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The Journal of Pathology. Clinical... May 2021Microglandular adenosis (MGA) represents a rare neoplasm of the mammary gland, which in a subset of cases may be associated with triple-negative breast cancer (BC). The...
Microglandular adenosis (MGA) represents a rare neoplasm of the mammary gland, which in a subset of cases may be associated with triple-negative breast cancer (BC). The biology of MGA is poorly understood. In this study, eight MGA cases (n = 4 with and n = 4 without associated BC) were subjected to a comprehensive characterization using immunohistochemistry, genome-wide DNA copy number (CN) profiling, fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and DNA methylation profiling using 850 K arrays and bisulfite pyrosequencing. Median patient age was 61 years (range 57-76 years). MGA lesions were estrogen receptor (ER)-negative, progesterone receptor-negative, HER2-negative, and S100-positive. DNA CN alterations (CNAs) were complex or limited to few gains and losses. CN gain on chromosome 2q was the most common CNA and was validated by FISH in five of eight cases. NGS demonstrated an average of two mutations per case (range 0-5) affecting 10 different genes (ARID1A, ATM, CTNNB1, FBXW7, FGFR2, MET, PIK3CA, PMS2, PTEN, and TP53). CNAs and mutations were similar in MGA and adjacent BC, indicating clonal relatedness. DNA methylation profiling identified aberrant hypermethylation of CpG sites within GATA3, a key transcription factor required for luminal differentiation. Immunohistochemistry showed regular GATA3 protein expression in the normal mammary epithelium and in ER-positive BC. Conversely, GATA3 was reduced or lost in all MGA cases tested (8/8). In conclusion, MGA is characterized by common CN gain on chromosome 2q and loss of GATA3. Epigenetic inactivation of GATA3 may provide a new clue to the peculiar biology of this rare neoplasia.
Topics: Aged; Biomarkers, Tumor; Chromosome Aberrations; Chromosomes, Human, Pair 2; DNA Methylation; Female; Fibrocystic Breast Disease; GATA3 Transcription Factor; Gene Silencing; Humans; Middle Aged; Molecular Diagnostic Techniques; Precancerous Conditions; Triple Negative Breast Neoplasms
PubMed: 33382535
DOI: 10.1002/cjp2.195 -
Journal of Dermatological Case Reports Mar 2011Cowden syndrome is a rare genodermatosis charactarized by presence of multiple hamartomas. The aim of the study was to specify the clinical, therapeutic and prognostic...
BACKGROUND
Cowden syndrome is a rare genodermatosis charactarized by presence of multiple hamartomas. The aim of the study was to specify the clinical, therapeutic and prognostic aspects of Cowden syndrome.
CASES REPORT
Our study included 4 patients with Cowden syndrome, 2 males and 2 females between 14 and 46 years old. Clinical examination of the skin revealed facials papules (4 cases), acral keratosis (1 case), translucent keratotic papules (2 cases). Oral examination revealed papules (4 cases), papillomatosis (4 cases), gingival hypertrophy (4 cases) and scrotal tongue (2 cases). Investigations revealed thyroid lesions (2 cases), fibrocystic disease and lipoma of the breast in 1 case, "glycogenic acanthosis" (1 case), macrocephaly (2 cases), dysmorphic face (1 case) and lichen nitidus (1 case). Oral etretinate and acitretine were temporary efficient in 2 patients. Topical treatment with tretinoin lotion resulted in some improvement in cutaneous, but not mucosal lesions in one patient. No cancer was revealed.
CONCLUSION
The pathognomonic mucocutaneous lesions were found in all patients. However, no degenerative lesions have been revealed. A new association of Cowden syndrome with lichen nitidus was found. Treatment with oral retinoids was efficient on cutaneous lesions.
PubMed: 21886759
DOI: 10.3315/jdcr.2011.1063 -
Journal of Clinical Imaging Science 2023Microglandular adenosis (MGA) and atypical microglandular adenosis (AMGA) are intensely rare and distinctive forms of adenosis of the breast, usually occurring in...
Microglandular adenosis (MGA) and atypical microglandular adenosis (AMGA) are intensely rare and distinctive forms of adenosis of the breast, usually occurring in middle-aged women. Carcinoma arising in MGA is an extremely rare subtype of breast carcinoma, and most reported cases are of invasive carcinoma. Ultrasound and magnetic resonance imaging are accurate imaging modalities for diagnosing these abnormalities. Our goal in this article was to report a rare instance of ductal carcinoma (DCIS) arising from MGA and AMGA in a very young Vietnamese woman who presented with a palpable mass in her right breast for 1 month. During clinical examination and imaging, suspected lesions were found and categorized as BI-RADS 4a. The final histopathological findings confirmed DCIS arising from MGA/AMGA. In this patient, the disease was detected and managed early when the lesion was localized in the duct and there were no signs of invasive ductal carcinoma.
PubMed: 37292245
DOI: 10.25259/JCIS_32_2023 -
Modern Pathology : An Official Journal... Jan 2017Acinic cell carcinoma is an indolent form of invasive breast cancer, whereas microglandular adenosis has been shown to be a neoplastic proliferation. Both entities...
Genetic analysis of microglandular adenosis and acinic cell carcinomas of the breast provides evidence for the existence of a low-grade triple-negative breast neoplasia family.
Acinic cell carcinoma is an indolent form of invasive breast cancer, whereas microglandular adenosis has been shown to be a neoplastic proliferation. Both entities display a triple-negative phenotype, and may give rise to and display somatic genomic alterations typical of high-grade triple-negative breast cancers. Here we report on a comparison of previously published data on eight carcinoma-associated microglandular adenosis and eight acinic cell carcinomas subjected to targeted massively parallel sequencing targeting all exons of 236 genes recurrently mutated in breast cancer and/or DNA repair-related. Somatic mutations, insertions/ deletions, and copy number alterations were detected using state-of-the-art bioinformatic algorithms. All cases were of triple-negative phenotype. A median of 4.5 (1-13) and 4.0 (1-7) non-synonymous somatic mutations per carcinoma-associated microglandular adenosis and acinic cell carcinoma were identified, respectively. TP53 was the sole highly recurrently mutated gene (75% in microglandular adenosis versus 88% in acinic cell carcinomas), and TP53 mutations were consistently coupled with loss of heterozygosity of the wild-type allele. Additional somatic mutations shared by both groups included those in BRCA1, PIK3CA, and INPP4B. Recurrent (n=2) somatic mutations restricted to microglandular adenosis or acinic cell carcinomas included those affecting PTEN and MED12 or ERBB4, respectively. No significant differences in the repertoire of somatic mutations were detected between microglandular adenosis and acinic cell carcinomas, and between this group of lesions and 77 triple-negative carcinomas from The Cancer Genome Atlas. Microglandular adenosis and acinic cell carcinomas, however, were genetically distinct from estrogen receptor-positive and/or HER2-positive breast cancers from The Cancer Genome Atlas. Our findings support the contention that microglandular adenosis and acinic cell carcinoma are part of the same spectrum of lesions harboring frequent TP53 somatic mutations, and likely represent low-grade forms of triple-negative disease with no/minimal metastatic potential, of which a subset has the potential to progress to high-grade triple-negative breast cancer.
Topics: BRCA1 Protein; Breast; Breast Neoplasms; Carcinoma, Acinar Cell; Class I Phosphatidylinositol 3-Kinases; Female; Fibrocystic Breast Disease; Gene Expression Regulation, Neoplastic; High-Throughput Nucleotide Sequencing; Humans; Mediator Complex; Neoplasm Grading; Phosphoric Monoester Hydrolases; Receptor, ErbB-4; Triple Negative Breast Neoplasms
PubMed: 27713419
DOI: 10.1038/modpathol.2016.161 -
Histopathology Jun 2018Despite the significant biological, behavioural and management differences between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast, they share many... (Review)
Review
Despite the significant biological, behavioural and management differences between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast, they share many morphological and molecular similarities. Differentiation of these two different lesions in breast pathological diagnosis is based typically on the presence of an intact barrier between the malignant epithelial cells and stroma; namely, the myoepithelial cell (MEC) layer and surrounding basement membrane (BM). Despite being robust diagnostic criteria, the identification of MECs and BM to differentiate in-situ from invasive carcinoma is not always straightforward. The MEC layer around DCIS may be interrupted and/or show an altered immunoprofile. MECs may be absent in some benign locally infiltrative lesions such as microglandular adenosis and infiltrating epitheliosis, and occasionally in non-infiltrative conditions such as apocrine lesions, and in these contexts this does not denote malignancy or invasive disease with metastatic potential. MECs may also be absent around some malignant lesions such as some forms of papillary carcinoma, yet these behave in an indolent fashion akin to some DCIS. In Paget's disease, malignant mammary epithelial cells extend anteriorly from the ducts to infiltrate the epidermis of the nipple but do not typically infiltrate through the BM into the dermis. Conversely, BM-like material can be seen around invasive carcinoma cells and around metastatic tumour cell deposits. Here, we review the role of MECs and BM in breast pathology and highlight potential clinical implications. We advise caution in interpretation of MEC features in breast pathology and mindfulness of the substantive evidence base in the literature associated with behaviour and clinical outcome of lesions classified as benign on conventional morphological examination before changing classification to an invasive lesion on the sole basis of MEC characteristics.
Topics: Breast; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Epithelial Cells; Female; Humans; Stromal Cells
PubMed: 29197112
DOI: 10.1111/his.13446 -
Cureus Apr 2023Microglandular adenosis (MGA) is a proliferative breast lesion composed of small, uniform glands lacking a myoepithelial cell layer while still invested by the basement...
Microglandular adenosis (MGA) is a proliferative breast lesion composed of small, uniform glands lacking a myoepithelial cell layer while still invested by the basement membrane. The glands percolate haphazardly through the breast parenchyma rather than maintaining a lobular architecture, typical of other forms of adenosis.MGA is a benign lesion though atypical forms have been well described, often in close association with carcinoma. MGA, atypical MGA (AMGA), and the vast majority of MGA-associated carcinomas (MGACA) are negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) by immunohistochemistry. In light of these findings and early molecular studies, MGA is hypothesized to represent a clonal process and nonobligate precursor of basal-type breast carcinomas. We present the case of a 58-year-old woman and the first published molecular comparison of a luminal-type invasive ductal carcinoma with its associated MGA/AMGA. Analysis of small nucleotide variants (SNVs) revealed that 63% of the SNVs identified in the MGA were present in the AMGA while only 10% of them were present in the MGACA, suggesting a direct relationship between MGA and AMGA but not MGA and MGACA.
PubMed: 37159793
DOI: 10.7759/cureus.37198 -
Asian Journal of Pharmaceutical Sciences May 2017Inflammation remains a key event during most of the diseases and physiological imbalance. Acute inflammation is an essential physiological event by immune system for a... (Review)
Review
Inflammation remains a key event during most of the diseases and physiological imbalance. Acute inflammation is an essential physiological event by immune system for a protective measure to remove cause of inflammation and failure of resolution lead to chronic inflammation. Over a period of time, a number of drugs mostly chemical have been deployed to combat acute and chronic inflammation. Recently, enzyme based anti-inflammatory drugs became popular over conventional chemical based drugs. Serratiopeptidase, a proteolytic enzyme from trypsin family, possesses tremendous scope in combating inflammation. Serine protease possesses a higher affinity for cyclooxygenase (COX-I and COX-II), a key enzyme associated with production of different inflammatory mediators including interleukins (IL), prostaglandins (PGs) and thromboxane (TXs) etc. Currently, arthritis, sinusitis, bronchitis, fibrocystic breast disease, and carpal tunnel syndrome, etc. are the leading inflammatory disorders that affected the entire the globe. In order to conquer inflammation, both acute and chronic world, physician mostly relies on conventional drugs. The most common drugs to combat acute inflammation are Nonsteroidal anti-inflammatory drugs (NSAIDs) alone and or in combination with other drugs. However, during chronic inflammation, NSAIDs are often used with steroidal drugs such as autoimmune disorders. These drugs possess several limitations such as side effects, ADR, etc. In order to overcome these limitations and complications, enzyme based drugs (anti-inflammatory) emerged, and aim for a new high since the last decade. Serine protease, the largest proteolytic family has been reported for several therapeutic applications, including anti-inflammatory. Serratiopeptidase is a leading enzyme which has a very long history in medical as an effective anti-inflammatory drug. Current study emphasizes present scenario and future prospect of serratiopeptidase as an anti-inflammatory drug. The study also illustrates a comparative analysis of conventional drugs and enzyme based therapeutic to combat inflammation.
PubMed: 32104332
DOI: 10.1016/j.ajps.2017.01.003 -
Archives of Pathology & Laboratory... Jul 2016-The morphologic spectrum of secretory breast lesions encompasses benign, borderline, and malignant lesions. They are characterized by luminal pink, proteinaceous... (Review)
Review
CONTEXT
-The morphologic spectrum of secretory breast lesions encompasses benign, borderline, and malignant lesions. They are characterized by luminal pink, proteinaceous secretions and variable degrees of cytologic atypia ranging from low grade to high grade, with frequent papillary formations. Other lesions, benign and malignant, can also show luminal and extraluminal secretions and share similar features with secretory lesions, making them diagnostically challenging.
OBJECTIVE
-To discuss the differential diagnosis of secretory breast lesions, emphasizing the most important diagnostic features of benign and malignant lesions. Lesions with intraluminal secretions discussed at length in this review include pregnancy-like hyperplasia, cystic hypersecretory hyperplasia, collagenous spherulosis, microglandular adenosis, hypersecretory carcinoma, and secretory carcinoma. Lesions with extravasated mucin, such as mucocele-like lesions and mucinous carcinoma, are also briefly discussed.
DATA SOURCES
-Published articles obtained from a PubMed search of the English literature were the primary source for this review.
CONCLUSIONS
-Lesions with secretory features described in this review show a pathologic spectrum, sometimes even within the same lesion. As a consequence, one should employ a low threshold for recommending reexcision on a core biopsy containing benign-appearing hypersecretory glands and use all ancillary data, including clinical presentation, imaging findings, morphology, immunohistochemistry, and molecular pathology, to render a final diagnosis.
Topics: Adenocarcinoma, Mucinous; Breast; Breast Neoplasms; Carcinoma; Female; Humans
PubMed: 27362569
DOI: 10.5858/arpa.2015-0250-RA -
Diagnostics (Basel, Switzerland) Jun 2022Microglandular adenosis is a non-lobulocentric haphazard proliferation of small round glands composed of a single layer of flat to cuboidal epithelial cells. The...
Microglandular adenosis is a non-lobulocentric haphazard proliferation of small round glands composed of a single layer of flat to cuboidal epithelial cells. The glandular structures lack a myoepithelial layer; however, they are surrounded by a basement membrane. Its clinical course is benign, when it is not associated with invasive carcinoma. In around 30% of cases, there is a gradual transition to atypical microglandular adenosis, carcinoma in situ, and invasive breast carcinoma of several different histologic subtypes, including an invasive carcinoma of no special type, metaplastic matrix-producing carcinoma, secretory carcinoma, metaplastic carcinoma with squamous differentiation, acinic cell carcinoma, spindle cell carcinoma, and adenoid cystic carcinoma. Recent molecular studies suggest that microglandular adenosis is a non-obligate precursor of triple-negative breast carcinomas. In this manuscript, we present a unique case of microglandular adenosis associated with metaplastic matrix-producing carcinoma and HER-2 neu oncoprotein positive pleomorphic lobular carcinoma in situ with apocrine differentiation in a 79-year-old patient.
PubMed: 35741268
DOI: 10.3390/diagnostics12061458 -
American Family Physician Nov 2003The breast mass is a clinical problem commonly encountered by family physicians. Fine-needle and core biopsy techniques require training and cytopathologist support. In... (Review)
Review
The breast mass is a clinical problem commonly encountered by family physicians. Fine-needle and core biopsy techniques require training and cytopathologist support. In contrast, breast cyst aspiration using a 21- or 22-gauge needle is a simple, cost-effective, minimally invasive procedure. The technique is easy to learn and can be practiced on a breast model. Breast cyst aspiration may be attempted in many women who present with a palpable, dominant breast mass. If clear fluid is aspirated and the mass resolves, malignancy is unlikely, and breast cyst is the probable diagnosis. In this situation, reevaluation in four to six weeks is appropriate; if the cyst has not recurred, only routine mammographic surveillance is required. Referral for fine-needle or excisional biopsy is indicated if the aspirate is bloody or extremely tenacious, if no fluid can be aspirated, or if there is residual mass after aspiration. Complications such as local discomfort, bruising, and infection are uncommon.
Topics: Biopsy, Needle; Breast; Exudates and Transudates; Family Practice; Female; Fibrocystic Breast Disease; Humans; Models, Anatomic
PubMed: 14655807
DOI: No ID Found