Despite screening programmes, numerous clinical studies and new breast imaging techniques, breast cancer incidence for women continues to rise. The arrival of predictive and personalized medicine could clearly redefine our screening recommendations. One promising approach to improving screening would be to use tools to predict the risk of developing breast cancer, including polygenic risk scores (PRS). This approach will enable us to offer women risk-based screening by adapting the frequency, type and age of screening. This article reviews some definitions of the PRS and breast cancer screening. We also explain the risk assessment models that have been developed and the various studies underway on personalized screening.

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.

We report the case of a 14 year-old teenager who has SC hemoglobinosis and presented with a tumor syndrome with a retro-peritoneal mass, a supraclavicular lymph node and a mid-renal lesion. The microscopic examination revealed an undifferentiated tumor proliferation infiltrating the lymph node parenchyma. This tumor proliferation was INI1/SMARCB1-deficient, and expressed cytokeratins. Given the fact that the histopathological data showed an undifferentiated INI1-deficient carcinoma and that the patient has a kidney lesion and a sickle cell trait, the final diagnosis was lymph node metastasis of SMARCB1-deficient renal medullary carcinoma (OMS 2022).

CONTRIBUTIONS OF MOLECULAR BIOLOGY TO THE MANAGEMENT OF COLORECTAL CANCER. Colorectal cancer (CRC) is a major public health problem affecting almost 43.000 people a year and causing 17.000 deaths. Advances in molecular biology have made it possible to identify some of the mechanisms involved in colorectal carcinogenesis and tumor proliferation. Some molecular alterations are now routinely investigated to adapt follow-up and therapeutic decisions in both localized and metastatic CRC.

Targeted therapies are the standard first-line treatment for metastatic lung adenocarcinoma with certain molecular abnormalities. These abnormalities are particularly common in Southeast Asia and French Polynesia. A 51-year-old Tahitian female non-smoker was diagnosed in 2018 with stage IV lung adenocarcinoma harboring a p.L858R EGFR mutation. She received gefitinib as first-line treatment. Due to locoregional progression and the presence of a resistance mutation (p.T790M of EFGR), she received osimertinib as second-line treatment, after which chemotherapy was proposed as 3rd-line treatment. An additional biopsy detected not only the previously known EGFR mutation, but also a BRAF p.V600E mutation. Following disease progression during chemotherapy, the patient received targeted therapies combining dabrafenib, trametinib and osimertinib. Due to a dissociated response after four months of treatment, a 5th line of paclitaxel bevacizumab was initiated. Subsequent to additional progression and given the ALK rearrangement shown on the re-biopsy, 6th-line treatment with alectinib was proposed. As the response was once again dissociated, a final line was proposed before stopping active treatments due to their toxicity and overall deterioration in the patient's state of health. This exceptional case is characterized by resistance to anti-EGFR through the successive and cumulative acquisition of two new oncogene addictions. The authors underline the importance of re-biopsy at each progression, leading (if at all feasible) to yet around round of targeted therapy.

Cystic lung diseases are rare, with numerous differential diagnoses. Iconographic discovery consequently necessitates medical examinations in view of proposing an etiological orientation.

One to 3% of gastric cancers are secondary to genetic predisposition, notably hereditary diffuse gastric cancers (HDGC) caused by CDH1 gene mutations. According to French recommendations, in case of CDH1 gene mutation, a prophylactic total gastrectomy should be performed between 20 and 30 years old. This gastrectomy should remove all the gastric mucosa at both extremities (duodenal and esophageal sides). Histopathological examinations of prophylactic total gastrectomies in asymptomatic CDH1-mutated patients reveal microscopic foci of diffuse-type cancer in 90 to 100% of cases. Lymph node involvement and lympho-vascular invasion are extremely rare, justifying the use of a D1-only lymphadenectomy. In the context of prophylaxis, limited lymphadenectomy and the development of minimally invasive oesogastric surgery, the minimally invasive approach might be the preferred approach, in expert centers. Surgical outcomes seem to be similar to those after gastrectomy for cancer. Prophylactic total gastrectomy is the cornerstone of CGDH management, associated with multidisciplinary follow-up and mammary surveillance in women.

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.

Cancer is an inevitable collateral problem inherent in the evolution of multicellular organisms, which appeared at the end of the Precambrian. Faced to this constraint, a range of diverse anticancer defenses has evolved across the animal kingdom. Today, investigating how animal organisms, especially those of large size and long lifespan, manage cancer-related issues has both fundamental and applied outcomes, as it could inspire strategies for preventing or treating human cancers. In this article, we begin by presenting the conceptual framework for understanding evolutionary theories regarding the development of anti-cancer defenses. We then present a number of examples that have been extensively studied in recent years, including naked mole rats, elephants, whales, placozoa, xenarthras (such as sloths, armadillos and anteaters) and bats. The contributions of comparative genomics to understanding evolutionary convergences are also discussed. Finally, we emphasize that natural selection has also favored anti-cancer adaptations aimed at avoiding mutagenic environments, for example by maximizing immediate reproductive efforts in the event of cancer. Exploring these adaptive solutions holds promise for identifying novel approaches to improve human health.

Lung cancer is the first cancer-related cause of death worldwide. This is in partially due to therapeutic resistance, which occurs in around 70% of patients, especially those receiving platinum salts, the gold-standard chemotherapy. The massive deregulation of alternative transcript splicing processes observed in many cancers has led to the development of a new class of pharmacological agents aimed at inhibiting the activity of the splicing machinery (spliceosome). The molecular mechanisms by which these inhibitors act remain largely unknown, as do the benefits of using them in combination with other therapies. In this context, our work is focused on an inhibitor of the SRPK1 kinase, a major regulator of the spliceosome.

Polycythemia is suspected when hemoglobin and/or hematocrit levels exceed established norms based on gender and age. This biological anomaly can arise from a myeloproliferative neoplasm known as polycythemia vera, or be secondary to excess erythropoietin (EPO) or decreased in plasma volume. Faced with polycythemia, the search for JAK2 mutations and measurement of serum EPO levels can guide toward the etiology. In polycythemia vera, thromboembolic events are the most lethal complications and unfortunately often the initial manifestation of the disease. The condition can also progress to myelofibrosis or acute leukemia. Management aims at reducing the hematocrit below 45 %, in order to limit, but not completely prevent, thrombo-embolic complications. This article elaborates on the clinical considerations around this biological anomaly, relevant complementary examinations, and briefly the therapeutic management.

In recent years, several nasal cavity and sinus entities have been described with fusion genes. Salivary gland tumors with fusion genes will not be discussed in this article, but it should be kept in mind that accessory salivary glands are present in the nasal cavity and sinuses and can therefore lead to tumoral lesions. Entities with specific or more frequently described rearrangements in the nasal cavities and sinuses are DEK::AFF2 squamous cell carcinomas,;non-intestinal and non-salivary nasosinusal adenocarcinomas, some of which displaying ETV6 gene rearrangements; biphenotypic nasosinusal sarcomas, most of which displaying PAX3 gene rearrangements; and Ewing's adamantinoma-like sarcomas, which display the same rearrangements as conventional Ewing's sarcomas, mainly the EWSR1::FLI1 rearrangement. Each entity will be described morphologically, immunohistochemically, and prognostically.

Salivary gland tumors represent a diagnostic challenge for pathologists due to their rarity, their very wide histopathological and immuno-phenotypic spectrum, and the recent identification of new entities. This article presents the main molecular characteristics of these tumors in order to allow any pathologist to perceive the diagnostic tracks of these ENT tumors and to better guide the molecular approach to establish the diagnosis and guide therapy.

The neuroepithelial tumor with PATZ1 fusion is a recently described tumor type, at the border between central nervous system and mesenchymal tumors. The histopathological diagnosis of this neoplasm, not recognized by the 2021 WHO classification, is challenging due to its varied and non-specific morphologic features. Most cases are densely cellular with monomorphous nuclei. Perivascular pseudo-rosettes of the ependymal type and astroblastic features are frequent. Blood vessels may be hyalinized. The tumor may display low- or high-grade features. OLIG2 and GFAP are variably expressed. Guided by DNA methylation profiling, a pathologist aware of this tumor type will search for a fusion involving PATZ1 and EWSR1 or MN1. The physiopathology of neuroepithelial tumor with PATZ1 fusion is not fully understood. The prognosis appears to align with that of intermediate-grade tumors but follow-up data are scarce. The therapeutic management is often similar to that of high-grade neoplasms. Nonetheless, PATZ1 fusion is a potential therapeutic avenue that may lead to personalized and less aggressive treatments.