Adebowale J Adeniran

Yale University, New Haven, Connecticut, United States

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Publications (32)81.48 Total impact

  • Adebowale J. Adeniran · Brian Shuch · Peter A. Humphrey
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    ABSTRACT: Renal cell carcinomas associated with syndromes of a heritable nature account for about 4% of all renal cell carcinomas. They are characterized by an earlier age of onset, and are often multicentric and bilateral. Some of these patients may fit into well-characterized kidney cancer syndromes, while many more may have a genetic component that is not fully recognized or understood. The presence of extrarenal clinical features may suggest a specific renal tumor susceptibility syndrome. Moreover, each syndrome is associated with specific renal pathology findings. Recognition of individuals and families with a high risk of renal neoplasia is important so that surveillance for renal tumors may be initiated. This manuscript reviews the clinical, pathological, and molecular features of hereditary renal cell carcinoma syndromes with emphasis on the morphologic features of these tumors and the molecular mechanisms of hereditary renal tumorigenesis.
    No preview · Article · Dec 2015 · American Journal of Surgical Pathology
  • Adebowale J. Adeniran · Peter A. Humphrey

    No preview · Article · Dec 2015 · Surgical Pathology Clinics
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    ABSTRACT: Aims . Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available. Methods and Results . MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases ( P = 0.1 ). MET expression weakly correlated between primary and matched metastatic sites ( R = 0.5 ) and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different ( P = 0.39 ). Conclusions . We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.
    No preview · Article · Sep 2015
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    ABSTRACT: Renal cell carcinoma (RCC) is one of the most chemo- and radio-resistant malignancies, with poor associated patient survival if the disease metastasizes. With recent advances in immunotherapy, particularly with PD-1/PD-L1 blockade, outcomes are improving, but a substantial subset of patients does not respond to the new agents. Identifying such patients and improving the therapeutic ratio has been a challenge, although much effort has been made to study PD-1/PD-L1 status in pre-treatment tumor. However, tumor infiltrating lymphocyte (TIL) content might also be predictive of response, and our goal was to characterize TIL content and PD-L1 expression in RCC tumors from various anatomic sites. Utilizing a quantitative immunofluorescence technique, TIL subsets were examined in matched primary and metastatic specimens. In metastatic specimens, we found an association between low CD8+ to Foxp3+ T-cell ratios and high levels of PD-L1. High PD-L1-expressing metastases were also found to be associated with tumors that were high in both CD4+ and Foxp3+ T-cell content. Taken together these results provide the basis for combining agents that target the PD-1/PD-L1 pathway with agonist of immune activation, particularly in treating RCC metastases with unfavorable tumor characteristics and microenvironment. In addition, CD8+ TIL density and CD8:Foxp3 T-cell ratio were higher in primary than metastatic specimens, supporting the need to assess distant sites for predictive biomarkers when treating disseminated disease.
    No preview · Article · Jul 2015 · Oncotarget
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    ABSTRACT: Papillary renal cell carcinoma (PRCC), a morphologically and genetically distinct subtype of RCC, is morphologically separated into 2 subtypes for therapeutic and prognostic purposes. Type 2 tumors are generally believed to have a poorer prognosis than type 1 tumors. In spite of multiple studies, many clinicopathological issues about PRCC remain vague. We studied the clinicopathological features associated with type 1 versus type 2 PRCC, and we compared the immunohistochemical profiles in both subtypes of PRCC. We identified a total of 144 cases (74 type 1, 46 type 2, and 24 mixed), 29 female and 115 male. Mean age was 56 years for type 1 and 59 years for type 2. Mean tumor size was 3.6 cm for type 1 and 4.6 cm for type 2. Type 1 tumors were more likely to have nuclear grade 2 and less, whereas type 2 tumors were more likely to have nuclear grade 3 and above (P = .0001). There was no significant association between tumor type and renal sinus fat invasion, invasion of muscular branches of renal vein, perinephric fat invasion, microvascular angiolymphatic invasion, and main renal vein invasion. Type 2 tumors have higher nuclear grades than type 1 tumors. Based on long follow-up data, both subtypes appear to have excellent prognosis when diagnosed at early stage. The immunohistochemical profiles of both types 1 and 2 PRCC are essentially the same. The similar immunohistochemical profile suggests that PRCC is one entity with divergent histologic features. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Jun 2015 · Human pathology
  • Li-Ying Fu · Adebowale J Adeniran

    No preview · Article · May 2015 · The Journal of urology
  • Liying Fu · Peter A Humphrey · Adebowale J Adeniran

    No preview · Article · Dec 2014 · The Journal of Urology
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    ABSTRACT: Aims Immunohistochemical stains have greatly improved the diagnostic accuracy of renal cell carcinoma (RCC) for primary and distant tumours. We evaluate a marker that has recently been incorporated in clinical practice, PAX-8, in primary and metastatic RCCs. Methods Two distinct tissue microarrays were used, one consisting of over 334 renal tumours, 294 with adjacent normal kidney and the other with 40 matched nephrectomy and metastatic sites of RCC. PAX-8 expression was assessed by a method of quantitative immunofluorescence. Results PAX-8 was positive in 96% (146/152) of normal renal tissue and 83% (227/272) of renal tumours. PAX-8 staining was positive in clear cell, papillary and chromophobe tumours in 80% (165/207), 95% (39/41) and 100% (6/6) of samples, respectively. Overall, intensity of PAX-8 expression was significantly higher in RCC metastatic sites than in the primary site (p=0.0047), however, in matched sites there was no statistically significant difference in the proportion of positive versus negative specimens (p=0.274). Conclusions As the role of molecular markers expands in the diagnostic algorithm, this study confirms that PAX-8 expression is a useful diagnostic marker for RCC. PAX-8 expression was found in the primary tumour and distant sites. Compared with normal tissue and other histological types, clear cell RCC has lower PAX-8 expression and is less frequently positive, therefore, the lack of expression does not exclude a tumour of renal origin.
    No preview · Article · Oct 2014 · Journal of Clinical Pathology
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    ABSTRACT: BACKGROUND Fine-needle aspiration of the thyroid is a common procedure, with an established role in reducing unnecessary thyroid surgery and identifying neoplasms and malignancies. METHODS The study evaluated 1558 responses in the American Society for Clinical Pathology (ASCP) Non-GYN Assessment program of aspirates of thyroid neoplasms and malignancies and placed them into the following groups: group A (target or correct interpretation), group B (incorrect interpretation as a benign thyroid nodule), group C (incorrect interpretation malignant aspirate as thyroid neoplasm), and group D (malignant diagnosis with incorrect interpretation). In clinical practice, responses in groups A, C, and D would lead to surgical excision, whereas responses in group B would not. RESULTS Of a total of 1558 responses, 78.5% of the responses were in group A, 8.5% in group B, 3.75% in group C, and 9.25% in group D. By individual diagnosis, the group rates were 86.5%, 0%, 11%, and 2.5% for anaplastic thyroid carcinoma; 83%, 5.5%, 4.25%, and 7.25% for papillary thyroid carcinoma; 79%, 7%, 6%, and 8% for medullary thyroid carcinoma; 83.5% 6.75%, 0%, and 9.75% for Hürthle cell neoplasm; and 61%, 22%, 0%, and 17% for follicular neoplasm in groups A, B, C, and D respectively. CONCLUSIONS Fine-needle aspiration was effective in diagnosing thyroid neoplasms and malignancies and in separating thyroid nodules into surgical and nonsurgical categories. Data from a large group of cytology professionals showed good performance; however, there is room for improvement, especially in making specific diagnoses. In particular, follicular neoplasm and follicular variant of papillary thyroid carcinoma were challenging diagnoses for participants.
    Full-text · Article · Oct 2014 · Cancer Cytopathology
  • Adebowale J Adeniran · Pei Hui
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    ABSTRACT: BRAF V600E mutation is the single most common genetic alteration identified in papillary thyroid carcinoma. There is significant association between BRAF V600E mutation and aggressive tumor behavior. BRAF V600E mutation has also been found to be an independent predictor of treatment failure and tumor recurrence even in patients with low-stage disease. Pre-operative BRAF mutation testing of thyroid fine needle aspiration specimens has become a routine clinical practice that enhances the predictability of malignancy in indeterminate fine needle aspiration cytology specimens especially those in the follicular lesion of undetermined significance/atypia of undetermined significance category. In addition to histological evaluation of subsequent core needle biopsy and BRAF immunohistochemistry, an expanded panel of mutation testing including BRAF V600E, NRAS, HRAS, RET/papillary thyroid carcinoma and PAX8/PPARγ rearrangements are currently advocated to further improve the diagnostic predictability in the detection of thyroid carcinomas using cytological specimens.
    No preview · Article · Aug 2014 · Expert Review of Endocrinology & Metabolism
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    ABSTRACT: The 2007 Bethesda classification for thyroid cytology defines follicular neoplasm as a category of cases with cellular specimens demonstrating abundant follicular cells arranged in a microfollicular pattern with little or no colloid. The current recommendation for the management of these cases is diagnostic lobectomy. There has been great difficulty and variability in triaging and reporting follicular neoplasm. To increase diagnostic accuracy, at the study institution, this category is subclassified further into 3 categories: 1) microfollicular-patterned neoplasm (MN); 2) Hürthle cell neoplasm (HN); and 3) follicular lesion with some features suggestive of but not diagnostic of the follicular variant of papillary thyroid carcinoma (FL). The authors reviewed the cases of follicular neoplasm observed over a period of 5 years to document the follow-up trend using this modified classification. A search of the cytology records was performed for the period between January 2008 and December 2012. All thyroid fine-needle aspiration cases were reviewed and those with a diagnosis of follicular neoplasm (including Hürthle cell neoplasm) were identified. Correlating follow-up surgical pathology reports were reviewed. A total of 399 cases of follicular neoplasm with surgical follow-up were identified. Malignancy was identified in 32% of all cases of follicular neoplasm and was found to be disproportionately higher in the FL category (73%). A cytological diagnosis of FL is more likely to be called malignant (73%) than benign neoplastic (9%) or benign nonneoplastic (18%). A cytological diagnosis of MN or HN is more likely to be benign neoplastic (46% and 46%, respectively) than malignant (29% and 26%, respectively) or benign nonneoplastic (25% and 28%, respectively). Of the cytological features examined, 2 (nuclear enlargement and nuclear grooves) were significantly associated with the follicular variant of papillary thyroid carcinoma. The results of the current study clearly indicate that follicular lesions with even subtle nuclear atypia have a high positive predictive value for malignancy and therefore should be distinguished from other follicular lesions because these cases require more aggressive surgical management. The current study also raises an important issue concerning the current thyroid classification based on the 2007 Bethesda classification for thyroid cytology. Future thyroid fine-needle aspiration classification schemes should consider subclassifying follicular neoplasms for the purpose of risk stratification. Cancer (Cancer Cytopathol) 2014. © 2014 American Cancer Society.
    No preview · Article · Jul 2014 · Cancer Cytopathology
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    ABSTRACT: Follicular variant of papillary thyroid carcinoma (FVPTC) creates a continuous diagnostic dilemma among pathologists because of the paucity of nuclear changes of papillary carcinoma and overlapping features with benign and other neoplastic follicular lesions. Current guidelines for the management of thyroid nodules recommend surgery for confirmed PTC, suspicious for PTC, and follicular neoplasm cases, while further immediate diagnostic studies or treatment are not routinely required if the nodule is benign on cytology. This study is designed to determine the accuracy of cytology in the diagnosis of FVPTC, based on the Bethesda classification system, and determine the implications for patient management based on the current recommendation. Based on a retrospective review of cytologic diagnoses between January 2008 and December 2011, thyroid fine needle aspiration (FNA) cytology specimens with subsequent surgical intervention and a final diagnosis of FVPTC were selected. The cytologic diagnoses were compared with the final diagnoses, and the percentage of cases contributing to the final diagnosis of FVPTC was calculated for each diagnostic category. Triage efficiency and diagnostic accuracy were calculated. One hundred and fifty-two cases with histologic confirmation of FVPTC were identified (representing 128 patients-101 female, 27 male). All patients had undergone either lobectomy with completion thyroidectomy or total thyroidectomy. The cytologic diagnosis of "positive for malignancy" accounted for only 27 % of the final histologic diagnosis of FVPTC, while suspicious for carcinoma, follicular neoplasm, follicular lesion of undetermined significance, and benign accounted for 11, 23, 23, and 16 % of the final diagnosis of FVPTC, respectively. Only 18 % of the 55 cases tested were positive for BRAF mutation. The subtle nuclear features of FVPTC pose challenges for an accurate diagnosis. Therefore, a better approach is to triage these cases for surgical intervention and/or further evaluation of the particular nodule. Our triage efficacy for FVPTC was 84 %; however, the diagnostic accuracy of PTC was 38 %. A negative diagnosis on FNA has diagnostic and management implications for up to 16 % of cases because they may have no further immediate diagnostic studies or treatment. BRAF mutation analysis provides minimal effect on diagnostic accuracy.
    No preview · Article · Apr 2014 · Endocrine Pathology
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    ABSTRACT: Merkel cell carcinoma (MCC) is a rare and highly aggressive primary neuroendocrine carcinoma of the skin with a high propensity for local, regional, and distant spread. Distant metastasis of MCC to the pancreas is uncommonly seen and may impose a diagnostic challenge cytologically. Here we report a case of MCC with pancreatic metastasis, which was diagnosed by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The aspirates revealed both single and clustered epithelial cells with scant cytoplasm and round nuclei with stippled chromatin and inconspicuous nucleoli. Immunocytochemically, the tumor cells were positive for CK20, synaptophysin, CD56, and CD117. The neoplastic cells were also identified by flow cytometry as non-hematopoietic cells which were positive for CD56 and negative for CD45. To our knowledge, this is only the second case report of MCC metastatic to the pancreas diagnosed by EUS-FNA. There have been several reports of MCC metastatic to the pancreas diagnosed only at the time of surgical resection. However, a preoperative diagnosis allows for appropriate management while sparing a patient the morbidity of unnecessary procedures. Diagn. Cytopathol. 2012; © 2012 Wiley Periodicals, Inc.
    No preview · Article · Mar 2014 · Diagnostic Cytopathology
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    ABSTRACT: This case confirms the observation that urothelial carcinomas can secrete beta-hCG, and that beta-hCG can potentially be used as a marker of a patient's clinical response to treatment. Prospective studies are clearly warranted by these observations.
    No preview · Article · Oct 2013 · Oncology (Williston Park, N.Y.)

  • No preview · Article · Oct 2013
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    ABSTRACT: Background: The tall cell variant of papillary thyroid carcinoma is an aggressive subtype that generally presents as a large tumor in the advanced stage; however, little is known about the tall cell variant of microcarcinoma (tumors measuring <1 cm). In this study, we compare the tall cell variant of microcarcinoma (microTCV) with classic papillary microcarcinomas to examine the hypothesis that, despite the small size, the microTCV may be more aggressive than the classic papillary microcarcinoma. Methods: We identified 27 microTCV patients and compared their clinicopathologic features and BRAF(V600E) mutational status with classic papillary microcarcinomas matched by age and size. The patients with microTCV included 22 women and 5 men aged 33 to 74 years (median age, 56 years). All patients underwent total thyroidectomy; 20 patients had lymph node dissection. Results: Tumor size in microTCV patients ranged from 2 mm to 10 mm (median, 7 mm). Extrathyroidal extension and lymphovascular invasion were seen in 9 (33%) and 4 (15%) tumors, respectively. Thirteen patients (48%) harbored multifocal papillary carcinomas. Metastasis to central compartment lymph nodes was seen in 8 patients and to lateral cervical nodes in 3 patients. Nine of the 25 patients (36%) presented at an advanced stage (stage III/IVA). The BRAF(V600E) mutation was detected in 25 of 27 tumors (92.6%). In contrast, age- and size-matched classic papillary microcarcinomas (n=26) showed no extrathyroidal extension (p=0.002), lymphovascular invasion in 1, central compartment lymph node metastasis in 2, lateral cervical node metastasis in 1, multifocal tumors in 10 (38.5%), the BRAF(V600E) mutation in 20 (76.9%), and it infrequently presented in stage III/IVA (7.7%, p=0.02). Conclusions: The microTCV form is associated with aggressive features at presentation, and it should be differentiated from other papillary thyroid microcarcinomas.
    No preview · Article · May 2013 · Thyroid: official journal of the American Thyroid Association
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    ABSTRACT: Various ultrasonographic characteristics of thyroid nodules have been associated with a higher likelihood of malignancy, and certain clinical features may also increase the likelihood of malignancy in patients. This study is designed to determine the ultrasonographic and clinical predictors of malignancy in the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category. A search through the cytology files at our institution was made for cases with diagnosis of AUS/FLUS. The clinical and radiologic findings were correlated with the final surgical pathology diagnosis. A total of 140 cases of AUS/FLUS with corresponding surgical intervention were identified (112 females and 28 males). There was a 79 % malignancy rate in nodules with irregular contours, compared to 51 % in nodules with regular outlines. Nodules demonstrating calcifications showed a 57 % malignancy rate, compared to 50 % in nodules without calcifications. Sixty-one percent of cases with an ultrasonographic diagnosis of indeterminate to suspicious were malignant following surgical resection. The rates of malignancy in patients with radiation exposure, symptomatic nodules, and positive family history of thyroid cancer were 22, 59, and 33 %, respectively. BRAF mutation was demonstrated in 57 % of malignant cases and in none of benign cases. No single clinical or ultrasonographic feature or combination of features is adequately sensitive or specific to identify all malignant nodules. However, a combination of solid nodules, nodules with irregular contours, symptomatic nodules, and positive BRAF mutation has high predictive value for malignancy in patients with a cytologic diagnosis of AUS/FLUS.
    No preview · Article · Apr 2013 · Endocrine Pathology
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    ABSTRACT: Background Targeted therapies in renal cell carcinoma can have different effects on primary and metastatic tumors. To pave the way for predictive biomarker development, we assessed differences in expression of targets of currently approved drugs in matched primary and metastatic specimens from 34 patients. Methods Four cores from each site were embedded in tissue microarray blocks. Expression of B-Raf, C-Raf, cKIT, FGF-R1, HIF-2α, mTOR, PDGF-Rβ, VEGF-R1, VEGF-R2, VEGF-R3, VEGF, VEGF-B, VEGF-C, VEGF-D, MEK1, and ERK1/2 was studied using a quantitative immunofluorescence method. Results No significant differences were observed in global expression levels in primary and metastatic renal cell carcinoma tumors, with the exception of MEK, which had higher expression in metastatic than primary specimens. Similarly, more ki67 positive cells were seen in metastatic specimens. Correlations between marker expression in primary and metastatic specimens were variable, with the lowest correlation seen for FGF-R1 and VEGF-D. There were no significant differences in the degree of heterogeneity in primary versus metastatic tumors. Conclusions Expression of most of the studied markers was similar in primary and metastatic renal cell carcinoma tumors, suggesting that predictive biomarker testing for these markers can be conducted on either the primary or metastatic tumors for most markers.
    Preview · Article · Feb 2013 · BMC Clinical Pathology
  • Helen Honarpisheh · David Chhieng · Kevin Schofield · Adebowale J. Adeniran

    No preview · Article · Feb 2013 · Modern Pathology
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    ABSTRACT: Recently, a six-tiered diagnostic risk classification system was created based on the recommendations of the National Cancer Institute (NCI) sponsored NCI Thyroid Needle Aspiration State of the Science Conference at Bethesda, MD in October 2007. The objective of the current study was to compare the frequency distribution of the various diagnostic categories to evaluate its diagnostic performance before and after implementation of The Bethesda System (TBS). A total of 5,897 thyroid Fine needle aspirations (FNAs) were reviewed; 3,207 were from 2008 after TBS implementation, and 2,690 were from 2007 immediately before TBS implementation. Follow-up consisted of reviewing corresponding histologic results. The rates of "Nondiagnostic" specimens and cases with a diagnosis of "Follicular Neoplasm" decreased from 13.1 to 11.1% and 8.6 to 5.5%, respectively, after implementation of TBS, while the rate of negative specimens increased from 68.2 to 73.8%. The other categories remained relatively stable. In addition, there also was a significant decrease in the use of noncommittal descriptive diagnoses. The diagnostic performance of thyroid FNA in identifying a neoplastic process as measured by area under the receiver operating characteristic curve increased from 0.88 to 0.89; the difference was statistically significant (P=0.03). Implementation of TBS showed a significant reduction of: nondiagnostic thyroid FNAs, of FNAs with a diagnosis of "Follicular Neoplasm," as well as cases with descriptive noncommittal diagnoses. TBS results in improved diagnostic performance and therefore more consistent and uniform reporting of thyroid FNA. Diagn. Cytopathol. 2013. © 2013 Wiley Periodicals, Inc.
    No preview · Article · Feb 2013 · Diagnostic Cytopathology

Publication Stats

544 Citations
81.48 Total Impact Points


  • 2010-2015
    • Yale University
      • School of Medicine
      New Haven, Connecticut, United States
  • 2011-2013
    • Yale-New Haven Hospital
      • Department of Pathology
      New Haven, Connecticut, United States
  • 2004-2006
    • University of Cincinnati
      • Department of Pathology and Laboratory Medicine
      Cincinnati, Ohio, United States