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Journal of Cancer Research and... 2023Metaplastic carcinoma breast (MCB) is a rare tumor comprising of both glandular and non-glandular patterns with epithelial and or mesenchymal components. Due to their... (Review)
Review
BACKGROUND
Metaplastic carcinoma breast (MCB) is a rare tumor comprising of both glandular and non-glandular patterns with epithelial and or mesenchymal components. Due to their varied clinicomorphological features, diagnosis has been challenging.
AIM
To study the clinicopathological and histomorphology of cases of metaplastic carcinoma breast diagnosed in a tertiary care hospital along with literature review.
MATERIALS AND METHODS
This is a retrospective study including data of 11 patients who were diagnosed with MCB either on trucut or mastectomy specimens conducted between January 2014 and December 2018.
RESULTS
The study includes 11 patients, out of which 10 were diagnosed on mastectomy while one on trucut specimen. All the patients were women with the mean age of presentation being 43.8 years. The most common presentation was palpable breast lump with mean tumor size of 7.3 cm in greatest dimension. Skin involvement was seen in 36.3% of cases. While eight cases (72.7%) were classified as epithelial, three (27.2%) were classified as mixed. Amongst epithelial variety, in eight cases, squamous component was seen along with infiltrating ductal carcinoma (IDC) while one was pure squamous type. In mixed variety, one case showed spindled areas along with squamous areas and areas of IDC. Other two showed focal sarcomatous and cartilaginous areas in one and angiosarcomatous, bone and cartilage formation admixed with areas of IDC in other case.
CONCLUSION
MCB are rare breast tumors with aggressive course and are characterized by their large size and rapid growth rate. Recently, there has been an upsurge in the cases of MCB due to increase in recognition of this entity. It has to be distinguished from other tumors by the pathologists so as to guide proper treatment.
Topics: Adult; Female; Humans; Breast; Breast Neoplasms; Carcinoma, Squamous Cell; Mastectomy; Metaplasia; Retrospective Studies
PubMed: 37787287
DOI: 10.4103/jcrt.jcrt_1229_21 -
Cancers Apr 2024Breast cancer is the most common cancer among women. Metaplastic breast carcinoma (MpBC) is a rare, heterogeneous group of invasive breast carcinomas, which are... (Review)
Review
Breast cancer is the most common cancer among women. Metaplastic breast carcinoma (MpBC) is a rare, heterogeneous group of invasive breast carcinomas, which are classified as predominantly triple-negative breast carcinomas (TNBCs; HR-negative/HER2-negative). Histologically, MpBC is classified into six subtypes. Two of these are considered low-grade and the others are high-grade. MpBCs seem to be more aggressive, less responsive to neoadjuvant chemotherapy, and have higher rates of chemoresistance than other TNBCs. MpBCs have a lower survival rate than expected for TNBCs. MpBC treatment represents a challenge, leading to a thorough exploration of the tumor immune microenvironment, which has recently opened the possibility of new therapeutic strategies. The epithelial-mesenchymal transition in MpBC is characterized by the loss of intercellular adhesion, downregulation of epithelial markers, underexpression of genes with biological epithelial functions, upregulation of mesenchymal markers, overexpression of genes with biological mesenchymal functions, acquisition of fibroblast-like (spindle) morphology, cytoskeleton reorganization, increased motility, invasiveness, and metastatic capabilities. This article reviews and summarizes the current knowledge and translational aspects of MpBC.
PubMed: 38611109
DOI: 10.3390/cancers16071433 -
Open Life Sciences 2023Metaplastic matrix-producing breast carcinoma is a type of metaplastic breast carcinoma (MBC), which is a rare malignancy, accounting for 0.2-1% of breast carcinomas. A... (Review)
Review
Metaplastic matrix-producing breast carcinoma is a type of metaplastic breast carcinoma (MBC), which is a rare malignancy, accounting for 0.2-1% of breast carcinomas. A 52-year-old female visited a hospital because of a palpable painless mass in the right breast and was diagnosed with Breast Imaging Reporting and Data System (BI-RADS) category 4A via ultrasound (US) with a suspected positive lymph node at the right axillary region. Excision of the breast mass was performed and histopathologically confirmed that it was MBC with osseous differentiation. No distant metastasis was revealed before a modified radical mastectomy; however, metastasis to a lymph node of the right axillary region was observed (1/22). She received six cycles of TEC scheme chemotherapy (docetaxel, epirubicin, and cyclophosphamide, 21 days) and 5 weeks of radiotherapy (48 Gy/25 f/5 days a week), but without any follow-up examinations since radiotherapy. Twenty-four months after surgery, distant metastases to lungs and liver were confirmed and died 3 months later. This case provides valuable information for clinicians on MBC and suggests that further examination or biopsy should be performed to US BI-RADS 4A masses before surgery. In addition, regular postoperative follow-up plays important roles in detecting metastases early and improving prognosis.
PubMed: 37528884
DOI: 10.1515/biol-2022-0640 -
Breast Cancer Research and Treatment Dec 2023Low-grade adenosquamous carcinoma (LGASC) is a rare type of metaplastic carcinoma of the breast (MBC) with an indolent clinical course. A few LGASC cases with high-grade...
PURPOSE
Low-grade adenosquamous carcinoma (LGASC) is a rare type of metaplastic carcinoma of the breast (MBC) with an indolent clinical course. A few LGASC cases with high-grade transformation have been reported; however, the genetics underlying malignant progression of LGASC remain unclear.
METHODS
We performed whole-genome sequencing analysis on five MBCs from four patients, including one case with matching primary LGASC and a lymph node metastatic tumor consisting of high-grade MBC with a predominant metaplastic squamous cell carcinoma component (MSC) that progressed from LGASC and three cases of independent de novo MSC.
RESULTS
Unlike de novo MSC, LGASC and its associated MSC showed no TP53 mutation and tended to contain fewer structural variants than de novo MSC. Both LGASC and its associated MSC harbored the common GNAS c.C2530T:p.Arg844Cys mutation, which was more frequently detected in the cancer cell fraction of MSC. MSC associated with LGASC showed additional pathogenic deletions of multiple tumor-suppressor genes, such as KMT2D and BTG1. Copy number analysis revealed potential 18q loss of heterozygosity in both LGASC and associated MSC. The frequency of SMAD4::DCC fusion due to deletions increased with progression to MSC; however, chimeric proteins were not detected. SMAD4 protein expression was already decreased at the LGASC stage due to unknown mechanisms.
CONCLUSION
Not only LGASC but also its associated high-grade MBC may be genetically different from de novo high-grade MBC. Progression from LGASC to high-grade MBC may involve the concentration of driver mutations caused by clonal selection and inactivation of tumor-suppressor genes.
Topics: Humans; Female; Carcinoma, Adenosquamous; Breast Neoplasms; Breast; Carcinoma
PubMed: 37650999
DOI: 10.1007/s10549-023-07078-9 -
Cancers Nov 2023Thymic epithelial tumors (TET) are rare and large molecular studies are therefore difficult to perform. However, institutional case series and rare multi-institutional... (Review)
Review
Thymic epithelial tumors (TET) are rare and large molecular studies are therefore difficult to perform. However, institutional case series and rare multi-institutional studies have identified a number of interesting molecular aberrations in TET, including gene fusions in a subset of these tumors. These gene fusions can aid in the diagnosis, shed light on the pathogenesis of a subset of tumors, and potentially may provide patients with the opportunity to undergo targeted therapy or participation in clinical trials. Gene fusions that have been identified in TET include rearrangements in 50% to 56% of mucoepidermoid carcinomas (), 77% to 100% of metaplastic thymomas (), and 6% of B2 and B3 thymomas (); rearrangements in NUT carcinomas (most commonly ); rearrangement in hyalinizing clear cell carcinoma (); and rearrangement in a thymoma (). This review focuses on TET in which these fusion genes have been identified, their morphologic, immunophenotypic, and clinical characteristics and potential clinical implications of the fusion genes. Larger, multi-institutional, global studies are needed to further elucidate the molecular characteristics of these rare but sometimes very aggressive tumors in order to optimize patient management, provide patients with the opportunity to undergo targeted therapy and participate in clinical trials, and to elucidate the pathogenesis of these tumors.
PubMed: 38067300
DOI: 10.3390/cancers15235596 -
International Journal of Molecular... Jul 2023Esophageal adenocarcinoma (EAC) is a rapidly increasing lethal tumor. It commonly arises from a metaplastic segment known as Barrett's esophagus (BE), which delineates... (Review)
Review
Esophageal adenocarcinoma (EAC) is a rapidly increasing lethal tumor. It commonly arises from a metaplastic segment known as Barrett's esophagus (BE), which delineates the at-risk population. Ample research has elucidated the pathogenesis of BE and its progression from metaplasia to invasive carcinoma; and multiple molecular pathways have been implicated in this process, presenting several points of cancer interception. Here, we explore the mechanisms of action of various agents, including proton pump inhibitors, non-steroidal anti-inflammatory drugs, metformin, and statins, and explain their roles in cancer interception. Data from the recent AspECT trial are discussed to determine how viable a multipronged approach to cancer chemoprevention would be. Further, novel concepts, such as the repurposing of chemotherapeutic drugs like dasatinib and the prevention of post-ablation BE recurrence using itraconazole, are discussed.
Topics: Humans; Barrett Esophagus; Esophageal Neoplasms; Adenocarcinoma; Risk Factors; Metaplasia
PubMed: 37511077
DOI: 10.3390/ijms241411318 -
Laboratory Investigation; a Journal of... Dec 2023Breast cancer is one of the most prominent types of cancers, in which therapeutic resistance is a major clinical concern. Specific subtypes, such as claudin-low and...
Breast cancer is one of the most prominent types of cancers, in which therapeutic resistance is a major clinical concern. Specific subtypes, such as claudin-low and metaplastic breast carcinoma (MpBC), have been associated with high nongenetic plasticity, which can facilitate resistance. The similarities and differences between these orthogonal subtypes, identified by molecular and histopathological analyses, respectively, remain insufficiently characterized. Furthermore, adequate methods to identify high-plasticity tumors to better anticipate resistance are lacking. Here, we analyzed 11 triple-negative breast tumors, including 3 claudin-low and 4 MpBC, via high-resolution spatial transcriptomics. We combined pathological annotations and deconvolution approaches to precisely identify tumor spots, on which we performed signature enrichment, differential expression, and copy number analyses. We used The Cancer Genome Atlas and Cancer Cell Line Encyclopedia public databases for external validation of expression markers. By focusing our spatial transcriptomic analyses on tumor cells in MpBC samples, we bypassed the negative impact of stromal contamination and identified specific markers that are neither expressed in other breast cancer subtypes nor expressed in stromal cells. Three markers (BMPER, POPDC3, and SH3RF3) were validated in external expression databases encompassing bulk tumor material and stroma-free cell lines. We unveiled that existing bulk expression signatures of high-plasticity breast cancers are relevant in mesenchymal transdifferentiated compartments but can be hindered by abundant stromal cells in tumor samples, negatively impacting their clinical applicability. Spatial transcriptomic analyses constitute powerful tools to identify specific expression markers and could thus enhance diagnosis and clinical care of rare high-plasticity breast cancers.
Topics: Humans; Female; Breast Neoplasms; Triple Negative Breast Neoplasms; Gene Expression Profiling; Breast; Transcriptome; Claudins; Prognosis; Carrier Proteins; Muscle Proteins; Cell Adhesion Molecules; Ubiquitin-Protein Ligases
PubMed: 37813278
DOI: 10.1016/j.labinv.2023.100258 -
Case Reports in Oncology 2023Metaplastic breast cancer (MpBC) is a rare form of breast malignancy with a poor prognosis and limited treatment guidance. Here, we report on a case of triple-negative...
Metaplastic breast cancer (MpBC) is a rare form of breast malignancy with a poor prognosis and limited treatment guidance. Here, we report on a case of triple-negative MpBC that was successfully treated following the Keynote-522 clinical algorithm using pembrolizumab, paclitaxel, carboplatin, adriamycin, and cyclophosphamide in a neo-adjuvant fashion. The radiographic and histologic findings of the tumor are reviewed here along with the treatment regimen and response. No major toxicities associated with pembrolizumab were observed in this case. This case report serves as an example of complete pathological response of triple-negative MpBC with pembrolizumab plus chemotherapy and demonstrates the need for further research on chemoimmunotherapy for MpBC.
PubMed: 37900847
DOI: 10.1159/000534146 -
Cureus Jul 2023Nephrogenic adenoma (NA) is a rare metaplastic entity commonly associated with a prior urothelial injury. Most are seen in the urinary bladder and a minority involve...
Nephrogenic adenoma (NA) is a rare metaplastic entity commonly associated with a prior urothelial injury. Most are seen in the urinary bladder and a minority involve the urethra. In this study, we evaluated the expression of p16 as a surrogate marker of this entity and correlated it with clinical pathological parameters. A total of 17 cases of NA were retrospectively studied to assess the immunohistochemical expression of p16 and its value for the diagnosis of this entity.
PubMed: 37533615
DOI: 10.7759/cureus.41285 -
World Journal of Surgical Oncology Nov 2023Metaplastic breast cancer(MBC) is a specific pathological type of invasive breast cancer. There are few studies related to MBC due to its rarity. This study aimed to...
BACKGROUND
Metaplastic breast cancer(MBC) is a specific pathological type of invasive breast cancer. There are few studies related to MBC due to its rarity. This study aimed to analyse the differences in clinicopathological characteristics and prognosis between Metaplastic breast cancer and triple-negative invasive ductal carcinoma (TN-IDC).
METHODS
We retrospectively compared the clinicopathological characteristics of patients diagnosed with MBC and TN-IDC at the Fourth Hospital of Hebei Medical University between 2011 and 2020 in a 1:2 ratio. The log-rank test was used to compare the two groups' disease-free survival (DFS) and overall survival (OS). For MBCs, we performed univariate and multivariate analyses using the Cox proportional hazards model to determine the characteristics that impacted OS and DFS.
RESULTS
A total of 81 patients with MBC and 162 patients with TN-IDC were included in this study. At initial diagnosis, MBC patients had larger tumour diameters(P = 0.03) and fewer positive lymph nodes (P = 0.04). Patients with MBC were more likely to have organ metastases after surgery (P = 0.03). Despite receiving the same treatment, MBC patients had worse DFS (HR = 1.66, 95%CI 0.90-3.08, P = 0.11) and OS (HR = 1.98, 95% CI 1.03-3.81, P = 0.04), and OS was statistically significant. Positive lymph nodes at initial diagnosis were associated with worse DFS (HR = 3.98, 95%CI 1.05-15.12, P = 0.04) and OS (HR = 3.70, 95%CI 1.03-13.34, P = 0.04) for patients with MBC. The efficacy of platinum-based agents is insensitive for MBC patients receiving chemotherapy. In addition, patients treated with preoperative chemotherapy had worse DFS compared to patients treated with postoperative chemotherapy (HR = 3.51, 95%CI 1.05-11.75, P = 0.04).
CONCLUSIONS
The clinicopathological characteristics and prognosis of MBC and TN-IDC differ in many ways. Further studies are required to determine suitable treatment guidelines for patients with MBC.
Topics: Humans; Female; Breast Neoplasms; Retrospective Studies; Carcinoma, Ductal, Breast; Prognosis; Disease-Free Survival
PubMed: 37996840
DOI: 10.1186/s12957-023-03261-w