Genomic landscape of clinically advanced KRAS wild-type pancreatic ductal adenocarcinoma

IntroductionKRAS mutation is a common occurrence in Pancreatic Ductal Adenocarcinoma (PDA) and is a driver mutation for disease development and progression. KRAS wild-type PDA may constitute a distinct molecular and clinical subtype. We used the Foundation one data to analyze the difference in Genomic Alterations (GAs) that occur in KRAS mutated and wild-type PDA.MethodsComprehensive genomic profiling (CGP) data, tumor mutational burden (TMB), microsatellite instability (MSI) and PD-L1 by Immunohistochemistry (IHC) were analyzed.Results and discussionOur cohort had 9444 cases of advanced PDA. 8723 (92.37%) patients had KRAS mutation. 721 (7.63%) patients were KRAS wild-type. Among potentially targetable mutations, GAs more common in KRAS wild-type included ERBB2 (mutated vs wild-type: 1.7% vs 6.8%, p <0.0001), BRAF (mutated vs wild-type: 0.5% vs 17.9%, p <0.0001), PIK3CA (mutated vs wild-type: 2.3% vs 6.5%, p <0.001), FGFR2 (mutated vs wild-type: 0.1% vs 4.4%, p <0.0001), ATM (mutated vs wild-type: 3.6% vs 6.8%, p <0.0001). On analyzing untargetable GAs, the KRAS mutated group had a significantly higher percentage of TP53 (mutated vs wild-type: 80.2% vs 47.6%, p <0.0001), CDKN2A (mutated vs wild-type: 56.2% vs 34.4%, p <0.0001), CDKN2B (mutated vs wild-type: 28.9% vs 23%, p =0.007), SMAD4 (mutated vs wild-type: 26.8% vs 15.7%, p <0.0001) and MTAP (mutated vs wild-type: 21.7% vs 18%, p =0.02). ARID1A (mutated vs wild-type: 7.7% vs 13.6%, p <0.0001 and RB1(mutated vs wild-type: 2% vs 4%, p =0.01) were more prevalent in the wild-type subgroup. Mean TMB was higher in the KRAS wild-type subgroup (mutated vs wild-type: 2.3 vs 3.6, p <0.0001). High TMB, defined as TMB > 10 mut/mB (mutated vs wild-type: 1% vs 6.3%, p <0.0001) and very-high TMB, defined as TMB >20 mut/mB (mutated vs wild-type: 0.5% vs 2.4%, p <0.0001) favored the wild-type. PD-L1 high expression was similar between the 2 groups (mutated vs wild-type: 5.7% vs 6%,). GA associated with immune checkpoint inhibitors (ICPIs) response including PBRM1 (mutated vs wild-type: 0.7% vs 3.2%, p <0.0001) and MDM2 (mutated vs wild-type: 1.3% vs 4.4%, p <0.0001) were more likely to be seen in KRAS wild-type PDA

Metastatic Melanoma of the Gallbladder in an Asymptomatic Patient

Malignant Melanoma (MM) is among the most dangerous malignancies with some of the least known survival rates. Melanoma most commonly metastasizes to regional lymph nodes, the lungs, and brain. Metastatic disease of the gallbladder (GB) is exceptionally rare making it difficult to diagnose. The fact that typically patients do not present until they are symptomatic—only after widespread metastatic disease has already occurred—is further complicating the diagnosis of MM of the GB. For this reason, MM of the GB is rarely discovered in living patients. In fact, review of the literature showed only 40 instances in which metastatic disease of the GB was reported in living patients. We describe the presentation and management of a patient who had metastatic disease of the GB. However, our case is unique because his malignancy was discovered incidentally while he was asymptomatic. He was successfully treated with an open cholecystectomy. We have presented this case in order to make the necessity of meticulous investigation of potential metastasis in patients with a known history of cutaneous melanoma clear

Mucoepidermoid carcinoma of the thymus incidentally diagnosed following two-years of non-productive cough

Mucoepidermoid carcinoma of the thymus is a rare primary thymic carcinoma. Radiologic imaging of this malignancy is rarely reported in literature. We present a patient who complained of a chronic cough for two years who was later found to have mucoepidermoid carcinoma of the thymus. Chest radiograph revealed a large anterior mediastinal mass. Follow-up computed tomography of the thorax demonstrated a large, heterogeneous anterior mediastinal mass with traversing vessels. F-18 fluorodeoxyglucose positron emission tomography-computed tomography demonstrated high avidity in the lesion with areas of diminished activity thought to represent necrosis. Following surgical resection, pathology revealed high-grade mucoepidermoid carcinoma of the thymus extending into the skeletal muscle and pericardium with evidence of lymphovascular invasion. The patient received external beam radiation therapy and has remained disease-free for three years

Relapsed Wilms’ Tumor Presenting as Metastasis to the Zygoma

Wilms’ tumor accounts for the majority of renal tumors in children. Rarely, Wilms’ tumor may metastasize to the bone. We present a case of a 15-month-old female who presented with severe abdominal distension and signs of cachexia. Abdominal ultrasonography and radiography of the abdomen both demonstrated a large abdominal mass. Follow-up computed tomography of the abdomen revealed a heterogeneous intra-abdominal mass arising from the left kidney which was surrounded by a thin rim of renal parenchyma. Biopsy of the mass revealed findings consistent with Wilms’ tumor. The patient was 14 months status-post nephrectomy and chemoradiation but returned to the clinic with left facial swelling. Magnetic resonance imaging of the face demonstrated a multilobulated, heterogeneously enhancing solitary mass lesion in the left temple centered in the left zygoma with signs of bone breakdown. Despite its rarity, metastatic Wilms’ tumor to bone should be considered in a child presenting with a new focal mass overlying bony-structures