[2021 update of the GEFPICS' recommendations for HER2 status assessment in invasive breast cancer in France]. / Mise à jour 2021 des recommandations du GEFPICS pour l'évaluation du statut HER2 dans les cancers infiltrants du sein en France.

The last international guidelines on HER2 determination in breast cancer have been updated in 2018 by the American Society of Clinical Oncology and College of American Pathologists, on the basis of a twenty-year practice and results of numerous clinical trials. Moreover, the emerging HER2-low concept for 1+ and 2+ non amplified breast cancers lead to refine French practices for HER2 status assessment. The GEFPICS group, composed of expert pathologists, herein presents the latest French recommendations for HER2 status evaluation in breast cancer, taking into account the ASCO/CAP guidelines and introducing the HER2-low concept. In the era of personalized medicine, HER2 status assessment remains one of the most important biomarkers in breast cancer and its quality guaranties the optimal patients' care. French pathologists' commitment in theranostic biomarker quality is more than ever required to provide the most efficient cares in oncology.

[GEFPICS' guidelines for management of breast cancer tissue samples in the neoadjuvant setting]. / Recommandations du GEFPICS pour la prise en charge des prélèvements dans le cadre du traitement néoadjuvant du cancer du sein.

Neoadjuvant therapy is an increasing treatment option in the management of breast cancer. The tumor response to neoadjuvant therapy, especially the pathological complete response, is a validated endpoint frequently used in clinical trials. However, there is still a lack of standardization for the surgical specimen management in the neoadjuvant setting. This leads to heterogeneity in the specimen handling and might lead to significant bias for the prognostic assessment of patients or in clinical trials. The GEFPICS group, composed of expert breast cancer pathologists, herein presents guidelines for the management of breast and axillary specimen before treatment (management of biopsy, items of the pathological report) and after neoadjuvant therapy (specimen handling, histological assessment of response, items of the pathological report and response grading systems).

Primary radical ablative surgery and fibula free-flap reconstruction for T4 oral cavity squamous cell carcinoma with mandibular invasion: oncologic and functional results and their predictive factors.

The aims of this study were to evaluate clinical outcomes and to determine their predictive factors in patients with oral cavity squamous cell carcinoma (OCSCC) invading the mandibular bone (T4) who underwent primary radical surgery and fibula free-flap reconstruction. Between 2001 and 2013, all patients who underwent primary surgery and mandibular fibula free-flap reconstruction for OCSCC were enrolled in this retrospective study. Predictive factors of oncologic and functional outcomes were assessed in univariate and multivariate analysis. 77 patients (55 men and 22 women, mean age 62 ± 10.6 years) were enrolled in this study. Free-flap failure and local and general complication rates were 9, 31, and 22 %, respectively. In multivariate analysis, ASA score (p = 0.002), pathologic N-stage (p = 0.01), and close surgical margins (p = 0.03) were independent predictors of overall survival. Six months after therapy, oral diet, speech intelligibility, and mouth opening functions were normal or slightly impaired in, respectively, 79, 88, and 83 % of patients. 6.5 % of patients remaining dependent on enteral nutrition 6 months after therapy. With acceptable postoperative outcomes and satisfactory oncologic and functional results, segmental mandibulectomy with fibula free-flap reconstruction should be considered the gold standard primary treatment for patients with OCSCC invading mandible bone. Oncologic outcomes are dependent on three main factors: ASA score, pathologic N-stage, and surgical margin status.

Nutritional status and feeding-tube placement in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy-based larynx preservation program.

The objective of the study is to evaluate the nutritional status and determine its impact on clinical outcomes in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy (ICT)-based larynx preservation program without prophylactic feeding-tube placement. All patients with locally advanced (T3/4, N0-3, M0) hypopharyngeal squamous cell carcinoma, technically suitable for total pharyngolaryngectomy, treated by docetaxel, cisplatin and 5-fluorouracil (TPF)-ICT for larynx preservation at our institution between 2004 and 2013, were included in this retrospective study. Patients' nutritional status was closely monitored. Enteral nutrition was used if and when a patient was unable to sustain per-oral nutrition and hydration. The impact of nutritional status on clinical outcomes was investigated in univariate and multivariate analysis. A total of 53 patients (42 men and 11 women, mean age = 58.6 ± 8.2 years) were included in this study. Six (11.3 %) patients had lost more than 10 % of their usual body weight before therapy. Compared with patients' usual weight, the mean maximum patient weight loss during therapeutic management was 8.7 ± 4.5 kg. Enteral nutrition was required in 17 patients (32 %). We found no influence of the tested nutritional status-related factors on response to ICT, toxicity of ICT, overall, cause-specific and recurrence-free survival, and on post-therapeutic swallowing outcome. Maximum weight loss was significantly associated with a higher risk of enteral tube feeding during therapy (p = 0.03) and of complications (grade ≥3, p = 0.006) during RT. Without prophylactic feeding-tube placement, approximately one-third of the patients required enteral nutrition. There was no significant impact of nutritional status on oncologic or functional outcomes.

[Pre-analytical stage for biomarker assessment in breast cancer: 2014 update of the GEFPICS' guidelines in France]. / Recommandations du GEFPICS concernant la phase pré-analytique pour l'évaluation de HER2 et des récepteurs hormonaux dans le cancer du sein : mise à jour 2014.

Biomarker assessment of breast cancer tumor samples is part of the routine workflow of pathology laboratories. International guidelines have recently been updated, with special regards to the pre-analytical steps that are critical for the quality of immunohistochemical and in situ hybridization procedures, whatever the biomarker analyzed. Fixation and specimen handling protocols must be standardized, validated and carefully tracked. Cooperation and training of the personnel involved in the specimen workflow (e.g. radiologists, surgeons, nurses, technicians and pathologists) are of paramount importance. The GEFPICS' update of the recommendations herein details and comments the different steps of the pre-analytical process. Application of these guidelines and participation to quality insurance programs are mandatory to ensure the correct evaluation of oncotheranostic biomarkers.

[2014 update of the GEFPICS' recommendations for HER2 status determination in breast cancers in France]. / Mise à jour 2014 des recommandations du GEFPICS pour l'évaluation du statut HER2 dans les cancers du sein en France.

International guidelines on HER2 determination in breast cancer have just been updated by the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP), on the basis of more than ten-year practice, results of clinical trials and concordance studies. The GEFPICS group, composed of expert pathologists in breast cancer, herein presents these recommendations, adapted to the French routine practice. These guidelines highlight the possible diagnosis difficulties with regards to HER2 status determination, such as intra-tumor heterogeneity, special histological subtypes and biomarker re-evaluation during metastatic relapse. Pre-analytical issues and updated scoring criteria (especially for equivocal cases) are detailed, in order to decrease the occurrence of false negative cases. In the era of personalized medicine, pathologists are more than ever involved in the quality of oncotheranostic biomarker evaluation.

Significance of circulating tumor cell detection using the CellSearch system in patients with locally advanced head and neck squamous cell carcinoma.

The objective of this study was to evaluate the potential detection of circulating tumor cells (CTCs) using the CellSearch (CS) Assay™ in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) and then to identify the clinical factors predictive of the presence of CTCs. The presence and number of CTCs were determined using the CS system before treatment, and in 10 healthy individuals (control group). The CS system was able to successfully identify the presence of CTCs in 8 of 49 patients (16 %) before therapy. No CTC was found in the control group. CTCs were detected before therapy in 1 of 19 patients (5 %) with N0 tumor and in 7 of 30 patients (23 %) with N1-2c tumor (p = 0.12; Fisher's exact test). CTCs were identified in a relatively low proportion of patients with locally advanced HNSCC.

Impact of patient comorbidities on head and neck microvascular reconstruction. A report on 423 cases.

The aim of this study was to assess the impact of the different subtypes of patient comorbidities on the outcomes of head and neck microvascular reconstruction. A total of 423 patients who underwent head and neck free flap reconstruction in our institution between 2000 and 2010 were included in this retrospective study. The impact of the different subtypes of patient comorbidities (as defined by the Kaplan-Feinstein Index) and other global health status-related factors on free flap success, local and general complications, postoperative mortality and length of stay was assessed in univariate and multivariate analysis. We found no correlation between patient comorbidities and free flap failure. In multivariate analysis, we demonstrated a significant correlation between tobacco consumption (p = 0.04) and local complications. Gastro-intestinal comorbidity (p = 0.005) and malnutrition (p = 0.02) were associated with a higher risk of fistula formation. Diabetes mellitus (p = 0.003), gastro-intestinal (p = 0.02), systemic (p = 0.02) and cardiac comorbidities (p = 0.03) were significant predictors of medical complications. We concluded that the different subtypes of patient comorbidities were relevant predictors of complications in head and neck microvascular reconstruction.

[Papillary meningioma: a very rare and aggressive variant of meningioma]. / Méningiome papillaire: une forme rarissime et agressive de méningiome.

Papillary meningioma (MP) is a rare and aggressive variant of meningioma, occurring preferentially in young subjects. Histopathological features of papillary meningiomas are characterized by papillary or perivascular pseudorosette patterns. We report the case of a right frontal MP in a 16-year-old boy. Differential diagnosis included other primitive or secondary intracranial papillary neoplasms. MP diagnosis should not be missed due to its aggressive behavior with brain invasion, local recurrence and metastases.

SENODAY: A New Perspective of Handling Breast Cancer.

BACKGROUND: To evaluate the feasibility of a same day breast cancer diagnosis and management protocol, consequently decreasing time to treatment and immediately reassuring patients with benign diagnosis. MATERIALS AND METHODS: A total of 60 women underwent breast exam during SENODAY in our cancer center between January 2020 and December 2022. Patients are first seen by a breast surgeon who mentions whether the patient's history and physical exam are suspicious of malignancy. Patients are then sent to the radiologist who performs a complete radiologic assessment, classifies the lesions, and performs a biopsy when necessary. The specimen is sent to the pathologist who uses the imprint cytology technique to obtain a preliminary diagnosis. Effective counseling is established in case of breast cancer diagnosis. RESULTS: Among 60 women, 25 patients were reassured by breast imaging and 35 underwent histopathological analysis (17 patients with a 1-day protocol and 18 with the standard definitive technique). Clinical examination was found to have a sensitivity of 100% and a specificity of 89.47%. The positive predictive value was 80 % and the negative predictive value was 100%. However, we did not find a strong correlation between imaging and definitive pathology. Moreover, on imprint cytology, sensitivity, specificity, PPV, and NPV were 100%. Finally, the mean time-to-treat was 28.6 days. CONCLUSIONS: SENODAY reassured 68.3% of patients. It also offered effective counseling and a treatment plan to newly diagnosed breast cancer patients within 1 day. Same day histological diagnosis by imprint cytology is effective and feasible with an excellent accuracy.

Validation of RUBY for Breast Cancer Knowledge Extraction From a Large French Electronic Medical Record System.

PURPOSE: RUBY is a tool for extracting clinical data on breast cancer from French medical records on the basis of named entity recognition models combined with keyword extraction and postprocessing rules. Although initial results showed a high precision of the system in extracting clinical information from surgery, pathology, and biopsy reports (≥92.7%) and good precision in extracting data from consultation reports (81.8%), its validation is needed before its use in routine practice. METHODS: In this work, we analyzed RUBY's performance compared with the manual entry and we evaluated the generalizability of the approach on different sets of reports collected on a span of 40 years. RESULTS: RUBY performed similarly or better than the manual entry for 15 of 27 variables. It showed similar performances when structuring newer reports but failed to extract entities for which changes in terminology appeared. Finally, our tool could automatically structure 15,990 reports in 77 minutes. CONCLUSION: RUBY can automate the data entry process of a set of variables and reduce its burden, but a continuous evaluation of the format and structure of the reports and a subsequent update of the system is necessary to ensure its robustness.

Pilot Study on the Use of Untargeted Metabolomic Fingerprinting of Liquid-Cytology Fluids as a Diagnostic Tool of Malignancy for Thyroid Nodules.

Although it is the gold standard for assessing the malignancy of thyroid nodules (TNs) preoperatively, the cytological analysis of fine-needle aspiration cytology (FNAC) samples results in 20-30% of cases in indeterminate lesions (ITNs). As two-thirds of these lesions will appear benign after diagnostic surgery, improved preoperative diagnostic methods need to be developed. In this pilot study, we evaluate if the metabolomic profiles of liquid-based (CytoRich®) FNAC samples of benign and malignant nodules can allow the molecular diagnosis of TNs. We performed untargeted metabolomic analyses with CytoRich® FNAC in a monocentric retrospective study. The cohort was composed of cytologically benign TNs, histologically benign or papillary thyroid carcinomas (PTCs) cytologically ITNs, and suspicious/malignant TNs histologically confirmed as PTCs. The diagnostic performance of the identified metabolomic signature was assessed using several supervised classification methods. Seventy-eight patients were enrolled in the study. We identified 7690 peaks, of which 2697 ions were included for further analysis. We selected a metabolomic signature composed of the top 15 metabolites. Among all the supervised classification methods, the supervised autoencoder deep neural network exhibited the best performance, with an accuracy of 0.957 (0.842-1), an AUC of 0.945 (0.833-1), and an F1 score of 0.947 (0.842-1). Here, we report a promising new ancillary molecular technique to differentiate PTCs from benign TNs (including among ITNs) based on the metabolomic signature of FNAC sample fluids. Further studies with larger cohorts are now needed to identify a larger number of biomarkers and obtain more robust signatures.

Let-7 microRNA and HMGA2 levels of expression are not inversely linked in adipocytic tumors: analysis of 56 lipomas and liposarcomas with molecular cytogenetic data.

The aim of our study was first to assess the role of HMGA2 expression in the pathogenesis of adipocytic tumors (AT) and, second, to seek a potential correlation between overexpression of HMGA2 and let-7 expression inhibition by analyzing a series of 56 benign and malignant AT with molecular cytogenetic data. We measured the levels of expression of HMGA2 mRNA and of eight members of the let-7 microRNA family using quantitative RT-PCR and expression of HMGA2 protein using immunohistochemistry. HMGA2 was highly overexpressed in 100% of well-differentiated/dedifferentiated liposarcomas (WDLPS/DDLPS), all with HMGA2 amplification, and 100% of lipomas with HMGA2 rearrangement. Overexpression of HMGA2 mRNA was detected in 76% of lipomas without HMGA2 rearrangement. HMGA2 protein expression was detected in 100% of lipomas with HMGA2 rearrangement and 48% of lipomas without HMGA2 rearrangement. We detected decreased expression levels of some let-7 members in a significant proportion of AT. Notably, let-7b and let-7g were inhibited in 61% of WDLPS/DDLPS. In lipomas, each type of let-7 was inhibited in approximately one-third of the cases. Although overexpression of both HMGA2 mRNA and protein in a majority of ordinary lipomas without HMGA2 structural rearrangement may have suggested a potential role for let-7 microRNAs, we did not observe a significant link with let-7 inhibition in such cases. Our results indicate that inhibition of let-7 microRNA expression may participate in the deregulation of HMGA2 in AT but that this inhibition is neither a prominent stimulator for HMGA2 overexpression nor a surrogate to genomic HMGA2 rearrangements.

RUBY: Natural Language Processing of French Electronic Medical Records for Breast Cancer Research.

PURPOSE: Electronic medical records are a valuable source of information about patients' clinical status but are often free-text documents that require laborious manual review to be exploited. Techniques from computer science have been investigated, but the literature has marginally focused on non-English language texts. We developed RUBY, a tool designed in collaboration with IBM-France to automatically structure clinical information from French medical records of patients with breast cancer. MATERIALS AND METHODS: RUBY, which exploits state-of-the-art Named Entity Recognition models combined with keyword extraction and postprocessing rules, was applied on clinical texts. We investigated the precision of RUBY in extracting the target information. RESULTS: RUBY has an average precision of 92.8% for the Surgery report, 92.7% for the Pathology report, 98.1% for the Biopsy report, and 81.8% for the Consultation report. CONCLUSION: These results show that the automatic approach has the potential to effectively extract clinical knowledge from an extensive set of electronic medical records, reducing the manual effort required and saving a significant amount of time. A deeper semantic analysis and further understanding of the context in the text, as well as training on a larger and more recent set of reports, including those containing highly variable entities and the use of ontologies, could further improve the results.

Clinical impact of cervical lymph node involvement and central neck dissection in patients with papillary thyroid carcinoma: a retrospective analysis of 368 cases.

The impact of cervical lymph node metastases and the optimal surgical management of the neck in patients with papillary thyroid carcinoma (PTC) remain controversial. The objectives of this retrospective study were to determine, in patients with PTC, the predictive factors and the impact on tumor recurrence rate of cervical lymph node involvement, and to evaluate the oncologic results and the morbidity of central neck dissection (CND). We reviewed the records of patients who had undergone surgical treatment for PTC at our institution between 1990 and 2000. A total of 368 patients (86 men and 282 women) were included in this study. Young age (p = 0.02), tumor size (p = 0.001) and extrathyroidal tumor extension (p = 0.003) were significant predictive factors of cervical lymph node metastatic involvement (multivariate analysis). Initial metastatic cervical lymph node involvement was identified as an independent risk factor of tumor recurrence (multivariate analysis, p = 0.01). Metastatic lymph node(s) were found in prophylactic CND specimens in 31% of the patients. CND increased the risk of postoperative hypocalcemia (p = 0.008) and of permanent hypoparathyroidism (p = 0.002). In conclusion, cervical lymph node metastatic involvement at the time of initial surgery is an independent risk factor of tumor recurrence. CND provided an up-staging of more than 30% of patients with a clinically N0 neck, but was associated with significant morbidity regarding parathyroid function.

[Is preoperative axillary radio-cytology justified after ACOSOG Z001?] / La radio-cytologie axillaire préopératoire est-elle justifiée après l'ACOSOG Z001 ?

INTRODUCTION: Invasive breast cancer without clinical adenopathy (cN0) is currently explored by the sentinel node (GS) technique, except in the case of positive preoperative radio-cytological screening, where axillary curage (CA) remains systematic from the outset. Since the publication of the ACOSOG-Z0011 trial, abstention from CA is possible in patients presenting less than three metastatic GS. As a result, the value of axillary radio-cytological screening is being questioned as it could potentially lead to axillary surgical over-treatment. The objective of this study was to study clinically N0 patients with positive axillary cytology and to compare it to a group of patients with positive GS. METHOD: One hundred and forty-seven patients with cN0 pN+ breast cancer treated between 2014 and 2016 were selected retrospectively. Two groups were constituted according to the initial radio-cytological evaluation. A CA was systematically performed. RESULTS: Thirty-one patients with positive axillary cytology (n=31 vs. n=116) had more metastatic lymph nodes (P=0.01) in the AC, larger (P<0.001), less differentiated (P<0.001) tumours, and shorter recurrence-free survival (P=0.0114). It also appeared that 38.7 % of patients with a positive cytology had at most two metastatic nodes and could, according to the results of ACOSOG, benefit from therapeutic de-escalation. CONCLUSION: X-ray cytological screening remains essential in order to select a subgroup of patients with a high lymph node tumour load. Additional studies are necessary in order to be able to offer therapeutic de-escalation to 1/3 of these patients without the risk of under-treatment for the remaining 2/3.

Phenotypic discordance between primary and metastatic breast cancer in the large-scale real-life multicenter French ESME cohort.

Expression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients. Patients with results available on both primary tumour and metastatic disease within 6 months of MBC diagnosis and before any tumour progression were eligible for the main analysis. Among the 16,703 patients included in the database, 1677 (10.0%) had available biopsy results at MBC diagnosis and on matched primary tumour. The change rate of either HR or HER2 was 27.0%. Global HR status changed (from positive = either ER or PR positive, to negative = both negative; and reverse) in 14.2% of the cases (expression loss in 72.5% and gain in 27.5%). HER2 status changed in 7.8% (amplification loss in 45.2%). The discordance rate appeared similar across different biopsy sites. Metastasis to bone, HER2+ and RH+/HER2- subtypes and previous adjuvant endocrine therapy, but not relapse interval were associated with an HR discordance in multivariable analysis. Loss of HR status was significantly associated with a risk of death (HR adjusted = 1.51, p = 0.002) while gain of HR and HER2 discordance was not. In conclusion, discordance of HR and HER2 expression between primary and metastatic breast cancer cannot be neglected. In addition, HR loss is associated with worse survival. Sampling metastatic sites is essential for treatment adjustment.

[Preoperative breast imaging review: Interests and limits of specialized validation in oncology]. / Relecture préopératoire en sénologie : intérêts et limites d'une validation spécialisée en oncologie.

OBJECTIVES: To evaluate the impact of systematic radiological review by breast specialist radiologist of malignant breast lesion imaging on the therapeutic management of patients. MATERIALS AND METHODS: Data collection was performed for patients with histopathologically proved breast cancer or suspicious breast lesion on imaging realized out of our institution. Patients underwent systematic mammary and axillary ultrasound, imaging review and if necessary complementary mammographic images. We analyzed the number of additional breast biopsies and axillary lymph node fine needle aspiration (FNA) with their histopathological results. We assessed their impact by comparing the final surgical treatment to the one planned before review. RESULTS: Two hundred and seventeen patients were included, with a total of 230 BIRADS 0, 4, 5 or 6 breast lesions. Seventy-six additional breast core biopsies were realized, leading to diagnose 43 additional BIRADS 6 lesions (24 infiltrative carcinomas, 9 DCIS and 10 atypical lesions) in 30 patients (13.82%). Thirty-five additional lymph node FNA were realized with 12 metastatic nodes and 3 false negative samples. Imaging review lead to change surgical treatment in 59 patients (27.19%, P<0.01) with modification in breast surgery in 37 patients, axillary surgery in 8 patients and both sites surgery in 12 patients. CONCLUSION: This study shows an impact of systematic radiological review by breast specialist radiologist in therapeutic management of patients treated for malignant breast lesion.

Primitive neuroectodermal tumor of the pelvis in an elderly patient.

BACKGROUND: Peripheral primitive neuroectodermal tumors (PNET) belong to the rare family of primary bone neoplasms. Recent clinicopathological studies have revealed that Ewing's sarcoma and PNET have overlapping features and they are now included in the same classification, the Ewing's sarcoma family of tumors (EFTs). PNET have a marked predilection for the extremities and are very rare in the pelvis. These tumors can occur at any age with a peak of incidence in the second and third decades but are very rare in patients over 40 years. CASE REPORT: We report the case of a 69-year-old man with PNET sarcoma. Outcome was favorable after combined modality treatment including chemotherapy based on the Memphis protocol - adapted from that used for Ewing's sarcoma in children - and surgery. CONCLUSION: Our case is uncommon because of the age at diagnosis, the fortuitous way of revelation, and the choice of dose-intense chemotherapy adapted from the Memphis protocol (cyclophosphamide- and doxorubicin-based) for children, which was efficient and safe. It supports the fact that an adult, and even an old patient, with good physical status, may be treated safely and radically even with dose-adapted aggressive chemotherapy.

[The presence of mycobacteria in bronchoalveolar lavage fluid from an immunocompetent patient does not necessarily imply tuberculosis]. / La présence de mycobactéries dans un LBA de sujet immunocompétent n'est pas synonyme de tuberculose.

Mycobacterium tuberculosis is the most frequently identified mycobacterium in the bronchoalveolar lavage fluid (BALF) of immunocompetent patients. Lung infections due to non-tuberculous mycobacteria (NTM) are rare in such patients and then often occur in the context of pre-existing chronic lung disease. We report the case of an immunocompetent 85-year-old woman without pre-existing lung disease in whom M. abscessus was recovered from BALF. Cytological examination of the BALF revealed an increased number of neutrophils and some acid-fast bacilli, all located within neutrophil cytoplasm. This case report contributes a cytological description of BALF in the context of M. abscessus infection, which is poorly detailed in the literature.