-
Medicine Oct 2020Breast adenomyoepithelioma (AME) is a rare tumor composed of myoepithelial cells and ductal or luminal cells. Most cases of AME are benign, but rare cases in which... (Review)
Review
Adenomyoepithelioma with a human epidermal growth factor receptor 2-fluorescence in situ hybridization-confirmed ductal carcinoma in situ component: A case report and review of the literature.
INTRODUCTION
Breast adenomyoepithelioma (AME) is a rare tumor composed of myoepithelial cells and ductal or luminal cells. Most cases of AME are benign, but rare cases in which either or both cell types exhibited malignant features have been reported. Due to its rarity, no diagnostic criteria for malignancy have been established for AME.
PATIENT CONCERNS
A 64-year-old woman presented with a mass in her right breast. Fine-needle aspiration cytology and biopsy examinations revealed lesions composed of spindle-shaped cells and round epithelial cells. AME was suspected, and partial mastectomy was performed.
DIAGNOSIS
The tumor specimen showed AME, which mainly consisted of spindle-shaped myoepithelial cells with slight atypia, admixed with tubular luminal cells and small areas of atypical intraductal proliferative lesions. No apparent features of malignancy, such as necrosis or invasion, were seen in the myoepithelial cells or the luminal or intraductal component. However, the atypical intraductal component exhibited focal nuclear atypia, a cribriform pattern, and moderate to strong membranous human epidermal growth factor receptor 2 (HER2) immunoreactivity. HER2 amplification was detected in focal regions of the atypical intraductal component by fluorescence in situ hybridization (FISH), which resulted in a diagnosis of AME with ductal carcinoma in situ.
OUTCOMES
The patient did not receive further therapy and was free from tumor recurrence at 23 months after the operation.
CONCLUSION
HER2 FISH might be useful for evaluating suspected AME tumors for malignancy when an atypical ductal lesion that lacks definitive features of malignancy is encountered.
Topics: Adenomyoepithelioma; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Female; Humans; In Situ Hybridization, Fluorescence; Middle Aged; Receptor, ErbB-2
PubMed: 33080708
DOI: 10.1097/MD.0000000000022665 -
Modern Pathology : An Official Journal... Jan 2021Breast cancer is a vastly heterogeneous disease encompassing a panoply of special histological subtypes. Although rare breast tumors have largely not been investigated... (Review)
Review
Breast cancer is a vastly heterogeneous disease encompassing a panoply of special histological subtypes. Although rare breast tumors have largely not been investigated systematically in large scale genomics series, recent studies have shed light on the genetic underpinnings of special histologic subtypes of breast cancer. Genomic analyses of estrogen receptor-positive special histologic types of breast cancer have not resulted in the identification of novel pathognomonic genetic alterations in addition to the confirmation of the presence of CDH1 loss-of-function mutations in invasive lobular carcinomas. By contrast, the analyses of triple-negative breast cancers have demonstrated that low-grade triple-negative breast cancers categorically differ from the common forms of high-grade triple-negative disease biologically and phenotypically and are underpinned by specific fusion genes or hotspot mutations. A subset of low-grade triple-negative disease has been shown to harbor highly recurrent if not pathognomonic genetic alterations, such as ETV6-NTRK3 fusion gene in secretory carcinomas, the MYB-NFIB fusion gene, MYBL1 rearrangements or MYB gene amplification in adenoid cystic carcinomas, and HRAS Q61 hotspot mutations coupled with mutations in PI3K pathway genes in estrogen receptor-negative adenomyoepitheliomas. A subset of these pathognomonic genetic alterations (e.g., NTRK1/2/3 fusion genes) now constitute an FDA approved indication for the use of TRK inhibitors in the advanced/metastatic setting. These studies have also corroborated that salivary gland-like tumors of the breast, other than acinic cell carcinomas, harbor the repertoire of somatic genetic alterations detected in their salivary gland counterparts. Reassuringly, the systematic study of special histologic types of breast cancer utilizing state-of-the-art sequencing approaches, rather than rendering pathology obsolete, has actually strengthened the importance of breast cancer histologic typing and is providing additional ancillary markers for the diagnosis of these rare but fascinating entities.
Topics: Adenomyoepithelioma; Antigens, CD; Biomarkers, Tumor; Breast; Breast Neoplasms; Cadherins; Carcinoma; Carcinoma, Acinar Cell; Carcinoma, Lobular; Diagnosis, Differential; Female; Genomics; Humans; Mutation; Neoplasm Grading; Oncogene Proteins, Fusion; Pathology, Molecular; Triple Negative Breast Neoplasms
PubMed: 33024304
DOI: 10.1038/s41379-020-00693-7 -
International Journal of Surgery Case... 2020Malignant breast adenomyoepithelioma (AME) is a rare subtype of breast cancer. AME is mostly a benign disease that uncommonly undergoes malignant transformation.
INTRODUCTION
Malignant breast adenomyoepithelioma (AME) is a rare subtype of breast cancer. AME is mostly a benign disease that uncommonly undergoes malignant transformation.
PRESENTATION OF CASE
Here we present a case of a young, previously healthy female who initially presented with a painless breast lump. The patient underwent wide local excision for atypical cells with squamous metaplasia by core biopsy, but final histopathology showed AME with carcinoma. Thus, a mastectomy and a sentinel lymph node biopsy was undertaken. The patient had an uneventful recovery and no recurrence after the second surgery.
DISCUSSION AND CONCLUSION
Malignant transformation of adenomyoepithelioma is reported in a small number of cases. Benign AME may be treated with wide local excision as recurrence is rare locally. Whereas malignant AME tends to be treated with simple mastectomy with or without lymph node biopsy.
PubMed: 32506031
DOI: 10.1016/j.ijscr.2020.05.061 -
Surgical Case Reports May 2020Adenomyoepithelioma (AME) of the breast is a very rare tumor and is generally considered to be benign. However, some show malignant transformation, which results in...
BACKGROUND
Adenomyoepithelioma (AME) of the breast is a very rare tumor and is generally considered to be benign. However, some show malignant transformation, which results in local recurrences or distant metastases. The morphological features of AME that might predict malignant potential have not been elucidated. Moreover, there is also no established multidisciplinary treatment for malignant AME aside from complete excision at an early stage.
CASE PRESENTATION
A 64-year-old female diagnosed with AME of the left breast underwent lumpectomy. The surgical margins were negative. Six months after the operation, however, malignant AME recurred locally in the left breast. MRI showed multiple masses, which invaded the skin. A left mastectomy with axillary lymph node dissection was performed. Additional areas of AME were found in about one third of the entire breast. Eight months after the mastectomy, lung metastases were detected. She underwent chemotherapy with fluorouracil, epirubicin, and cyclophosphamide (FEC) for 9 cycles with little response. Lung metastasectomy was performed. Nine months after lung metastasectomy, the metastases were widespread to the brain, heart, and kidney; she subsequently died 2 months later.
CONCLUSIONS
Malignant AME has various morphological features, and in this report, we characterize new findings from both imaging and pathology/autopsy. Malignant potency is related to the tumor size, tumor appearance, and mitoses, even if only a few. Given that ductal spread is one of the morphological features of malignant AME, it is of paramount importance to assess the surgical margins.
PubMed: 32472226
DOI: 10.1186/s40792-020-00881-2 -
Modern Pathology : An Official Journal... Sep 2020Adenomyoepitheliomas (AMEs) of the breast are uncommon and span the morphologic spectrum of benign, atypical, in situ, and invasive forms. In exceptionally rare cases,...
Adenomyoepitheliomas (AMEs) of the breast are uncommon and span the morphologic spectrum of benign, atypical, in situ, and invasive forms. In exceptionally rare cases, these tumors metastasize to regional lymph nodes or distant sites. In the era of genomic characterization, data is limited regarding AMEs. The aim of this study was to provide insight into the molecular underpinnings of a spectrum of AMEs. Seven cases of AMEs of the breast (benign-1, atypical-2, in situ-1, invasive-3) were identified in our files. The seven samples were interrogated using the Oncomine Comprehensive Assay v3 (ThermoFisher). Two atypical AMEs and the malignant in situ AME harbored the same gain-of-function PIK3CA mutation. The malignant in situ AME also showed EGFR amplification, not described previously. Both a benign AME and a malignant invasive AME shared the same gain-of-function AKT1 variant. The benign AME also showed a GNAS mutation. Moreover, the same gain-of-function HRAS mutation was present in an atypical AME and a malignant invasive AME. We also identified co-occurring HRAS and PIK3CA mutations in an ER-positive atypical AME, which has not been previously described. No fusion drivers were detected. We describe the molecular characteristics of the spectrum of AME tumors of the breast, which harbor alterations in the PI3K/AKT pathway. Our findings are clinically relevant with respect to the current options of targeted therapy in the rare instances where malignant AME tumors of the breast progress.
Topics: Adenomyoepithelioma; Adult; Aged; Breast; Breast Neoplasms; Class I Phosphatidylinositol 3-Kinases; Female; Humans; Middle Aged; Mutation; Proto-Oncogene Proteins c-akt; Receptors, Estrogen
PubMed: 32355271
DOI: 10.1038/s41379-020-0552-x -
Virchows Archiv : An International... Aug 2020As one of the most common target organs for hematogenous spread from diverse cancers, biopsy interpretation of lung tumors is complicated by the challenging question of...
Prominent entrapment of respiratory epithelium in primary and metastatic intrapulmonary non-epithelial neoplasms: a frequent morphological pattern closely mimicking adenofibroma and other biphasic pulmonary lesions.
As one of the most common target organs for hematogenous spread from diverse cancers, biopsy interpretation of lung tumors is complicated by the challenging question of primary versus metastatic and by frequent entrapment of native respiratory glands. Nevertheless, the literature dealing with this issue is surprisingly sparse and no single study has been devoted to this topic. We reviewed 47 surgical lung specimens of non-epithelial neoplasms (38 metastases, mainly from sarcomas and 9 primary lesions) for frequency and pattern of intralesional epithelial entrapment. Respiratory epithelium entrapment was noted in 23/47 (49%) cases (diffuse in 15 and peripheral in 8). Entrapped glands frequently showed prominent regenerative and reactive changes mimicking neoplastic glands. Based on cellularity of the mesenchymal component and the extent, distribution and shape of entrapped respiratory glands, four morphological patterns were recognized: paucicellular sclerosing low-grade neoplasms containing leaflet-like glands indistinguishable from adenofibroma and fibroepithelial hamartomas (n = 11), and biphasic cellular lesions mimicking adenomyoepithelioma (n = 1), biphasic synovial sarcoma (n = 2), and pleuropulmonary blastoma (n = 1). Only a single genuine pulmonary adenofibroma was identified. This study highlights frequent respiratory epithelium entrapment in diverse non-epithelial lung tumors, both primary and metastatic. Recognition of this finding and use of adjunct IHC combined with clinical history should help to avoid misinterpretation as primary pulmonary biphasic neoplasm or as harmless adenofibroma. The vast majority of morphologically defined lung adenofibromas represent adenofibroma-like variants of histogenetically diverse entities so that a diagnosis of adenofibroma should be rendered only very restrictively and then as a diagnosis by exclusion.
Topics: Adenofibroma; Adolescent; Adult; Aged; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Respiratory Mucosa; Young Adult
PubMed: 32193604
DOI: 10.1007/s00428-020-02796-7 -
Journal of Breast Cancer Feb 2020Breast adenomyoepitheliomas are composed of a biphasic proliferation of myoepithelial cells around small epithelial-lined spaces. Due to the rarity of...
Breast adenomyoepitheliomas are composed of a biphasic proliferation of myoepithelial cells around small epithelial-lined spaces. Due to the rarity of adenomyoepitheliomas, the molecular data describing them are limited. Adenomyoepitheliomas are considered to be benign or have low malignant potential, and be prone to local recurrence. Malignant transformation has been associated with homozygous deletion of or somatic mutations in , but remains unexplained in many cases. Here, we describe a case of carcinomatous transformation of both epithelial and myoepithelial cells in an estrogen receptor-negative adenomyoepithelioma caused by amplification of . Break-apart fluorescence hybridization revealed an increase in the gene copy number (3-4 copies/cell in 37%, > 4 copies/cell in 40%). Deregulation of is responsible for uncontrolled proliferation and cellular immortalization in basal-like breast cancers. Our case demonstrates that genomic instability events associated with gene amplification may be involved in the carcinogenesis of malignant adenomyoepitheliomas.
PubMed: 32140273
DOI: 10.4048/jbc.2020.23.e2 -
International Journal of Surgery Case... 2020Adenomyoepithelioma of the breast is a rare benign breast neoplasm with a particular behaviour.
INTRODUCTION
Adenomyoepithelioma of the breast is a rare benign breast neoplasm with a particular behaviour.
PRESENTATION OF CASES
We report two cases of adenomyoepithelioma of the breast in two old female patients, diagnosed over a period of 5 years. The clinical presentation, the radiological and the histopathologic findings are discussed.
DISCUSSION
Adenomyoepithelioma of the breast is characterized by the proliferation of both epithelial and myoepithelial cells belonging to the breast lobules and ducts. The imaging features are not pathognomonic and FNAB is usually not diagnostic. The morphologic appearance of this tumor varies, and it has to be considered in the differential diagnosis with other breast tumors. Although benign, adenomyoepithelioma has a potential for local recurrence, and malignant transformation is possible; therefore, wide excision is recommended to lower the recurrence rate.
CONCLUSION
The rarity of this histological type and the finding of two cases in a relatively short period makes this case report unique.
PubMed: 31991375
DOI: 10.1016/j.ijscr.2020.01.010 -
Taehan Yongsang Uihakhoe Chi Jan 2020Adenomyoepithelioma (AME) is a rare breast neoplasm composed of both epithelial and myoepithelial cells with biphasic proliferation. Although most AMEs are benign,...
Adenomyoepithelioma (AME) is a rare breast neoplasm composed of both epithelial and myoepithelial cells with biphasic proliferation. Although most AMEs are benign, malignant transformation of either or both cellular components may occur. This report describes an unusual rapid local tumor recurrence a month after excision of the myoepithelial carcinoma arising in an AME. Ultrasound and MRI showed small recurrent masses in the superficial part of a hematoma. This report suggests the benefit of immediate postoperative breast imaging in patients with malignant AME with potential for local recurrence, such as those with narrow resection margins or high mitotic activity.
PubMed: 36238122
DOI: 10.3348/jksr.2020.81.1.207 -
Histopathology May 2020Breast adenomyoepitheliomas (AMEs) are uncommon tumours. Most oestrogen receptor (ER)-positive AMEs have mutations in phosphoinositide 3-kinase (PI3K) pathway genes,...
AIMS
Breast adenomyoepitheliomas (AMEs) are uncommon tumours. Most oestrogen receptor (ER)-positive AMEs have mutations in phosphoinositide 3-kinase (PI3K) pathway genes, whereas ER-negative AMEs usually harbour concurrent mutations affecting the HRAS Q61 hotspot and PI3K pathway genes. Here, we sought to determine the sensitivity and specificity of RAS Q61R immunohistochemical (IHC) analysis for detection of HRAS Q61R mutations in AMEs.
METHODS AND RESULTS
Twenty-six AMEs (14 ER-positive; 12 ER-negative) previously subjected to massively parallel sequencing (n = 21) or Sanger sequencing (n = 5) of the HRAS Q61 hotspot locus were included in this study. All AMEs were subjected to IHC analysis with a monoclonal (SP174) RAS Q61R-specific antibody, in addition to detailed histopathological analysis. Nine ER-negative AMEs harboured HRAS mutations, including Q61R (n = 7) and Q61K (n = 2) mutations. Five of seven (71%) AMEs with HRAS Q61R mutations were immunohistochemically positive, whereas none of the AMEs lacking HRAS Q61R mutations (n = 17) were immunoreactive. RAS Q61R immunoreactivity was restricted to the myoepithelium in 80% (4/5) of cases, whereas one case showed immunoreactivity in both the epithelial component and the myoepithelial component. RAS Q61R immunohistochemically positive AMEs were associated with infiltrative borders (P < 0.001), necrosis (P < 0.01) and mitotic index in the epithelial (P < 0.05) and myoepithelial (P < 0.01) components. RAS Q61R IHC assessment did not reveal Q61K mutations (0/2).
CONCLUSIONS
IHC analysis of RAS Q61R shows high specificity (100%) and moderate sensitivity (71%) for detection of HRAS Q61R mutations in breast AMEs, and appears not to detect HRAS Q61K mutations. IHC analysis of RAS Q61R may constitute a useful technique in the diagnostic workup of ER-negative AMEs.
Topics: Adenomyoepithelioma; Adult; Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Immunohistochemistry; Mutation; Proto-Oncogene Proteins p21(ras); Sensitivity and Specificity
PubMed: 31887226
DOI: 10.1111/his.14057