Annals of Diagnostic Pathology最新文献

{"title":"Intraparenchymal low-grade B-cell lymphomas of the central nervous system: Clinicopathologic and molecular analysis of three cases and a review of the literature","authors":"Maria Teresa Dawid de Vera ,&nbsp;Francisco Javier Díaz Crespo ,&nbsp;Rebeca Manso ,&nbsp;Agustín Penedo Coello ,&nbsp;Daniel Morillo-Giles ,&nbsp;Socorro María Rodríguez-Pinilla ,&nbsp;Francisco Javier Díaz de la Pinta","doi":"10.1016/j.anndiagpath.2024.152376","DOIUrl":"10.1016/j.anndiagpath.2024.152376","url":null,"abstract":"<div><div>Primary central nervous system (CNS) lymphomas represent 1 % of all non-Hodgkin lymphomas, with diffuse large B-cell lymphomas as the prevailing subtype. Low-grade B-cell lymphomas are exceptional with only 24 marginal zone B-cell lymphomas (EMZL) and 1 follicular lymphoma (FL) previously reported so far. While their molecular profiles are studied elsewhere, data on primary intraparenchymal CNS cases remain limited. The objective of the present study is to contribute new cases of primary intraprenchymal low-grade B-cell lymphomas in the CNS and characterize their mutational profile. We conducted a comprehensive review of cases and a literature review to identify similar instances. Clinical, imaging, histological, immunohistochemical, and molecular characteristics were analyzed. Diagnoses were established according to established criteria. We present three novel cases of intraparenchymal CNS low-grade B-cell lymphomas. One case of intraparenchymal EMZL exhibited plasmacytic differentiation, while another lacked a plasma cell component. The third case was diagnosed as FL. The L265P mutation of <em>MYD88</em> was absent in all cases. Next generation sequencing revealed pathogenic mutations in <em>SPEN</em> (Glu1970ValfsTer64) and <em>ARID1A</em> (Pro1355LeufsTer118) genes in one EMZL case. In conclusion, intraparenchymal CNS low-grade B-cell lymphomas are rare, with few reported cases. Our findings expand knowledge on their clinical and molecular features. We present the first molecular profile of primary CNS intraparenchymal EMZL, underscoring the need for further research to understand their biology and optimize treatment strategies.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152376"},"PeriodicalIF":1.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314739","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}

{"title":"The prognostic significance of growth pattern, tumor budding, poorly differentiated clusters, desmoplastic reaction pattern and tumor-stroma ratio in colorectal cancer and an evaluation of their relationship with KRAS, NRAS, BRAF mutations","authors":"Duygu Unal Kocabey,&nbsp;I. Ebru Cakir","doi":"10.1016/j.anndiagpath.2024.152375","DOIUrl":"10.1016/j.anndiagpath.2024.152375","url":null,"abstract":"<div><div>Growth pattern (GP), tumor budding (TB), poorly differentiated clusters (PDC), desmoplastic reaction pattern (DRP) and tumor-stroma ratio (TSR) are prognostic histomorphological parameters in colorectal cancer (CRC). Correlations between these parameters, their individual prognostic values, and their relationship with <em>KRAS/NRAS/BRAF</em> mutations have not been comprehensively examined. We aimed to investigate these associations, which have not been previously explored in this combination. 126 CRC cases were included. GP, TB, PDC, DRP and TSR were evaluated by two experienced pathologists. <em>KRAS/NRAS</em>/<em>BRAF</em> mutation profile were determined using qPCR. Demographic, clinicopathological and survival data were recorded. Interrelations were investigated by statistical analysis. Infiltrative GP was more frequent in high-score TB, PDC-G3, and stroma-high tumors (<em>p</em> &lt; 0.05). High-score TB was more common in PDC-G3 and stroma-high tumors (p &lt; 0.05). Immature DRP was more frequent in stroma-high tumors (<em>p</em> = 0.014). Among histomorphological parameters, a significant relationship was found only between infiltrative GP and the presence of <em>KRAS</em> mutation (<em>p</em> = 0.023). Moreover, GP was significantly associated with pT, lymphatic invasion, perineural invasion (<em>p</em> &lt; 0.05). Effects on survival were assessed using Kaplan-Meier method and Cox proportional hazards model. TB and PDC were identified as independent predictors of overall survival. Higher TB score (<em>p</em> = 0.008) and higher PDC grade (<em>p</em> = 0.013) lead to worse survival. Interestingly, GP, DRP<em>,</em> TSR or <em>KRAS/NRAS/BRAF</em> mutations were not associated with overall survival. Our results highlight the prognostic significance of TB and PDC. We suggest incorporating TB and PDC into routine CRC reports. The association of <em>KRAS</em> mutation with infiltrative GP supports its role in the acquisition of invasive behavior.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152375"},"PeriodicalIF":1.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309006","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}

{"title":"Prognostic significance of anatomic site-specific depth of invasion in oral squamous cell carcinoma - An eastern Indian multi-center study","authors":"Anitha Emmanuel ,&nbsp;Surya Narayan Das ,&nbsp;Rachna Rath ,&nbsp;Mamita Nayak ,&nbsp;B. Selvamani ,&nbsp;Sharmila Behera","doi":"10.1016/j.anndiagpath.2024.152374","DOIUrl":"10.1016/j.anndiagpath.2024.152374","url":null,"abstract":"<div><p>A crucial parameter in determining the prognosis of oral cavity cancer is depth of invasion (DOI). This research aimed to correlate pathological DOI at different intra-oral anatomical sites for oral squamous cell carcinoma (OSCC) with the risk of regional lymph node metastasis (LNM). This study also investigated the correlation of 3-year overall survival (OS) and disease-specific survival (DSS) with tumor depth. DOI measurement of the primary tumor at different intra-oral anatomic sites of clinically node negative patients who underwent curative surgery with elective neck dissection (END) was carried out as per AJCC 8th Edition staging guidelines in 3 DOI groups of ≤5 mm(A), &gt;5 to ≤10 mm(B) and &gt;10 mm(C). Association of groupwise DOI values with histopathological parameters including LNM and 3 years survival was evaluated. Univariate and multivariate logistic regression analysis (Odds ratio (OR) = 1.1 95 % CI: 1.0–1.2, <em>p</em> &lt; 0.05) showed DOI to be a significant predictor for sub-clinical nodal metastasis observed in 136/382 OSCC patients. Receiver operating curve suggested that at 5 mm DOI (4 mm for early-stage OSCC), the risk of occult LNM was &gt;20 % for all intra-oral sites combined. DOI &lt;5 mm group demonstrated a superior 3-year OS (OR = 19.8 % CI: 7.8–49.9) and DSS (OR = 14.7 % CI: 5.9–37.0). Thus, DOI is an independent predictor of nodal metastasis and has significant association with LNM, OS and DSS. Our findings suggest that a DOI of ≥4 mm is an accurate cut-off value for performing END in early-stage OSCC and &gt; 5 mm for advanced cases across all evaluated oral anatomic sites.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152374"},"PeriodicalIF":1.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142172834","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}

{"title":"Validation of histopathological chronicity scores in native kidney biopsies using light microscopy and digital morphometry for predicting renal outcome","authors":"Nandhini Gangadaran ,&nbsp;Debasis Gochhait ,&nbsp;Dhanajayan Govindan ,&nbsp;P.S. Priyamvada ,&nbsp;Sriram Krishnamurthy ,&nbsp;Srinivas Bheemanathi Hanuman ,&nbsp;Rajesh Nachiappa Ganesh","doi":"10.1016/j.anndiagpath.2024.152368","DOIUrl":"10.1016/j.anndiagpath.2024.152368","url":null,"abstract":"<div><p>Quantitative assessment of chronicity changes in native kidney biopsies offer valuable insights in to disease prognosis, despite the strength of qualitative information. Yet, standardization and reproducibility remain challenging. The present study aims to assess and compare the prognostic utility and reproducibility of two chronicity scoring systems based on light microscopy and whole slide imaging with morphometry and also to evaluate the prognostic utility of structural measurements: cortical non-sclerotic glomerular (NSG) density and NSG area/volume. We designed a retrospective longitudinal study involving 101 adult and paediatric patients who underwent native kidney biopsies. Chronicity scoring was performed using two semi-quantitative methods: Method 1 (method proposed in PMID: <span><span>28314581</span><svg><path></path></svg></span>) and Method 2 (method proposed in PMID: <span><span>32516862</span><svg><path></path></svg></span>), under light microscopy as well as on whole-slide scanned images, and assessed for prognostic utility. Kidney-Failure-Risk-Equation (KFRE) was employed in combination with chronicity-scoring-methods and assessed for predictive capability. Interobserver reproducibility for the two chronicity methods was studied among three renal pathologists. Structural measurements were performed on whole-slide- scanned-images. Both the chronicity scoring methods significantly predicted decline in estimated glomerular filtration rate (eGFR) and persistent need for renal replacement therapy in follow-up. Method 1 combined with KFRE, outperformed Method 2 in predicting renal survival. Method 2 however showed higher interobserver reproducibility. Combined KFRE plus histopathological scoring methods showed better predictive accuracy. The study validates the precision of chronicity scoring using whole slide scanned images. The morphometric structural measurements showed significant correlations with follow-up eGFR, thereby providing supplementary prognostic information.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152368"},"PeriodicalIF":1.5,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142097481","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}

{"title":"The association between variant histology and prognostic, histomorphological and clinical aspects of bladder urothelial carcinoma","authors":"Pelin Akbas ,&nbsp;Sibel Bektas ,&nbsp;Gokhan Yazici","doi":"10.1016/j.anndiagpath.2024.152373","DOIUrl":"10.1016/j.anndiagpath.2024.152373","url":null,"abstract":"<div><p>This study underscores the imperative consideration of histological subtypes and divergent differentiation in accurately estimating bladder urothelial carcinoma prognosis and guiding treatment decisions. A comparative analysis was conducted, examining clinical, histological, and prognostic factors between conventional urothelial carcinoma and urothelial carcinoma with variant histology in a clinical sample. A retrospective analysis of slides and other clinicopathologic data was conducted these cases, with an emphasis on key diagnostic elements. We examined 829 cases of urothelial carcinoma of the bladder, comprising of 744 transurethral resection (TUR) and 85 radical cystectomy (RS) specimens, an analysis that showed that 80.5 % (667 cases) were conventional urothelial carcinoma (CUC) and that 19.5 % (162 cases) exhibited variant histology (hereafter “urothelial carcinoma with subtype histology” [UCSH]). TNM classifications for the RS cases were as follows: 2 cases were stage group 0a, 11 stage group 1, 16 stage group 2, 45 stage group 3a, 2 stage group 3b, 1 stage group 4a, and 8 stage group 4b. Only 2 of the RS cases were found to be non-invasive. Among 744 TUR specimens, 387 were found to have a non-invasive tumor whereas 357 had invasive tumors. The most prevalent subtype in the UCSH group was urothelial carcinoma with squamous differentiation, accounting for 54.3 % (88 cases). Notably, 8.02 % (13 cases) exhibited more than one histological subtype. Papillary configuration, histological grade, lamina propria, muscularis mucosa and serosa invasion, lymphovascular invasion, presence of urothelial carcinoma in situ, and overall survival significantly differed between the UCSH and CUC groups (<em>p</em> &lt; 0.05). However, mean age, gender, tumor size, lymphocytic response, disease-free survival, and survival status did not differ significantly (<em>p</em> &gt; 0.05). Among the UCSH group, lower levels of papillary configuration, higher histological grade, higher degree of lamina propria, muscularis mucosa and serosa invasion, and the presence of carcinoma in situ corresponded to higher percentage of histological subtype morphology (<em>p</em> &lt; 0.05). No significant difference in survival status was observed between the groups with and without subtype histology (<em>p</em> = 0.083). This study found that clinical and histopathological prognostic factors associated with a more aggressive disease were linked to the presence and percentage of histological subtypes. Recognizing histological subtype is crucial for treatment decisions and prognosis prediction in urothelial carcinoma cases with these subtypes.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152373"},"PeriodicalIF":1.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048661","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}

{"title":"From the archives of MD Anderson Cancer Center: Composite mantle cell lymphoma and lymphoplasmacytic lymphoma involving bone marrow at presentation","authors":"Yiannis Petros Dimopoulos,&nbsp;Beenu Thakral,&nbsp;Pei Lin,&nbsp;Gokce Toruner,&nbsp;Zhuang Zuo,&nbsp;L. Jeffrey Medeiros,&nbsp;Vasiliki Leventaki","doi":"10.1016/j.anndiagpath.2024.152372","DOIUrl":"10.1016/j.anndiagpath.2024.152372","url":null,"abstract":"<div><p>Composite lymphoma, defined as two or more distinct well-defined entities involving the same anatomic site, is rare. Here we report a 79-year-old woman with composite mantle cell lymphoma (MCL) and lymphoplasmacytic lymphoma (LPL) involving bone marrow at the time of initial diagnosis. The patient presented with splenomegaly and lymphadenopathy and laboratory studies showed an elevated serum IgM level and IgM kappa paraprotein. Bone marrow evaluation showed concurrent involvement by MCL and LPL, supported by immunophenotypic studies that revealed two distinct aberrant B-cell populations. Next-generation sequencing analysis identified concurrent <em>MYD88</em> and <em>CXCR4</em> mutations and fluorescence in-situ hybridization showed <em>CCND1</em> translocation, supporting the diagnosis of concomitant MCL and LPL. In conclusion, composite lymphoma can present in the bone marrow. The use of ancillary studies was essential in reaching the diagnosis in this case, as the results excluded the possibility of MCL lymphoma with plasmacytic differentiation, as well as other CD5- and CD10-negative small B-cell lymphomas.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152372"},"PeriodicalIF":1.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142087594","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}

{"title":"Diagnosis of autoimmune bullous dermatoses: Comparative analysis of immunohistochemical staining using C4d, C3d, IgG, and IgG4 in lesional tissues and perilesional frozen skin samples","authors":"Sevil Karabağ ,&nbsp;Özge Zorlu","doi":"10.1016/j.anndiagpath.2024.152367","DOIUrl":"10.1016/j.anndiagpath.2024.152367","url":null,"abstract":"<div><p>Immunohistochemical staining with immunoglobulins and complements may aid the diagnosis of patients whose clinical and histological findings are consistent with autoimmune bullous dermatoses (AIBD). We aimed to investigate the diagnostic value of immunohistochemical markers in lesional biopsy and perilesional frozen samples in AIBD. We included 136 cases from whom lesional biopsies and perilesional samples for direct immunofluorescence (DIF) examination were collected with a preliminary diagnosis of AIBD between January 2019 and January 2023. All diagnoses were reconfirmed by evaluating the clinical, histopathological, and serological findings and DIF results (C3, IgG, IgA, or IgM positivity compatible with the clinical diagnosis) altogether, although DIF results were considered a priority. After confirming the diagnoses, the samples were categorized as AIBD or the others. The perilesional tissues obtained for DIF simultaneously with skin biopsy and stored at −80 °C were thawed, and FFPE tissues were prepared. We performed immunohistochemical staining (C4d, C3d, IgG, and IgG4) on FFPE tissues of both lesional and perilesional samples. Strong, linear, or granular staining patterns at the dermoepidermal junction or the intraepidermal blistering space were considered positive in line with the diagnosis of the case. Cases other than AIBD were used as negative control tissues to assess the specificity of immunohistochemical markers. Of the 136 cases, 52 were diagnosed with AIBD. In lesional samples, the sensitivity of C4d, C3d, IgG, and IgG4 was 80.6 %, 69.4 %, 75 %, and 5.7 % with corresponding specificity of 100 %, 98.7 %, 89.6 %, and 97.4 %, respectively in pemphigoid diseases compared to a sensitivity of 18.2 %, 9.1 %, 70 %, and 9.1 % and specificity of 98.7 %, 100 %, 89.6 %, and 97.4 %, respectively in pemphigus diseases. In frozen samples, we detected expression in a limited number of cases. The sensitivity of C4d, C3d, IgG, and IgG4 was 8.7 %, 2.2 %, 19.4 %, and 2.2 %, with corresponding specificity of 100 %, 100 %, 98.5 %, and 98.6, respectively. There was a none to slight concordance rate between the IHC results of lesional tissues and perilesional frozen samples. Kappa coefficients for C4d, C3d, IgG, and IgG4 were 0.120 (<em>P</em> = 0.029), 0.111 (<em>P</em> = 0.050), 0.203 (<em>P</em> = 0.003), and - 0.15 (<em>P</em> = 0.846), respectively. Immunohistochemical staining with C4d, C3d, IgG, and IgG4 on biopsy samples collected from lesions may guide the diagnosis of AIBD, thereby eliminating the need for an additional biopsy and accelerating the diagnostic process.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152367"},"PeriodicalIF":1.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048660","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}

{"title":"An assessment of “neuroendocrine differentiation” in malignant melanomas of the sinonasal and oral region","authors":"Funda Canaz ,&nbsp;Zeynep Özcan ,&nbsp;Mustafa Fuat Açıkalın ,&nbsp;Evrim Yılmaz ,&nbsp;Mehmet Özgür Pınarbaşlı ,&nbsp;Serap Işıksoy ,&nbsp;Ertuğrul Çolak","doi":"10.1016/j.anndiagpath.2024.152371","DOIUrl":"10.1016/j.anndiagpath.2024.152371","url":null,"abstract":"<div><p>Mucosal melanomas often require a detailed differential diagnosis and immunochemical study due to their different morphology and pattern characteristics. The tumors may also show fibroblastic, schwannian, smooth muscle, rhabdomyosarcomatous, gangliocytic, epithelial, and neuroendocrine differentiation. All these features can lead to serious diagnostic difficulties. The study aimed to determine the frequency of neuroendocrine differentiation in melanomas of the sinonasal and oral regions and to assess whether there is any relationship between neuroendocrine differentiation and clinical, histopathological, and other immunophenotypic features of this neoplasm. The study included 18 cases diagnosed with oral or sinonasal malignant melanoma. Neuroendocrine differentiation was determined by immunohistochemistry using synaptophysin, chromogranin, CD56, and INSM-1. A cut-off defining neuroendocrine differentiation in malignant melanomas has not been established in the literature. Because of this, any degree of neuroendocrine marker expression was considered as indicative of “neuroendocrine differentiation” without setting any cut-off. Neuroendocrine differentiation was observed in 13 of 18 cases (72.2 %) when a single positive neuroendocrine marker was considered sufficient. The number of cases with at least two positive neuroendocrine markers was 8/18 (44.4 %). Synaptophysin, chromogranin A, CD56, and INSM1 were positive in 33.3 %, 13.3 %, 56.2 %, and 47.1 % of cases, respectively. The results of our study suggest that neuroendocrine differentiation is not uncommon in oral and sinonasal melanomas. Knowing that malignant melanomas can show neuroendocrine differentiation will prevent diagnostic pitfalls.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152371"},"PeriodicalIF":1.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142172743","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}

{"title":"Papillary microcarcinoma of the thyroid gland: Evaluation of TERT and BRAFV-600E expression and their relationship with clinicopathological findings","authors":"Aslı Aydoğdu Yeşiloğlu ,&nbsp;Aysun Hatice Uğuz ,&nbsp;Kıvılcım Eren Erdoğan ,&nbsp;Gürhan Sakman","doi":"10.1016/j.anndiagpath.2024.152369","DOIUrl":"10.1016/j.anndiagpath.2024.152369","url":null,"abstract":"<div><p>Papillary microcarcinomas (PMCs) are papillary carcinomas ≤1 cm in size, with an increasing incidence. Although generally indolent, some cases exhibit aggressive behavior. Recently, active surveillance has been recommended to avoid surgical treatment. Identifying molecular changes that predict aggressiveness in PMCs has gained importance, but studies are limited. We aimed to demonstrate <em>TERT</em> expression and <em>BRAF V600E</em> positivity immunohistochemically in PMCs and correlate them with histomorphological features, subtypes, and clinicopathological findings. We included 95 PMC cases diagnosed between 2010 and 2019 at the Department of Pathology, Faculty of Medicine, XXX University. We investigated <em>TERT</em> expression using RT-PCR. We evaluated <em>BRAF V600E</em> mutation immunohistochemically. We evaluated the relationship between genetic, histomorphological, and clinicopathological findings. In patients with multifocality and those with a tumor size ≥0.5 cm, the frequency of lymph node metastasis was significantly higher. A positive correlation was shown between BRAF V600E positivity and lymph node metastasis, lymphovascular invasion, advanced disease stage, and classical subtype by univariate analyses. We detected <em>TERT</em> expression in 18 of 95 patients (7.8 %). No relationship could be detected between <em>TERT</em> expression alone or combined with <em>BRAF</em> positivity and clinicopathological features. Although <em>TERT</em> mutations are associated with aggressiveness in thyroid cancers, this association was absent in PMCs. The presence of <em>TERT</em> expression was demonstrated in some cases. However, <em>TERT</em> expression could not be associated with clinicopathological findings, which is consistent with the literature suggesting that <em>TERT</em> plays a role in advanced stages of carcinogenesis.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152369"},"PeriodicalIF":1.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1092913424001060/pdfft?md5=91f25ec86c9502d3ccc960a349638e8b&pid=1-s2.0-S1092913424001060-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044639","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}

{"title":"Next-generation sequencing has diagnostic utility in challenging small/flat urothelial lesions","authors":"Amélie Pinard,&nbsp;Constance Chen,&nbsp;Jessica Van Ziffle,&nbsp;Jeffry P. Simko,&nbsp;Bradley A. Stohr,&nbsp;Emily Chan","doi":"10.1016/j.anndiagpath.2024.152370","DOIUrl":"10.1016/j.anndiagpath.2024.152370","url":null,"abstract":"<div><p>Small/flat urothelial lesions are challenging and currently available ancillary immunohistochemistry testing often cannot reliably distinguish between reactive lesions and urothelial carcinoma (UCa). UCa has a characteristic molecular profile, but small/flat urothelial lesions are typically considered too small to perform next generation sequencing (NGS). Herein, we present our institution's experience with utilizing comprehensive DNA-based NGS to evaluate small/flat urothelial lesions (<em>n</em> = 13 cases). NGS was ordered on 7/13 small/flat urothelial lesions initially diagnosed as urothelial atypia, ordered by the pathologist to aid in further diagnosis; the remaining 6/13 cases were diagnosed as urothelial carcinoma in situ (uCIS), ordered by a treating oncologist. The test was considered as adding value if it yielded pathogenic or likely pathogenic alterations previously associated with urothelial carcinoma in the literature. Macroscopic dissection was determined necessary in all cases and obtained either by scraping (7), punch biopsy (5) or scooping (1) of paraffin tissue blocks. In 4/13 cases, tumor content was considered low (&lt;25%); in 2/13 cases, DNA quantity yield was considered below optimal (&lt;250 ng); all cases met required DNA quantity for testing (&gt;50 ng). Mean target coverage ranged: 498 to 985 (optimal &gt;500 reads). NGS testing identified mutations compatible with urothelial carcinoma in all 7 cases initially diagnosed as atypical; and in one case, the tumor recurred as a lung metastasis. All 6 uCIS had NGS testing results concordant with UCa. In conclusion, despite small sample quantity with low tumor content and DNA concentration yield, NGS testing with appropriate methodology can be considered in the setting of small/flat urothelial lesions to aid in diagnosis or per oncologist request and yield interpretable results.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152370"},"PeriodicalIF":1.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1092913424001072/pdfft?md5=75ca0b88f7ac8e18f6cefc13838a9be7&pid=1-s2.0-S1092913424001072-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048662","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}