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Article: Navigating the challenges of establishing a new residency program in anatomic pathology based on the Accreditation Council for Graduate Medical Education International standards in the post-Soviet era Kazakhstan: strategies and successes.

Tanko, Naanlep Matthew / Pignatelli, Massimo / DeFrances, Marie C / Dhir, Rajiv

2024 Volume 11, Issue 2, Page(s) 100121

Abstract: In 1991, after the dissolution of the Soviet Union, newly independent Kazakhstan faced challenges of a healthcare system in transition. Anatomic pathology practice remains one of the least developed medical specialties in Kazakhstan. Acute shortage of ... ...

Abstract	In 1991, after the dissolution of the Soviet Union, newly independent Kazakhstan faced challenges of a healthcare system in transition. Anatomic pathology practice remains one of the least developed medical specialties in Kazakhstan. Acute shortage of pathologists is a universal phenomenon. There is no subspecialty pathology practice as yet. Residency programs in anatomic pathology are found only in a few tertiary health institutions in the big cities. Nazarbayev University School of Medicine was established in 2015 to reform medical education in Kazakhstan. Prior to this time, in 2010, Nazarbayev University was established to lead higher education reforms in the country. Each school in Nazarbayev University was paired with an international partner to jump-start its trajectory to excellence. Establishing a new residency program in anatomic pathology based on a western pedagogy was a new innovation that needed multi-level stakeholder consultation and support. In partnership with the University of Pittsburgh School of Medicine and its hospital system, the University of Pittsburgh Medical Center, we established the first residency program in anatomic pathology based on the Accreditation Council for Graduate Medical Education International standards in Central Asia. We have identified 5 strategic approaches that led to our rapid success, including targeted strategic partnership; robust engagement with the local stakeholders; adoption and contextualizing of an existing pedagogy; ensuring adequate and fit-for-purpose infrastructure; and organizational restructuring and optimization. We hope that these suggestions will be translatable to help those facing the arduous but exciting task of establishing a new residency program from scratch.
Language	English
Publishing date	2024-04-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2819382-9
ISSN	2374-2895
ISSN	2374-2895
DOI	10.1016/j.acpath.2024.100121
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Article ; Online: Morphological characteristics of SETD2-mutated locally advanced clear cell renal cell carcinoma: Comparison with BAP1-mutated clear cell renal cell carcinoma.

Takeda, Kotaro / Bastacky, Sheldon / Dhir, Rajiv / Mohebnasab, Maedeh / Quiroga-Garza, Gabriela M

Annals of diagnostic pathology

2023 Volume 68, Page(s) 152223

Abstract: SET-domain containing 2 (SETD2) and BRCA1-associated protein 1 (BAP1), both chromatin remodeling genes, are frequently mutated in clear cell renal cell carcinoma (ccRCC) and involved in tumor progression and metastasis. Herein, we studied ... ...

Abstract	SET-domain containing 2 (SETD2) and BRCA1-associated protein 1 (BAP1), both chromatin remodeling genes, are frequently mutated in clear cell renal cell carcinoma (ccRCC) and involved in tumor progression and metastasis. Herein, we studied clinicopathologic features of 7 cases of locally advanced ccRCC with single SETD2 mutation, and compared to 7 cases of locally advanced ccRCC with single BAP1 mutation. SETD2-mutated ccRCC showed high-grade transformation, comprising of enlarged tumor cells with voluminous clear cytoplasm, enlarged irregular nuclei with prominent nucleoli, eosinophilic cytoplasmic granules, arranged in various architectural patterns such as large nested, tubular, tubulopapillary and solid. 71 % (5 of 7 cases) of SETD2-mutated ccRCC showed a rhabdoid morphology. SETD2-mutated ccRCC have striking propensity for invasive growth; all cases have vascular invasion and perirenal (extracapsular) adipose tissue invasion. After nephrectomy, distant metastasis was found in 67 % (4 of 7 cases) of patients with SETD2-mutated ccRCC. The most common metastatic site was the lung (3 cases), followed by precaval lymph nodes (1 case). BAP1-mutated ccRCC also showed a similar high-grade morphology, with rhabdoid and/or sarcomatoid features. Their high-grade features mostly overlapped with those of SETD2-mutated ccRCC, which makes difficult to predict the presence of BAP1 or SETD2 mutation solely from morphology. These findings justify the use of molecular testing to detect these mutations, especially when we encounter high-grade ccRCC. Detecting SETD2 and BAP1 mutation in ccRCC is useful for risk stratification and proper therapeutic strategy.
MeSH term(s)	Humans ; Carcinoma, Renal Cell/pathology ; DNA-Binding Proteins/genetics ; Kidney Neoplasms/pathology ; Mutation ; Transcription Factors/genetics ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics
Chemical Substances	BAP1 protein, human ; DNA-Binding Proteins ; Transcription Factors ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase (EC 3.4.19.12) ; SETD2 protein, human (EC 2.1.1.43)
Language	English
Publishing date	2023-11-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1440011-x
ISSN	1532-8198 ; 1092-9134
ISSN (online)	1532-8198
ISSN	1092-9134
DOI	10.1016/j.anndiagpath.2023.152223
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Article ; Online: The osteoclast-type giant cell rich carcinoma of urinary bladder: A case series.

Satturwar, Swati / Parwani, Anil V / Thomas, Roby / Bastacky, Sheldon / Dhir, Rajiv / Quiroga-Garza, Gabriela M

Pathology, research and practice

2022 Volume 239, Page(s) 154164

Abstract: Background: Osteoclast-type giant cell-rich carcinomas (OGCRCs) of urinary bladder are extremely rare, aggressive tumors that are often diagnosed as undifferentiated carcinomas. The morphology overlaps with other giant cell-rich benign and malignant ... ...

Abstract	Background: Osteoclast-type giant cell-rich carcinomas (OGCRCs) of urinary bladder are extremely rare, aggressive tumors that are often diagnosed as undifferentiated carcinomas. The morphology overlaps with other giant cell-rich benign and malignant bladder lesions. Little is known about the pathogenesis and clinical management of this aggressive variant. The aim of this study was to review clinico-pathologic features, and survival characteristics in a series of OGCRCs. Materials and methods: Five cases of OGCRCs of bladder were retrospectively reviewed. Clinical presentation, histomorphology, ancillary tests, treatment and follow-up data were retrieved and analyzed. Results: All patients were adult males (age range 63-86 years) and presented with painless gross hematuria. All cases showed biphasic morphology with polygonal to epithelioid to spindle mononuclear cells (MCs) and scattered multinucleated osteoclast-like giant cells (OGCs). Background urothelium showed urothelial carcinoma in-situ (CIS) (4/5) and/or invasive urothelial carcinoma (UC) (2/5) and invasive high-grade papillary urothelial carcinoma (PUC) (2/5). MCs showed focal expression of at least one epithelial marker and focal/diffuse expression of urothelial markers. OGCs were positive only for histiocytic markers. Oncomine test showed presence of p53 mutation (p.R282W) in case 3. Pathologic stage was T1 (n = 3), T2b (n = 1) and T3a (n = 1). 2/5 patients died of disease within 3 years of diagnosis. Conclusions: OGCRC is an extremely rare and potentially aggressive malignant neoplasm of bladder. Most cases have associated conventional in-situ or invasive UC supporting undifferentiated or de-differentiated nature of this neoplasm. Surgery should be considered given the potential for aggressive behavior. However optimal treatment for OGCRCs remains unknown.
MeSH term(s)	Adult ; Male ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Carcinoma, Transitional Cell/pathology ; Urinary Bladder/pathology ; Urinary Bladder Neoplasms/pathology ; Osteoclasts/pathology ; Retrospective Studies ; Urothelium/pathology ; Giant Cells/pathology
Language	English
Publishing date	2022-10-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	391889-0
ISSN	1618-0631 ; 0344-0338
ISSN (online)	1618-0631
ISSN	0344-0338
DOI	10.1016/j.prp.2022.154164
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Article ; Online: Intravesical Contrast-Enhanced MRI: A Potential Tool for Bladder Cancer Surveillance and Staging.

Tyagi, Pradeep / Moon, Chan-Hong / Connell, Marc / Ganguly, Anirban / Cho, Kang Jun / Tarin, Tatum / Dhir, Rajiv / Sholosh, Biatta / Maranchie, Jodi

Current oncology (Toronto, Ont.)

2023 Volume 30, Issue 5, Page(s) 4632–4647

Abstract: This review article gives an overview of the current state of the art of bladder cancer imaging and then discusses in depth the scientific and technical merit of a novel imaging approach, tracing its evolution from murine cancer models to cancer patients. ...

Abstract	This review article gives an overview of the current state of the art of bladder cancer imaging and then discusses in depth the scientific and technical merit of a novel imaging approach, tracing its evolution from murine cancer models to cancer patients. While the poor resolution of soft tissue obtained by widely available imaging options such as abdominal sonography and radiation-based CT leaves them only suitable for measuring the gross tumor volume and bladder wall thickening, dynamic contrast-enhanced magnetic resolution imaging (DCE MRI) is demonstrably superior in resolving muscle invasion. However, major barriers still exist in its adoption. Instead of injection for DCE-MRI, intravesical contrast-enhanced MRI (ICE-MRI) instills Gadolinium chelate (Gadobutrol) together with trace amounts of superparamagnetic agents for measurement of tumor volume, depth, and aggressiveness. ICE-MRI leverages leaky tight junctions to accelerate passive paracellular diffusion of Gadobutrol (604.71 Daltons) by treading the paracellular ingress pathway of fluorescein sodium and of mitomycin (<400 Daltons) into bladder tumor. The soaring cost of diagnosis and care of bladder cancer could be mitigated by reducing the use of expensive operating room resources with a potential non-surgical imaging option for cancer surveillance, thereby reducing over-diagnosis and over-treatment and increasing organ preservation.
MeSH term(s)	Humans ; Animals ; Mice ; Neoplasm Staging ; Magnetic Resonance Imaging/methods ; Urinary Bladder Neoplasms/diagnostic imaging ; Organometallic Compounds
Chemical Substances	gadobutrol (1BJ477IO2L) ; Organometallic Compounds
Language	English
Publishing date	2023-04-30
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	1236972-x
ISSN	1718-7729 ; 1198-0052
ISSN (online)	1718-7729
ISSN	1198-0052
DOI	10.3390/curroncol30050350
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Article: Prostate cancer biobanking.

Dhir, Rajiv

Current opinion in urology

2008 Volume 18, Issue 3, Page(s) 309–314

Abstract: Purpose of review: This review is intended to provide an overview of 'best practices' pertaining to prostate biobanking. It addresses issues related to collection and appropriate annotation of prostate samples, ethics and administrative aspects of ... ...

Abstract	Purpose of review: This review is intended to provide an overview of 'best practices' pertaining to prostate biobanking. It addresses issues related to collection and appropriate annotation of prostate samples, ethics and administrative aspects of biorepository functioning. Recent findings: Paraffin tissue microarrays have emerged as a significant mechanism for high throughput evaluation of markers of interest. In addition, modification of guidelines and definitions of 'human research' have served to provide mechanisms for expediting biological specimen disbursement. Summary: A well developed biobank is a critical prerequisite for high-quality research. This review provides an outline of certain critical elements that would need careful attention as a prostate cancer biobank is developed.
MeSH term(s)	Biomarkers, Tumor/analysis ; Humans ; Male ; Prostatic Neoplasms/pathology ; Tissue Banks
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2008-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1091792-5
ISSN	1473-6586 ; 0963-0643
ISSN (online)	1473-6586
ISSN	0963-0643
DOI	10.1097/MOU.0b013e3282fb7cbe
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Zs.A 3345: Show issues

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Article: Tissue microarrays: an overview.

Dhir, Rajiv

Methods in molecular biology (Clifton, N.J.)

2008 Volume 441, Page(s) 91–103

Abstract: Traditionally, screening for new markers involves using a slide from each of several different patients. A more efficient way is to have one slide that contains several minute specimens, one from each patient. These slides are prepared by transferring ... ...

Abstract	Traditionally, screening for new markers involves using a slide from each of several different patients. A more efficient way is to have one slide that contains several minute specimens, one from each patient. These slides are prepared by transferring paraffin tissue cores from many "donor" blocks to one "recipient" block. Each slide cut from this recipient block is called a tissue microarray (TMA) slide. It can have various histological types of disease that need to be compared or can have the same histological type but different behavior (e.g., responders versus non-responders, etc.). TMAs are ideal for efficient screening of prospective biomarkers by a variety of different mechanisms including immunohistochemistry, fluorescence in situ hybridization of nucleic acids (FISH) and RNA in situ hybridization. Selection and number of cases from patient subsets in a given microarray slide is amenable to statistical modeling to enhance analysis of results. In addition, different microarrays can be constructed to answer different scientific questions. The microarrays can also be produced from retrospective paraffin blocks of well-characterized cases, with clinical follow-up. The TMA slides can be "whole-slide" imaged. This provides a mechanism to share results of experiments with other investigators. There are also ongoing efforts to generate software tools for automated analysis of TMA localization data. There has also been a significant body of work done to standardize data capture, thus facilitating subsequent exchange of information. The preferred current mechanism is to use an "XLM"-based data capture and transfer. There have also been efforts to create "frozen" TMAs. This has been attempted using "donor" frozen tissues embedded in OCT compound. These samples are then arrayed into a recipient OCT block. The presence of OCT can sporadically interfere with certain assays. However, it does provide a novel mechanism for high-throughput evaluation of frozen tissue, with corresponding visualization of tissue morphology.
MeSH term(s)	Automation ; Biopsy ; Cell Culture Techniques ; DNA/analysis ; DNA/genetics ; Freezing ; Humans ; Microarray Analysis/methods ; Neoplasms/genetics ; Neoplasms/pathology ; Proteins/analysis ; Proteins/genetics ; RNA/analysis ; RNA/genetics
Chemical Substances	Proteins ; RNA (63231-63-0) ; DNA (9007-49-2)
Language	English
Publishing date	2008
Publishing country	United States
Document type	Journal Article
ISSN	1064-3745
ISSN	1064-3745
DOI	10.1007/978-1-60327-047-2_6
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Article: Abnormal expression of Rab27B in prostatic epithelial cells of benign prostatic hyperplasia alters intercellular communication

Dai, Yu / Ai, Bo / Liu, Ying / Pascal, Laura E / Wang, Zhou / Dhir, Rajiv / Sun, Xuegang / Jiang, Yu

international journal of biochemistry & cell biology. 2021 Feb., v. 131

2021

Abstract: Abnormal intraglandular stromal-epithelial interactions have been known as a main key contributing factor for development of Benign Prostatic Hyperplasia (BPH). However, the underlying mechanism for the dysregulated intercellular communication remains ... ...

Abstract	Abnormal intraglandular stromal-epithelial interactions have been known as a main key contributing factor for development of Benign Prostatic Hyperplasia (BPH). However, the underlying mechanism for the dysregulated intercellular communication remains unclear. In this study we compared the proteomic profiles of hyperplastic tissue with adjacent normal tissue of BPH and identified Rab27B small GTPase, a key regulator of exocytosis, as a protein that was overexpressed in the epithelium of BPH tissue. Overexpression of Rab27B in prostatic epithelial cells strongly increased the signaling activities of the PI3K/AKT and ERK1/2 pathways, whereas, downregulation of Rab27B expression in the epithelial cells of BPH reduced the signaling activities and decreased cell proliferation. The elevated Rab27B expression caused an overall increase in cell surface presentation of growth factor receptors without affecting their expression. However, the small GTPase also possesses an inhibitory activity against mTORC1 independent of its role in cell surface presentation of growth factor receptors. Our findings demonstrate a pivotal role of the small GTPase in autocrine and paracrine signaling and suggest that its abnormal expression underlies the dysregulated stromal-epithelial interactions in BPH.
Keywords	autocrine signaling ; cell proliferation ; epithelium ; exocytosis ; guanosinetriphosphatase ; hyperplasia ; proteomics
Language	English
Dates of publication	2021-02
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	1228429-4
ISSN	1878-5875 ; 1357-2725
ISSN (online)	1878-5875
ISSN	1357-2725
DOI	10.1016/j.biocel.2020.105898
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Data Representation, Coding, and Communication Standards.

Amin, Milon / Dhir, Rajiv

Surgical pathology clinics

2015 Volume 8, Issue 2, Page(s) 109–121

Abstract: The immense volume of cases signed out by surgical pathologists on a daily basis gives little time to think about exactly how data are stored. An understanding of the basics of data representation has implications that affect a pathologist's daily ... ...

Abstract	The immense volume of cases signed out by surgical pathologists on a daily basis gives little time to think about exactly how data are stored. An understanding of the basics of data representation has implications that affect a pathologist's daily practice. This article covers the basics of data representation and its importance in the design of electronic medical record systems. Coding in surgical pathology is also discussed. Finally, a summary of communication standards in surgical pathology is presented, including suggested resources that establish standards for select aspects of pathology reporting.
MeSH term(s)	Clinical Coding/methods ; Clinical Coding/standards ; Communication ; Documentation/methods ; Documentation/standards ; Electronic Health Records/standards ; Humans ; Information Storage and Retrieval/methods ; Information Storage and Retrieval/standards ; Interdisciplinary Communication ; International Classification of Diseases ; Pathology, Surgical/methods ; Pathology, Surgical/standards ; Terminology as Topic
Language	English
Publishing date	2015-06
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1875-9157
ISSN (online)	1875-9157
DOI	10.1016/j.path.2015.02.001
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Article ; Online: Calyceal diverticula: Clinical, radiological and histopathological findings of an uncommon entity with presumed congenital origin.

Srivastava, Pooja / Satturwar, Swati / Bastacky, Sheldon / Dhir, Rajiv / Reyes-Múgica, Miguel / Beasley, H Scott / Quiroga-Garza, Gabriela M

Annals of diagnostic pathology

2022 Volume 58, Page(s) 151932

Abstract: Calyceal diverticula (CD) are relatively uncommon urologic conditions that generally follow an asymptomatic course and rarely require medical intervention. CD are thought to have a congenital origin due to abnormalities during the process of ureteral bud ...

Abstract	Calyceal diverticula (CD) are relatively uncommon urologic conditions that generally follow an asymptomatic course and rarely require medical intervention. CD are thought to have a congenital origin due to abnormalities during the process of ureteral bud formation. Clinically and radiologically, they can mimic multiple neoplastic and non-neoplastic renal processes, with potentially relevant differences in the management of these patients. Symptoms are usually associated with the presence of stones, obstruction to the drainage of the diverticulum, large size, or secondary infection. In chronic cases, surgery might become necessary, creating an opportunity to examine the histopathological characteristics of this condition. Although these are benign in the majority of patients, some rare instances of malignancy arising from the CD have been reported. In this series, we addressed the clinical, radiological, and histopathological findings of CD.
MeSH term(s)	Cysts/pathology ; Diverticulum/diagnostic imaging ; Humans ; Kidney/diagnostic imaging ; Kidney Calices/diagnostic imaging ; Kidney Calices/pathology ; Kidney Calices/surgery ; Kidney Neoplasms/pathology
Language	English
Publishing date	2022-03-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1440011-x
ISSN	1532-8198 ; 1092-9134
ISSN (online)	1532-8198
ISSN	1092-9134
DOI	10.1016/j.anndiagpath.2022.151932
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Article ; Online: Malignant germ cell tumors in men aged 50 years and over are associated with adverse pathologic features and higher stage at presentation.

Almutairi, Fawaz / Geisler, Daniel / Rammal, Rayan / Korentzelos, Dimitrios / Bastacky, Sheldon / Dhir, Rajiv / Bhattu, Amit / Quiroga-Garza, Gabriela M

Annals of diagnostic pathology

2022 Volume 62, Page(s) 152070

Abstract: Background: Germ cell tumors (GCT) are the most common malignancy in men in the third and fourth decades of life. The occurrence of malignant GCT in men aged 50 years or over is rare, and their histopathologic characteristics and outcome is ... ...

Abstract	Background: Germ cell tumors (GCT) are the most common malignancy in men in the third and fourth decades of life. The occurrence of malignant GCT in men aged 50 years or over is rare, and their histopathologic characteristics and outcome is insufficiently characterized in the medical literature. Hence, we report the histopathologic features and clinical outcome of malignant GCTs in men aged ≥50 years at our institution. Design: We performed a retrospective search of our database from 2005 to 2021 to identify men aged 50 years or older with malignant GCT. Cases of spermatocytic tumor were excluded. Clinical and histopathologic features of the tumors were reviewed. Results: Forty-seven cases were identified, showing a sharp decline in incidence over the age of 65. Thirty-nine (83 %) tumors were testicular while eight (17 %) were non-testicular in presentation. Cases included 26 (55 %) seminomas, 15 (32 %) non-seminoma/mixed malignant GCT, and 5 (11 %) regressed testicular germ cell tumors. The most common component in mixed malignant GCTs was embryonal carcinoma (77 %), followed by seminoma and yolk sac tumor (62 % each). Germ cell neoplasia in situ (GCNIS) accompanied 57 % of the cases. Aggressive pathologic features, including lymphovascular invasion, retroperitoneal/lymph node involvement and higher stage at presentation, were identified in a significant proportion of cases (36/47, 77 %). Clinical follow up showed six patients (14 %) died of disease-related causes. Conclusion: Our findings expand and corroborate the previously reported data on malignant GCT in older men. Unique characteristics include tendency for higher stage at presentation with adverse pathologic features and more aggressive clinical course.
Language	English
Publishing date	2022-11-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	1440011-x
ISSN	1532-8198 ; 1092-9134
ISSN (online)	1532-8198
ISSN	1092-9134
DOI	10.1016/j.anndiagpath.2022.152070
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