Pub Date : 2025-07-19DOI: 10.1016/j.anndiagpath.2025.152530
Sean R. Williamson , Khaleel I. Al-Obaidy
{"title":"Papillary renal neoplasm with reverse polarity: A distinct entity ready for the World Health Organization classification","authors":"Sean R. Williamson , Khaleel I. Al-Obaidy","doi":"10.1016/j.anndiagpath.2025.152530","DOIUrl":"10.1016/j.anndiagpath.2025.152530","url":null,"abstract":"","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152530"},"PeriodicalIF":1.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711862","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 : 2025-07-19DOI: 10.1016/j.anndiagpath.2025.152533
Jing Zhou, L. Jeffrey Medeiros
Warthin tumor is uncommonly associated with lymphoma. We describe a case of a 73-year-old man with persistent left neck swelling in the submandibular region. Core needle biopsy with aspiration showed Warthin tumor and small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL). Histologic sections showed fragments of a Warthin tumor composed of oncocytic ductal epithelium in a background of a diffuse infiltration of small lymphocytes with small proliferation centers. The lymphocytes were predominantly CD5-positive monotypic B-cells by immunophenotypic analysis. This is the first report in the literature describing a concurrent Warthin tumor and SLL/CLL diagnosed by needle biopsy with aspiration. Based on our review of the literature and including the current case, 45 cases of lymphoma involving Warthin tumor have been reported previously. Forty-four of these lymphomas were lymph node-based neoplasms, with follicular lymphoma most common (n = 15; 34 %). Five (11 %) cases of SLL/CLL associated with Warthin tumor including the current case have been reported. Notably, extranodal marginal zone lymphoma is rarely associated with Warthin tumor, reported in a single case. These findings support the hypothesis that Warthin tumor arises from heterotopic salivary gland ducts within lymph nodes. We review the pathogenesis of this uncommon phenomenon and discuss the differential diagnosis.
{"title":"From the archives of MD Anderson Cancer Center: Small lymphocytic lymphoma/chronic lymphocytic leukemia diagnosed in Warthin tumor","authors":"Jing Zhou, L. Jeffrey Medeiros","doi":"10.1016/j.anndiagpath.2025.152533","DOIUrl":"10.1016/j.anndiagpath.2025.152533","url":null,"abstract":"<div><div>Warthin tumor is uncommonly associated with lymphoma. We describe a case of a 73-year-old man with persistent left neck swelling in the submandibular region. Core needle biopsy with aspiration showed Warthin tumor and small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL). Histologic sections showed fragments of a Warthin tumor composed of oncocytic ductal epithelium in a background of a diffuse infiltration of small lymphocytes with small proliferation centers. The lymphocytes were predominantly CD5-positive monotypic B-cells by immunophenotypic analysis. This is the first report in the literature describing a concurrent Warthin tumor and SLL/CLL diagnosed by needle biopsy with aspiration. Based on our review of the literature and including the current case, 45 cases of lymphoma involving Warthin tumor have been reported previously. Forty-four of these lymphomas were lymph node-based neoplasms, with follicular lymphoma most common (<em>n</em> = 15; 34 %). Five (11 %) cases of SLL/CLL associated with Warthin tumor including the current case have been reported. Notably, extranodal marginal zone lymphoma is rarely associated with Warthin tumor, reported in a single case. These findings support the hypothesis that Warthin tumor arises from heterotopic salivary gland ducts within lymph nodes. We review the pathogenesis of this uncommon phenomenon and discuss the differential diagnosis.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"79 ","pages":"Article 152533"},"PeriodicalIF":1.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679487","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 : 2025-07-14DOI: 10.1016/j.anndiagpath.2025.152531
Dan Zhang , Chaoshan Wang , Haorui Zhang , Wenmin Yang , Ling Nie
Parotid carcinoma showing thymus-like element (CASTLE) is positive for the immunohistochemical markers CD5 and CD117. However, the specificity of the markers has not been evaluated in parotid tumors with a squamous phenotype. This study aims to validate the efficiency of CD5, CD117, and INSM1 in distinguishing CASTLE from other parotid tumors with a squamous phenotype, including squamous cell carcinoma (SCC, n = 4), lymphoepithelial carcinoma (LEC, n = 5), and pleomorphic adenoma with squamous differentiation (PA-SD, n = 3). The parotid CASTLE exhibited diffusely CD5 membranous positivity (Immunoreactive Score, IRS = 12) and moderate INSM1 nuclear expression (IRS = 6), while SCC, PA-SD, and LEC showed negligible CD5 (IRS ≤ 2) and weak/focal INSM1 (IRS ≤ 3) expression. Although CD117 was diffusely positive in CASTLE, it was moderately to strongly expressed in the LECs (IRS = 9), limiting its diagnostic utility in differential diagnosis. EBER in situ hybridization (ISH) confirmed EBV association in all LECs but not in the CASTLE. In summary, simultaneous CD5 and INSM1 expression may serve as a distinct feature for parotid CASTLE, facilitating differential diagnosis in salivary gland pathology. In addition, EBER ISH remains essential to exclude LEC.
腮腺癌呈胸腺样元素（CASTLE），免疫组化标志物CD5和CD117阳性。然而，标志物的特异性尚未评估与鳞状表型腮腺肿瘤。本研究旨在验证CD5、CD117和INSM1在区分CASTLE与其他鳞状表型腮腺肿瘤的有效性，包括鳞状细胞癌（SCC, n = 4）、淋巴上皮癌（LEC, n = 5）和鳞状分化多形性腺瘤（PA-SD, n = 3）。腮腺CASTLE表现为弥散性CD5膜性阳性（Immunoreactive Score, IRS = 12）和中度INSM1核表达（IRS = 6），而SCC、PA-SD和LEC表现为可忽略性CD5 （IRS≤2）和弱/局灶性INSM1 （IRS≤3）表达。尽管CD117在CASTLE中呈弥漫性阳性，但在LECs中表达为中至强表达（IRS = 9），限制了其在鉴别诊断中的诊断价值。EBER原位杂交（ISH）证实EBV在所有lec中都存在，但在CASTLE中没有。综上所述，CD5和INSM1同时表达可能是腮腺CASTLE的一个明显特征，有助于在唾液腺病理中进行鉴别诊断。此外，EBER ISH对于排除LEC仍然是必不可少的。
{"title":"Simultaneous expression of CD5 and INSM1 may distinguish parotid CASTLE from other primary tumors with a squamous phenotype","authors":"Dan Zhang , Chaoshan Wang , Haorui Zhang , Wenmin Yang , Ling Nie","doi":"10.1016/j.anndiagpath.2025.152531","DOIUrl":"10.1016/j.anndiagpath.2025.152531","url":null,"abstract":"<div><div>Parotid carcinoma showing thymus-like element (CASTLE) is positive for the immunohistochemical markers CD5 and CD117. However, the specificity of the markers has not been evaluated in parotid tumors with a squamous phenotype. This study aims to validate the efficiency of CD5, CD117, and INSM1 in distinguishing CASTLE from other parotid tumors with a squamous phenotype, including squamous cell carcinoma (SCC, <em>n</em> = 4), lymphoepithelial carcinoma (LEC, <em>n</em> = 5), and pleomorphic adenoma with squamous differentiation (PA-SD, <em>n</em> = 3). The parotid CASTLE exhibited diffusely CD5 membranous positivity (Immunoreactive Score, IRS = 12) and moderate INSM1 nuclear expression (IRS = 6), while SCC, PA-SD, and LEC showed negligible CD5 (IRS ≤ 2) and weak/focal INSM1 (IRS ≤ 3) expression. Although CD117 was diffusely positive in CASTLE, it was moderately to strongly expressed in the LECs (IRS = 9), limiting its diagnostic utility in differential diagnosis. EBER <em>in situ</em> hybridization (ISH) confirmed EBV association in all LECs but not in the CASTLE. In summary, simultaneous CD5 and INSM1 expression may serve as a distinct feature for parotid CASTLE, facilitating differential diagnosis in salivary gland pathology. In addition, EBER ISH remains essential to exclude LEC.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"79 ","pages":"Article 152531"},"PeriodicalIF":1.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654789","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 : 2025-07-13DOI: 10.1016/j.anndiagpath.2025.152532
Xiaoyan Yang , William M. Rehrauer , Paul S. Weisman , Jin Xu
Recently in this journal, Ramalingam et al described the clinicopathological features of mucinous ovarian tumors arising in association with mature cystic teratomas (MT). Of particular interest to us are the appendix-like histological features including prominent subepithelial stromal clefts and pseudomyxoma ovarii described by Ramalingam et al and others.
In our own practice, we have encountered a handful of mucinous ovarian tumors with the above-noted histological features for which no MT and no appendiceal tumor could be found, leaving the tumors' origin in question.
Here we share our experience using short tandem repeat (STR) analysis in order to address this very scenario using 4 illustrative cases. Using STR analysis, we show that the above-noted histological features may indeed suggest a teratomatous origin even in the absence of a histologically apparent MT. We also show that these same histological features may be seen in bona fide primary ovarian mucinous tumors that have a purely somatic origin.
{"title":"Appendix-like morphology in primary ovarian mucinous tumors lacking a concurrent mature teratoma: A series of 4 cases illustrating the utility of STR analysis","authors":"Xiaoyan Yang , William M. Rehrauer , Paul S. Weisman , Jin Xu","doi":"10.1016/j.anndiagpath.2025.152532","DOIUrl":"10.1016/j.anndiagpath.2025.152532","url":null,"abstract":"<div><div>Recently in this journal, Ramalingam et al described the clinicopathological features of mucinous ovarian tumors arising in association with mature cystic teratomas (MT). Of particular interest to us are the appendix-like histological features including prominent subepithelial stromal clefts and pseudomyxoma ovarii described by Ramalingam et al and others.</div><div>In our own practice, we have encountered a handful of mucinous ovarian tumors with the above-noted histological features for which no MT and no appendiceal tumor could be found, leaving the tumors' origin in question.</div><div>Here we share our experience using short tandem repeat (STR) analysis in order to address this very scenario using 4 illustrative cases. Using STR analysis, we show that the above-noted histological features may indeed suggest a teratomatous origin even in the absence of a histologically apparent MT. We also show that these same histological features may be seen in bona fide primary ovarian mucinous tumors that have a purely somatic origin.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"79 ","pages":"Article 152532"},"PeriodicalIF":1.5,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654788","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 : 2025-07-12DOI: 10.1016/j.anndiagpath.2025.152526
Camila Souto Aguiar , Marcos Adriano Garcia Campos , Antonio Augusto Lima Teixeira Júnior , Syomara Pereira da Costa Melo , Liseana de Oliveira Barbosa , Denner Rodrigo Diniz Duarte , Lucas Vieira de Lima , Pedro Manuel Barros de Sousa , Jaqueline Diniz Pinho , Joyce Santos Lages , Isabela Werneck da Cunha , Gyl Eanes Barros Silva
Histopathological evaluation of lymph nodes in penile cancer remains the gold standard for identifying lymph node metastases; however, it is an invasive procedure that can lead to postoperative complications. Several studies have reported that tumor budding is an independent prognostic factor for locoregional disease recurrence in many solid cancers. We evaluated the relationship between tumor budding categories and other histological parameters of aggressiveness in 218 patients diagnosed with penile squamous cell carcinoma. We performed a prospective cohort study with a 6-month follow-up period. Clinical data were extracted from the medical records and patient interviews, and pathologists evaluated histopathological data. Tumor budding was associated with histopathological characteristics and the appearance of nodal metastasis within 6 months of diagnosis. The chi-square test was applied at a significance level of 5 %. Our study demonstrated a statistically significant association between tumor budding scores of 2 and 3 and the following variables: high histological grade (G2 and G3), presence of angiolymphatic invasion, presence of perineural invasion, higher pathological stage (pT3 and pT4), and presence of nodal metastasis. This may indicate that moderate/high-grade tumor growth (scores of 2 and 3) is related to a more aggressive behavior of penile squamous cell carcinoma. Tumor budding shows promise as a prognostic tool in histopathological evaluations, particularly for predicting lymph node metastases. Its simplicity makes it an accessible method, especially in underdeveloped countries and regions with high incidence rates of this neoplasm.
{"title":"Association of tumor budding with prognostic factors and lymph node metastasis in penile cancer: A prospective cohort of 218 cases","authors":"Camila Souto Aguiar , Marcos Adriano Garcia Campos , Antonio Augusto Lima Teixeira Júnior , Syomara Pereira da Costa Melo , Liseana de Oliveira Barbosa , Denner Rodrigo Diniz Duarte , Lucas Vieira de Lima , Pedro Manuel Barros de Sousa , Jaqueline Diniz Pinho , Joyce Santos Lages , Isabela Werneck da Cunha , Gyl Eanes Barros Silva","doi":"10.1016/j.anndiagpath.2025.152526","DOIUrl":"10.1016/j.anndiagpath.2025.152526","url":null,"abstract":"<div><div>Histopathological evaluation of lymph nodes in penile cancer remains the gold standard for identifying lymph node metastases; however, it is an invasive procedure that can lead to postoperative complications. Several studies have reported that tumor budding is an independent prognostic factor for locoregional disease recurrence in many solid cancers. We evaluated the relationship between tumor budding categories and other histological parameters of aggressiveness in 218 patients diagnosed with penile squamous cell carcinoma. We performed a prospective cohort study with a 6-month follow-up period. Clinical data were extracted from the medical records and patient interviews, and pathologists evaluated histopathological data. Tumor budding was associated with histopathological characteristics and the appearance of nodal metastasis within 6 months of diagnosis. The chi-square test was applied at a significance level of 5 %. Our study demonstrated a statistically significant association between tumor budding scores of 2 and 3 and the following variables: high histological grade (G2 and G3), presence of angiolymphatic invasion, presence of perineural invasion, higher pathological stage (pT3 and pT4), and presence of nodal metastasis. This may indicate that moderate/high-grade tumor growth (scores of 2 and 3) is related to a more aggressive behavior of penile squamous cell carcinoma. Tumor budding shows promise as a prognostic tool in histopathological evaluations, particularly for predicting lymph node metastases. Its simplicity makes it an accessible method, especially in underdeveloped countries and regions with high incidence rates of this neoplasm.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"79 ","pages":"Article 152526"},"PeriodicalIF":1.5,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634184","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 : 2025-07-08DOI: 10.1016/j.anndiagpath.2025.152527
Runlin Feng , Tao Zhang , Changxing Ke , Yanping Tao
Objective
Myxoid adrenocortical adenoma (MAA) with a pseudoglandular pattern is a rare variant of adrenal cortical tumors, characterized by a prominent myxoid matrix and diverse architectural patterns. Due to its overlapping features with malignant and metastatic myxoid tumors, it poses significant diagnostic challenges. This study aimed to delineate the clinicopathologic, immunohistochemical, and differential diagnostic features of MAA based on a case series.
Methods
We retrospectively analyzed nine cases of MAA diagnosed between 2015 and 2023. Comprehensive clinicoradiologic, histopathologic, and immunophenotypic data were collected. Histologic evaluation included Weiss scoring, mitotic activity, and reticulin framework analysis. Immunohistochemistry was performed using a panel of markers including α-inhibin, Melan-A, Synaptophysin, CD56, CK, Vimentin, S100, and HMB45. Alcian blue and AB-PAS staining were applied to assess mucin content. All cases were followed for postoperative outcomes.
Results
The cohort included 5 females and 4 males, with a median age of 40 years (range 27–53). Tumor sizes ranged from 2.2 to 7.4 cm (mean 4.1 cm). Grossly, all tumors were well-demarcated, solid, and mucin-rich without evidence of necrosis or vascular invasion. Histologically, all cases exhibited abundant extracellular myxoid stroma (mean proportion: 78.3 %) and diverse pseudoglandular, cord-like, and sieve-like architectures. Tumor cells were polygonal with eosinophilic or hyaline cytoplasm and minimal atypia. No mitotic figures >2/20 HPF were observed. Immunohistochemistry showed diffuse positivity for α-inhibin (100 %), Melan-A (88.9 %), CD56 (77.8 %), Synaptophysin (66.7 %), and Vimentin (100 %), while S100, HMB45, and Chromogranin A were consistently negative. Ki-67 index was <3 % in all cases. Alcian blue was strongly positive in 77.8 % of tumors, supporting the myxoid component. During a median follow-up of 14 months, no recurrence or metastasis occurred.
Conclusions
MAA with a pseudoglandular pattern is a benign but diagnostically challenging adrenal neoplasm due to its histologic overlap with myxoid adrenal cortical carcinoma and metastatic mucinous tumors. Recognition of its characteristic morphology, immunoprofile, and benign clinical course is critical to prevent overtreatment. Incorporating Weiss criteria, reticulin staining, and a myxoid tumor differential panel enhances diagnostic accuracy in clinical practice.
{"title":"Myxoid adrenocortical adenoma with pseudoglandular pattern: A clinicopathological study of a rare histologic variant and its diagnostic challenges","authors":"Runlin Feng , Tao Zhang , Changxing Ke , Yanping Tao","doi":"10.1016/j.anndiagpath.2025.152527","DOIUrl":"10.1016/j.anndiagpath.2025.152527","url":null,"abstract":"<div><h3>Objective</h3><div>Myxoid adrenocortical adenoma (MAA) with a pseudoglandular pattern is a rare variant of adrenal cortical tumors, characterized by a prominent myxoid matrix and diverse architectural patterns. Due to its overlapping features with malignant and metastatic myxoid tumors, it poses significant diagnostic challenges. This study aimed to delineate the clinicopathologic, immunohistochemical, and differential diagnostic features of MAA based on a case series.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed nine cases of MAA diagnosed between 2015 and 2023. Comprehensive clinicoradiologic, histopathologic, and immunophenotypic data were collected. Histologic evaluation included Weiss scoring, mitotic activity, and reticulin framework analysis. Immunohistochemistry was performed using a panel of markers including α-inhibin, Melan-A, Synaptophysin, CD56, CK, Vimentin, S100, and HMB45. Alcian blue and AB-PAS staining were applied to assess mucin content. All cases were followed for postoperative outcomes.</div></div><div><h3>Results</h3><div>The cohort included 5 females and 4 males, with a median age of 40 years (range 27–53). Tumor sizes ranged from 2.2 to 7.4 cm (mean 4.1 cm). Grossly, all tumors were well-demarcated, solid, and mucin-rich without evidence of necrosis or vascular invasion. Histologically, all cases exhibited abundant extracellular myxoid stroma (mean proportion: 78.3 %) and diverse pseudoglandular, cord-like, and sieve-like architectures. Tumor cells were polygonal with eosinophilic or hyaline cytoplasm and minimal atypia. No mitotic figures >2/20 HPF were observed. Immunohistochemistry showed diffuse positivity for α-inhibin (100 %), Melan-A (88.9 %), CD56 (77.8 %), Synaptophysin (66.7 %), and Vimentin (100 %), while S100, HMB45, and Chromogranin A were consistently negative. Ki-67 index was <3 % in all cases. Alcian blue was strongly positive in 77.8 % of tumors, supporting the myxoid component. During a median follow-up of 14 months, no recurrence or metastasis occurred.</div></div><div><h3>Conclusions</h3><div>MAA with a pseudoglandular pattern is a benign but diagnostically challenging adrenal neoplasm due to its histologic overlap with myxoid adrenal cortical carcinoma and metastatic mucinous tumors. Recognition of its characteristic morphology, immunoprofile, and benign clinical course is critical to prevent overtreatment. Incorporating Weiss criteria, reticulin staining, and a myxoid tumor differential panel enhances diagnostic accuracy in clinical practice.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"79 ","pages":"Article 152527"},"PeriodicalIF":1.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144580784","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 : 2025-07-08DOI: 10.1016/j.anndiagpath.2025.152525
Ling-Ling Wang , Xue-Jing Wei , Qiao-Chu Zhang , Feng Li , Guang-Yong Chen
This study aimed to analyze the expression of three immune markers, succinate dehydrogenase (SDHB), S-100, and alpha thalassemia retardation syndrome X-linked (ATRX), in pheochromocytoma and paraganglioma (PPGL) tumor tissues and to evaluate their correlation with histopathological parameters to predict the recurrence risk in PPGLs. A retrospective analysis was conducted using a cohort of 173 patients with PPGLs with definite pathological diagnoses and complete follow-up data. The expression of SDHB, S-100, and ATRX in the tumor tissues was detected using the EnVision immunohistochemical method. Histological grading of PPGLs was performed using the Compound Adrenal Pheochromocytoma and Paraganglioma Grading System (COPPS), and the correlation between the expression of the three immune markers and metastasis or recurrence of PPGLs was analyzed. Among 173 patients with PPGLs, 57 (32.9 %) had metastasis or recurrence. Of these 57 patients, 57.9 % (33/57) had tumors in the retroperitoneum. In 83 % (53/57) of the cases, the maximum diameter of the tumors was ≥5 cm. Vascular invasion was observed in 46 patients (80.7 %). SDHB, ATRX, and S-100 were negatively stained in 33 (57.9 %), 40(70.2 %), and 43(75.4 %) PPGL patients with metastasis or recurrence, respectively, which was significantly higher than that in those without metastasis or recurrence. These differences were statistically significant (P < 0.001). Multivariate analysis showed that tumor diameter ≥ 5 cm, negative ATRX and SDHB expressions, and vascular invasion were independent risk factors for tumor metastasis and recurrence. SDHB, ATRX and S-100 can be used as immunohistochemical indicators to predict the metastatic risk of PPGLs.
{"title":"Analysis of clinicopathological and immunohistochemical features of pheochromocytoma/paraganglioma","authors":"Ling-Ling Wang , Xue-Jing Wei , Qiao-Chu Zhang , Feng Li , Guang-Yong Chen","doi":"10.1016/j.anndiagpath.2025.152525","DOIUrl":"10.1016/j.anndiagpath.2025.152525","url":null,"abstract":"<div><div>This study aimed to analyze the expression of three immune markers, succinate dehydrogenase (SDHB), S-100, and alpha thalassemia retardation syndrome X-linked (ATRX), in pheochromocytoma and paraganglioma (PPGL) tumor tissues and to evaluate their correlation with histopathological parameters to predict the recurrence risk in PPGLs. A retrospective analysis was conducted using a cohort of 173 patients with PPGLs with definite pathological diagnoses and complete follow-up data. The expression of SDHB, S-100, and ATRX in the tumor tissues was detected using the EnVision immunohistochemical method. Histological grading of PPGLs was performed using the Compound Adrenal Pheochromocytoma and Paraganglioma Grading System (COPPS), and the correlation between the expression of the three immune markers and metastasis or recurrence of PPGLs was analyzed. Among 173 patients with PPGLs, 57 (32.9 %) had metastasis or recurrence. Of these 57 patients, 57.9 % (33/57) had tumors in the retroperitoneum. In 83 % (53/57) of the cases, the maximum diameter of the tumors was ≥5 cm. Vascular invasion was observed in 46 patients (80.7 %). SDHB, ATRX, and S-100 were negatively stained in 33 (57.9 %), 40(70.2 %), and 43(75.4 %) PPGL patients with metastasis or recurrence, respectively, which was significantly higher than that in those without metastasis or recurrence. These differences were statistically significant (<em>P</em> < 0.001). Multivariate analysis showed that tumor diameter ≥ 5 cm, negative ATRX and SDHB expressions, and vascular invasion were independent risk factors for tumor metastasis and recurrence. SDHB, ATRX and S-100 can be used as immunohistochemical indicators to predict the metastatic risk of PPGLs.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"79 ","pages":"Article 152525"},"PeriodicalIF":1.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604728","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 : 2025-07-08DOI: 10.1016/j.anndiagpath.2025.152528
Matthew Romanish, Rana Naous
Metastatic malignancies to pancreas are extremely rare with most common origins being kidney and melanoma. This study aims to evaluate types of solid malignant metastasis in pancreatic FNAs at our institution along with comprehensive review of reported literature. Our laboratory information system was queried over years 2000–2024 to identify all pancreatic FNAs with metastasis. “Positive for Malignant Cells” diagnosis was included in our review. “Atypical” or “Suspicious for malignancy” were excluded. Type of metastatic malignancy, location and presence of synchronous metastasis were documented. Our results show that out of 4051 pancreatic FNAs with “Positive for Malignant Cells”, 83 (2 %) cases were metastatic, while remaining 127 cases represented primary pancreatic adenocarcinomas or neuroendocrine tumors. 43 (52 %) renal cell carcinomas, 15 lung carcinomas (17.6 %), 7 skin melanoma (8.2 %),4 breast ductal adenocarcinoma (4.7 %), 3 urothelial carcinomas (3.5 %), 2 leiomyosarcoma (2.4 %), 2 ovarian serous carcinoma (2.4 %),1 uterine adenocarcinoma (1.2 %),1 prostatic carcinoma (1.2 %), 1 skin Merkel-cell carcinoma (1.2 %),1 gastric adenocarcinoma (1.2 %),1 colorectal adenocarcinoma (1.2 %), and 1 vulvar Squamous-cell carcinoma (1.2 %) were identified. Majority (~59 %) of tumors had synchronous presentation. Most common synchronous organs were lungs, liver, and mesenteric lymph nodes. In conclusion, our study demonstrated further support for lung being the second most common primary site of pancreatic metastasis. Renal origin is the most common secondary tumor in our institutional review, followed by combination of lung, breast, and melanoma. Sarcomas can rarely present as pancreatic metastasis, and thorough clinical and histomorphology correlation is warranted. Origin-specific immunostains and molecular testing may help in challenging secondary pancreatic tumors.
{"title":"Metastatic tumors to the pancreas: An institutional experience","authors":"Matthew Romanish, Rana Naous","doi":"10.1016/j.anndiagpath.2025.152528","DOIUrl":"10.1016/j.anndiagpath.2025.152528","url":null,"abstract":"<div><div>Metastatic malignancies to pancreas are extremely rare with most common origins being kidney and melanoma. This study aims to evaluate types of solid malignant metastasis in pancreatic FNAs at our institution along with comprehensive review of reported literature. Our laboratory information system was queried over years 2000–2024 to identify all pancreatic FNAs with metastasis. “Positive for Malignant Cells” diagnosis was included in our review. “Atypical” or “Suspicious for malignancy” were excluded. Type of metastatic malignancy, location and presence of synchronous metastasis were documented. Our results show that out of 4051 pancreatic FNAs with “Positive for Malignant Cells”, 83 (2 %) cases were metastatic, while remaining 127 cases represented primary pancreatic adenocarcinomas or neuroendocrine tumors. 43 (52 %) renal cell carcinomas, 15 lung carcinomas (17.6 %), 7 skin melanoma (8.2 %),4 breast ductal adenocarcinoma (4.7 %), 3 urothelial carcinomas (3.5 %), 2 leiomyosarcoma (2.4 %), 2 ovarian serous carcinoma (2.4 %),1 uterine adenocarcinoma (1.2 %),1 prostatic carcinoma (1.2 %), 1 skin Merkel-cell carcinoma (1.2 %),1 gastric adenocarcinoma (1.2 %),1 colorectal adenocarcinoma (1.2 %), and 1 vulvar Squamous-cell carcinoma (1.2 %) were identified. Majority (~59 %) of tumors had synchronous presentation. Most common synchronous organs were lungs, liver, and mesenteric lymph nodes. In conclusion, our study demonstrated further support for lung being the second most common primary site of pancreatic metastasis. Renal origin is the most common secondary tumor in our institutional review, followed by combination of lung, breast, and melanoma. Sarcomas can rarely present as pancreatic metastasis, and thorough clinical and histomorphology correlation is warranted. Origin-specific immunostains and molecular testing may help in challenging secondary pancreatic tumors.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"79 ","pages":"Article 152528"},"PeriodicalIF":1.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144580781","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 : 2025-07-08DOI: 10.1016/j.anndiagpath.2025.152529
Pierre Tran , Khalid Shittu , Ehsan Aliniagerdroudbari , Sumit Singla , Momal Tara Chand , Beena U. Ahsan
Sebaceous gland ectopia (SGE) is a disorder in which sebaceous gland lobules appear in atypical anatomical locations. Sebaceous glands are normally found in the skin, particularly abundant on the face, scalp and other areas with hair follicles. SGE in the esophagus is an extremely rare, benign condition that morphologically may mimic epidermoid metaplasia due to the presence of excretory duct, lined by keratinized squamous epithelium. We present a retrospective case series of patients with evidence of SGE per endoscopic biopsy tissue analysis between 2000 and 2025. A total of 12 biopsy analyses from 10 patients were included: 7 women (70 %) and 3 men (30 %). The mean age at diagnosis was 63 years. There were 7 patients who reported previous or current alcohol use (70 %); one patient reported previous tobacco use (10 %). Gastrointestinal reflux disease, the most common clinical indication, was seen in six patients (60 %). The lesions, when visible on endoscopy, were located in the proximal and/or mid esophagus (100 %); three endoscopies noted no lesions (25 %). Two repeat biopsies in one patient showed persistent SGE. No biopsies showed dysplasia (0 %). Additionally, we performed a literature review of articles in the PubMed database, identifying 65 other reported patients. The clinicopathologic findings in this study add additional evidence on this rare entity.
{"title":"Sebaceous gland ectopia of the esophagus: A clinical, endoscopic, and pathologic study of a rare condition with literature review","authors":"Pierre Tran , Khalid Shittu , Ehsan Aliniagerdroudbari , Sumit Singla , Momal Tara Chand , Beena U. Ahsan","doi":"10.1016/j.anndiagpath.2025.152529","DOIUrl":"10.1016/j.anndiagpath.2025.152529","url":null,"abstract":"<div><div>Sebaceous gland ectopia (SGE) is a disorder in which sebaceous gland lobules appear in atypical anatomical locations. Sebaceous glands are normally found in the skin, particularly abundant on the face, scalp and other areas with hair follicles. SGE in the esophagus is an extremely rare, benign condition that morphologically may mimic epidermoid metaplasia due to the presence of excretory duct, lined by keratinized squamous epithelium. We present a retrospective case series of patients with evidence of SGE per endoscopic biopsy tissue analysis between 2000 and 2025. A total of 12 biopsy analyses from 10 patients were included: 7 women (70 %) and 3 men (30 %). The mean age at diagnosis was 63 years. There were 7 patients who reported previous or current alcohol use (70 %); one patient reported previous tobacco use (10 %). Gastrointestinal reflux disease, the most common clinical indication, was seen in six patients (60 %). The lesions, when visible on endoscopy, were located in the proximal and/or mid esophagus (100 %); three endoscopies noted no lesions (25 %). Two repeat biopsies in one patient showed persistent SGE. No biopsies showed dysplasia (0 %). Additionally, we performed a literature review of articles in the PubMed database, identifying 65 other reported patients. The clinicopathologic findings in this study add additional evidence on this rare entity.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"79 ","pages":"Article 152529"},"PeriodicalIF":1.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662959","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 : 2025-07-07DOI: 10.1016/j.anndiagpath.2025.152524
Serena Salzano , Rosario Caltabiano , Gaetano Magro , Antonio D'Amati , Cristina Pizzimenti , Andrea Maugeri , Antonella Agodi , Giuseppe Barbagallo , Francesco Certo , Francesco Fiorentino , Giovanni Tuccari , Maurizio Martini , Antonio Ieni , Valeria Barresi , Giuseppe Broggi
Objective
To evaluate the diagnostic performance of MTAP and p16 immunohistochemistry (IHC) as surrogate markers for CDKN2A/B homozygous deletion (HD) in central nervous system (CNS) tumors, and to assess their prognostic significance.
Methods
Molecular tests including gene sequencing or fluorescence in situ hybridization (FISH) have traditionally been used to assess CDKN2A/B HD. However, due to lower costs and wider availability, IHC surrogates such as MTAP and p16 are gaining interest. We investigated the concordance between MTAP and p16 IHC expression and CDKN2A/B status as determined by FISH.
Results
Our cohort consisted of 227 patients with various CNS tumor types: glioblastoma IDH-wild type (n = 64; 28.2 %), meningioma (n = 61; 26.9 %), IDH-mutant astrocytoma (n = 52; 22.9 %), IDH-mutant and 1p/19q-codeleted oligodendroglioma (n = 35; 15.4 %), and pleomorphic xanthoastrocytoma (n = 15; 6.6 %). In all tumor types, most cases with CDKN2A/B HD showed MTAP loss and p16 negativity (p-values < 0.05). The combination of MTAP and p16 IHC yielded a sensitivity of 92 %, specificity of 80 %, positive predictive value of 86 %, and negative predictive value of 88 % in detecting CDKN2A/B HD. Survival analysis demonstrated significantly reduced disease-free and overall survival among patients with MTAP loss, p16 negativity, and CDKN2A/B HD.
Conclusions
MTAP immunohistochemistry, alone or combined with p16, represents a cost-effective and feasible surrogate for detecting CDKN2A/B homozygous deletion in CNS tumors and provides relevant prognostic information.
{"title":"MTAP and p16 as immunohistochemical surrogates of CDKN2A/B homozygous deletion in central nervous system tumors: A multicentre Italian experience","authors":"Serena Salzano , Rosario Caltabiano , Gaetano Magro , Antonio D'Amati , Cristina Pizzimenti , Andrea Maugeri , Antonella Agodi , Giuseppe Barbagallo , Francesco Certo , Francesco Fiorentino , Giovanni Tuccari , Maurizio Martini , Antonio Ieni , Valeria Barresi , Giuseppe Broggi","doi":"10.1016/j.anndiagpath.2025.152524","DOIUrl":"10.1016/j.anndiagpath.2025.152524","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the diagnostic performance of MTAP and p16 immunohistochemistry (IHC) as surrogate markers for CDKN2A/B homozygous deletion (HD) in central nervous system (CNS) tumors, and to assess their prognostic significance.</div></div><div><h3>Methods</h3><div>Molecular tests including gene sequencing or fluorescence in situ hybridization (FISH) have traditionally been used to assess CDKN2A/B HD. However, due to lower costs and wider availability, IHC surrogates such as MTAP and p16 are gaining interest. We investigated the concordance between MTAP and p16 IHC expression and CDKN2A/B status as determined by FISH.</div></div><div><h3>Results</h3><div>Our cohort consisted of 227 patients with various CNS tumor types: glioblastoma IDH-wild type (n = 64; 28.2 %), meningioma (n = 61; 26.9 %), IDH-mutant astrocytoma (n = 52; 22.9 %), IDH-mutant and 1p/19q-codeleted oligodendroglioma (n = 35; 15.4 %), and pleomorphic xanthoastrocytoma (n = 15; 6.6 %). In all tumor types, most cases with CDKN2A/B HD showed MTAP loss and p16 negativity (<em>p</em>-values < 0.05). The combination of MTAP and p16 IHC yielded a sensitivity of 92 %, specificity of 80 %, positive predictive value of 86 %, and negative predictive value of 88 % in detecting CDKN2A/B HD. Survival analysis demonstrated significantly reduced disease-free and overall survival among patients with MTAP loss, p16 negativity, and CDKN2A/B HD.</div></div><div><h3>Conclusions</h3><div>MTAP immunohistochemistry, alone or combined with p16, represents a cost-effective and feasible surrogate for detecting CDKN2A/B homozygous deletion in CNS tumors and provides relevant prognostic information.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"79 ","pages":"Article 152524"},"PeriodicalIF":1.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144580780","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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