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Pleomorphic adenoma is a common benign salivary gland neoplasm which very rarely occurs in the breast. Its radiologic and pathologic appearance may be mistaken for other benign or malignant lesions such as a fibroadenoma or invasive ductal carcinoma. Due to the risk of local recurrence and, rarely, malignant transformation, wide local excision with clear margins is recommended. As such, a correct diagnosis of this lesion is important to ensure appropriate surgical treatment. We report a case of an atypically located pleomorphic adenoma with radiologic-pathologic correlation in an asymptomatic 63-year-old woman.
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Adenoma Pleomórfico , Neoplasias de la Mama , Neoplasias de las Glándulas Salivales , Adenoma Pleomórfico/diagnóstico por imagen , Adenoma Pleomórfico/cirugía , Femenino , Humanos , Persona de Mediana Edad , Radiografía , Neoplasias de las Glándulas Salivales/diagnóstico por imagenRESUMEN
BACKGROUND: Breast magnetic resonance imaging (MRI) use for surgical staging is increasing, though remains controversial. We aimed to evaluate the accuracy of MRI in surgical decision-making to determine if mastectomy prompted by MRI was appropriate. METHODS: A single-centre observational study in Perth, Western Australia, with the inclusion of all preoperative and postoperative studies (e.g. involved margins after breast-conserving surgery) undergoing staging breast MRI from 1 January 2015 to 26 August 2019. A standard protocol using gadolinium contrast was used. The reference standard was postoperative histopathology or, for studies without additional surgery after MRI following breast-conserving surgery, the next and subsequent annual screening episodes. By reviewing the final histopathology, the medical case notes and multidisciplinary team decision process, we evaluated whether the reported MRI disease extent was accurate in prompting an appropriate upgrade to mastectomy. Outcomes are reported with descriptive statistics. RESULTS: Of 130 cancers staged with MRI; seven were excluded as information was incomplete, 104 were performed preoperatively and 19 postoperatively. The majority (60%) staged lobular carcinoma (invasive 59%, in situ 1%) compared to ductal carcinoma (invasive 31%, in situ 8%). For preoperative MRI, half (54% - 56/104) underwent subsequent mastectomy. Of these, MRI prompted mastectomy in 45% (25/56), all appropriate for disease extent. In the postoperative staging group, two mastectomies were performed, one planned before imaging, the other prompted when MRI diagnosed residual disease and confirmed on histopathology. No false-negative staging MRI was identified. CONCLUSIONS: In our cohort, MRI prompted an upgrade to mastectomy in 21% (26/123), appropriate for cancer extent.
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Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/cirugía , Carcinoma Lobular/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Mastectomía , Mastectomía Segmentaria , Estadificación de Neoplasias , Cuidados Preoperatorios , Estudios RetrospectivosRESUMEN
Triple negative breast cancers (TNBC) are aggressive malignancies for which chemotherapy is the only treatment option. Many TNBC acquire chemotherapy resistance, notably docetaxel, which has been associated with the overexpression of transcription factors (TFs), such as ENGRAILED1 (EN1). Here, we have developed a tumor delivery system for docetaxel-PGMA-PAA-nanoparticles and interference peptides designed to specifically inhibit EN1 (EN1-iPeps). To promote tumor specific targeting, we functionalized these nanoparticles with EN1-iPeps engineered with RGD sequences. We found that these peptides reduce cell viability and induce apoptosis in TNBC cells with negligible effects on normal cells (EN1-). Moreover, EN1-RGD-iPeps-mediated nanoparticle internalization into breast cancer cells was via integrins and intravenous injection of this nanoformulation increased tumor accumulation. Furthermore, docetaxel nanoparticles functionalized with EN1-RGD-iPeps significantly reduced TNBC growth both in vitro and in vivo without showing toxicity. Our results suggest that this targeted nanoformulation represents a new and safe therapeutic approach for chemoresistant TNBCs.
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Docetaxel/uso terapéutico , Proteínas de Homeodominio/metabolismo , Nanopartículas/química , Oligopéptidos/química , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Docetaxel/farmacología , Endocitosis/efectos de los fármacos , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Células 3T3 NIH , Polímeros/química , Distribución Tisular/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Granular cell tumours (GCT) are uncommon, usually solitary tumours of neural/Schwann cell origin that occur at any site of the body, and typically run an indolent clinical course. Treatment by excision is recommended. Distant or nodal metastases are the only reliable signs of malignancy. We describe the case of a 47-year-old woman with a multi-focal, multi-centric GCT involving the pulmonary and gastrointestinal systems, highlighting the imaging and pathological features and the challenge faced in establishing its malignant potential.
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INTRODUCTION: There is controversy on the optimal work-up of screen-detected widespread breast calcifications: whether to biopsy a single target or multiple targets. This study evaluates agreement between multiple biopsy targets within the same screen-detected widespread (≥25 mm) breast calcification to determine if the second biopsy adds value. METHODS: Retrospective observational study of women screened in a statewide general population risk breast cancer mammographic screening program from 2009 to 2016. Screening episodes recalled for widespread calcifications where further views indicated biopsy, and two or more separate target areas were sampled within the same lesion were included. Percentage agreement and Cohen's Kappa were calculated. RESULTS: A total of 293317 women were screened during 761124 separate episodes with recalls for widespread calcifications in 2355 episodes. In 171 women, a second target was biopsied within the same lesion. In 149 (86%) cases, the second target biopsy result agreed with the first biopsy (κ = 0.6768). Agreement increased with increasing mammography score (85%, 86% and 92% for score 3, 4 and 5 lesions). Same day multiple biopsied lesions were three times more likely to yield concordant results compared to post-hoc second target biopsy cases. CONCLUSION: While a single target biopsy is sufficient to discriminate a benign vs. malignant diagnosis in most cases, in 14% there is added value in performing a second target biopsy. Biopsies performed prospectively are more likely to yield concordant results compared to post-hoc second target biopsy cases, suggesting a single prospective biopsy may be sufficient when results are radiological-pathological concordant; discordance still requires repeat sampling.
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Neoplasias de la Mama , Calcinosis , Biopsia , Femenino , Humanos , Mamografía , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
AIM: Breast carcinoma proliferative activity, histological grade and commercial molecular tests are all important in prognostication and treatment. There is a particular need for improved, standardised techniques for subclassification of grade 2 breast cancers into low-risk and high-risk prognostic groups. In this study we investigated whether gene expression profiling of five proliferation genes was feasible using breast cancer tissue in a clinical setting and whether these profiles could enhance pathological assessment. METHODS: Expression of five proliferation gene mRNAs; Ki-67, STK 15, CCNB1, CCND1 and MYBL2, was quantified in 27 breast carcinomas and compared with Ki-67 proliferation index (PI) and Nottingham mitotic score. RESULTS: Expression of Ki-67, STK15 and MYBL2 mRNA showed moderate Spearman's correlation with Ki-67 PI (p<0.01), but CCND1 and CCNB1 showed weak, non-significant correlation. Individual gene expression did not associate with mitotic score but combined mRNA expression correlated with both Ki-67 PI (p=0.018) and mitotic score (p=0.03; 0.007). CONCLUSIONS: This study confirms mRNA analysis in breast carcinoma formalin-fixed, paraffin-embedded samples is feasible and suggests gene expression profiling, using a small set of five proliferation genes, has potential in aiding histological grading or assessment of proliferative activity of breast cancers. To fully evaluate the clinical applicability of this approach, a larger cohort study with long-term follow-up data is required.
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Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/genética , Perfilación de la Expresión Génica/métodos , Aurora Quinasa A/genética , Aurora Quinasa A/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Ciclina B1/genética , Ciclina B1/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Estudios de Factibilidad , Femenino , Formaldehído , Regulación Neoplásica de la Expresión Génica , Humanos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Índice Mitótico , Adhesión en Parafina , Pronóstico , Fijación del Tejido/métodos , Transactivadores/genética , Transactivadores/metabolismoRESUMEN
Commercial molecular tests which rely heavily on proliferation markers to stratify breast cancer are in increasing demand, but are expensive and not widely available. There is heightened interest in the use of Ki-67 immunohistochemistry as a marker of proliferation. This study sought to examine practical issues in the incorporation of Ki-67 measurement into breast cancer reporting.We conducted a prospective study of Ki-67 proliferative activity in 85 breast carcinomas in 70 patients. We considered whether dual staining with cytokeratin and Ki-67 was necessary to exclude background cells in automated digital image analysis (DIA) and how well a semi-quantitative assessment (SQA) method of Ki-67 proliferation and formal manual counting by two pathologists correlated with DIA.Our study showed good correlation between single and dual stained specimens by DIA (Spearman correlation coefficient 0.8), with a kappa statistic of 0.51 (moderate agreement) but with significantly fewer positive cells identified in dual stained sections. There was fair correlation between SQA and DIA by two pathologists (Spearman correlation coefficient 0.7 and 0.7). Using a ≥10% cut-off to define cases with a 'low' and 'high' proliferative index gave a kappa statistic of 0.25 and 0.32 (fair agreement). There was fair correlation between formal manual counts between two pathologists (Spearman correlation coefficient 0.7; kappa 0.32). Repeat DIA on all cases showed excellent correlation (Spearman coefficient 0.98; kappa 1.0).Automated digital analysis of Ki-67 PI is likely to be more accurate and consistent than semi-quantitative assessment and more practicable than formal manual counting. There remain challenges in standardisation of technique within and across laboratories, interpretation of results and in evaluating clinical relevance.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Antígeno Ki-67/metabolismo , Neoplasias de la Mama/química , Carcinoma Ductal de Mama/química , Proliferación Celular , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Inmunohistoquímica , Antígeno Ki-67/análisis , Variaciones Dependientes del ObservadorRESUMEN
BACKGROUND: Multiple minute digitate hyperkeratosis (MMDH) is a rare disorder of keratinization with many different names. OBJECTIVE: We present a case of MMDH and review the literature. We propose and discuss the classification the digitate keratoses, which include MMDH, lichen spinulosus, phrynoderma, spiny keratoderma, arsenical keratosis, multiple filiform verrucae, postirradiation digitate keratosis, trichodysplasia spinulosa, and hyperkeratotic spicules. We present a table of suggested and synonymous terms and propose a diagnostic algorithm for these digitate keratoses. METHODS: A literature search using PubMed and MEDLINE was performed. This included the search terms "MMDH," "familial disseminated filiform hyperkeratosis," "punctate porokeratotic keratoderma," "disseminated spiked keratosis," "minute aggregate keratosis," "digitate keratosis," "conical keratosis," "hyperkeratotic spicules," and "music box spine dermatosis." A case of MMDH in an 89-year-old woman is described. RESULTS: The digitate keratoses are presented alongside their synonymous terms and are divided into those that are generalized or localized using an algorithm. LIMITATIONS: Separate disease entities are likely to arise within the digitate keratoses with increased reporting of immunohistochemical keratin analysis and molecular genetic studies. CONCLUSION: We report a new case of MMDH and provide a clinical approach to diagnosis of the digitate keratoses.