Browsing by Author "Magers, Martin J."

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    Clinical Utility and Concordance of Upper Urinary Tract Cytology and Biopsy in Predicting Clinicopathologic Features of Upper Urinary Tract Urothelial Carcinoma
    (Elsevier, 2019) Talsma Simon, Caroline; Skala, Stephanie L.; Weizer, Alon Z.; Ambani, Sapan N.; Chinnaiyan, Arul M.; Palapattu, Ganesh; Hafez, Khaled; Magers, Martin J.; Kaffenberger, Samuel D.; Spratt, Daniel E.; Montgomery, Jeffrey S.; Morgan, Todd M.; Udager, Aaron M.; Lew, Madelyn; Mehra, Rohit; Pathology and Laboratory Medicine, School of Medicine
    5% of urothelial carcinoma occurs in the upper urinary tract (UUT), a challenging location to biopsy. We aim to evaluate concordance between biopsy, cytology, and resection specimens in a large upper tract urothelial carcinoma (UTUC) cohort.117 UTUC resections with UUT biopsy and/or cytology specimens from 2000–2016 were retrieved; pathologic material was re-reviewed, evaluated for concordance, and correlated with clinical information. 14% pre-operative biopsies, including 8 from renal pelvis and 6 from ureter, lacked neoplastic diagnoses. 77% diagnostic biopsies included subepithelial tissue; 11% demonstrated reclassification of grade and 30% demonstrated reclassification of invasion status. 26% of renal pelvis UTUC and 36% ureter UTUC were invasive only on resection. Of 18 UTUC reclassified from noninvasive high-grade papillary urothelial carcinoma (HGPUC) to invasive HGPUC, 39% had prior radical cystectomy (versus 8% invasive UTUC and 11% noninvasive UTUC with concordant biopsies). Most high-grade UTUC (88%) and some low-grade UTUC (58%) resections had abnormal cytology results. Biopsy-resection pairs with concordant invasion status and pairs with discordant invasion status showed similar rates of recurrence (38% versus 38%) and metastasis (25% versus 27%). 14% of UUT biopsies lacked diagnostic neoplastic material. Grade concordance between biopsy and resection was high (89%), but 30% of cases showed invasion only on resection. Subepithelial tissue was less commonly present in ureter biopsies, particularly from mid or proximal ureter. UTUC in patients with prior cystectomy were more likely to show invasion on resection but not biopsy.
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    Clinicopathological characteristics of ypT0N0 urothelial carcinoma following neoadjuvant chemotherapy and cystectomy
    (BMJ, 2019-08) Magers, Martin J.; Kaimakliotis, Hristos Z.; Barboza, Marcelo P.; Bandali, Elhaam; Adra, Nabil; Koch, Michael O.; Cheng, Liang; Pathology and Laboratory Medicine, School of Medicine
    Aims To describe a large tertiary care academic centre’s experience with patients who achieve a complete pathological response (ie, ypT0N0) following neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) with emphasis on morphological features present in the RC and clinical outcome. Methods 41 patients with ypT0N0 disease following transurethral resection of bladder tumour (TURBT), NAC and RC with available clinical follow-up information were analysed. Slides from all RCs were reviewed to confirm pathological stage and assess for morphological parameters (eg, foreign body giant cell reaction, dystrophic calcification, scar and fat necrosis). Results With median follow-up of 32.8 months, the recurrence-free survival at 1 and 5 years was 97.4% and 93.5%, while the overall survival at 3 and 5 years was 94.2% and 88.6%, respectively. No patients died of urothelial carcinoma. Stage assigned at TURBT was 1 pTa (2%), 1 pT1 (2%), 38 pT2 (93%) and 1 pT3a (2%). 17 TURBTs demonstrated variant histology, with the majority of these being squamous (65%). The most common morphological features present at RC were scar (100%), foreign body giant cell reaction (80%), chronic inflammation within lamina propria (68%) and dystrophic calcifications (39%). Other morphological features were less common or absent. Conclusion ypT0N0 disease at RC portends an excellent prognosis, regardless of stage or variant histology in the TURBT; scar, foreign body giant cell reaction, chronic inflammation and dystrophic calcifications are often present.
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    Immunophenotypic Characterization of Germ Cell Tumor-Derived Primitive Neuroectodermal Tumors: Evidence for Frequent Neuronal and/or Glial Differentiation
    (Allen Press, 2021) Magers, Martin J.; Perrino, Carmen M.; Ulbright, Thomas M.; Idrees, Muhammad T.; Pathology and Laboratory Medicine, School of Medicine
    Context: Primitive neuroectodermal tumors (PNETs) may arise as a somatic-type malignancy in germ cell tumors. In this setting, most PNETs resemble those of the central nervous system and lack chromosome 22 translocations. However, description of the morphologic and differentiation spectrum of PNETs arising from germ cell tumors is lacking. Objective: To investigate the morphologic and immunohistochemical features of these tumors, concentrating on neuronal and glial features. Design: We selected cases based on a morphologically identifiable glial and/or differentiated neuronal component in association with the undifferentiated PNET. Immunohistochemistry for glial fibrillary acidic protein, S100 protein, synaptophysin, chromogranin A, and SOX11 was performed on tumors with available material, with the scoring of both staining intensity (0-3) and extent (0-3). Thirteen qualifying PNETs of testicular origin with available immunohistochemical stains or stainable material were identified. The complete stain panel was performed in 10 tumors. Results: SOX11 demonstrated positive staining in the undifferentiated PNET component of all tumors (10 of 10) and was rarely positive in the differentiated (ie, neuronal/glial) component (1 of 10; focal and weak); synaptophysin was slightly less sensitive in the undifferentiated component (12 of 13; often focal and weak) and also showed positivity in the neuronal/glial component (5 of 13). Glial fibrillary acidic protein and S100 were more frequently positive in the differentiated areas (83% and 77%, respectively) compared with undifferentiated areas (25% and 17%, respectively). Conclusions: SOX11 is a sensitive immunohistochemical marker for testicular PNET, particularly those lacking differentiation. Testicular PNETs often demonstrate glial and/or neuronal differentiation. Differentiation is marked by the acquisition of S100 and glial fibrillary acidic protein expression and SOX11 loss.
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    Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice
    (2011-11-15) Farrow, Emily G.; Yu, Xijie; Summers, Leila J.; Davis, Siobhan I.; Fleet, James C.; Allen, Matthew R.; Robling, Alexander G.; Stayrook, Keith R.; Jideonwo, Victoria; Magers, Martin J.; Garringer, Holly J.; Vidal, Ruben; Chan, Rebecca J.; Goodwin, Charles B.; Hui, Siu L.; Peacock, Munro; White, Kenneth E.
    Autosomal dominant hypophosphatemic rickets (ADHR) is unique among the disorders involving Fibroblast growth factor 23 (FGF23) because individuals with R176Q/W and R179Q/W mutations in the FGF23 (176)RXXR(179)/S(180) proteolytic cleavage motif can cycle from unaffected status to delayed onset of disease. This onset may occur in physiological states associated with iron deficiency, including puberty and pregnancy. To test the role of iron status in development of the ADHR phenotype, WT and R176Q-Fgf23 knock-in (ADHR) mice were placed on control or low-iron diets. Both the WT and ADHR mice receiving low-iron diet had significantly elevated bone Fgf23 mRNA. WT mice on a low-iron diet maintained normal serum intact Fgf23 and phosphate metabolism, with elevated serum C-terminal Fgf23 fragments. In contrast, the ADHR mice on the low-iron diet had elevated intact and C-terminal Fgf23 with hypophosphatemic osteomalacia. We used in vitro iron chelation to isolate the effects of iron deficiency on Fgf23 expression. We found that iron chelation in vitro resulted in a significant increase in Fgf23 mRNA that was dependent upon Mapk. Thus, unlike other syndromes of elevated FGF23, our findings support the concept that late-onset ADHR is the product of gene-environment interactions whereby the combined presence of an Fgf23-stabilizing mutation and iron deficiency can lead to ADHR.
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    PSMA Targeted Positron Emission Tomography in Evaluation of Patients with Primary Prostate Cancer: Comparison of Preoperative [68Ga]Ga-PSMA-11 Positron Emission Tomography/Computerized Tomography Immediate Postoperative Specimen [68Ga]Ga-PSMA-11 Imaging and Whole Mount Pathology
    (AUA, 2020) Bahler, Clinton D.; Green, Mark; Hutchins, Gary D.; Cheng, Liang; Magers, Martin J.; Fletcher, James; Koch, Michael O.; Urology, School of Medicine
    Purpose: We evaluated which lesions are detected and missed on [ 68Ga]Ga-PSMA-11 positron emission tomography in patients with primary prostate cancer. Materials and Methods: Patients undergoing radical prostatectomy were enrolled in this prospective observational study. Patients underwent [ 68Ga]Ga-PSMA (prostate specific membrane antigen)-11 positron emission tomography/computerized tomography or positron emission tomography/magnetic resonance imaging prior to surgery and received a dose of [ 68Ga]Ga-PSMA-11 intraoperatively for positron emission tomography of extirpated specimens. Whole mount pathology was performed with lesion and intralesion based analysis to determine the characteristics of lesions detected or not detected by PSMA positron emission tomography. Lesion volume was determined by planimetry and clinically significant lesion volume was calculated as lesion volume × fraction pattern 4/5. Results: On whole mount analysis 30 cancerous lesions were found in a total of 15 patients, including 4, 15, 4, 1 and 6 which were Grade Group 1, 2, 3, 4 and 5, respectively. PSMA-positron emission tomography detected 100% of primary/index lesions and 8 of 11 (82%) secondary lesions. All Grade Group 3-5 lesions were detected vs 12 of 15 Grade Group 2 lesions. When comparing Grade Group 2 vs 3-5, lesion size was similar (p=0.48) but the standardized uptake value was lower for Grade Group 2 vs 3-5 (5.3 vs 7.9, p=0.03). The 3 missed lesions showed of 10% or less of pattern 4 and a Gleason pattern 4/5 volume of less than 0.1 cm 3. Conclusions: PSMA positron emission tomography detected 100% of primary/index lesions in this study. The 3 missed secondary lesions were small and had a low percent of pattern 4. This argues for further study to better understand what defines clinically significant prostate cancer, which would assist in determining whether small lesions that become challenging to detect by [ 68Ga]Ga-PSMA-11 positron emission tomography confer a risk to the patient.