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Histopathology Jan 2016Phyllodes tumours constitute an uncommon but complex group of mammary fibroepithelial lesions. Accurate and reproducible grading of these tumours has long been... (Review)
Review
Phyllodes tumours constitute an uncommon but complex group of mammary fibroepithelial lesions. Accurate and reproducible grading of these tumours has long been challenging, owing to the need to assess multiple stratified histological parameters, which may be weighted differently by individual pathologists. Distinction of benign phyllodes tumours from cellular fibroadenomas is fraught with difficulty, due to overlapping microscopic features. Similarly, separation of the malignant phyllodes tumour from spindle cell metaplastic carcinoma and primary breast sarcoma can be problematic. Phyllodes tumours are treated by surgical excision. However, there is no consensus on the definition of an appropriate surgical margin to ensure completeness of excision and reduction of recurrence risk. Interpretive subjectivity, overlapping histological diagnostic criteria, suboptimal correlation between histological classification and clinical behaviour and the lack of robust molecular predictors of outcome make further investigation of the pathogenesis of these fascinating tumours a matter of active research. This review consolidates the current understanding of their pathobiology and clinical behaviour, and includes proposals for a rational approach to the classification and management of phyllodes tumours.
Topics: Breast; Breast Neoplasms; Carcinoma; Consensus; Diagnosis, Differential; Female; Fibroadenoma; Humans; Phyllodes Tumor; Sarcoma
PubMed: 26768026
DOI: 10.1111/his.12876 -
Pathologica Mar 2020The World Health Organization's new classification of breast tumors has just been published. This review aims to examine the morphological categorization of breast... (Review)
Review
The World Health Organization's new classification of breast tumors has just been published. This review aims to examine the morphological categorization of breast carcinomas which is still principally based on histological features and follows the traditions of histological typing. It gives a subjective and critical view on the WHO classifications and their changes over time, and describes the changes related to some of the most common or challenging breast carcinomas: in situ carcinomas, invasive breast carcinomas of no special type, lobular, cribriform, tubular, mucinous, papillary, metaplastic carcinomas and carcinomas with medullary pattern and those with apocrine differentiation are discussed in more details. Although the 5 edition of the classification is not perfect, it has advantages which are mentioned along with problematic issues of classifications.
Topics: Breast Neoplasms; Humans; Neoplasm Grading; Time Factors; World Health Organization
PubMed: 32202537
DOI: 10.32074/1591-951X-1-20 -
Modern Pathology : An Official Journal... Apr 2021Currently there is no highly specific and sensitive marker to identify breast cancer-the most common malignancy in women. Breast cancer can be categorized as estrogen... (Comparative Study)
Comparative Study
Currently there is no highly specific and sensitive marker to identify breast cancer-the most common malignancy in women. Breast cancer can be categorized as estrogen receptor (ER)/progesterone receptor (PR)-positive luminal, human epidermal growth factor receptor 2 (HER2)-positive, or triple-negative breast cancer (TNBC) types based on the expression of ER, PR, and HER2. Although GATA3 is the most widely used tumor marker at present to determine the breast origin, which has been shown to be an excellent marker for ER-positive and low-grade breast cancer, but it does not work well for TNBC with sensitivity as low as <20% in metaplastic breast carcinoma. In the current study, through TCGA data mining we identified trichorhinophalangeal syndrome type 1 (TRPS1) as a specific gene for breast carcinoma across 31 solid tumor types. Moreover, high mRNA level of TRPS1 was found in all four subtypes of breast carcinoma including ER/PR-positive luminal A and B types, HER2-positive type, and basal-type/TNBC. We then analyzed TRPS1 expression in 479 cases of various types of breast cancer using immunochemistry staining, and found that TRPS1 and GATA3 had comparable positive expression in ER-positive (98% vs. 95%) and HER2-positive (87% vs. 88%) breast carcinomas. However, TRPS1 which was highly expressed in TNBC, was significantly higher than GATA3 expression in metaplastic (86% vs. 21%) and nonmetaplastic (86% vs. 51%) TNBC. In addition, TRPS1 expression was evaluated in 1234 cases of solid tumor from different organs. In contrast to the high expression of GATA3 in urothelial carcinoma, TRPS1 showed no or little expression in urothelial carcinomas or in other tumor types including lung adenocarcinoma, pancreatic adenocarcinoma, colon and gastric adenocarcinoma, renal cell carcinoma, melanoma, and ovarian carcinoma. These findings suggest that TRPS1 is a highly sensitive and specific marker for breast carcinoma and can be used as a great diagnostic tool, especially for TNBC.
Topics: Biomarkers, Tumor; Carcinoma; Databases, Genetic; Female; GATA3 Transcription Factor; Humans; Immunohistochemistry; Predictive Value of Tests; Repressor Proteins; Reproducibility of Results; Tissue Array Analysis; Triple Negative Breast Neoplasms
PubMed: 33011748
DOI: 10.1038/s41379-020-00692-8 -
Cell Discovery Oct 2022Gallbladder carcinoma (GBC) is the most common biliary tract malignancy with the lowest survival rate, primarily arising from chronic inflammation. To better...
Gallbladder carcinoma (GBC) is the most common biliary tract malignancy with the lowest survival rate, primarily arising from chronic inflammation. To better characterize the progression from inflammation to cancer to metastasis, we performed single-cell RNA sequencing across samples of 6 chronic cholecystitis, 12 treatment-naive GBCs, and 6 matched metastases. Benign epithelial cells from inflamed gallbladders displayed resting, immune-regulating, and gastrointestinal metaplastic phenotypes. A small amount of PLA2G2A epithelial cells with copy number variation were identified from a histologically benign sample. We validated significant overexpression of PLA2G2A across in situ GBCs, together with increased proliferation and cancer stemness in PLA2G2A-overexpressing GBC cells, indicating an important role for PLA2G2A during early carcinogenesis. Malignant epithelial cells displayed pervasive cancer hallmarks and cellular plasticity, differentiating into metaplastic, inflammatory, and mesenchymal subtypes with distinct transcriptomic, genomic, and prognostic patterns. Chronic cholecystitis led to an adapted microenvironment characterized by MDSC-like macrophages, CD8 T cells, and CCL2 immunity-regulating fibroblasts. By contrast, GBC instigated an aggressive and immunosuppressive microenvironment, featured by tumor-associated macrophages, Treg cells, CD8 T cells, and STMN1 tumor-promoting fibroblasts. Single-cell and bulk RNA-seq profiles consistently showed a more suppressive immune milieu for GBCs with inflammatory epithelial signatures, coupled with strengthened epithelial-immune crosstalk. We further pinpointed a subset of senescence-like fibroblasts (FN1TGM2) preferentially enriched in metastatic lesions, which promoted GBC migration and invasion via their secretory phenotype. Collectively, this study provides comprehensive insights into epithelial and microenvironmental reprogramming throughout cholecystitis-propelled carcinogenesis and metastasis, laying a new foundation for the precision therapy of GBC.
PubMed: 36198671
DOI: 10.1038/s41421-022-00445-8 -
Virchows Archiv : An International... Jan 2022Spindle cell lesions of the breast comprise a heterogeneous group of lesions, ranging from reactive and benign processes to aggressive malignant tumours. Despite their... (Review)
Review
Spindle cell lesions of the breast comprise a heterogeneous group of lesions, ranging from reactive and benign processes to aggressive malignant tumours. Despite their rarity, they attract the attention of breast pathologists due to their overlapping morphological features and diagnostic challenges, particularly on core needle biopsy (CNB) specimens. Pathologists should recognise the wide range of differential diagnoses and be familiar with the diverse morphological appearances of these lesions to make an accurate diagnosis and to suggest proper management of the patients. Clinical history, immunohistochemistry, and molecular assays are helpful in making a correct diagnosis in morphologically challenging cases. In this review, we present our approach for the diagnosis of breast spindle cell lesions, highlighting the main features of each entity and the potential pitfalls, particularly on CNB. Breast spindle cell lesions are generally classified into two main categories: bland-appearing and malignant-appearing lesions. Each category includes a distinct list of differential diagnoses and a panel of immunohistochemical markers. In bland-appearing lesions, it is important to distinguish fibromatosis-like spindle cell metaplastic breast carcinoma from other benign entities and to distinguish fibromatosis from scar tissue. The malignant-appearing category includes spindle cell metaplastic carcinoma, stroma rich malignant phyllodes tumour, other primary and metastatic malignant spindle cell tumours of the breast, including angiosarcoma and melanoma, and benign mimics such as florid granulation tissue and nodular fasciitis.
Topics: Breast; Breast Neoplasms; Carcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Phyllodes Tumor
PubMed: 34322734
DOI: 10.1007/s00428-021-03162-x -
Journal of Thoracic Oncology : Official... Feb 2022This overview of the fifth edition of the WHO classification of thymic epithelial tumors (including thymomas, thymic carcinomas, and thymic neuroendocrine tumors... (Review)
Review
This overview of the fifth edition of the WHO classification of thymic epithelial tumors (including thymomas, thymic carcinomas, and thymic neuroendocrine tumors [NETs]), mediastinal germ cell tumors, and mesenchymal neoplasms aims to (1) list established and new tumor entities and subtypes and (2) focus on diagnostic, molecular, and conceptual advances since publication of the fourth edition in 2015. Diagnostic advances are best exemplified by the immunohistochemical characterization of adenocarcinomas and the recognition of genetic translocations in metaplastic thymomas, rare B2 and B3 thymomas, and hyalinizing clear cell carcinomas. Advancements at the molecular and tumor biological levels of utmost oncological relevance are the findings that thymomas and most thymic carcinomas lack currently targetable mutations, have an extraordinarily low tumor mutational burden, but typically have a programmed death-ligand 1 phenotype. Finally, data underpinning a conceptual advance are illustrated for the future classification of thymic NETs that may fit into the classification scheme of extrathoracic NETs. Endowed with updated clinical information and state-of-the-art positron emission tomography and computed tomography images, the fifth edition of the WHO classification of thymic epithelial tumors, germ cell tumors, and mesenchymal neoplasms with its wealth of new diagnostic and molecular insights will be a valuable source for pathologists, radiologists, surgeons, and oncologists alike. Therapeutic perspectives and research challenges will be addressed as well.
Topics: Adenocarcinoma; Germ Cells; Humans; Lung Neoplasms; Mediastinum; Thymus Neoplasms; World Health Organization
PubMed: 34695605
DOI: 10.1016/j.jtho.2021.10.010 -
Archives of Pathology & Laboratory... Aug 2022Few studies have investigated the features of FOXC1 protein expression in invasive breast cancer subtypes as defined by immunohistochemistry (IHC)-based surrogate...
CONTEXT.—
Few studies have investigated the features of FOXC1 protein expression in invasive breast cancer subtypes as defined by immunohistochemistry (IHC)-based surrogate molecular classification.
OBJECTIVE.—
To investigate the diagnostic utility of the IHC-based FOXC1 test in breast cancer subtyping and to evaluate the correlation between FOXC1 expression and clinicopathologic parameters in triple-negative breast cancer (TNBC).
DESIGN.—
FOXC1 expression was evaluated with IHC in a large cohort of 2443 patients with breast cancer. Receiver operating characteristic (ROC) curves were used to assess the diagnostic ability of FOXC1 expression to predict the triple-negative phenotype and to identify the best cutoff value. FOXC1 expression was correlated with the clinicopathologic parameters of TNBC.
RESULTS.—
The expression rate of FOXC1 in TNBC was significantly higher than in other subtypes. The area under the ROC curve confirmed the high diagnostic value of FOXC1 for the prediction of the triple-negative phenotype. The cutoff value of 1% showed a maximized sum of sensitivity and specificity. In TNBC, FOXC1 expression was significantly associated with aggressive tumor phenotypes. Furthermore, FOXC1 expression was primarily observed in invasive breast carcinoma of no special type and metaplastic carcinoma but rarely in invasive carcinoma with apocrine differentiation. Correspondingly, FOXC1 expression was significantly associated with the expression of basal markers but was negatively correlated with apocrine-related markers in TNBC.
CONCLUSIONS.—
In conclusion, FOXC1 is a highly specific marker for the triple-negative phenotype. Moreover, IHC detection of FOXC1 expression can be used as an additional diagnostic tool for the triple-negative phenotype and subclassification in TNBC.
Topics: Biomarkers, Tumor; Carcinoma; Forkhead Transcription Factors; Humans; Immunohistochemistry; ROC Curve; Sensitivity and Specificity; Triple Negative Breast Neoplasms
PubMed: 34784418
DOI: 10.5858/arpa.2021-0039-OA -
Nature Communications Sep 2020Acinar metaplasia is an initial step in a series of events that can lead to pancreatic cancer. Here we perform single-cell RNA-sequencing of mouse pancreas during the...
Acinar metaplasia is an initial step in a series of events that can lead to pancreatic cancer. Here we perform single-cell RNA-sequencing of mouse pancreas during the progression from preinvasive stages to tumor formation. Using a reporter gene, we identify metaplastic cells that originated from acinar cells and express two transcription factors, Onecut2 and Foxq1. Further analyses of metaplastic acinar cell heterogeneity define six acinar metaplastic cell types and states, including stomach-specific cell types. Localization of metaplastic cell types and mixture of different metaplastic cell types in the same pre-malignant lesion is shown. Finally, single-cell transcriptome analyses of tumor-associated stromal, immune, endothelial and fibroblast cells identify signals that may support tumor development, as well as the recruitment and education of immune cells. Our findings are consistent with the early, premalignant formation of an immunosuppressive environment mediated by interactions between acinar metaplastic cells and other cells in the microenvironment.
Topics: Acinar Cells; Animals; Animals, Genetically Modified; Biopsy; Carcinoma, Pancreatic Ductal; Cell Differentiation; Disease Models, Animal; Female; Forkhead Transcription Factors; Gene Expression Regulation, Neoplastic; Genetic Heterogeneity; Homeodomain Proteins; Humans; Kaplan-Meier Estimate; Male; Metaplasia; Mice; Mutation; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Precancerous Conditions; Proto-Oncogene Proteins p21(ras); RNA-Seq; Single-Cell Analysis; Transcription Factors; Tumor Microenvironment
PubMed: 32908137
DOI: 10.1038/s41467-020-18207-z -
Archives of Pathology & Laboratory... Jun 2015Metaplastic carcinoma of the breast is a rare but aggressive type of breast cancer that has been recognized as a unique pathologic entity by the World Health... (Review)
Review
Metaplastic carcinoma of the breast is a rare but aggressive type of breast cancer that has been recognized as a unique pathologic entity by the World Health Organization. Morphologically, it is characterized by the differentiation of neoplastic epithelium into squamous cells and/or mesenchymal-looking elements (squamous cells, spindle cells, cartilage or bone, etc). It shares many similarities with invasive ductal carcinoma and benign lesions on mammography, which further complicates the diagnosis. Treatment for metaplastic breast carcinoma is relatively unknown because of the rarity of the disease, but studies suggest that removal of the tumor and adjuvant radiation therapy has the greatest benefit.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast; Breast Neoplasms; Chemoradiotherapy; Etoposide; Female; Humans; Ifosfamide; Metaplasia; Prognosis
PubMed: 26030252
DOI: 10.5858/arpa.2013-0358-RS -
Pathology Jan 2021The histopathological diagnosis of prostatic adenocarcinoma is challenged by the existence of numerous benign mimics. Most of these lesions have no clinical significance... (Review)
Review
The histopathological diagnosis of prostatic adenocarcinoma is challenged by the existence of numerous benign mimics. Most of these lesions have no clinical significance and many do not need to be reported. Their clinical relevance lies in the risk that they are misinterpreted as cancer. This review presents the histopathological features of benign mimics and discusses their distinction from cancer. The lesions that are most often misdiagnosed as cancer are atrophy and its variants, including simple atrophy, partial atrophy and post-atrophic hyperplasia. Benign proliferations are a group of lesions with crowded small glands with no or little nuclear atypia. The most problematic entity of this group is adenosis, which may have a more alarming architecture than some cancers. A diagnostic problem with atrophy and several of the benign proliferations is that the glands often have a discontinuous or absent basal cell layer. Hyperplastic and metaplastic lesions include basal cell hyperplasia. Basal cell hyperplasia may especially mimic prostate cancer with its small dark glands, variable nuclear atypia and a pseudoinfiltrative pattern, which may be present. The anatomical structure that most often causes diagnostic problems is the seminal vesicle. The mucosa of the seminal vesicle contains small acini, often with very pronounced nuclear atypia that may be misinterpreted as cancer. Pathologists need to be familiar with these mimics, as a false positive diagnosis of prostate cancer may lead to unnecessary radical treatment.
Topics: Adenocarcinoma; Atrophy; Diagnosis, Differential; Humans; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms
PubMed: 33070957
DOI: 10.1016/j.pathol.2020.08.006