Human Pathology[JOURNAL]
Sun
200 papers
Sarcomatoid carcinoma of the prostate - A single institution experience with emphasis on molecular genetic findings.
Tekin B, Datta L, Zargham R … +7 more , Sukov WR, Cheville JC, Herrera Hernandez L, Boorjian SA, Karnes RJ, Gupta S, Jimenez RE
Hum Pathol · 2026 Jan · PMID 41285178 · Publisher ↗
OBJECTIVES: Sarcomatoid carcinoma of the prostate (SCP) is a rare neoplasm known for its diagnostic difficulties and aggressive clinical course. Given the paucity of literature on its molecular landscape, we aimed to inv...
OBJECTIVES: Sarcomatoid carcinoma of the prostate (SCP) is a rare neoplasm known for its diagnostic difficulties and aggressive clinical course. Given the paucity of literature on its molecular landscape, we aimed to investigate a cohort of SCP, using a multi-modal approach. METHODS: Our surgical pathology archive was queried for patients diagnosed with SCP (2006-2022), followed by re-review of archived slides. For each case, a panel of immunohistochemical stains (including programmed death-ligand 1 [PD-L1] clones SP142, SP263, and 22C3) was performed on a representative block. Fluorescence in situ hybridization (FISH) was used to evaluate chromosomes 10 (including PTEN) and 17 (including TP53). All cases were evaluated using a next-generation sequencing (NGS) panel. RESULTS: Eight patients were included. Three (37.5 %) had a prior history of acinar adenocarcinoma, while a concomitant adenocarcinoma was present in five patients (62.5 %). The median duration of follow-up was 20.5 months. Seven patients (87.5 %) presented with or developed systemic metastases during follow-up. At last follow-up, 6 patients (75 %) were dead of disease. Three of the 7 cases (42.9 %) assessed for PD-L1 expression showed some staining. The most common pathogenic alterations identified by NGS involved TP53 (n = 5), followed by APC, BRCA2, CHECK2, CTNNB1, and RB1 (n = 1, each). On FISH testing, copy number changes involving chromosome 10 and 17 were found in 80 % and 60 % of the cases, respectively. CONCLUSIONS: This study sheds light on the molecular landscape of SCP, which may be valuable to elucidate the prognostic and therapeutic implications for this uncommon disease.
Impact of gender and age on the histologic severity of metabolic syndrome associated steatohepatitis.
Acharya EK, Lam R, Lim JK … +2 more , Deng Y, Jain D
Hum Pathol · 2026 Jan · PMID 41276023 · Publisher ↗
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are leading causes of chronic liver disease. Although clinic...
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are leading causes of chronic liver disease. Although clinical studies suggest age and gender may influence disease severity, histologic data remain limited. We investigated the relationship between age, gender, and histologic features of MASH. METHODS: We retrospectively reviewed 407 liver biopsies (2012-2019) with histologic steatosis. Clinical, demographic, and laboratory data were collected. Biopsies were assessed for steatosis, inflammation, ballooning, and fibrosis, and the NAFLD activity score (NAS) was calculated. Patients were divided into four groups: women 18-50 years, men 18-50 years, women >50 years, and men >50 years. Statistical analyses included univariable and multivariable ordinal logistic regression. RESULTS: Younger patients (18-50 years) had higher steatosis and NAS irrespective of gender, while older patients (>50 years) had higher fibrosis scores. Fibrosis was most severe in older men (mean stage 2.41 ± 1.41), compared with younger men (1.21 ± 1.21) and younger women (1.52 ± 1.30). Severe ballooning and lobular inflammation were more frequent in women, particularly younger women. In multivariable regression, age > 50 years remained independently associated with higher fibrosis stage (OR 2.17), while gender was not significant. BMI did not differ between groups. CONCLUSIONS: Older age is strongly associated with higher fibrosis in MASH, independent of BMI and other clinical covariates. Gender-related differences in histologic features contributed to NAS but were not statistically significant. These findings highlight age as a potentially important driver of fibrosis progression in MASH. Hormonal factors may play a role but further investigation is warranted.
Conventional FLCN-mutated tumor: a retrospective study of 5 cases with emphasis on diagnostic challenges.
Wan L, Xie B, Li Q … +5 more , Ma Q, Huang Y, Hu Z, Feng J, Tong K
Hum Pathol · 2026 Jan · PMID 41276022 · Publisher ↗
BACKGROUND: Conventional FLCN-mutated tumors (c-FMTs) occur in Birt-Hogg-Dubé syndrome (BHD), posing diagnostic challenges due to their overlapping histology with chromophobe renal cell carcinoma (ChRCC) and renal oncocy...
BACKGROUND: Conventional FLCN-mutated tumors (c-FMTs) occur in Birt-Hogg-Dubé syndrome (BHD), posing diagnostic challenges due to their overlapping histology with chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO). METHODS AND RESULTS: Clinicopathological analysis, immunohistochemistry, fluorescence in situ hybridization, and whole exome sequencing (WES) were performed in this study. This cohort comprised 4 males and 1 female with ages from 31 to 69 years (median: 53 years) and tumor diameters from 0.8 to 3.5 cm (median: 2.6 cm). Four of 5 cases showed a solitary lesion macroscopically. These cases were initially diagnosed as ChRCC (n = 3), RO (n = 1), and eosinophilic vacuolated tumor (EVT, n = 1) and displayed variable nested, acinar, solid structures, and mixtures of oncocytic and pale/clear cells, lacking marked tubules, cysts, and papillae in nonconventional FMT. All tumors exhibited mutually exclusive FOXI1 and L1CAM staining. L1CAM was negative in ChRCCs (10/10) and most ROs (7/8), but positive in low grade oncocytic tumors (5/5) and EVT (1/1). WES identified (likely) pathogenic FLCN mutations in all cases and biallelic inactivation of FLCN was detected in 4 (80 %) of 5 cases. Copy number analysis revealed no characteristic chromosomal loss of ChRCCs. Although metachronous TFE3-traslocation RCC occurred in 1 of 4 patients, all patients remained disease-free, except for 1 patient alive with tumors. CONCLUSIONS: Conventional FMTs are indolent tumors, harboring hybrids of likely multiple cell populations. These tumors are usually misdiagnosed as sporadic ChRCCs or ROs. The panel of CK7, CD117, FOXI1, and L1CAM is useful for the diagnosis of c-FMTs.
Prevalence and distribution of human papillomavirus type 16 in esophageal squamous cell carcinoma and its association with p16 expression: A large-scale study in Japan.
Jiang K, Ishida H, Taniyama Y … +8 more , Sato C, Okamoto H, Ozawa Y, Yamazaki Y, Sasano H, Unno M, Suzuki T, Kamei T
Hum Pathol · 2025 Dec · PMID 41238131 · Publisher ↗
The infection rate of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) varies widely (0 %-88.9 %), and the diagnostic utility of p16 as a surrogate marker remains controversial. Moreover, the distr...
The infection rate of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) varies widely (0 %-88.9 %), and the diagnostic utility of p16 as a surrogate marker remains controversial. Moreover, the distribution of HPV infection in ESCC has not been previously investigated. Patients with ESCC who underwent esophagectomy without neoadjuvant therapy between 2007 and 2022 were included in this study. Three formalin-fixed, paraffin-embedded blocks (oral side, tumor, and esophagogastric junction (EGJ)) were collected. p16 expression was assessed by immunohistochemistry (positivity defined as a labeling index of ≥10 %), whereas HPV type 16 DNA was detected by polymerase chain reaction. The distribution of HPV distribution was also assessed. In total, 158 patients were analyzed. p16 was detected in 19.0 % (30/158) and HPV DNA in 3.8 % (6/158) of tumor samples. The sensitivity and positive predictive value of p16 immunohistochemistry for detecting HPV DNA were 100 % and 20.0 %, respectively. HPV DNA was also detected in 3.6 % (5/137) of the oral side and 2.7 % (4/146) of EGJ samples. Infectious mapping revealed a random distribution pattern across the three anatomical regions. This large-scale study demonstrated a low prevalence of HPV infection in ESCC and indicated that p16 immunohistochemistry may aid in reducing the risk of missing patients with HPV-positive tumors. Notably, the random-like distribution of HPV DNA across the three anatomical sites suggests partial viral clearance by the host immune response. These findings underscore the potential for false-negative results in biopsy specimens obtained from non-infected regions in otherwise HPV-positive patients.
Integrating computational pathology and multi-transcriptomics to characterize glioblastoma heterogeneity and identify prognostic biomarkers.
Dai Y, Shi C, Zhao K … +6 more , Tie J, Lian K, Li W, Li Y, Wang Y, Zhao N
Hum Pathol · 2025 Dec · PMID 41232838 · Publisher ↗
BACKGROUND: Glioblastoma (GBM) remains a lethal brain cancer with median survival of 12-15 months, hindered by pronounced heterogeneity. Integrating histopathological, molecular, and microenvironmental data is critical f...
BACKGROUND: Glioblastoma (GBM) remains a lethal brain cancer with median survival of 12-15 months, hindered by pronounced heterogeneity. Integrating histopathological, molecular, and microenvironmental data is critical for improving outcomes. METHODS: Pathological features from TCGA-GBM whole-slide images were combined with bulk RNA-seq (pan-apoptosis genes), scRNA-seq (monocytes), and spatial transcriptomics. A machine learning model (Lasso + plsRcox) was developed using 60 % training and 40 % validation data. RESULTS: The prognostic model achieved C-indices of 0.75 (training) and 0.616 (validation). High-risk patients had shorter median survival (14 vs. 28 months; HR = 3.87, P = 0.001). BCL2A1 was identified as a key risk gene (r = 0.42 with risk score) and correlated with poor survival (11 vs. 26 months, P = 0.004) and abnormal nuclear morphology. scRNA-seq revealed BCL2A1+ monocytes (12.3 % of cells) with high stemness and enriched angiogenesis pathways. Spatial analysis showed these monocytes localize at the invasive front (21.4 %) near endothelial cells, promoting VEGF signaling. CONCLUSION: Integration of computational pathology and multi-transcriptomic data identified BCL2A1+ monocytes as drivers of angiogenesis and progression. This approach offers a prognostic tool and potential therapeutic targets for GBM.
EWSR1-and FUS-rearranged acute leukemias: Clinicopathological and genomic characterization.
Nguyen VT, Zahid MF, Han L … +11 more , Botten GA, Slone T, Goldman S, Ghisoli M, Fuda F, Koduru P, Kumar K, Weinberg OK, Cantu MD, Xu J, Chen W
Hum Pathol · 2025 Dec · PMID 41230857 · Publisher ↗
BACKGROUND: EWSR1::FEV and FUS::FEV fusions, belonging to the FET-ETS family gene fusions, are extremely rare in acute leukemias. Our study aims to characterize the clinicopathologic and genomic profiles of this rare ent...
BACKGROUND: EWSR1::FEV and FUS::FEV fusions, belonging to the FET-ETS family gene fusions, are extremely rare in acute leukemias. Our study aims to characterize the clinicopathologic and genomic profiles of this rare entity. METHODS: Clinical, morphologic, immunophenotypic, cytogenetic, and genomic features were analyzed in three patients with leukemia harboring these rare fusions. RESULTS: These leukemias were characterized by a female predominance with variable age of onset (a median age of 27 years), heterogenous leukemia phenotypes [acute myeloid leukemia/AML with EWSR1::FEV (n = 1) and mixed phenotype acute leukemia/MPAL (n = 2) with B/myeloid (EWSR1::FEV) and T/myeloid (FUS::FEV) phenotype], additional cytogenetic abnormalities (3/3) in addition to cryptic (2) or non-cryptic (1) fusion related chromosomal translocations, and co-occurring gene mutations in signaling pathway (PTPN11, 2/3) and cohesin complex (STAG2, 1/3). The prognosis of EWSR1::FEV and FUS::FEV leukemias is largely unknown; all three patients were alive with a median follow-up of 46 months, but one patient relapsed. CONCLUSION: This is the first case series study, including the first case description of FUS::FEV leukemia, to characterize clinicopathologic and genomic features of leukemias with EWSR1::FEV and FUS::FEV and provide insights into the leukemogenesis of this rare entity. Furthermore, we recommend inclusion of FET-ETS fusions in future acute leukemia classification schemes.
Cytopathologic and histopathologic characteristics of SMARCB1 deficient neoplasm and correlation with molecular and immunohistochemical findings.
Sanchez SI, Adams C, Illei P … +4 more , Ali SZ, Rooper L, Lih TM, Li QK
Hum Pathol · 2025 Dec · PMID 41224025 · Publisher ↗
INTRODUCTION: SMARCB1 deficient neoplasm is an aggressive and heterogeneous group of neoplasms. The morphology of the neoplasm is highly variable. Recent clinical trials show that targeted therapy with EZH2 inhibitor taz...
INTRODUCTION: SMARCB1 deficient neoplasm is an aggressive and heterogeneous group of neoplasms. The morphology of the neoplasm is highly variable. Recent clinical trials show that targeted therapy with EZH2 inhibitor tazemetostat can improve patients' survival. Thus, it is important to recognize the entity for appropriate clinical management. MATERIAL AND METHODS: The pathology archive was searched over 10-year period for cases with diagnosis of SMARCB1 deficient neoplasm and aberrant expression of SMARCB1 (INI-1). Cyto- and histomorphology, immunohistochemistry (IHC) and molecular findings were characterized. RESULTS: 54 cases with complete loss of SMARCB1 (INI-1) on IHC staining were identified, including 5 serous fluids, 10 fine needle aspirations (FNA), 18 biopsy cores and 21 surgical resections. The median age of patients was 35.8 years, ranging from 14 days to 87 years. The female to male ratio was 1.07:1.00. The most involved anatomic sites in descending order were: head and neck (n = 14), CNS (n = 11), lymph node (n = 8), thorax/lung (n = 6), liver (n = 5) and others (n = 10). In addition to published morphology patterns, characteristic cytomorphology included phenotypic features of poorly differentiated carcinoma with pleomorphic tumor cells, basaloid, rhabdoid or epithelioid sarcomas. These tumors had frequently positive cytokeratin stains. Complex genetic abnormalities were identified, including aberrant SMARCB1/INI-1, PIK3C2B, RAF, MAP3K14, FBXO11 and others. 10 cases of partial loss of SMARCB1 (/INI-1) were also included. CONCLUSIONS: The ancillary testing of SMARCB1 (INI-1) should be considered in a subset of patients whose tumor demonstrates bizarre cytomorphology, especially in poorly differentiated or markedly pleomorphic tumors. The cytological recognition is critical for appropriate management.
Histomorphological and molecular spectrum of ciliated muconodular papillary tumors with implication for malignant potential: Insights from a literature review and series report.
Wu J, Lin X, Li D … +5 more , Tong G, Quan S, Jiang D, He P, Fu X
Hum Pathol · 2025 Dec · PMID 41224024 · Publisher ↗
Although the lung ciliated muconodular papillary tumor (CMPT) is defined as a benign tumor by the 5th WHO classification, recent studies have shown that its morphology and genetic alteration may indicate it has undetermi...
Although the lung ciliated muconodular papillary tumor (CMPT) is defined as a benign tumor by the 5th WHO classification, recent studies have shown that its morphology and genetic alteration may indicate it has undetermined malignant potential. In clinical pathology, CMPT is easily misdiagnosed as mucinous adenocarcinoma; meanwhile, it has been reported to harbor multiple types of gene aberrant. To further study the relation between histomorphology and genetic alterations in CMPT, we collected 15 CMPT patients' surgical samples with analysis of histomorphology, immunohistochemistry (IHC), and gene status. We found CMPT features a double-layered structure with papillary, glandular, and micropapillary formations. IHC typically shows basal cells with p40/p63/CK5/6 expression and TTF-1 immunoreactivity in both luminal and basal cells. Next-generation sequencing showed that two cases harbored anaplastic lymphoma kinase (ALK) rearrangements. A new type of COX7C::ALK rearrangement is firstly revealed in one of our collected cases. One case is overexpressed BRAF (V600E) protein. We further summarized the histomorphology and molecular features of nine previous studies, finding that despite most cases follow an indolent clinical course with no recurrence or metastasis after surgical resection, rare instances of malignant transformation have been reported, underscoring the need for careful pathological evaluation and genetic testing. Our study highlights the importance of recognizing CMPT's distinct histological and molecular features and considering targeted therapies, such as ALK inhibitors, in cases with malignant progression and ALK rearrangements.
Myoepithelial and epithelial-myoepithelial clinically advanced and metastatic carcinomas of salivary gland: A comparative comprehensive genomic profiling study.
Hardy CSC, Lin KM, Pavlick D … +3 more , Huang RSP, Ross JS, Zaccarini DJ
Hum Pathol · 2025 Dec · PMID 41177178 · Publisher ↗
Myoepithelial carcinoma (MECA) and Epithelial-myoepithelial carcinomas (EMC) are rare salivary gland carcinomas (SGCA) that may arise de novo or in the background of a prior pleomorphic adenoma (carcinoma ex pleomorphic...
Myoepithelial carcinoma (MECA) and Epithelial-myoepithelial carcinomas (EMC) are rare salivary gland carcinomas (SGCA) that may arise de novo or in the background of a prior pleomorphic adenoma (carcinoma ex pleomorphic adenoma CAEXPLA). Despite being clinically distinct entities, MECA and EMC share morphologic similarities which can make them difficult to distinguish on histologic examination. Further, there is a currently an evolving understanding of the characteristic genomic and immunohistochemical biomarkers for these tumors. In this study, we characterize the genomic profiles of a relatively large cohort of clinically advanced MECA (n = 52) and EMC (n = 26) cohorts. Both tumor types demonstrated single copy number changes, short variant mutations, and gene rearrangements. The most common alterations in MECA were in CDKN2A and CDKN2B. In EMC, HRAS mutations were the most common alteration, while both PIK3CA and MDM2 mutations were also common. Although not significantly different, CDKN2A and CDKN2B alterations were more frequent in MECA, while PIK3CA alterations were more frequent in EMC. Overall, EMC and MECA had both overlapping and unique molecular alterations that have potential for targeted therapies.
HPV-related multiphenotypic sinonasal carcinoma: Clinicopathologic and immunohistochemical characterization of 3 cases with comprehensive literature review and emphasis on differential diagnosis.
Speakman GC, Wakely PE, Argyris PP
Hum Pathol · 2026 Apr · PMID 41173400 · Publisher ↗
HPV-related multiphenotypic sinonasal carcinoma (HMSC) represents a rare malignancy exhibiting surface and salivary gland-derived properties, and a strong association with high-risk HPV. We present the clinicopathologic...
HPV-related multiphenotypic sinonasal carcinoma (HMSC) represents a rare malignancy exhibiting surface and salivary gland-derived properties, and a strong association with high-risk HPV. We present the clinicopathologic and immunohistochemical characteristics of 3 examples of HMSC involving the nasal cavity (M:F = 2:1, age median = 66 years; range = 51-75 years). Histopathologically, all 3 HMSCs exhibited infiltrative lobules and nests of basaloid cells with focal cribriform and microcystic configuration. Neoplastic cells featured high N:C ratio with round-to-ovoid, vesicular or angulated nuclei, scant cytoplasm, and numerous mitoses. Pleomorphism, comedonecrosis and focal squamous differentiation were noted. High-grade surface dysplasia was easily identified in one HMSC. Surrounding stroma varied from myxohyaline-to-densely fibrous. By immunohistochemistry, lesional cells were positive for epithelial markers as well as SMA, calponin, SOX10, and S100. All HMSCs showed strong, diffuse p16 staining and harbored high-risk HPV by DNA ISH. A total of 124 previously reported HMSC cases were identified (M:F = 1:1.26, mean age = 56.6 years; range = 28-90 years) with 83.7 % involving the nasal cavity with or without extension into adjacent anatomic structures. Approximately 60 % of HMSCs clinically presented as T1/T2 lesions with lymph node metastases identified in 15.3 % at diagnosis. HPV33 was detected in 75 % of HMSCs. Locoregional recurrences occurred in 38.7 % of cases but 85.3 % of patients were alive after a mean follow-up period of 29 months (range = 1-256). CONCLUSION: Diagnosis of HMSC may be challenging, particularly in small biopsy specimens, owing to its relative rarity and significant histopathologic and immunophenotypic similarities to other sinonasal malignancies. Despite its high-grade histomorphologic features, prognosis for HMSC is considered favorable.
Recent updates and debates on basal crypt dysplasia, serrated epithelial change, and p53 immunostaining in inflammatory bowel disease.
Bahceci D, Choi WT
Hum Pathol · 2026 Mar · PMID 41159918 · Publisher ↗
Early detection of dysplasia, followed by endoscopic or surgical resection, remains the cornerstone of colorectal cancer (CRC) prevention in patients with inflammatory bowel disease (IBD). Most dysplastic lesions in IBD...
Early detection of dysplasia, followed by endoscopic or surgical resection, remains the cornerstone of colorectal cancer (CRC) prevention in patients with inflammatory bowel disease (IBD). Most dysplastic lesions in IBD resemble sporadic adenomas and pose little diagnostic difficulty, but several distinct morphologic patterns (collectively termed "nonconventional dysplasia") have recently been described. Among these, basal crypt dysplasia presents particular diagnostic challenges, as it is characterized by mild atypia confined to the crypt bases without surface involvement, contrasting with the traditional expectation that dysplasia involves both crypts and surface epithelium. Identification of basal crypt dysplasia is crucial because it typically appears as invisible or flat dysplasia, is frequently associated with synchronous and/or metachronous neoplasia, and is considered a high-risk marker for subsequent advanced neoplasia. Serrated epithelial change (SEC) represents another controversial entity in IBD. Often defined as hyperplastic polyp-like mucosal changes detected on random or non-targeted colon biopsies, SEC has been linked to synchronous/metachronous neoplasia, including invisible/flat dysplasia, nonconventional dysplasia, and advanced neoplasia, which is often found adjacent to or within the same colonic segment as SEC. Ancillary studies, such as p53 immunohistochemistry, can assist in diagnosing dysplasia, including basal crypt dysplasia and subtle dysplasia associated with SEC. This review summarizes the morphologic criteria, clinicopathologic features, and recommended reporting practices for basal crypt dysplasia and SEC, and highlights the diagnostic utility of p53 immunohistochemistry in identifying dysplasia.
Porto-sinusoidal vascular disorder (PSVD): Survey-based analysis of the usage and drawbacks of this newly proposed terminology.
Albayrak NE, Jain D, Torbenson M … +18 more , Bellizzi AM, Chatterjee D, Fiel MI, Gill RM, Gonzalez RS, Guindi M, Hart JA, Kleiner DE, Kim GE, Naini BV, Pai RK, Ranguelov RD, Shafizadeh N, Stevenson HL, Wang H, Ward SC, Wen KW, Kakar S
Hum Pathol · 2025 Dec · PMID 41135708 · Publisher ↗
The term "porto-sinusoidal vascular disorder" (PSVD) has been proposed for morphologic findings commonly seen in non-cirrhotic portal hypertension (PH) but can also be observed without clinically evident PH. To assess cu...
The term "porto-sinusoidal vascular disorder" (PSVD) has been proposed for morphologic findings commonly seen in non-cirrhotic portal hypertension (PH) but can also be observed without clinically evident PH. To assess current practice patterns among U.S. liver pathologists, a 16-question survey was distributed along with two publications outlining the PSVD proposal. Nearly all respondents (n = 22, 95.75 %) were familiar with the PSVD terminology, but only 5 (21.75 %) used it as a final diagnosis, while 11 (47.75 %) had never used the term. In the presence of PH, 17 (74 %) preferred "obliterative portal venopathy", while only 1 (4.25 %) used PSVD. Notably, fewer than 5 % used PSVD in the context of nodular regenerative hyperplasia or incomplete septal fibrosis, although these have been proposed as part of the diagnostic criteria. A significant majority (n = 18, 78.25 %) disagreed with the proposed PSVD terminology, citing the following key concerns: labelling it as a disease entity is misleading (n = 20, 87 %), proposed diagnostic criteria are not supported by data (n = 15, 65.25 %), and labelling a process as PSVD does not seem accurate when only portal vein (n = 12, 52.25 %) or sinusoidal (n = 16, 69.5 %) changes are present. Over half (n = 13, 56.5 %) found it arbitrary to exclude certain vascular diseases from definition of PSVD (e.g., hepatic vein obstruction, sarcoidosis, schistosomiasis), given frequent histologic overlap across pre-hepatic, sinusoidal and post-hepatic etiologies of PH. In conclusion, "PSVD" terminology has not been adopted as a diagnostic term by most US liver pathologists who participated in this survey, emphasizing the need for a clearer, evidence-based terminology to describe these vascular changes.
Histological characteristics of primary biliary cholangitis in patients with incomplete responses to ursodeoxycholic acid.
Harada K, Kakuda Y, Tanaka A … +15 more , Abe M, Namisaki T, Shimoda S, Zeniya M, Ido A, Yoshiji H, Ohira H, Umeda A, Kamiya Y, Higashine Y, Hojo S, Imai T, Kawano T, Tsubouchi H, Nakanuma Y
Hum Pathol · 2025 Dec · PMID 41135707 · Publisher ↗
BACKGROUND AND AIMS: Ursodeoxycholic acid (UDCA) is the standard first-line therapy for primary biliary cholangitis (PBC), yet approximately 30-40 % of patients exhibit incomplete biochemical responses. This study aimed...
BACKGROUND AND AIMS: Ursodeoxycholic acid (UDCA) is the standard first-line therapy for primary biliary cholangitis (PBC), yet approximately 30-40 % of patients exhibit incomplete biochemical responses. This study aimed to identify the histopathological features associated with incomplete UDCA response by comparing liver biopsy specimens from these patients with those from treatment-naïve individuals, using the Nakanuma classification. METHODS: We analyzed liver biopsy samples from 33 UDCA-incomplete responders and 152 treatment-naïve patients with PBC. Histological staging and grading were performed using the Nakanuma classification, which evaluates fibrosis, bile duct loss, and orcein-positive granule deposition for staging. Chronic cholangitis activity (CA) and hepatitis activity (HA) were categorized using a four-point scale. RESULTS: Patients with incomplete UDCA responses showed significantly higher scores for bile duct loss, orcein-positive granule deposition, and HA compared with treatment-naïve patients, regardless of fibrosis stage. Notably, 82 % of incomplete responders were classified as stage 4 (advanced disease) by the Nakanuma system, whereas classical systems such as Scheuer and Ludwig frequently underestimated disease severity. Approximately half of the incomplete responders lacked histologically detectable bile ducts (CA0), indicating extensive ductopenia. CONCLUSIONS: Liver histology in patients with incomplete responses to UDCA is characterized predominantly by advanced disease features, including severe hepatitis, bile duct loss, and orcein-positive granule deposition, rather than by fibrosis alone. The Nakanuma classification offers a more accurate evaluation of disease severity compared to conventional classifications. These histological findings provide valuable insights for interpreting the outcomes of recent clinical trials of second-line therapies for PBC, particularly those targeting immune-mediated mechanisms.
Loss of androgen receptor expression is associated with aggressive tumor features and reduced survival in breast cancer patients.
Stefansson IM, Knutsvik G, Arnes J … +3 more , Collett K, Askeland C, Akslen LA
Hum Pathol · 2025 Nov · PMID 41135706 · Publisher ↗
Androgen receptor (AR) is reported to be expressed in the majority of breast cancers (BC) with different expression rates across breast cancer subtypes. AR might influence cell proliferation, DNA damage repair, apoptosis...
Androgen receptor (AR) is reported to be expressed in the majority of breast cancers (BC) with different expression rates across breast cancer subtypes. AR might influence cell proliferation, DNA damage repair, apoptosis, cellular migration and metastasis. The prognostic role of AR varies significantly across breast cancer subtypes. Here, we studied the expression pattern and prognostic relevance of AR in BC, with special focus on molecular stratification. We analyzed a large population-based cohort of breast carcinomas with long and complete follow up. AR expression was evaluated by immuno-histochemistry on tissue microarray slides. Loss of AR was significantly associated with features indicative of poor prognosis (larger tumor diameter, higher histologic grade, estrogen (ER) and progesterone hormone (PR) receptor negativity, elevated proliferation by Ki67, and expression of basal markers). Also, expression of AR was associated with lower proliferation by Ki67 regardless of ER-status. Regarding survival, loss of AR was significantly correlated with decreased breast cancer-specific survival in univariate analysis, both in the overall cohort and within the Luminal A and basal-like (CK5/6+) subgroups. In summary, AR expression emerged as a favorable prognostic factor in breast cancer, demonstrating independent prognostic significance within the basal-like (CK5/6+) subgroup.
Genitourinary mesenchymal neoplasms with tumor-defining genetic alterations: A clinicopathologic and molecular correlative study of 71 cases.
Chou CC, Lee JC, Wu PS … +13 more , Kao YC, Chang YM, Huang SC, Hsu YC, Pan CC, Hang JF, Liang PI, Tsai JW, Lee PH, Li CH, Hu CF, Yu SC, Huang HY
Hum Pathol · 2025 Dec · PMID 41130522 · Publisher ↗
Genitourinary mesenchymal neoplasms (GMNs) encompass diverse tumors with limited research on clinicopathologic and genetic characteristics across different organs and age groups. We investigated 71 GMNs with tumor-defini...
Genitourinary mesenchymal neoplasms (GMNs) encompass diverse tumors with limited research on clinicopathologic and genetic characteristics across different organs and age groups. We investigated 71 GMNs with tumor-defining genetic alterations (GMN-TDGA), categorizing tumors into spindle, round, or epithelioid based on predominant patterns. Pediatric GMN-TDGAs primarily involved the kidney, with six congenital mesoblastic nephromas showing spindly histology, including three cellular variants with ETV6::NTRK3 fusion, two classical variants with EGFR exon 18-25 duplications, and one novel TFG::NTRK3-positive case. Four renal clear cell sarcomas exhibited spindly and round cell patterns, harboring BCOR exon 15 duplications (n = 3) or YWHAE rearrangement (n = 1). Two renal EWSR1::FLI1-positive Ewing sarcomas (EWS) and one vesical ALK-rearranged inflammatory myofibroblastic tumor (IMT) occurred in children. In adults, recurrent histotypes included vesical IMTs (n = 15: 14 ALK-rearranged/positive, 1 RET-rearranged), renal synovial sarcomas (SS, n = 13: 7 poorly differentiated, 5 monophasic, 1 biphasic), renal EWS (n = 4, including one unreported EWSR1::ERG-positive atypical variant), renal sclerosing epithelioid fibrosarcomas (SEF, n = 3, all with EWSR1::CREB3L1), renal and vesical TFE3-rearranged PEComas (n = 3, 1 malignant), renal and preputial CIC-rearranged sarcomas (CICRS, n = 3), and multi-organ NAB2::STAT6-positive solitary fibrous tumors (SFTs, n = 10). Event-free survival varied significantly across adult GMN-TDGAs (P < 0.001), with CICRS (100 %), SS (61.5 %), and EWS (50 %) showing higher event rates compared to SEF (33.3 %), PEComa (33.3 %), SFT (20 %), and IMT (0 %). Ultra-rare GMN-TDGAs included a PTCH1::GLI1-positive renal epithelioid mesenchymal neoplasm, a BRAF-deleted renal spindle cell tumor, and a MYOD1-mutated prostatic spindle cell rhabdomyosarcoma. Conclusively, molecular profiling highlights the histologic and genetic diversity of GMNs, supporting challenging diagnoses and informing personalized therapies.
Dual amyloidosis: A clinicopathologic and proteomic analysis of 111 patients.
Dalland JC, Dasari S, Theis JD … +10 more , Howard MT, Vrana JA, Dao LN, Chiu A, Rech KL, Larson DP, Nasr SH, Grogan M, Dispenzieri A, McPhail ED
Hum Pathol · 2025 Dec · PMID 41101392 · Publisher ↗
BACKGROUND: Patients with two different amyloid types are rare. It is critical to identify all types of amyloid in a patient as amyloid therapies vary dramatically depending on the specific precursor protein. OBJECTIVE:...
BACKGROUND: Patients with two different amyloid types are rare. It is critical to identify all types of amyloid in a patient as amyloid therapies vary dramatically depending on the specific precursor protein. OBJECTIVE: To analyze the clinicopathologic and proteomic features in patients with two types of amyloid. METHODS: We queried our reference laboratory database of 51,309 amyloid specimens from all anatomic sites typed by mass spectrometry-based proteomics (LC-MS/MS) for patients diagnosed with two different amyloid types. Demographic data (patient age, sex, and anatomic site), mass spectrometry proteomic features, and clinical history, when available, were reviewed. RESULTS: We identified 111 patients with two amyloid types: 83 male (75 %), 28 female (25 %). The median age at initial diagnosis was 78 years (range 45-96 years). 56 patients (50 %) had cardiac involvement. The two amyloid types were present either in the same anatomic compartment within a single specimen (48 patients, 43 %), in different anatomic compartments within a single specimen (43 patients, 39 %), or in two different anatomic locations (20 patients, 18 %). The most common combination was AL plus ATTR (69 patients, 62 %), which occurred in 68 % of patients with cardiac involvement. CONCLUSION: It is crucial to identify all amyloid types in all cases, including careful morphologic review to evaluate for distinct areas with different distribution, and consider the possibility of a second amyloid type when the clinical findings are not explained by the initial amyloid type. In some patients, this may require biopsy from a second anatomic site.
Clinicopathologic and radio-genomic insights into hepatic epithelioid hemangioma: An illustrated review.
Brown E, Schoedel K, Barwad A … +3 more , Furlan A, Zhang PJL, Khurram NA
Hum Pathol · 2026 Apr · PMID 41101391 · Publisher ↗
Epithelioid hemangioma (EH) of the liver is an exceptionally rare vascular neoplasm, with only one pathology-confirmed case previously reported. We describe the second such instance, and the first to incorporate detailed...
Epithelioid hemangioma (EH) of the liver is an exceptionally rare vascular neoplasm, with only one pathology-confirmed case previously reported. We describe the second such instance, and the first to incorporate detailed radiologic characterization and RNA sequencing. A 68-year-old man presented with hepatic masses, portal lymphadenopathy, and a lytic pubic lesion initially concerning for metastatic carcinoma. Liver biopsy demonstrated a vascular proliferation of hobnail endothelial cells within myxoid stroma, with associated hemorrhage, hemosiderin, and eosinophil-rich inflammation. Immunohistochemistry showed diffuse ERG and focal FOSB expression, weak TFE3 staining, and a low proliferative index, while CAMTA1 and HMB-45 were negative. Imaging revealed multifocal, mildly FDG-avid hepatic lesions with nodal and osseous involvement. Whole-transcriptome sequencing was negative for pathogenic fusions. These findings confirmed a diagnosis of EH, illustrating its capacity to mimic malignancy. This case highlights the diagnostic value of integrating radio-genomic analysis and underscores the need for comprehensive workup to distinguish EH from epithelioid hemangioendothelioma, angiosarcoma, and Kaposi sarcoma, entities with distinct prognostic and therapeutic implications.
HMGA2 and RB1 profiling in uterine and broad ligament leiomyomas with adipocytic differentiation: An immunohistochemical and fluorescence in situ hybridization study of 14 conventional and variant lipoleiomyomas.
Schoolmeester JK, Hodge JC, Swanson AA
Hum Pathol · 2026 Apr · PMID 41086997 · Publisher ↗
Abstract loading — click title to view on PubMed.
Clinicopathological significance and prognostic impact of perineural invasion in intrahepatic cholangiocarcinoma: a single-center, retrospective study.
Kami S, Kojima M, Kudo M … +7 more , Kamiya H, Une N, Sasahara Y, Sugimoto M, Kobayashi S, Konishi M, Gotohda N
Hum Pathol · 2025 Dec · PMID 41077256 · Publisher ↗
Perineural invasion (PNI) is a recognized prognostic factor in various malignancies, but its clinical relevance in intrahepatic cholangiocarcinoma (ICC) remains unclear. This retrospective study aimed to evaluate the imp...
Perineural invasion (PNI) is a recognized prognostic factor in various malignancies, but its clinical relevance in intrahepatic cholangiocarcinoma (ICC) remains unclear. This retrospective study aimed to evaluate the impact of PNI on clinical outcomes in patients with ICC who underwent liver resection between April 2009 and December 2023. Patients who underwent lymphadenectomy or extrahepatic bile duct resection were excluded. PNI was defined as tumor invasion or spread along peripheral nerve bundles within the Glissonean sheath. A total of 52 patients were included, with 26 (50.0 %) identified as PNI-positive. Compared to PNI-negative patients, those with PNI had a significantly worse overall survival (OS) (5-year OS: 50.0 % vs. 85.8 %, P = 0.036) and recurrence-free survival (RFS) (5-year RFS: 14.5 % vs. 46.8 %, P = 0.010). Univariate analysis identified PNI as a risk factor for a poor OS, although this was not significant in multivariate analysis. Both PNI and portal vein invasion were independent predictors of poor RFS. Subgroup analysis revealed that postoperative adjuvant therapy significantly improved RFS in PNI-positive patients (3-year RFS: 53.6 % vs. 11.1 %, P = 0.036), while no such benefit was observed in PNI-negative patients. These findings suggest that PNI is a clinically relevant prognostic marker in ICC and may help identify patients who could benefit from postoperative adjuvant therapy. Routine assessment of PNI should be incorporated into pathological evaluations following ICC resection.
Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in the adolescent and young adult population: A pediatric center experience.
Bedell M, Skaugen JM, Nikiforov Y … +5 more , Reyes-Múgica M, Salgado CM, Simons JP, Wang Q, Gestrich CK
Hum Pathol · 2025 Nov · PMID 41052728 · Publisher ↗
Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a well-demarcated tumor with follicular growth pattern and papillary thyroid carcinoma-like nuclear features. Only rare reports exi...
Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a well-demarcated tumor with follicular growth pattern and papillary thyroid carcinoma-like nuclear features. Only rare reports exist in the literature describing the clinicopathologic features and incidence of NIFTP in the adolescent and young adult age group. The aim of this study was to address these gaps in the literature and characterize NIFTPs arising in this population. We retrieved all cases of NIFTP diagnosed from 2017 to 2023 at the UPMC Children's Hospital of Pittsburgh. Clinical information, cytologic and histologic features, and molecular testing results were reviewed, alongside a literature review. We identified 10 cases of NIFTP in 8 females and 2 males with an age distribution of 15-26 years old out of 152 fine needle aspirates (6.6%). All nodules were classified as low to moderate malignant risk on sonography (TI-RADS 3 and 4: n = 5 each). Cytologic reporting varied with Bethesda III (n = 6) and IV (n = 2) predominately. All cases exhibited RAS (n = 7) or RAS-like (n = 3) alterations on molecular testing. No disease recurrence was noted on follow-up (13-86 months, median 39 months). We describe the clinicopathologic and molecular features of NIFTP in our adolescent and young adult cohort and compare them with those published in the literature. We demonstrate that NIFTP is rare in young children and largely restricted to adolescents and young adults. Clinicopathologic features and behavior show marked resemblance to those of adult-diagnosed NIFTP and thus may benefit from similar conservative treatment modalities.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe