Uterine smooth muscle tumors are a heterogeneous group of mesenchymal neoplasms with diagnostic challenges and overlapping histopathologic features. Recently, the molecular or immunohistochemical evaluation of dystrophin in the diagnosis of mesenchymal tumors with muscle differentiation has gained attention. In this retrospective study, the immunohistochemical expression of dystrophin was examined in 105 cases of uterine smooth muscle neoplasms, including 71 cases of leiomyoma (LM) and its variants, 6 cases of smooth muscle tumor of uncertain malignant potential (STUMP), and 28 cases of leiomyosarcoma (LMS). After thorough analysis, dystrophin expression was positive in 83.3 % of STUMP cases and 96.7 % of leiomyoma cases. In contrast, only 8 cases of LMS (28.6 %) expressed dystrophin. A significant difference in dystrophin expression was noted between STUMP and LMS, as well as LMS and LM and its variants. The median H-score in LM was significantly higher than in leiomyoma variants, STUMP, and LMS. In conclusion, dystrophin expression may be useful in distinguishing uterine LM, LM variants, and STUMP from LMS.
{"title":"Diagnostic value of dystrophin immunostaining for histopathologic diagnosis of uterine smooth muscle tumors","authors":"Fatemeh Nili , Kiana Anousha , Soheila Sarmadi , Fereshteh Ameli","doi":"10.1016/j.anndiagpath.2025.152604","DOIUrl":"10.1016/j.anndiagpath.2025.152604","url":null,"abstract":"<div><div>Uterine smooth muscle tumors are a heterogeneous group of mesenchymal neoplasms with diagnostic challenges and overlapping histopathologic features. Recently, the molecular or immunohistochemical evaluation of dystrophin in the diagnosis of mesenchymal tumors with muscle differentiation has gained attention. In this retrospective study, the immunohistochemical expression of dystrophin was examined in 105 cases of uterine smooth muscle neoplasms, including 71 cases of leiomyoma (LM) and its variants, 6 cases of smooth muscle tumor of uncertain malignant potential (STUMP), and 28 cases of leiomyosarcoma (LMS). After thorough analysis, dystrophin expression was positive in 83.3 % of STUMP cases and 96.7 % of leiomyoma cases. In contrast, only 8 cases of LMS (28.6 %) expressed dystrophin. A significant difference in dystrophin expression was noted between STUMP and LMS, as well as LMS and LM and its variants. The median H-score in LM was significantly higher than in leiomyoma variants, STUMP, and LMS. In conclusion, dystrophin expression may be useful in distinguishing uterine LM, LM variants, and STUMP from LMS.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"81 ","pages":"Article 152604"},"PeriodicalIF":1.4,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883326","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 : 2025-12-26DOI: 10.1016/j.anndiagpath.2025.152603
Justin A. Bishop , Masato Nakaguro , Doreen Palsgrove , Anna Trzcinska , Anne C. McLean , Jeffrey Gagan , Junji Shibahara , Toshitaka Nagao
Keratocystoma is a rare salivary gland tumor described in 2002. Recently our group identified IRF2BP2::RUNX2 as a consistent genetic feature which may define keratocystoma. On the other hand, rare keratocystoma-like tumors were negative for this fusion, including two cases from our previous study. Herein we describe 3 cystic squamous salivary gland tumors harboring novel RUNX1 or RUNX2 fusions. Cases were identified from our practices. RNA-sequencing was performed for fusion identification, while reverse-transcriptase polymerase chain reaction (RT-PCR) and RUNX1 or RUNX2 break apart fluorescence in situ hybridization (FISH) were performed to confirm the identified fusions. Three tumors were identified, each with a unique fusion: RUNX1::IKZF3, RUNX1::VGLL4, and RUNX2::CDK2AP1, respectively. All fusions were confirmed by FISH and RT-PCR. Two had been diagnosed as keratocystoma and 1 as low-grade cystadenocarcinoma. All 3 arose in parotid glands of men, aged 48, 52, and 61 years. The tumors diagnosed as keratocystoma had features reminiscent of that tumor, except for a well-developed granular cell layer in one case, and foci of mucinous/glandular epithelium in the other. The third case was also cystic but only focally lined by mature keratinized squamous epithelium; the remaining epithelium was transitional and micropapillary. Cellular atypia and mitotic activity was minimal in all cases. All tumors were treated with surgery only; two patients had no recurrences (after 5 and 24 months), while follow-up was unavailable in the third case. Instead of keratocystoma being defined narrowly by IRF2BP2::RUNX2 fusions, there may exist a broader spectrum of RUNX1/2-rearranged cystic, squamous salivary gland tumors. More cases will be needed to further define this emerging family of neoplasms.
{"title":"Novel RUNX1/2 fusions in unclassified cystic squamous salivary gland tumors: Possible expansion of the keratocystoma family","authors":"Justin A. Bishop , Masato Nakaguro , Doreen Palsgrove , Anna Trzcinska , Anne C. McLean , Jeffrey Gagan , Junji Shibahara , Toshitaka Nagao","doi":"10.1016/j.anndiagpath.2025.152603","DOIUrl":"10.1016/j.anndiagpath.2025.152603","url":null,"abstract":"<div><div>Keratocystoma is a rare salivary gland tumor described in 2002. Recently our group identified <em>IRF2BP2</em>::<em>RUNX2</em> as a consistent genetic feature which may define keratocystoma. On the other hand, rare keratocystoma-like tumors were negative for this fusion, including two cases from our previous study. Herein we describe 3 cystic squamous salivary gland tumors harboring novel <em>RUNX1</em> or <em>RUNX2</em> fusions. Cases were identified from our practices. RNA-sequencing was performed for fusion identification, while reverse-transcriptase polymerase chain reaction (RT-PCR) and <em>RUNX1</em> or <em>RUNX2</em> break apart fluorescence in situ hybridization (FISH) were performed to confirm the identified fusions. Three tumors were identified, each with a unique fusion: <em>RUNX1</em>::<em>IKZF3</em>, <em>RUNX1</em>::<em>VGLL4</em>, and <em>RUNX2</em>::<em>CDK2AP1</em>, respectively. All fusions were confirmed by FISH and RT-PCR. Two had been diagnosed as keratocystoma and 1 as low-grade cystadenocarcinoma. All 3 arose in parotid glands of men, aged 48, 52, and 61 years. The tumors diagnosed as keratocystoma had features reminiscent of that tumor, except for a well-developed granular cell layer in one case, and foci of mucinous/glandular epithelium in the other. The third case was also cystic but only focally lined by mature keratinized squamous epithelium; the remaining epithelium was transitional and micropapillary. Cellular atypia and mitotic activity was minimal in all cases. All tumors were treated with surgery only; two patients had no recurrences (after 5 and 24 months), while follow-up was unavailable in the third case. Instead of keratocystoma being defined narrowly by <em>IRF2BP2</em>::<em>RUNX2</em> fusions, there may exist a broader spectrum of <em>RUNX1</em>/<em>2</em>-rearranged cystic, squamous salivary gland tumors. More cases will be needed to further define this emerging family of neoplasms.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"81 ","pages":"Article 152603"},"PeriodicalIF":1.4,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145866097","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 : 2025-12-21DOI: 10.1016/j.anndiagpath.2025.152601
Badr AbdullGaffar , Fatma B. Zarooni , Mohamed Alaqqad
There are a few studies that have focused on histopathologic findings in interval appendectomies compared to acute appendicitis and negative appendectomies. Our aim is to compare histopathologic features in interval appendectomies to a similar control group of stump appendectomies. A retrospective review study was conducted over a 10-year period. We found 21 (0.3 %) patients [age range: 10–70 years, average age: 40 years, male to female ratio: 1.3 to 1.0, average time interval: 6 weeks] who had interval appendectomies. Seventeen patients (81 %) showed three main patterns: xanthogranulomatous inflammatory infiltrates (48 %), Crohn-like transmural inflammatory infiltrates (33 %), and granulomatous inflammation (33 %). Postinflammatory structural changes included diverticulosis (33 %), mucosal hyperplasia (19 %), and fibrous obliteration (33 %). Other findings included fecalith (24 %), Actinomyces (19 %), hemosiderin pigment deposits (14 %) and fecal foreign body giant cells (24 %). No appendiceal neoplasms were detected. Two cases with complicated appendiceal diverticulosis showing mucosal hyperplasia, mucocele and extruded mucin pools were initially mistaken for low-grade appendiceal mucinous neoplasms. Ten patients (48 %) had residual acute inflammation, four of whom were associated with appendicolith and Actinomyces. We found eleven (0.13 %) patients [age range: 8–68 years, average age: 34 years, male to female ratio: 1.7 to 1.0, average time interval: 15 months] who had stump appendectomies. Five patients (45 %) showed xanthogranulomatous and Crohn-like changes. Epithelioid granulomas were not identified. Recurrent acute inflammation, mucosal hyperplasia, foreign body giant cell reaction and hemosiderin pigments were also found in stump appendectomies. There were no significant differences between xanthogranulomatous, Crohn-like, acute inflammatory, and hemosiderin-related changes, but there were significant differences in granulomatous inflammation, diverticulosis, mucosal hyperplasia, mucin pools, fibrous obliteration, appendicolith and Actinomyces between interval and stump appendicitis. These patterns were not correlated with age, gender or time intervals. Delayed interval and stump appendectomies exhibit a variety of subacute to chronic postinflammatory organizing reparative processes interspersed with acute inflammation.
{"title":"Interval appendicitis","authors":"Badr AbdullGaffar , Fatma B. Zarooni , Mohamed Alaqqad","doi":"10.1016/j.anndiagpath.2025.152601","DOIUrl":"10.1016/j.anndiagpath.2025.152601","url":null,"abstract":"<div><div>There are a few studies that have focused on histopathologic findings in interval appendectomies compared to acute appendicitis and negative appendectomies. Our aim is to compare histopathologic features in interval appendectomies to a similar control group of stump appendectomies. A retrospective review study was conducted over a 10-year period. We found 21 (0.3 %) patients [age range: 10–70 years, average age: 40 years, male to female ratio: 1.3 to 1.0, average time interval: 6 weeks] who had interval appendectomies. Seventeen patients (81 %) showed three main patterns: xanthogranulomatous inflammatory infiltrates (48 %), Crohn-like transmural inflammatory infiltrates (33 %), and granulomatous inflammation (33 %). Postinflammatory structural changes included diverticulosis (33 %), mucosal hyperplasia (19 %), and fibrous obliteration (33 %). Other findings included fecalith (24 %), Actinomyces (19 %), hemosiderin pigment deposits (14 %) and fecal foreign body giant cells (24 %). No appendiceal neoplasms were detected. Two cases with complicated appendiceal diverticulosis showing mucosal hyperplasia, mucocele and extruded mucin pools were initially mistaken for low-grade appendiceal mucinous neoplasms. Ten patients (48 %) had residual acute inflammation, four of whom were associated with appendicolith and Actinomyces. We found eleven (0.13 %) patients [age range: 8–68 years, average age: 34 years, male to female ratio: 1.7 to 1.0, average time interval: 15 months] who had stump appendectomies. Five patients (45 %) showed xanthogranulomatous and Crohn-like changes. Epithelioid granulomas were not identified. Recurrent acute inflammation, mucosal hyperplasia, foreign body giant cell reaction and hemosiderin pigments were also found in stump appendectomies. There were no significant differences between xanthogranulomatous, Crohn-like, acute inflammatory, and hemosiderin-related changes, but there were significant differences in granulomatous inflammation, diverticulosis, mucosal hyperplasia, mucin pools, fibrous obliteration, appendicolith and Actinomyces between interval and stump appendicitis. These patterns were not correlated with age, gender or time intervals. Delayed interval and stump appendectomies exhibit a variety of subacute to chronic postinflammatory organizing reparative processes interspersed with acute inflammation.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"81 ","pages":"Article 152601"},"PeriodicalIF":1.4,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839748","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 : 2025-12-21DOI: 10.1016/j.anndiagpath.2025.152602
Doaa Alqaidy , Hong Fang , Cesar A. Moran , L. Jeffrey Medeiros , Annikka Weissferdt
Paraneoplastic autoimmune multiorgan syndrome (PAMS) is a rare, often fatal condition that occurs in association with a range of neoplasms, most commonly lymphoproliferative disorders. PAMS often presents as paraneoplastic pemphigus, an autoimmune bullous disease affecting the skin and mucosal surfaces and bronchiolitis obliterans, a small airway disease that can result in respiratory failure and death. We describe a 39-year-old woman with an incidentally discovered paratracheal mass that was followed clinically. Seven years later, she developed ulcerative oral lesions followed by progressive dyspnea. Biopsy of the oral lesions showed intraepithelial clefting and interface mucositis. Immunofluorescence and serologic studies revealed IgG and complement deposition within intercellular epithelial spaces and along the basement membrane zone, together with circulating anti-plakin antibodies, establishing a diagnosis of paraneoplastic pemphigus. Resection of the paratracheal mass revealed lymphoid tissue with follicular and interfollicular stromal changes, atretic germinal centers and thickened mantle zones, consistent with unicentric Castleman disease, stroma-rich hyaline vascular variant. Wedge resection of the lung showed focal bronchiolar scarring supporting the clinical impression of bronchiolitis obliterans. The patient was treated with steroids and rituximab and recently underwent bilateral lung transplantation due to progressive respiratory symptoms. This report underscores a rare and potentially life-threatening complication of Castleman disease and presents an updated review of the literature. Bronchiolitis obliterans, in particular, has been identified as a marker of poor prognosis in patients with PAMS and lung transplantation often represents the only viable treatment option once the underlying neoplasm has been controlled.
{"title":"From the archives of MD Anderson Cancer Center: Paraneoplastic autoimmune multiorgan syndrome (PAMS) associated with stroma-rich Castleman disease","authors":"Doaa Alqaidy , Hong Fang , Cesar A. Moran , L. Jeffrey Medeiros , Annikka Weissferdt","doi":"10.1016/j.anndiagpath.2025.152602","DOIUrl":"10.1016/j.anndiagpath.2025.152602","url":null,"abstract":"<div><div>Paraneoplastic autoimmune multiorgan syndrome (PAMS) is a rare, often fatal condition that occurs in association with a range of neoplasms, most commonly lymphoproliferative disorders. PAMS often presents as paraneoplastic pemphigus, an autoimmune bullous disease affecting the skin and mucosal surfaces and bronchiolitis obliterans, a small airway disease that can result in respiratory failure and death. We describe a 39-year-old woman with an incidentally discovered paratracheal mass that was followed clinically. Seven years later, she developed ulcerative oral lesions followed by progressive dyspnea. Biopsy of the oral lesions showed intraepithelial clefting and interface mucositis. Immunofluorescence and serologic studies revealed IgG and complement deposition within intercellular epithelial spaces and along the basement membrane zone, together with circulating anti-plakin antibodies, establishing a diagnosis of paraneoplastic pemphigus. Resection of the paratracheal mass revealed lymphoid tissue with follicular and interfollicular stromal changes, atretic germinal centers and thickened mantle zones, consistent with unicentric Castleman disease, stroma-rich hyaline vascular variant. Wedge resection of the lung showed focal bronchiolar scarring supporting the clinical impression of bronchiolitis obliterans. The patient was treated with steroids and rituximab and recently underwent bilateral lung transplantation due to progressive respiratory symptoms. This report underscores a rare and potentially life-threatening complication of Castleman disease and presents an updated review of the literature. Bronchiolitis obliterans, in particular, has been identified as a marker of poor prognosis in patients with PAMS and lung transplantation often represents the only viable treatment option once the underlying neoplasm has been controlled.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"81 ","pages":"Article 152602"},"PeriodicalIF":1.4,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883327","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 : 2025-12-17DOI: 10.1016/j.anndiagpath.2025.152600
Anna Laura Santunione , Jessika Camatti , Silvia Corradi , Enrico Silingardi , Rossana Cecchi
Pulmonary intravascular mononuclear cell accumulations have been described in mechanical asphyxia, but their diagnostic value and independence from demographic or post-mortem factors remain uncertain. This study assessed the frequency of these accumulations in asphyxial deaths due to external neck compression compared with non-asphyxial deaths, and evaluated whether the association persists after adjustment for potential confounders.
Lung tissue samples from 31 external neck-compression deaths and 151 non-asphyxial controls were examined histologically. A subset underwent immunohistochemical phenotyping. Univariable comparisons were performed using χ2 and Mann–Whitney U tests. A multivariable logistic regression model—including age, sex, post-mortem interval (PMI), and body mass index (BMI)—was used to evaluate the independence of the association.
Intravascular mononuclear accumulations were observed in 41.9 % of neck-compression deaths versus 17.2 % of controls (p < 0.01; unadjusted OR 3.47, 95 % CI 1.52–7.96). In the multivariable model, external neck compression remained independently associated with the presence of intravascular accumulations (adjusted OR 2.93, 95 % CI 1.14–7.52; p = 0.025), while age, sex, PMI, and BMI showed no significant effect. Immunohistochemistry confirmed that accumulations consisted of mature mononuclear cell subsets.
Pulmonary intravascular mononuclear accumulations occur significantly more often in asphyxial deaths involving external neck compression, and this association persists after adjustment for key demographic and post-mortem variables. Although not specific to mechanical asphyxia, these accumulations represent a practical ancillary marker that may support the diagnosis of neck-compression vitality, especially in cases with limited external findings.
{"title":"Pulmonary intravascular mononuclear cell accumulation in cases of mechanical asphyxia due to external neck compression","authors":"Anna Laura Santunione , Jessika Camatti , Silvia Corradi , Enrico Silingardi , Rossana Cecchi","doi":"10.1016/j.anndiagpath.2025.152600","DOIUrl":"10.1016/j.anndiagpath.2025.152600","url":null,"abstract":"<div><div>Pulmonary intravascular mononuclear cell accumulations have been described in mechanical asphyxia, but their diagnostic value and independence from demographic or post-mortem factors remain uncertain. This study assessed the frequency of these accumulations in asphyxial deaths due to external neck compression compared with non-asphyxial deaths, and evaluated whether the association persists after adjustment for potential confounders.</div><div>Lung tissue samples from 31 external neck-compression deaths and 151 non-asphyxial controls were examined histologically. A subset underwent immunohistochemical phenotyping. Univariable comparisons were performed using χ<sup>2</sup> and Mann–Whitney <em>U</em> tests. A multivariable logistic regression model—including age, sex, post-mortem interval (PMI), and body mass index (BMI)—was used to evaluate the independence of the association.</div><div>Intravascular mononuclear accumulations were observed in 41.9 % of neck-compression deaths versus 17.2 % of controls (<em>p</em> < 0.01; unadjusted OR 3.47, 95 % CI 1.52–7.96). In the multivariable model, external neck compression remained independently associated with the presence of intravascular accumulations (adjusted OR 2.93, 95 % CI 1.14–7.52; <em>p</em> = 0.025), while age, sex, PMI, and BMI showed no significant effect. Immunohistochemistry confirmed that accumulations consisted of mature mononuclear cell subsets.</div><div>Pulmonary intravascular mononuclear accumulations occur significantly more often in asphyxial deaths involving external neck compression, and this association persists after adjustment for key demographic and post-mortem variables. Although not specific to mechanical asphyxia, these accumulations represent a practical ancillary marker that may support the diagnosis of neck-compression vitality, especially in cases with limited external findings.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"81 ","pages":"Article 152600"},"PeriodicalIF":1.4,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145790135","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 : 2025-12-01Epub Date: 2025-08-05DOI: 10.1016/j.anndiagpath.2025.152535
Eiichi Sasaki, Katsuhiro Masago
{"title":"Expression of INSM1 in salivary carcinoma showing thymus-like elements (CASTLE).","authors":"Eiichi Sasaki, Katsuhiro Masago","doi":"10.1016/j.anndiagpath.2025.152535","DOIUrl":"10.1016/j.anndiagpath.2025.152535","url":null,"abstract":"","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"79 ","pages":"152535"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800870","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 : 2025-11-25DOI: 10.1016/j.anndiagpath.2025.152599
Alishba Irfan
This letter evaluates the study by Milev and Ivanov (2025) comparing MIB1 and SP6 antibodies for Ki-67 assessment in breast carcinoma and outlines key methodological limitations that weaken the reliability of their conclusions. The use of a single, non blinded pathologist without interobserver or intraobserver reproducibility assessment raises concerns about scoring subjectivity. The absence of formal agreement analyses, such as Bland Altman plots, further limits confidence in the reported concordance between the two clones. Additionally, the study lacks a predefined primary endpoint, sample size justification, and power calculation, reducing its interpretive strength. Addressing these issues would enhance reproducibility, analytical validity, and the translational relevance of Ki-67 evaluation.
{"title":"“Letter to the editor: Comparative analysis of MIB1 and SP6 antibodies for Ki-67 assessment in breast carcinoma with focus on the influence of molecular subtyping”","authors":"Alishba Irfan","doi":"10.1016/j.anndiagpath.2025.152599","DOIUrl":"10.1016/j.anndiagpath.2025.152599","url":null,"abstract":"<div><div>This letter evaluates the study by Milev and Ivanov (2025) comparing MIB1 and SP6 antibodies for Ki-67 assessment in breast carcinoma and outlines key methodological limitations that weaken the reliability of their conclusions. The use of a single, non blinded pathologist without interobserver or intraobserver reproducibility assessment raises concerns about scoring subjectivity. The absence of formal agreement analyses, such as Bland Altman plots, further limits confidence in the reported concordance between the two clones. Additionally, the study lacks a predefined primary endpoint, sample size justification, and power calculation, reducing its interpretive strength. Addressing these issues would enhance reproducibility, analytical validity, and the translational relevance of Ki-67 evaluation.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"81 ","pages":"Article 152599"},"PeriodicalIF":1.4,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684727","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 : 2025-11-23DOI: 10.1016/j.anndiagpath.2025.152584
Dazhou Li , Xiaodong Lin , Wenqing Huang
Gastric amphicrine carcinoma (GAC) is a rare malignancy exhibiting dual neuroendocrine and exocrine differentiation. Claudin 18.2 expression patterns in GAC remain poorly characterized. We retrospectively analyzed four GAC cases diagnosed between 2020 and 2024 were retrospectively analyzed. Diagnosis required expression of at least two neuroendocrine markers and intracellular mucin, with amphicrine components comprising >30 % of tumor. Immunohistochemical evaluation included neuroendocrine markers, HER2, and Claudin 18.2. All patients were males aged 52–72 years (mean: 61.5 years). Tumors were located in gastric antrum (n = 2), cardia (n = 1), and body (n = 1), ranging from 4.0 to 4.5 cm. Three morphological patterns were identified: sheet-like/nested, tubular, and signet-ring trabecular. All cases expressed synaptophysin, with variable expression of chromogranin A (3/4), INSM1 (2/4), and CD56 (3/4). HER2 was negative in all cases. Claudin 18.2 expression correlated with morphological patterns: moderate to strong staining in sheet-like/nested areas (3/4) and tubular structures (3/4), but absent in signet-ring trabecular components (2/4). Follow-up demonstrated hepatic metastasis (n = 1) and death (n = 1) at 6 months, while two patients remained alive without recurrence. GAC may demonstrate distinctive morphology-dependent Claudin 18.2 expression, suggesting potential implications for targeted therapy selection and molecular subtyping. The morphological heterogeneity and aggressive clinical behavior underscore the importance of accurate diagnosis through comprehensive integrated assessment.
{"title":"Clinicopathological characterization of gastric amphicrine carcinoma: A case series","authors":"Dazhou Li , Xiaodong Lin , Wenqing Huang","doi":"10.1016/j.anndiagpath.2025.152584","DOIUrl":"10.1016/j.anndiagpath.2025.152584","url":null,"abstract":"<div><div>Gastric amphicrine carcinoma (GAC) is a rare malignancy exhibiting dual neuroendocrine and exocrine differentiation. Claudin 18.2 expression patterns in GAC remain poorly characterized. We retrospectively analyzed four GAC cases diagnosed between 2020 and 2024 were retrospectively analyzed. Diagnosis required expression of at least two neuroendocrine markers and intracellular mucin, with amphicrine components comprising >30 % of tumor. Immunohistochemical evaluation included neuroendocrine markers, HER2, and Claudin 18.2. All patients were males aged 52–72 years (mean: 61.5 years). Tumors were located in gastric antrum (<em>n</em> = 2), cardia (<em>n</em> = 1), and body (n = 1), ranging from 4.0 to 4.5 cm. Three morphological patterns were identified: sheet-like/nested, tubular, and signet-ring trabecular. All cases expressed synaptophysin, with variable expression of chromogranin A (3/4), INSM1 (2/4), and CD56 (3/4). HER2 was negative in all cases. Claudin 18.2 expression correlated with morphological patterns: moderate to strong staining in sheet-like/nested areas (3/4) and tubular structures (3/4), but absent in signet-ring trabecular components (2/4). Follow-up demonstrated hepatic metastasis (<em>n</em> = 1) and death (n = 1) at 6 months, while two patients remained alive without recurrence. GAC may demonstrate distinctive morphology-dependent Claudin 18.2 expression, suggesting potential implications for targeted therapy selection and molecular subtyping. The morphological heterogeneity and aggressive clinical behavior underscore the importance of accurate diagnosis through comprehensive integrated assessment.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"81 ","pages":"Article 152584"},"PeriodicalIF":1.4,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617909","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 : 2025-11-19DOI: 10.1016/j.anndiagpath.2025.152598
Sinem Eser Polat Ünal , Canan Sadullahoğlu , Hacer Boztepe Yeşilçay , Şencan Akdağ
Spread through air spaces (STAS) has emerged as a distinct invasion pattern in lung adenocarcinoma, but the prognostic implications of its morphologic features remain incompletely defined. In this study, we analyzed STAS presence, morphologic subtypes, density, and extent with clinicopathologic parameters and survival. We analyzed 184 surgically resected lung adenocarcinomas. We histopathologically examined the presence of STAS, STAS morphological subtypes (solid nests, micropapillary clusters, and single-cell spread), STAS extension, STAS density and evaluated the relationship of the findings with clinicopathological parameters. STAS was detected in 67.9 % of the tumors. The most common STAS subtype was solid (53.6 %), followed by micropapillary (30.4 %) and single-cell (16.0 %) subtypes. STAS density was categorized as low (1–4 tumor cell clusters) or high (≥5 clusters) at ×200 magnification, and STAS extent was classified as limited (≤3 alveolar spaces) or extensive (>3 spaces). High-density STAS was observed in 56 %, low-density STAS in 44 %; limited-STAS in 57.6 %, and extensive-STAS in 42.4 %. STAS positivity was significantly associated with predominant tumor pattern (p = 0.002), tumor grade (p < 0.001), pleural invasion (p = 0.004), lymphovascular invasion (LVI) (p < 0.001), recurrence (p < 0.001), metastasis (p < 0.001), pN (p = 0.003), overall survival (OS) (p < 0.001) and recurrence-free survival (DFS) (p < 0.001). Among morphologic subtypes, significant correlations were found with predominant tumor pattern (p < 0.001), grade (p = 0.001) and LVI (p = 0.005). We found STAS density to show a significant difference in OS (p = 0.009). Extensive STAS correlated with surgical resection type (p = 0.002), necrosis (p = 0.049), pN (p = 0.033), OS (p = 0.016) and DFS (p = 0.037). Our study shows that STAS and its features have prognostic significance with clinically meaningful differences in lung adenocarcinomas. These results highlight the potential clinical relevance of STAS subtype, density, and extent in risk stratification.
{"title":"Spread through air spaces (STAS) in lung adenocarcinoma: Prognostic impact of morphologic patterns, density, and extent","authors":"Sinem Eser Polat Ünal , Canan Sadullahoğlu , Hacer Boztepe Yeşilçay , Şencan Akdağ","doi":"10.1016/j.anndiagpath.2025.152598","DOIUrl":"10.1016/j.anndiagpath.2025.152598","url":null,"abstract":"<div><div>Spread through air spaces (STAS) has emerged as a distinct invasion pattern in lung adenocarcinoma, but the prognostic implications of its morphologic features remain incompletely defined. In this study, we analyzed STAS presence, morphologic subtypes, density, and extent with clinicopathologic parameters and survival. We analyzed 184 surgically resected lung adenocarcinomas. We histopathologically examined the presence of STAS, STAS morphological subtypes (solid nests, micropapillary clusters, and single-cell spread), STAS extension, STAS density and evaluated the relationship of the findings with clinicopathological parameters. STAS was detected in 67.9 % of the tumors. The most common STAS subtype was solid (53.6 %), followed by micropapillary (30.4 %) and single-cell (16.0 %) subtypes. STAS density was categorized as low (1–4 tumor cell clusters) or high (≥5 clusters) at ×200 magnification, and STAS extent was classified as limited (≤3 alveolar spaces) or extensive (>3 spaces). High-density STAS was observed in 56 %, low-density STAS in 44 %; limited-STAS in 57.6 %, and extensive-STAS in 42.4 %. STAS positivity was significantly associated with predominant tumor pattern (<em>p</em> = 0.002), tumor grade (<em>p</em> < 0.001), pleural invasion (<em>p</em> = 0.004), lymphovascular invasion (LVI) (<em>p</em> < 0.001), recurrence (p < 0.001), metastasis (p < 0.001), pN (<em>p</em> = 0.003), overall survival (OS) (p < 0.001) and recurrence-free survival (DFS) (p < 0.001). Among morphologic subtypes, significant correlations were found with predominant tumor pattern (p < 0.001), grade (<em>p</em> = 0.001) and LVI (<em>p</em> = 0.005). We found STAS density to show a significant difference in OS (<em>p</em> = 0.009). Extensive STAS correlated with surgical resection type (<em>p</em> = 0.002), necrosis (<em>p</em> = 0.049), pN (<em>p</em> = 0.033), OS (<em>p</em> = 0.016) and DFS (<em>p</em> = 0.037). Our study shows that STAS and its features have prognostic significance with clinically meaningful differences in lung adenocarcinomas. These results highlight the potential clinical relevance of STAS subtype, density, and extent in risk stratification.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"81 ","pages":"Article 152598"},"PeriodicalIF":1.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571866","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 : 2025-11-13DOI: 10.1016/j.anndiagpath.2025.152587
Midori Imai , Asami Nishikori , Tomoka Haratake , Midori Filiz Nishimura , Rio Yamada , Syoma Kato , Mizuha Tabe , Hiroyuki Yanai , Hidetaka Yamamoto , Yasuharu Sato
Plasma cell myeloma (PCM) is a hematological malignancy characterized by systemic proliferation of neoplastic plasma cells within the bone marrow. Diagnosis requires clinical findings and immunohistochemical staining, including CD138, CD79a, cyclin D1, immunoglobulin κ (Igκ), and λ (Igλ). However, CD79a and cyclin D1 have limited sensitivity and specificity, and Igκ/Igλ assessment is often difficult due to overstaining. Therefore, more reliable antibodies are needed to accurately diagnose PCM. In this study, we examined the diagnostic utility of CD56 expression in PCM. We retrospectively performed immunostaining for CD138, CD56, CD79a, cyclin D1, Igκ, and Igλ in bone marrow samples from 116 patients with PCM.
CD56 expression was observed in 85/116 cases (73.3 %), CD79a was downregulated in 46/116 cases (39.7 %), and cyclin D1 expression was observed in 42/116 cases (36.2 %). The expression of CD56 was significantly higher than that of CD79a and cyclin D1 (both p < 0.001). The combination of two antibodies resulted in the highest detection rate when combining CD56 and CD79a (105/116, 90.5 %), which was significantly higher than the detection rates of CD56 and cyclin D1 (93/116, 80.2 %) and CD79a and cyclin D1 (75/116, 64.7 %) (both p < 0.001). In contrast, lymphoplasmacytic lymphoma and marginal zone lymphoma lacked CD56 and cyclin D1 expression. Furthermore, in cases where light chain restriction was undetectable (11/116, 9.5 %), all could be diagnosed as PCM based on CD56, CD79a, and cyclin D1. Among these, CD56 showed the highest detection rate (8/11, 72.7 %).
These findings highlight CD56 as a helpful marker for PCM diagnosis and support further clinical research.
{"title":"The diagnostic utility and frequency of CD56 expression in plasma cell myeloma","authors":"Midori Imai , Asami Nishikori , Tomoka Haratake , Midori Filiz Nishimura , Rio Yamada , Syoma Kato , Mizuha Tabe , Hiroyuki Yanai , Hidetaka Yamamoto , Yasuharu Sato","doi":"10.1016/j.anndiagpath.2025.152587","DOIUrl":"10.1016/j.anndiagpath.2025.152587","url":null,"abstract":"<div><div>Plasma cell myeloma (PCM) is a hematological malignancy characterized by systemic proliferation of neoplastic plasma cells within the bone marrow. Diagnosis requires clinical findings and immunohistochemical staining, including CD138, CD79a, cyclin D1, immunoglobulin κ (Igκ), and λ (Igλ). However, CD79a and cyclin D1 have limited sensitivity and specificity, and Igκ/Igλ assessment is often difficult due to overstaining. Therefore, more reliable antibodies are needed to accurately diagnose PCM. In this study, we examined the diagnostic utility of CD56 expression in PCM. We retrospectively performed immunostaining for CD138, CD56, CD79a, cyclin D1, Igκ, and Igλ in bone marrow samples from 116 patients with PCM.</div><div>CD56 expression was observed in 85/116 cases (73.3 %), CD79a was downregulated in 46/116 cases (39.7 %), and cyclin D1 expression was observed in 42/116 cases (36.2 %). The expression of CD56 was significantly higher than that of CD79a and cyclin D1 (both <em>p</em> < 0.001). The combination of two antibodies resulted in the highest detection rate when combining CD56 and CD79a (105/116, 90.5 %), which was significantly higher than the detection rates of CD56 and cyclin D1 (93/116, 80.2 %) and CD79a and cyclin D1 (75/116, 64.7 %) (both <em>p</em> < 0.001). In contrast, lymphoplasmacytic lymphoma and marginal zone lymphoma lacked CD56 and cyclin D1 expression. Furthermore, in cases where light chain restriction was undetectable (11/116, 9.5 %), all could be diagnosed as PCM based on CD56, CD79a, and cyclin D1. Among these, CD56 showed the highest detection rate (8/11, 72.7 %).</div><div>These findings highlight CD56 as a helpful marker for PCM diagnosis and support further clinical research.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"81 ","pages":"Article 152587"},"PeriodicalIF":1.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532983","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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