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Cureus Aug 2023Breast carcinoma in males is a rare and unique condition that differs from breast cancer in females and is typically diagnosed at an advanced stage in older male...
Breast carcinoma in males is a rare and unique condition that differs from breast cancer in females and is typically diagnosed at an advanced stage in older male patients. Late diagnosis is often due to the rarity of male breast carcinoma. Among the various types of breast carcinomas, metaplastic breast carcinoma is one of the rarest kind of breast malignancy and is associated with poorer outcomes. This case report presents a singular case of a young male in his early thirties who presented with a breast lump and was diagnosed with metaplastic breast carcinoma. Breast cancer in males is a topic that is often overlooked and lacks extensive research. However, with an increasing incidence of breast carcinoma in males, including even the rarest forms, such as metaplastic carcinoma, and its occurrence in young patients as highlighted in this case report, it is crucial to initiate more discussions, enhance education, and promote further research in male breast carcinoma. In addition, the psychosocial impacts of the disease should be carefully considered, as men with breast cancer face unique emotional challenges that require attention and support.
PubMed: 37753001
DOI: 10.7759/cureus.44174 -
Nature Communications Sep 2023The biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a...
The biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to ductal epithelial cells in normal breasts of women of African ancestry compared to those of European ancestry. In this study, we demonstrate that these cells have properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFRα and transdifferentiate into adipogenic and osteogenic lineages. PROCR + /ZEB1 + /PDGFRα+ (PZP) cells are enriched in normal breast tissues of women of African compared to European ancestry. PZP: epithelial cell communication results in luminal epithelial cells acquiring basal cell characteristics and IL-6-dependent increase in STAT3 phosphorylation. Furthermore, level of phospho-STAT3 is higher in normal and cancerous breast tissues of women of African ancestry. PZP cells transformed with HRas ± SV40-T/t antigens generate metaplastic carcinoma suggesting that these cells are one of the cells-of-origin of metaplastic breast cancers.
Topics: Humans; Female; Incidence; Breast Neoplasms; Endothelial Protein C Receptor; Receptor, Platelet-Derived Growth Factor alpha; Epithelial Cells
PubMed: 37709737
DOI: 10.1038/s41467-023-41473-6 -
Cancers Aug 2023A better understanding of the mechanisms generating tumour heterogeneity will allow better targeting of current therapies, identify potential resistance mechanisms and...
A better understanding of the mechanisms generating tumour heterogeneity will allow better targeting of current therapies, identify potential resistance mechanisms and highlight new approaches for therapy. We have previously shown that in genetically modified mouse models carrying conditional oncogenic alleles, mammary tumour histotype varies depending on the combination of alleles, the cell type to which they are targeted and, in some cases, reproductive history. This suggests that tumour heterogeneity is not a purely stochastic process; rather, differential activation of signalling pathways leads to reproducible differences in tumour histotype. We propose the NOTCH signalling pathway as one such pathway. Here, we have crossed conditional knockout or alleles into an established mouse mammary tumour model. deletion had no effect on tumour-specific survival; however, loss of alleles resulted in a dose-dependent increase in metaplastic adenosquamous carcinomas (ASQCs). ASQCs and adenomyoepitheliomas (AMEs) also demonstrated a significant increase in AKT signalling independent of status. Therefore, the NOTCH pathway is a suppressor of the ASQC phenotype, while increased PI3K/AKT signalling is associated with ASQC and AME tumours. We propose a model in which PI3K/AKT and NOTCH signalling act interact to determine mouse mammary tumour histotype.
PubMed: 37686600
DOI: 10.3390/cancers15174324 -
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 -
Medicina (Kaunas, Lithuania) Aug 2023Cutaneous mixed tumor is a rare benign neoplasm that exhibits a wide range of metaplastic changes and differentiation in the epithelial, myoepithelial, and stromal... (Review)
Review
Cutaneous mixed tumor is a rare benign neoplasm that exhibits a wide range of metaplastic changes and differentiation in the epithelial, myoepithelial, and stromal components, which is often confused with various other skin lesions. We present an unusual case of a 58-year-old woman with a mixed tumor of the upper lip, previously misdiagnosed as adnexal carcinoma on a preoperative biopsy. The excision biopsy shows a well-circumscribed lesion composed of various cells and structures featuring folliculo-sebaceous differentiation embedded in a prominent chondromyxoid stroma. The immunohistochemical study proves the various lineages of differentiation and classifies the neoplasm as the less common eccrine subtype of cutaneous mixed tumor. The common embryologic origin of the folliculo-sebaceous apocrine complex leads to a great histological variety of cellular components of mixed tumors and the formation of structures that resemble established types of adnexal neoplasms, which could be a diagnostic pitfall, especially on a small incision biopsy.
Topics: Female; Humans; Middle Aged; Skin Neoplasms; Adenoma, Pleomorphic; Biopsy; Cell Differentiation; Confusion
PubMed: 37629755
DOI: 10.3390/medicina59081465 -
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 -
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 -
Asian Journal of Surgery Oct 2023
Topics: Humans; Female; Breast; Carcinoma, Squamous Cell; Cell Differentiation; Breast Neoplasms; Biomarkers, Tumor
PubMed: 37268459
DOI: 10.1016/j.asjsur.2023.05.069 -
Archives of Pathology & Laboratory... Dec 2023Low-grade fibromatosis-like metaplastic carcinoma (FLMC) is a very rare subtype of triple-negative metaplastic (spindle cell) breast carcinoma. It is characterized by...
CONTEXT.—
Low-grade fibromatosis-like metaplastic carcinoma (FLMC) is a very rare subtype of triple-negative metaplastic (spindle cell) breast carcinoma. It is characterized by the proliferation of spindle cells closely resembling fibromatosis, which represents a benign fibroblastic/myofibroblastic breast proliferation. Unlike most triple-negative and basal-like breast cancers, FLMC has a very low potential for metastases, but demonstrates frequent local recurrences.
OBJECTIVE.—
To genetically characterize FLMC.
DESIGN.—
To this end, we analyzed 7 cases by targeted next-generation sequencing for 315 cancer-related genes and performed comparative microarray copy number analysis in 5 of these cases.
RESULTS.—
All cases shared TERT alterations (6 patients with recurrent c.-124C>T TERT promoter mutation and 1 patient with copy number gain encompassing the TERT locus), had oncogenic PIK3CA/PIK3R1 mutations (activation of the PI3K/AKT/mTOR pathway), and lacked mutations in TP53. TERT was overexpressed in all FLMCs. CDKN2A/B loss or mutation was observed in 4 of 7 cases (57%). Furthermore, tumors displayed chromosomal stability, with only few copy number variations and a low tumor mutational burden.
CONCLUSIONS—
We conclude that FLMCs typically show the recurrent TERT promoter mutation c.-124C>T, activation of the PI3K/AKT/mTOR pathway, low genomic instability, and wild-type TP53. In conjunction with previous data of metaplastic (spindle cell) carcinoma with and without fibromatosis-like morphology, FLMC is most likely distinguished by TERT promoter mutation. Thus, our data support the notion of a distinct subgroup within low-grade metaplastic breast cancer with spindle cell morphology and associated TERT mutations.
Topics: Humans; Female; DNA Copy Number Variations; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Breast Neoplasms; Carcinoma; TOR Serine-Threonine Kinases; Mutation; Fibroma; Telomerase
PubMed: 36897999
DOI: 10.5858/arpa.2022-0159-OA