[Cutaneous adnexal tumours: Development and synthesis of diagnostic fusion genes]. / Tumeurs annexielles cutanées : mise au point et synthèse des gènes de fusion à connaître pour le diagnostic.

Cutaneous adnexal tumours are a heterogeneous group of epithelial lesions that includes tumours with follicular, sudoral and/or sebaceous differentiation, or even several combined lines of differentiation. Over the last few years, molecular analysis of these lesions has allowed to identify specific molecular events responsible for tumour development in an increasing number of tumour types. Like other rare neoplasms, such as soft tissue tumours, adnexal tumours display fusion genes resulting from chromosomal translocations that may be specific for the diagnosis if molecular data are properly integrated in the clinical and morphological setting. Molecular testing of adnexal tumours is valuable as it allows to strengthen the robustness of the diagnosis for a group of tumours displaying a wide morphological spectrum. It has allowed to refine the diagnostic criteria and to develop increasingly specific diagnostic immunostainings. Finally, molecular testing has been responsible for the identification of new entities or morphological subtypes of previously known entities. The aim of this review is to provide an update on cutaneous adnexal tumours associated with fusion genes and to evaluate the impact of molecular data on the diagnosis of these lesions.

[Creation, implementation and objectives of CARADERM, a national network for rare skin carcinomas - Adnexal neoplasm part]. / Développement, mise en œuvre et objectifs de CARADERM, réseau national cancers cutanés rares ­ partie carcinomes annexiels.

INTRODUCTION: CARADERM is a French national network that includes patients with rare skin adnexal neoplasms. The present paper describes only the adnexal neoplasm part of this network. The primary objective of CARADERM is to improve medical care for malignant skin adnexal neoplasms. A multidisciplinary review group and a centralized pathological review group have been set up. PATIENTS AND METHODS: A dual network of clinicians and pathologists has been set up. Data are recorded in a secure database. RESULTS: The CARADERM network comprises of 38 clinical centres and 22 pathology centres. Between 2014 and 2017, 1598 patients with an adnexal neoplasm were included. Data of interest were documented in 80% of cases. Median patient age was 72 years. Major histological subtypes were sweat gland carcinomas (50%), hair follicle carcinomas (37.7%), and sebaceous gland carcinomas (9.8%). Surgery was the first-line treatment for 81% of patients, including 76.9% with standard surgical margin analysis, and 5.5% with exhaustive margin analysis. 920 patients (57.6%) underwent a national pathology review process. DISCUSSION: The CARADERM network aims at providing assistance in difficult situations concerning diagnosis and care in skin adnexal neoplasms. Analysis of the CARADERM data should allow the creation of a prognostic classification of these rare neoplasms together with recommendations. A national multidisciplinary consensus exists. Translational and therapeutic research is ongoing. CONCLUSION: The CARADERM network is currently recruiting and more data should lead to improved knowledge of these tumours in the coming years.

[Therapeutic failure in skin carcinomas of the face]. / Chirurgie secondaire des tumeurs cutanées de la face.

Therapeutic failures in the management of skin carcinomas of the face are not rare, because of the very high frequency of these lesions. They come in 3 aspects: (a) tumor recurrence at the site of resection: reminders concerning the margins of excision in first surgery and in case of recurrence are made, as well as a focus on the behavior to take in case of incomplete margins; (b) Functional drawbacks related to surgery: abnormalities are addressed by anatomical location (eyelids and lips) through some examples and decisional algorithms. The nose and the ear are treated in other chapters of the book; (c) the aesthetic sequelae are finally presented thanks to new clinical cases.

[Multiple lung carcinoma: Primary or intrapulmonary metastasis?] / Adénocarcinomes pulmonaires multiples : primitifs ou métastases ?

Multiple lung carcinomas are 5 to 11,5% of lung carcinomas. The distinction between primary lung carcinomas from carcinomas with intrapulmonary metastasis is essential for optimal patient management. The histopathological analysis is very useful but it has to be completed by genotypic assessment using molecular biology (NGS). Molecular biology can also identify genetic alterations with therapeutic implications. We present the case of a patient with a history of surgery for multiple lung carcinomas diagnosed from 2013 to 2017.

Xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a form of general dermatosis characterised by photo-induced cutaneous-ocular impairment and by skin cancers. In addition to these signs, there may also be neurological involvement. This disease is related to a defect in genes within the nucleotide excision repair system for the first seven genetic groups (A-G), and to an abnormality in transcription groups for the eighth group (xeroderma pigmentosum variant - XPV). Cutaneous carcinomas are the most common types of cancer seen. They may begin in childhood. Multiple melanoma commonly occurs during the course of XP but given the frequency of spontaneous regression, the incidence is underestimated. The clinical appearance is characterised by polymorphous lesions with characteristic dyschromia and in most cases it is sufficient to establish the diagnosis. Investigation of unscheduled DNA synthesis (UDS) and cell survival following ultraviolet (UV) radiation were formerly considered the reference examination for laboratory diagnosis. However, these tests are now being replaced by new molecular biology techniques to screen for the genetic mutations characteristic of the disease. These techniques have proved extremely useful in identifying heterozygous patients and in antenatal diagnosis. Photoprotection is the key preventive measure: patients must avoid all exposure to the sun and to artificial sources of UV radiation. The therapeutic arsenal has recently been enriched by several modern therapeutic methods used to destroy cutaneous tumours such as imiquimod and photodynamic therapy (PDT). These approaches are valuable since they eliminate incipient tumours while sparing healthy skin. Surgery and cryosurgery are the most suitable methods for treating cutaneous tumours in children. Chemotherapy may be considered an alternative for the treatment of keratoacanthomas and squamous cell carcinomas (SCC). Cryosurgery may be combined with other therapeutic approaches to eliminate SCC of the lip. Management of these patients in reference centres, coupled with assistance from associations providing support for patients' families, has resulted in improved quality of therapy while slowing down disease progression.

[What's new in oncodermatology?] / Quoi de neuf en oncodermatologie ?

This 'What's new in oncodermatology?' addresses the developments in 2017 on the epidemiology and management of skin cancers. We observe a constant increase in carcinomas, risk factors for squamous cell carcinoma, especially in transplant recipients where skin cancer mortality is important. Among epidemiological developments in melanoma are increased mortality despite screening, occupational exposure to UV, second melanoma and higher risk after carcinoma. New classifications that should be considered are AJCC8 for melanoma and carcinoma. In a near future artificial intelligence could change skin cancer screening practices through deep learning. For the sentinel lymph node, there is no interest in systematic lymphadenectomy that does not improve survival. Radiation therapy is essential for the prognosis of Merkel's carcinoma, and Mohs' surgery can be of interest. In metastatic melanoma, results on immunotherapy and targeted treatments include duration, dose, combinations, and the study of resistance mechanisms. The great novelty is immunotherapy or targeted therapy as an adjuvant treatment, giving an improvement in survival without relapse.

[Pulmonary sarcomatoid carcinoma]. / Carcinomes sarcomatoïdes pulmonaires.

Pulmonary sarcomatoid carcinomas are a rare group of tumors accounting for about one percent of non-small cell lung carcinoma (NSCLC). In 2015, the World Health Organization classification united under this name all the carcinomas with sarcomatous-like component with spindle cell or giant cell appearance, or associated with a sarcomatous component sometimes heterologous. There are five subtypes: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. Clinical characteristics are not specific from the other subtypes of NSCLC. Epithelial to mesenchymal transition pathway may play a key role. Patients, usually tobacco smokers, are frequently symptomatic. Tumors are voluminous more often peripherical than central, with strong fixation on FDG TEP CT. Distant metastases are frequent with atypical visceral locations. These tumors have poorer prognosis than the other NSCLC subtypes because of great aggressivity, and frequent chemoresistance. Here we present pathological description and a review of literature with molecular features in order to better describe these tumors and perhaps introduce new therapeutics.

Nasal basal cell carcinomas. Can we reduce surgical margins to 3mm with complete excision?

BACKGROUND: The purpose of this study was to evaluate the incomplete excision rate of nasal basal cell carcinomas (BCC) resected with different margins to demonstrate that 3-mm surgical margins could be used as safety margins to reduce esthetic consequences with a low risk of incomplete excision. METHODS: All patients with BCC of the nose excised from January 1st 2008 to December 31st 2011 were included. Data were analyzed and reviewed retrospectively. Tumors were treated with different surgical margins of excision: 3mm, 4mm, and 5mm. The primary outcome variable was the rate of incomplete excision. Other study variables were the histologic subtype, size, and recurrent lesions. RESULTS: Of the 132 patients, 115 were included corresponding on with 127 BCC. Median age was 75.5 (64-83) and sex ratio M:F=1.05. Of the 127 BCC, 80 were aggressive histologic subtype (63%), and 11 were recurrent (8.7%). The overall rate of incomplete excision was 17.3% (n=22). Of these 22, 17 (77.3%) were of an aggressive subtype. The incomplete excision rates within the groups were 12.5% (n=4), 22.2% (n=10), and 16% (n=8), respectively within the group with 3-, 4- and 5-mm surgical margins. No significant difference was observed between the groups (P=.519). The incomplete excision rate was not independently associated with the surgical margins, histologic subtype and recurrent type (P>.05). CONCLUSION: Three-millimeters margins could possibly be used to treat nasal BCC in chosen cases. Regarding the high rate of incomplete excision, reconstruction should be performed after receiving the pathologic report.

[Locally advanced basal-cell carcinoma: Combined alternative treatments beyond surgery]. / Carcinomes basocellulaires localement avancés: intérêt de traitements combinés, alternatifs à la chirurgie.

The vismodegib, inhibitor of the hedgehog signaling pathway, is a new therapeutic option in locally advanced BCC when surgery or radiotherapy are inappropriate. If the response rate is high with rapid and sustained efficacy, complete responses are rare. Furthermore, the common side effects may limit continuous and prolonged treatment and lead to discuss sequential treatments. We report two cases that illustrate the severity of LaCBC, tumors neglected by patients and their families limiting therapeutic choice especially surgery that become impossible and for which vismodegib is indicated. These observations illustrate the possible interest of radiotherapy in combination or after tumor debulking by vismodegib. Vismodegib must be known by surgeons for LaCBC, mainly as an alternative beyond surgery but also as a possible neoadjuvant treatment to surgery that have to be evaluated.

[Mammary analog secretory carcinoma of the parotid gland]. / Carcinome salivaire sécrétoire, analogue des carcinomes sécrétoires mammaires.

Mammary analog secretory carcinoma (MASC) of the parotid gland is a rare and recently described lesion. We report the case of a 46-year-old man with a tumor of the parotid gland which was carried to the diagnosis of MASC. Diagnostic was confirmed by highlighting the ETV6-NTRK3 gene translocation. However, some morphologic and immunohistochemical features are suggestive of this entity. This carcinoma should be distinguished from its main differential diagnoses: acinic cell carcinoma and low grade cribriform cystadenocarcinoma.

[French national standard for the treatment of squamous cell carcinoma of upper aero-digestive tract - General principles of treatment]. / Référentiel national de traitement des carcinomes épidermoïdes des voies aérodigestives supérieures ­ Principes généraux de traitement.

OBJECTIVES: The management of upper aerodigestive tract cancers is a complex specialty. It is essential to provide an update to establish optimal care. At the initiative of the INCa and under the auspices of the SFORL, the scientific committee, led by Professor Béatrix Barry, Dr. Gilles Dolivet, and Dr. Dominique De Raucourt, decided to develop a reference framework aimed at defining, in a scientific and consensus-based manner, the general principles of treatment for upper aerodigestive tract cancers applicable to all sub-locations. METHODOLOGY: To develop this framework, a multidisciplinary team of practitioners was formed. A systematic analysis of the literature was conducted to produce recommendations classified by grades, in accordance with the standards of the French National Authority for Health (HAS). RESULTS: The grading of recommendations according to HAS standards has allowed the establishment of a reference for patient care based on several criteria. In this framework, patients benefit from differentiated care based on prognostic factors they present (age, comorbidities, TNM status, HPV status, etc.), conditions of implementation, and quality criteria for indicated surgery (operability, resectability, margin quality, mutilation, salvage surgery), as well as quality criteria for radiotherapy (target volume, implementation time, etc.). The role of medical and postoperative treatments was also evaluated based on specific criteria. Finally, supportive care must be organized from the beginning and throughout the patients' care journey. CONCLUSION: All collected data have led to the development of a comprehensive framework aimed at harmonizing practices nationally, facilitating decision-making in multidisciplinary consultation meetings, promoting equality in practices, and providing a state-of-the-art and reference practices for assessing the quality of care. This new framework is intended to be updated every 5 years to best reflect the latest advances in the field.

Hypofractionated radiotherapy for invasive squamous cell carcinoma of the scalp in the elderly: Efficacy and tolerance, preliminary results.

PURPOSE: Skin squamous cells carcinomas (SCC) are frequently tumor, especially in the elderly population. Surgical excision is the standard treatment. But for patients suffering large tumor or/with comorbidity, a conservative approach with irradiation can be proposed. The hypofractionated schedule is used to shorten the overall treatment time with same results and without compromising therapeutic outcomes. The aim of this study is to assess the efficacy and tolerance of hypofractionated radiotherapy for invasive SCC of the scalp in elderly. PATIENTS AND METHODS: We included patients suffering from SCC of the scalp and treated by hypofractionated radiotherapy at the Institut de cancérologie de Lorraine or centre Émile-Durkeim d'Épinal, from January 2019 to December 2021. Characteristics of patients, size of the lesion and side effects were collected retrospectively. Tumor size at 6 months corresponded to the primary endpoint. Toxicity was collected for the secondary endpoint. RESULTS: Twelve patients with a median age of 85 years old were included. The mean size was 4,5cm with a bone invasion in 2/3 of cases. Radiotherapy was delivered after surgical excision for half of the patient. The dose delivered was 54Gy in 18 daily fractions size. Six months after irradiation: 6/11 patients had no residual lesion, 2/11 had a partial response with a residual lesion of about 1cm. 3 patients presented local recurrence. One patient died within 6 months of radiotherapy because of another comorbidity. In total, 25% had presented a grade 3 acute radiation dermatitis, no grade 4 toxicity. CONCLUSION: Short term of moderately hypofractionated schedule radiotherapy was a success with complete or partial response for more than 70% of the patients in squamous cell carcinomas. There is no major side effect.

[Idiopathic granulomatous mastitis and breast carcinoma: What difference on elastography?] / Mastite granulomateuse idiopathique et carcinome mammaire : quelle différence à l'élastographie ?

OBJECTIVES: To determine the elastographic characteristics of idiopathic granulomatous mastitis compared to breast carcinoma. MATERIALS AND METHODS: Retrospective study of 63 breast masses. Ultrasound B mode and strain elastography were performed for each mass. Qualitative criteria (strain score) and semi-quantitative criteria (strain and length ratio) of strain elastography were studied. The pathological findings were used as the reference standard. RESULTS: Sixty-three breast masses, there were 15 idiopathic granulomatous mastitis and 48 breast carcinomas. The mean strain ratio of idiopathic granulomatous mastitis was significantly lower than that of breast carcinoma, respectively 3.34±2.50 and 21.22±20.57 (P<0.0001). However, there was no significant difference between the mean length ratio of idiopathic granulomatous mastitis and breast carcinoma, respectively 1.17±0.18 and 1.22±0.23 (P=0.381). CONCLUSION: Breast elastography helps to differentiate idiopathic granulomatous mastitis from breast carcinoma.

[Place of radiotherapy in the treatment of cutaneous carcinomas]. / Place de la radiothérapie dans le traitement des carcinomes cutanés.

Basal cell carcinomas and cutaneous squamous cell carcinomas are among the most common cancerous tumors in the world. Their treatment is most often based on surgery. Adjuvant radiotherapy may be indicated in case of risk factors for recurrence or as an alternative to surgery if surgery is not feasible due to the patient's advanced age and/or co-morbidities or as an alternative to potentially mutilating surgery. Radiotherapy is also part of the therapeutic arsenal for rarer skin tumors such as Merkel cell carcinoma, cutaneous lymphomas, Kaposi's disease and cutaneous adnexal carcinomas.

[Circulating tumor DNA assessment for gynaecological cancers management]. / Apports de l'ADN tumoral circulant dans la compréhension et la prise en charge des carcinomes d'origine gynécologique.

Gynaecological cancers are frequent, with more than 16,000 cases per year in France for 6500 deaths. Few improvements in diagnostic methods, prognostic tools, and therapeutic strategies have occurred in the last two decades. Tumour genomic analyses from, at least in part, the Cancer Genome Atlas have identified some of the molecular alterations involved in gynaecological tumours growth and spreading. However, these data remain incomplete and have not led to dramatic changes in the clinical management of our patients. Moreover, they require invasive samples that are not suitable to objectives like screening/early diagnosis, assessment of treatment efficacy, monitoring of residual disease or early diagnosis of relapse. In the last years, the analysis of circulating tumour biomarkers (also called "liquid biopsies") based on tumour cells (circulating tumour cells) or tumour nucleotides (circulating DNA or RNA) has been massively explored through various indications, platforms, objectives; data related to circulating tumour DNA being the most important in terms of number of publications and interest for clinical practice. This review aims to describe the methods of analysis as well as the observations from the analysis of circulating tumour DNA in gynaecological tumours, from screening/early diagnosis to the adaptation of treatment for advanced stages, through choice of treatments and monitoring of subclinical disease.

Lung and digestive neuroendocrine neoplasms. From WHO classification to biomarker screening: Which perspectives?

The recent classifications of lung and digestive neuroendocrine neoplasms (NENs) make a fundamental distinction between well- and poorly-differentiated neoplasms. Well-differentiated NENs are termed carcinoids in the lung and neuroendocrine tumors in the gastroenteropancreatic sphere; their risk of malignancy is highly variable; histological grading is used to stratify patients into prognostically significant groups. Poorly-differentiated NENs are termed neuroendocrine carcinoma in both the lung and the digestive sphere; they constantly are of high grade of malignancy; two types are recognized on the basis of tumor cell morphology, the small cell and the large cell types. Recent studies have largely uncovered the genetic landscape of several subsets of well-differentiated NENs (lung, pancreas, small intestine) and of poorly-differentiated NENs. Some molecular markers may help to the differential diagnosis between highly proliferative neuroendocrine tumors and neuroendocrine carcinomas, especially in the pancreas. In well-differentiated tumors, MGMT status is proposed as a predictive marker of the response to temozolomide, but remains to be validated. In poorly-differentiated neoplasms, large cell neuroendocrine carcinoma has been shown to be a heterogeneous category, with some cases presenting the same molecular signature than small cell carcinoma and others the same signature than adenocarcinomas of the same body site. Rb protein has been recently shown to be a potential marker of response to platinum salts in neuroendocrine carcinoma. Much remains to be done to translate the rapid progress in the molecular understanding of NENS into diagnostic, prognostic or predictive markers.

[Reirradiation for head and neck squamous cell carcinoma: Indications and results]. / Réirradiations des carcinomes épidermoïdes des voies aérodigestives supérieures : indications et résultats.

Despite progress in the management of head and neck squamous cell carcinoma (HNSCC), a significant proportion of patients previously irradiated for head-and-neck cancer will develop locoregional recurrence or a second primary. Because of the heterogeneity of this population with respect to disease-related factors (localization, volume, recurrence or second primary, time interval from previous irradiation…) and patient-related factors (comorbidities, sequelae of previous irradiation…), the optimal reirradiation treatment remains to be defined. Salvage therapy using reirradiation, despite some encouraging results, has historically been avoided because of concerns regarding toxicity. The results of more recent studies using contemporary treatment techniques and conformal delivery methods such as intensity modulated radiation therapy (IMRT) or stereotactic radiotherapy (SBRT) have been somewhat more promising. The aim of this review is to discuss the reirradiation of HNSCC in terms of patient selection and modern radiotherapy techniques.

[Biopathology of ovarian carcinomas early and advanced-stages: Article drafted from the French guidelines in oncology entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY under the aegis of CNGOF and endorsed by INCa]. / Biopathologie des carcinomes ovariens des stades précoces et avancés. Article rédigé sur la base de la recommandation nationale de bonnes pratiques cliniques en cancérologie intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY sous l'égide du CNGOF et labellisée par l'INCa.

OBJECTIVES: Ovarian carcinomas represent a heterogeneous group of lesions with specific therapeutic management for each histological subtype. Thus, the correct histological diagnosis is mandatory. MATERIAL AND METHODS: References were searched by PubMed from January 2000 to January 2018 and original articles in French and English literature were selected. RESULTS AND CONCLUSIONS: In case of ovarian mass suspicious for cancer, a frozen section analysis may be proposed, if it could impact the surgical management. A positive histological diagnosis of ovarian carcinoma (type and grade) has to be rendered on histological (and not cytological) material before any chemotherapy with multiples and large sized biopsies. In case of needle biopsy, at least three fragments with needles>16G are needed. Histological biopsies need to be formalin-fixed (4% formaldehyde) less than 1h after resection and at least 6hours fixation is mandatory for small size biopsies. Tissue transfer to pathological labs up to 48hours under vacuum and at +4°C (in case of large surgical specimens) may be an alternative. Gross examination should include the description of all specimens and their integrity, the site of the tumor and the dimension of all specimens and nodules. Multiples sampling is needed, including the capsule, the solid areas, at least 1 to 2 blocks per cm of tumor for mucinous lesions, the Fallopian tube in toto, at least 3 blocks on grossly normal omentum and one block on the largest omental nodule. WHO classification should be used to classify the carcinoma (type and grade), with the use of a panel of immunohistochemical markers. High-grade ovarian carcinomas (serous and endometrioid) should be tested for BRCA mutation and in case of a detectable tumor mutation, the patient should be referred to an oncogenetic consultation.

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. / Atézolizumab (Tecentriq®) : activité, indication et modalités d'utilisation dans les carcinomes urothéliaux localement avancés ou métastatiques.

Treatments for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin are currently limited. Atezolizumab (Tecentriq®) is a monoclonal antibody targeting PD-L1. The first of IMVIGOR 210 phase II trial (NCT02951767) investigated atezolizumab as front line treatment among 119 patients with metastatic urothelial cancer unfit for cisplatin. Response rate was 23% and median overall survival 15.9 months. The second cohort (NCT02108652) included 310 patients whose tumors were progressing after first line platinum-based chemotherapy. Response rate was 15% and median overall survival 7.9 months. Among patients with high PD-L1 expression on infiltrating immune cells (ICs), response rate was 26% and median overall survival 11 months. Atezolizumab was well-tolerated in both cohorts with 66% of treatment-related toxicities including 12% (cohort 1) and 7% (cohort 2) of grade 3-4 adverse events. These results led to an approval by the FDA in United States and the EMA in Europe. In France, atezolizumab was available through an early access agreement by the French National Agency for Medicines and Health Products (ANSM) for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin. So far, its avaibility in France within the EMA approval is pending its pricing.

Immunothérapie dans les carcinomes urothéliaux.

IMMUNOTHERAPIES FOR UROTHELIAL CARCINOMA: Therapeutic advances in the last 3 decades in bladder cancer were very limited. The 21th century will be more promising with the advent of immunotherapies, with at the top of the list the immune-checkpoint inhibitors. The promising results of the early trials let us hope that these new therapies will soon enroll in the therapeutic landscape of urothelial carcinoma. This article reviews the clinical data of ongoing immunotherapeutic trials (checkpoint inhibitors, vaccine, cytokine) and also the association of the therapies with chemotherapy, antiangiogenics and radiotherapy.