Recent genomic studies on cancer tissues obtained during rapid autopsy have provided insights into the clonal evolution and heterogeneity of cancer. However, post-mortem blood has not been subjected to genetic analyses in relation to cancer. We first confirmed that substantial quantities of cell-free DNA were present in the post-mortem plasma of 12 autopsy cases. Then, we focused on a pilot case of prostate cancer with multiple metastases for genetic analyses. Whole-exome sequencing of postmortem plasma-derived cell-free DnA and eight frozen metastatic cancer tissues collected during rapid autopsy was performed, and compared their mutational statuses. The post-mortem plasma cell-free DNA was successfully sequenced and 344 mutations were identified. Of these, 160 were detected in at least one of the metastases. Further, 99% of the mutations shared by all metastases were present in the plasma. Sanger sequencing of 30 additional formalin-fixed metastases enabled us to map the clones harboring mutations initially detected only in the plasma. In conclusion, post-mortem blood, which is usually disposed of during conventional autopsies, can provide valuable data if sequenced in detail, especially regarding cancer heterogeneity. Furthermore, post-mortem plasma cell-free DNA sequencing (liquid autopsy) can be a novel platform for cancer research and a tool for genomic pathology. Evidence of the clonal evolution of cancer is rapidly accumulating, and tumor heterogeneity is now recognised as a critical issue in the era of personalised cancer medicine 1,2. To precisely evaluate the clonal evolution and heterogeneity of cancer, sequence analysis of multiple cancer lesions is essential. Considering the difficulties associated with sampling multiple cancer tissues from living patients, particularly from those who have undergone chemoor immunotherapy, autopsies are highly valuable. In fact, several rapid autopsy studies have led to important findings in the fields of prostate cancer, pancreatic cancer, renal cell carcinoma, and breast cancer 3-6. However, the genotypes of cell-free DNA (cfDNA) in post-mortem blood samples have never been analyzed in relation to cancer. Circulating cfDNA from cancer patients contains tumor DNA (circulating tumor DNA); therefore, sequencing analyses of cfDNA from cancer patients provide information about genomic changes in tumors within a patient without surgical resection or tissue biopsy 7,8. The identification of cancer-associated gene mutations in

Rare cases of metastatic squamous cell carcinoma with chondroid differentiation from esophageal primary have been reported but none from the uterine cervix. Given the rarity of this phenomenon and potential diagnostic pitfall, we present this unusual case. The patient is a 25-year-old woman who presented with shortness of breath. Computerized tomography (CT) showed several lung and pleural-based nodules. CT-guided core biopsy with touch preparations were performed on the pleural-based nodule. The touch preparations showed large, spindle-to-oval shaped cells with pleomorphic nuclei embedded in metachromatic chondroid stroma. The core biopsies also showed predominantly round-to-spindle shaped cells with hyperchromatic nuclei and prominent nucleoli embedded in a cartilaginous matrix. Her past medical history is significant for a poorly differentiated squamous cell carcinoma of the cervix, which on review showed a typical non-keratinizing squamous cell carcinoma without sarcomatous differentiation. Immunohistochemical stains performed on the pleural-based mass showed tumor positivity for AE1/AE3, CK5/6, p16, and S-100. Similar results were seen when the cervical tumor was stained retrospectively. Human papilloma virus (HPV) in situ hybridization performed on both the pleural-based mass and cervical tumor detected the presence of high-risk HPV subtypes including 16 and 18. These findings supported a lung metastasis from the prior cervical carcinoma. This case emphasizes that cervical carcinoma can develop mesenchymal (chondrosarcomatous) differentiation in metastasis even in tumors presenting with pure epithelial phenotype. Awareness of this occurrence especially on limited cytology material, knowledge of the prior history and use of ancillary tests are extremely helpful in arriving at the correct diagnosis. Diagn. Cytopathol. 2017;45:750-753. © 2017 Wiley Periodicals, Inc.