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  • 1
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    Cathepsin K (Clone EPR19992) Demonstrates Uniformly Positive Immunoreactivity in Renal Oncocytoma, Chromophobe Renal Cell Carcinoma, and Distal Tubules
    SAGE Publications ; 2021
    In:  International Journal of Surgical Pathology Vol. 29, No. 6 ( 2021-09), p. 600-605
    Details
    In: International Journal of Surgical Pathology, SAGE Publications, Vol. 29, No. 6 ( 2021-09), p. 600-605
    Abstract: Introduction. Cathepsin K is overexpressed in several tumors associated with microphthalmia transcription factor (MiTF) family or mechanistic target of rapamycin (mTOR) upregulation. Among renal neoplasms, MiTF translocation renal cell carcinoma (RCC), perivascular epithelioid cell neoplasms (PEComa), and eosinophilic solid and cystic RCC have demonstrated Cathepsin K immunoreactivity. In this study, we demonstrate a uniform Cathepsin K expression in oncocytoma, chromophobe RCC (CHRCC), and distal tubules. Design. We stained 13 oncocytomas, 13 CHRCC, 14 clear cell RCC (CCRCC), 9 papillary RCC (PRCC), 9 PEComas, and 5 MiTF RCC. Additionally, we assessed immunoreactivity for Cathepsin K in non-neoplastic renal parenchyma. Immunolabeling was performed on regularly charged slides from formalin-fixed paraffin-embedded tissue with monoclonal anti-rabbit antibodies to human Cathepsin K (clone EPR19992, Abcam). Results. All oncocytomas demonstrated diffuse strong cytoplasmic immunolabeling. CHRCC demonstrated uniform less intense immunolabeling in all cases with membranous accentuation. The assessment of the non-neoplastic renal parenchyma in all cases showed strong cytoplasmic immunoreaction in distal tubules and proximal tubules stained faintly. Mesangial cells were not immunoreactive. All MiTF RCC and PEComas were immunoreactive for Cathepsin K, whereas CCRCC and PRCC were negative in all cases. Conclusions. In this study, we expand the spectrum of renal neoplasms reactive with a particular clone of Cathepsin K (EPR19992). Distal tubules are strongly immunoreactive for Cathepsin K. Our conclusions need to be taken into consideration when differential diagnosis includes MiTF RCC or PEComa and this Cathepsin K clone is included in the immunohistochemical panel. This newer antibody clone was not tested in prior publications, potentially explaining the difference in conclusions.
    Type of Medium: Online Resource
    ISSN: 1066-8969 , 1940-2465
    URL: Article
    DOI: 10.1177/1066896921991588
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 2
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    Patterns of Immunoreactivity with TTF-1 Antibodies 8G7G3/1 and SPT24 Suggest Distinct Immunoprofiles Between Most Pulmonary and Nonpulmonary Small Cell Carcinomas
    SAGE Publications ; 2023
    In:  International Journal of Surgical Pathology
    Details
    In: International Journal of Surgical Pathology, SAGE Publications
    Abstract: Introduction. Small cell carcinoma can arise from various sites. Herein, we analyze the ability of 2 thyroid transcription factor-1 (TTF-1) antibodies (SPT24 and 8G7G3/1) to separate pulmonary from nonpulmonary small cell carcinoma. Materials and Methods. We analyzed 26 pulmonary and 83 nonpulmonary small cell carcinomas, and 14 Merkel cell carcinomas. Each tumor was stained with SPT24 and 8G7G3/1. Extent of nuclear staining was scored as diffuse ( 〉 50%), focal (11%-50%), rare (1%-10%), or negative ( 〈 1%). Results. All pulmonary small cell carcinomas were positive for SPT24 and 8G7G3/1. Four Merkel cell carcinomas (29%) were positive for SPT24 (ranging from rare-to-diffuse), while 2 (14%) showed rare expression with 8G7G3/1. For nonpulmonary small cell carcinomas, 69 (83%) were positive for SPT24 and 40 (48%) were positive for 8G7G3/1. For SPT24 positive tumors, the extent of 8G7G3/1 expression was equal in 17 (25%) and less in 52 tumors (75%), including 29 (42%) that were negative for 8G7G3/1. No nonpulmonary small cell carcinoma had more staining with 8G7G3/1 compared to SPT24. The differences in staining between 8G7G3/1 and SPT24 in the nonpulmonary cohort were statistically significant ( P  〈  0.0001) with no significant difference between primary and metastatic lesions for 8G7G3/1 ( P  =  0.66) or SPT24 ( P  =  0.77). Conclusion. Most pulmonary small cell carcinomas are diffusely positive for both SPT24 and 8G7G3/1, whereas most nonpulmonary small cell carcinomas exhibit focal-to-no staining with 8G7G3/1 and significantly less staining with 8G7G3/1 compared to SPT24. However, these trends are not absolute and should be interpreted in conjunction with clinical and radiological findings.
    Type of Medium: Online Resource
    ISSN: 1066-8969 , 1940-2465
    URL: Article
    DOI: 10.1177/10668969231171940
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
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  • 3
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    Characterization of Fibromuscular Pseudocapsule in Renal Cell Carcinoma
    SAGE Publications ; 2015
    In:  International Journal of Surgical Pathology Vol. 23, No. 5 ( 2015-08), p. 359-363
    Details
    In: International Journal of Surgical Pathology, SAGE Publications, Vol. 23, No. 5 ( 2015-08), p. 359-363
    Abstract: Pseudocapsule in renal cell carcinoma (RCC) has been described but little is known about its prevalence and extent. Pseudocapsule was analyzed in 105 RCCs (44 clear cell, 44 chromophobe, 17 papillary). Pseudocapsule was graded as follows: grade 1, thickness comparable to adjacent muscular arteries; grade 2, thickness more than twice the diameter of adjacent muscular arteries; grade 3, grade 2 findings with vasculopathy. Tumor size, tumor regression, and International Society of Urologic Pathology (ISUP) nucleolar grade were recorded. Cases with grade 3 pseudocapsule were stained with elastic silver stain, Alcian blue, smooth muscle actin, and CD31. More clear cell RCCs had pseudocapsule (89%, 39/44) than chromophobe (30%, 13/44) and papillary (35%, 6/17). Average tumor size with pseudocapsule was 3.9 cm; average tumor size without pseudocapsule was 3.8 cm ( P = .77). Grade 2 pseudocapsule was common in clear cell RCC (56%, 22/39). Chromophobe and papillary RCC had grade 1 pseudocapsule in 77% (10/13) and 83% (5/6) of cases. Grade 3 pseudocapsule was only seen in clear cell RCC (10%, 4/39). No correlation was noted between degenerative tumor changes, tumor size, ISUP nucleolar grade, and presence and grade of pseudocapsule. Smooth muscle actin and CD31 showed abundant smooth muscle component and rich vasculature within the pseudocapsule. Arterial elastic membrane disruption and/or fibrointimal mucin deposits were present in grade 3 pseudocapsule. Thus, pseudocapsule is rather characteristic and more prominent in clear cell, less frequent in chromophobe, and rare in papillary RCC. Its presence may be evaluated radiologically or in biopsy specimens with scant tumor fragments.
    Type of Medium: Online Resource
    ISSN: 1066-8969 , 1940-2465
    URL: Article
    DOI: 10.1177/1066896915579198
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
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  • 4
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    Utility of GATA-3 and Cytokeratin 5/6 Immunostains in Separating Condyloma Acuminatum Arising in the Urinary Tract From Non-Invasive Papillary Urothelial Carcinoma
    SAGE Publications ; 2022
    In:  International Journal of Surgical Pathology Vol. 30, No. 3 ( 2022-05), p. 260-264
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    In: International Journal of Surgical Pathology, SAGE Publications, Vol. 30, No. 3 ( 2022-05), p. 260-264
    Abstract: Background Condyloma acuminatum is a squamous epithelial lesion which uncommonly involves the urinary tract. In this location, non-invasive papillary urothelial carcinoma constitutes one of the main differential diagnoses with significant prognostic and therapeutic implications. To date, no ancillary immunohistochemical stain has been described to differentiate these two entities. We assess the utility of cytokeratin 5/6 (CK5/6) and GATA-3 immunohistochemistry in distinguishing condyloma acuminatum from non-invasive papillary urothelial carcinoma. Design We reviewed 9 condylomata acuminata involving the urinary tract, 12 low-grade and 8 high-grade non-invasive papillary urothelial carcinomas. CK5/6 immunostaining was performed in all cases. GATA-3 immunostaining and low-risk human papilloma virus (HPV) chromogenic in situ hybridization was performed in all condyloma cases and 2 urothelial carcinomas with squamous differentiation. Results 8/9 condylomata acuminata were positive for low-risk HPV. All condylomata acuminata exhibited strong full-thickness cytoplasmic staining for CK5/6. In 10 of 12 low-grade non-invasive papillary urothelial carcinomas, CK5/6 expression was continuous and limited to the basal cell layer, while it was patchy and limited to the basal cell layer in all 8 high-grade non-invasive papillary urothelial carcinomas. Two low-grade non-invasive papillary urothelial carcinomas showed focal full-thickness CK5/6 expression in the areas of squamous differentiation. These 2 cases were negative for low-risk HPV. GATA-3 immunostaining was positive in all condylomata acuminata. Conclusions CK5/6 immunostaining is a useful and simple tool that can help separate low-grade and high-grade non-invasive papillary urothelial carcinomas from condyloma acuminatum involving the urothelium-lined organs. GATA-3 has no discriminatory role between condyloma acuminatum and papillary urothelial carcinomas.
    Type of Medium: Online Resource
    ISSN: 1066-8969 , 1940-2465
    URL: Article
    DOI: 10.1177/10668969211052235
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
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  • 5
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    Average Weight of Seminal Vesicles : An Adjustment Factor for Radical Prostatectomy Specimens Weighed With Seminal Vesicles
    SAGE Publications ; 2015
    In:  International Journal of Surgical Pathology Vol. 23, No. 8 ( 2015-12), p. 617-622
    Details
    In: International Journal of Surgical Pathology, SAGE Publications, Vol. 23, No. 8 ( 2015-12), p. 617-622
    Abstract: The International Society of Urological Pathology in 2010 recommended weighing prostates without seminal vesicles (SV) to include only prostate weight in prostate-specific antigen (PSA) density (PSAD) calculation, because SV do not produce PSA. Large retrospective cohorts exist with combined weight recorded that needs to be modified for retrospective analysis. Weights of prostates and SV were separately recorded in 172 consecutive prostatectomies. The average weight of SV and proportion of prostate weight from combined weight were calculated. The adjustment factors were then validated on databases of 2 other institutions. The average weight of bilateral SV was 6.4 g (range = 1-17.3 g). The prostate constituted on average 87% (range = 66% to 98%) of the total specimen weight. There was no correlation between patient age and prostate weight with SV weight. The best performing correction method was to subtract 6.4 g from total radical prostatectomy weight and to use this weight for PSAD calculation. The average weights of retrospective specimens weighed with SV were not significantly different between the 3 institutions. Using our data allowed calibration of the weights and PSAD between the cohorts weighed with and without SV. Thus, prostate weight in specimens including SV weight can be adjusted by subtracting 6.4 g, resulting in significant change of PSAD. Some institution-specific variations may exist, which could further increase the precision of retrospective analysis involving prostate weight and PSAD. However, unless institution-specific adjustment parameters are developed, we recommend that this correction factor be used for retrospective cohorts or in institutions where combined weight is still recorded.
    Type of Medium: Online Resource
    ISSN: 1066-8969 , 1940-2465
    URL: Article
    DOI: 10.1177/1066896915600519
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
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  • 6
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    Metastatic Clear Cell Renal Cell Carcinoma Involving the Thyroid Gland: A Clinicopathologic Study of 17 Patients
    SAGE Publications ; 2022
    In:  International Journal of Surgical Pathology Vol. 30, No. 7 ( 2022-10), p. 743-752
    Details
    In: International Journal of Surgical Pathology, SAGE Publications, Vol. 30, No. 7 ( 2022-10), p. 743-752
    Abstract: Background. Metastatic clear cell renal cell carcinoma (RCC) is one of the most common secondary thyroid malignancies. Diagnosis can be challenging, particularly if presenting many years after initial diagnosis. We reviewed clinicopathologic features and immunoprofile of metastatic clear cell RCC in thyroid. Design. We identified 17 patients from 2003-2021. Clinical data were obtained from medical records, and slides were retrieved and reviewed. Results. Seventeen patients (12 male and 5 female) included 12 thyroidectomies, 3 core biopsies, 1 excisional biopsy, and 1 fine-needle aspiration. The average patient age was 68.7 years (range, 45-88 years). Sixteen patients had history of clear cell RCC, and in 1 patient, the clear cell RCC was discovered after the thyroid metastasis was found. Thyroid gland metastases were on average diagnosed 90.7 months after the diagnosis of the renal primary (range, 24-240 months). Patients presented with a new palpable mass (n = 11) or dyspnea/stridor (n = 1). Five tumors were incidentally found via surveillance imaging. In 2 patients, metastases occurred within follicular thyroid neoplasms. All metastases showed conspicuous sinusoidal vasculature between the tumor nests and areas of myxoid degeneration. A prominent thick fibromuscular pseudocapsule was evident in 10 resections. Immunohistochemistry (n = 5) showed that the metastases were positive for PAX8, CA9, and CD10, while negative for keratin 7, thyroglobulin, and TTF1. Conclusions. Metastatic clear cell RCC involving the thyroid gland is infrequent and typically occurs remotely after the initial diagnosis. Cytologic and histologic features may show significant overlap with primary thyroid lesions. Immunohistochemistry can help reliably distinguish metastases from primary thyroid neoplasms.
    Type of Medium: Online Resource
    ISSN: 1066-8969 , 1940-2465
    URL: Article
    DOI: 10.1177/10668969221081729
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
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  • 7
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    Characteristics of Pelvic Lymph Node Metastases in Prostatic Adenocarcinoma : A Study of 83 Cases
    SAGE Publications ; 2012
    In:  International Journal of Surgical Pathology Vol. 20, No. 5 ( 2012-10), p. 449-454
    Details
    In: International Journal of Surgical Pathology, SAGE Publications, Vol. 20, No. 5 ( 2012-10), p. 449-454
    Abstract: Pelvic lymph node dissection (PLND) is currently the most accurate staging modality for lymph node metastases in prostate adenocarcinoma. There is no consensus on the optimal sampling method of PLND specimens among pathologists. This study analyzed the effectiveness of the submission of entire adipose tissue in 451 cases and its impact on total lymph node yield and detection of positive lymph nodes. The sizes of metastatic foci and positive lymph nodes in 83 cases were also studied. Submission of entire adipose tissue increased the lymph node yield and positive lymph node detection by 36.7 % and 1.99 %, respectively. Three cases had positive lymph nodes exclusively in adipose tissue. Of the patients examined, 68% had the largest positive lymph node, 〈 1 cm. In conclusion, it was noted that metastases from prostate cancer were frequently small and seen within small lymph nodes. Submission of entire adipose tissue substantially increased the lymph node yield, but its impact on the detection of additional positive lymph nodes was low. Submission of the entire adipose tissue may be considered as an option in patients with high-risk factors for lymph node metastases.
    Type of Medium: Online Resource
    ISSN: 1066-8969 , 1940-2465
    URL: Article
    DOI: 10.1177/1066896912445921
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2012
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  • 8
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    Experimental Support for the Possibility of Retrograde Genesis of Intraductal Carcinoma of the Prostate
    SAGE Publications ; 2023
    In:  International Journal of Surgical Pathology Vol. 31, No. 2 ( 2023-04), p. 184-189
    Details
    In: International Journal of Surgical Pathology, SAGE Publications, Vol. 31, No. 2 ( 2023-04), p. 184-189
    Abstract: Background. Historically, intraductal carcinoma of the prostate (IDC-P) was postulated to be a retrograde spread of high-grade invasive prostate cancer. There is evidence that IDC-P can primarily originate in the prostatic ducts. The retrograde genesis has never been experimentally or clinically confirmed before. Methods. Biopsy proven intermediate or high-risk prostate cancer was orthotopically grafted in the prostate of severe combined immunodeficiency gamma mice. Cancer growth was monitored by serum PSA levels. The animals were sacrificed and grafted areas were histological examined. Results. Twenty-one of 23 mice survived and demonstrated rising serum PSA. In 10 of 21 animals, human prostate cancer was identified orthotopically. Except for one case where the human biopsy showed a Grade Group 2 prostate cancer and mouse graft was Grade Group 5, other 9 specimens showed comparable grades. One of the specimens demonstrated a cribriform invasive prostate cancer and adjacent IDC-P. Conclusion. These experimental data offer some evidence that invasive prostate cancer can demonstrate a retrograde spread in the prostatic ducts as IDC-P. Its ability to primarily arise in the ducts has been demonstrated in other studies. However, the issue which remains unresolved is in its most common presentation of IDC-P intermixed with high-grade invasive cancer if it is the former or the latter which came first. Possibly resolving this dilemma will shed some light on the existing controversies if IDC-P should or should not be graded when invasive cancer is present.
    Type of Medium: Online Resource
    ISSN: 1066-8969 , 1940-2465
    URL: Article
    DOI: 10.1177/10668969221098080
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
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  • 9
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    Diagnostic Accuracy of Renal Mass Biopsy : An Ex Vivo Study of 100 Nephrectomy Specimens
    SAGE Publications ; 2016
    In:  International Journal of Surgical Pathology Vol. 24, No. 3 ( 2016-05), p. 213-218
    Details
    In: International Journal of Surgical Pathology, SAGE Publications, Vol. 24, No. 3 ( 2016-05), p. 213-218
    Abstract: We investigated the diagnostic accuracy of renal mass biopsy in an ex vivo model, as well as compared the agreement of the preoperative radiological diagnosis with the final pathologic diagnosis. Two 18-gauge needle-core and 2 vacuum-needle biopsies were performed ex vivo from the tumors of 100 consecutive patients undergoing radical nephrectomy between 2006 and 2010. The median tumor size was 5.5 cm. There was no significant difference with regard to cylinder length or tissue quality between the sampling methods. At least 1 of 4 needle cores contained diagnostic tissue in 88% of patients. Biopsy specimens identified clear cell (54%), papillary (13%), or chromophobe (5%) renal cell carcinoma; urothelial carcinoma (6%); oncocytoma (5%); liposarcoma (1%); metastatic colorectal carcinoma (1%); squamous cell carcinoma (1%); unclassified renal cell neoplasm (1%); and no tumor sampled (12%). The sensitivity of the biopsy for accurately determining the diagnosis was 88% (95% CI: 79% to 93%). The specificity was 100% (95% CI: 17% to 100%). Biopsy grade correlated strongly with final pathology (83.5% agreement). There was no difference in average tumor size in cases with the same versus higher grade on final pathology (5.87 vs 5.97; P = .87). Appraisal of tumor histology by radiology agreed with the pathologic diagnosis in 68% of cases. Provided that the biopsy samples the tumor tissue in a renal mass, pathologic analysis is of great diagnostic value in respect of grade and tumor type and correlates well with excisional pathology. This constitutes strong ground for increasingly used renal mass biopsy in patients considering active surveillance or ablation therapy.
    Type of Medium: Online Resource
    ISSN: 1066-8969 , 1940-2465
    URL: Article
    DOI: 10.1177/1066896915625178
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
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  • 10
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    Angiolipoma of the Female Breast: Clinicomorphological Correlation of 52 Cases
    SAGE Publications ; 2011
    In:  International Journal of Surgical Pathology Vol. 19, No. 1 ( 2011-02), p. 35-43
    Details
    In: International Journal of Surgical Pathology, SAGE Publications, Vol. 19, No. 1 ( 2011-02), p. 35-43
    Abstract: The authors analyzed 52 cases of female breast angiolipoma (AL). Age distribution was 25 to 80 years of age (56.81 ± 12.78). Most cases showed vascularity below 50%, and 14 cases had vascularity 〉 50%. Cellular and low-vascularity ALs had different clinical and radiological presentations. The mean size was 7.00 ± 3.62 mm for cellular ALs and 19.61 ± 7.58 mm for low-vascularity ALs. In any paucicellular area, the authors could identify a cluster of at least 3 interconnected vessels. The endothelium was mostly flat with uniform, hyperchromatic nuclei, and mitoses and nucleoli were absent. Fibrin thrombi in proliferating capillaries were noted in 96% of cases. Low-vascularity AL can be reliably distinguished on needle core biopsy from other lipomatous and vascular tumors of the breast. Tortuosity and proliferation of capillaries with at least 3 interconnected capillary channels in 1 focus with associated fibrin thrombi constitute a very strong clue for the diagnosis of AL on a breast needle core biopsy. Definite diagnosis of cellular AL is not always feasible because of rare cases with mitotic activity and cellular atypia. Excision is often recommended for cellular AL.
    Type of Medium: Online Resource
    ISSN: 1066-8969 , 1940-2465
    URL: Article
    DOI: 10.1177/1066896910385679
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2011
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