The currently adopted prognostic factors for ILC are usually borrowed from the ductal histotype, despite the differences in terms of clinico-pathological features and outcome. Thus, the aim of this analysis was to more precisely stratify the prognosis of ILC undergone (neo)adjuvant therapy, and to explore the addition of chemotherapy (CT) to endocrine therapy (ET) in adjuvant setting. Clinico-pathological data of consecutive patients (pts) affected by pure luminal/HER2-negative ILC (stage I-III), undergone surgery, were collected into 2 cohorts according to treatment setting: 1) adjuvant; 2) neoadjuvant. Independent predictors of overall- and disease free- survival (OS/DFS) were investigated with a Cox model, taking into account: 1) a previously validated prognostic score combining clinico-pathological factors (independently predicting the risk of recurrence and death) and clustering pts into 3 classes (low/intermediate/high risk: <2/=2/>2 score) in adjuvant cohort; 2) the pCR and CPS-EG score in neoadjuvant cohort. Data from 471 pts were gathered. Adjuvant/neoadjuvant cohorts: 386/85 pts (median follow up 86 months [Interquartile range (IQR) 62-124]/96 months [IQR 53-130]). In the adjuvant cohort, 10-yrs DFS was 85%, 72% and 55% in pts with low, intermediate and high-risk score (p<0.001); 10-yrs OS was 99%, 89% and 96% (p=0.06), respectively. Overall, DFS and OS were not significantly improved with CT (administered in 107 pts, 28%) in the overall sample, neither according to stage and prognostic score. In the neoadjuvant cohort, with a pCR rate of 7.1%, no statistically significant difference was found in DFS according to pCR: 5-yrs/10-yrs DFS was 76.6%/80.0% and 42.0%/80% in pts without and with pCR (p=0.34). Conversely, the CPS-EG score was able to distinguish into 2 prognostic groups (CPS-EG≤2 and >2): the 10-yrs DFS was 51% vs. 38% (p=0.028) and 10-yrs OS 86% vs. 66.2% (p=0.009), respectively. While the combination of clinico-pathological factors is able to discriminate the prognosis of ILC, no predictive role for the benefit of adjuvant CT was found. In the neoadjuvant setting, the CPS-EG score stratifies ILC pts according to outcome, more powerfully than pCR.

Introduction: Granular cell tumor is a rare neoplasm of soft tissue and only in 1% of cases, it can shows a malignant behaviour. It is presumed to be a tumor originating from perineural or putative Schwann cells of peripheral nerves. Materials and Methods: We reviewed five patients affected by Granular cell tumor of the breast treated between January 2011 and January 2021 at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS of Rome, Italy. Results: All of the granular cell tumors presented as solitary, painless and firm lump, highly suggestive of malignancy. The radiological findings were heterogeneous and non-specific. All lesions presented as masses, more clearly evident on ultrasound as hypoechoic lesions, with irregular shape, blurred contours and borderline features. The tumors were composed of large polygonal cells with abundant eosinophilic granular cytoplasm and small, central nuclei, being immunohistochemically positive for S100, Vimentin (with variable staining), CD56; negative for HMB45, MelanA, AE1/AE3, EMA, and Desmin. Conclusion: Granular cell tumor is a rare, usually benign breast disease that can have very similar characteristics to breast cancer both clinically and radiologically. Treatment of choice consists in wide resection or lumpectomy with margin assessment (no ink on tumor).

OBJECTIVE:Triple-negative breast cancers (TNBC) include a heterogeneous group of diseases, characterized by the lack of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) expression. TNBC that shows an overexpression of the androgen receptor (AR) defines the phenotype known as "luminal androgen receptor" (LAR), while the absence of the AR defines a "quadruple negative breast cancer" (QNBC). Several reports have associated AR positivity with a lower response to neoadjuvant chemotherapy (NAC), while divergent data have been reported about the impact of AR positivity on survival. The aim of this study was to retrospectively review our series of patients with TNBC tested for AR and submitted to NAC and compare pathologic complete response (pCR) rates in patients with a LAR phenotype or with QNBC.PATIENTS AND METHODS:The clinical records of all patients with TNBC tested for AR that underwent NAC at our Institution from January 1, 2015 to June 30, 2019 were reviewed. Histopathological features as well as ER, PgR, Ki67, HER2 values, clinical and pathological stage, and results of BRCA gene expression profiling were registered for all patients.RESULTS:Of the 145 TNBC patients treated by NAC, 20 (13.8%) had a LAR phenotype, while 125 (86.2%) had a QNBC. Overall, a pCR was achieved in 52 patients (35.8%). Patients with LAR phenotype had a lower rate of pCR as compared to patients with QNBC phenotype (25% vs. 37.6%). High Ki67 values (>50%) were observed less frequently in patients with a LAR phenotype (50% vs. 76.8% in QNBC).CONCLUSIONS:Our data seem to confirm that the LAR phenotype is associated to lower rates of pCR after neoadjuvant chemotherapy; routine assessment of AR expression in addition to classical biomarkers in patients with TNBC could help to better personalize treatment.

Secondary malignancies arising within mature teratomas are a rare event, originating from malignant transformation of the tissues derived from one of the three germ cell layers. Osteogenic melanoma is exceedingly rare histologic variant of malignant melanoma, in which the melanoma is associated to an osteogenic sarcoma component. To the best of our knowledge, first case of osteogenic melanoma arising within mature ovarian teratoma in a 30-year-old woman without evidence of a primary cutaneous or visceral melanoma. The present case showed an unusual morphological and immunohistochemical pattern and was incorrectly diagnosed as undifferentiated carcinoma. After a 15 years follow-up period, the patient presented a peritoneal recurrence histologically constituted by epithelioid cells with prominent osteoid formation and with immunohistochemical expression of melanocytic markers (S100, HMB-45). Heterozygote Mutation V600E/E complex has been detected in the BRAF exon 15 sequence. The case was then interpreted as osteogenic melanoma. The present case contributes to widen the spectrum of neoplasms derived from malignant transformation of ovarian teratomas and provides also new insights about the clinical behavior of osteogenic melanoma when arising outside its usual anatomical location.

Dermatofibrosarcoma protuberans (DFSP) is a soft tissue tumor, usually occurring as a cutaneous lesion localized to the trunk or extremities; although it has a high rate of local recurrence, its metastatic potential is very low and complete surgical excision is frequently curative. Most of the cases reported as "DFSP of the breast" are tumors arising in the subcutaneous tissue infiltrating the underlying breast parenchyma. To the best of our knowledge, only 5 cases of DFSP of the breast have been reported to date. We herein present a rare case of DFSP of the breast parenchyma in a 41-year-old female with emphasis on the diagnostic clues and the differential diagnosis with other benign and malignant spindle cell lesions of the breast.

Purpose or ObjectiveAdjuvant radiotherapy for breast cancer treatment has been long shown to reduce the risk of recurrence, but also results in incidental exposure of organs at risk (OAR) such as the heart and lungs.Several studies have reported on cardiac toxicity, showing an increase in the rate of ischemic heart disease after radiotherapy for left-sided breast cancer; and meta-analyses of women treated with breast radiotherapy have shown an increased risk of primary lung cancer, which is even more appreciable in the smoking population.Other potential lung complications from breast radiotherapy include pneumonitis and subsequent fibrosis, the risk of which further increases with the addition of chemotherapy.In this retrospective dosimetric study, we report on the cardiac and lung doses from over 400 breast cancer patients treated with radiotherapy at our centre, with the long-term goal of correlating dose to toxicity.Material and Methods 412 breast cancer patients treated with 50Gy in 25 fractions or 42.56Gy in 16 fractions were identified retrospectively.Cohorts were stratified based on the radiation technique including (i) 2-field tangential beam arrangement (n=256) (ii) 3-and 4-field techniques with standard tangents (n=92) and (iii) 4-field technique with wide tangents (n=64) to include the internal mammary chain (IMC), which was further stratified between treatment of right (n=34) and left-sided disease (n=30).Of the latter, patients simulated in free-breathing (n=8) and those simulated with a modified deep inspiration breathhold technique (mDIBH) (n=22) were analysed separately.Standardized contouring based on the RTOG breast cancer atlas, in combination with standard field based planning was used.Dosimetric heart parameters evaluated included mean heart dose (MHD) and V(50%).Metrics for the combined lung volumes included V5Gy, V20Gy and Mean Lung Dose (MLD).ANOVA was also used to compare the dose between the techniques for statistical significance. ResultsDosimetric parameters for heart and lung are reported in table 1 for the different techniques, with the differences shown to be statistically significant.Breast cancer patients treated with radiotherapy which included regional nodal irradiation increased dose to both heart and lungs.mDIBH significantly reduced the dose to the heart as compared to the free-breathing technique.

Background OncotypeDX (ODX®) can enhance prediction of breast cancer recurrence, guiding adjuvant treatment options. However, the opportunity to access this test is not always possible. The aim of this study is to investigate the correlation between phenotypical tumor characteristics, quantitative classical immunohistochemistry (IHC) and recurrent score (RS) resulting from ODX®. Methods All breast cancer patients who underwent ODX® between 2014 and 2018 were retrospectively included in the study. The data selected for analysis were age, menopausal status, pathological and IHC features. IHC was performed with standardized quantitative methods. Dataset was split into two subsets (70% for training and 30% for internal validation). Logistic models were built with statistically significant features for predicting RS ≤ 25 or ≤ 20. An external validation set, provided by another center, was used to test reliability of prediction models. Results The internal dataset included 407 patients (Table) who underwent ODX®. Mean age was 53.7 (31-80) and 222 patients (54.55%) were > 50 years old. ODX® results showed: 67 patients (16.6%) between 0-10, 272 patients between 11-25 (66.8%) and 68 pts > 26 (16.6%). At the logistic regression analysis, RS score was significantly associated with ER (p = 0.004), PgR (p Table . 261P Tumor characteristics training set + internal test set Training + internal test set – Tumor characteristics Histological subtype classification Invasive Ductal Carcinoma 318 pts (78,1%) Invasive Lobular Carcinoma 47 pts (11,5%) Other 42 pts (10,3%) Grading 1 28 pts (6.8%) 2 268 pts (65,8%) 3 111 pts (27,3%) pT 1a 3 pts (0,7%) 1b 38 pts (9,3%) 1c 216 pts (53,1%) 2 143 pts (35,1%) 3 6 pts (1,5%) 4 1 pt (0,3%) pN 0 233 pts (57,2%) 0i+ 12 pts (3%) 1mic 43 pts (10,6%) 1 108 pts (26,5%) NA 11 pts (2,7%) Mean T diameter [cm] 1.9 (Range 0,2-8,5) Mean Sentinel Lymph Node (SLN) diameter [mm] 1.7 (Range 0-40) Mean Axillary Lymph Node (ALN) diameter [mm] 0.8 (Range 0-25) Mean N Ratio 0.14 (0.00 – 1.00) SLN involvement [n° of nodes] 0 261 pts (64,1%) 1 112 pts (27,5%) 2 24 pts (5,8%) 3 1 pt (0,2%) NA 9 pts (2,2%) ALN involvement [n° of nodes] 0 338 pts (83%) 0i+ 4 pts (1%) 1mic 3 pts (0,7%) 1 31 pts (7,6%) 2 8 pts (2%) 3 5 pts (1,2%) 5 1 pt (0,2%) NA 17 pts (4,1%) Multifocality Yes 97 pts (23,8%) No 300 pts (73,7%) NA 10 pts (2.5%) Multicentricity Yes 20 pts (4,9%) No 376 pts (92,4%) NA 11 pts (2,7%) PVI Absent 242 pts (59,4%) Focal 51 pts (12,5%) Moderate 32 pts (7,8%) Massive 59 pts (14,5%) NA 23 pts (5,6%) Mean ER expression 87,9% (Range 1-100) Mean PgR expression 62.2% (Range 0-100) Mean AR expression 7.7% (Range 0-90) Mean Ki67% expression 29.8% (Range 0-90) Her2 Expression 0 187 pts (46%) 1 112 pts (27,5%) 2 104 pts (25,5%) NA 4 pts (0,9%) Fluorescence in situ hybridization (FISH) for HER-2 Not determined 300 pts (73,7%) Not amplificated 100 pts (23,7%) Undetermined 1 pt (0,2%) Equivocal 1 pt (0,2%) Conclusions Quantitative IHC presents a good correlation with RS score in patients with RS ≤ 25, also in external validation set. A nomogram for physician that enhances a cost/effectiveness clinical approach practice has been developed. Prospective clinical application will be tested in further studies. Legal entity responsible for the study Fabio Marazzi. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

OBJECTIVETo explore the role of diffusion-weighted imaging (DWI) in the staging of axillary lymph nodes and the restaging after neoadjuvant chemotherapy (NAD) in advanced breast cancer.PATIENTS AND METHODSMRI examinations of forty-two patients diagnosed with advanced breast cancer addressed to NAD and axillary lymph node dissection (ALND) were reviewed. Apparent diffusion coefficients (ADC) of each visible node in DWI in the pathologic axilla (PA) and healthy axilla (HA) were measured at the time of diagnosis (t0) and after chemotherapy (t1); mean values of the ADC were calculated. Patients were classified as responders (R), non-responders (NR), macrometastasis (MA), micrometastasis (Mi).RESULTSMean ADC was 0.92 ± 0.07 x 10-3 mm2/sec at t0 and 0.97 ± 0.06 x 10-3 mm2/sec at t1 (p = 0.284) in PA, 0.89 ± 0.06 x 10-3 mm2/sec at t0 and 0.92 ± 0.06 x 10-3 mm2/sec at t1 (p = 0.403) in HA, 0.95 ± 0.111 x 10-3 mm2/sec at t0 and 0.95 ± 0.14 x 10-3 mm2/sec at t1 (p = 0.954) in R group, 0.90 ± 0.09 x 10-3 mm2/sec at t0 and 0.97 ± 0.07 x 10-3 mm2/sec at t1 (p = 0.085) in NR group, 0.86 ± 0.10 x 10-3 mm2/sec at t0 and 0.99 ± 0.09 x 10-3 mm2/sec at t1 (p = 0.055) in MA, and 0.99 ± 0.23 x 10-3 mm2/sec at t0 and 0.95 ± 0.15 x 10-3 mm2/sec at t1 in Mi (p = 0.667).CONCLUSIONSMean ADC between PA and HA, R and NR, MA and Mi did not significantly differ at t0 and t1 (p > 0.05). Variation in mean ADC between t0 and t1 was not significant in all groups (p > 0.05), except for a trend toward significance (p = 0.055) in MA. DWI has a potential role in restaging of macrometastatic axillary nodes after NAD.

Objectives: We address the diagnostic performance of breast MRI and the efficacy of neoadjuvant radiochemotherapy (NRC) treatment (NRC protocol) vs conventional neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer.Methods: The NRC protocol consists of six anthracycline/taxane cycles and concomitant low-dose radiotherapy on breast tumour volume. Breast MRI was performed at baseline and after the last therapy cycle in 18 and 36 patients undergoing the NRC protocol or conventional NAC (propensity matching).Results: In both groups, we observed reduced tumour dimensions after the last cycle (p<0.001), and the response evaluation criteria in solid tumours (RECIST) class directly correlated with the tumour regression grade class after the last cycle (p<0.001). Patients in the NRC group displayed a higher frequency of complete/partial response than those in the NAC group (p=0.034). 17 out of 18 patients in the NRC group met the criteria for avoiding mastectomy based on final MRI evaluation. The RECIST classification displayed a superior diagnostic performance in the prediction of the response to treatment [area under the receiver operating characteristic curve (AUC)=0.72] than time-to-intensity curves and apparent diffusion coefficient (AUC 0.63 and 0.61). The association of the three above criteria yielded a better diagnostic performance, both in the general population (AUC=0.79) and in the NRC and the NAC group separately (AUC=0.82 and AUC=0.76).Conclusions: The pathological response is predicted by MRI performed after the last cycle, if both conventional MRI and diffusion imaging are integrated. The NRC treatment yields oncological results superior to NAC.Advances in knowledge: MRI could be used to establish the neoadjuvant protocol in breast cancer patients.

Malacoplakia is a rare inflammatory condition characterized by the accumulation of benign macrophages associated with pathognomonic Michaelis-Gutmann bodies (MGBs). It is usually found in the genito-urinary tract, and has been associated with immunocompromised states. In this short report, we present 5 patients with pulmonary nodules clinically suspicious for primary or metastatic lung cancer. The histologic examination of the surgical specimens revealed a nonspecific granulomatous chronic disease, and despite the paucity of classical MGBs, a pulmonary malacoplakia was suspected. In all cases the opportunistic pathogen Rhodococcus equi (R. equi) was identified by 16S rRNA gene sequence analysis, leading to the final pathological diagnosis of malacoplakia. We conclude that pulmonary malacoplakia associated with R. equi is a rare disease affecting also immunocompetent patients. The pathogenesis and the diagnostic problems are discussed. Since infection by R. equi is treatable, the importance of its early recognition should be emphasized.

Background: Anti-angiogenic therapy with bevacizumab (an anti-vascular endothelial growth factor (VEGF) antibody) predominantly targets immature blood vessels. Bevacizumab has shown a survival benefit in non-small cell lung carcinoma (NSCLC) and has recently been demonstrated to be safe in patients with brain metastases. However, it is not known whether bevacizumab is effective against brain metastases or whether metastases are representative of their primary in terms of VEGF expression, hypoxia, proliferation and vascular phenotype. The aim of this study was to evaluate these factors in a series of matched primary NSCLCs and brain metastases. Methods and Results: Immunohistochemistry showed strong correlation of carbonic anhydrase 9 expression (a marker of hypoxia) in primary and secondary cancers ( P =0.0002). However, the proliferation index, VEGF expression, microvessel density and the proportion of mature vessels were discordant between primary and secondary cancers. The mean proportion of mature vessels was 63.2% higher in the brain metastases than the primary tumours ( P =0.004). Moreover, the vascular pattern of the primary tumour was not representative of the metastasis. Conclusions: Brain metastases have a significantly higher proportion of mature vasculature, suggesting that they may be refractory to anti-VEGF therapy. These findings may have implications for clinical trials and biomarker studies evaluating anti-angiogenic agents in brain metastases.

Parotid gland tumours are very heterogeneous, being benign in 80% of cases, and generally arising from epithelial cells. Nevertheless, a small group of non-epithelial tumours representing just 5% of all salivary gland neoplasms has also been reported, the most common of these being haemangioma, especially in children. However, lymphomas, neuromas, neurofibromas, lipomas and sarcomas can also be found. Synovial cell sarcoma is a high grade histological variety of sarcoma and is generally located near large joints and bursae of the lower extremities, such as knee, tendon sheaths and bursal structures. It is rarely found in the head and neck region due to its lack of synovioblastic tissue. Herewith, the case of a young female, affected by a synovial sarcoma of the left parotid gland, is presented and a review is made of the literature on this rare specific localization focusing on management and outcome.

Long-awaited results from randomized clinical trials designed to test the validity of sentinel lymph node biopsy (SLNB) as replacement of axillary lymph node dissection (ALND) in management of early breast cancer have recently been published. All the trials conclude SLNB has survival rates comparable to those of ALND (up to 10 years in one study) and conclude SLNB has less morbidity than ALND. All the trials support replacing ALND with SLNB for staging in early breast cancer; all support SLNB as the standard of care for such cancer. The SLNB protocols used in the trials varied, and no consensus that would suggest a standard protocol exists. The results of the trials and of other peer-reviewed research do, however, suggest a framework for including some specific methodologies in accepted practice. This article highlights the overall survival and disease-free survival data as reported from the clinical trials. This article also reviews the status of SLN procedures and the following: male breast cancer, the roles of various imaging modalities (single-photon emission computed tomography/computed tomography, positron emission tomography/computed tomography, and ultrasound), ductal carcinoma in situ, extra-axillary SLNs, SLNB after neoadjuvant chemotherapy, radiation exposure to patients and medical personnel, and a new radiotracer that is the first to label SLNs not by particle trapping but by specific macrophage receptor binding. The proper Current Procedural Terminology (CPT) code for lymphoscintigraphy and SLN localization prior to surgery is 78195.