Abstract:Metaplastic breast carcinoma is a rare and aggressive condition, accounting less than 1% of breast malignancies. It presents with large mass and frequently with distant metastasis at time of diagnosis. Morphologically, it is characterized by the differentiation of neoplastic epithelium into epithelial or mesenchymal-looking elements like squamous cells, spindle cells, cartilage, or bone and has poor prognosis with its triple negative status.
“…They displayed a cytoplasm rich in filamentous structures, that suggested the start of the keratinization process. Indeed, the enrichment in keratins expression and the presence of traces of keratinization were features observed in squamous cell carcinoma, which is a very rare and aggressive BC subtype and seemed to be related to a transition to metaplastic cell carcinoma [ 19 – 22 ]. Fig.…”
Background
Breast cancer Patient Derived Organoids (PDO) have been demonstrated to be a reliable model to study cancer that promised to replace and reduce the use of animals in pre-clinical research. They displayed concordance with the tissue of origin, resuming its heterogenicity and representing a good platform to develop approaches of personalized medicines. Although obtain PDOs from mammary tumour, was a very challenging process, several ongoing studies evaluated them as a platform to study efficacy, sensitivity and specificity of new drugs and exploited them in personalized medicine. Despite tissue organization represented a crucial point to evaluate in a 3-dimensional model, since it could influence drug penetration, morphology of breast cancer PDOs has not been analysed yet. Here, we proposed a complete ultrastructural analysis of breast PDOs obtained from tumour and healthy tissues to evaluate how typical structures observed in mammary gland were resumed in this model.
Methods
81 samples of mammary tissue (healthy or tumour) resulting from surgical resections have been processed to obtain PDO. The resulting PDOs embedded in matrigel drop have been processed for transmission electron microscopy and analysed. A comparison between ones from healthy and ones from cancerous tissue has been performed and PDOs derived from tumour tissue have been stratified according to their histological and molecular subtype.
Result
The morphological analysis performed on 81 PDO revealed an organized structure rich in Golgi, secretion granules and mitochondria, which was typical of cells with a strong secretory activity and active metabolism. The presence of desmosomes, inter and intracellular lumens and of microvilli and interdigitations signified a precise tissue-organization. Each PDO has been classified based on whether or not it possessed (i) peripheral ridges in mitochondria, (ii) intracellular lumens, (iii) intercellular lumens, (iv) micro-vesicles, (v) open desmosomes, (vi) cell debris, (vii) polylobed nuclei, (viii) lysosomes and (ix) secretion granules, in order to identify features coupled with the cancerous state or with a specific histological or molecular subtype.
Conclusion
Here we have demonstrated the suitability of breast cancer PDO as 3-dimensional model of mammary tissue. Besides, some structural features characterizing cancerous PDO have been observed, identifying the presence of distinctive traits.
“…They displayed a cytoplasm rich in filamentous structures, that suggested the start of the keratinization process. Indeed, the enrichment in keratins expression and the presence of traces of keratinization were features observed in squamous cell carcinoma, which is a very rare and aggressive BC subtype and seemed to be related to a transition to metaplastic cell carcinoma [ 19 – 22 ]. Fig.…”
Background
Breast cancer Patient Derived Organoids (PDO) have been demonstrated to be a reliable model to study cancer that promised to replace and reduce the use of animals in pre-clinical research. They displayed concordance with the tissue of origin, resuming its heterogenicity and representing a good platform to develop approaches of personalized medicines. Although obtain PDOs from mammary tumour, was a very challenging process, several ongoing studies evaluated them as a platform to study efficacy, sensitivity and specificity of new drugs and exploited them in personalized medicine. Despite tissue organization represented a crucial point to evaluate in a 3-dimensional model, since it could influence drug penetration, morphology of breast cancer PDOs has not been analysed yet. Here, we proposed a complete ultrastructural analysis of breast PDOs obtained from tumour and healthy tissues to evaluate how typical structures observed in mammary gland were resumed in this model.
Methods
81 samples of mammary tissue (healthy or tumour) resulting from surgical resections have been processed to obtain PDO. The resulting PDOs embedded in matrigel drop have been processed for transmission electron microscopy and analysed. A comparison between ones from healthy and ones from cancerous tissue has been performed and PDOs derived from tumour tissue have been stratified according to their histological and molecular subtype.
Result
The morphological analysis performed on 81 PDO revealed an organized structure rich in Golgi, secretion granules and mitochondria, which was typical of cells with a strong secretory activity and active metabolism. The presence of desmosomes, inter and intracellular lumens and of microvilli and interdigitations signified a precise tissue-organization. Each PDO has been classified based on whether or not it possessed (i) peripheral ridges in mitochondria, (ii) intracellular lumens, (iii) intercellular lumens, (iv) micro-vesicles, (v) open desmosomes, (vi) cell debris, (vii) polylobed nuclei, (viii) lysosomes and (ix) secretion granules, in order to identify features coupled with the cancerous state or with a specific histological or molecular subtype.
Conclusion
Here we have demonstrated the suitability of breast cancer PDO as 3-dimensional model of mammary tissue. Besides, some structural features characterizing cancerous PDO have been observed, identifying the presence of distinctive traits.
“…The prognosis of patients with MBC depends on its grading and staging and also varies with the subtypes where fibromatosis-like carcinomas and low-grade adenosquamous carcinomas show more indolent behavior, while high-grade spindle cell, squamous cell, adenosquamous, and mixed metaplastic carcinoma are associated with the worst prognosis ( 8 , 9 ). Compared to breast cancer overall, metaplastic breast cancer is faster growing and more likely to metastasize to other parts of the body.…”
Section: Discussionmentioning
confidence: 99%
“…Compared to breast cancer overall, metaplastic breast cancer is faster growing and more likely to metastasize to other parts of the body. It is also more likely to recur after a successful initial treatment ( 8 , 9 ). The overall 5-year survival rate of patients with MBC is 40%, and local recurrence rate is reported to be 35-62% in the first 2-5 years ( 8 , 9 ).…”
Section: Discussionmentioning
confidence: 99%
“…It is also more likely to recur after a successful initial treatment ( 8 , 9 ). The overall 5-year survival rate of patients with MBC is 40%, and local recurrence rate is reported to be 35-62% in the first 2-5 years ( 8 , 9 ).…”
Background: Metaplastic breast cancer is a clinically rare subtype of breast carcinomas, accounting for less than 1% of all breast neoplasms, and was not officially recognized till the end of the 20th century as an independent pathological diagnosis. Objective: In this paper, we report a case of metaplastic breast cancer with squamous differentiation in a 51-year-old female, with a succinct review of the literature. Case Report: The patient presented to our outpatient department with a complaint of left breast mass for 2 months duration with a diagnostic workup found to be grade three metaplastic carcinoma with squamous differentiation. The management decision was to proceed with neoadjuvant chemotherapy, followed by surgical intervention based on the tumor cell response to neoadjuvant therapy. Conclusion: Metaplastic breast cancer represents a rare clinical entity, encountered in a minority of patients. The clinical presentation of metaplastic carcinomas in general is similar to other breast cancers, however, metaplastic breast cancer tend to present in later stages as a rapidly growing mass with poor prognosis. The recognized poor prognosis along with rarity necessities having a high index of suspicion for early detection and appropriate management of metaplastic breast cancer.
“…Metaplastic squamous cell carcinoma constitutes 0.25-1 per cent of invasive duct carcinoma of breast, which is an aggressive tumor with a prognosis worse than triple negative invasive duct carcinoma of breast. [9][10][11][12][13] In the present study, a case report of metaplastic squamous cell carcinoma of breast carcinoma which masqueraded as tuberculous mastitis is being presented.…”
Tuberculous mastitis and invasive breast cancers are known to co-exist or occur in the breast independently of each other, albeit the former being less common in developed countries. Tuberculous mastitis with its clinical presentation and morphological features can caricature invasive breast carcinoma. The overlapping features of tuberculous mastitis and metaplastic squamous cell carcinoma often lead to, if no due clinical diligence and discretion is used, bewildering misinterpretation with the vicissitude of diagnostic implications of tuberculous mastitis ensuing catastrophic and perilous ramifications. A 42-year-old woman presented with exophytic growth with extensive areas of ulceration. Clinically, the lesion was diagnosed as disseminated tuberculous mastitis based on clinical and morphological features, which was surgically resected. On histological examination, the lesion was diagnosed as invasive metaplastic squamous cell carcinoma. Thecase being presented here displays the vagary involved in clinical diagnosis of tuberculous mastitis inasmuch as it often shares clinical and morphological features with a devastatingly perilous variant of invasive duct carcinoma, metaplastic squamous cell carcinoma, the inadvertent eschewing of or misapprehending of which may engender devastating prognostic implications.
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