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Cureus Apr 2021Introduction Metaplastic breast carcinoma (MBC) is defined as breast cancer with a heterologous non-glandular component. MBC is considered a special type of breast...
Introduction Metaplastic breast carcinoma (MBC) is defined as breast cancer with a heterologous non-glandular component. MBC is considered a special type of breast cancer with a prognosis that is worse than invasive ductal carcinoma (IDC) of the breast. MBC is the most common breast cancer with a triple-negative profile. Therefore, in this study, we evaluated the clinicopathological parameters, recurrence and survival of MBC in our population. Methods We conducted a retrospective observational study in the Department of Histopathology at Prince Faisal Oncology Centre, Buraidah, Saudi Arabia, over a period of five years. All cases diagnosed as MBC were included in the study. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) immunohistochemistry (IHC) was performed on representative tissue blocks. Results Total 183 cases of MBCs were included in the study, out of which 120 cases were excision specimens. The mean age of the patients was 48.84±12.99 years, and the most common age group was between 36 and 50 years of age. Most of the cases were tumor (T) stage T3 (50%), and nodal metastasis was present in 40% of cases. Most cases were grade III (78.7%). ER, PR and HER2/neu positivity was noted in 15.8%, 13.1%, and 9.8% cases, respectively. Follow-up data were available for 70 cases, with a median follow-up period of 4 (1-7) years. Tumor recurrence was noted in 31.4% cases, with a survival rate of 71.4%. Squamous, chondroid, spindle cell differentiation, and matrix production were noted in 70.5%, 7.1%, 13.7%, and 2.2% cases, respectively. A significant association of squamous differentiation was noted with HER2/neu positivity. An inverse association of spindle cell differentiation was seen with axillary metastasis. Survival analysis by Kaplan-Meier revealed a significant association of survival with tumor recurrence. Conclusion MBC is an important subtype of breast cancer, histopathological identification of which is challenging, owing to varied histological differentiation. We found squamous differentiation to be the most common in MBC, which was associated with HER2/neu positivity. A high recurrence rate of MBC was also observed in our study that was significantly associated with survival.
PubMed: 33987039
DOI: 10.7759/cureus.14347 -
Cancers Nov 2021Triple-negative breast cancers (TNBC), as a group of tumours, have a worse prognosis than stage-matched non-TNBC and lack the benefits of routinely available targeted... (Review)
Review
Triple-negative breast cancers (TNBC), as a group of tumours, have a worse prognosis than stage-matched non-TNBC and lack the benefits of routinely available targeted therapy. However, TNBC is a heterogeneous group of neoplasms, which includes some special type carcinomas with a relatively indolent course. This review on behalf of the European Working Group for Breast Screening Pathology reviews the literature on the special histological types of BC that are reported to have a triple negative phenotype and indolent behaviour. These include adenoid cystic carcinoma of classical type, low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, low-grade mucoepidermoid carcinoma, secretory carcinoma, acinic cell carcinoma, and tall cell carcinoma with reversed polarity. The pathological and known molecular features as well as clinical data including treatment and prognosis of these special TNBC subtypes are summarised and it is concluded that many patients with these rare TNBC pure subtypes are unlikely to benefit from systemic chemotherapy. A consensus statement of the working group relating to the multidisciplinary approach and treatment of these rare tumour types concludes the review.
PubMed: 34830849
DOI: 10.3390/cancers13225694 -
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 -
World Journal of Gastroenterology Jul 2017Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor... (Review)
Review
Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett's oesophagus is an acquired condition whereby the native squamous mucosa of the lower oesophagus is replaced by columnar epithelium following prolonged gastro-oesophageal reflux and is the recognised precursor lesion for oesophageal adenocarcinoma. There are multiple national and society guidelines regarding screening, surveillance and management of Barrett's oesophagus, however all are limited regarding a clear evidence base for a well-demonstrated benefit and cost-effectiveness of surveillance, and robust risk stratification for patients to best use resources. Currently the accepted risk factors upon which surveillance intervals and interventions are based are Barrett's segment length and histological interpretation of the systematic biopsies. Further patient risk factors including other demographic features, smoking, gender, obesity, ethnicity, patient age, biomarkers and endoscopic adjuncts remain under consideration and are discussed in full. Recent evidence has been published to support earlier endoscopic intervention by means of ablation of the metaplastic Barrett's segment when the earliest signs of dysplasia are detected. Further work should concentrate on establishing better risk stratification and primary and secondary preventative strategies to reduce the risk of adenocarcinoma of the oesophagus.
Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers; Biopsy; Chemoprevention; Cost-Benefit Analysis; Endosonography; Epidemiological Monitoring; Esophageal Neoplasms; Esophagoscopy; Esophagus; Gastroesophageal Reflux; Humans; Incidence; Mass Screening; Metabolomics; Patient Selection; Practice Guidelines as Topic; Prevalence; Prognosis; Risk Assessment; Risk Factors; Time Factors
PubMed: 28811703
DOI: 10.3748/wjg.v23.i28.5051 -
Virchows Archiv : An International... Jan 2018Barrett's oesophagus surveillance biopsies represent a significant share of the daily workload for a busy histopathology department. Given the emphasis on endoscopic... (Review)
Review
Barrett's oesophagus surveillance biopsies represent a significant share of the daily workload for a busy histopathology department. Given the emphasis on endoscopic detection and dysplasia grading, it is easy to forget that the benefits of these screening programs remain unproven. The majority of patients are at low risk of progression to oesophageal adenocarcinoma, and periodic surveillance of these patients is burdensome and costly. Here, we investigate the parallels in the development of Barrett's oesophagus and other scenarios of wound healing in the intestine. There is now increased recognition of the full range of glandular phenotypes that can be found in patients' surveillance biopsies, and emerging evidence suggests parallel pathways to oesophageal adenocarcinoma. Greater understanding of the conditions that favour progression to cancer in the distal oesophagus will allow us to focus resources on patients at increased risk.
Topics: Adenocarcinoma; Barrett Esophagus; Disease Progression; Early Detection of Cancer; Esophageal Neoplasms; Humans; Risk Factors
PubMed: 29500519
DOI: 10.1007/s00428-018-2317-1 -
Hereditary Cancer in Clinical Practice Jan 2021Metaplastic carcinoma of the breast consists of both invasive ductal carcinoma and metaplastic carcinoma. This rare subtype of cancer has a poor prognosis. The...
BACKGROUND
Metaplastic carcinoma of the breast consists of both invasive ductal carcinoma and metaplastic carcinoma. This rare subtype of cancer has a poor prognosis. The development of metaplastic breast cancer and relationship with BRCA1 are not well known. Here, we report a rare case of germline BRCA1 mutation-positive breast cancer with chondroid metaplasia.
CASE PRESENTATION
A 39-year-old Japanese woman with a family history of breast cancer in her mother and ovarian cancer in her maternal grandmother consulted at our hospital with a left breast mass. Needle biopsy for the mass was performed, leading to a diagnosis of invasive breast cancer with chondroid metaplasia. We performed left mastectomy + sentinel lymph node biopsy + tissue expander insertion and replaced with a silicone implant later. Pathological examination revealed that the patient had triple-negative breast cancer. Four courses of doxorubicin+ cyclophosphamide therapy were performed as adjuvant therapy after surgery. We performed genetic counseling and genetic testing, and the results suggested the germline BRCA1 mutation 307 T> A (L63*). She has currently lived without a relapse for 2 years post-surgery.
CONCLUSIONS
There have been only 6 cases of metaplastic breast carcinoma with germline BRCA1 mutations including our case. Patients with BRCA1 mutations may develop basal-like subtypes or M type of triple-negative breast cancer besides metaplastic breast cancers.
PubMed: 33407746
DOI: 10.1186/s13053-020-00162-x -
Cancers Jul 2019Endometrial carcinosarcoma (ECS) represents one of the most extreme examples of tumor heterogeneity among human cancers. ECS is a clinically aggressive, high-grade,... (Review)
Review
Endometrial carcinosarcoma (ECS) represents one of the most extreme examples of tumor heterogeneity among human cancers. ECS is a clinically aggressive, high-grade, metaplastic carcinoma. At the morphological level, intratumor heterogeneity in ECS is due to an admixture of epithelial (carcinoma) and mesenchymal (sarcoma) components that can include heterologous tissues, such as skeletal muscle, cartilage, or bone. Most ECSs belong to the copy-number high serous-like molecular subtype of endometrial carcinoma, characterized by the mutation and the frequently accompanied by a large number of gene copy-number alterations, including the amplification of important oncogenes, such as and . However, a proportion of cases (20%) probably represent the progression of tumors initially belonging to the copy-number low endometrioid-like molecular subtype (characterized by mutations in genes such as , or ), after the acquisition of the mutations. Only a few ECS belong to the microsatellite-unstable hypermutated molecular type and the -mutated, ultramutated molecular type. A common characteristic of all ECSs is the modulation of genes involved in the epithelial to mesenchymal process. Thus, the acquisition of a mesenchymal phenotype is associated with a switch from E- to N-cadherin, the up-regulation of transcriptional repressors of E-cadherin, such as Snail Family Transcriptional Repressor 1 and 2 (SNAI1 and SNAI2), Zinc Finger E-Box Binding Homeobox 1 and 2 (ZEB1 and ZEB2), and the down-regulation, among others, of members of the miR-200 family involved in the maintenance of an epithelial phenotype. Subsequent differentiation to different types of mesenchymal tissues increases tumor heterogeneity and probably modulates clinical behavior and therapy response.
PubMed: 31324031
DOI: 10.3390/cancers11070964 -
Cell Death & Disease Oct 2022Acinar-to-ductal metaplasia (ADM) is a precursor lesion of pancreatic ductal adenocarcinoma (PDAC); however, the regulators of the ADM-mediated PDAC development and its...
Acinar-to-ductal metaplasia (ADM) is a precursor lesion of pancreatic ductal adenocarcinoma (PDAC); however, the regulators of the ADM-mediated PDAC development and its targeting are poorly understood. RNA polymerase II-associated factor 1 (PAF1) maintains cancer stem cells leading to the aggressiveness of PDAC. In this study, we investigated whether PAF1 is required for the YAP1-mediated PDAC development and whether CA3 and verteporfin, small molecule inhibitors of YAP1/TEAD transcriptional activity, diminish pancreatic cancer (PC) cell growth by targeting the PAF1/YAP1 axis. Here, we demonstrated that PAF1 co-expresses and interacts with YAP1 specifically in metaplastic ducts of mouse cerulein- or Kras-induced ADM and human PDAC but not in the normal pancreas. PAF1 knockdown (KD) reduced SOX9 in PC cells, and the PC cells showed elevated PAF1/YAP1 complex recruitment to the promoter of SOX9. The PAF1 KD reduced the 8xTEAD and SOX9 promoter-luciferase reporter activities in the mouse KC (Kras; Pdx-1 Cre) cells and human PC cells, indicating that the PAF1 is required for the YAP1-mediated development of ADM and PC. Moreover, treatment with CA3 or verteporfin reduced the expressions of PAF1, YAP1, TEAD4, and SOX9 and decreased colony formation and stemness in KC and PC cells. CA3 treatment also reduced the viability and proliferation of PC cells and diminished the duct-like structures in KC acinar explants. CA3 or verteporfin treatment decreased the recruitment of the PAF1/YAP1 complex to the SOX9 promoter in PC cells and reduced the 8xTEAD and SOX9 promoter-luciferase reporter activities in KC and PC cells. Overall, PAF1 cooperates with YAP1 during ADM and PC development, and verteporfin and CA3 inhibit ADM and PC cell growth by targeting the PAF1/YAP1/SOX9 axis in vitro and ex vivo models. This study identified a regulatory axis of PDAC initiation and its targeting, paving the way for developing targeted therapeutic strategies for pancreatic cancer patients.
Topics: Acinar Cells; Animals; Carcinoma, Pancreatic Ductal; Cell Transformation, Neoplastic; Ceruletide; DNA-Binding Proteins; Humans; Luciferases; Metaplasia; Mice; Pancreatic Ducts; Pancreatic Neoplasms; Proto-Oncogene Proteins p21(ras); RNA Polymerase II; TEA Domain Transcription Factors; Transcription Factors; Verteporfin; YAP-Signaling Proteins
PubMed: 36180487
DOI: 10.1038/s41419-022-05258-x -
Pathobiology : Journal of... 2022Immunohistochemistry (IHC) plays an important role in the evaluation of breast pathology specimens to provide both diagnostic and prognostic/therapeutic information.... (Review)
Review
Immunohistochemistry (IHC) plays an important role in the evaluation of breast pathology specimens to provide both diagnostic and prognostic/therapeutic information. Although most IHCs used in breast pathology can be easily interpreted, pitfalls do exist, especially in some uncommon scenarios. This review intends to focus on the challenging areas such as the interpretation of myoepithelial cell markers in differentiating benign proliferation and in situ carcinoma from invasive carcinoma, lobular cell markers in differentiating lobular from ductal carcinoma, cytokeratin and other markers in diagnosing metaplastic carcinoma, and breast tissue origin markers in diagnosing breast primary carcinoma. The challenges in interpreting prognostic and predictive markers will be also discussed.
Topics: Biomarkers, Tumor; Breast; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Female; Humans; Immunohistochemistry; Keratins
PubMed: 35249034
DOI: 10.1159/000521682 -
Cancer Microenvironment : Official... Dec 2017Metaplastic breast carcinoma (MBC) is a rare subtype of invasive breast cancer and has poor prognosis. In general, cancers are heterogeneous cellular masses comprised of...
Metaplastic breast carcinoma (MBC) is a rare subtype of invasive breast cancer and has poor prognosis. In general, cancers are heterogeneous cellular masses comprised of different cell types and their extracellular matrix (ECM). However, little is known about the composition of the ECM and its constituents in MBC. Decorin is a ubiquitous ECM macromolecule known of its oncosuppressive activity. As such, it provides an intriguing molecule in the development of novel therapeutics for different malignancies such as MBC. In this study, decorin immunoreactivity and the effect of adenoviral decorin cDNA (Ad-DCN) transduction were examined in MBC. Multiple immunohistochemical stainings were used to characterize a massive breast tumour derived from an old woman. Furthermore, three-dimensional (3D) explant cultures derived from the tumour were transduced with Ad-DCN to study the effect of the transduction on the explants. The MBC tumour was shown to be completely negative for decorin immunoreactivity demonstrating that the malignant cells were not able to synthesize decorin. Ad-DCN transduction resulted in a markedly altered cytological phenotype of MBC explants by decreasing the amount of atypical cells and by inhibiting cell proliferation. The results of this study support approaches to develop new, decorin-based adjuvant therapies for MBC.
PubMed: 28653173
DOI: 10.1007/s12307-017-0195-8