Metastatic SDH-Deficient GIST Diagnosed during Pregnancy: Approach to a Complex Case.

Gastrointestinal stromal tumors (GISTs) account for 1% of GI neoplasms in adults, and epidemiological data suggest an even lower occurrence in pregnant women. The majority of GISTs are caused by KIT and PDGFRA mutations. This is not the case in women of childbearing age. Some GISTs do not have a KIT/PDGFRA mutation and are classified as wild-type (WT) GISTs. WT-GIST includes many molecular subtypes including SDH deficiencies. In this paper, we present the first case report of a metastatic SDH-deficient GIST in a 23-year-old pregnant patient and the challenges encountered given her concurrent pregnancy. Our patient underwent a surgical tumor resection of her gastric GIST as well as a lymphadenectomy a week after induction of labor at 37 + 1 weeks. She received imatinib, sunitinib as well as regorafenib afterward. These drugs were discontinued because of disease progression despite treatment or after side effects were reported. Hence, she is currently under treatment with ripretinib. Her last FDG-PET showed a stable disease. This case highlights the complexity of GI malignancy care during pregnancy, and the presentation and management particularities of metastatic WT-GISTs. This case also emphasizes the need for a multidisciplinary approach and better clinical guidelines for offering optimal management to women in this specific context.

Contraceptive vaginal ring-induced cholestasis in a patient with a history of intrahepatic cholestasis of pregnancy.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is a heterogeneous group of liver disorders with a high recurrence rate. Patients with a history of ICP are at risk of developing contraceptive-induced cholestasis, especially if they harbour a biliary transporter mutation. We report the first case of drug-induced cholestasis associated with a contraceptive vaginal ring (CVR) in a patient with a prior history of ICP. PRESENTATION: Our patient was a women with a history of multiple pregnancies and spontaneous abortions and early and severe ICP. Two to four weeks after initiation of CVR, she developed signs and symptoms of cholestasis, which resolved after discontinuation of the CVR. A thorough investigation to exclude other plausible causes of cholestasis was performed, including a liver biopsy. Genetic testing revealed pathogenic mutations in both the ABCB11 and ABCB4 genes. DISCUSSION: Although a history of ICP used to be an absolute contraindication for oral contraceptive pills (OCP), recent studies suggest a lower risk of cholestasis associated with low-dose oestrogen pills (20-35 mcg compared to the original 50 mcg). No previous case report could confirm the theoretical risk associated with the use of a CVR, which delivers a very low estrogen dose (15 mcg). The two biliary transporter mutations identified in our case could potentially explain the patient's susceptibility to the cholestatic effect of oestrogen. CONCLUSION: This case illustrates that CVR can trigger drug-induced cholestasis in a susceptible patient. While such cases should not discourage the trial of low-dose hormonal contraception in women with prior ICP, an appropriate follow-up is necessary to ensure early detection and treatment of drug-induced cholestasis.

[Large scale teaching in pathology]. / Pédagogie à grande échelle en ACP.

Medical education is currently facing great changes that affect all medical specialties, including anatomical pathology. Due to rapidly increasing medical knowledge and diagnostic complexity, we are living an era of teaching resources mutualization. We present different tools that allow large numbers of students to access courses, self-evaluations, and competencies assessments. MOOC platforms and e-learning platforms are central to these new online tools, which include the French National Platform of Medical Specialties, dedicated to the teaching of 50,000 medical residents in France. We also discuss "serious games" and the use of images and virtual slides in anatomical pathology teaching. These new modalities can deliver essential knowledge to large student populations, but they must be used in conjunction with adapted teacher-led courses focusing on competencies and professional skills in order to be fully effective.

A challenging case of squamous metaplasia in a pleomorphic adenoma: diagnostic and clinical pitfalls.

Squamous metaplasia in a pleomorphic adenoma (PA) has been reported, but rarely has it been documented as being extensive enough to cause significant misdiagnosis. We present a case of a 37-year-old man presenting with a 1.7-cm minor salivary gland PA of the palate. It exhibited extensive squamous metaplasia mimicking a squamous cell carcinoma (SCC) on multiple preoperative biopsies. The final diagnosis was only made after a complete oncological excision with margins and free flap reconstruction. Florid squamous metaplasia in a PA, although rare, should be recognized and distinguished from SCC. Failure to differentiate these entities can lead to patient overtreatment.

Safety and efficacy of Gamma Knife surgery for brain metastases in eloquent locations.

OBJECT: Brain metastases are the most frequently occurring cerebral tumors. Tumors that are located in eloquent cerebral parenchyma can cause considerable morbidity and may pose a significant challenge during surgery. Gamma Knife surgery (GKS) is a recognized treatment modality for brain metastases. This study was undertaken to assess the safety and efficacy of GKS, specifically for brain metastases in eloquent locations. METHODS: Charts of patients harboring brain metastases that were treated by GKS at the Centre Hospitalier Universitaire de Sherbrooke between August 2004 and April 2008 were reviewed. Planning images were assessed by an independent neurosurgeon to assess tumor location. Eloquent locations included the primary motor, somatosensory, speech, and visual cortices; the basal ganglia; the thalamus; and the brainstem. Data on survival, tumor response, and complications were analyzed and compared with data published on surgical treatment of these lesions. RESULTS: During the study period, 650 metastases in 295 patients were treated with GKS; of these, 164 metastases in 95 patients were located in eloquent areas. In this subgroup, the median age of patients was 59 years and women constituted 57.9% of the population. The median Karnofsky Performance Scale score was 80% (range 50%-100%). Patients were categorized according to their recursive partitioning analysis class: Class 1, 22.1%; Class 2, 70.5%; and Class 3, 7.4% of patients. Non-small cell lung cancer was the most common primary tumor (63.2% of metastases), followed by small cell lung (8.4%), breast (7.4%), colorectal (5.3%), and renal cell (4.2%) cancers, as well as melanoma (4.2%). The median dose to the tumor margin was 18 Gy (range 14-24 Gy). The median duration of survival after GKS was 8.2 months. The recursive partitioning analysis class was the most significant variable affecting survival (p < 0.0001). Immediate control was achieved in 92.9% of tumors, and 68.6% of tumors were still controlled at the last follow-up. The median time to tumor progression was 16 months. Higher margin dose (p = 0.002), the absence of edema (p = 0.009), and the non-small cell lung cancer tissue type (p = 0.035) positively affected response rates. Steroid medications were no longer used in 46% of patients after GKS. New neurological deficits occurred in 5.7% of patients and seizures in 5.7%. All these deficits were transient and patients completely recovered in response to a temporary course of steroids. Imaging studies showed that new edema occurred in 8.6% of treated metastases and biopsy-proven radiation necrosis in 1.4%. CONCLUSIONS: Gamma Knife surgery is safe and effective for brain metastases located in eloquent areas.