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Optimal Method for Reporting Prostate Cancer Grade in MRI-targeted Biopsies

Deng, Fang-Ming; Isaila, Bogdan; Jones, Derek; Ren, Qinghu; Kyung, Park; Hoskoppal, Deepthi; Huang, Hongying; Mirsadraei, Leili; Xia, Yuhe; Melamed, Jonathan
When multiple cores are biopsied from a single magnetic resonance imaging (MRI)-targeted lesion, Gleason grade may be assigned for each core separately or for all cores of the lesion in aggregate. Because of the potential for disparate grades, an optimal method for pathology reporting MRI lesion grade awaits validation. We examined our institutional experience on the concordance of biopsy grade with subsequent radical prostatectomy (RP) grade of targeted lesions when grade is determined on individual versus aggregate core basis. For 317 patients (with 367 lesions) who underwent MRI-targeted biopsy followed by RP, targeted lesion grade was assigned as (1) global Grade Group (GG), aggregated positive cores; (2) highest GG (highest grade in single biopsy core); and (3) largest volume GG (grade in the core with longest cancer linear length). The 3 biopsy grades were compared (equivalence, upgrade, or downgrade) with the final grade of the lesion in the RP, using κ and weighted κ coefficients. The biopsy global, highest, and largest GGs were the same as the final RP GG in 73%, 68%, 62% cases, respectively (weighted κ: 0.77, 0.79, and 0.71). For cases where the targeted lesion biopsy grade scores differed from each other when assigned by global, highest, and largest GG, the concordance with the targeted lesion RP GG was 69%, 52%, 31% for biopsy global, highest, and largest GGs tumors (weighted κ: 0.65, 0.68, 0.59). Overall, global, highest, and largest GG of the targeted biopsy show substantial agreement with RP-targeted lesion GG, however targeted global GG yields slightly better agreement than either targeted highest or largest GG. This becomes more apparent in nearly one third of cases when each of the 3 targeted lesion level biopsy scores differ. These results support the use of global (aggregate) GG for reporting of MRI lesion-targeted biopsies, while further validations are awaited.
PMID: 34115670
ISSN: 1532-0979
CID: 4900372

Methylation Profiling of Papillary Renal Neoplasm with Reverse Polarity [Meeting Abstract]

Park, Kyung; Serrano, Jonathan; Tran, Ivy; Feng, Xiaojun; Chen, Fei; Vasudevaraja, Varshini; Mirsadraei, Leili; Snuderl, Matija; Deng, Fang-Ming
ISSN: 0023-6837
CID: 5208632

Methylation Profiling of Papillary Renal Neoplasm with Reverse Polarity [Meeting Abstract]

Park, Kyung; Serrano, Jonathan; Tran, Ivy; Feng, Xiaojun; Chen, Fei; Vasudevaraja, Varshini; Mirsadraei, Leili; Snuderl, Matija; Deng, Fang-Ming
ISSN: 0893-3952
CID: 5208642

Multilocular cystic renal cell tumors with Xp11 translocation-associated renal cell features; report of 2 cases and review of literature

Mirsadraei, Leili; Vo, Duc; Ren, Qinghu; Deng, Fang Ming; Melamed, Jonathan
ISSN: 2214-3300
CID: 4896262

Anal Cancer with Mediastinal Lymph Node Metastasis [Case Report]

Shenoy, Mangalore Amith; Winnicka, Lydia; Mirsadraei, Leili; Marks, Douglas
Squamous cell carcinoma of the anal canal remains rare, with metastatic disease even less commonly reported. We present a case of a patient with both a prior history of squamous cell carcinoma of the anal canal as well as breast cancer, who was without evidence of disease for 1 year. She was subsequently found to have FDG-avid mediastinal lymphadenopathy, initially assumed to be related to her more recent breast cancer. However, a biopsy confirmed recurrent anal cancer, with HPV infection. This represents a novel site of spread for anal cancer, one not yet reported in the literature.
PMID: 34307312
ISSN: 2296-3774
CID: 4949022

Autosomal dominant polycystic kidney disease associated renal neoplasia [Meeting Abstract]

Jones, D; Mirsadraei, L; Argyropoulos, K; Melamed, J; Deng, F; Park, K; Ren, Q
Background: Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in the genes encoding polycystin 1 and polycystin 2 (PKD1 and PKD2, respectively), leading to florid cystic change of the renal parenchyma. The incidence of carcinoma associated with ADPKD remains unclear although there are studies to suggest that the incidence may be higher.
Design(s): We queried our department pathology database for surgical specimens with ADPKD from 1990 to 2020. We evaluated these cases for the presence of associated malignant or benign neoplasia, as well as pathological and clinical parameters.
Result(s): The majority of the surgical specimens are kidney explants with a clinical diagnosis of ADPKD and the status of end stage kidney diseases. All specimens showed radiological, gross and microscopic features of ADPKD. Eight of 33 ADPKD patients with kidney resection specimens examined contained a malignant neoplasm, including 2 patients with bilateral malignancy. The types of renal cell carcinoma (RCC) associated with the following types: four cases of clear cell RCC, two cases of papillary RCC, type 2, two cases of unclassified high grade RCC, one case of unclassified low grade, as well as one case of TFE3 translocated RCC. Associated carcinomas ranged in size from less than 1 cm to 12 cm. One case with a concurrent oncocytoma and several cases with associated papillary adenoma were also reported.
Conclusion(s): In this cohort, a wide distribution of renal cell carcinoma subtypes were observed, with clear cell RCC being the most common type. The incidence of associated malignancy (24%) is higher than previously reported by Jilg et al. 2013 (5%), possibly due to differences in patient management or patient populations between the institutions. This case series highlights the high occurrence of carcinoma in APKD nephrectomies suggesting a clinical risk of malignancy in patients with ADPKD. Additionally this case series reports the first case of a TFE3 translocated renal cell carcinoma arising synchronously with a contralateral clear cell renal cell carcinoma in a patient with ADPKD. The heterogeneity of renal carcinoma subtypes within the group (and within contralateral kidneys in one patient with bilateral involvement) suggests that stimuli for tumorigenesis arise at the kidney microenvironment level rather than on the basis of gene mutation alone. Accrual of an expanded cohort of patients is planned to enable confirmation of differences between carcinomas arising in the setting of ADPKD versus those arising in end stage renal disease due to other causes, and in the sporadic setting. Furthermore a role for molecular studies is suggested to evaluate if any of the ADPKD causing mutations (PKD1, PKD2, or other) is associated with the development of carcinoma
ISSN: 1530-0307
CID: 4857022

Somatic Mutations of TSC2 or MTOR Characterize a Morphologically Distinct Subset of Sporadic Renal Cell Carcinoma With Eosinophilic and Vacuolated Cytoplasm

Chen, Ying-Bei; Mirsadraei, Leili; Jayakumaran, Gowtham; Al-Ahmadie, Hikmat A; Fine, Samson W; Gopalan, Anuradha; Sirintrapun, S Joseph; Tickoo, Satish K; Reuter, Victor E
The differential diagnosis of renal cell neoplasms with solid or nested architecture and eosinophilic cytoplasm has become increasingly complex. Despite recent advances in classifying a number of entities exhibiting this morphology, some tumors remain in the unclassified category. Here we describe a morphologically distinct group of sporadic renal cell carcinoma (RCC) with predominantly nested architecture, eosinophilic, and remarkably vacuolated cytoplasm retrospectively identified from a cohort of previously unclassified tumors. We examined the clinicopathologic and immunohistochemical features of these tumors and investigated their mutational and copy number alterations using a targeted next-generation sequencing platform. The study included 7 patients with a mean age of 54 years (range: 40 to 68 y) and a male to female ratio of 3:4. All patients presented with a solitary renal mass and had no prior medical or family history raising concern for syndromic conditions. Tumors were well-circumscribed, unencapsulated, and comprised of nests of eosinophilic cells in a hypocellular and often edematous stroma. Tumor cells had round nuclei with prominent nucleoli and granular cytoplasm with striking vacuolization. Thick-walled vessels and calcifications were also frequently present, whereas increased mitotic activity, necrosis, foamy histiocytes or lymphocytic infiltrates were not identified. All cases were positive for PAX8, had retained expression of SDHB and FH, and exhibited a CK7-/CK20- phenotype. While cathepsin-K was positive in 5 cases, none exhibited immunoreactivity to HMB45 or Melan A, or TFE3 immunostaining. Next-generation sequencing identified somatic inactivating mutations of TSC2 (3/5 tumors tested) or activating mutations of MTOR (2/5) as the primary molecular alterations, consistent with hyperactive mTOR complex 1 signaling which was further demonstrated by phospho-S6 and phospho-4E-BP1 immunostaining. Copy number analysis revealed a loss of chromosome 1 in both cases with MTOR mutation. These tumors represent a novel subset of sporadic RCC characterized by alterations in TSC1-TSC2 complex or the mTOR complex 1 pathway. Recognition of their characteristic morphologic and immunophenotypic features will allow them to be readily identified and separated from the unclassified RCC category.
PMID: 30303819
ISSN: 1532-0979
CID: 3584192

Clues to recognition of fumarate hydratase-deficient renal cell carcinoma: Findings from cytologic and limited biopsy samples

Shyu, Irene; Mirsadraei, Leili; Wang, Xiaoyan; Robila, Valentina; Mehra, Rohit; McHugh, Jonathan B; Chen, Ying-Bei; Udager, Aaron M; Gill, Anthony J; Cheng, Liang; Amin, Mahul B; Lin, Oscar; Smith, Steven Christopher
BACKGROUND:Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is rare and highly aggressive and is believed to arise mostly in the setting of hereditary leiomyomatosis-RCC syndrome with a germline mutation of FH. Because of the aggressiveness of these tumors and a frequent lack of ascertainable family history, these tumors may first present as metastases and be sampled by cytology. The cytologic findings of FH-deficient RCC have not previously been reported. METHODS:Cytologic and limited biopsy samples from patients with FH-deficient RCC were reviewed retrospectively. RESULTS:In total, 24 cytologic and limited biopsy samples from 19 patients (6 women and 13 men; age range, 22-69 years) who had FH-deficient RCC and metastasis at presentation were evaluated. These included 21 cytology samples ranging from malignant effusions (n = 7) to metastases (n = 11), to samples of primary kidney tumors (n = 3). The samples exhibited cells, often in clusters and abortive papillae, with voluminous, finely vacuolated cytoplasm and large, pleomorphic nuclei with prominent, viral inclusion-like nucleoli. A distinctive finding of peripheral cytoplasmic clearing frequently was apparent, and intranuclear cytoplasmic pseudoinclusions were less frequent. Of 7 cell block and biopsy samples, several of which represented sampling from the same patient, all demonstrated tissue fragments that had discernable morphologic patterns associated with FH-deficient RCC, including tubulocystic and intracystic papillary growth. CONCLUSIONS:Features characteristic and suggestive of FH-deficient RCC may be identified in cytologic and small biopsy samples. Although the current samples were identified retrospectively in well characterized cases of FH-deficient RCC, the authors argue that, with appropriate clinical correlation, these features are sufficiently distinctive to trigger recognition and confirmatory workup.
PMID: 30339328
ISSN: 1934-6638
CID: 3584202

A Single Institutional Experience With the Paris System for Reporting Urinary Cytology: Correlation of Cytology and Histology in 194 Cases

Zare, Somaye; Mirsadraei, Leili; Reisian, Niloufar; Liao, Xiaoyan; Roma, Andres; Shabaik, Ahmed; Hasteh, Farnaz
Objectives/UNASSIGNED:The Paris System for Reporting Urinary Cytology (TPS) is designed to standardize the criteria and terminology used in urinary tract cytology reporting. The aim of this study was to evaluate the impact of implementing TPS and to analyze the correlation with follow-up biopsies in order to assess its reproducibility. Methods/UNASSIGNED:Urinary tract cytology specimens with follow-up biopsies over a 2-year period were reviewed and reclassified according to TPS criteria. Surgical follow-up diagnoses were correlated with the initial cytology diagnoses and TPS interpretations, and the results were compared. Results/UNASSIGNED:Applying TPS in comparison to our previous reporting system resulted in fewer cases in the atypia category (11.8% vs 24.2%) and higher specificity, accuracy, and predictive value. We observed acceptable interobserver agreement in diagnostic categories of this reporting system. Conclusions/UNASSIGNED:TPS improves the overall performance of urinary tract cytology by standardizing the criteria and terminology.
PMID: 29878037
ISSN: 1943-7722
CID: 3584182

Cytological characteristics of Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC)-associated renal cell carcinomas [Meeting Abstract]

Mirsadraei, Leili; Chen, Ying-Bei; Reuter, Victor; Lin, Oscar
ISSN: 0893-3952
CID: 3584032