Human Pathology Reports最新文献

{"title":"Primary adenosquamous carcinoma of the appendix with genomic profiling of the adenocarcinoma and squamous cell carcinoma components using next-generation sequencing","authors":"Sara Bohjanen,&nbsp;Areeba H. Rizvi,&nbsp;Kevin Turner,&nbsp;Andrew C. Nelson,&nbsp;Khalid Amin","doi":"10.1016/j.hpr.2026.300816","DOIUrl":"10.1016/j.hpr.2026.300816","url":null,"abstract":"<div><div>Adenosquamous carcinoma (ASC) is characterized by the presence of adenocarcinoma and squamous cell carcinoma components in one tumor. Primary appendiceal ASC is extremely rare, and only 7 cases have been reported in the medical literature. We present a case of primary appendiceal ASC, where both tumor components were subjected to next-generation sequencing. Both components shared the same <em>BRAF, TP53, PLCG2</em>, and <em>RUNX1</em> variants, but only the adenocarcinoma component demonstrated a mutation in the <em>SMAD4</em> gene. This suggests appendiceal ASC components may diverge from a shared evolutionary clone. We then discuss the therapeutic implications of our findings. To our knowledge, this is the first next-generation sequencing analysis performed on appendiceal ASC.</div></div>","PeriodicalId":100612,"journal":{"name":"Human Pathology Reports","volume":"43 ","pages":"Article 300816"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of KI-67 in renal cell carcinoma: correlation with clinicopathological parameters and survival outcomes","authors":"Krutika Kantilal Raskar ,&nbsp;Sachin Sebastian Francis ,&nbsp;Swati Sharma","doi":"10.1016/j.hpr.2026.300829","DOIUrl":"10.1016/j.hpr.2026.300829","url":null,"abstract":"<div><h3>Background</h3><div>Renal cell carcinoma (RCC) is a heterogeneous malignancy with variable clinical behaviour. Ki-67, a nuclear antigen associated with cellular proliferation, has been investigated for its prognostic relevance in RCC. However, its utility in predicting metastatic potential remains controversial, particularly in the Indian population. This study aimed to evaluate Ki-67 expression in RCC and its association with clinicopathological features and metastatic risk.</div></div><div><h3>Methods</h3><div>A retrospective analysis of 95 RCC cases was performed at a tertiary care centre between January 2018 and December 2020. Clinicopathological data were retrieved from electronic records, and histological slides were reviewed. Ki-67 immunohistochemistry was performed on tissue microarray (TMA) sections using MIB-1 antibody. The labelling index was calculated, and cases were categorized into low (≤10%) and high (&gt;10%) Ki-67 expression groups. Statistical analysis included chi-square tests, Mann-Whitney U tests, Kruskal-Wallis tests, logistic regression, ROC curve analysis, and Kaplan-Meier survival analysis using SPSS v27.</div></div><div><h3>Results</h3><div>The mean age was 57.09 years; 62.1% were males. Clear cell RCC was the predominant subtype (82.1%). Ki-67 expression was low in 86.3% and high in 13.7% of cases. A higher ISUP grade was significantly associated with increased Ki-67 expression (p = 0.002), and sarcomatoid differentiation correlated with high Ki-67 expression in univariate analysis (OR = 24.3, p = 0.008). However, Ki-67 was not significantly associated with tumour size, stage, or histologic subtype. Metastasis occurred in 13.7% of cases but was not significantly associated with Ki-67 expression (p = 0.49; AUC = 0.438). Event-free survival did not differ significantly between the low and high Ki-67 groups (p = 0.71).</div></div><div><h3>Conclusions</h3><div>Ki-67 showed a significant association with tumour grade and dedifferentiation in RCC, reflecting increased proliferative activity in biologically aggressive tumours. However, Ki-67 lacks independent prognostic value for metastasis or event-free survival, suggesting that Ki-67 should be integrated into a broader multiparametric model rather than used in isolation.</div></div>","PeriodicalId":100612,"journal":{"name":"Human Pathology Reports","volume":"43 ","pages":"Article 300829"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A unique presentation of multiple synchronous tumors in a patient with POT1 tumor predisposition syndrome","authors":"Wangpan Shi ,&nbsp;Mitchell Zhao ,&nbsp;Dong Ren ,&nbsp;Frederick Millard ,&nbsp;Jason K. Sicklick ,&nbsp;Haiyan Zhang","doi":"10.1016/j.hpr.2025.300814","DOIUrl":"10.1016/j.hpr.2025.300814","url":null,"abstract":"<div><div><em>POT1</em> (Protection of Telomeres 1) is a gene on chromosome 7 that is essential for telomere stability. Germline mutations in <em>POT1</em> are well recognized for conferring a lifelong risk of various malignancies. We present a 63-year-old female who developed a sudden cough and was found to have a large adrenal mass abutting adjacent organs, along with an incidental pancreatic lesion. Her medical history was significant for renal cancer, uterine carcinosarcoma, pituitary adenoma, and chronic lymphocytic leukemia (CLL). Next-generation sequencing identified a pathogenic germline mutation in <em>POT1</em> (c.854_855del (p.Val285Glyfs*27)). Microscopically, the adrenal mass showed tumor cells arranged in sheets and nests with high-grade nuclei and abundant cytoplasm. Immunohistochemistry (IHC) study showed diffuse AE1/AE3 positivity but was negative for markers of other metastatic carcinomas or melanoma. Given the unusual immunoprofile and clinical history, SF-1 was performed and was diffusely positive, confirming the diagnosis of adrenal cortical carcinoma. The pancreatic lesion was composed of well-formed nests of tumor cells with speckled chromatin in a background of lymphocyte aggregates. Synaptophysin was positive in the tumor nests, and the lymphoid component was positive for CD5, CD23, and CD20, while negative for CD3. The findings supported a diagnosis of a well-differentiated neuroendocrine tumor involved by small cell lymphoma. Retrospectively, similar lymphoma cells were also identified in the adrenal mass. Overall, this is the first case report describing a unique malignancy profile in patient with <em>POT1</em> tumor predisposition syndrome, highlighting the diagnostic challenge posed by diffuse cytokeratin positivity in adrenal cortical carcinoma.</div></div>","PeriodicalId":100612,"journal":{"name":"Human Pathology Reports","volume":"43 ","pages":"Article 300814"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epstein-Barr Virus–Negative Fibrin-Associated large B-cell lymphoma arising in an atrial Myxoma: A case report","authors":"AlMothana Manasrah ,&nbsp;Farid Khan ,&nbsp;Jagmohan Sidhu","doi":"10.1016/j.hpr.2026.300823","DOIUrl":"10.1016/j.hpr.2026.300823","url":null,"abstract":"<div><h3>Introduction</h3><div>Primary cardiac tumors are rare, with lymphomas representing a small subset, most often diffuse large B-cell lymphoma (DLBCL). Fibrin-associated large B-cell lymphoma (FA-LBCL), newly recognized as a distinct entity in the 2022 World Health Organization (WHO) classification, typically arises in fibrin-rich, immune-privileged spaces and is usually Epstein–Barr virus (EBV)-positive.</div></div><div><h3>Case Presentation</h3><div>We describe a 50-year-old female who presented with progressive dyspnea and palpitations and was found to have a 6-cm left atrial mass attached to the interatrial septum. Surgical excision revealed a myxomatous lesion with fibrin deposition harboring large atypical B cells. Immunophenotyping confirmed EBV-negative FA-LBCL with a Ki-67 index approaching 100% and probable <em>BCL6</em> rearrangement. Next-generation sequencing identified pathogenic <em>PIM1</em> and <em>ETV6</em> mutations. No adjuvant therapy was administered. The patient has remained disease-free over a 24-year follow-up period.</div></div><div><h3>Conclusion</h3><div>This case illustrates an indolent EBV-negative FA-LBCL arising within an atrial myxoma, successfully managed with surgery alone and demonstrating exceptionally durable remission. High-level MGMT promoter methylation suggested a possible EBV “hit-and-run” pathogenesis, underscoring the biologic heterogeneity of FA-LBCL.</div></div>","PeriodicalId":100612,"journal":{"name":"Human Pathology Reports","volume":"43 ","pages":"Article 300823"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the peripheral count: multiorgan leukemic infiltration in the absence of hyperleukocytosis, an autopsy case report","authors":"Saima Haleem Siddiqui ,&nbsp;Changcheng Zhu ,&nbsp;Stephen Peeke ,&nbsp;Mendel Goldfinger ,&nbsp;Yanhua Wang","doi":"10.1016/j.hpr.2026.300824","DOIUrl":"10.1016/j.hpr.2026.300824","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is a hematological malignancy of predominantly older adults but also occurs in younger patients who have a better prognosis. Despite favorable cytogenetics and higher treatment tolerance, early mortality can still occur especially in cases where the underlying malignancy masquerades as benign conditions, such as infection. We report the case of a 28-year-old previously healthy woman who presented with progressive dyspnea and non-productive cough. Imaging revealed ground-glass opacities and interlobular septal thickening, initially attributed to atypical pneumonia. Despite broad-spectrum antibiotics, her condition deteriorated rapidly, culminating in death shortly after the initiation of chemotherapy. Laboratory investigations revealed leukocytosis, anemia, thrombocytopenia, and circulating blasts. Bone marrow biopsy demonstrated 90% cellularity with diffuse infiltration by myeloid blasts. Flow cytometry revealed an aberrant immature monocytic immunophenotype: CD4, CD9, CD11b (partial), CD11c, CD15, CD33, CD38, CD45, CD56, CD58, CD64, CD117 (partial) were positive; whereas MPO, CD7, CD13, CD14 (essentially negative), CD34, HLA-DR, and other B or T lineage-specific markers were negative. Next-generation sequencing identified <em>KMT2A::MLLT3</em> fusion with <em>KRAS</em> G13D, <em>KRAS</em> G12V, and <em>NRAS</em> G12D mutations, without <em>FLT3</em>, <em>NPM1</em>, <em>IDH1/2</em>, or <em>TP53</em> alterations. Autopsy revealed diffuse leukemic infiltration of the lungs, heart, liver, spleen, kidneys, and thyroid in the absence of hyperleukocytosis. This case illustrates the potential for early, widespread extramedullary disease in young AML patients and highlights the diagnostic challenge posed by pulmonary leukemic infiltration mimicking infection. It underscores the importance of considering hematological malignancy in unexplained systemic illness and the value of autopsy in uncovering a clinically silent disease.</div></div>","PeriodicalId":100612,"journal":{"name":"Human Pathology Reports","volume":"43 ","pages":"Article 300824"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of p16INK4a and its clinicopathological and survival outcomes in cholangiocarcinoma: A retrospective cohort study","authors":"Porramate Khaikhuayart,&nbsp;Prakasit Sa-ngiamwibool","doi":"10.1016/j.hpr.2026.300819","DOIUrl":"10.1016/j.hpr.2026.300819","url":null,"abstract":"<div><h3>Background</h3><div>Cholangiocarcinoma (CCA) is an aggressive adenocarcinoma arising from the epithelium of intrahepatic and extrahepatic bile ducts with distinct growth patterns. CCA is associated with poor clinical outcomes. The <em>CDKN2A</em> and one of its protein products, p16INK4a, which is frequently downregulated in CCA, may contribute to disease pathogenesis.</div></div><div><h3>Objective</h3><div>To evaluate the prognostic significance of p16INK4a expression using immunohistochemistry in CCA patients and analyze its correlation with clinicopathological parameters.</div></div><div><h3>Methods</h3><div>A retrospective cohort study analyzing 180 CCA patients diagnosed at Srinagarind Hospital, Khon Kaen, Thailand, between 2017 and 2023.</div></div><div><h3>Results</h3><div>Positive/high p16INK4a expression was detected in 61 cases (33.9 %) and showed association with mixed tumor growth patterns (p = 0.041). While p16INK4a expression did not significantly impact overall survival in Kaplan–Meier analysis (p = 0.745), the patients with positive/high expression showed a trend toward shorter median survival time compared to that of the negative/low expression group (13 vs. 18 months, p = 0.015).</div></div><div><h3>Conclusion</h3><div>p16INK4a expression is not independently associated with survival, however high expression is associated with histologically mixed growth patterns and might influence tumor differentiation in CCA. These results suggest p16INK4a may contribute to CCA progression, particularly in complex growth patterns and poor differentiation. Further study is warranted to fully elucidate its clinical significance and potential therapeutic implications.</div></div>","PeriodicalId":100612,"journal":{"name":"Human Pathology Reports","volume":"43 ","pages":"Article 300819"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large cell neuroendocrine carcinoma of the breast – A case report with the diagnostic and therapeutic challenges and a review of selected cases","authors":"Hiroshi Kobayashi ,&nbsp;Riuko Ohashi ,&nbsp;Tetsuya Tada ,&nbsp;Saori Takashima ,&nbsp;Takashi Kawasaki ,&nbsp;Yoshiro Otsuski","doi":"10.1016/j.hpr.2026.300826","DOIUrl":"10.1016/j.hpr.2026.300826","url":null,"abstract":"<div><div>Large cell neuroendocrine carcinoma (LCNEC) of the breast (LCNECB) is exceedingly rare. We encountered a case of combined LCNEC, invasive breast carcinoma of no special type (IBC-NST), and squamous cell carcinoma (SCC) of the breast. The tumor was initially diagnosed on biopsy as high-grade triple-negative breast carcinoma (TNBC). The surgical specimen after neoadjuvant chemo-immunotherapy showed no residual TNBC but revealed ductal carcinoma in situ and luminal type A-like IBC-NST. Based on these findings, anti-estrogen therapy and radiotherapy were initiated. However, brain metastasis developed seven months after mastectomy. After morphological and immunohistochemical comparison among the biopsy, mastectomy, and brain specimens, the final diagnosis was combined LCNEC with IBC-NST and SCC. Although the diagnosis of LCNECB can often be challenging, accurate histologic identification is essential for selecting the optimal treatment strategy of breast carcinoma. No established therapeutic regimen exists for LCNECB because of its extreme rarity and overlapping histologic features with high-grade IBC-NST and neuroendocrine tumor (NET) of the breast. We discuss non-morphological diagnostic features of LCNECB that may aid in recognizing LCNECB, and review selected cases from the literature to summarize its clinicopathological characteristics and current treatment modalities for this rare tumor.</div></div>","PeriodicalId":100612,"journal":{"name":"Human Pathology Reports","volume":"43 ","pages":"Article 300826"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large uterine lipoleiomyoma clinically considered as a sarcoma in a premenopausal woman: A case report and brief review of literature","authors":"Birhanu Kassie Reta ,&nbsp;Demelash Darota Dojamo ,&nbsp;Melaku Abay Muluneh ,&nbsp;Seblewengel Maru Wubalem ,&nbsp;Musie Negasi Gebreslase ,&nbsp;Yemane Leake Gebremichael ,&nbsp;Tsegay Teklehaymanot Haftu ,&nbsp;Shunun Gidena Abrha","doi":"10.1016/j.hpr.2026.300820","DOIUrl":"10.1016/j.hpr.2026.300820","url":null,"abstract":"<div><div>Uterine lipoleiomyoma is a rare subtype of leiomyoma composed of bundles of smooth muscle and fat. The majority of cases tend to be small and are usually diagnosed incidentally in obese postmenopausal women. Hereby we presented a large uterine lipoleiomyoma in a premenopausal woman who presented with abnormal uterine bleeding. This case report highlights clinicoradiopathologic features of uterine lipoleiomyoma and briefly reviews the existing literature.</div></div>","PeriodicalId":100612,"journal":{"name":"Human Pathology Reports","volume":"43 ","pages":"Article 300820"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A unique case of follicular large B-cell lymphoma arising in the background of thymic follicular hyperplasia","authors":"Gord Guo Zhu ,&nbsp;Tina B. Edmonston ,&nbsp;Eric Behling ,&nbsp;Roland Schwarting","doi":"10.1016/j.hpr.2025.300810","DOIUrl":"10.1016/j.hpr.2025.300810","url":null,"abstract":"<div><div>Follicular large B-cell lymphoma (FLBCL) is an aggressive variant of follicular lymphoma, rarely reported at extranodal sites. We describe, to our knowledge, the first case of FLBCL arising in a background of thymic follicular hyperplasia (TFH). A 76-year-old man undergoing evaluation for cardiac surgery was incidentally found to have a mediastinal mass, which revealed thymic tissue with prominent TFH on resection. Within this TFH background, follicles with sheets of centroblasts and brisk mitotic activity and a “starry sky” pattern were identified. Immunohistochemistry confirmed germinal center B-cell phenotype (CD20, CD10, BCL6, weak BCL2) with a Ki-67 &gt; 90 %. Molecular studies demonstrated a clonal <em>IGK</em> rearrangement, <em>IGH::MYC</em> fusion, and <em>DDX3X</em> mutation, while hyperplastic areas lacked clonal rearrangements. This case highlights the thymus as a rare site of B-cell lymphomagenesis and underscores the importance of recognizing FLBCL in unusual locations.</div></div>","PeriodicalId":100612,"journal":{"name":"Human Pathology Reports","volume":"43 ","pages":"Article 300810"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unusual and aggressive evolution of primary Epstein Barr virus infection with intestinal presentation mimicking a post transplant lymphoproliferative disorder","authors":"Giusella M.F. Moscato ,&nbsp;Francesca Servadei ,&nbsp;Massimo Andreoni ,&nbsp;Lucia Anemona ,&nbsp;Alessandro Mauriello ,&nbsp;Erica Giacobbi","doi":"10.1016/j.hpr.2026.300821","DOIUrl":"10.1016/j.hpr.2026.300821","url":null,"abstract":"<div><div>Epstein Barr virus (EBV) is responsible for infection in 95% of the general population worldwide mainly among adolescents and young adults. Although in immunocompetent hosts the primary infection is self-limited and asymptomatic, in literature it has been reported that it could evolve as mononucleosis with severe clinical course. Our patient suffered from primary EBV infection evolved into ileum perforation with a circumscribed lesion showing pathological features resembling a post-transplant lymphoproliferative disorder with positivity for EBV in situ hybridization and CD20. Since the genetic analysis and the immunophenotyping did not reveal alterations and the family history was not remarkable, it has been considered anusual and aggressive evolution of a primary EBV infection.</div></div>","PeriodicalId":100612,"journal":{"name":"Human Pathology Reports","volume":"43 ","pages":"Article 300821"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}