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Artificial intelligence (AI)-systems can improve cancer diagnosis, yet their development often relies on subjective histological features as ground truth for training. Here, we developed an AI-model applied to histological whole-slide images (WSIs) using CDH1 bi-allelic mutations, pathognomonic for invasive lobular carcinoma (ILC) in breast neoplasms, as ground truth. The model accurately predicted CDH1 bi-allelic mutations (accuracy=0.95) and diagnosed ILC (accuracy=0.96). A total of 74% of samples classified by the AI-model as having CDH1 bi-allelic mutations but lacking these alterations displayed alternative CDH1 inactivating mechanisms, including a deleterious CDH1 fusion gene and non-coding CDH1 genetic alterations. Analysis of internal and external validation cohorts demonstrated 0.95 and 0.89 accuracy for ILC diagnosis, respectively. The latent features of the AI-model correlated with human-explainable histopathologic features. Taken together, this study reports the construction of an AI-algorithm trained using a genetic rather than histologic ground truth that can robustly classify ILCs and uncover CDH1 inactivating mechanisms, providing the basis for orthogonal ground truth utilization for development of diagnostic AI-models applied to WSI.
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AIMS: Radial sclerosing lesions (RSLs) are benign breast lesions composed of glandular and epithelial proliferations with stellate architecture and fibro-elastotic stroma, which can mimic invasive carcinoma on imaging. Surgical management following a core biopsy diagnosis of RSLs remains controversial. METHODS AND RESULTS: We retrospectively identified core biopsies with RSLs without atypia who underwent subsequent surgical excision between 2015 and 2021. All core biopsy slides were reviewed to confirm the diagnosis. Imaging was reviewed to determine radiological-pathological concordance. An upgrade was defined as invasive carcinoma or ductal carcinoma in situ (DCIS) in the excision. The final cohort consisted of 130 core biopsies from 124 women (median age = 52 years, range = 27-76). The imaging modality was mammogram in 52 (40%) cases, MRI in 52 (40%) and ultrasound in 26 (20%). One hundred and seven (82%) core biopsies were vacuum-assisted and 23 (18%) were ultrasound-guided without vacuum assistance. The median lesion size on imaging was 9 mm (range = 2-41). Overall, two (1%) cases were upgraded at excision, including one microinvasive lobular carcinoma and one 2 mm focus of invasive mammary carcinoma with associated DCIS. In both cases, the upgraded foci of carcinoma were not closely associated with the biopsy site and were considered incidental upgrades. CONCLUSIONS: This study adds to the body of literature supporting observation, rather than routine excision of radial sclerosing lesions without atypia.
Subject(s)
Breast Neoplasms , Humans , Female , Middle Aged , Biopsy, Large-Core Needle/methods , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/diagnosis , Retrospective Studies , Aged , Adult , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Intraductal, Noninfiltrating/surgery , Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Breast/pathology , Breast/surgery , Breast/diagnostic imaging , Mammography/methods , Sclerosis/pathologyABSTRACT
Genetic alterations in the retinoblastoma susceptibility gene (RB1) are present in up to 40% of triple-negative breast cancers (BCs) and frequent in tumors with neuroendocrine differentiation, including small cell neuroendocrine carcinoma. Data on RB1 genetic alterations in estrogen receptor (ER)-positive BCs are scarce. In this study, we sought to define the morphologic, immunohistochemical, and genetic features of ER-positive BCs harboring somatic alterations in RB1, with emphasis on neuroendocrine differentiation. ER-positive BCs with pathogenic RB1 genetic alterations were identified in <1% of cases (N = 55) from a cohort of 6026 BCs previously subjected to targeted next-generation sequencing, including 23 primary BCs (pBCs) and 32 recurrent/metastatic BCs (mBCs). In cases where loss of heterozygosity of the wild-type RB1 allele could be assessed (93%, 51/55), most pBCs (82%, 18/22) and mBCs (90%, 26/29) exhibited biallelic RB1 inactivation, primarily through loss-of-function mutation and loss of heterozygosity (98%, 43/44). Upon histologic review, a subset of RB1-altered tumors exhibited neuroendocrine morphology (13%, 7/55), which correlated with expression of neuroendocrine markers (39%, 9/23) in both pBCs (27%, 3/11) and mBCs (50%, 6/12). Loss of Rb protein expression was observed in BCs with biallelic RB1 loss only, with similar frequency in pBCs (82%, 9/11) and mBCs (75%, 9/12). All cases with neuroendocrine marker expression (n = 9) and/or neuroendocrine morphology (n = 7) harbored biallelic genetic inactivation of RB1 and exhibited Rb loss of expression. TP53 (53%, 29/55) and PIK3CA (45%, 25/55) were the most frequently comutated genes across the cohort. Overall, these findings suggest that ER-positive BCs with biallelic RB1 genetic alterations frequently exhibit Rb protein loss, which correlates with neuroendocrine differentiation in select BCs. This study provides insights into the molecular and phenotypic heterogeneity of BCs with RB1 genetic inactivation, underscoring the need for further research into the potential clinical implications associated with these tumors.
Subject(s)
Breast Neoplasms , Carcinoma, Neuroendocrine , Receptors, Estrogen , Retinoblastoma Binding Proteins , Ubiquitin-Protein Ligases , Humans , Female , Retinoblastoma Binding Proteins/genetics , Receptors, Estrogen/metabolism , Receptors, Estrogen/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Carcinoma, Neuroendocrine/genetics , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/metabolism , Ubiquitin-Protein Ligases/genetics , Mutation , Cell Differentiation , Middle Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , Aged , Adult , Loss of HeterozygosityABSTRACT
PURPOSE: Several data sets have demonstrated a correlation between lymphovascular invasion (LVI) and locoregional recurrence (LRR). Whether the observation of "extensive LVI" is a further and incremental determinant of LRR risk is unknown. We describe clinical outcomes in women with invasive breast cancer stratified by (1) absence of LVI (neg), (2) LVI focal or suspicious (FS-LVI), (3) usual (nonextensive) LVI (LVI), and (4) extensive LVI (E-LVI). METHODS AND MATERIALS: Between December 2009 and August 2021, 8837 patients with early-stage breast cancer were treated with curative intent and were evaluable. Clinical-pathologic details were abstracted by retrospective review. The description of LVI was abstracted from pathology reports. Recurrence and survival outcomes were compared based on the extent of LVI. A matched propensity score analysis compared outcomes between patients with LVI versus E-LVI. RESULTS: Of the 8837 patients studied, 5584 were negative, 461 had FS-LVI, 2315 had LVI, and 477 had E-LVI. Patients with E-LVI had an adverse risk profile compared with the other groups. The 5- and 10-year LRR cumulative incidence estimates in patients with E-LVI were 9.6% (95% CI, 7.1-13) and 13% (95% CI, 10-17), respectively, which were significantly higher than those observed in the usual LVI group (6.8% [5.7-7.9] and 10% [8.8-12], respectively). A statistically significant difference in LRR was demonstrated in univariable (HR, 1.4; 95% CI, 1.03-1.89; P = .029) and multivariable regression analysis (HR, 1.62; 95% CI, 1.15-2.27; P = .005) compared with nonextensive LVI. In an alternative approach, we performed a 2:1 propensity score matching analysis comparing patients with LVI to those with E-LVI. The hazard ratio for LRR (HR, 1.47; CI 1.02-2.14; P = .041) was suggestive of a higher risk associated with E-LVI. CONCLUSIONS: Our work suggests that patients with E-LVI are at a higher risk for LRR than those with usual LVI. For patients who are borderline candidates for regional nodal irradiation or post-mastectomy radiation therapy, the finding of E-LVI might be decisive in favor of intensified treatment.
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Local cryoablation can engender systemic immune activation/anticancer responses in tumors otherwise resistant to immune checkpoint blockade (ICB). We evaluated the safety/tolerability of preoperative cryoablation plus ipilimumab and nivolumab in 5 early-stage/resectable breast cancers. The primary endpoint was met when all 5 patients underwent standard-of-care primary breast surgery undelayedly. Three patients developed transient hyperthyroidism; one developed grade 4 liver toxicity (resolved with supportive management). We compared this strategy with cryoablation and/or ipilimumab. Dual ICB plus cryoablation induced higher expression of T cell activation markers and serum Th1 cytokines and reduced immunosuppressive serum CD4+PD-1hi T cells, improving effector-to-suppressor T cell ratio. After dual ICB and before cryoablation, T cell receptor sequencing of 4 patients showed increased T cell clonality. In this small subset of patients, we provide preliminary evidence that preoperative cryoablation plus ipilimumab and nivolumab is feasible, inducing systemic adaptive immune activation potentially more robust than cryoablation with/without ipilimumab.
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CDH1 (E-cadherin) bi-allelic inactivation is the hallmark alteration of breast invasive lobular carcinoma (ILC), resulting in its discohesive phenotype. A subset of ILCs, however, lack CDH1 genetic/epigenetic inactivation, and their genetic underpinning is unknown. Through clinical targeted sequencing data reanalysis of 364 primary ILCs, we identified 25 ILCs lacking CDH1 bi-allelic genetic alterations. CDH1 promoter methylation was frequent (63%) in these cases. Targeted sequencing reanalysis revealed 3 ILCs harboring AXIN2 deleterious fusions (n = 2) or loss-of-function mutation (n = 1). Whole-genome sequencing of 3 cases lacking bi-allelic CDH1 genetic/epigenetic inactivation confirmed the AXIN2 mutation and no other cell-cell adhesion genetic alterations but revealed a new CTNND1 (p120) deleterious fusion. AXIN2 knock-out in MCF7 cells resulted in lobular-like features, including increased cellular migration and resistance to anoikis. Taken together, ILCs lacking CDH1 genetic/epigenetic alterations are driven by inactivating alterations in other cell adhesion genes (CTNND1 or AXIN2), endorsing a convergent phenotype in ILC.
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PURPOSE: The 21-gene recurrence score (RS) assay predicts the recurrence risk and magnitude of chemotherapy benefit in patients with invasive breast cancer (BC). This study examined low-grade tumors yielding a high-risk RS and their outcomes.Kindly check the edit made in the article titleOk METHODS: We compared patients with grade 1 BC and a high-risk RS to those with low-risk RS. Histologic sections were reviewed and features reported to elevate the RS were noted, mainly biopsy cavity and reactive stromal changes (BXC). RESULTS: A total of 54 patients had high-risk RS (median RS of 28, range 26-36). On review, BXC were seen in all cases. Thirty BCs in this group also had low to negative PR. Treatment regimens included: chemoendocrine therapy (63%), endocrine therapy alone (31%) and no adjuvant therapy (6%). There were no additional breast cancer events over a median follow-up of 54.0 months (range 6.2 to 145.3). A total of 108 patients had low-risk RS (median RS of 7, range 0-9). BXC were seen in 47% of cases and none were PR negative. One patient had a recurrence at 64.8 months while the rest had no additional events over a median of 68.1 months (2.4 to 100). CONCLUSION: We provide further evidence that reactive stromal changes and/or low-PR scores enhance the elevation of the RS. A high-RS result in low grade, PR-positive BC may not reflect actual risk and any suspected discrepancies should be discussed with the management teams. Multigene testing results should be interpreted after correlation with pathologic findings to optimize patient care.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Receptors, Estrogen/analysis , Breast/pathology , Combined Modality Therapy , Disease-Free Survival , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Prognosis , Biomarkers, Tumor/geneticsABSTRACT
CDH1 encodes for E-cadherin, and its loss of function is the hallmark of invasive lobular carcinoma (ILC). Albeit vanishingly rare, biallelic CDH1 alterations may be found in nonlobular breast carcinomas (NL-BCs). We sought to determine the clinicopathologic characteristics and repertoire of genetic alterations of NL-BCs harboring CDH1 biallelic genetic alterations. Analysis of 5842 breast cancers (BCs) subjected to clinical tumor-normal sequencing with an FDA-cleared multigene panel was conducted to identify BCs with biallelic CDH1 pathogenic/likely pathogenic somatic mutations lacking lobular features. The genomic profiles of NL-BCs with CDH1 biallelic genetic alterations were compared with those of ILCs and invasive ductal carcinomas (IDCs), matched by clinicopathologic characteristics. Of the 896 CDH1-altered BCs, 889 samples were excluded based on the diagnosis of invasive mixed ductal/lobular carcinoma or ILC or the detection of monoallelic CDH1 alterations. Only 7 of the 5842 (0.11%) BCs harbored biallelic CDH1 alterations and lacked lobular features. Of these, 4/7 (57%) cases were ER-positive/HER2-negative, 1/7 (14%) was ER-positive/HER2-positive, and 2/7 (29%) were ER-negative/HER2-negative. In total, 5/7 (71%) were of Nottingham grade 2, and 2/7 (29%) were of grade 3. The NL-BCs with CDH1 biallelic genetic alterations included a mucinous carcinoma (n = 1), IDCs with focal nested growth (n = 2), IDC with solid papillary (n = 1) or apocrine (n = 2) features, and an IDC of no special type (NST; n = 1). E-cadherin expression, as detected by immunohistochemistry, was absent (3/5) or aberrant (discontinuous membranous/cytoplasmic/granular; 2/5). However, NL-BCs with CDH1 biallelic genetic alterations displayed recurrent genetic alterations, including TP53, PIK3CA (57%, 4/7; each), FGFR1, and NCOR1 (28%, 2/7, each) alterations. Compared with CDH1 wild-type IDC-NSTs, NL-BCs less frequently harbored GATA3 mutations (0% vs 47%, P = .03), but no significant differences were detected when compared with matched ILCs. Therefore, NL-BCs with CDH1 biallelic genetic alterations are vanishingly rare, predominantly comprise IDCs with special histologic features, and have genomic features akin to luminal B ER-positive BCs.
Subject(s)
Breast Neoplasms , Carcinoma, Ductal, Breast , Carcinoma, Lobular , Humans , Female , Carcinoma, Lobular/pathology , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Cadherins/genetics , Genomics , Antigens, CD/geneticsABSTRACT
Because of the unique anatomic structure of the nipple, a few specific breast lesions occur only at this site. Large lactiferous sinuses may be involved by inflammatory conditions such as squamous metaplasia of lactiferous ducts and ductal ectasia or be the site of uncommon superficial epithelial neoplasms such as nipple adenoma or syringomatous tumor of the nipple. Paget disease of the nipple may be secondary to intraepidermal extension of ductal carcinoma in situ in the underlying lactiferous ducts or develop from malignant transformation of Toker cells. Invasive breast cancer may also arise primarily in the nipple. Most of these conditions present as a palpable mass and/or skin changes with or without nipple discharge. Due to the delicate location and often relatively small size of nipple lesions, biopsy specimens are often superficial and fragmented, and the interpretation is challenging. Knowledge of the morphologic and immunophenotypic features of nipple lesions is essential in making the correct diagnosis. Information on the molecular alterations underpinning nipple neoplasms is currently very limited.
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Pathology clinical practice has evolved by adopting technological advancements initially regarded as potentially disruptive, such as electron microscopy, immunohistochemistry, and genomic sequencing. Breast pathology has a critical role as a medical domain, where the patient's pathology diagnosis has significant implications for prognostication and treatment of diseases. The advent of digital and computational pathology has brought about significant advancements in the field, offering new possibilities for enhancing diagnostic accuracy and improving patient care. Digital slide scanning enables to conversion of glass slides into high-fidelity digital images, supporting the review of cases in a digital workflow. Digitization offers the capability to render specimen diagnoses, digital archival of patient specimens, collaboration, and telepathology. Integration of image analysis and machine learning-based systems layered atop the high-resolution digital images offers novel workflows to assist breast pathologists in their clinical, educational, and research endeavors. Decision support tools may improve the detection and classification of breast lesions and the quantification of immunohistochemical studies. Computational biomarkers may help to contribute to patient management or outcomes. Furthermore, using digital and computational pathology may increase standardization and quality assurance, especially in areas with high interobserver variability. This review explores the current landscape and possible future applications of digital and computational techniques in the field of breast pathology.
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Brain metastasis is a dismal cancer complication, hinging on the initial survival and outgrowth of disseminated cancer cells. To understand these crucial early stages of colonization, we investigated two prevalent sources of cerebral relapse, triple-negative (TNBC) and HER2+ breast cancer (HER2BC). We show that these tumor types colonize the brain aggressively, yet with distinct tumor architectures, stromal interfaces, and autocrine growth programs. TNBC forms perivascular sheaths with diffusive contact with astrocytes and microglia. In contrast, HER2BC forms compact spheroids prompted by autonomous extracellular matrix components and segregating stromal cells to their periphery. Single-cell transcriptomic dissection reveals canonical Alzheimer's disease-associated microglia (DAM) responses. Differential engagement of tumor-DAM signaling through the receptor AXL suggests specific pro-metastatic functions of the tumor architecture in both TNBC perivascular and HER2BC spheroidal colonies. The distinct spatial features of these two highly efficient modes of brain colonization have relevance for leveraging the stroma to treat brain metastasis.
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BACKGROUND: The core-needle biopsy (CNB) diagnosis of atypical ductal hyperplasia (ADH) generally mandates follow-up excision, but controversy exists on whether small foci of ADH require surgical management. This study evaluated the upgrade rate at excision of focal ADH (fADH), defined as 1 focus spanning ≤ 2 mm. METHODS: We retrospectively identified in-house CNBs with ADH as the highest-risk lesion obtained between January 2013 and December 2017. A radiologist assessed radiologic-pathologic concordance. All CNB slides were reviewed by two breast pathologists, and ADH was classified as fADH and nonfocal ADH based on extent. Only cases with follow-up excision were included. The slides of excision specimens with upgrade were reviewed. RESULTS: The final study cohort consisted of 208 radiologic-pathologic concordant CNBs, including 98 fADH and 110 nonfocal ADH. The imaging targets were calcifications (n = 157), a mass (n = 15), nonmass enhancement (n = 27), and mass enhancement (n = 9). Excision of fADH yielded seven (7%) upgrades (5 ductal carcinoma in situ (DCIS), 2 invasive carcinoma) versus 24 (22%) upgrades (16 DCIS, 8 invasive carcinoma) at excision of nonfocal ADH (p = 0.01). Both invasive carcinomas found at excision of fADH were subcentimeter tubular carcinomas away from the biopsy site and deemed incidental. CONCLUSIONS: Our data show a significantly lower upgrade rate at excision of focal ADH than nonfocal ADH. This information can be valuable if nonsurgical management of patients with radiologic-pathologic concordant CNB diagnosis of focal ADH is being considered.
Subject(s)
Breast Neoplasms , Carcinoma, Intraductal, Noninfiltrating , Humans , Female , Carcinoma, Intraductal, Noninfiltrating/pathology , Retrospective Studies , Tertiary Care Centers , Breast/pathology , Biopsy, Large-Core Needle , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Hyperplasia/surgery , Hyperplasia/pathologyABSTRACT
Core needle biopsy (CNB) of breast lesions is routine for diagnosis and treatment planning. Despite refinement of diagnostic criteria, the diagnosis of breast lesions on CNB can be challenging. At many centers, including ours, confirmation of diagnoses rendered in other laboratories is required before treatment planning. We identified CNBs first diagnosed elsewhere that were reviewed in our department over the course of 1 year because the patients sought care at our center and in which a change in diagnosis had been recorded. The outside and in-house CNB diagnoses were then classified based on Breast WHO Fifth Edition diagnostic categories. The impact of the change in diagnosis was estimated based on the subsequent surgical management. Findings in follow-up surgical excisions (EXCs) were used for validation. In 2018, 4950 outside cases with CNB were reviewed at our center. A total of 403 CNBs diagnoses were discrepant. Of these, 147 had a change in the WHO diagnostic category: 80 (54%) CNBs had a more severe diagnosis and 44 (30%) a less severe diagnosis. In 23 (16%) CNBs, the change of diagnostic category had no impact on management. Intraductal proliferations (n=54), microinvasive carcinoma (n=18), and papillary lesions (n=35) were the most disputed diagnoses. The in-house CNB diagnosis was confirmed in most cases with available excisions. Following CNB reclassification, 22/147 (15%) lesions were not excised. A change affecting the surgical management at our center occurred in 2.5% of all CNBs. Our results support routine review of outside breast CNB as a clinically significant practice before definitive treatment.
Subject(s)
Breast Neoplasms , Breast , Humans , Female , Biopsy, Large-Core Needle , Tertiary Care Centers , Retrospective Studies , Breast/surgery , Breast/pathology , Breast Neoplasms/diagnosis , Breast Neoplasms/surgery , Breast Neoplasms/etiologyABSTRACT
The current histological classification of in-situ and invasive lobular carcinomas (ILCs) includes different morphological variants, some of which have been recently described. In this review, we will focus upon: (i) the diagnostic criteria of non-invasive lobular neoplasia and treatment implications across different countries; (ii) utility and limitations of immunohistochemistry; (iii) recently described variants of ILC; and (iv) the significance of lobular differentiation in invasive carcinoma for clinical management.
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AIMS: Activating somatic mutations or gene amplification of KIT result in constitutive activation of its receptor tyrosine kinase, which is targetable in various solid tumours. Here, we sought to investigate the presence of KIT genetic alterations in breast cancer (BC) and characterise the histological and genomic features of these tumours. METHODS: A retrospective analysis of 5,575 BCs previously subjected to targeted sequencing using the FDA-authorised Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Targets (MSK-IMPACT) assay was performed to identify BCs with KIT alterations. A histological assessment of KIT-altered BCs was conducted, and their repertoire of genetic alterations was compared with that of BCs lacking KIT genetic alterations, matched for age, histological type, oestrogen receptor/HER2 status and sample type. RESULTS: We identified 18 BCs (0.32%), including 9 primary and 9 metastatic BCs, with oncogenic/likely oncogenic genetic alterations affecting KIT, including activating somatic mutations (n=4) or gene amplification (n=14). All KIT-altered BCs were of high histological grade, although no distinctive histological features were observed. When compared with BCs lacking KIT genetic alterations, no distinctive genetic features were identified. In two metastatic KIT-altered BCs in which the matched primary BC had also been analysed by MSK-IMPACT, the KIT mutations were found to be restricted to the metastatic samples, suggesting that they were late events in the evolution of these cancers. CONCLUSIONS: KIT genetic alterations are vanishingly rare in BC. KIT-altered BCs are of high grade but lack distinctive histological features. Genetic alterations in KIT might be late events in the evolution and/or progression of BC.
Subject(s)
Breast Neoplasms , Humans , Female , Retrospective Studies , Breast Neoplasms/genetics , Mutation , Gene Amplification , GenomicsABSTRACT
Despite a wide spectrum of clinical presentations, including primary or secondary, most angiosarcomas are considered high grade. One exception is primary breast angiosarcoma, where historically, histologic grading has shown to predict outcome using the Rosen 3-tier system. However, more recent studies have challenged this concept suggesting that even in this specific clinical context angiosarcomas should be considered high grade. This study aimed to critically reevaluate the impact of histologic grade in a clinically uniform cohort managed at a single institution using a newly proposed grading system. Our study included 49 primary breast angiosarcomas diagnosed during 1994 to 2022 (median follow-up: 33 mo), classified as low grade (29%), intermediate grade (20%), and high grade (51%), based on mitotic count, extent of solid components, and necrosis. At last follow-up, 22% patients developed locoregional recurrences, 63% distant metastases, and 47% patients died of disease. As patients with low and intermediate-grade angiosarcomas had relatively similar outcomes, our cohort was further analyzed using a 2-tier system (low grade and high grade). Targeted-DNA next-generation sequencing (505 cancer gene panel) performed in 11 cases found KDR mutations in 78% and PIK3CA mutations in 44% of high-grade lesions. Histologic grade, by either 3-tier or 2-tier grading systems, had a strong impact on survival, with the 2-tier system being an independent predictor of disease-specific survival and overall survival. Based on 2-tier system, the 5-year overall survival was 38% for high-grade angiosarcoma and 74% for low-grade angiosarcoma. PIK3CA mutations alone or concurrent with KDR alterations were identified in angiosarcomas with worse prognosis.
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Hemangiosarcoma , Humans , Prognosis , Hemangiosarcoma/pathology , Neoplasm Recurrence, Local , Class I Phosphatidylinositol 3-Kinases , Neoplasm GradingABSTRACT
CONTEXT.: The International Collaboration on Cancer Reporting (ICCR), supported by major pathology and cancer organizations, aims at the standardization of evidence-based pathology reporting of different types of cancers, with the inclusion of all parameters deemed to be relevant for best patient care and future data collection. Lymph node metastasis is one of the most important prognostic factors in breast cancer. OBJECTIVE.: To produce a histopathology reporting guide by a panel of recognized experts from the fields of pathology and surgery with elements deemed to be core (required) and noncore (recommended) to report when assessing regional lymph nodes of patients with breast cancer. DATA SOURCES.: Published literature, previous guidelines/recommendations, and current cancer staging principles were the basis of the data set drafted by the expert panel. This was discussed in a series of teleconferences and email communications. The draft data set was then made available for public consultation through the ICCR Web site. After this consultation and ICCR ratification, the data set was finalized. CONCLUSIONS.: The ICCR has published a data set for the reporting of surgically removed lymph nodes (including sentinel lymph node biopsy, axillary lymph node dissection, targeted axillary surgery, and lymph node sampling specimens) for breast tumors. This is part of a series of 4 ICCR breast cancer-related data sets. It includes 10 core elements along with 2 noncore elements. This should allow for synoptic reporting, which is more precise, uniform, and complete than nonsynoptic reporting, and leads to improved patient outcomes.
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Breast Neoplasms , Pathology, Clinical , Humans , Female , Sentinel Lymph Node Biopsy , Breast Neoplasms/surgery , Lymphatic Metastasis , Lymph Nodes/surgeryABSTRACT
Breast adenoid cystic carcinoma (AdCC) is a rare subtype of triple negative breast cancer. Two morphologic variants are described, namely classic AdCC (C-AdCC) and solid basaloid (SB-AdCC). Recent studies have shown that the SB-AdCC variant has significantly worse prognosis than C-AdCC. Due to the rarity of SB-AdCC, no standard recommendations are available for its management. Data on the use and benefit of chemotherapy in patients with SB-AdCC are sparse and the response to neoadjuvant chemotherapy has not been reported. We present the clinical and pathologic findings of a patient with SB-AdCC treated with neoadjuvant chemotherapy who achieved a remarkable pathologic response.
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INSM1, ASCL1, and POU2F3 are novel transcription factors involved in neuroendocrine (NE) differentiation of neoplasms in several organs, but data on their expression in breast carcinomas (BCs) are limited. We retrospectively evaluated the expression of these markers in a series of 97 BCs (58 with NE morphology and 39 with otherwise uncommon morphology) tested prospectively using immunohistochemistry (IHC). Nuclear staining in >50% of the cells was used as the positive cut-off. Thirty-two of the 97 BCs (33%) were INSM1-positive. INSM1-positivity correlated significantly with histologic type and presence of stromal mucin. INSM1 also correlated with synaptophysin and chromogranin, established markers of NE differentiation (P < .0001 and P = .0023, respectively). In BC with NE morphology, the expression of INSM1 supported NE differentiation, and INSM1 was more specific than synaptophysin and more sensitive and specific than chromogranin. INSM1 was the most expressed NE marker in 17 BCs. INSM1-positive BCs included 56% of solid papillary BCs, 88% of BCs with solid papillary features, and 75% of high-grade NE carcinomas. Of 35 BCs tested for POU2F3 and ASCL1, only 1 and 4 cases were positive, respectively. Our results show that INSM1 is a sensitive marker of NE differentiation in BC and should be included with synaptophysin and chromogranin in the IHC panel used to evaluate NE differentiation in BC with NE morphology. ASCL1 and POU2F3 are uncommon in BC and their routine assessment is not warranted.