Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer.

BACKGROUND: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. MATERIALS AND METHODS: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. RESULTS: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. CONCLUSIONS: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.

Improved nationwide survival of sarcoma patients with a network of reference centers.

BACKGROUND: We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020. RESULTS: A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers. CONCLUSIONS: The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved.

OSNA Total Tumor Load for the Prediction of Axillary Involvement in Breast Cancer Patients: Should We use Different Thresholds According to the Intrinsic Molecular Subtype? MOTTO Study.

Aims: To assess the impact of the molecular subtype (MS) on the total number of CK19 mRNA copies in all positive SLN (TTL) threshold, to predict non-SLN affectation, and to compare 5 years progression-free survival (PFS) according to the risk of recurrence (ROR) group by PAM50. Methods: Cohort with infiltrating breast cancer with intra-operative metastatic SLN detected by one-step nucleic acid amplification (OSNA) assay who underwent subsequent ALND. Logistic regression was used to assess a possible interaction between TTL and MS(Triple Negative, Her-2-Enriched, Luminal A, or Luminal B), or hormone receptors (HR: positive or negative) by immunohistochemistry (IMH). Cox regression was used to compare PFS and OS in the 3 ROR groups (high, medium, or low). Results: TTL was predictive of non-SLN affectation in both univariate (OR [95% CI]: 1.72 [1.43, 2.05], P < .001) and multivariate (1.55 [95% CI: 1.04, 2.32], P = .030) models, but MS-IMH or HR-IMH, and their interactions with TTL were not (best multivariate model: HR + main effect OR 1.16 [95% CI: 0.18, 7.64], P = .874; interaction OR: 1.04 [0.7, 1.55], P = .835; univariate model: HR + main effect OR: 1.44 [95% CI: 0.85, 2.44], P = .180). PFS was lower in the high-risk ROR group (81.1%) than in the low-risk group (93.9%) (HR: 3.68 [95 CI: 1.70, 7.94], P < .001). Conclusions: our results do not provide evidence to support the utilization of subtype-specific thresholds for TTL values to make therapeutic decisions on the axilla. The ROR group was predictive of 5 years-PFS.

Photoswitching/back-switching assessment of biobased cellulose acetate/azobenzene handleable films under visible-light LED irradiation.

The light-induced processes performed by photofunctional polymer films are crucial aspects of developing integrated energy storage devices properly. Herein, we report the preparation, characterization, and study of the optical properties of a series of biobased cellulose acetate/azobenzene (CA/Az1) handleable films at different compositions. The photoswitching/back-switching behavior of the samples was investigated using varied LED irradiation sources. Additionally, poly(ethylene glycol) (PEG) was deposited onto cellulose acetate/azobenzene films to study the back-switching process's effect and nature in the fabricated films. Interestingly, the melting enthalpies of PEG before and after being irradiated with blue LED light were 2.5 mJ and 0.8 mJ, respectively. Conveniently, FTIR and UV-visible spectroscopy, thermogravimetry (TGA), contact angle, differential scanning calorimetry (DSC), polarized light microscopy (PLM), and atomic force microscopy (AFM) were used for the characterization of the sample films. Complementarily, theoretical electronic calculations provided a consistent approach to the energetic change in the dihedral angles and non-covalent interaction for the trans and cis isomer in the presence of cellulose acetate monomer. The results of this study revealed that CA/Az1 films are viable photoactive materials displaying handleability attributes with potential uses in harvesting, converting, and storing light energy.

Radiotherapy for penile cancers.

Penile cancers are uncommon and should be treated in expert center. Radiotherapy indications are mainly limited to exclusive brachytherapy for early stage penile glans cancer. Brachytherapy yields to excellent outcome for disease control and organ and function preservation. Only scarce data are available for external beam radiation therapy. It could be considered as palliative setting for irradiation of the primary tumor. For lymph node irradiation, external beam radiation therapy (with or without chemotherapy) could be discussed either as neoadjuvant approach prior to surgery for massive inguinal lymph node invasion or as adjuvant approach in case of high-risk of relapse. However, these cases should be discussed on an individual basis, as the level of evidence is poor. We present the recommendations of the French Society of Oncological Radiotherapy on the indications and techniques for external beam radiotherapy and brachytherapy for penile glans cancer.

The sacral chordoma margin.

OBJECTIVE: Aim of the manuscript is to discuss how to improve margins in sacral chordoma. BACKGROUND: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery. METHODS: A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed. RESULTS: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment. CONCLUSION: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients.

Adjuvant management of operated uterine sarcomas: A single institution experience.

PURPOSE: The purpose of this study was to describe the adjuvant management of high grade uterine sarcoma and highlight prognostic factors for overall survival and progression-free survival. MATERIAL AND METHODS: Between 01/2000 and 01/2015, 91 patients undergoing surgery were presented at the multidisciplinary team meeting of our institution. The type of surgery, the anatomopathological features, adjuvant treatments, dates and sites of recurrence were collected. The prognostic value of the various factors was evaluated with the multivariate Cox model. RESULTS: A total of 50 women with uterine sarcoma were identified and lesions included 43 leiomyosarcomas (86%) and seven high grade sarcomas (14%). Eighteen patients received adjuvant pelvic radiotherapy (36%) and six adjuvant systemic therapy (12%). The median follow-up time was 63 months. Thirty-nine patients (78%) had a recurrence: 22 had only metastatic recurrence (58%), two had isolated pelvic recurrence (5%) and 15 had pelvic and metastatic recurrence (38%). Adjuvant radiotherapy was associated with survival without pelvic recurrence in univariate analysis (P=0.005, hazard ratio [HR]=0.15); age greater than 55 years and adjuvant radiotherapy were associated with metastatic free survival in multivariate analysis (P=0.015, HR=2.37, and P=0.013, HR=0.41 respectively) CONCLUSION: According to the results of our series, there is a benefit of radiotherapy after surgery in terms of local control of uterine sarcoma. It is necessary to identify the subgroup of patients who will benefit from an adjuvant radiotherapy in order to provide them with more optimal care.

Localized high grade endometrial stromal sarcoma and localized undifferentiated uterine sarcoma: a retrospective series of the French Sarcoma Group.

OBJECTIVE: High grade endometrial stromal sarcoma and undifferentiated uterine sarcomas are associated with a very poor prognosis. Although large surgical resection is the standard of care, the optimal adjuvant strategy remains unclear. METHODS: A retrospective analysis of patients with localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas (stages I-III) treated in 10 French Sarcoma Group centers was conducted. RESULTS: 39 patients with localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas treated from 2008 to 2016 were included. 24/39 patients (61.5%) were stage I at diagnosis. 38/39 patients underwent surgical resection, with total hysterectomy and bilateral oophorectomy completed in 26/38 (68%). Surgeries were mostly resection complete (R0, 23/38, 60%) and microscopically incomplete resection (R1, 6/38, 16%). 22 patients (58%) underwent postoperative radiotherapy (including brachytherapy in 11 cases), and 11 (29%) underwent adjuvant chemotherapy. After a median follow-up of 33 months (range 2.6-112), 17/39 patients were alive and 21/39 (54%) had relapsed (9 local relapses and 16 metastases). The 3 year and 5 year overall survival rates were 49.8% and 31.1%, respectively, and 3 year and 5 year disease free survival rates were 42.7% and 16.0%, respectively. Median overall survival and disease free survival were 32.7 (95% CI 16.3-49.1) and 23 (4.4-41.6) months, respectively. Medians were, respectively, 46.7 months and 39.0 months among those who underwent adjuvant radiotherapy and 41.0 months and 10.3 months for those who underwent adjuvant chemotherapy. In multivariate analysis, adjuvant radiotherapy was an independent prognostic factor for overall survival (P=0.012) and disease free survival (P=0.036). Chemotherapy, International Federation of Gynecology and Obstetrics I-II stages, and Eastern Cooperative Oncology Group-performance status 0 correlated with improved overall survival (P=0.034, P=0.002, P=0.006), and absence of vascular invasion (P=0.014) was associated with better disease free survival. CONCLUSIONS: The standard treatment of primary localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas is total hysterectomy and bilateral oophorectomy. The current study shows that adjuvant radiotherapy and adjuvant chemotherapy appear to improve overall survival. A prospective large study is warranted to validate this therapeutic management.

Mannheimia haemolytica OmpP2-like is an amyloid-like protein, forms filaments, takes part in cell adhesion and is part of biofilms.

Mannheimia haemolytica causes respiratory disease in cattle. Amyloid proteins are a major component of biofilms; they aid in adhesion and confer resistance against several environmental insults. The amyloid protein curli is highly resistant to protease digestion and physical and chemical denaturation and binds Congo red (CR) dye. The purpose of this study was to characterize an approximately 50-kDa CR-binding amyloid-like protein (ALP) expressed by M. haemolytica. This protein resisted boiling and formic acid digestion and was recognized by a polyclonal anti-Escherichia coli curli serum, suggesting its relationship with amyloid proteins. Immunolabeling and transmission electron microscopy showed that antibodies bound long, thin fibers attached to the bacterial surface. Mass spectrometry analysis indicated that these fibers are M. haemolytica OmpP2-like proteins. The purified protein formed filaments in vitro, and antiserum against it reacted positively with biofilms. An in silico analysis of its amino acid sequence indicated it has auto-aggregation properties and eight amyloid peptides. Rabbit polyclonal antibodies generated against this ALP diminished the adhesion of ATCC 31612 and BA1 M. haemolytica strains to A549 human epithelial cells, indicating its participation in cell adhesion. ALP expressed by M. haemolytica may be important in its pathogenicity and ability to form biofilms.

[Quality in the anesthesia department of San Cecilio Hospital from the professionals' perspective]. / La calidad en el Bloque Quirúrgico del Hospital Clínico San Cecilio. La perspectiva del cliente interno.

OBJECTIVE: To evaluate the quality of the services provided by the anaesthesia department of the San Cecilio Clinical University Hospital, from the health professionals' point of view. MATERIAL AND METHODS: Location: Andalusia. PARTICIPANTS: 134 health professionals in contact with the hospital anaesthesia department. Tool: self-administered questionnaire, measuring: accessibility, personal treatment, comfort, scientific and technical quality (scale 1 to 5), overall satisfaction (scale 0 to 10), and suggestions for improvement. A descriptive statistical and correlation analysis were performed, including mean differences (by sex, frequency of contact with the anaesthesia department, and unit), as well as a regression model. RESULTS: The quality of personal treatment received a mean of 4.2 points (SD 0.651), the scientific and technical quality 4.00 points (SD 0.532), accessibility 3.3 (SD 0.795), professional comfort 3.30 (SD 0.988), and patient comfort 2.62 points (SD 1.051). Overall satisfaction obtained a mean of 7.1 points (0 to 10 scale). Women and professionals working in units with less than 10 people had a better general evaluation of the anaesthesia department. The worse perspective was that of staff with daily contact with the anaesthesia department. Among the suggestions for improvement there were: Reducing waiting lists, creating special rooms to give information to families, improving working conditions, training and work satisfaction for staff, and achieving better communication and collaboration between health professionals. CONCLUSIONS: The internal evaluation shows the need for training strategies and organisational interventions in the anaesthesia department, in order to achieve a better quality and satisfaction for both professionals and patients.

[Intraprostatic fiducials in stereotactic radiotherapy for prostate cancer]. / Fiduciels intraprostatiques dans le cadre de la radiothérapie stéréotaxique du cancer de la prostate.

PURPOSE: Image-guided radiotherapy for prostate cancer is widely used in radiotherapy departments. Intraprostatic gold fiducial markers are used to visualize prostate position and motion before and during treatment. The aim of this report is to describe our experience of implanting intraprostatic fiducial markers under local anesthesia before hypofractionated stereotactic radiotherapy for prostate cancer and to assess its tolerance and reproducibility. PATIENTS AND METHODS: Over a 6 and a half year period, 226 patients with prostate cancer received a stereotactic radiotherapy using the CyberKnife® system (Accuray) in our institution. Eighteen patients were treated for recurrence after prostatectomy; these patients were excluded from the study. Among the 208 remaining patients, 94 patients (45.2%) received stereotactic radiotherapy as a boost after external beam radiotherapy (three fractions of 6Gy); 36 patients (17.3%) were had a re-irradiation (six fractions of 6Gy) and 78 patients (37.5%) had a exclusive stereotactic radiotherapy (68 patients received five fractions of 7.25Gy and 11 patients five fractions of 6.25Gy). Four markers were implanted in all patients using transrectal ultrasound; the procedure was performed under local anesthesia, using transperineal access. The four fiducial markers were implanted in two strands with two fiducial each one, 1cm apart. In order to follow the recommendations of the image-guided radiotherapy system, the two strands of the two markers were located on the same plane in the middle of the prostate, at least 2cm apart from the midline. After insertion, correct positioning of fiducials markers was verified by X-ray. Dosimetry scanning was performed after the implantation procedure; prostate position tracking was possible before and during treatment through the kilovoltage incorporated system of the robotic accelerator. Clinical data, X-ray verification and dosimetry scanner have been retrospectively reviewed for all patients. RESULTS: The tolerance to procedure was excellent; only four patients (1.8%) described pain related to implant. No urinary side effects were reported. Median time from fiducial implantation to dosimetry scanner was 16 days (4-113 days). Four fiducials were found within the prostate at dosimetry scanner in 181 patients and three in 27 remaining patients. All intraprostatic fiducials were used to track the prostate gland before and during treatment. CONCLUSIONS: Intraprostatic fiducial markers implantation is a safe and reproducible procedure that allows us to have reliable prostate information before and during stereotactic radiotherapy.

Symptomatic Venous Thromboembolism and Major Bleeding After Renal Transplantation: Should We Use Pharmacologic Thromboprophylaxis?

BACKGROUND: Venous thromboembolism (VTE) is a major health issue that may result in complications such as post-thrombotic syndrome, pulmonary hypertension, and death. Appropriate thromboprophylaxis in individuals undergoing kidney transplantation remains unclear. The aim of this study was to determine the prevalence of symptomatic VTE and major bleeding within 90 days after renal transplantation (RT). METHODS: This was a retrospective study on consecutive patients undergoing RT at Hospital Privado Córdoba, Argentina, from January 1, 2006, to December 31, 2013. Exclusion criteria were age <18 years and combined organ transplantation. Pharmacologic or mechanical thromboprophylaxis was not used routinely. Symptomatic VTE and major bleeding were documented. RESULTS: A total of 511 RTs were performed; 62 patients received combined organ transplantation, and 8 patients (1.5%) were lost to follow-up. Overall, follow-up was completed on 441 patients, 4 (0.9%) of whom developed deep venous thrombosis and 14 (3%) of whom died. The most frequent causes of death were septic shock and severe hemorrhage. Duration of surgery >4 hours (P = .006) and a history of VTE (P < .001) were associated with VTE. Twenty-three patients (5.2%) had major bleeding, 2 (0.4%) died from bleeding complications, and 17 (3.85%) required a reoperation to control bleeding. CONCLUSIONS: This study shows a low prevalence of symptomatic VTE in patients undergoing RT despite not having used thromboprophylaxis routinely. Major bleeding was significant, and despite the high risk of VTE assigned by the Caprini score, which suggests pharmacologic prophylaxis, our data raise questions about the appropriate prophylaxis for these patients.

Low-dose brachytherapy for early stage penile cancer: a 20-year single-institution study (73 patients).

PURPOSE/OBJECTIVES: The aim of this study is to analyze the results of exclusive interstitial brachytherapy (IBT) as a conservative approach in the treatment of penile cancer confined to the glans or the shaft with long-term follow-up in a single institution. MATERIALS/METHODS: Between July 1992 and November 2013, 73 consecutive patients with non-metastatic invasive penile cancer were treated by Low dose rate (LDR) IBT in our institution. The localization of the primary lesion was glands in 67 patients (91.8 %) and shaft in 6 patients (8.2 %). All 73 patients presented with squamous cell carcinoma with grades of differentiation as follows: 34 patients with grade 1 (44.7 %), 9 patients with grade 2 (11.8 %), 9 patients with grade 3 (11.8 %) and 21 patients unknown (28.8 %). Six patients (7.8 %) presented with in situ carcinoma, 55 patients (75,3 %) presented with T1, 11 patients (15 %) presented with T2, and one patient (1.3 %) presented with Tx. Inguinal nodal dissection was performed in 29 patients (38.2 %); 13 patients (17.8 %) presented with histologically confirmed positive ganglion. After circumcision, IBT was performed using a hypodermic needle. The median dose delivered was 60 Gy (range, 40 to 70 Gy). The median activity of the iridium-192 wire was 1.12 mCi/cm, and the median reference isodose rate was 0.4 Gy/h (range, 0.2-1.2). Patients with histological inguinal metastases received external beam radiotherapy to the selected inguinal affected area with a median dose of 45 Gy (30-55 Gy). RESULTS: The median follow-up time was 51.8 months (range 34.4 to 68.7). The 5-year overall survival was 82.0 %, with eight deaths from cancer and five non-cancer-related deaths. Disease-specific survival was 91.4 %, relapse-free survival was 64.4 %, and local relapse-free survival as 74 %. Total or partial penile preservation was 87.9 % at 5-years. Complications rates at 5 years were 6.6 % urethral stenosis (five patients), two patients (2.6 %) with pain related to sexual intercourse and four patients (5.3 %) with dysuria grade 2. Five patients (6.8 %) required penile amputation for necrosis. CONCLUSIONS: IBT provides good local control with organ preservation, excellent tolerance and low complication rates in early-stage penile cancers.

Gene promoter hypermethylation is found in sentinel lymph nodes of breast cancer patients, in samples identified as positive by one-step nucleic acid amplification of cytokeratin 19 mRNA.

We analysed the promoter methylation status of five genes, involved in adhesion (EPB41L3, TSLC-1), apoptosis (RASSF1, RASSF2) or angiogenesis (TSP-1), in intraoperative sentinel lymph node (SLN) biopsy samples from patients with breast cancer, that had been processed by the one-step nucleic acid amplification (OSNA) technique. SLN resection is performed to estimate the risk of tumour cells in the clinically negative axilla, to avoid unnecessary axillary lymph node dissection. OSNA is currently one of the eligible molecular methods for detecting tumour cells in SLNs. It is based on the quantitative evaluation of cytokeratin 19 mRNA which allows distinguishing between macrometastasis, micrometastasis and isolated tumour cells, on the basis of the quantity of tumour cells present. There have been no prior studies on the question whether or not samples processed by OSNA can be used for further molecular studies, including epigenetic abnormalities which are some of the most important molecular alterations in breast cancer. Genomic DNA was extracted from samples obtained from 50 patients diagnosed with primary breast cancer. The content of tumour cells in SLNs was evaluated by OSNA, and the promoter methylation status of the selected genes was analysed by methylation-specific PCR. All were found to be hypermethylated to a variable degree, and RASSF1 hypermethylation was significantly associated with macrometastasis, micrometastasis and isolated tumour cells (p = 0.002). We show that samples used for OSNA are suitable for molecular studies, including gene promoter methylation. These samples provide a new source of material for the identification of additional biomarkers.

Consistency in recognizing microinvasion in breast carcinomas is improved by immunohistochemistry for myoepithelial markers.

Microinvasion is the smallest morphologically identifiable stage of invasion. Its presence and distinction from in situ carcinoma may have therapeutic implications, and clinical staging also requires the recognition of this phenomenon. Microinvasion is established on the basis of several morphological criteria, which may be difficult and not perfectly reproducible among pathologists. The aim of this study was to assess the consistency of diagnosing microinvasion in the breast on traditional haematoxylin and eosin (HE) stained slides and to evaluate whether immunohistochemistry (IHC) for myoepithelial markers could improve this. Digital images were generated from representative areas of 50 cases stained with HE and IHC for myoepithelial markers. Cases were specifically selected from the spectrum of in situ to microinvasive cancers. Twenty-eight dedicated breast pathologists assessed these cases at different magnifications through a web-based platform in two rounds: first HE only and after a washout period by both HE and IHC. Consistency in the recognition of microinvasion significantly improved with the use of IHC. Concordance rates increased from 0.85 to 0.96, kappa from 0.5 to 0.85, the number of cases with 100% agreement rose from 9/50 to 25/50 with IHC and the certainty of diagnosis also increased. The use of IHC markedly improves the consistency of identifying microinvasion. This corroborates previous recommendations to use IHC for myoepithelial markers to clarify cases where uncertainty exists about the presence of microinvasion. Microinvasive carcinoma is a rare entity, and seeking a second opinion may avoid overdiagnosis.

Paradoxical reaction to antituberculosis therapy in a patient with lupus vulgaris.

Patients receiving treatment for tuberculosis may experience an unexpected deterioration of their disease; this is known as a paradoxical reaction. We present the case of a 59-year-old man with lupus vulgaris who experienced a paradoxical deterioration of cutaneous lesions after starting antituberculosis therapy. The reaction was self-limiting; the lesions gradually improved, and the final outcome was very good. Paradoxical reactions are well-known in patients with human immunodeficiency virus (HIV) infection who start antiretroviral therapy, but they can also occur in non-HIV-infected patients with tuberculosis who start antituberculosis therapy. In the literature reviewed, paradoxical reactions involving skin lesions were described in patients with miliary tuberculosis. The case we report is the first of a paradoxical reaction in lupus vulgaris. The increasing frequency of tuberculosis in Spain could lead to a rise in the number of paradoxical reactions.

Pathological non-response to chemotherapy in a neoadjuvant setting of breast cancer: an inter-institutional study.

To identify markers of non-response to neoadjuvant chemotherapy (NAC) that could be used in the adjuvant setting. Sixteen pathologists of the European Working Group for Breast Screening Pathology reviewed the core biopsies of breast cancers treated with NAC and recorded the clinico-pathological findings (histological type and grade; estrogen, progesterone receptors, and HER2 status; Ki67; mitotic count; tumor-infiltrating lymphocytes; necrosis) and data regarding the pathological response in corresponding surgical resection specimens. Analyses were carried out in a cohort of 490 cases by comparing the groups of patients showing pathological complete response (pCR) and partial response (pPR) with the group of non-responders (pathological non-response: pNR). Among other parameters, the lobular histotype and the absence of inflammation were significantly more common in pNR (p < 0.001). By ROC curve analyses, cut-off values of 9 mitosis/2 mm(2) and 18% of Ki67-positive cells best discriminated the pNR and pCR + pPR categories (p = 0.018 and < 0.001, respectively). By multivariable analysis, only the cut-off value of 9 mitosis discriminated the different response categories (p = 0.036) in the entire cohort. In the Luminal B/HER2- subgroup, a mitotic count <9, although not statistically significant, showed an OR of 2.7 of pNR. A lobular histotype and the absence of inflammation were independent predictors of pNR (p = 0.024 and <0.001, respectively). Classical morphological parameters, such as lobular histotype and inflammation, confirmed their predictive value in response to NAC, particularly in the Luminal B/HER2- subgroup, which is a challenging breast cancer subtype from a therapeutic point of view. Mitotic count could represent an additional marker but has a poor positive predictive value.