Unlike other malignancies, therapeutic options in pancreatic ductal adenocarcinoma (PDAC) are largely limited to cytotoxic chemotherapy without the benefit of molecular markers predicting response. Here we report tumor-cell-intrinsic chromatin accessibility patterns of treatment-naïve surgically resected PDAC tumors that were subsequently treated with (Gem)/Abraxane adjuvant chemotherapy. By ATAC-seq analyses of EpCAM+ PDAC malignant epithelial cells sorted from 54 freshly resected human tumors, we show here the discovery of a signature of 1092 chromatin loci displaying differential accessibility between patients with disease free survival (DFS) < 1 year and patients with DFS > 1 year. Analyzing transcription factor (TF) binding motifs within these loci, we identify two TFs (ZKSCAN1 and HNF1b) displaying differential nuclear localization between patients with short vs. long DFS. We further develop a chromatin accessibility microarray methodology termed “ATAC-array”, an easy-to-use platform obviating the time and cost of next generation sequencing. Applying this methodology to the original ATAC-seq libraries as well as independent libraries generated from patient-derived organoids, we validate ATAC-array technology in both the original ATAC-seq cohort as well as in an independent validation cohort. We conclude that PDAC prognosis can be predicted by ATAC-array, which represents a low-cost, clinically feasible technology for assessing chromatin accessibility profiles.
Liposarcoma is one of the most common sarcomas in adults, but very rarely presents as a primary in the upper gastrointestinal system. Herein, we present a 71-year-old male patient who underwent wedge excision biopsy twice and then fine needle aspiration and total gastrectomy for a recurrent gastroeosophageal junction mass. In microscopic sections, both well-differentiated and dedifferentiated components were seen. Tumor cells were positive for MDM2, CDK4 and negative for CD117, DOG1, CD34, SMA, Desmin, S-100, HMB45, SOX10, AE1/AE3, CAM5.2, CK18. Fluorescence in situ hybridization (FISH) was performed and MDM2 gene (12q15) amplification was detected. According to these findings, a diagnosis of dedifferentiated liposarcoma was supported. We believe this is the first reported case of dedifferentiated liposarcoma of the gastroesophageal junction.
Backround. Thyroglossal duct cyst (TDC) is a developmental abnormality of the thyroid gland. Due to embryological remnants of thyroid tissue located in the TDC, the same malignant tumors that develop in the thyroid gland can also develop in the TDC. Methods. We present the unique case of a 39-year-old female with simultaneous de novo papillary carcinoma in a TDC and the thyroid gland. Results. With the suspicion of simultaneous papillary carcinoma in the TDC and the thyroid gland, Sistrunk procedure with total thyroidectomy and central neck exploration was performed.
Conclusion. The clinician should have a high index of suspicion upon encountering papillary carcinoma of the TDC to differentiate de novo papillary carcinoma in the TDC from those originating from the thyroid gland, because papillary carcinoma in TDC may originate from an occult thyroid papillary carcinoma.
We present a woman aged 50 years who underwent a Tru-cut biopsy for a BI-RADS 4 lesion on her right breast and received a histopathology diagnosis of a fibroadenoma. In her one year follow-up, the lesion had progressed and she underwent an excisional biopsy. Her final diagnosis was a periductal stromal tumor. Periductal stromal tumor is an extremely rare and different entity from phylloides tumor, which makes appropriate diagnosis difficult in Tru-cut biopsy and care should be taken. Lesion progression of should require a re-biopsy. Their tendency to recur warrants follow-up. We believe that radiologic, pathologic, and clinical correlation is key in decision-making and diagnosis of these tumors.
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