Modern Pathology最新文献

Obliterative portal venopathy (OPV) is a cause of noncirrhotic portal hypertension and the diagnosis is challenging as the features are heterogenerous, subtle, and may be mistaken as "normal". We sought to compare OPV cases (n=72; 326 total portal tracts [PT]) with two control groups: control group 1 normal liver (n=40; 192 PTs) and control group 2 comprised of liver biopsies with chronic liver disease with OPV features (n = 40; 200 PTs). Morphometry was applied to determine the overall PT area & the luminal area of dystrophic portal veins (PVs). The frequency of absent native PVs was determined. Using trichrome-stained slides, approximately 5 PTs were randomly selected for morphometry utilizing the Philips IntelliSite Pathology Solution 3.3. Clinical data were extracted from electronic health records. Of the 326 PTs in the OPV cases, phlebosclerosis was found in 31.6%, densely fibrotic PTs in 12.7%, dystrophic PVs in 31.4%, and absent native PVs in 44.5%. When comparing the OPV group with control group 1, dystrophic PVs, absent native PVs, phlebosclerosis, fibrotic PTs, greater luminal area of dystrophic PV and higher ratio of dystrophic PV area to PT area were more frequently found in the OPV group. No significant difference in overall PT area was found. When comparing control group 2 with OPV cases, densely fibrotic PTs were more frequent as compared to OPV cases. This study shows that absent native PVs are the most frequent feature in OPV. Other features that are less frequent but still significantly different from normal liver include dystrophic PVs, greater luminal area of dystrophic PVs, phlebosclerosis, and PT fibrosis. Except for densely fibrotic PTs in control group 2, all other features showed similar frequency as OPV. Pathologists should be aware that OPV features may be present in liver biopsies from both normal and chronic liver disease.

RET-fused Spitz neoplasms are rare and poorly characterized. We describe clinical, histologic and molecular findings of 31 Spitz neoplasms with RET fusion diagnosed as 16 Spitz nevus (SN), 13 atypical Spitz tumors (AST) and 2 Spitz melanoma (SM). The lesions mainly occurred in children and young adults of both sexes with predilection for the extremities. Microscopically, there were mainly symmetrical compound melanocytic neoplasms with a dome-shaped/slightly raised silhouette predominantly composed of epithelioid, spindled and/or smaller nevoid melanocytes arranged in confluent nests. Dyscohesive melanocytes within the nests in the upper part of the lesions, prominent Kamino bodies, giant multinucleated melanocytes, variable pigmentation and increased vascularity with vascular ectasia were frequent features. RNA sequencing detected 9 different 5' (N-terminus) fusion partners, including KIF5B (n= 8), LMNA (n= 7), CCDC6 (n= 6), OPTN (n= 3), MYO5A (n= 2) and NCOA4, ERC1, MYH9, AGAP3 (n= 1). Of these, OPTN::RET and AGAP3::RET represent novel fusions, and 3 further 5' fusion partners, namely NCOA4, ERC1 and MYH9 have never been reported in Spitz tumors. Although as a whole group, the tumors showed a heterogenous histopathologic presentation, correlation of the morphological features and the 5' fusion partners demonstrated certain associations. Nevoid melanocytes were exclusively encountered in cases with KIF5B fusion partner. Neuroid-like appearances with intersecting fascicles of spindled cells typified both MYO5A-fused cases. Epithelioid melanocyte population dominated cases with LMNA and CCDC6 fusion partners. Transepidermal elimination/floating intraepidermal nests of pigmented both spindled and epithelioid melanocytes were observed in the OPTN subgroup. The remaining cases with less frequent 5' fusion partners manifested in general more atypical histopathologic features, including nuclear pleomorphism, high mitotic count, atypical mitoses and sheet-like growth pattern. Melanoma fluorescence in situ hybridization (FISH) Probe Kit targeting RREB1, MYC, CDKN2A, and CCND1, was negative for copy number variation in 4 cases tested, including 2 cases with complete p16 nuclear loss on immunohistochemistry. Array comparative genomic hybridization (aCGH) performed in 3 lesions detected numerous segmental chromosomal imbalances in 2 cases diagnosed SM. DNA and RNA sequencing detected several further genomic alterations, including POU2F3 overexpression in 3 highly pigmented lesions. Further studies are needed to confirm possible correlations between the microscopic features and a particular fusion partner (or additional genetic events) in RET-fused Spitz neoplasms.

The tumor-stroma ratio (TSR) has shown prognostic value in various cancers, including colon cancer. This retrospective, multicenter cohort study aimed to investigate the prognostic value of TSR in a screened stage II colon cancer population, both independently and in combination with tumor budding. The cohort included 497 patients who underwent surgical resection for stage II colon cancer. TSR was determined based on the procedures proposed by van Pelt et al., and tumor budding was evaluated according to the guidelines from the International Tumor Budding Consensus Conference (ITBCC). Our findings demonstrate that patients with tumors categorized as having a high proportion of stroma (> 50% stroma area) had a shorter 5-year time to recurrence (TTR) (HR = 1.95, p = 0.05), recurrence-free survival (RFS) (HR = 1.63, p = 0.02), and overall survival (OS) (HR = 1.05, p = 0.07) compared to patients with tumors categorized as having a low proportion of stroma (≤ 50% stroma area). The prognostic effect was specific to TSR determination at the deepest invasive front of the tumor and lost significance as the examination area expanded. Combining TSR and tumor budding further improved prognostic stratification. Tumors with high stromal content and high-grade budding exhibited a significantly more aggressive risk profile and poorer 5-year survival outcomes compared to patients with stroma-low and budding-low tumors (TTR; HR 4.47 p < 0.01, RFS; HR 2.71 p < 0.01, and OS; HR 2.20 p = 0.01). The study highlights the importance of standardized procedures for TSR assessment and suggests that evaluating both TSR and tumor budding could improve prognostic accuracy and aid in clinical decision-making.

The immune cell component of the tumor microenvironment is an important modulator of tumor progression. In patients with breast cancer, tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLS) represent core aspects of anti-tumor immunity, both increasingly recognized for clinical relevance. In this study, we evaluated immune-related histology features using whole slide H&E images of the TCGA-BRCA dataset (n=1035) and analyzed these distinct features relative to gene expression, PAM50 subtypes, and patient survival. H&E images were evaluated for TILs, plasma cells (PCs), high-endothelial venule associated lymphoid aggregates (HALA) and mature TLS. For HALA and TLS, location relative to tumor (non-tumor, peritumor, and intratumor) was determined. HER2-enriched (HER2E) and basal-like breast tumors exhibited the highest mean TILs and presence of PCs. HALA were present in 35.1% of cases and TLS in 6.5% of cases, also predominantly in HER2E and basal-like tumors. We derived gene expression signatures for 10 histologically defined immune features and tested their clinical significance using transcriptomic and survival data from the SCAN-B cohort. Signatures related to TILs, PCs, HALA/TLS, TLS, and specifically intratumor HALA and TLS were associated with better survival in HER2E and basal-like tumors. Peritumor HALA/TLS and non-tumor signatures were non-significant or associated with worse outcomes. Further, we compared the immune microenvironment of high-TIL (TILs > 10%) tumors from TCGA-BRCA by PAM50 subtype through supervised analyses of 200+ immune gene expression signatures, and unique immune features were identified for each subtype. In high-TIL luminal tumors, enriched immune signatures had little relation to prognosis. High-TIL HER2E and basal-like tumors had distinct immune signatures linked to improved survival, related to B and T cells, respectively. Overall, PAM50 subtypes of breast cancer exhibit distinct immune microenvironments, both histologically and molecularly. These differences in immune properties should be considered when developing precise treatment strategies to achieve optimal therapeutic efficacy for patients.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive cutaneous neoplasm driven by PDGFB or, rarely, PDGFD gene fusions. In some cases, DFSP progresses to a fibrosarcomatous form with metastatic potential, which may respond to tyrosine kinase inhibitors. This study explores whether comprehensive genomic profiling can reveal a broader clinical, anatomic, and pathologic spectrum for DFSP. Using the database of a large tumor sequencing reference lab, we identified tumors with PDGFB or PDGFD fusions and reviewed their histologic features, clinical information, exome sequencing data, and copy number alterations. Statistical significance was determined using Mann-Whitney U and Fisher's exact tests. A total of 59 cases with PDGFB or PDGFD fusions were identified: 55 COL1A1::PDGFB, 3 EMILIN2::PDGFD, and 1 COL1A2::PDGFB. The cohort included 51 primary tumors and 8 metastases (31 males, 28 females, median age 49 years). Primary tumors were mainly located in the skin and soft tissues, including 35 in the trunk, 9 in the head and neck, and 9 in the extremities. Additionally, 6 tumors arose in visceral organs (4 in the uterus, 1 in the cervix, and 1 in the lung). Among cases with slides available for pathology review, 21 were classified as classic DFSP and 31 as fibrosarcomatous DFSP (FS-DFSP). Notably, 21 tumors (36%) were initially misclassified, often due to atypical locations or histology. FS-DFSPs displayed a higher incidence of genomic alterations beyond PDGFB/PDGFD (75% vs. 23.8%, p=0.0005), including TERT promoter and NF1 variants, and demonstrated a significantly elevated tumor mutational burden (p=0.0037) and TERT mRNA expression (1.27 vs. 0.13 transcripts per million, p<0.0001) compared to classic DFSP. These findings underscore the value of genomic profiling for recognizing FS-DFSPs with unusual clinical or histologic features, particularly in guiding targeted therapy. Furthermore, by identifying molecular features specific to fibrosarcomatous variants, such as TERT reactivation, this study offers insights into potential molecular drivers of tumor progression in DFSP.

Due to its rarity, there is limited information on the clinicopathologic features of dysplasia in pediatric patients with inflammatory bowel disease (IBD). The existing surveillance guidelines for these patients do not include dysplasia as a potential risk factor for colorectal cancer (CRC), and there is no clear guidance on the optimal strategy for detecting dysplasia. As such, we analyzed the clinicopathologic features of 20 IBD patients who developed at least one instance of dysplasia (n = 56) before the age of 21 years. The results were then compared with data from a previously published adult cohort, which included 315 dysplastic lesions from 167 consecutive adult IBD patients. The study group consisted of 11 males and 9 females, with a mean age of 11 years at the time of IBD diagnosis. The mean age at the time of the first dysplasia diagnosis was 18 years for the study group compared to 54 years for the adult group. The study group had a lower incidence of ulcerative colitis (65% vs. 92% in the adult group, p < 0.001), but the proportion of patients with concurrent primary sclerosing cholangitis (PSC) was nearly double that of the adult group (25% vs. 13%, p = 0.129). Dysplasia in the study group was more likely to be nonconventional (38%, p = 0.047) and invisible or flat (50%, p < 0.001) compared to the adult group (25% and 24%, respectively). High-risk nonconventional dysplastic subtypes, including crypt dysplasia (13%, p = 0.016), goblet cell-deficient dysplasia (11%, p = 0.010), and hypermucinous dysplasia (9%, p = 0.009), were more common in the study group compared to the adult group (4%, 3%, and 2%, respectively). The mean duration from IBD diagnosis to the first dysplasia diagnosis was significantly shorter in the study group (8 years) than in the adult group (16 years) (p = 0.005). While dysplastic lesions in the adult group were more likely to present as high-grade dysplasia (HGD) at initial diagnosis (17% vs. 4% in the study group, p = 0.008), the rate of advanced neoplasia (HGD or CRC) on follow-up was similar between the two groups (26% in the adult group vs. 22% in the study group, p = 1.000). In conclusion, dysplasia in pediatric IBD patients is often associated with nonconventional features (including the high-risk subtypes), an invisible/flat appearance, concurrent PSC, and early development (within 8 years of IBD diagnosis).

Fibroepithelial lesions (FELs) of the breast constitute a heterogeneous group of biphasic tumours with variable morphology and behaviour. The classification of FELs is mainly based on a constellation of diagnostic criteria and intralesional heterogeneity is not uncommon. Therefore, reporting of FELs in a core needle biopsy (CNB) with limited tissue material can be challenging as not all the features may be represented for assessment. Distinction between classic fibroadenoma and representatively sampled phyllodes tumour is generally straightforward. However, cellular fibroadenoma, morphologically heterogeneous benign phyllodes tumour and myoid hamartoma can overlap histologically. Accurate grading of phyllodes tumour is also challenging on CNB and carries significant management implications. In this article, we provide an overview and propose a pragmatic approach to reporting FELs on CNB, particularly for lesions with overlapping features. Guidance using the UK/European 'B' classification of FELs, as well as free text descriptions of the various lesions, is also presented to help further management decision making.

Breast cancer (BC) presents significant molecular heterogeneity, complicating prognosis and treatment strategies. While molecular testing enhances our understanding of BC, high costs can limit accessibility in certain healthcare settings. This retrospective cohort study evaluates the prognostic value of Magee Equation 3 (ME3) and Residual Cancer Burden (RCB) in patients with HR-positive, HER2-negative BC treated at the Instituto do Câncer do Estado de São Paulo from January 2011 to January 2024. We included 203 women, with a mean age of 50.2 years, diagnosed with HR-positive, HER2-negative BC (stages I-III), who completed neoadjuvant chemotherapy (NAC) followed by surgery. ME3 scores were categorized as low (<18), intermediate (18-25), and high (>25), while RCB was classified into four groups (0, 1, 2, or 3). Associations between ME3 and RCB categories were analyzed using chi-square and Cochran-Mantel-Haenszel tests. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method with log-rank tests. Prior to NAC, 60.1% of patients had tumors >5 cm, 69.5% had positive lymph nodes, and 85.7% had invasive carcinoma of non-special type, with a mean Ki67 index of 35.5%. Analysis revealed that 22.2% of patients had ME3 > 25, 39.9% had ME3 18-25, and 37.9% had ME3 < 18. A significant inverse association was found between RCB and ME3 (p<0.0001). At a median follow-up of 91.4 months (range: 8-157 months), significant associations were noted for OS (log-rank p=0.0059) and DFS (log-rank p=0.0028) with ME3 categories; patients with low ME3 showed better outcomes. In patients with RCB-3, those with ME3 < 18 had a lower risk of recurrence compared to those with ME3 18-25 (HR: 4.70, 95% CI 2.00-11.02; p = 0.0004) and ME3 > 25 (HR: 5.18, 95% CI 1.85-14.15; p = 0.0017). Similarly, lower risks of death were observed for ME3 < 18 versus higher ME3 categories. In conclusion, ME3 significantly correlates with OS and DFS, suggesting it may serve as a valuable alternative to molecular assays in resource-limited settings. Combining ME3 with RCB enhances individualized risk stratification, providing a more precise prognostic assessment for patients with high RCB.