Human Pathology[JOURNAL]
Sun
200 papers
Radiological over- and underestimation of DCIS extent in breast conserving surgery specimens: radiological-pathological correlation in slice radiographs and respective histological large-format slides.
Radzinski B, Loebsin T, van Diest PJ … +4 more , Gläser D, Kiesel L, Heindel W, Focke CM
Hum Pathol · 2026 Jun · PMID 42242394 · Publisher ↗
PURPOSE: Disease extent is an independent risk factor for local recurrence in ductal carcinoma in situ (DCIS) of the breast. Surgical strategies mainly depend on area size of microcalcifications in mammograms which, howe...
PURPOSE: Disease extent is an independent risk factor for local recurrence in ductal carcinoma in situ (DCIS) of the breast. Surgical strategies mainly depend on area size of microcalcifications in mammograms which, however, may differ considerably from final DCIS size found histopathologically. Our aim was to analyse the extent and causes of discrepancies between radiological and pathological DCIS size in breast conserving surgery (BCS) specimens. METHODS: The slices of the BCS specimens were radiographed in the department of radiology using digital technique without magnification. Microcalcifications area size in 276 slice radiographs of 46 BCS specimens was measured by two radiologists and compared to histological DCIS size in the large format slides of the matching slices. Size differences >5 mm were considered discrepant. RESULTS: 216 BCS specimen slices contained microcalcifications, 228 slices contained DCIS. Positive predictive value of microcalcifications for DCIS was 0.77, negative predictive value was 0.86. Overestimation of DCIS size in the slice radiograph occurred in 58 (35%) and underestimation in 67 (40%) of 168 slices containing both DCIS and microcalcifications. Discrepancy rates of 6-9, 10-15, 16-19 and ≥ 20 mm between radiological and pathological DCIS extent were 20.8%, 14.9%, 8.9% and 19% for 168 slices containing DCIS and microcalcifications, respectively. CONCLUSION: More than two thirds of DCIS sizes were radiologically either over- or underestimated in the slice radiographs. In 89.1% of the analysed 46 BCS specimens, discrepancies between radiological size of microcalcification area and histopathological DCIS extent did not exceed 15 mm. This should be considered in planning of BCS.
The role of advanced molecular diagnostics in informing targeted therapies for AML.
Marvin-Peek J, Loghavi S, Issa GC … +4 more , Daver NG, Kadia TM, Ravandi F, DiNardo CD
Hum Pathol · 2026 May · PMID 42219116 · Publisher ↗
The application of advanced molecular diagnostics has transformed the clinical management of patients with acute myeloid leukemia (AML), a heterogeneous disease characterized by a diverse genomic landscape. Comprehensive...
The application of advanced molecular diagnostics has transformed the clinical management of patients with acute myeloid leukemia (AML), a heterogeneous disease characterized by a diverse genomic landscape. Comprehensive molecular profiling is now central to diagnosis, risk stratification, therapeutic decision-making and disease monitoring. While conventional diagnostic approaches including karyotyping, fluorescence in situ hybridization (FISH) and quantitative polymerase chain reaction (qPCR) remain essential, advances in next-generation sequencing have enabled the rapid and broad identification of recurrent genomic alterations, many of which are now directly targetable. These developments have accelerated the integration of genotype-directed treatment strategies into routine clinical practice. Expansion sequencing capabilities, including whole-exome and whole-genome approaches is further enhancing the detection of clinically relevant alterations, refining disease classification and offers the possibility of a single diagnostic platform that can detect all relevant alterations. At the same time, increasingly sensitive molecular techniques for measurable residual disease (MRD) assessment are providing new opportunities to dynamically evaluate treatment response and guide post-remission strategies. The growing volume and complexity of molecular data present ongoing challenges in interpretation, necessitating careful integration with clinical context and continued validation in prospective studies. Collectively, advances in molecular diagnostics are reshaping AML management to promote an adaptive, precision-based approach aimed at improving patient outcomes.
Optical genome mapping in myeloid neoplasms.
Tang G, Wei Q, Klausner M … +2 more , Zou YS, Toruner GA
Hum Pathol · 2026 May · PMID 42217833 · Publisher ↗
We summarize the technical principles of optical genome mapping (OGM) and evaluate its current clinical applications across myeloid neoplasms, with emphasis on acute myeloid leukemia and myelodysplastic syndromes. We hig...
We summarize the technical principles of optical genome mapping (OGM) and evaluate its current clinical applications across myeloid neoplasms, with emphasis on acute myeloid leukemia and myelodysplastic syndromes. We highlight evidence demonstrating high concordance with standard cytogenetic methods, while also showing incremental diagnostic yield through detection of cryptic abnormalities and/or refinement complex rearrangements. We further discuss clinically relevant cytogenomic abnormalities that may be underrecognized by conventional cytogenetics, including chromoanagenesis, KMT2A partial tandem duplication and cryptic rearrangements involving genes such as NUP98 and MECOM. We also address practical considerations for implementation of OGM in a clinical cytogenetic laboratory, including pre-analytical DNA quality requirements, assay sensitivity, bioinformatic interpretation and workflow integration. Current data support OGM as a complementary component of genomic workups rather than a replacement for all existing assays. As analytical standards mature and outcome-linked evidence expands, OGM has strong potential to improve genomic risk stratification, refine disease classification and advance precision diagnostics in myeloid neoplasms.
Multimodal measurable residual disease detection in acute myeloid leukemia: From technology to clinical integration.
Mason G, Hanamshet A, Othman J
Hum Pathol · 2026 May · PMID 42217832 · Publisher ↗
Measurable residual disease (MRD) is an increasingly vital tool in predicting the risk of relapse in patients with acute myeloid leukemia (AML), with a growing role in directing therapeutic choices. The vast phenotypic a...
Measurable residual disease (MRD) is an increasingly vital tool in predicting the risk of relapse in patients with acute myeloid leukemia (AML), with a growing role in directing therapeutic choices. The vast phenotypic and genomic heterogeneity of AML precludes a universal MRD assay, thereby requiring multiple complementary assays with unique advantages and limitations. This review aims to provide hematologists and pathologists with guidance in the selection, use and interpretation of MRD testing across multiple modalities. Assay characteristics, laboratory considerations and MRD targets are reviewed, accompanied by case-based discussions.
Advances in digital pathology and artificial intelligence in the diagnosis of myeloid neoplasms.
Patel P, Pozdnyakova O
Hum Pathol · 2026 May · PMID 42214762 · Publisher ↗
Recent advances in digital pathology and artificial intelligence (AI) are transforming our ability to diagnose myeloid neoplasms, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloprolifer...
Recent advances in digital pathology and artificial intelligence (AI) are transforming our ability to diagnose myeloid neoplasms, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPN). Modern AI systems now achieve expert-level performance across peripheral blood smear assessment, bone marrow aspirate and biopsy interpretation, flow cytometry, cytogenetics, and next-generation sequencing; with many platforms surpassing 90% accuracy and enabling detection of subtle morphologic and immunophenotypic signatures beyond human perception. Moreover, AI tools increasingly integrate multimodal inputs to support classification, risk stratification, and treatment predictions, often outperforming conventional methods. These systems augment pathologists by streamlining workflows, enhancing consistency, reducing interobserver variability, and accelerating turnaround times, paving the way for advanced precision diagnostics in hematopathology. However, challenges remain in clinical adoption, including cost, security, regulatory oversight, and validation across diverse populations. Despite these hurdles, early regulatory successes such as digital peripheral blood smear morphology analyzers illustrate the feasibility of real-world implementation. Broader adoption will however require coordinated efforts among developers, laboratories, pathologists, and regulatory agencies to ensure safety, transparency, and interoperability.
TFEC-rearranged renal cell carcinoma.
Tekin B, Pitel BA, Al-Kateb H … +6 more , Halling KC, Whaley RD, Cheville JC, Sharma V, Leibovich BC, Gupta S
Hum Pathol · 2026 May · PMID 42214761 · Publisher ↗
Abstract loading — click title to view on PubMed.
Single cell sequencing in acute myeloid leukemia: Linking genotype to functional phenotype for precision risk stratification and treatment decisions.
Anandappa AJ, Xiao W, Miles LA
Hum Pathol · 2026 May · PMID 42208774 · Publisher ↗
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by clonal expansion of myeloid precursor cells. The pathologic evaluation of AML integrates multiple levels of characterization, includin...
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by clonal expansion of myeloid precursor cells. The pathologic evaluation of AML integrates multiple levels of characterization, including morphology of cells circulating in peripheral blood and bone marrow, identification of blast lineage by immunohistochemistry and flow cytometry immunophenotyping, and genetic studies including karyotype, fluorescence in-situ hybridization, and next generation sequencing (NGS). NGS analysis is utilized routinely to define the mutational landscape of AML, which informs risk stratification and choice of therapy. However, the current methods of immunophenotypic classification in clinical practice use a relatively small number of surface markers to coarsely determine hematopoietic lineage, and bulk sequencing approaches are largely unable to accurately capture clonal complexity, resolve mutational order, and distinguish residual leukemia from clonal hematopoiesis. Single-cell sequencing techniques have transformed our understanding of normal and malignant hematopoiesis by moving beyond the classical hematopoietic hierarchy to define transitional cell states, thereby unraveling clonal complexity with unprecedented resolution. Single-cell multi-omic approaches that span genomics, transcriptomics, proteomics, epigenomics, and metabolomics have the potential to unravel the vast disease heterogeneity in AML, address the discordance between genetic subtypes and functional phenotypes, and improve risk stratification. The latest frontier, spatial single-cell techniques apply these multi-omic approaches to study cells in situ, offering new insights into the bone marrow microenvironment. Here, we review how single cell sequencing technologies have been utilized to study AML throughout the course of disease, including initial diagnosis, assessment of measurable residual disease in remission, and clonal evolution at relapse, and we look ahead to future applications that may impact clinical practice.
Revisiting nuclear grade as a high-risk marker for predicting upgrade in ductal carcinoma in situ.
Ueki Y, Horimoto Y, Harada K … +13 more , Ushiyama Y, Nozaki Y, Ishizuka Y, Semba R, Uenaka N, Kawate T, Ushigusa T, Sato E, Onagi H, Hayashi T, Kutomi G, Ishikawa T, Yamaguchi R
Hum Pathol · 2026 May · PMID 42208773 · Publisher ↗
Ductal carcinoma in situ (DCIS) diagnosed by needle biopsy harbors invasive carcinoma in about one-third of cases. Nuclear grade (NG) has long been used to stratify risk, with NG3 regarded as "high risk," particularly fo...
Ductal carcinoma in situ (DCIS) diagnosed by needle biopsy harbors invasive carcinoma in about one-third of cases. Nuclear grade (NG) has long been used to stratify risk, with NG3 regarded as "high risk," particularly for upgrade and local recurrence. However, the extent to which NG contributes to predicting upgrade remains uncertain. We retrospectively analyzed 1015 patients diagnosed as DCIS by needle biopsy at two Japanese institutions (2013-2024) and subsequently treated surgically. Biopsy specimens were evaluated for NG and other pathological factors including Ki67 labeling index. Logistic regression was performed to identify predictors of upgrade. Upgrade to invasive carcinoma was observed in 347 of 1015 surgical specimens (34%). Upgrade rates increased only modestly with NG (NG1, 32.8%; NG2, 34.3%; NG3, 38.8%) and were not significantly associated with upgrade. When NG3 was used as a binary predictor, it showed high specificity (88.9%) but very low sensitivity (13.5%), indicating limited discriminatory ability. Both univariable and multivariable analyses revealed that older age (P = 0.002) and a higher Ki67 labeling index (P < 0.001) were independently associated with upgrade. Ki67 showed the highest area under the curve (0.593; cutoff 12%), although its discriminatory ability remained limited when used alone. Despite its long-standing role as a high-risk marker, NG showed limited value in predicting upgrade from DCIS to invasive carcinoma. These findings suggest that risk stratification relying on NG warrants reconsideration. Ki67 may be a more informative pathological factor than NG.
Gastrointestinal Tract Endometriosis: Clinicopathologic Features and Anatomic Distribution in an Institutional Cohort.
Jamshed A, Zhu F, Cartwright D … +6 more , Turner K, Amin K, Khalifa MA, Adeyi O, Mukhtar Z, Park BU
Hum Pathol · 2026 May · PMID 42208772 · Publisher ↗
Endometriosis is defined by the presence of endometrial glands and stroma outside the uterine cavity. Although it typically presents within the pelvis, extragenital manifestations are well documented with gastrointestina...
Endometriosis is defined by the presence of endometrial glands and stroma outside the uterine cavity. Although it typically presents within the pelvis, extragenital manifestations are well documented with gastrointestinal (GI) involvement being the most frequently affected organ system. We performed a retrospective study of histologically confirmed cases of endometriosis diagnosed at a single healthcare system between 2017 and 2024 to characterize the clinicopathologic features, anatomic distribution, and frequency within our institutional pathology cohort of GI tract involvement. A total of 1,964 cases of endometriosis were identified, of which 150 (7.7%) demonstrated GI tract involvement, which comprised our main cohort. The majority of patients had no documented prior history of endometriosis (97%). CT/MRI was the most common modality used for diagnosis with 51%. Non-specific abdominal or pelvic pain (53%) followed by uterine bleeding (23%) were the most common presenting symptoms. GI-specific symptoms were found in only 17% of cases. Appendix was the most frequently involved site (77 cases) followed by rectum (45 cases), and sigmoid colon (40 cases). Involvement of a single isolated organ was seen in 56% of cases, with multi-site disease found in 44% of patients, and concurrent gynecological organ involvement found in 39% of cases. In 88% of cases, regular hematoxylin and eosin was used to render the diagnosis without the use of immunohistochemistry (IHC). The heterogeneity in both clinical presentation and pathologic findings for gastrointestinal endometriosis highlights the diagnostic complexity, and emphasizes the need for increased awareness to avoid histologic misinterpretation and facilitate timely recognition and management of patients.
Non-langerhans cell histiocytosis: A growing category of emerging entities.
Delio M, Duarte C, Siegele BJ … +2 more , Medeiros LJ, Pan Z
Hum Pathol · 2026 May · PMID 42208771 · Publisher ↗
Histiocytoses are uncommon and comprise a diverse group of disorders of myeloid-derived cells with a macrophage or dendritic cell phenotype. They encompass a large number of subtypes, including Langerhans cell histiocyto...
Histiocytoses are uncommon and comprise a diverse group of disorders of myeloid-derived cells with a macrophage or dendritic cell phenotype. They encompass a large number of subtypes, including Langerhans cell histiocytosis (LCH) and non-LCH. LCH is most common and perhaps best understood. The non-LCH in the current World Health Organization Classification of Hematolymphoid Tumors (WHO-HAEM5) includes Erdheim-Chester disease, juvenile xanthogranuloma, Rosai-Dorfman disease, ALK histiocytosis, and histiocytic sarcoma. Due to the rarity of non-LCH, there is a lack of awareness, knowledge and experience among general pathologists in the diagnosis of these entities, often resulting in significant delays or even misinterpretation. These histiocytic neoplasms also exhibit clinical, pathological and molecular heterogeneity. Given that these neoplasms all resemble histiocytes to some degree, there is substantial morphologic overlap between these entities, reactive histiocytes, and some non-histiocytic neoplasms. The diagnostic process can be further complicated by unusual morphologic features, such as epithelioid and spindle cell cytology, a marked inflammatory reaction, and prominent fibrosis. Beginning in 2010 with the discovery of BRAF mutations in LCH, our biologic understanding of histiocytic neoplasms greatly expanded with recognition of the importance of the mitogen activated protein kinase (MAPK) pathway in pathogenesis. The biologic spectrum of histiocytic neoplasms continues to expand, in large part driven by discovery of novel molecular genetic aberrations, suggesting that additional non-LCH or modifications to the classification of these entities may be included to future editions of the WHO classification. In this article, we systemically review the clinicopathologic and molecular genetic features of each type of non-LCH. We also provide differential diagnoses and diagnostic algorithms to assist pathologists in establishing the diagnosis of these entities.
TSC gene-associated lesions of the lung.
Szalai F, Krencz I, Burger CD … +2 more , Kornafeld A, Khoor A
Hum Pathol · 2026 May · PMID 42208770 · Publisher ↗
Pathogenetic alterations of tumor suppressor genes TSC1 and TSC2 are responsible for the development of tuberous sclerosis complex (TSC) and various sporadic diseases, including sporadic lymphangioleiomyomatosis (LAM). T...
Pathogenetic alterations of tumor suppressor genes TSC1 and TSC2 are responsible for the development of tuberous sclerosis complex (TSC) and various sporadic diseases, including sporadic lymphangioleiomyomatosis (LAM). TSC can be inherited and non-inherited and is characterized by indolent tumor formation in multiple organs. The most important pulmonary manifestation of TSC is LAM. It affects the majority of female and a small subset of male patients, heavily impacting their quality of life and survival. It is a cystic lung disease, which is now considered a PEComa-type neoplasm. In addition to the TSC-associated form (TSC-LAM), LAM can also occur sporadically (S-LAM), almost exclusively in women. Both forms present with proliferation of immature smooth muscle cells, resulting in cystic destruction of the pulmonary parenchyma and emergence of respiratory symptoms, including dyspnea and pneumothorax. Currently, sirolimus is the only FDA-approved treatment option for LAM patients; however, a subgroup of patients either do not respond or tolerate therapy. Recently published data has shed light on the heterogeneity of LAM and the importance of the tumor microenvironment, which may serve as new aspects for future research. Other TSC gene-associated lesions of the lung include multifocal micronodular pneumocyte hyperplasia (MMPH) and non-LAM PEComa (clear cell sugar tumor). While MMPH may not be progressive or require clinical treatment, it might require differentiation from atypical adenomatous hyperplasia or lepidic adenocarcinoma of the lung.
Comprehensive Clinicopathological Analysis of Sloughing Esophagitis: A Large Single-center Series.
Wang L, Yang Z
Hum Pathol · 2026 May · PMID 42208769 · Publisher ↗
Sloughing esophagitis (SE), a.k.a. esophagitis dissecans superficialis, is a desquamative disorder of the esophagus characterized by superficial squamous cell layer sloughing with normal underlying mucosa. The etiology i...
Sloughing esophagitis (SE), a.k.a. esophagitis dissecans superficialis, is a desquamative disorder of the esophagus characterized by superficial squamous cell layer sloughing with normal underlying mucosa. The etiology is poorly understood. We collected 72 SE cases spanning 15 years from our health system and investigated their clinicopathological features. Endoscopic findings of SE usually included characteristic sloughed mucosa with strips or ribbon-like mucosal breaks, though rare cases had normal upper endoscopy. Histologically, there was two-toned appearance with superficial parakeratosis in all cases. In our study, while the majority of SE (57%) were completely devoid of inflammation, 43% of them exhibited neutrophilic / lymphocytic inflammation (2 were severe). Fifty-seven patients (79%) were taking 5 or more prescriptions, most commonly NSAIDs and/or antiplatelets/anticoagulants (39%). Twenty patients (28%) had malignancy, and additional eleven patients (15%) were on immunosuppressive therapy. Although the precise pathogenesis of SE is unknown, it appears that it was associated with polypharmacy, malignancy, and/or immunosuppression. Acid suppressants were prescribed as the treatment for 83% SE patients. Most patients resolved at follow-up. The presence of inflammation at initial biopsy does not appear to be related to any identifiable etiology or clinical outcome.
Histomorphologic analysis and clinical correlation of atypical apocrine lesions in breast pathology.
Podany P, Zhan H, Colón-Cartagena L … +4 more , Ai D, Du J, Krishnamurti U, Liang Y
Hum Pathol · 2026 May · PMID 42176994 · Publisher ↗
INTRODUCTION: Apocrine change is common in breast pathology, yet atypical apocrine lesions remain poorly defined and diagnostically challenging. This study aimed to clarify the terminology of atypical apocrine proliferat...
INTRODUCTION: Apocrine change is common in breast pathology, yet atypical apocrine lesions remain poorly defined and diagnostically challenging. This study aimed to clarify the terminology of atypical apocrine proliferations and assess their clinical significance by correlating histologic features with clinical outcomes. METHODS: We retrospectively analyzed 59 specimens initially diagnosed as atypical apocrine adenosis (AAA) or atypical apocrine hyperplasia (AAH), including apocrine atypical ductal hyperplasia, from 2014 to 2024. Cases with coexisting in situ or invasive ductal carcinoma were excluded. Histologic features and clinical follow-up data were reviewed. RESULTS: No significant differences were observed between AAA and AAH with respect to patient age, lesional size, most architectural patterns, lobular involvement, nuclear features, necrosis, calcifications, or carcinoma upstaging on subsequent excision. Cribriform architecture was significantly more frequent in AAH than AAA (63% vs. 33%, p = 0.047). Lesions upstaged to in situ or invasive ductal carcinoma demonstrated a significantly larger extent of atypia on biopsy (1.3 cm vs. 0.8 cm, p = 0.043), higher frequencies of marked nuclear enlargement (≥3-fold compared with background epithelium; 92% vs. 54%, p = 0.027), nuclear irregularity (54% vs. 17%, p = 0.028), and necrosis (23% vs. 0%, p = 0.037). Lesional extent, nuclear irregularity, and necrosis were independently associated with carcinoma upstaging (p < 0.05). CONCLUSIONS: Cribriform architecture supports classification as AAH, though AAA and AAH show no significant clinical differences. Marked nuclear enlargement, nuclear irregularity, and necrosis in larger atypical apocrine lesions are strongly associated with carcinoma upstaging and should prompt consideration of apocrine DCIS.
Thermal resection-margin artifact mimicking goblet cell adenocarcinoma in appendectomy specimens: clinicopathologic correlation with appendiceal stump technique.
Hamed A, Hoskuldsson T, Aldaraiseh B … +10 more , Alutaibi M, Karzoun MZ, Jamshed A, Paz M, Hamed N, Cartwright D, Turner KO, Khalifa MA, Amin K, Park BU
Hum Pathol · 2026 May · PMID 42167614 · Publisher ↗
BACKGROUND: Goblet cell adenocarcinoma (GCA) of the appendix is a rare but clinically significant neoplasm characterized by infiltrative nests of mucin-rich goblet-like cells that may exhibit minimal cytologic atypia. Du...
BACKGROUND: Goblet cell adenocarcinoma (GCA) of the appendix is a rare but clinically significant neoplasm characterized by infiltrative nests of mucin-rich goblet-like cells that may exhibit minimal cytologic atypia. During routine sign-out, we observed a reproducible alteration of the resection margin in appendectomy specimens that closely mimicked low-grade GCA. Following institutional review board approval, we retrospectively reviewed 33 appendectomy specimens to characterize this finding and assess associated clinicopathologic factors. METHODS: A goblet cell-like artifact was identified in 12 of 33 cases (36%). The altered areas consisted of optically clear, vacuolated profiles arranged in linear arrays or small clusters within the appendiceal wall, often associated with thermal-type tissue injury. AE1/AE3 immunohistochemistry was performed in all artifact-positive cases, which were negative, supporting a non-epithelial, non-neoplastic interpretation. RESULTS: The finding was strongly associated with appendiceal base management using endoloop ligation with energy-assisted transection (12/12 artifact cases, 100%), whereas stapler-only transection was observed exclusively in non-artifact cases (p = 0.001). Thermal injury (p < 0.001), mucin depletion (p = 0.009), marked wall edema (p < 0.001), and receipt of an open proximal margin (p = 0.031) were also significantly associated. Clinical follow-up (median 6.2 months in artifact cases) demonstrated no subsequent neoplasms, additional surgery, or oncologic therapy. CONCLUSION: These findings support a reproducible, procedure-related artifact that can mimic GCA, particularly in specimens managed with endoloop ligation and energy-assisted transection. Awareness of the associated morphologic constellation and operative context may help prevent overinterpretation of this benign alteration as infiltrative neoplasia.
Dedifferentiated/undifferentiated endometrial carcinoma:SWI/SNF-deficiency and molecular heterogeneity indicating novel prognostic stratification in a single-center study of 71 cases.
Qi Y, Yao Q, Xu Y … +8 more , Yu L, Tu X, Cheng Y, Ge H, Tang S, Zhou X, Yang W, Bi R
Hum Pathol · 2026 May · PMID 42162929 · Publisher ↗
Deficiency of SWI/SNF proteins, particularly BRG1 (SMARCA4) and INI1 (SMARCB1), has frequently been associated with poor clinical outcomes in dedifferentiated/undifferentiated endometrial carcinoma (DDEC/UDEC). However,...
Deficiency of SWI/SNF proteins, particularly BRG1 (SMARCA4) and INI1 (SMARCB1), has frequently been associated with poor clinical outcomes in dedifferentiated/undifferentiated endometrial carcinoma (DDEC/UDEC). However, the prognostic significance of BRM (SMARCA2) remains unclear. Additionally, although the TCGA classification predicts outcomes in endometrioid adenocarcinoma, its prognostic value in DDEC/UDEC is still unproven. In this study, 71 DDEC/UDEC cases were assessed for the expression of BRG1, BRM, INI1 and ARID1A. BRG1, BRM, INI1 and ARID1A deficiency were observed in 36% (26/71), 55% (27/49), 8% (6/69), 55% (19/34) of cases, respectively. BRG1-deficiency, and BRG1 or INI1-deficiency were both associated with poorer overall survival (OS) (P = 0.048, P = 0.013, respectively). Only BRG1 or INI1-deficiency was significantly correlated with worse disease-free survival (DFS) (P = 0.039). No significant differences in either DFS or OS were observed between patients with isolated loss of BRM or INI1 expression and those with intact expression. Genetic alterations in 31 cases predominantly involved the PI3K-AKT-MTOR pathway. TCGA molecular subtyping showed no significant differences in OS (P = 0.488) or DFS (P = 0.425) among the molecular subtypes. However, patients with concurrent microsatellite instability-high (MSI-H) and PIK3CA mutation exhibited more favorable OS (P = 0.021) and DFS (P = 0.012). Therefore, our research shows that BRG1 or INI1 deficiency, especially BRG1 deficiency, predicts a poorer prognosis in patients with DDEC/UDEC. Furthermore, other integrated molecular classification strategies--such as the combination of MSI-H status and PIK3CA mutation--may provide a novel prognostic stratification approach for this aggressive tumor entity.
Association of genomic driver mutation, histologic subtype, and mTORC1 biomarker expression in mTOR pathway-altered renal tumors.
Bhardwaj S, Amaral A, Dairo O … +7 more , Akbari A, Pivovarcikova K, Williamson SR, Antic T, Argani P, Asrani K, Lotan TL
Hum Pathol · 2026 May · PMID 42155824 · Publisher ↗
A widening spectrum of renal tumors is driven by alterations in mTOR pathway genes. We examined the relationship between the specific underlying genomic driver mutation, mTOR signaling activation and tumor histologic sub...
A widening spectrum of renal tumors is driven by alterations in mTOR pathway genes. We examined the relationship between the specific underlying genomic driver mutation, mTOR signaling activation and tumor histologic subtype among mTOR pathway-altered tumors. mTOR pathway activation was assessed by quantifying expression of GPNMB in 16 cases of eosinophilic vacuolated tumor (EVT), 13 cases of low grade oncocytic tumor (LOT), 10 cases of eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), and 1 case of xanthomatous giant cell renal cell carcinoma (XGC-RCC), all with previous sequencing. p-S6 expression was additionally quantified in the LOT and EVT cases. A literature review of 217 previously reported mTOR pathway-altered renal tumors identified the frequency of driver alterations by histologic subtype. GPNMB and p-S6 expression were correlated with one another (r = 0.51, p = 0.007) and GPNMB expression was higher among tumors with underlying TSC1/2 alterations compared to MTOR/PIK3CA alterations (p = 0.02) with a nonsignificant trend for p-S6 (p = 0.15). There was no significant association of GPNMB or pS6 with tumor histologic subtype in this series. In the literature, TSC1/2 alterations predominated in ESC-RCC (84%), though were less common in LOT (24%) where MTOR or other mTOR pathway mutations (PIK3CA, PTEN, RHEB, RICTOR, NF1/2) were frequent (55%). In EVT, RCC-FMS and renal hemangioblastoma, TSC1/2 and MTOR mutations occurred with similar frequency, with a slight predominance of the former. GPNMB expression is associated with p-S6 activation and is higher in renal tumors driven by TSC1/2 compared to MTOR/PIK3CA alterations, suggesting that it may be most useful in ESC-RCC.
Lymph node ratio, not nodal stage, predicts overall and disease-free survival in non-ampullary primary small intestine adenocarcinoma.
Honaker EC, Saeed O, González IA
Hum Pathol · 2026 May · PMID 42144080 · Publisher ↗
Lymph node ratio (LNR) has emerged as a strong prognostic indicator in colorectal cancer (CRC), but its significance in non-ampullary primary small intestine adenocarcinoma (SIA) has been only sparsely reported in the li...
Lymph node ratio (LNR) has emerged as a strong prognostic indicator in colorectal cancer (CRC), but its significance in non-ampullary primary small intestine adenocarcinoma (SIA) has been only sparsely reported in the literature. Moreover, LNR has not been examined alongside key CRC histologic prognostic variables, including tumor budding (TB), desmoplastic reaction (DR), and tumor-infiltrating lymphocytes (TILs). Eighty-nine cases (mean age: 63 years, range: 20-88) of SIA were included from 2008 to 2023; most tumors arose in the duodenum (40%). Mean follow-up was 40.9 months (range: 0-189). The mean carcinoembryonic antigen (CEA) level was 38.4 ng/mL (range: 0.2-1183.9). Low-grade histology predominated (69%), and lymphovascular invasion was seen in 42% and perineural invasion in 16%. TB was low in 55%, intermediate in 30%, and high in 15%. DR was mature in 45%, intermediate in 43%, and immature in 12%. TILs were present in 34%. The average International TILs Working Group score was 29% (range: 0-80%). The mean LNR was 0.2, and 49% of cases were pN0. Most tumors were pT3 (54%) or pT4 (34%), and 12% were pM1. Only CEA level and LNR independently predicted disease-free survival (HR: 1.01; 95%CI 1.00-1.02; P = 0.010 and HR 14.64; 95%CI 1.82-117.59; P = 0.012, respectively), and LNR independently predicted overall survival (HR 14.55; 95%CI 1.76-120.06; P = 0.013). Higher LNR was significantly associated with adverse tumor characteristics, including features of the tumor microenvironment such as TB, DR, and TILs. LNR and pre-operative CEA level outperformed nodal stage and other histologic factors as prognostic markers in SIA.
Prognostic value of Combined Progression Index (CPI) in 132 patients with unresectable peritoneal metastasis treated with Pressurized IntraPeritoneal Aerosol Chemotherapy.
Jørgensen MS, Ainsworth AP, Fristrup CW … +3 more , Mortensen MB, Graversen M, Detlefsen S
Hum Pathol · 2026 May · PMID 42144079 · Publisher ↗
Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a palliative treatment for patients with unresectable peritoneal metastasis (PM) from gastrointestinal and gynecological cancers. Few prognostic markers for str...
Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a palliative treatment for patients with unresectable peritoneal metastasis (PM) from gastrointestinal and gynecological cancers. Few prognostic markers for stratification of patients with PM receiving PIPAC directed treatments exist. The Combined Progression Index (CPI) has been proposed as a prognostic tool in these patients. CPI combines overall change in the histological Peritoneal Regression Grading Score (PRGS) from peritoneal quadrant biopsies taken prior to PIPAC treatments 1 and 3 and peritoneal fluid (PF) cytology at PIPAC 3. Our aim was to investigate the prognostic value of CPI in unresectable PM patients treated with PIPAC. We performed a retrospective study of prospectively collected data based on all PM patients treated with PIPAC at Odense PIPAC Center from 2015 to 2024. Positive CPI was defined as an increase in PRGS from peritoneal quadrant biopsies taken prior to PIPAC 1 and PIPAC 3 and/or positive PF cytology at PIPAC 3. Positive PF cytology was defined as malignant cells or cells suspicious of malignancy. Survival data were analyzed using Kaplan-Meier graphs, log-rank test, and univariable and multivariable Cox proportional hazards regression. Inclusion criteria were fulfilled by 132 patients. In the entire cohort and PM from gastric cancer (GC-PM), but not in PM from colon or pancreatic cancer, CPI-positivity was associated with shorter OS (P < 0.01). In both GC-PM and the entire cohort, CPI-positivity had independent negative prognostic value (P = 0.005). In conclusion, our data indicate that CPI holds clinically relevant prognostic information. As it in some PIPAC-treated patients is only possible to perform either cytology or PRGS, we recommend using both methods whenever feasible, as this also enables assessment of CPI.
Evaluating the diagnostic performance of multimodal large language models in thyroid cytology.
Laohawetwanit T, Dixit S, Agarwal S … +2 more , Yoshikawa AL, Bychkov A
Hum Pathol · 2026 May · PMID 42144078 · Publisher ↗
Thyroid fine-needle aspiration (FNA) cytology is a widely used, cost-effective method for evaluating thyroid nodules. However, interpretation of thyroid FNA smears remains challenging, particularly in settings with limit...
Thyroid fine-needle aspiration (FNA) cytology is a widely used, cost-effective method for evaluating thyroid nodules. However, interpretation of thyroid FNA smears remains challenging, particularly in settings with limited access to experienced cytopathologists. Multimodal large language models (LLMs) have shown potential in static image interpretation in histopathology and may serve as supportive tools when expert review is unavailable. Nevertheless, data regarding their application in cytopathology, including thyroid cytology, remain limited. In this study, we evaluated the diagnostic accuracy and consistency of ChatGPT and Gemini in interpreting 100 thyroid FNA cytology images, comprising 50 cases of papillary thyroid carcinoma (PTC) and 50 non-PTC lesions, including follicular nodular disease, follicular neoplasm, medullary thyroid carcinoma, and anaplastic thyroid carcinoma. Representative images were captured at 40× magnification and reviewed by expert pathologists to confirm the reference diagnoses. Each image was analyzed by ChatGPT and Gemini across five separate rounds. For the class-based analysis, ChatGPT and Gemini achieved mean diagnostic accuracies of 26.2% and 23.6%, respectively, based on Bethesda categories, and 39.2% and 20.2%, respectively, for specific diagnostic entities. ChatGPT rendered a higher number of suspicious for malignancy and atypia of undetermined significance diagnoses than Gemini. Five-image submission and inclusion of TIRADS data improved performance metrics in some instances. Medullary and anaplastic thyroid carcinomas were rarely correctly identified. In conclusion, although ChatGPT and Gemini demonstrated the potential of LLMs in cytologic image interpretation and drafting descriptive reports, their diagnostic performance in thyroid FNA cytology was limited, underscoring the current constraints of LLMs in this domain.
TSC2, cathepsin K, and β-catenin as immunohistochemical markers for lymphangioleiomyomatosis.
Alfayez A, Belanger E, Cheung S … +1 more , Churg A
Hum Pathol · 2026 Aug · PMID 42102978 · Publisher ↗
The diagnosis of lymphangioleiomyomatosis (LAM) can be straightforward when LAM cells are abundant, but may be difficult with subtle lesions mimicking emphysema or with lung architecture obscured by parenchymal collapse....
The diagnosis of lymphangioleiomyomatosis (LAM) can be straightforward when LAM cells are abundant, but may be difficult with subtle lesions mimicking emphysema or with lung architecture obscured by parenchymal collapse. A variety of markers have been proposed for immunohistochemical confirmation of LAM. The is increasing evidence from sequencing studies that tuberous sclerosis 2 (TSC2) is frequently mutated in sporadic LAM, and TSC2 expression/loss can now be demonstrated by immunohistochemistry but TSC2 immunohistochemistry has not been reported in LAM. Here we examined the immunohistochemical performance of TSC2, β-catenin, cathepsin K, and HMB-45 in 10 cases of pulmonary LAM (4 with florid lesions, 6 with only subtle lesions), 6 cases of pelvic nodal LAM, and two cases of micronodular pneumocyte hyperplasia (MNPH), the latter a common finding in TSC LAM cases. TSC2 loss was observed in all cases in both florid and subtle lesions, nodal LAM, and MNPH. HMB45 was focally positive in 5/10 pulmonary and 3/6 nodal cases. β-catenin was variably, but sometimes weakly, expressed in 6/6 nodal cases and 10/10 pulmonary case but was often difficult to interpret in subtle lesions. Cathepsin K showed consistent strong positivity in all pulmonary and nodal cases. We conclude that, in well inflated lung with obvious LAM lesions, β-catenin, cathepsin K, and TSC2 are easy to interpret. In subtle cases Cathepsin K staining is the easiest to interpret but TSC2 staining also picks up subtle cases and offers the advantage of confirming the genetic change that implies a potential response to mTOR inhibitor therapy.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe