RESUMO
Patients with pathological nipple discharge (PND) often undergo local surgical procedures because standard radiologic imaging fails to identify the underlying cause. MicroRNA (MiRNA) expression analysis of nipple fluid holds potential for distinguishing between breast diseases. This study aimed to compare miRNA expression levels between nipple fluids from patients with PND to identify possible relevant miRNAs that could differentiate between intraductal papillomas and no abnormalities in the breast tissue. Nipple fluid samples from patients with PND without radiological and pathological suspicion for malignancy who underwent a ductoscopy procedure were analyzed. We used univariate and multivariate regression analyses to identify nipple fluid miRNAs differing between pathologically confirmed papillomas and breast tissue without abnormalities. A total of 27 nipple fluid samples from patients with PND were included for miRNA expression analysis. Out of the 22 miRNAs examined, only miR-145-5p was significantly differentially expressed (upregulated) in nipple fluid from patients with an intraductal papilloma compared to patients showing no breast abnormalities (OR 4.76, p = 0.046), with a diagnostic accuracy of 92%. miR-145-5p expression in nipple fluid differs for intraductal papillomas and breast tissue without abnormalities and, therefore, has potential as a diagnostic marker to signal presence of papillomas in PND patients. However, further refinement and validation in clinical trials are necessary to establish its clinical applicability.
Assuntos
Doenças Mamárias , Neoplasias da Mama , MicroRNAs , Derrame Papilar , Papiloma Intraductal , Papiloma , Humanos , Feminino , Papiloma Intraductal/diagnóstico , Papiloma Intraductal/genética , Papiloma Intraductal/patologia , Endoscopia/métodos , Derrame Papilar/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Doenças Mamárias/metabolismo , Mamilos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Papiloma/diagnóstico , Papiloma/genética , Papiloma/metabolismoRESUMO
AIMS: Breast hamartomas are an under-recognised lesion because they lack a distinctive microscopic appearance. Microscopic diagnosis can often conclude 'no significant lesion' or 'normal breast tissue', leading to repeated biopsies and diagnostic delay. We describe the histological, immunohistochemical and radiological features of breast hamartomas with the aim of identifying specific signs to facilitate their diagnosis and to differentiate them from normal breast and fibroepithelial lesions. METHODS AND RESULTS: Forty-seven breast hamartomas were reassessed (histological diagnosis and imaging features). An immunohistochemical study [oestrogen receptor (ER), progesterone receptor (PR), CD34, high-mobility group A2 (HMGA2)] was performed. On breast imaging, hamartomas most often presented as probably benign solid masses with circumscribed margins and variable densities. Histologically, breast hamartomas resembled normal breast, although their stromal component was predominant, separating randomly scattered epithelial elements with areas of pure collagenous stroma. Pseudoangiomatous stromal hyperplasia (PASH) was present in 93.6% of cases and CD34 antibody highlighted intralobular, perilobular and interlobular distribution of CD34-positive fibroblasts. By comparison, CD34 was mainly expressed in the intralobular normal breast tissue stroma. Hamartoma stromal cells expressed HMGA2, ER and PR in 79%, 66% and 76.3% of our cases, respectively, compared to 7.7%, 23% and 19% in normal breast tissue, respectively (P < 0.0001; P = 0.0005; P < 0.0001). CONCLUSIONS: After ascertaining that core needle biopsy is effectively intralesional, breast hamartomas can be diagnosed with confidence by taking into account the presence of stromal changes, PASH, interlobular distribution of CD34-positive fibroblasts, HMGA2 and hormonal receptor stromal expression.
Assuntos
Doenças Mamárias/diagnóstico , Hamartoma/diagnóstico , Adolescente , Adulto , Idoso , Antígenos CD34/metabolismo , Doenças Mamárias/metabolismo , Doenças Mamárias/patologia , Proteína HMGA2/metabolismo , Hamartoma/metabolismo , Hamartoma/patologia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto JovemRESUMO
Breast amyloidosis is a rare condition which is mostly associated with hematological disorders or hereditary genetic disorders. Imaging findings of breast amyloidosis can mimic malignancy, which often leads to biopsy or excision of the lesion. Here, we presented a case of localized lactotransferrin-related breast amyloidosis in an elderly female patient. Histologic examination revealed extensive involvement of breast lobules by amorphous amyloid materials, with attenuation of lobular structures and prominent calcifications. Positive immunostains for myoepithelial cells helped to exclude the possibility of invasive carcinoma. The patient had no hematologic malignancy besides immunoglobulin G lambda monoclonal gammopathy of undetermined significance. Mass spectrometry of the breast amyloid identified lactotransferrin and no immunoglobulin or its light chain. On follow-up, the patient showed no recurrence of the breast lesion after local excision nor showed other systematic comorbidities, indicating the benign nature of the lesion. This first report of lactotransferrin-related amyloidosis may represent a special type of localized breast amyloidosis that has no correlation with systematic disorders.
Assuntos
Amiloidose/patologia , Doenças Mamárias/patologia , Lactoferrina/metabolismo , Amiloidose/diagnóstico , Amiloidose/metabolismo , Biomarcadores/metabolismo , Doenças Mamárias/diagnóstico , Doenças Mamárias/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Anaplastic lymphoma kinase (ALK)-positive histiocytosis is a rare emerging entity characterized by systemic or localized proliferation of histiocytes harboring ALK rearrangements. Breasts are reportedly affected by ALK-positive histiocytosis. Here, we evaluated 2 localized cases of breast ALK-positive histiocytosis through a comprehensive clinicopathologic, molecular, and genomic analysis to further delineate this entity and better understand its pathogenesis. The cases involved 2 undiagnosed ALK-positive spindle-cell breast lesions. Both cases were Asian women aged 30s to 40s who underwent excisions for asymptomatic breast masses. Macroscopically, both lesions were well-circumscribed, solid masses. Microscopically, both lesions were predominantly composed of fascicles with uniform, bland spindle cells, admixed with epithelioid histiocyte-like cells and lymphoid aggregates. Immunohistochemically, the spindle and epithelioid cells coexpressed ALK and histiocytic markers (eg, CD68, CD163). Genetically, both lesions harbored KIF5B-ALK, confirmed by fluorescence in situ hybridization and polymerase chain reaction-direct sequencing analyses. Combining these results, both cases were successfully diagnosed as ALK-positive histiocytosis. Furthermore, no common or previously annotated somatic alterations were identified by whole-exome sequencing. One case harbored clonal immunoglobulin gene rearrangements according to the polymerase chain reaction-based BIOMED-2 protocol. Therefore, ALK-positive histiocytosis can be accurately diagnosed through a combination of morphologic, immunohistochemical, and molecular analyses. In this entity, breast cases may have distinct clinicopathologic features: Asian women aged 30s to 40s, asymptomatic masses, and predominant spindled morphology. For pathogenesis, ALK rearrangements could be the driver alteration, and a subset of ALK-positive histiocytosis may harbor a lymphoid lineage. These findings can be utilized to improve the diagnosis of ALK-positive histiocytosis and better understand its pathogenesis.
Assuntos
Quinase do Linfoma Anaplásico/metabolismo , Doenças Mamárias/diagnóstico , Histiocitose/diagnóstico , Proteínas de Fusão Oncogênica/genética , Adulto , Quinase do Linfoma Anaplásico/genética , Biomarcadores/metabolismo , Doenças Mamárias/genética , Doenças Mamárias/metabolismo , Doenças Mamárias/patologia , Feminino , Rearranjo Gênico , Marcadores Genéticos , Histiocitose/genética , Histiocitose/metabolismo , Histiocitose/patologia , Humanos , Proteínas de Fusão Oncogênica/metabolismoRESUMO
BACKGROUND: Elevated mammographic breast density is a strong breast cancer risk factor with poorly understood etiology. Increased deposition of collagen, one of the main fibrous proteins present in breast stroma, has been associated with increased mammographic density. Collagen fiber architecture has been linked to poor outcomes in breast cancer. However, relationships of quantitative collagen fiber features assessed in diagnostic biopsies with mammographic density and lesion severity are not well-established. METHODS: Clinically indicated breast biopsies from 65 in situ or invasive breast cancer cases and 73 frequency matched-controls with a benign biopsy result were used to measure collagen fiber features (length, straightness, width, alignment, orientation and density (fibers/µm2)) using second harmonic generation microscopy in up to three regions of interest (ROIs) per biopsy: normal, benign breast disease, and cancer. Local and global mammographic density volumes were quantified in the ipsilateral breast in pre-biopsy full-field digital mammograms. Associations of fibrillar collagen features with mammographic density and severity of biopsy diagnosis were evaluated using generalized estimating equation models with an independent correlation structure to account for multiple ROIs within each biopsy section. RESULTS: Collagen fiber density was positively associated with the proportion of stroma on the biopsy slide (p < 0.001) and with local percent mammographic density volume at both the biopsy target (p = 0.035) and within a 2 mm perilesional ring (p = 0.02), but not with global mammographic density measures. As severity of the breast biopsy diagnosis increased at the ROI level, collagen fibers tended to be less dense, shorter, straighter, thinner, and more aligned with one another (p < 0.05). CONCLUSIONS: Collagen fiber density was positively associated with local, but not global, mammographic density, suggesting that collagen microarchitecture may not translate into macroscopic mammographic features. However, collagen fiber features may be markers of cancer risk and/or progression among women referred for biopsy based on abnormal breast imaging.
Assuntos
Densidade da Mama , Mama/metabolismo , Mama/patologia , Colágeno/metabolismo , Adulto , Idoso , Mama/diagnóstico por imagem , Doenças Mamárias/diagnóstico por imagem , Doenças Mamárias/metabolismo , Doenças Mamárias/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Biópsia Guiada por Imagem , Mamografia , Microscopia , Pessoa de Meia-Idade , Células Estromais/metabolismo , Células Estromais/patologiaRESUMO
Lineage tracing in mice indicates that LGR5 is an adult stem cell marker in multiple organs, such as the intestine, stomach, hair follicles, ovary, and mammary glands. Despite many studies exploring the presence of LGR5 cells in human tissues, little is known about its expression profile in either human mammary tissue or pathological lesions. In this study we aim to investigate LGR5 expression in normal, benign, and malignant lesions of the human breast using RNA in situ hybridization. LGR5 expression has not been observed in normal lactiferous ducts and terminal duct lobular units, whereas LGR5-positive cells have been specifically observed in the basal myoepithelium of ducts in the regenerative tissues, ductal carcinoma in situ, and in ducts surrounded by invasive cancer cells. These findings suggest LGR5 marks facultative stem cells that are involved in post injury regeneration instead of homeostatic stem cells. LGR5 positivity was found in 3% (9 of 278 cases) of invasive breast cancers (BC), and it showed positive associations with higher histologic grades (P = 0.001) and T stages (P < 0.001), while having negative correlations with estrogen receptor (P < 0.001) and progesterone receptor (P < 0.001) expression. Remarkably, all LGR5-positive BC, except one, belong to triple-negative BC (TNBC), representing 24% (9 of 38 cases) of all of them. LGR5 histoscores have no correlations with EGFR, CK5/6, Ki-67, or P53 expression. Additionally, no ß-catenin nuclear localization was observed in LGR5-positive BC, indicating that canonical Wnt pathway activation is less likely involved in LGR5 expression in BC. Our results demonstrate that LGR5 expression is induced in regenerative conditions in the myoepithelium of human mammary ducts and that its expression is only observed in TNBC subtype among all invasive BC. Further studies regarding the functional and prognostic impact of LGR5 in TNBC are warranted.
Assuntos
Mama/metabolismo , Células Epiteliais/metabolismo , Proteínas de Neoplasias/biossíntese , Receptores Acoplados a Proteínas G/biossíntese , Neoplasias de Mama Triplo Negativas/metabolismo , Adulto , Idoso , Mama/citologia , Mama/fisiologia , Doenças Mamárias/genética , Doenças Mamárias/metabolismo , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/metabolismo , Feminino , Fibroadenoma/genética , Fibroadenoma/metabolismo , Humanos , Hibridização In Situ , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Papiloma Intraductal/genética , Papiloma Intraductal/metabolismo , Tumor Filoide/genética , Tumor Filoide/metabolismo , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Receptores Acoplados a Proteínas G/genética , Regeneração/genética , Neoplasias de Mama Triplo Negativas/genéticaRESUMO
BACKGROUND: Among women diagnosed with invasive breast cancer, 30% have a prior diagnosis of benign breast disease (BBD). Thus, it is important to identify factors among BBD patients that elevate invasive cancer risk. In the general population, risk factors differ in their associations by clinical pathologic features; however, whether women with BBD show etiologic heterogeneity in the types of breast cancers they develop remains unknown. METHODS: Using a nested case-control study of BBD and breast cancer risk conducted in a community healthcare plan (Kaiser Permanente Northwest), we assessed relationships of histologic features in BBD biopsies and patient characteristics with subsequent breast cancer risk and tested for heterogeneity of associations by estrogen receptor (ER) status, tumor grade, and size. The study included 514 invasive breast cancer cases (median follow-up of 9 years post-BBD diagnosis) and 514 matched controls, diagnosed with proliferative or non-proliferative BBD between 1971 and 2006, with follow-up through mid-2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multivariable polytomous logistic regression models. RESULTS: Breast cancers were predominantly ER-positive (86%), well or moderately differentiated (73%), small (74% < 20 mm), and stage I/II (91%). Compared to patients with non-proliferative BBD, proliferative BBD with atypia conferred increased risk for ER-positive cancer (OR = 5.48, 95% CI = 2.14-14.01) with only one ER-negative case, P-heterogeneity = 0.45. The presence of columnar cell lesions (CCLs) at BBD diagnosis was associated with a 1.5-fold increase in the risk of both ER-positive and ER-negative tumors, with a 2-fold increase (95% CI = 1.21-3.58) observed among postmenopausal women (56%), independent of proliferative BBD status with and without atypia. We did not identify statistically significant differences in risk factor associations by tumor grade or size. CONCLUSION: Most tumors that developed after a BBD diagnosis in this cohort were highly treatable low-stage ER-positive tumors. CCL in BBD biopsies may be associated with moderately increased risk, independent of BBD histology, and irrespective of ER status.
Assuntos
Doenças Mamárias/epidemiologia , Neoplasias da Mama/epidemiologia , Adulto , Idoso , Biópsia , Mama/patologia , Doenças Mamárias/metabolismo , Doenças Mamárias/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Hiperplasia , Pessoa de Meia-Idade , Razão de Chances , Receptores de Estrogênio/metabolismo , Fatores de RiscoRESUMO
Several gene expression studies have been previously conducted to characterize molecular basis of Wooden Breast myopathy in commercial broiler chickens. These studies have generally used a limited sample size and relied on a binary disease outcome (unaffected or affected by Wooden Breast), which are appropriate for an initial investigation. However, to identify biomarkers of disease severity and development, it is necessary to use a large number of samples with a varying degree of disease severity. Therefore, in this study, we assayed a relatively large number of samples (n = 96) harvested from the pectoralis major muscle of unaffected (U), partially affected (P) and markedly affected (A) chickens. Gene expression analysis was conducted using the nCounter MAX Analysis System and data were analyzed using four different supervised machine-learning methods, including support vector machines (SVM), random forests (RF), elastic net logistic regression (ENET) and Lasso logistic regression (LASSO). The SVM method achieved the highest prediction accuracy for both three-class (U, P and A) and two-class (U and P+A) classifications with 94% prediction accuracy for two-class classification and 85% for three-class classification. The results also identified biomarkers of Wooden Breast severity and development. Additionally, gene expression analysis and ultrastructural evaluations provided evidence of vascular endothelial cell dysfunction in the early pathogenesis of Wooden Breast.
Assuntos
Doenças Mamárias/patologia , Endotélio Vascular/fisiopatologia , Regulação da Expressão Gênica , Doenças das Aves Domésticas/patologia , Aprendizado de Máquina Supervisionado , Animais , Biomarcadores/metabolismo , Doenças Mamárias/genética , Doenças Mamárias/metabolismo , Galinhas , Endotélio Vascular/citologia , Endotélio Vascular/ultraestrutura , Metabolismo dos Lipídeos/genética , Lipase Lipoproteica/genética , Modelos Logísticos , Microscopia Eletrônica de Transmissão , Contração Muscular/fisiologia , Músculos Peitorais/metabolismo , Músculos Peitorais/ultraestrutura , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/metabolismoRESUMO
The presence of calcium deposits in human lesions is largely used as imaging biomarkers of human diseases such as breast cancer. Indeed, the presence of micro- or macrocalcifications is frequently associated with the development of both benign and malignant lesions. Nevertheless, the molecular mechanisms involved in the formation of these calcium deposits, as well as the prognostic significance of their presence in human tissues, have not been completely elucidated. Therefore, a better characterization of the biological process related to the formation of calcifications in different tissues and organs, as well as the understanding of the prognostic significance of the presence of these calcium deposits into human tissues could significantly improve the management of patients characterized by microcalcifications associated lesions. Starting from these considerations, this narrative review highlights the most recent histopathological and molecular data concerning the formation of calcifications in breast, thyroid, lung, and ovarian diseases. Evidence reported here could deeply change the current point of view concerning the role of ectopic calcifications in the progression of human diseases and also in the patients' management. In fact, the presence of calcifications can suggest an unfavorable prognosis due to dysregulation of normal tissues homeostasis.
Assuntos
Biomarcadores/metabolismo , Calcinose/patologia , Prognóstico , Doenças Mamárias/metabolismo , Progressão da Doença , Transição Epitelial-Mesenquimal , Feminino , Homeostase , Humanos , Pneumopatias/metabolismo , Metástase Neoplásica , Osteoblastos/metabolismo , Doenças Ovarianas/metabolismo , Neoplasias Ovarianas/metabolismo , Doenças da Glândula Tireoide/metabolismoRESUMO
BACKGROUND: Benign breast disease (BBD) is one of main breast cancer risk factors. Dysfunctions on p53 protein, which has a genome protective role, have been related to breast cancer developments. However, its role on BBD development is still unclear. METHODS: A systematic review of literature was proceeded according to PRISMA-P guidelines. PubMed, BVS, MEDLINE and Scholar Google were used as databases, complemented by a manual search in articles references. Articles searches were conducted from May to July 2019 and publications in English, Spanish and Portuguese were selected. P53 expression was set as outcome among women with BBD and were included only articles with good quality according STROBE tools. Data concerning p53 expression frequencies were independently extracted by two review authors, and eligible articles were synthesized. RESULTS: From 12 studies selected for this review, the majority analyzed p53 expression in non-proliferative lesions and general p53 expressions ranged from 0 to 100%. P53 expression was more frequently observed in cases series studies (91.7%) and in studies conducted in Occidental Europe (41.7%). P53 expression was more frequent among tissues with fibrocystic disease (22.5%) and fibroadenoma (22.5%). CONCLUSION: When compared with all breast tissues types, benign breast disease corresponds to 34.39% of p53 expression. Second outcomes were not evaluated because the heterogeneity observed in selected studies. In addition, more studies considering ethnicity and benign breast disease classification should also be considered for further analysis.
Assuntos
Doenças Mamárias/patologia , Fibroadenoma/patologia , Proteína Supressora de Tumor p53/metabolismo , Doenças Mamárias/metabolismo , Feminino , Fibroadenoma/metabolismo , HumanosRESUMO
BACKGROUND/AIM: The study aimed at investigating the correlation between ductoscopic and histopathological findings and clarify whether the former allow for accurate prediction of malignancy. PATIENTS AND METHODS: The prospective national multi-center study covered a sample of 224 patients with pathologic nipple discharge. A total of 214 patients underwent ductoscopy with subsequent extirpation of the mammary duct. The ductoscopic findings were categorized according to shape, number, color and surface structure of lesions and vascularity and compared to the histological results and analyses. RESULTS: Ductoscopy revealed lesions in 134 of 214 patients (62.2%). The criteria "multiple versus solitary lesion" differed significantly between malignant and benign lesions. All other criteria were not statistically significant. Malignant tumors were more frequently presented as multiple lesions, benign lesions or masses as solitary lesions (80% vs. 24.8%; p=0.018). CONCLUSION: The ductoscopic criterion "solitary vs. multiple lesion" appears to have a low diagnostic prediction of malignancy or benignity.
Assuntos
Doenças Mamárias/diagnóstico , Neoplasias da Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Endoscopia/métodos , Derrame Papilar , Mamilos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Mamárias/metabolismo , Doenças Mamárias/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Diagnóstico Diferencial , Feminino , Alemanha , Humanos , Pessoa de Meia-Idade , Mamilos/metabolismo , Estudos Prospectivos , Adulto JovemRESUMO
Breast microcalcifications are a common mammographic finding. Microcalcifications are considered suspicious signs of breast cancer and a breast biopsy is required, however, cancer is diagnosed in only a few patients. Reducing unnecessary biopsies and rapid characterization of breast microcalcifications are unmet clinical needs. In this study, 473 microcalcifications detected on breast biopsy specimens from 56 patients were characterized entirely by Raman mapping and confirmed by X-ray scattering. Microcalcifications from malignant samples were generally more homogeneous, more crystalline, and characterized by a less substituted crystal lattice compared with benign samples. There were significant differences in Raman features corresponding to the phosphate and carbonate bands between the benign and malignant groups. In addition to the heterogeneous composition, the presence of whitlockite specifically emerged as marker of benignity in benign microcalcifications. The whole Raman signature of each microcalcification was then used to build a classification model that distinguishes microcalcifications according to their overall biochemical composition. After validation, microcalcifications found in benign and malignant samples were correctly recognized with 93.5% sensitivity and 80.6% specificity. Finally, microcalcifications identified in malignant biopsies, but located outside the lesion, reported malignant features in 65% of in situ and 98% of invasive cancer cases, respectively, suggesting that the local microenvironment influences microcalcification features. This study confirms that the composition and structural features of microcalcifications correlate with breast pathology and indicates new diagnostic potentialities based on microcalcifications assessment. SIGNIFICANCE: Raman spectroscopy could be a quick and accurate diagnostic tool to precisely characterize and distinguish benign from malignant breast microcalcifications detected on mammography.
Assuntos
Doenças Mamárias/metabolismo , Doenças Mamárias/patologia , Mama/patologia , Calcinose/metabolismo , Calcinose/patologia , Análise Espectral Raman/métodos , Biomarcadores/análise , Biópsia , Mama/química , Carcinoma de Mama in situ/química , Carcinoma de Mama in situ/diagnóstico , Carcinoma de Mama in situ/patologia , Doenças Mamárias/diagnóstico , Neoplasias da Mama/química , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Calcinose/diagnóstico , Fosfatos de Cálcio/análise , Carbonatos/análise , Feminino , Humanos , Fosfatos/análise , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To assess the additional value of quantitative tCho evaluation to diagnose malignancy and lymph node metastases in suspicious lesions on multiparametric breast MRI (mpMRI, BI-RADS 4, and BI-RADS 5). METHODS: One hundred twenty-one patients that demonstrated suspicious multiparametric breast MRI lesions using DCE, T2w, and diffusion-weighted (DW) images were prospectively enrolled in this IRB-approved study. All underwent single-voxel proton MR spectroscopy (1H-MRS, point-resolved spectroscopy sequence, TR 2000 ms, TE 272 ms) with and without water suppression. The total choline (tCho) amplitude was measured and normalized to millimoles/liter according to established methodology by two independent readers (R1, R2). ROC-analysis was employed to predict malignancy and lymph node status by tCho results. RESULTS: One hundred three patients with 74 malignant and 29 benign lesions had full 1H-MRS data. The area under the ROC curve (AUC) for prediction of malignancy was 0.816 (R1) and 0.809 (R2). A cutoff of 0.8 mmol/l tCho could diagnose malignancy with a sensitivity of > 95%. For prediction of lymph node metastases, tCho measurements achieved an AUC of 0.760 (R1) and 0.788 (R2). At tCho levels < 2.4 mmol/l, no metastatic lymph nodes were found. CONCLUSION: Quantitative tCho evaluation from 1H-MRS allowed diagnose malignancy and lymph node status in breast lesions suspicious on multiparametric breast MRI. tCho therefore demonstrated the potential to downgrade suspicious mpMRI lesions and stratify the risk of lymph node metastases for improved patient management. KEY POINTS: ⢠Quantitative tCho evaluation can distinguish benign from malignant breast lesions suspicious after multiparametric MRI assessment. ⢠Quantitative tCho levels are associated with lymph node status in breast cancer. ⢠Quantitative tCho levels are higher in hormonal receptor positive compared to hormonal receptor negative lesions.
Assuntos
Neoplasias da Mama/metabolismo , Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Lobular/metabolismo , Colina/metabolismo , Linfonodos/metabolismo , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/diagnóstico por imagem , Mama/patologia , Doenças Mamárias/diagnóstico por imagem , Doenças Mamárias/metabolismo , Doenças Mamárias/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Pessoa de Meia-Idade , Espectroscopia de Prótons por Ressonância Magnética/métodos , Curva ROC , Sensibilidade e Especificidade , Adulto JovemRESUMO
Amyloidosis is characterized by extracellular deposition of insoluble protein fibrils in a beta-pleated sheet configuration. Breast amyloidosis is a rare entity which has previously been reported to present with localized involvement, or as a late manifestation of systemic amyloidosis. However, descriptions of the clinicopathologic features of localized breast amyloidosis remain limited. A retrospective search for breast amyloidosis diagnosed at our institution yielded 10 cases of breast amyloidosis. All patients were female, with a mean age of 69. Median follow-up for survival or progression was 13 months. Indications for breast or axilla biopsy included mammographic calcifications, mass, and axillary lymphadenopathy. Amyloid showed positive staining with Congo red in all cases, and amyloid typing revealed light chain lambda in 3 cases, amyloid transthyretin in 2 cases, light chain kappa in 1 case, and iatrogenic insulin-derived amyloidosis in 1 case. Amyloid occurred within axillary lymph nodes and alongside both benign and neoplastic breast tissue, including atypical ductal hyperplasia, lobular carcinoma in situ and ductal carcinoma in situ. Most cases were associated with predisposing clinical conditions, including autoimmune disease in 4 cases, B cell lymphomas in 2 cases, and diabetes mellitus treated with insulin in 1 case. In contrast to previously published case series, no patient had clinical evidence of systemic amyloidosis. Amyloidosis of the breast should be considered in the differential diagnosis of all mammographic calcifications and masses of the breast or axilla. When recognized correctly on biopsy, the diagnosis of amyloidosis can not only prevent further unnecessary surgical interventions due to radiology-pathology discordance, but initiate the necessary amyloidosis work-up. Although rare, an awareness of the clinicopathologic characteristics of this easily overlooked entity is of great importance for every practicing pathologist reviewing breast biopsies.
Assuntos
Amiloidose/patologia , Doenças Mamárias/patologia , Neoplasias da Mama/patologia , Calcinose/patologia , Linfadenopatia/patologia , Idoso , Idoso de 80 Anos ou mais , Amiloide/análise , Amiloidose/etiologia , Amiloidose/metabolismo , Biópsia , Doenças Mamárias/etiologia , Doenças Mamárias/metabolismo , Calcinose/etiologia , Calcinose/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Linfadenopatia/etiologia , Linfadenopatia/metabolismo , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoRESUMO
Core needle biopsy (CNB) is the most common sampling technique for the histologic evaluation of breast abnormalities. Diagnosing benign proliferative, borderline and some in-situ lesions in CNB is challenging and subject to a significant degree of interobserver variability. In addition, due to the inherent limitations of CNB, "upgrading" to a more significant pathology at excision is an important consideration for some lesions. Pathologists carry a major responsibility in patient diagnosis, risk stratification and management. Familiarity with the histologic features and the clinical significance of these common and problematic lesions encountered in CNB is necessary for adequate treatment and patient follow-up. This review will focus on benign, atypical and in-situ epithelial proliferations, papillary lesions, radial sclerosing lesions, adenosis and cellular fibroepithelial lesions. Highlights of histologic features, useful strategies for accurate diagnosis, basic immunohistochemistry and management will be presented.
Assuntos
Biópsia com Agulha de Grande Calibre/normas , Doenças Mamárias/patologia , Neoplasias da Mama/patologia , Mama/patologia , Imuno-Histoquímica/métodos , Adulto , Assistência ao Convalescente , Idoso , Idoso de 80 Anos ou mais , Mama/ultraestrutura , Doenças Mamárias/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/ultraestrutura , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Diagnóstico Diferencial , Feminino , Doença da Mama Fibrocística/patologia , Indicadores Básicos de Saúde , Humanos , Hiperplasia/patologia , Pessoa de Meia-Idade , Variações Dependentes do Observador , Patologistas/ética , PrognósticoRESUMO
Rosai-Dorfman disease (RDD) is an uncommon disorder, characterized by an atypical expansion of histiocytes which classically shows emperipolesis and immunoreactivity with S-100 protein. RDD affects the lymph nodes as well as extranodal sites; however, RDD of the breast is exceptionally rare. Herein, we describe the histopathologic features of 22 cases of RDD occurring in the breast, with an emphasis on the differential diagnosis. All cases were notable for an exuberant lymphocytic infiltrate with and without germinal center formation, and the majority (19/22) showed numerous plasma cells: 5 to 132/high-power field (HPF). IgG and IgG4 immunohistochemical stains were available for 13 cases; in no instance were criteria for IgG4-related sclerosing disease met, though in a single case the IgG4/IgG ratio was increased to 25%. Sclerosis was present in the majority of cases (18/22), and was frequently prominent. RDD cells showing emperipolesis were present in all cases (22/22), and ranged from rare (<1/50 HPF) to numerous (>50/50 HPF). Two of the cases in our series were initially misdiagnosed as inflammatory myofibroblastic tumor and plasma cell mastitis with granulomatous inflammation. As emperipolesis can be indistinct, the presence of stromal fibrosis and a prominent lymphoplasmacytic inflammatory infiltrate should prompt a careful search for the characteristic histiocytes, which can be aided by the use of S-100 immunohistochemistry.
Assuntos
Doenças Mamárias/imunologia , Mama/imunologia , Histiocitose Sinusal/imunologia , Imunoglobulina G/análise , Neoplasias Inflamatórias Mamárias/imunologia , Mastite/imunologia , Plasmócitos/imunologia , Adolescente , Adulto , Idoso , Mama/química , Mama/patologia , Doenças Mamárias/metabolismo , Doenças Mamárias/patologia , Diagnóstico Diferencial , Emperipolese , Feminino , Fibrose , Histiocitose Sinusal/metabolismo , Histiocitose Sinusal/patologia , Humanos , Neoplasias Inflamatórias Mamárias/química , Neoplasias Inflamatórias Mamárias/patologia , Mastite/metabolismo , Mastite/patologia , Pessoa de Meia-Idade , Plasmócitos/química , Plasmócitos/patologia , Prognóstico , Proteínas S100/análise , Estados Unidos , Adulto JovemRESUMO
AIMS: Mammary angiomatosis is a rare, benign vascular lesion that morphologically mimics low-grade angiosarcoma (LGAS). To date, only occasional reports of this entity have been published, none of which included analysis by immunohistochemistry. The purpose of this study was to further characterise mammary angiomatosis by clinical, histological, and immunohistochemical means while emphasising distinguishing features from LGAS. METHODS: Seven cases of primary mammary angiomatosis were evaluated. For one patient, a subsequent recurrence was also evaluated. RESULTS: All patients were female with a median age at presentation of 51 years (range: 19-58 years). The most common clinical presentation was that of a palpable abnormality or mass (5/8) and the median primary tumour size was 3.1 cm (range: 2-9 cm). Of the six patients with follow-up, one developed a recurrence 6 years after initial presentation. Histologically, all cases were composed of variably sized ectatic, thin-walled vessels lined by flat normochromic endothelium diffusely infiltrating mammary stroma. Where present, lesional vessels infiltrated between and around terminal duct lobular units but not into individual intralobular stroma. Most cases (6/8) showed a combination of lymphatic-appearing and haemangiomatous-appearing vessels. Lymphatic-appearing vessels were D2-40 positive in all but one case. D2-40 was negative or weak in haemangiomatous-appearing vessels. All lesional vessels were CD31 positive. Ki-67 indices were <1% in all but one case (5%). CONCLUSIONS: Mammary angiomatosis is a rare vascular lesion that shares clinical, morphological and immunohistochemical features with LGAS; however, certain key traits make the distinction possible.
Assuntos
Angiomatose/metabolismo , Antígenos de Neoplasias/análise , Doenças Mamárias/metabolismo , Neoplasias da Mama/química , Hemangiossarcoma/química , Imuno-Histoquímica , Imunofenotipagem/métodos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Adulto , Angiomatose/patologia , Anticorpos Monoclonais Murinos , Biópsia , Doenças Mamárias/patologia , Neoplasias da Mama/patologia , Diagnóstico Diferencial , Feminino , Hemangiossarcoma/patologia , Humanos , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Adulto JovemRESUMO
Mammary lesions in sows can prevent suckling piglets from consuming colostrum that provides fundamental nutrients and protective immunity. Although mammary gross lesions are frequently found in sows at farms or slaughterhouses, with the exception of mastitis, they have received little research attention. In this study, we investigated mammary lesions observed in South Korean sows between 2015 and 2016. Mammary tissue samples of 82 sows showing gross lesions during meat inspection were histologically classified and immunohistochemical analysis was conducted to assess the expression of estrogen receptor (ER)-α, ER-ß, and progesterone receptor (PR) for mammary hyperplastic lesions as well as that of cluster of differentiation (CD) 3, CD79a, interleukin (IL)-1α, IL-1ß, IL-6, and IL-8 for mastitis. Furthermore, 20 swab samples were cultured, and the isolated bacteria were identified using polymerase chain reactions for 16S ribosomal RNA genes. The lesions were classified as hyperplasia, mastitis, or hyperplasia with mastitis. Immunohistochemistry results revealed that there was neither expression of ER-α nor of ER-ß, but all examined hyperplastic samples expressed PR. In addition, there was a significant correlation between CD3 and IL-1ß expressions, as well as between IL-1ß and IL-6 expressions. Regarding the identity of the isolated bacteria, Pseudomonas spp. were most frequently detected. The results of this study have revealed the incidence and characteristics of porcine mammary lesions.
Assuntos
Doenças Mamárias/veterinária , Citocinas/metabolismo , Glândulas Mamárias Animais/patologia , Receptores de Estrogênio/metabolismo , Doenças dos Suínos/patologia , Matadouros , Animais , Doenças Mamárias/metabolismo , Doenças Mamárias/microbiologia , Doenças Mamárias/patologia , Complexo CD3/metabolismo , Antígenos CD79/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/microbiologia , Mastite/metabolismo , Mastite/microbiologia , Mastite/patologia , Mastite/veterinária , Pseudomonas , Receptores de Progesterona/metabolismo , Suínos , Doenças dos Suínos/classificação , Doenças dos Suínos/metabolismo , Doenças dos Suínos/microbiologiaRESUMO
PURPOSE: Use of a wire to localize a non-palpable breast lesion for surgery is standard but archaic. We sought to evaluate a new radiofrequency localization system (RFLS) as an effective, non-radioactive alternative to the wire. METHODS: Patients who required surgical excision of a non-palpable breast lesion were consented for the study. Patients underwent localization with a radiofrequency Tag and surgical removal guided by the handheld LOCalizer probe. The primary study endpoint was successful placement and retrieval of the Tag, and secondary endpoints included marker migration; days prior to surgery of Tag insertion; patient, radiologist, and surgeon experience; distance of Tag from skin; and positive margin and re-excision rates for cancer. RESULTS: Fifty patients had successful placement and retrieval of the radiofrequency Tag. Likert questionnaire data revealed that most patients thought the procedure went smoothly and was easier than expected. Radiologists and surgeons thought that the Tag was as reliable as the wire. Of the 33 patients who had surgery for in situ or invasive cancer, one had a positive margin on final pathology (3%) and two underwent re-excision (6%). CONCLUSIONS: Data from this pilot study suggest that the RFLS is an effective localization system for non-palpable breast lesions intended for surgical removal. Unlike most other technologies, the LOCalizer probe detects distance from the Tag, and this unique feature may have contributed to the low positive margin rate seen in this study. The RFLS appears to offer advantages over current localization procedures and should be explored as an alternative to wire. ClinicalTrials.gov Identifier: NCT03202472.