PTCs using both bivariate and multivariate analytic approaches. Nuclear features are evaluated histologically using the 3-point and 8-point scoring systems established by the World Health Organization and the Asian Thyroid Working Group, respectively. We found the presence of membrane irregularities, nuclear elongation, nuclear groove, sickle-shaped nuclei, nuclear pseudoinclusion, and higher nuclear scores are significantly associated with <em>BRAF</em>V600E. Multivariate analysis showed that nuclear pseudoinclusion is predictive for the presence of <em>BRAF</em>V600E mutation (OR = 10.97, 95%CI = 2.81–42.96, <em>p</em> = 0.001) and has sensitivity of 55 %, specificity of 92.5 %, positive predictive value of 88 %, negative predictive value of 67.3 %, and accuracy of 73.8 %. There are various pathways and protooncogenes associated with the development of thyroid neoplasm. This study found significant differences in nuclear features between <em>BRAF</em>V600E and <em>RAS</em>-mutated PTC. <em>BRAF</em>V600E tend to display florid nuclear features, whereas the RAS- mutation is associated with subtle nuclear features. These findings emphasize the distinct cytological profiles of BL and RL PTC, reinforcing the need for precise subtyping to guide tailored management.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"75 ","pages":"Article 152434"},"PeriodicalIF":1.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06DOI: 10.1016/j.anndiagpath.2024.152435
Jingli Shi, Kunkun Sun, Fangzhou Kong
Rosai–Dorfman disease (RDD) is a rare proliferative disorder of histiocytes, and primary solitary RDD of the bone is extremely rare. Some RDDs exhibit increased immunoglobulin (Ig)G4 positive (IgG4+) plasma cell infiltration and the histopathological features of IgG4-related disease (IgG4-RD). However, the association between RDD and IgG4-RD remains unclear. Therefore, this study aimed to investigate the relationship between primary intraosseous RDD and IgG4-RD. We collected data on 11 primary intraosseous Rosai–Dorfman diseases to summarize their clinicopathological features and to investigate their relationship with IgG4-RD. The most common sites were the long bones, followed by the vertebrae. The age of onset was higher in our Chinese cohort as compared with Western patients reported in the literature, with an average age of 39.2 and a median age of 34 years. Sclerosis was present in seven cases and storiform arrangement was observed in only one case. Obliterative phlebitis was not observed in any patient. The number of IgG4+ plasma cells ranged from 5 to 50 cells per high-power field, with IgG4/IgG ratios ranging from 5 to 25 %. Primary intraosseous RDD may show fibrosis and increased IgG4+ plasma cell infiltration, but does not meet the criteria for IgG4-RD. We concluded that RDD did not belong to the IgG4-RD spectrum.
{"title":"Primary intraosseous Rosai-Dorfman disease: Clinicopathological features and an assessment of a possible relationship with IgG4-related disease","authors":"Jingli Shi, Kunkun Sun, Fangzhou Kong","doi":"10.1016/j.anndiagpath.2024.152435","DOIUrl":"10.1016/j.anndiagpath.2024.152435","url":null,"abstract":"<div><div>Rosai–Dorfman disease (RDD) is a rare proliferative disorder of histiocytes, and primary solitary RDD of the bone is extremely rare. Some RDDs exhibit increased immunoglobulin (Ig)G4 positive (IgG4+) plasma cell infiltration and the histopathological features of IgG4-related disease (IgG4-RD). However, the association between RDD and IgG4-RD remains unclear. Therefore, this study aimed to investigate the relationship between primary intraosseous RDD and IgG4-RD. We collected data on 11 primary intraosseous Rosai–Dorfman diseases to summarize their clinicopathological features and to investigate their relationship with IgG4-RD. The most common sites were the long bones, followed by the vertebrae. The age of onset was higher in our Chinese cohort as compared with Western patients reported in the literature, with an average age of 39.2 and a median age of 34 years. Sclerosis was present in seven cases and storiform arrangement was observed in only one case. Obliterative phlebitis was not observed in any patient. The number of IgG4+ plasma cells ranged from 5 to 50 cells per high-power field, with IgG4/IgG ratios ranging from 5 to 25 %. Primary intraosseous RDD may show fibrosis and increased IgG4+ plasma cell infiltration, but does not meet the criteria for IgG4-RD. We concluded that RDD did not belong to the IgG4-RD spectrum.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"75 ","pages":"Article 152435"},"PeriodicalIF":1.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.anndiagpath.2024.152432
Badr AbdullGaffar , Tasnim Keloth , Fatma B. Zarooni , Eman Al-Zahmi
Isthmoceles are defects related to Caesarean section (CS) scars, known to cause secondary infertility and interfere with in-vitro fertilization in women who have had Caesarean deliveries. The etiologies are multifactorial. Isthmoceles, similar to dehiscent CS scars, can be potential sites for ectopic pregnancies and abnormal placentation. There are a few case reports of pregnancies occurring within isthmoceles. However, there is a lack of studies focusing on the histopathologic details of gestations occurring within isthmoceles. Our main aim is to address this gap by illustrating the different histopathologic patterns of products of conception and gestational trophoblastic lesions involving isthmoceles. We also aim to determine the potential clinical relevance of gestational isthmoceles. We have conducted a retrospective review study of isthmocele specimens obtained from hysteroscopic isthmoplasty and hysterectomies. We found 14 (7.4 %) isthmocele ectopic pregnancies. The involved pouches were large, wide-based, predominantly low-level endocervical mucosa-lined isthmoceles. Six patients (43 %) presented with placental site nodule and plaque, four patients (28 %) with incomplete abortus material, two patients with atypical placental nodules, one patient with an exaggerated placental site, and one patient with epithelioid trophoblastic tumor. The features were highlighted by special stains and accentuated by appropriate immunohistochemistry. Some small and focal placental site nodule gestational trophoblastic lesions were found to have been missed, overlooked or misinterpreted by the original pathologists. The presence of zonation layers, typified by a hemosiderotic inflammatory stromal band, was found to be a useful clue in order to perform deeper levels to uncover small hidden residual trophoblastic foci. The larger atypical placental site nodule and epithelioid trophoblastic cell tumor lesions were initially confused with cervical squamous cell carcinoma, which was excluded by trophoblast-specific immunomarkers. Large, wide-based, low-level endocervical mucosa-lined isthmoceles are more prone to harboring ectopic pregnancies. A history of previous scar pregnancies was found to be a risk factor for developing subsequent isthmocele ectopic pregnancies. Gestational isthmocele is a common phenomenon that exhibits a variety of histopathologic changes. Pathologists should be aware of these changes in resected isthmocele specimens in order to properly guide gynecologists in patient management and avoid potential diagnostic pitfalls.
{"title":"Histopathologic patterns in isthmocele pregnancies","authors":"Badr AbdullGaffar , Tasnim Keloth , Fatma B. Zarooni , Eman Al-Zahmi","doi":"10.1016/j.anndiagpath.2024.152432","DOIUrl":"10.1016/j.anndiagpath.2024.152432","url":null,"abstract":"<div><div>Isthmoceles are defects related to Caesarean section (CS) scars, known to cause secondary infertility and interfere with in-vitro fertilization in women who have had Caesarean deliveries. The etiologies are multifactorial. Isthmoceles, similar to dehiscent CS scars, can be potential sites for ectopic pregnancies and abnormal placentation. There are a few case reports of pregnancies occurring within isthmoceles. However, there is a lack of studies focusing on the histopathologic details of gestations occurring within isthmoceles. Our main aim is to address this gap by illustrating the different histopathologic patterns of products of conception and gestational trophoblastic lesions involving isthmoceles. We also aim to determine the potential clinical relevance of gestational isthmoceles. We have conducted a retrospective review study of isthmocele specimens obtained from hysteroscopic isthmoplasty and hysterectomies. We found 14 (7.4 %) isthmocele ectopic pregnancies. The involved pouches were large, wide-based, predominantly low-level endocervical mucosa-lined isthmoceles. Six patients (43 %) presented with placental site nodule and plaque, four patients (28 %) with incomplete abortus material, two patients with atypical placental nodules, one patient with an exaggerated placental site, and one patient with epithelioid trophoblastic tumor. The features were highlighted by special stains and accentuated by appropriate immunohistochemistry. Some small and focal placental site nodule gestational trophoblastic lesions were found to have been missed, overlooked or misinterpreted by the original pathologists. The presence of zonation layers, typified by a hemosiderotic inflammatory stromal band, was found to be a useful clue in order to perform deeper levels to uncover small hidden residual trophoblastic foci. The larger atypical placental site nodule and epithelioid trophoblastic cell tumor lesions were initially confused with cervical squamous cell carcinoma, which was excluded by trophoblast-specific immunomarkers. Large, wide-based, low-level endocervical mucosa-lined isthmoceles are more prone to harboring ectopic pregnancies. A history of previous scar pregnancies was found to be a risk factor for developing subsequent isthmocele ectopic pregnancies. Gestational isthmocele is a common phenomenon that exhibits a variety of histopathologic changes. Pathologists should be aware of these changes in resected isthmocele specimens in order to properly guide gynecologists in patient management and avoid potential diagnostic pitfalls.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"75 ","pages":"Article 152432"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-18DOI: 10.1016/j.anndiagpath.2024.152429
Lucas Antônio Fernandes Torres , Davi Said Gonçalves Celso , Maria L.R. Defante , Victoria Alzogaray , Mayara Bearse , Ana Claudia Frota Machado de Melo Lopes
Previously published studies raise the possibility of a link between breast phyllodes tumors (PT) grading and Ki-67 expression. In the current study, the authors conducted a literature review and meta-analysis to evaluate the association between the histological grades of PT and Ki-67 positivity, as well as the potential role of this immunomarker for the grading of PT. Observational studies grading PT and providing Ki-67 expression levels were retrieved from databases searches up to 11 August 2024, with 10 % or more of positive stromal cells being considered the cut-off point. A subgroup analysis included studies using the World Health Organization (WHO) criteria for PT grading. A total of 416 PT from 10 studies were included, with 25 % (106/416) showing increased Ki-67 expression. A significant association was found with increased Ki-67 expression in borderline PT compared to benign PT (OR 19.44; CI 3.11–121.74; P = 0.008; I2 = 71 %). When comparing malignant and borderline tumors, a significant difference between the groups was observed (OR 7.87; 95 % CI 2.31–26.81; P < 0.01; I2: 49 %). However, in the subgroup of tumors using only the WHO classification, the association was non-significant (OR 5.50; 95 % CI 0.89–34.03; P = 0.07; I2 = 64 %). Our meta-analysis showed an association between increased Ki-67 expression and borderline PT compared to benign tumors. The findings suggest Ki-67 may be a tool in the classification of PT, especially in histologically challenging cases.
{"title":"Ki-67 as a marker for differentiating borderline and benign phyllodes tumors of the breast: A meta-analysis and systematic review","authors":"Lucas Antônio Fernandes Torres , Davi Said Gonçalves Celso , Maria L.R. Defante , Victoria Alzogaray , Mayara Bearse , Ana Claudia Frota Machado de Melo Lopes","doi":"10.1016/j.anndiagpath.2024.152429","DOIUrl":"10.1016/j.anndiagpath.2024.152429","url":null,"abstract":"<div><div>Previously published studies raise the possibility of a link between breast phyllodes tumors (PT) grading and Ki-67 expression. In the current study, the authors conducted a literature review and meta-analysis to evaluate the association between the histological grades of PT and Ki-67 positivity, as well as the potential role of this immunomarker for the grading of PT. Observational studies grading PT and providing Ki-67 expression levels were retrieved from databases searches up to 11 August 2024, with 10 % or more of positive stromal cells being considered the cut-off point. A subgroup analysis included studies using the World Health Organization (WHO) criteria for PT grading. A total of 416 PT from 10 studies were included, with 25 % (106/416) showing increased Ki-67 expression. A significant association was found with increased Ki-67 expression in borderline PT compared to benign PT (OR 19.44; CI 3.11–121.74; <em>P</em> = 0.008; I<sup>2</sup> = 71 %). When comparing malignant and borderline tumors, a significant difference between the groups was observed (OR 7.87; 95 % CI 2.31–26.81; <em>P</em> < 0.01; I<sup>2</sup>: 49 %). However, in the subgroup of tumors using only the WHO classification, the association was non-significant (OR 5.50; 95 % CI 0.89–34.03; <em>P</em> = 0.07; I<sup>2</sup> = 64 %). Our meta-analysis showed an association between increased Ki-67 expression and borderline PT compared to benign tumors. The findings suggest Ki-67 may be a tool in the classification of PT, especially in histologically challenging cases.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"75 ","pages":"Article 152429"},"PeriodicalIF":1.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-18DOI: 10.1016/j.anndiagpath.2024.152430
Rajesh Nachiappa Ganesh , Edward A. Graviss , Duc Nguyen , Stephanie G. Yi , Ziad El-Zaatari , Lillian Gaber , Roberto Barrios , Luan Truong
BK Polyomavirus nephropathy (PVN) with definitive diagnosis on biopsy, presents incidentally or with varying degrees of graft dysfunction. Banff working group on PVN has proposed a novel scoring system in renal biopsies, to identify patients with higher risk of graft failure. In this study, we attempted to validate the Banff scoring system at index biopsies and correlate with a novel index score, plasma BK-virus load and graft outcome. 48 patients with index biopsies of PVN diagnosed from 2019 to 2022, with simultaneous plasma BKV-virus loads and SV-40 stains were chosen. Biopsies were scored for Banff PVN Class and by novel PVN index. Inter-observer reproducibility was tested between 3 renal pathologists for all parameters and findings were correlated with graft outcome, in a median follow-up of 42 months. Banff PVN classes 2 and 3 and novel index 3 were associated with higher percentage of graft failure and persistent viremia. The novel index score showed a stronger and consistent temporal association with plasma BK-virus levels. Kappa scores revealed a 68 % agreement for Banff PVN class scoring. Our study highlights the prognostic utility of Banff PVN scheme and novel PVN index in correlation with plasma BKV viremia and graft outcome.
{"title":"A novel histologic index for polyomavirus nephropathy in comparison with the Banff scoring system: Clinical validation, prognostic implication, and correlation with plasma viral load","authors":"Rajesh Nachiappa Ganesh , Edward A. Graviss , Duc Nguyen , Stephanie G. Yi , Ziad El-Zaatari , Lillian Gaber , Roberto Barrios , Luan Truong","doi":"10.1016/j.anndiagpath.2024.152430","DOIUrl":"10.1016/j.anndiagpath.2024.152430","url":null,"abstract":"<div><div>BK Polyomavirus nephropathy (PVN) with definitive diagnosis on biopsy, presents incidentally or with varying degrees of graft dysfunction. Banff working group on PVN has proposed a novel scoring system in renal biopsies, to identify patients with higher risk of graft failure. In this study, we attempted to validate the Banff scoring system at index biopsies and correlate with a novel index score, plasma BK-virus load and graft outcome. 48 patients with index biopsies of PVN diagnosed from 2019 to 2022, with simultaneous plasma BKV-virus loads and SV-40 stains were chosen. Biopsies were scored for Banff PVN Class and by novel PVN index. Inter-observer reproducibility was tested between 3 renal pathologists for all parameters and findings were correlated with graft outcome, in a median follow-up of 42 months. Banff PVN classes 2 and 3 and novel index 3 were associated with higher percentage of graft failure and persistent viremia. The novel index score showed a stronger and consistent temporal association with plasma BK-virus levels. Kappa scores revealed a 68 % agreement for Banff PVN class scoring. Our study highlights the prognostic utility of Banff PVN scheme and novel PVN index in correlation with plasma BKV viremia and graft outcome.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"75 ","pages":"Article 152430"},"PeriodicalIF":1.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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