Apparent diffusion coefficient in estrogen receptor-positive and lymph node-negative invasive breast cancers at 3.0T DW-MRI: A potential predictor for an oncotype Dx test recurrence score.

PURPOSE: To measure the apparent diffusion coefficient (ADC) values in estrogen receptor-positive (ER+) and axillary lymph node-negative (LN-) invasive breast cancer and investigate the correlation of ADC with Oncotype Dx test recurrence scores (ODxRS). MATERIALS AND METHODS: This was a Health Insurance Portability and Accountability Act (HIPAA)-compliant single-site retrospective study. Patients underwent preoperative 3.0T MRI scans with additional diffusion-weighted imaging sequential scans (b = 0, 600 and b = 0, 1000 s/mm2 ) from January 2011 to 2013. The study population included 31 ER+/LN- invasive breast cancers, which underwent ODxRS genomic testing. ADC600 and ADC1000 parametric maps were generated, and ADC values were calculated from a user-drawn region of interest. ODxRS predicts 10-year recurrence risk in individual patients: low (RS <18), intermediate (RS: 18-30), or high (RS >30). All breast lesions, including subgroups of invasive ductal carcinoma (IDC) lesions and mass-only lesions were dichotomized by RS scores, low-risk versus intermediate/high-risk, and statistical analysis was performed using Mann-Whitney's test (statistical significance at P < 0.05) and receiver operating characteristic (ROC) curves. Multivariate analysis was also performed. RESULTS: Invasive breast cancers, when scored as low-risk by ODxRS, had significantly higher ADC values compared with intermediate/high-risk lesions for both ADC600 (P = 0.007) and ADC1000 (P = 0.008) mean values. This was true both when analyzing only mass-lesions (P = 0.03 and 0.01) or only IDCs (P = 0.001 and 0.009). CONCLUSION: Preliminary findings suggest that lesion ADC values correlate with recurrence risk likelihood stratified using ODxRS. Hence, ADC is a potential surrogate biomarker for tumor aggressiveness. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;47:401-409.

Intravoxel incoherent motion (IVIM) histogram biomarkers for prediction of neoadjuvant treatment response in breast cancer patients.

OBJECTIVE: To examine the prognostic capabilities of intravoxel incoherent motion (IVIM) metrics and their ability to predict response to neoadjuvant treatment (NAT). Additionally, to observe changes in IVIM metrics between pre- and post-treatment MRI. METHODS: This IRB-approved, HIPAA-compliant retrospective study observed 31 breast cancer patients (32 lesions). Patients underwent standard bilateral breast MRI along with diffusion-weighted imaging before and after NAT. Six patients underwent an additional IVIM-MRI scan 12-14 weeks after initial scan and 2 cycles of treatment. In addition to apparent diffusion coefficients (ADC) from monoexponential decay, IVIM mean values (tissue diffusivity Dt, perfusion fraction fp, and pseudodiffusivity Dp) and histogram metrics were derived using a biexponential model. An additional filter identified voxels of highly vascular tumor tissue (VTT), excluding necrotic or normal tissue. Clinical data include histology of biopsy and clinical response to treatment through RECIST assessment. Comparisons of treatment response were made using Wilcoxon rank-sum tests. RESULTS: Average, kurtosis, and skewness of pseudodiffusion Dp significantly differentiated RECIST responders from nonresponders. ADC and Dt values generally increased (∼70%) and VTT% values generally decreased (∼20%) post-treatment. CONCLUSION: Dp metrics showed prognostic capabilities; slow and heterogeneous pseudodiffusion offer poor prognosis. Baseline ADC/Dt parameters were not significant predictors of response. This work suggests that IVIM mean values and heterogeneity metrics may have prognostic value in the setting of breast cancer NAT.

Benign vascular lesions of the breast diagnosed by core needle biopsy do not require excision.

AIMS: Surgical excision of all benign vascular lesions of the breast identified by core needle biopsy has been recommended in the past to rule out a more serious lesion. In this study we investigated the clinical, radiological and pathological findings in patients diagnosed with a benign vascular lesion at our institution to assess whether excision may be spared for lesions without atypia. METHODS AND RESULTS: We searched the electronic medical record for patients with a vascular lesion of the breast diagnosed between 2000 and 2015. The study population consisted of 84 patients, 83 females and one male. The index diagnoses included 76 benign vascular lesions, five vascular lesions with cytological atypia and three angiosarcomas. A radiologist reviewed all pre- and post-biopsy imaging studies; all cases had concordant radiological and pathological findings. Based on radiological and histological correlation, the vascular lesion accounted for the radiological target in 40 (48%) cases and was deemed an incidental finding in 44 (52%). Seven of 32 (22%) targeted and 10 of 44 (23%) incidental benign vascular lesions underwent surgical excision; there were no upgrades at excision. No recurrences or clinical events were observed in patients with a targeted or incidental benign vascular lesion with a median follow-up of 39 months and 40.6 months, respectively. CONCLUSION: Our data suggest that benign vascular lesions diagnosed on core biopsy with concordant radiological and pathological findings do not warrant surgical excision.

Quantitative apparent diffusion coefficient measurement obtained by 3.0Tesla MRI as a potential noninvasive marker of tumor aggressiveness in breast cancer.

PURPOSE: To assess the association between apparent diffusion coefficient (ADC), and histological prognostic parameters in malignant breast lesions. The ability of ADC to identify lesions with the presence of Lymphovascular invasion (LVI) in breast carcinoma was also examined. MATERIALS AND METHODS: This HIPAA-compliant retrospective study consisted of 212 consecutive patients with known cancers who underwent 3.0T MRI between January 2011 and 2013. In this study, a total of 126 malignant lesions in 114 women, who had undergone DWI (b-values of 0 and 1000s/mm(2)) in addition to diagnostic MRI, were included. Patients with less than 0.8cm lesions, or those who underwent neoadjuvant chemotherapy or suboptimal DW images were excluded. Classical prognostic factors [lesion size, histopathological type and grade, lymph node (LN) status and lymphovascular invasion (LVI)], molecular prognostic markers [estrogen receptor (ER), progesterone receptor (PR) and human epidermal grow factor receptor 2 (HER2)] were reviewed and recorded. A region of interest (ROI) was drawn within the lesions to measure ADC values. Statistical analyses were performed by the Wilcoxon rank sum test (statistical significance at P<0.05). Adjusted p values from multiple comparison analysis were also calculated. RESULTS: This study demonstrates an inverse correlation between ADC and LVI in malignant lesions and the ability of ADC to identify aggressiveness in lesions with positive LVI. Tumor size, grade, ER, PR, HER2 and lymph node status did not impact tumor ADC value. However, tumors with LVI showed significantly lower ADC values when compared to tumors without LVI, regardless of the enhancement type, histological grade, histological type, and LN status. CONCLUSION: Our study shows that ADC could be a potential clinical adjunct in the evaluation of prognostic factors related to malignant lesion aggressiveness such as LVI.

Avaliação imunofenotípica das subpopulações de linfócitos no infiltrado linfocitário tumoral em melanomas / Immunophenotypic evaluation of lymphocyte subpopulations in tumor-Infiltrating lymphocytes of melanomas

JUSTIFICATIVA E OBJETIVOS: Estudos com novas terapias utilizando transplante autólogo de infiltrado linfocitário têm mostrado resultados promissores no tratamento de melanomas, justificando pesquisas nesta área. O objetivo deste estudo foi avaliar a expressão fenotípica do infiltrado linfocitário tumoral (TIL), através de marcadores imuno-histoquímicos de moléculas de superfície de células inflamatórias em melanomas cutâneos primários e estudar a sua correlação com outros fatores prognósticos já estabelecidos. MÉTODO: Análise da infiltração linfocitária tumoral em 43 melanomas primários utilizando técnicas de imuno-histoquímica (anticorpos anti-CD3, CD20, CD4, CD8, CD25 e anti-CD57). As variáveis prognósticas foram: clínicas (idade, sexo, localização, metástases e evolução) e anatomopatológicas: Breslow (se fino = < 1 mm = 21 casos ou grosso > 1 mm = 22 casos), nível de Clark, número de mitoses, ulceração, regressão, satelitose e tipo TIL (caso brisk ou nonbrisk). RESULTADOS: Os tumores finos apresentaram maior concentração de linfócitos TCD4+ (p = 0,01) e CD57+ (p = 0,008). Os tumores de cabeça-tronco-pescoço apresentam predomínio de linfócitos TCD8+ e de TCD25+ (p = 0,02). CONCLUSÃO: Tumores centrais, que geralmente são de pior prognóstico, apresentaram maior resposta imune humoral (predomínio de linfócitos CD20+) e são a forma mais prevalente no sexo masculino. Os tumores grossos, que são de pior prognóstico, estavam associados com o padrão nonbrisk de TIL, com maior taxa de mitoses, com maior incidência de satelitoses e com predomínio de ulceração. A presença de ulceração ocorreu em maior número de vezes em pacientes com faixa etária mais elevada. Os tumores finos, que são de melhor prognóstico, apresentaram maior resposta imune celular (predomínio de linfócitos CD4+ e CD57+).

BACKGROUND AND OBJECTIVES: Studies of new therapies that use lymphocytic infiltrate autologous transplantation have shown promising results for the treatment of melanomas, warranting researches in this area. The objective of this study was to assess the phenotypic expression of tumor-infiltrating lymphocytes through immunohistochemical markers of surface molecules of inflammatory cells in primary cutaneous melanomas, and to study its correlation with other established prognostic factors. METHOD: Tumor lymphocytic infiltration analysis in 43 primary melanomas using immunohistochemical techniques (CD3, CD20, CD4, CD8, CD25 and CD57 antibodies). The prognostic variables were: clinical (age, sex, location, metastases and evolution) and anatomopathological variables: Breslow thickness (if thin = < 1 mm = 21 cases or thick > 1 mm = 22 cases), Clark level, number of mitoses, ulceration, regression, satellitosis and type of TIL (if brisk or nonbrisk). RESULTS: The thin tumors showed higher concentration of CD4+ (p = 0.01) and CD57+ (p = 0.008) T lymphocytes. The head-trunk-neck tumors exhibit a predominance of CD8 and CD25 (p = 0.02) T lymphocytes. CONCLUSION: Central tumors, which generally have poorer prognosis, had a higher humoral immune response (CD20 lymphocyte predominance) and are the most prevalent form in males. The thick tumors, which have worse prognosis, were associated with the non-brisk pattern of TIL with a higher rate of mitosis, a higher incidence of satelitoses and ulceration predominance. The presence of ulceration occurred more often in older patients. The thin tumors, which have the best prognosis, had a higher cellular immune response (predominance of CD4+ and CD57+ lymphocytes).

Immunohistochemical assessment of E-cadherin, beta-catenin, CEACAM-1 and PTEN: tumor progression markers in melanoma / Análise imuno-histoquímica dos marcadores de progressão tumoral, E-caderina, beta-catenina, CEACAM-1 e PTEN em melanomas

INTRODUCTION AND OBJECTIVE: The aim of the present study is the immunohistochemical assessment of tumor progression markers (E-cadherin, β-catenin, CEACAM-1 and PTEN) in primary cutaneous melanomas and their correlation with prognostic factors. METHOD: Primary lesions in patients with cutaneous melanoma were recorded as to clinical data (age, gender, location and metastases) and anatomopathologic data (Breslow, Clark level, margins, histological type, mitosis, ulceration, regression, satellitosis and TIL type). It was made a comparison between immunohistochemical expression of the markers and prognostic and anatomopathologic factors. RESULTS: Breslow thickness was > 1 mm (thick) in 21 patients (48.83 percent) and < 1 mm (thin) in 22 (51.16 percent). There was a higher CEACAM-1 positive expression in thick melanomas than in thin ones (p = 0.002). There was a more frequent E-cadherin (p = 0.008), b-catenin (p = 0.001) and PTEN (p = 0.005) positive expression in thin melanomas than in thick ones. There was a more frequent CEACAM-1 positive expression in superficial (p = 0.003) and deep (p = 0.002) samples of thick melanomas than in thin ones. No statistically significant differences between clinical and histopathological data were found when comparing patients with (n = 6) and without metastasis (n = 15). DISCUSSION AND CONCLUSION: There was a higher positivity for E-cadherin, b-catenin and PTEN in thin melanomas, whereas there was a higher positivity for CEACAM-1 in thick melanomas.

INTRODUÇÃO E OBJETIVO: O objetivo do presente estudo está na avaliação imuno-histoquímica de marcadores de progressão tumoral (E-caderina, β-catenina, CEACAM-1 e PTEN) em melanomas cutâneos primários e sua correlação com fatores prognósticos. MÉTODO: Lesões primárias de pacientes portadores de melanoma cutâneo foram tabuladas quanto a dados clínicos (idade, sexo, localização e metástases) e anatomopatológicos (Breslow, nível de Clark, margens, tipo histológico, mitoses, ulceração, regressão, satelitose e tipo de TIL). Foi realizada comparação da expressão imuno-histoquímica dos marcadores em estudo com fatores prognósticos clínicos e anatomopatológicos. RESULTADOS: Breslow foi > 1 mm (espesso) em 21 pacientes (48,83 por cento) e ≤ 1 mm (fino) em 22 (51,16 por cento). CEACAM-1 foi mais positivo em melanomas grossos que em finos (p = 0,002). E-caderina (p = 0,008), β-catenina (p = 0,001) e PTEN (p = 0,005) foram mais frequentemente positivos em melanomas finos que em grossos. CEACAM-1 foi mais frequentemente positivo nas porções superficiais (p = 0,003) e profundas (p = 0,002) dos melanomas grossos que nas dos finos. Não houve diferenças estatisticamente significativas entre dados clínicos e histopatológicos quando comparamos os pacientes com (n = 6) e sem (n = 15) metástases. DISCUSSÃO E CONCLUSÃO: Observou-se maior tendência de positividade para E-caderina, b-catenina e PTEN em melanomas finos. Por sua vez, CEACAM-1 demonstrou maior frequência de positividade nos melanomas grossos.