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Browsing by Author "Tracy, Katharine"
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Item Current Understanding of “Mixed Corticomedullary Adrenal Tumor” and an Insight into Genomic Profiling(MDPI, 2022-11-11) Ullah, Asad; Mohamed, Farah Ayman Elsaid; Khan, Jaffar; Tracy, Katharine; Khan, Muhabat; Mohsen, Samiha; Yasinzai, Abdul Qahar Khan; Badini, Kaleemullah; Sobash, Philip T.; Heneidi, Saleh; Karim, Nagla Abdel; Pathology and Laboratory Medicine, School of MedicineBackground: Malignant mixed corticomedullary adrenal tumors (MCMTs) are extremely rare, with limited cases reported in the literature. The pathophysiology of malignant MCMTs is not well understood; the most prevailing theories are that it is a composite tumor of embryologically derived mesodermal (adrenal cortex) and neural crest (medulla) origin, perpetuating as two distinct cell lines forming a singular mass. Clinical features and laboratory diagnosis are associated with hypersecretions of the adrenal cortex and medulla. Surgical resection is curative in an isolated tumor. We reviewed and compared cases in the literature highlighting the pathogenesis and genetics of benign and malignant MCMT. Methods: Comprehensive literature analysis was conducted on PubMed and all the cases of mixed corticomedullary adrenal tumor published in English were included. Results: Most patients were female (73.1%) with a median age of 49 in women and 50 in men. Surgery was performed in all patients, and in four patients with malignant disease, chemotherapy was used as well. Clinically, most patients presented with hypertension (69%) followed by Cushing syndrome (42%) and diabetes (19%). Tumors often produced cortisol (74%), catecholamines (50%), and adrenocorticotrophic hormone (ACTH) (38%), with lower incidence of aldosterone- (7%) or dopamine (4%)-producing tumors. Immunohistochemical staining of 96% of cases showed Chromogranin-A (73%) and Synaptophysin (62%), followed by Inhibin-α (50%), Melan-A (31%), and S-100 (23%). Of the reported four cases with malignant disease, three showed a Ki-67 index of 40-50% with one showing less than 5%. Conclusion: Mixed corticomedullary adrenal tumors rarely present as a malignant disease requiring chemotherapy. Most MCMTs confer a good prognosis and respond well to surgical resection, though their pathogenesis is largely up to speculation because of limited data. Current theories regarding MCMT pathogenesis should be investigated further with genetic testing. Future research on MCMT may provide ways to guide physician diagnosis and subsequent treatment for refractory cases.Item Metaplastic Breast Carcinoma in U.S. Population: Racial Disparities, Survival Benefit of Adjuvant Chemoradiation and Future Personalized Treatment with Genomic Landscape(MDPI, 2023-05-28) Ullah, Asad; Khan, Jaffar; Yasinzai, Abdul Qahar Khan; Tracy, Katharine; Nguyen, Tena; Tareen, Bisma; Garcia, Andrea Agualimpia; Heneidi, Saleh; Segura, Sheila E.; Pathology and Laboratory Medicine, School of MedicinePurpose: In this population-based study, we aim to identify factors that are influential on the survival outcome in MBC and investigate novel molecular approaches in personalized disease management. Methods: The data of this study were collected from the SEER database from 2000-2018. A total of 5315 cases were extracted from the database. The data were evaluated for demographics, tumor characteristics, metastasis, and treatment. Survival analysis was completed by using SAS software for multivariate analysis, univariate analysis, and non-parametric survival analysis. The molecular data with the most common mutations in MBC were extracted from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Results: The mean age at the time of presentation was 63.1 with a standard deviation (SD) of 14.2 years. Most patients were White (77.3%) with 15.7% Black patients, 6.1% Asian or Pacific Islander, and 0.5% American Indian. Histologically, most of the reported tumors were grade III (74.4%); 37% of the cases were triple negative (ER-, PR- and HER2-), whereas the hormone status was unknown in 46% of the cases. Spread was localized in 67.3% of patients while 26.3% had regional spread and 6.3% had distant metastases. Most tumors were unilateral (99.9%) and between 20-50 mm in size (50.6%). The lungs were the most common site for distant metastasis at diagnosis (3.42%) followed by bone (1.94%), liver (0.98%), and brain (0.56%). A combination of surgery, chemotherapy, and radiation therapy was the most common treatment with a cause-specific survival rate of 78.1% (95% CI = 75.4-80.4). The overall survival rate at 5 years was 63.6% (95% confidence interval (CI) = 62.0-65.1) with a cause-specific survival of 71.1% (95% CI = 69.5-72.6). Cause-specific survival was found to be 63.2% (95% CI = 58.9-67.1) in Black patients as compared to 72.4% (95% CI = 70.1-74.1) in White patients. Black patients also presented with higher rates of grade III disease, distant metastasis, and larger tumor size. On multivariate analysis, age > 60, grade III+, metastasis, and tumor size > 50 mm were associated with worse survival. The most common mutations in MBC identified in COSMIC data were TP53, PIK3CA, LRP1B, PTEN, and KMT2C. Conclusion: Though rare, MBC is aggressive, with poor prognosis associated with high-grade tumors, metastasis, tumor size over 50 mm, and advanced age at the time of presentation. Overall, Black women had worse clinical outcomes. MBC is difficult to treat and carries a poor prognosis that affects various races disproportionately. Continued enhancement of treatment strategies to foster more individualized care as well as continued enrollment in clinical trials are needed to improve outcomes among patients with MBC.