Background/Objectives Pancreatic ductal adenocarcinoma is a highly lethal disease with increasing incidence. Due to high resistance, chemo/radiotherapy has limited success in pancreatic cancer and only marginally prolongs patient survival. Therefore, novel biomarkers and therapeutic targets are needed. In the present review, we performed a comprehensive summary of therapeutic approaches targeting the GP130/JAK/STAT3 pathway. Methods We systematically reviewed the PubMed and Embase databases for preclinical and clinical studies, from inception to October 4, 2020, on drugs targeting the GP130/JAK/STAT3 pathway. Bias assessments and qualitative analyses were performed. Results Twenty-five preclinical and nine clinical trials were included in the review. All preclinical studies reported a favorable outcome in terms of pancreatic ductal adenocarcinoma progression. Futhermore, drugs targeting the GP130/JAK/STAT3 pathway were shown to be efficient chemosensitizers. However, high publication bias was assumed. In the clinical setting, bazedoxifene and itacitinib improved patient outcomes. Conclusion Preclinical studies strongly suggest significant efficacy of drugs targeting GP130/JAK/STAT3 in the treatment of pancreatic ductal adenocarcinoma and that these molecules are effective chemosensitizers. Though only a few trials have shown the efficacy in a clinical setting, the STAT3 pathway remains a promising drug target for future treatment of pancreatic ductal adenocarcinoma and may help overcome chemotherapy resistance.

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Thyroid fine needle aspiration cytology (FNAC) is one of the most frequently performed medical procedures worldwide. 1 It is used as a diagnostic test to separate benign thyroid nodules (colloidal and hyperplastic nodules) from thyroid malignancies, either primary (papillary thyroid carcinoma [PTC], medullary thyroid carcinoma, poorly differentiated thyroid carcinoma [PDTC], anaplastic thyroid carcinoma [ATC]) or, less often, metastatic. 2 The negative and positive predictive values of this procedure in The Bethesda System for Reporting Thyroid Cytopathology are, respectively, 97% and 98% for the benign and malignant categories. 3 Being so frequent a procedure, it is not rare in general cytopathology practice to encounter unusual lesions that pose diagnostic problems. The modern cytopathologist should also be aware of the clinical setting in which a lesion is aspirated and should interpret cytomorphology and ancillary tests results as a whole, to maintain high thyroid FNAC diagnostic accuracy.We report one such difficult case that required integration of clinical, morphological and immunohistochemical findings to reach a correct diagnosis. | CASE HISTORYA 54-year-old man with unremarkable past medical history presented with a rapidly growing right laterocervical nodule that, as he said, had become palpable within a month. However, he also complained of pharyngeal discomfort with right shoulder pain for several months. On examination, the patient was in overall good physical condition. Cervical palpation confirmed a diffusely enlarged right thyroid lobe, as well as a right cervical mass measuring approximatively 5 cm. No sign of thyroid dysfunction was noted. A cervical ultrasound (US) confirmed the clinical appreciation and revealed multiple and bilateral enlarged lymph nodes, all of them with highly suspicious features. This presentation suggested a primary malignant thyroid neoplasm with local metastatic spread. FNAC under US guidance was then performed on the right thyroid lobe and the largest pathological lymph node. Following a cytopathological diagnosis of a high-grade B-cell lymphoma, a lymph node biopsy was performed for precise subtyping and final diagnosis. Meanwhile, 18-fludeoxyglucose positron emission tomography/computed tomography revealed multiple pathological uptake in the liver and spleen, as well as in the previously described cervical lesions. 3 | MATERIALS AND METHODS, RESULTS Cervical echography showed a 3.8 × 3.3 × 2.5 cm hypoechoic and hypovascular thyroid lesion with digitiform outline and heterogeneous content (Figure 1A, upper part), as well as multiple hypoechoic and partly ill-defined lymph nodes showing pathological vascularization and measuring up to 5.0 × 4.1 x 2.4 cm in the right neck levels II, III and IV (Figure 1A, lower part). FNAC material aspirated from the thyroid lesion and the largest pathological lymph node showed similar cytomorphological features, consisting mainly of numerous malignant cells, isolated (Figure 1B) or forming loosely cohesive clusters on a background of ...