Browsing by Author "Mesa, Hector"
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Item AB025. Evaluation of potential therapeutic immunohistochemical targets with experimental or FDA-approved therapies in thymic epithelial tumor microarrays(AME, 2023-12-30) Ardeshir-Larijani, Fatemeh; Loehrer, Patrick J.; Maniar, Rohan; Hou, Tieying; DeBrock, Victoria; Mesa, Hector; Pathology and Laboratory Medicine, School of MedicineBackground: Thymus epithelial tumors (TETs) are rare malignancies of the anterior mediastinum. The current standard of care for metastatic TETs is a combination of platinum-based chemotherapy. Here, we have evaluated the experimental and FDA-approved makers in a large TET tissue array with the hope of identifying a new therapeutic option. Methods: A tissue microarray (TMA) containing ninety malignant thymic tumors (A, AB, B1 and B2, n=62, B2/B3 and B3, n=16, and thymic carcinoma, n=12) and seven normal adult thymus were assembled. The protein expressions of GLUT1, TROP2, PSMA, ROS1, ALK, HER2, and PDL-1 were tested with immunohistochemical assays. Expression was quantified using a “staining score (SS)”, which is a 0–3 numerical score that results from the product of the intensity of expression: 0= negative, 1= weak, 2= moderate, 3= strong, and the area of expression in fractions of a percent (0= no expression, 1= 100% area). Expression of HER2 and PDL-1 was quantified according to existing guidelines [HER2 score and combined positive score (CPS)]. Results: Trop-2 had the highest expression in thymic carcinoma (TC) (100%, SS 2.6±0.6) followed by thymoma B2/B3 (78%, SS 1.3±1.3), types A/AB/B1 (54%, SS 1.1±1.1) (P=0.01). In TC, all patients with squamous histology had immunohistochemistry (IHC) SS of 3. Patients with thymoma who had Trop-2 expression experienced significantly worse survival [hazard ratio (HR): 3.3, P=0.008]. GLUT1 was highly expressed in TC (81.8%, SS: 2.1±1, TC vs. normal thymus, P=0.0003). PDL-1 was expressed in all TET tissues (mean, 2.5–52 CPS). No significant expression of ALK, ROS1, or HER2 observed in normal thymus or TETs. Conclusions: Trop-2 expression is a prognostic marker in TETs. High expression of Trop-2 protein in thymoma and TC appears a promising therapeutic target for Trop-2 antibody-drug conjugates.Item Acinic Cell Carcinoma in the 21st Century: A Population-Based Study from the SEER Database and Review of Recent Molecular Genetic Advances(MDPI, 2023-06-27) Khan, Jaffar; Ullah, Asad; Goodbee, Mya; Lee, Kue Tylor; Yasinzai, Abdul Qahar Khan; Lewis, James S., Jr.; Mesa, Hector; Pathology and Laboratory Medicine, School of MedicineBackground: Acinic cell carcinoma (AciCC) comprises 6-7% of all salivary gland neoplasms and is the second most common salivary gland malignancy in children. Like many salivary gland carcinomas, it is considered low grade but occasionally it behaves aggressively. Understanding the risk factors associated with recurrence, metastasis, and death is important to determine the counseling and management of individual patients. Older population-based studies are presumed to have been confounded by the misclassification of other neoplasms as AciCC, in particular secretory carcinoma and cystadenocarcinoma. Since diagnostic tools to reliably separate these entities have been available for over a decade, reevaluation of epidemiologic data limited to the 21st century should allow a better characterization of the clinicopathological characteristics of AciCC. Methods: Our study extracted data from the Surveillance, Epidemiology, and End Results (SEER) database for the period 2000 to 2018. Cox regression model analysis was performed to identify risk factors independently affecting survival. Results: Data for 2226 patients with AciCC were extracted from the database. Most patients were females: 59%, and white: 80.5%, with a mean age at diagnosis of 51.2 (SD ± 18.7) years. Most cases (81%) were localized at presentation. Tumor size was less than 2 cm in 42%, 2-4 cm in 47%, and >4 cm in 11%. Low-grade tumors had 5-year survival > 90%, whereas high-grade tumors had survival < 50%. Of the patients with known lymph node status only 7.3% had nodal metastases. Distant metastases were documented in 1.1%, involving lungs 44%, bone 40%, liver 12%, and brain 4%. The most common treatment modality was surgery alone: 63.6% followed by surgery and adjuvant radiation: 33%. A few received chemotherapy (1.8%) or multimodality therapy (1.2%). The 5-year overall survival rate was 90.6% (95%CI 89.1-91.9), and disease-specific survival was 94.6% (95%CI 93.3-95.6). Multivariable cox regression analysis showed that undifferentiated (HR = 8.3) and poorly differentiated tumor grade (HR = 6.4), and metastasis (HR = 5.3) were the worst independent prognostic factors. Other poor risk factors included age > 50 (HR = 3.5) and tumor size > 4 cm (HR = 2.5). Conclusions: In the US, AciCC is more common in middle age white females, and most tumors are less than 4 cm and localized at diagnosis. The most relevant negative prognostic factor was high tumor grade which was associated with higher hazard ratios for death than all other variables, including regional or distant metastases at presentation.Item Fatal eosinophilic myocarditis and submassive hepatic necrosis in lamotrigine induced DRESS syndrome(BMC, 2023-10-25) Doan, Khanh Duy; Akinsanya, Adeyinka; Kuhar, Matthew; Mesa, Hector; Pathology and Laboratory Medicine, School of MedicineDrug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a rare but severe and sometimes fatal adverse drug reaction that is known to occur with a number of antiepileptic drugs. It often follows a prolonged clinical course, which can worsen even after discontinuing the causative drug and administering steroid treatment. Failure to promptly identify the delayed involvement of vital organs, such as the heart and liver, may result in irreversible organ failure and death. We report a case of a presumed sudden death of a young woman who had a documented history of a protracted intermittent hypersensitivity reaction to lamotrigine. Postmortem examination revealed the presence of eosinophilic myocarditis and submassive hepatic necrosis diagnostic of fatal DRESS syndrome that progressed despite early discontinuation of the medication and improvement of dermatologic and hematologic symptoms following steroid therapy.Item Gastrointestinal Stromal Tumors (GIST): A Population-Based Study Using the SEER Database, including Management and Recent Advances in Targeted Therapy(MDPI, 2022-07-28) Khan, Jaffar; Ullah, Asad; Waheed, Abdul; Karki, Nabin Raj; Adhikari, Nawaraj; Vemavarapu, Lakshmi; Belakhlef, Sami; Bendjemil, Samy Malik; Seraj, Siamak Mehdizadeh; Sidhwa, Feroze; Ghleilib, Intisar; Foroutan, Shahin; Blakely, Andrew M.; Del Rivero, Jaydira; Karim, Nagla Abdel; Vail, Eric; Heneidi, Saleh; Mesa, Hector; Pathology and Laboratory Medicine, School of MedicineIntroduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal (GI) system. Most GISTs originate from the interstitial cells of Cajal (ICC), the pacemaker cell situated between the circular and longitudinal layers of the muscularis propria along the GI tract. In this population-based study using the SEER database, we sought to identify demographic, clinical, and pathologic factors that affect the prognosis and survival of patients with this neoplasm. Molecular genetic advances, current management guidelines, and advances in targeted therapy are discussed. Methods: Demographic and clinical data from GIST patients were retrieved from the SEER research plus database for the period 2000−2018. Statistical analysis was performed with IBM SPSS® v20.2 software using the Chi-square test, paired t-test, multivariate analysis, and Kaplan−Meier functions. Results: A total of 10,833 patients with GIST were identified. Most patients were between 60−74 years of age: 40%, Caucasian: 68%, and the male to female ratio was 1.1:1. The most common primary tumor sites were stomach: 63%, small intestine: 30%, rectum: 3%, and esophagus: 0.7%. When reported, the grade of differentiation was well: 38%, moderately: 32%, undifferentiated: 19%, poorly: 12%. The size of most tumors ranged between 6−10 cm: 36% and they were treated by surgical intervention: 82% and/or chemotherapy/targeted therapy: 39%. The stage was localized: 66%, advanced: 19%, and regional: 15%. The 5-year survival was 74% (95% confidence interval (95% CI) = 72.6−74.7), and the 5-year cause-specific survival 82% (95% CI = 80.7−82.6). The 5-year cause-specific survival by treatment included surgery at 86% (95% CI = 85.4−87.3), chemotherapy/targeted therapy with or without surgery at 77% (95% CI = 75.7−78.9), and radiation at 75% (95% CI = 74.5−80). On multivariable analysis tumor size > 5 cm, poorly and undifferentiated grade, age > 60, and distant metastases at presentation were associated with worse overall survival. Conclusion: GISTs comprise 1−2% of malignancies of the GI tract, usually affect male Caucasians between the ages of 60 and 74 years, most tumors occur in the stomach and small intestine, and are usually >5 cm, but still localized, at the time of diagnosis. Most tumors receive multimodality surgical and chemotherapy/targeted therapy treatment, with a 5-year overall survival of 74% and cause-specific survival of 82%. GIST patients would benefit from enrollment in large clinical trials to establish better therapy guidelines for unresectable, treatment-refractory, and recurrent tumors.Item Immunophenotypic Comparison of Testicular Sclerosing Sertoli Cell Tumors and Sertoli Cell Tumors Not Otherwise Specified(Elsevier, 2017-09) Mesa, Hector; Zhang, Chen; Manivel, Juan C.; Ulbright, Thomas M.; Department of Pathology and Laboratory Medicine, School of MedicineTesticular Sertoli cell tumors (SCTs) are rare, and most fall into the category of SCT–not otherwise specified (SCT-NOS). Only a few additional types of SCT are recognized. Sclerosing SCT (S-SCT), originally described in 1991, comprises a small fraction of SCTs and was considered a specific entity until the 2016 revision of the World Health Organization classification of non–germ cell tumors, where it was classified as a morphologic variant of SCT-NOS. In a recent study, differences in expression of PAX2/PAX8, inhibin, androgen receptor, and S100 protein between SCT-NOS and S-SCT were noted in a small number of cases. In this interinstitutional study, we compared the expression of these markers and β-catenin in 11 cases each of SCT-NOS and S-SCT to determine if differences exist that could justify keeping a separate classification of these neoplasms. PAX2/PAX8 cocktail was the only marker that was significantly overexpressed in S-SCT. Expression of androgen receptors was strong in S-SCT and variable in SCT-NOS but did not reach statistical significance. Expression of β-catenin was common in both, whereas inhibin was infrequent. The available material was insufficient for a conclusive evaluation of S100 protein expression. Overall, our results support the inclusion of S-SCT as a morphologic variant of SCT-NOS. Expression of PAX2/PAX8 in S-SCT may reflect an overactive epithelial-to-mesenchymal transition as has been shown in experimental models of acute and chronic seminiferous tubular injury and might be related to the process generating the stroma in these tumors.Item Incidental adrenal hemangioma clinically suspicious for malignancy: diagnostic considerations and review of the literature(e-Century Publishing, 2022-11-15) Toklu, Ani; Mesa, Hector; Collins, Katrina; Pathology and Laboratory Medicine, School of MedicineAdrenal hemangiomas are rare lesions often found incidentally during unrelated diagnostic work-up. We report a case of a 67-year-old man with history of hypertension, hyperlipidemia, anemia, arthralgia, joint swelling and unexplained weight loss, which prompted imaging studies. Computed tomography scan revealed a 5.4 cm adrenal mass. The patient had no clinical manifestations of adrenal medullary or cortical hyperfunction. Urine and plasma metanephrines and aldosterone/renin ratio were within normal range. The patient was taking prednisone for hand and ankle swelling, precluding assessment for Cushing syndrome. Given the size of the lesion, the possibility of malignancy was considered, and the patient elected for surgical management. The left adrenalectomy specimen weighed 54 g and revealed a 4.9 cm tan-brown mass with congested cut surface and a thin rim of residual adrenal gland parenchyma. Histologic examination showed thick and thin-walled vessels intermingled with adrenocortical elements at the periphery characteristic of a hemangioma. Surgical resection is the mainstay treatment for large, isolated adrenal masses to exclude malignancy and prevent retroperitoneal hemorrhage. Herein, we report a case of adrenal hemangioma, review a variety of other diagnostic considerations occurring in the adrenal gland, and highlight useful distinguishing features to assist in accurate diagnosis.Item Invasive Fungal Infections of the Head and Neck: A Tertiary Hospital Experience(MDPI, 2024-06-23) Hou, Tieying; Bell, W. Robert; Mesa, Hector; Pathology and Laboratory Medicine, School of MedicineFrom the existing millions of fungal species, only a few cause disease. In this study, we investigated invasive fungal infections in the head and neck (H&N) over a 19-year period (2005 to 2024) at a large academic healthcare system. Among the 413 documented fungal H&N infections, 336 were noninvasive, and 77 were invasive. The highest incidence of invasive infections occurred in the sinonasal cavities, with a 15-fold difference compared to other sites. Most infections affected adults over 40 years old. The most common organisms were Mucorales (51%), hyaline molds (29%), and Candida (11%). Risk factors included malignancy, transplant, diabetes, and illicit drug use. Mortality was high in patients with malignancy and/or transplant. Infections affecting the mandible were usually a complication of osteoradionecrosis and were associated with the coinfection of Candida and Actinomyces. At other sites, infections were rare and were usually the result of penetrating injuries or immunosuppression. Treatment typically involved a combination of antifungals and surgical procedures.Item Isolated Kaposi sarcoma of the upper aerodigestive tract in immunocompetent individuals, an underrecognized entity with favorable prognosis(Sage, 2022-09-15) Shabaan, Abdelrahman; Alkashash, Ahmad; Hou, Tieying; Saeed, Omer; Yesensky, Jessica; Roshal, Anna; Mesa, Hector; Otolaryngology -- Head and Neck Surgery, School of MedicineKaposi sarcoma (KS) is a rare vascular neoplasm that most commonly arises in the setting of immunosuppression, in areas with high prevalence of Human Herpesvirus-8 infection, and when both situations coexist. Most cases affect the skin, isolated involvement of the upper respiratory tract without skin involvement is extremely rare with only a few cases reported in the literature. We present a case of isolated nasopharyngeal KS in an immunocompetent patient who achieved remission after multimodality therapy. Recent advances in KS-therapy are discussed.Item Jejunal Intussusception Secondary to a Large Inflammatory Fibroid Polyp: A Case Report and Discussion of Differential Diagnosis(Hindawi, 2023-04-13) Abu-Salah, Asma Khalid; Brocken, Eric; Mesa, Hector; Collins, Katrina; Pathology and Laboratory Medicine, School of MedicineInflammatory fibroid polyp (IFP), initially considered a reactive process, is now recognized as a benign mesenchymal neoplasm of the gastrointestinal tract. We report a case of a 68-year-old woman with medically refractory Crohn disease that presented with intussusception requiring surgical intervention. The resection revealed a jejunal mass consisting of a submucosal proliferation of bland spindle cells in a fibrous stroma infiltrated by numerous eosinophils. By immunohistochemistry, the lesion was positive for vimentin and negative for desmin, smooth muscle actin (SMA), S-100, CD117, DOG1, ALK (D5F3), Melan-A, HMB-45, CD34, and STAT6. Ki-67 proliferative index was low (<1%). The mass was classified as IFP by its characteristic morphology and associated eosinophilia. IFP should be considered in the differential diagnosis of adults with intussusception or bowel obstruction. Definitive treatment typically requires surgical resection of the involved bowel segment.Item Metabolic Interplay in the Tumor Microenvironment: Implications for Immune Function and Anticancer Response(MDPI, 2023-12-05) Youssef, Reem; Maniar, Rohan; Khan, Jaffar; Mesa, Hector; Pathology and Laboratory Medicine, School of MedicineMalignant tumors exhibit rapid growth and high metabolic rates, similar to embryonic stem cells, and depend on aerobic glycolysis, known as the "Warburg effect". This understanding has enabled the use of radiolabeled glucose analogs in tumor staging and therapeutic response assessment via PET scans. Traditional treatments like chemotherapy and radiotherapy target rapidly dividing cells, causing significant toxicity. Despite immunotherapy's impact on solid tumor treatment, gaps remain, leading to research on cancer cell evasion of immune response and immune tolerance induction via interactions with the tumor microenvironment (TME). The TME, consisting of immune cells, fibroblasts, vessels, and the extracellular matrix, regulates tumor progression and therapy responses. TME-targeted therapies aim to transform this environment from supporting tumor growth to impeding it and fostering an effective immune response. This review examines the metabolic disparities between immune cells and cancer cells, their impact on immune function and therapeutic targeting, the TME components, and the complex interplay between cancer cells and nontumoral cells. The success of TME-targeted therapies highlights their potential to achieve better cancer control or even a cure.