Oncogenetic Consultation Research Articles

Classification OMS 2022 des cancers du rein : focus sur le carcinome rénal papillaire

Renal cell carcinomas (RCC) represent a group of heterogeneous tumors whose classification has greatly evolved since 1981. The latest update in 2022 classifies all renal cell carcinomas into six categories according to their morphology or the detection of specific molecular alterations. Molecular disassembly of renal cell carcinomas with papillary features has enabled the identification of new entities characterized by a specific molecular alteration, such as Fumarate Hydratase (FH) deficient RCC, TFE3-rearranged RCC or TFEB-altered RCC. This new classification allows for a more accurate diagnosis but requires a thorough knowledge of the genomic alterations to search for with immunohistochemical or molecular biology techniques. According to the new WHO 2022 classification, papillary renal cell carcinoma (PRC) type 1 or type 2 classification is no longer recommended. A classification based on nucleolar ISUP grade must be preferred: low-grade PRC (ISUP 1-2) or high-grade PRC (ISUP 3-4). The other prognostic factors remain the same: the pTNM stage, lymphovascular invasion, and the presence or absence of dedifferentiated areas referring to sarcomatoid or rhabdoid features. Of note, the presence of necrosis is not currently recognized as a poor prognostic element for this type of carcinoma. The diagnosis of high-grade PRC is from now on a diagnosis of exclusion. It can only be sustained after having ruled out TFE3-rearranged RCC, TFEB-altered RCC, and FH-deficient RCC. For clinicians, the diagnosis of PRC implies suggesting an oncogenetic consultation to screen for an associated genetic tumor syndrome regardless of the patient's age.

Dedicated overseas consultation for patients evacuated from the south Pacific: Report of experience after six months of existence.

e18542 Background: The management of rare and/or complex cancers between patients living in metropolitan France and those living overseas remains unequal. Herein, medical transfer to metropolitan France is required in about 20% of overseas-living patients and is often experienced as an additional source of distress, which requires multidisciplinary support (social, psychological, medical, and cultural). Therefore, we developed a dedicated “Overseas” consultation (OC) to provide personalized cancer care in this specific population. We aim to present the evaluation of the first 6 months experience. Methods: The OC was dedicated to patients from the South Pacific (French Polynesia or New Caledonia) requiring “highly specialized” cancer treatments in Gustave Roussy, including surgery, chemotherapy, or diagnostic procedures, which were considered non-achievable in the local hospital after multidisciplinary discussion by videoconference. Multiple interventions including medical, administrative and psychological support were provided. Results: Between July 15, 2022, and January 15, 2023, 25 patients with rare and/or complex cancer diagnosis / treatments benefited from an OC. Median age was 57 years (30-81), 19 patients (76%) were women, 18 (72%) came from French Polynesia and 7 (28%) from New Caledonia. Median number of OC for each patient was 1 (range 1-3), and median length of stay in metropolitan France was 23 days (range 4-95 days). At the time of analysis, 7 patients had not yet returned back home. The most common cancer locations were breast (52%), lung (16%) and gastrointestinal (16%). Patient presented localized disease in 52% of cases. At the first OC, 92% patients were ECOG Performance Status 0-1. The main reasons for metropolitan France medical transfer were an imaging procedure (64%) or a complex surgical or interventional radiology biopsy (24%). Seven patients (28%) had complex management (defined as two or more procedures) during their stay. Eleven patients (44%) benefited from molecular profiling, 7 (27%) from an oncogenetic consultation and 1 (4%) from inclusion in a clinical research trial. Conclusions: OC, set up 6 months ago in our institution, has optimized diagnostic workflow and disease management of these complex patients living overseas and has demonstrated its feasibility. However, it requires the involvement of multiple health-care professionals, multidisciplinary concertation, paramedical interventions such as social and psychological support and the overarching support from institutions.

Darier Ferrand Mammary Dermatofibrosarcoma Simulating a Breast-Type Myofibroblastoma: A Case Report

Myofibroblastoma and Darier Ferrand’s dermatofibrosarcoma are rare entities that are similar both in terms of clinical morphological characteristics and histological characteristics. We report the case of a 49-year-old non-menopausal woman with a history of right breast lumpectomy. Supported by the Chompret criteria, an oncogenetic consultation was performed. Clinical examination revealed a firm 25 mm mass on the medial part of the left breast with skin involvement. A biopsy was performed and analysis result came back in favor of a cellular type myofibroblastoma showing a fibrous component consisting of spindle cells with a herringbone arrangement. Anatomopathological results concluded to a dermatofibrosarcoma of Darier Ferrand while immunohistochemistry stated a tumor population strongly positive for CD34 expression. The search for a rearrangement of the collagen type I alpha 1 gene (COL1A1) by fluorescence in situ hybridization (FISH) was positive. The diagnosis of Dermatofibrosarcoma of Darier Ferrand can be suspected on imaging and confirmed by histology. Surgical treatment of Darier Ferrand dermatofibrosarcoma consists of wide excision of the lesions with margins greater than 2 cm, on which the prognosis mainly depends. Micrographic surgery and oncoplastic breast surgery are of major interest in this location.

Consultation personnalisée d’évaluation du risque de cancer du sein : premiers résultats

In France, participation in the organized breast cancer screening program remains insufficient. A personalized approach adapted to the risk factors for breast cancer (RBC) should make screening more efficient. A RBC evaluation consultation would therefore make it possible to personalize this screening. Here we report our initial experience. This is a prospective study on women who were seen at the RBC evaluation consultation and analyzing: their profile, their risk assessed according to Tyrer Cuzick model (TC)±Mammorisk© (MMR), the existence of an indication of oncogenetic consultation (Eisinger and Manchester score), their satisfaction and the recommended monitoring. Among the women who had had a TCS and/or MMR evaluation of SCR (n=153), 76 (50%) had a high risk (n=67) or a very high risk (n=9). Almost half (47%) had a possible (15%) or certain (32%) indication to an oncogenetic consultation. Regarding this consultation, 98% of women were satisfied or very satisfied. In total, 60% of women had a change in screening methods. This RBC evaluation consultation satisfies women and for a majority of them, modifies their methods of breast cancer screening.

Les cancers colorectaux héréditaires vus par le pathologiste

The pathologist's role in the management of hereditary colorectal cancer is important. The pathologist may suspect a familial cancer when particular morphological and/or clinical criteria are present or give a response to a clinical request in the context of a possible hereditary cancer. In this setting, the pathologist's conclusions have necessarily to be integrated to a precise environment, and if needed, followed by an oncogenetic consultation and a germline mutation research. The aim of this article is to present the main aspects of hereditary colon cancers that a pathologist may see, but also to highlight the histopathological characteristics and the place of the pathologist in the management of these different entities.

Prédispositions héréditaires aux tumeurs thyroïdiennes de souche folliculaire

Familial thyroid cancers of follicular origin are rare and include syndromic and non-syndromic tumours. In familial adenomatous polyposis, the prevalence of papillary thyroid cancer is 2-12% and in 20-40% of cases it is a cribriform-morular papillary thyroid carcinoma. Morules and cribriform pattern are the two main typical criteria, associated with a nuclear and cytoplasmic immunopositivity for beta catenin. DICER1 syndrome is associated with pleuropneumoblastoma, ovarian tumors and thyroid pathology (multinodular goiter and less frequently a well-differentiated thyroid cancer without microscopic particularity). Cowden syndrome is characterized by multiple hamartomas and two-thirds of patients develop thyroid pathology, including multinodular goiter (50-67%) and cancer (35%), the latter being one of the major diagnostic criteria of the syndrome. Classic triad of Carney complex associates lentiginosis, myxoid tumors, and various endocrine abnormalities; thyroid pathology occurs in 10% of cases and may be benign or malignant. In Werner's syndrome, thyroid cancer is present in 18% of cases. McCune-Albright syndrome is characterized by fibrous dysplasia, café-au-lait spots and various endocrinopathies including hyperthyroidism and nodular hyperplasia. Non-syndromic thyroid cancers, which represent the majority of familial cancers, are most often papillary carcinomas. In daily practice, in the presence of multiple benign thyroid nodules and/or thyroid cancer in a young person, or with family thyroid diseases, the pathologist should be aware about hereditary predispositions to propose an oncogenetic consultation.

Fortuitous discovery of ganglionic tuberculosis after conservative treatment of breast cancer: a case report and review of the literature

BackgroundGanglionic tuberculosis is the most common extrapulmonary localization in Morocco. It is still a diagnostic and therapeutic problem especially when the infection is concomitant to the management of a cancer.Case presentationHere, we report the uncommon case of a fortuitous discovery of ganglionic tuberculosis in the anatomopathological analysis of an axillary node dissection after conservative treatment of breast cancer for a 29-year-old patient without medical history. Her file was discussed in a multidisciplinary consultation meeting during which several decisions were made. We decided to start her antituberculosis treatment then after three weeks her adjuvant chemotherapy with radiotherapy and hormone therapy. Furthermore, giver her young age, she had an oncogenetic consultation. Despite difficulties of therapeutic compliance, the patient completed her cancer treatments after two years, she also cured of her tuberculosis. Being in remission, she is still on hormone therapy and consults every 3-months as part of her follow-up.ConclusionsCancer and tuberculosis presenting simultaneously creates clinical and histopathological difficulties for differential diagnosis and for therapeutic decisions. Anticancer chemotherapy is not an obstacle in anti-tuberculosis treatment but the compliance of patients to receive both at the same time with the associated side effects is one to consider.

Les formes familiales de cancers bronchiques

Cancer is a genetic disease and some of the cancers can be familial. There are syndromes or cancers that are clearly identified as having a hereditary origin. In lung cancers, family origin is rare but possible. We will try to make you aware of these family forms and the importance of an oncogenetic consultation in case of doubt about a hereditary origin.

Effectiveness of oncogenetics training on general practitioners’ consultation skills: a randomized controlled trial

Purpose:General practitioners are increasingly called upon to deliver genetic services and could play a key role in translating potentially life-saving advancements in oncogenetic technologies to patient care. If general practitioners are to make an effective contribution in this area, their genetics competencies need to be upgraded. The aim of this study was to investigate whether oncogenetics training for general practitioners improves their genetic consultation skills.Methods:In this pragmatic, blinded, randomized controlled trial, the intervention consisted of a 4-h training (December 2011 and April 2012), covering oncogenetic consultation skills (family history, familial risk assessment, and efficient referral), attitude (medical ethical issues), and clinical knowledge required in primary-care consultations. Outcomes were measured using observation checklists by unannounced standardized patients and self-reported questionnaires.Results:Of 88 randomized general practitioners who initially agreed to participate, 56 completed all measurements. Key consultation skills significantly and substantially improved; regression coefficients after intervention were equivalent to 0.34 and 0.28 at 3-month follow-up, indicating a moderate effect size. Satisfaction and perceived applicability of newly learned skills were highly scored.Conclusion:The general practitioner–specific training proved to be a feasible, satisfactory, and clinically applicable method to improve oncogenetics consultation skills and could be used as an educational framework to inform future training activities with the ultimate aim of improving medical care.

Diagnosis, prognosis and treatment of patients with gastrointestinal stromal tumour (GIST) and germline mutation of KIT exon 13

BackgroundThe demonstration of the role of activating mutations of KIT or PDGFRA and the development of targeted therapies have modified the prognosis of patients with gastrointestinal stromal tumours (GISTs). Identification of kindreds with KIT or PDGFRA germline mutation raised new questions, especially regarding the diagnosis, management, monitoring and treatment of these patients. MethodsWe identified index patients of three different families with a KIT exon 13 germline mutation. Pedigree of GIST kindred was assessed in oncogenetic consultation, and medical records were reviewed. Efficacy of imatinib in GISTs with KIT exon 13 was evaluated and compared with published data. ResultsAll KIT germline mutations were p.K642E. Twenty affected patients were identified in the three families. GISTs were multiple and occurred before 45years in all but one case. All resected tumours were of spindle cell histology, CD117 positive, and had low or intermediate risk of relapse. Lentigines involving the palms and soles were detected in four patients, and three patients had motrice dysphagia. Nine affected patients died of their disease, all but one before 65years. Affected patients were most often symptomatic and required iterative surgical resections. Imatinib was efficient in GISTs with p.K642E mutation with a disease control rate superior to 90% whatever the sporadic or inherited origin of the tumour. ConclusionsWe propose a regular screening of kindreds who have germline mutation. Treatment with imatinib should be considered for those with symptomatic tumour, larger than 3cm and/or growing rapidly.

An oncogenetics consultation dedicated to children suffering from cancer.

e20006 Background: When a child suffers from a cancer, parents worry about a probable hereditary cause. If a cancer occurs in the context of a genetic mutation, this can worsen the situation and make it more complicated. On the other hand, when the hereditary cause is rejected, the reinsurance for the family is clear. Methods: A partnership has been set between the Oncogenetics department in Centre Antoine Lacassagne Hospital in Nice and the Archet hospital in Nice (CHU) who takes in charge the children suffering from a cancer. Fifty little patients are seen every year in the paediatric oncology service at the Archet hospital (CHU). A consultation in oncogenetics is suggested to each family and insistently when a known syndrome is suspected. This consultation is also about to provide an other kind of care, in an other hospital, focused on the family with the aim to free of guilt the parents. Psychological care for families is in backdrop as they can express freely their questioning. Results: Twenty one families have been seen and fifteen different types of cancers recorded: mostly haematological cancers and neurological cancers. For each family, a pedigree was drawn. Data concerning the child’s disease and familial data were gathered. Most of the time, these information led to reassure the families. Therefore two Li and Fraumeni syndrome have been evoked. The first child suffered from a plexus choroid carcinoma and the second one had two distinct cancers: a nephroblastoma and a medulloblastoma. On the other hand, 2 children had had a LAL within a family with history of malignant haemopaties. Interestingly, 3 children with isolated LAL in the family where suggested to contribute to a research trial. Conclusions: This oncogenetic pediatric consultation allows to detect known hereditary predisposition syndromes and to contribute to researches in paediatric oncology. Above all, this strong bound between the oncogentics department and the pediatric oncology service permitted to reach an objective: offering families a specialised consultation with psychological support with a gap from disease.

Familial transmission of information dealing with BRCA1/2 mutations in hereditary breast and ovarian cancer.

Abstract Abstract #1104 Background: A mutation of the BRCA1/2 genes is implicated in 5 to 10% of the breast and ovarian cancer cases. In France, when such a genetic mutation is discovered in a family, the consulting persons are expected to transmit themselves this medical information to their relatives. Indeed, for legal reasons, physicians are not allowed to contact them personally. An important gap has been observed however between the number of persons who are potentially concerned by this genetic information and the number of persons actually consulting. We then wondered about (1) the actual transmission of genetic information to relatives, (2) possible reasons for the non-transmission of this information, (3) the rate of concerned consulting relatives and (4) presumed reasons for not consulting when informed.
 Methods: This sample includes 31 target consultants (index cases) of mutated families who received the result of the genetic test between January 2003 and June 2005. Data were gathered in two successive steps: some were first referring to consultants' medical files, then we called these target consultants asking them standardized questions about their relatives. Final analyses concern 264 relatives complying with our selection criteria.
 Results: According to information gathered thanks to medical files and calls to target consultants, most of the relatives (73.1 %) are informed that a deleterious mutation is present in the family. Women are more often informed (80.7 %) than men (63.2 %). The non-informational motives are on the one hand mainly social and emotional distance and, on the other hand, the stressful content of this information. It would be disclosed through family by the women who are alive and carry the mutation. Moreover, a minority of the presumed informed women (39.7 %) have attended the oncogenetic consultation. This rate represents 32 % of all concerned women. Almost no man has consulted. We can just assume the motives for short-term absence of consultation. They seem to be especially linked to relatives' disinterest towards genetic information. The studied characteristics just allow us to point out the closeness with a mutated relative as a determinant factor of consultation.
 Discussion: This study brings two main results linked to relatives' information and consultation when a breast and ovarian cancer genetic risk has been identified in the family. On the first hand, it confirms that familial transmission of the medical information is pretty good. On the other hand, despite the good communication among family members, the rate of consultation remains low in informed women. According to these findings, efforts have to be made to give better explanations about the goals of oncogenetic consultation as well as enhancing the quality of information transmission in mutated families. These improvements could raise consultation rates and then increase the efficiency of screening and preventive measures. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1104.

Information spreading about hereditary carriage of a BRCA1/2 mutation and ovarian cancer and rate of consultation of the concerned relatives

Five to 10% of breast and ovarian cancer are linked to a BRCA1 or BRCA2 mutation. In our country, the information given to the relatives is inevitably mediated by the persons who have consulted. The report of a gap between the number of presumed persons concerned by the genetic information according to our genealogies and the actual number of consultants brought us to question about the transmission of the information in the family, about the possible motives for the lack of transmission, about the rate of consultation of the concerned relatives and on the presumed motives of non-consultation. This sample includes 31 target consultants (index cases) of mutated families which received the result of the genetic test during the period from January, 2003 till June, 2005. According to the information gathered, most of the relatives (73.1%) are informed about the presence of a deleterious mutation in the family, especially women (80.7%). The motives for non-information are the social and emotional distance, as well as the stressful character of the information. Apparently the information is disclosed through the family by the women who are alive and carry the mutation. On the other hand, a minority of the women (39.7%) who are supposed to be informed and living in the region attended the oncogenetic consultation, which represents 32 % of all concerned women who come of age. The motives for short-term absence of consultation can just be presumed. The characteristics which we studied do not allow us to point out some particularities among women who consulted except the nearness with one mutated relative.

Consultation d'oncogénétique pour le cancer du sein

Five percent of breast cancers are associated with a genetic predisposition, transmitted as an autosomal dominant trait of either maternal or paternal origin. Mutations of the BRCA1 or BRCA2 genes are associated with a high risk of breast and ovarian cancer and depend in part on these predispositions. The objectives of an oncogenetic consultation are to understand the origin of a personal and family history of breast cancer by using the resources of formal and molecular genetics and to guide the management of the consulting patient and her relatives. The diagnostic genetic test performed from an "index case" is intended to identify genetic alterations specific to each family. The failure to identify a mutation in a diagnostic test does not rule out the existence of a predisposing factor. On the other hand, the identification of a mutation makes it possible to offer a simple test to relatives, and its negative result can provide reassurance. Optimal management of patients with a mutation of the BRCA1 or BRCA2 genes requires frequent clinical examinations and at least annual imaging (mammography, ultrasound or breast MRI as part of a protocol) from the age of 25-30 years. Prophylactic mastectomy may be envisioned. Prophylactic adnexectomy is also usually recommended to prevent ovarian cancer, around the age of 40 years.

Prédispositions héréditaires aux cancers gynécologiques

The breast, ovary and endometrial cancers are hereditary in 5 to 10% of the cases. These genetic predisposition syndromes can be classified into two major classes: ovarian cancer and breast cancer predisposition family cases (genes BRCA1 and BRCA2) and family cases of colon cancer, endometrial cancer and ovarian cancer (Lynch syndrome or HNPCC) (genes hMLH1, hMSH2, hMLH6). The estimate of the family and individual risk can contribute in a determining manner to the management of these patients, by the practice of screening or an adapted prevention. Indeed, the risk of cancer of an individual having a positive test for a gene of predisposition to breast cancer (BRCA1, BRCA2) or to the colon cancer (hMLH1, hMSH2, hMLH6) lies between 50 and 70% at the age of 70 years. The indication of a genetic test must be discussed within the framework of an oncogenetic consultation. An individual and family medical management ranging from simple monitoring to prophylactic surgery is proposed to these predisposed people.

Cancer genetics clinics: Target population and consultees' expectations

The aim of this study was to determine in healthy consultees attending cancer genetics clinics their risk status, their pathways leading to the clinics, their expectations and perception of cancer risk. In 1994, the consultees at six French centres completed a questionnaire before their first oncogenetic consultation. The oncogeneticists subsequently filled in a standardised form giving their risk assessment. Among the 206 healthy consultees, 91.3% were women, 92.2% had at least one cancer-affected first-degree relative and 73% had a “cancer family risk” as assessed by the oncogeneticist. Sixty-nine per cent of the consultees were referred to the clinics by a physician, 10.4% by their family and 18.8% on their own initiative: 83.5% of the sample perceived their family risk of cancer as being high and this belief was confirmed in 74.3% of the cases studied by the oncogeneticist. The families of self-referred consultees were less often at risk than those of consultees referred by a physician or by their family (P = 0.012). The majority (78%) expected to be informed about cancer prevention and screening, and this expectation depended on the consultee's level of education (P = 0.001). This study shows that medical pathways are more effective than the media as a means of reaching the members of the general population who are genuinely at risk, and shows that fuller information about prevention needs to be provided at cancer genetic consultations.