Annals of Diagnostic Pathology最新文献

{"title":"Clinicopathological features analysis of Paraganglioma of urinary bladder: A retrospective study","authors":"Wenhua Li ,&nbsp;Wei Wei ,&nbsp;Lijun Yuan ,&nbsp;Ying Zhang ,&nbsp;MinYi","doi":"10.1016/j.anndiagpath.2025.152477","DOIUrl":"10.1016/j.anndiagpath.2025.152477","url":null,"abstract":"<div><div>Paraganglioma of urinary bladder (PUB) is a rare neuroendocrine neoplasm. This study is a retrospective analysis of clinicopathological features in 11 cases of PUB. The studied cohort included seven male and four female patients with a median age of 64 years (range 37–73 years). The maximum tumor diameter ranged from 1 to 4 cm (median: 2.5 cm). Macroscopically, most lesions appeared as smooth, polypoid intraluminal protrusions; one case exhibited a nodular mass extending into the outer bladder wall. Microscopic evaluation demonstrated tumor infiltration into the muscularis propria (6 cases) or both lamina propria and muscularis propria (5 cases). Tumor cells were arranged in nested (Zellballen) or organoid patterns. Tumor cells uniformly expressed CD56, synaptophysin, and chromogranin. The Ki-67 proliferation index was ≤8 % in 10 cases; one case with a 4 cm tumor demonstrated a higher Ki-67 index (20 %), correlating with infiltrative growth and increased mitotic activity. Among the 10 cases that were evaluated, 2 (20 %) showed a loss of SDHB expression; Eight (80 %) of 10 cases were GATA3-positive, and all cases were negative for OCT3/4. Nine (81.8 %) underwent transurethral resection of bladder tumor, and 2 (18.2 %) underwent partial cystectomy. Intraoperative blood pressure fluctuations were observed in 2 patients (18.2 %). The median follow-up time was 26 months (range 4–73 months); one patient experienced a recurrence of endometrial cancer 4 years later and was lost to follow-up at 73 months; the remaining 10 patients survived without recurrence or metastasis. Improved preoperative recognition of PUBs relies on integrating clinical, biochemical, and imaging findings. Standardized immunohistochemical panels may enhance diagnostic accuracy.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"77 ","pages":"Article 152477"},"PeriodicalIF":1.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725826","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":"Histopathological and prognostic variability of ampullary tumors: A comprehensive study on tumor location, histological subtypes, and survival outcomes","authors":"Dilara Ozyigit Buyuktalanci ,&nbsp;Eylul Gun ,&nbsp;Osman Nuri Dilek ,&nbsp;Fatma Husniye Dilek","doi":"10.1016/j.anndiagpath.2025.152476","DOIUrl":"10.1016/j.anndiagpath.2025.152476","url":null,"abstract":"<div><div>Ampullary tumors present diagnostic challenges due to the complex anatomical and histological structure of the ampullary region. They can be classified into four types based on location: Periampullary-duodenal, intra-ampullary, ampullary-ductal, and ampullary-NOS (not otherwise specified). Periampullary-duodenal tumors are exophytic, ulcerovegetative, and often intestinal-type adenocarcinomas with frequent lymph node metastasis. Intra-ampullary tumors are polypoid and confined to the ampullary canal. Ampullary-ductal tumors exhibit sclerotic thickening in the bile or pancreatic duct and are typically pancreatobiliary-type adenocarcinomas. Ampullary-NOS includes tumors that do not fit other classifications. This study aimed to classify ampullary tumors by their anatomical localization, compare histopathological features, and assess the prognostic outcomes for each group. A total of 111 ampullary tumors were selected from 229 pancreaticoduodenectomy specimens over 10 years at our hospital. Clinical, imaging, and macroscopic findings were re-evaluated microscopically. Tumors were classified into four anatomical groups, and their histopathological characteristics and prognosis were analyzed. The cohort had a mean age of 62 ± 10.49 years, with 69 (62.2 %) males and 42 (37.8 %) females. The median survival was 28.23 months. Tumor distribution was as follows: 14.4 % intra-ampullary, 25.2 % ampullary-ductal, 10.8 % periampullary-duodenal, and 49.5 % not otherwise specified (NOS). Pancreatobiliary-type adenocarcinoma (p = 0.003), perineural invasion (p &lt; 0.0001), and lymphovascular invasion (p = 0.002) were significantly more frequent in the ampullary-ductal and NOS groups, which were associated with poorer overall survival (p = 0.011). In addition, lymphovascular invasion and surgical margin positivity were identified as independent prognostic markers. Classifying ampullary tumors based on anatomical location is crucial due to significant histopathological and prognostic differences between the groups.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"77 ","pages":"Article 152476"},"PeriodicalIF":1.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725820","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":"Utility and limitations of Merlin immunohistochemistry for mesothelioma diagnosis in tissue sections and cell blocks","authors":"Kazuki Nabeshima ,&nbsp;Makoto Hamasaki ,&nbsp;Tomomi Furukawa ,&nbsp;Shinji Matsumoto ,&nbsp;Katsumi Takizawa ,&nbsp;Makiko Adachi ,&nbsp;Yuko Goto","doi":"10.1016/j.anndiagpath.2025.152475","DOIUrl":"10.1016/j.anndiagpath.2025.152475","url":null,"abstract":"<div><div>Distinguishing pleural mesothelioma (PM) from reactive mesothelial proliferations (RMP) can be challenging. In such cases, immunohistochemistry (IHC)-detected BAP1 or MTAP loss and FISH-detected <em>CDKN2A</em> homozygous deletion are effective. Merlin is the protein product of the <em>NF2</em> gene, which is frequently altered in mesotheliomas. Recently, IHC-detected loss of Merlin was also shown to be useful in differentiating PM from RMP. To validate these findings, we examined Merlin IHC in PM cases, including for the first time cytologic material. Merlin IHC was performed on 67 PM cases, including 47 samples from tissues and 20 from cell blocks (CBs), and 29 RMP cases. In RMP, Merlin was expressed in cell membranes and cytoplasm, with no loss. Merlin expression was lost in 49 % of PM tissues. In discriminating PM from RMP, addition of Merlin IHC to the combination of BAP1 and MTAP IHC increased sensitivity from 77 % to 95 %. However, Merlin expression could not be assessed in 8.5 % of tissues and 25 % of CBs. In CBs, Merlin loss could be assessed only in sheeted or clustered tumor cells, because PM cells could not be identified precisely in few scattered tumor cells. In cases where both tissue biopsy and CBs were available, results matched in only 50 % of cases, suggesting uneven occurrence of Merlin loss in PM tissues. Our observations support the effectiveness of Merlin IHC in differentiating PM from RMP. However, investigators should be familiar with potential challenges in interpreting Merlin IHC results, especially in CBs.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"77 ","pages":"Article 152475"},"PeriodicalIF":1.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705342","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":"Application of an in situ hybridization method for fungal diagnosis in formalin-fixed, paraffin-embedded allergic fungal rhinosinusitis tissue","authors":"Donglin Ma ,&nbsp;Jing Ding ,&nbsp;Luo Zhang ,&nbsp;Yingshi Piao","doi":"10.1016/j.anndiagpath.2025.152474","DOIUrl":"10.1016/j.anndiagpath.2025.152474","url":null,"abstract":"<div><div>Allergic fungal rhinosinusitis (AFRS) is a chronic inflammatory disease of the sinuses that can involve serious late complications; thus, prompt diagnosis is essential to determine the appropriate treatment. The most important diagnostic element of AFRS is the detection of noninvasive fungi within eosinophilic mucin. However, the rarity of fungal hyphae in ARFS makes it difficult to specifically identify them using histochemical staining alone. In this study, we designed a new <em>in situ</em> fungal detection probe for the diagnosis of fungi in formalin-fixed, paraffin-embedded AFRS tissues. Tissue sections from 49 patients with confirmed (<em>n</em> = 40) or suspected (<em>n</em> = 9) AFRS were selected for testing. A newly designed broad-spectrum probe for <em>in situ</em> hybridization (ISH) was compared with an anti-<em>Aspergillus</em> antibody in immunohistochemistry (IHC) and staining with hematoxylin and eosin and periodic acid-Schiff (PAS) to detect fungi. Hematoxylin and eosin staining had a lower detection rate (30/40 samples) than the other three methods. PAS staining led to two false-positive results in the AFRS-confirmed group and two false-negative results in the AFRS-suspected group. ISH and IHC exhibited high concordance (ĸ = 0.716); however, there was a high degree of nonspecific immunoreactivity to the anti-<em>Aspergillus</em> polyclonal antibody in some samples. The fungal detection rate of ISH was 95 % (38/40), with no background or nonspecific reactivity. Our novel broad-spectrum ISH probe provides more specific identification of fungi than PAS and IHC staining, exhibits no background reactivity, and may represent an essential upgrade to the <em>in situ</em> diagnosis of AFRS.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"77 ","pages":"Article 152474"},"PeriodicalIF":1.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680971","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":"Clinicopathologic features of 6 cases of segmental atrophy of liver and review of the literature","authors":"Shuying Hu ,&nbsp;Dan Zuo ,&nbsp;Lili Meng","doi":"10.1016/j.anndiagpath.2025.152467","DOIUrl":"10.1016/j.anndiagpath.2025.152467","url":null,"abstract":"<div><div>Segmental atrophy (SA) of the liver is a rare and frequently under-recognized condition that can lead to the formation of pseudotumors, posing significant challenges in both clinical and imaging diagnoses. To date, this disease has been infrequently reported in the literature. To elucidate the clinicopathological characteristics of SA and enhance clinicians' understanding, we collected clinical and pathological data from 6 cases of SA and summarized the clinical information and pathological features of 22 previously reported SA patients. Among all cases, 19 patients were female and 9 were male, with a median age of 60 years. Lesion sizes varied widely, ranging from 1.5 to 10.5 cm. 17 patients exhibited notable right upper quadrant abdominal pain. Histological examination revealed a sequence of changes: early-stage lesions exhibited varying degrees of hepatic parenchyma collapse, brisk bile ductular proliferation, and extensive infiltration of chronic inflammatory cells, accompanied by very mild elastosis. In subsequent stages, the lesions exhibited reduced bile duct proliferation and inflammatory response alongside a notable increase in elastic fibers. Advanced-stage lesions presented with extensive elastic fiber deposition, occasionally interspersed with scattered islands of hepatocytes, and the terminal phase manifested as dense fibrotic nodules. Abnormally thick-walled blood vessels were identified in nearly all cases (<em>n</em> = 25), and bile duct cysts were observed in some cases (<em>n</em> = 11). In summary, SA primarily affects middle-aged individuals, with a female predominance, and presents with nonspecific clinical symptoms, predominantly right upper quadrant pain. Pathologically, it displays a continuous histomorphological spectrum. Elastic fiber staining has proven beneficial for both diagnosis and differential diagnosis of this condition. Proficiency in recognizing its diverse morphological features is essential for accurate diagnosis.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"77 ","pages":"Article 152467"},"PeriodicalIF":1.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642079","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 and clinicopathological significance of the new grading system for invasive pulmonary adenocarcinoma: A systematic review and meta-analysis","authors":"Wen Guo ,&nbsp;Huanrong Ruan ,&nbsp;Miao Zhou ,&nbsp;Siyuan Lei ,&nbsp;Jiansheng Li","doi":"10.1016/j.anndiagpath.2025.152466","DOIUrl":"10.1016/j.anndiagpath.2025.152466","url":null,"abstract":"<div><div>In 2020, the International Association for the Study of Lung Cancer (IASLC) introduced a new grading system for invasive pulmonary adenocarcinoma (IPA). This meta-analysis aimed to validate the prognostic utility of this grading system and identify relevant clinicopathological features. The PubMed, Embase, Web of Science, and Cochrane Library databases were searched for relevant studies published between January 1, 2020 and March 5, 2024. Hazard ratios (HRs) with corresponding 95 % confidence intervals (CIs) were pooled to evaluate the effect of IASLC grading on prognosis. Odds ratios with corresponding 95 % CIs were pooled to assess relevant clinicopathological features. Twenty-two studies comprising 12,515 patients with IPA were included. Regarding overall survival, grade 3 adenocarcinomas had a worse prognosis compared with grades 1–2 (HR: 2.26, 95 % CI: 1.79–2.85, <em>P</em>&lt;0.001), grade 1 (HR: 4.75, 95 % CI: 2.61–8.66, <em>P</em>&lt;0.001), or grade 2 (HR: 1.71, 95 % CI: 1.28–2.29, <em>P</em>&lt;0.001). Considering recurrence-free survival, grade 3 tumors had a higher recurrence risk than grades 1–2 (HR: 1.92, 95 % CI: 1.53–2.41, <em>P</em>&lt;0.001), grade 1 (HR: 4.43, 95 % CI: 2.91–6.73, <em>P</em>&lt;0.001), or grade 2 (HR: 1.67, 95 % CI: 1.33–2.10, <em>P</em>&lt;0.001). In the subgroup analysis of stage I patients, grade 3 tumors exhibited a similarly poor prognosis. In addition, grade 3 adenocarcinomas were associated with aggressive clinicopathological features. This study demonstrated that the IASLC grading system is a robust predictor of prognostic stratification in patients with IPA, and warrants further promotion and worldwide implementation.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"77 ","pages":"Article 152466"},"PeriodicalIF":1.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641998","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":"Molecular classification of medulloblastoma using immunohistochemistry: A single centre study","authors":"Jason L. Harry ,&nbsp;Nomusa B. Shezi ,&nbsp;Absalom Mwazha","doi":"10.1016/j.anndiagpath.2025.152463","DOIUrl":"10.1016/j.anndiagpath.2025.152463","url":null,"abstract":"<div><div>Medulloblastoma (MB) is the second most common malignant paediatric central nervous system (CNS) tumour. The World Health Organisation (WHO) advocates an integrated pathological and molecular approach to diagnosis. Immunohistochemistry (IHC) has been proven to be a valid surrogate for molecular subtyping in low resource settings. This study aimed to use IHC to classify MB into different molecular subtypes.</div><div>Patients diagnosed with medulloblastoma between 2011 and 2021 were included in the study. Clinicopathological characteristics, treatment patterns and outcomes were reviewed. Molecular subgrouping into wingless signalling activated (WNT), sonic hedgehog (SHH), and non-WNT/non-SHH was performed by immunohistochemical staining, using β-catenin, Yes-associated protein 1 (YAP1) and GRB2-Associated Binding Protein 1 (GAB1) antibodies.</div><div>Of the 32 children evaluated, the mean age at diagnosis was 9.9 years with M: F ratio of 1.5:1. Classic (75.8 %) and desmoplastic/nodular (24.2 %) were the only two histopathological variants reported. Non-WNT/non-SHH constituted the majority of cases (54.5 %), followed by SHH (36.4 %) and WNT subgroups (9.1 %). The 5-year overall survival and 5-year progression-free survival was 41 % and 38 % respectively. The 30-day operative mortality rate was 28.1 %.</div><div>Molecular subgroups determined by immunohistochemistry, can be easily incorporated into routine practice in low resource settings. The overall survival rate in our cohort is lower than thate reported in the literature due to high post-operative mortality and low uptake of adjuvant oncotherapy.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"76 ","pages":"Article 152463"},"PeriodicalIF":1.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561714","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":"Metastases from uveal melanoma may lack S100 expression: A clinico-pathologic and immunohistochemical study with emphasis on potential causes and diagnostic implications","authors":"Serena Salzano ,&nbsp;Giada Maria Vecchio ,&nbsp;Maria Failla ,&nbsp;Andrea Russo ,&nbsp;Teresio Avitabile ,&nbsp;Antonio Longo ,&nbsp;Rosario Caltabiano ,&nbsp;Giuseppe Broggi","doi":"10.1016/j.anndiagpath.2025.152464","DOIUrl":"10.1016/j.anndiagpath.2025.152464","url":null,"abstract":"<div><div>Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, with a high mortality rate due to metastasis, primarily to the liver. The differential diagnosis of metastatic UM, particularly in distinguishing it from cutaneous melanoma (CM), can be challenging due to overlapping histopathological features. This study investigates the immunohistochemical expression of S100 in a cohort of 41 cases, including 13 metastatic UMs, 18 metastatic CMs, and 10 primary UMs. Our results demonstrate a significant lack of S100 immunoreactivity in metastatic UM, with 84.6 % of cases showing negativity, in contrast to the diffuse positivity seen in both primary UM and metastatic CM. This finding suggests that the absence of S100 could serve as a useful marker to differentiate metastatic UM from CM, especially in cases where the primary tumor is unknown. Furthermore, the study highlights the potential diagnostic pitfall of relying solely on S100 expression on small biopsies. The absence of S100 in metastatic UM may reflect a shift in antigenic expression, possibly due to tumor dedifferentiation or clonal selection of S100-negative cells with a higher metastatic potential. Our findings emphasize the importance of employing a comprehensive immunohistochemical panel, including markers such as HMB45, SOX10, and Melan-A, in the accurate diagnosis of metastatic melanomas.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"76 ","pages":"Article 152464"},"PeriodicalIF":1.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561713","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":"Pitfalls and considerations in the diagnosis of Hirschsprung's disease: A focus on pathological assessment","authors":"Farzaneh Afshari","doi":"10.1016/j.anndiagpath.2025.152465","DOIUrl":"10.1016/j.anndiagpath.2025.152465","url":null,"abstract":"<div><div>Hirschsprung's disease (HSCR) is a congenital disorder of the intestine characterized by the absence of ganglion cells (GCs) in the myenteric and submucosal plexuses of the distal colon, leading to functional obstruction. The diagnosis of HSCR relies heavily on histopathological examination, yet pitfalls abound. Underdiagnosis can lead to delayed diagnosis, the need for reoperation, or risk of complications; conversely, overdiagnosis can lead to unnecessary surgery and its associated side effects. This comprehensive pictorial review addresses common diagnostic challenges using cases from our hospital, a tertiary pediatric facility and referral center for HSCR patients, and emphasizes the need for close cooperation among pathologists, surgeons, pediatric gastroenterologists, and radiologists to achieve optimal management for patients with HSCR.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"76 ","pages":"Article 152465"},"PeriodicalIF":1.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561715","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":"Development of a digital algorithm for assessing tumor-stroma ratio, tumor budding and tumor infiltrating lymphocytes in vulvar squamous cell carcinomas","authors":"Louise Baandrup ,&nbsp;Susanne K. Kjær ,&nbsp;Óli Jacobsen ,&nbsp;Michael Bzorek ,&nbsp;Thomas Thiilmark Eriksen ,&nbsp;Lise Grupe Larsen ,&nbsp;Anne-Marie Kanstrup Fiehn","doi":"10.1016/j.anndiagpath.2025.152462","DOIUrl":"10.1016/j.anndiagpath.2025.152462","url":null,"abstract":"<div><div>Tumor-stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) are prognostic markers in some cancers but with unknown significance in vulvar squamous cell carcinoma (VSCC). This pilot study primarily aimed to develop a digital method for evaluating TSR, TB and TILs in VSCC and secondarily to investigate variation in these factors by p16 status. An independent training set stained with CD3/cytokeratin and CD8/cytokeratin was used to develop a deep learning-based Application Protocol Package (APP) segmenting tissue into background, epithelium, or stroma. TSR was defined as percentage of tumor epithelium relative to total tumor area, and tumor buds were defined as clusters of 1–4 tumor cells. A second APP quantified CD3+ and CD8+ lymphocytes in the intraepithelial and stromal compartments, respectively. The digital algorithms were applied to the study cohort of 41 VSCC cases, achieving satisfactory performance without manual corrections. TSR ranged between 33 and 91% with median of 64%, and median number of buds was 4 (range: 0–48) buds/mm². Median density and range of CD3+ lymphocytes were 222 (13-2320) cells/mm² in the intraepithelial and 1978 (397–6683) cells/mm² in the stromal compartment, respectively. CD8+ lymphocyte counts were lower. There was a tendency towards lower TSR and higher number of buds in p16-negative compared with p16-positive VSCC. Finally, automated measures were compared with manual evaluations showing high concordance. The developed automated method provided precise and objective measurements of TSR, TB and TILs. The algorithms should be validated in a larger cohort and correlated with clinicopathological characteristics and prognosis to determine their clinical relevance.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"76 ","pages":"Article 152462"},"PeriodicalIF":1.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143553007","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}