Browsing by Author "Akgul, Mahmut"

Now showing 1 - 4 of 4
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    A Simplified Diagnostic Approach on TFE3 Gene Fusion-Associated Renal Cell Carcinoma
    (Allen Press, 2020-11-04) Akgul, Mahmut; Cheng, Liang; Idrees, Muhammad; Urology, School of Medicine
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    Distinct Mutational Landscape of Inverted Urothelial Papilloma
    (Wiley, 2019-09) Akgul, Mahmut; MacLennan, Gregory T.; Cheng, Liang; Pathology and Laboratory Medicine, School of Medicine
    A recent study has identified gene mutations involving the MAPK/ERK pathway, particularly the HRAS gene, in all inverted urothelial papillomas (IUPs), in the absence of pathway mutations in TERT promoter, FGFR3, and TP53/RB1genes. Neither recurrence nor progression was observed in IUPs. These data support several longstanding hypotheses: (1) IUPs are benign and do not recur or progress; (2) they harbor mutations that are different from those of urothelial carcinoma; and (3) they arise through different molecular mechanisms than low‐ or high‐grade urothelial carcinoma. As the most critical differential diagnosis in this context is inverted‐type urothelial carcinoma, more comprehensive studies are needed to compare and contrast these entities.
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    GATA3 expression in clear cell adenocarcinoma of the lower urinary tract: a potential diagnostic pitfall
    (Springer, 2022-11-01) Akgul, Mahmut; Humble, Robert; Osme, Abdullah; Yuce, Servet; Kocak, Elif N.; Najafzade, Parisa; Sangoi, Ankur; Pattnaik, Niharika; Mishra, Sourav; Sharma, Shivani; Shaker, Nada; Kaushal, Seema; Baisakh, Manas; Lightle, Andrea R.; Balzer, Bonnie L.; Xiao, Guang-Qian; MacLennan, Gregory T.; Osunkoya, Adeboye O.; Parwani, Anil; Cheng, Liang; Bellizzi , Andrew; Mohanty, Sambit K.; Pathology and Laboratory Medicine, School of Medicine
    Background Clear cell adenocarcinoma of the lower urinary tract (CCACLUT) is a rare primary malignant neoplasm with heterogenous morphology. There is a paucity of data in the literature regarding its immunohistochemical profile. Methods The immunohistochemical features (extent and intensity) of a multinational cohort of CCACLUT were evaluated with comparison between clear cell adenocarcinoma of the female genital tract (CCACFGT, tissue microarray) and nephrogenic adenoma (NA). Results 33 CCACLUT (24 female, 9 male; mean age 59 years) were collected. CCACLUT most commonly arose from the urinary bladder (26/33, 78%), particularly from the trigone (10/33, 30.3%) followed by the urethra (8/33, 22%). All 12 NA cases were located at the urinary bladder, whereas the most common CCACFGT location was the ovary (29/56, 52%). None of the CCACLUT patients had, intestinal metaplasia, NA, or urothelial carcinoma. One patient had concurrent endometriosis of the sigmoid colon. Most frequently observed morphology in CCACLUT was papillary/tubulocystic (9/3; 27.3%), followed by papillary/tubular (6/33; 18.2%) and papillary/solid (5/33; 15.2%). GATA3 expression was significantly higher in CCACLUT (18/33, 54.5%) and NA (6/12, 50%), when compared to CCACFGT cases 6/56, 11.7%)(p = 0.001 and p = 0.022, respectively). The extent of GATA3 was significantly higher in CCACLUT group (19.2 ± 16.6%) than the other groups (9.6 ± 22.5% in NA and 2.6 ± 9% in CCACFGT group) (p = 0.001). 4/33 patients (12.1) had weak, 10/33 patients (30.3%) had moderate, and 4/33 patients (12.1%) had strong GATA3 intensity in CCACLUT group. In NA group, one patient (8.3%, 1/12) had weak, one patient (8.3%, 1/12) had moderate and 4 patients (33.3%, 4/12) had strong GATA3 intensity. Most cases (CCACLUT 29/33, 88%; NA 11/12, 92%; CCACFGT 46/56, 82.1%) had positive Napsin A expression, by which CCACLUT had significantly more cases with Napsin A expression (p = 0.034). p63 was consistently negative in all cases (30/33 (91.9%) CCACLUT; 12/12 (100%) NA; 42/56 (75%) CCACFGT. Ki67 (MIB) proliferation index was significantly higher in CCACLUT group (54.6 ± 21%) when compared to NA group (4.5 ± 2.7%) and CCACFGT group (35.5 ± 25.8%) (p = 0.001). Conclusion CCACLUT has consistent GATA3 expression, which may cause challenge in the diagnosis of urothelial carcinoma but can be used to distinguish CCACLUT from CCACFGT.
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    Immunophenotypic and pathologic heterogeneity of unclassified renal cell carcinoma: a study of 300 cases
    (Elsevier, 2020-08) Akgul, Mahmut; Cheng, Liang; Urology, School of Medicine
    Renal cell carcinoma, unclassified (RCC-U), is a heterogenous group of tumors that do not fit in any of the recognized histologic types. Immunohistochemical studies are frequently used to characterize these tumors. Herein, we sought to investigate the immunophenotypes of 300 cases of RCC-U. The cases were morphologically classified into three groups: oncocytoma/chromophobe renal cell carcinoma–like, group 1; clear cell renal cell carcinoma–like, group 2; and others (ie, papillary renal cell carcinoma–like/collecting duct–like/pure sarcomatoid), group 3. The male-to-female ratio was 1.4. Most cases (168, 66%) were group 1. Group 3 was associated with larger tumor size, advanced stage, and frequent lymph node metastases. The most commonly used immunohistochemical stains were CK7 (n = 270; 89.5%), vimentin (n = 186, 82%), CD10 (n = 181; 59.9%), and AMACR (n = 162; 54%). Pancytokeratin (79/101; 78.2%) and PAX8 (54/61; 88.5%) were diffusely positive in most cases, followed by AMACR (69/117; 59%). CD117 was positive in 53 of 118 cases (45%). RCC-U is a morphologically and immunophenotypically heterogenous group of tumors, and comprehensive workup is needed before rendering the diagnosis.