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CONTEXT.: Mitochondria and mitochondrial DNA have been suggested to play a role in cancer initiation and progression. Knowledge of mitochondrial DNA could provide a breakthrough to advance cancer management. OBJECTIVE.: To identify the mitochondrial DNA landscape in non-small cell lung carcinoma. DESIGN.: The adenocarcinoma set consisted of 365 pairs of adenocarcinomas and normal lung tissues, whereas the metastasis set included 12 primary non-small cell carcinomas, 15 metastatic tumors, and their normal counterparts. Tumor-specific somatic variants were identified, and if a variant showed heteroplasmy, the proportion of minor alleles was evaluated. Variants with greater than 10% change in allele frequency between tumor and normal pairs were identified as "heteroplasmic shifts." RESULTS.: Tumor-specific variants appeared throughout the whole mitochondrial genome, without a common hot spot. Distinct variant profiles were seen in 289 (79.18%) of all individual adenocarcinomas. The presence of a unique profile and the number and loading of heteroplasmic shifts in tumors increased with higher stage or lymph node metastasis, and were related to shorter survival. In the metastasis set, the primary tumor variants were generally found in metastatic tumors. CONCLUSIONS.: This study shows that somatic mitochondrial DNA mutations present with diverse locations and unique profiles in each individual tumor, implying their clinicopathologic utility.
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BACKGROUND: Detection of glandular abnormalities in Papanicolaou (Pap) tests is challenging. This study aimed to review our institute's experience interpreting such abnormalities, assess cytohistologic concordance, and identify cytomorphologic features associated with malignancy in follow-up histology. METHODS: Patients with cytologically-detected glandular lesions identified in our pathology records from 1995 to 2020 were included in this study. RESULTS: Of the 683,197 Pap tests performed, 985 (0.144%) exhibited glandular abnormalities, 657 of which had tissue follow-up available. One hundred eighty-eight cases were cytologically interpreted as adenocarcinoma and histologically diagnosed as malignant tumors of various origins. There were 213 cases reported as atypical glandular cells (AGC) and nine cases as adenocarcinoma in cytology, yet they were found to be benign in follow-up histology. In addition, 48 cases diagnosed with AGC and six with adenocarcinoma cytology were found to have cervical squamous lesions in follow-up histology, including four squamous cell carcinomas. Among the cytomorphological features examined, nuclear membrane irregularity, three-dimensional clusters, single-cell pattern, and presence of mitoses were associated with malignant histology in follow-up. CONCLUSIONS: This study showed our institute's experience detecting glandular abnormalities in cervical cytology over a 25-year period, revealing the difficulty of this task. Nonetheless, the present study indicates that several cytological findings such as membrane irregularity, three-dimensional clusters, single-cell pattern, and evidence of proliferation could help distinguishing malignancy from a benign lesion.
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OBJECTIVE: Pathological features indicating metastatic mucinous carcinoma to the ovary (MMCO) have been rarely reported in primary mucinous ovarian carcinoma (PMOC). However, little is known about how often they are observed in PMOC and how they relate to patient prognosis. In this study, we investigated the pathological features indicating MMCO in a large cohort of PMOCs and analyzed their association with patient prognosis. METHODS: We reviewed surgically treated PMOC patients diagnosed at the Seoul National University Hospital from 1995 to 2019, according to the updated WHO classification, and investigated the presence of pathological features indicating MMCO. RESULTS: A total of 144 patients with PMOCs were included. The 5 pathological findings indicating MMCO, including an infiltrative invasive pattern, the absence of benign or borderline components, a smaller tumor size, the presence of signet ring cells and the presence of extracellular mucin were observed in PMOC (21.6%, 43.1%, 20.8%, 4.3% and 12.9%, respectively), and were significantly correlated with poor overall and progression-free survival rates in PMOC. The patient's prognosis worsened as the extent of the infiltrative invasive pattern increased (p<0.001). In addition, the prognostic power was stronger when the 5 pathological factors were analyzed together (new grouping system) than when analyzed individually (p<0.001) and the new grouping system was identified as an independent prognostic factor regardless of FIGO stage. CONCLUSION: Five pathological findings indicating MMCO in PMOC were significantly associated with poor prognosis in PMOC patients. Also, the new grouping system combining these findings was identified as an independent prognostic factor.
