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Aims: To review our experience with metastases to the kidney in surgical pathology material., Methods and Results: The clinicopathological features of all metastases to the kidney in surgical pathology cases between May 1987 and May 2013 at our institution were reviewed. Autopsy cases were excluded. Forty-three cases (16 nephrectomies, 25 biopsies, and two fine needle aspirations) were included; the primary malignancy was diagnosed prior to/concurrently with the metastasis in nearly all cases. Common primary sites included the lung, breast, female genital tract, and head and neck; the majority were carcinomas. A primary renal tumour was suspected prior to the pathological diagnosis in 35% of cases. Unusual features included: common unilateral (77%) and unifocal (70%) involvement, lack of other distant organ metastases (37%), >10 years between primary and metastasis diagnoses (19%), lack of a discrete mass (5%), and renal vein extension (19% of resections). The most common dilemma was excluding urothelial or high-grade renal cell carcinoma; however, metastases from the thyroid commonly mimicked low-grade renal cell carcinomas., Conclusions: In surgical pathology material, metastases to the kidney most commonly present as solitary unilateral masses, and in a substantial subset of cases mimic a primary renal tumour., (© 2014 John Wiley & Sons Ltd.)

Aims: We performed a head-to-head comparison of an antibody against uroplakin III (UP3) and a new uroplakin II (UP2) antibody that remains untested in diagnostically challenging settings., Methods and Results: We immunostained high-grade bladder neck carcinomas (n = 35), high-grade upper tract urothelial carcinomas (UC) and renal carcinomas (n = 85), metastases of UC (n = 30) and a multicancer tissue microarray (n = 88) for UP3 and UP2, and scored staining intensity and proportion. UP3 showed membranous plaque-like expression, while UP2 staining showed both membranous and cytoplasmic positivity. Significantly greater intensity (P = 0.003) and proportion (P = 0.03) of staining was noted for UP2 among bladder neck lesions, with UP2 staining showing greater sensitivity (63% versus 19%) and similar specificity (95% versus 100%) for UC over prostate carcinoma (P = 0.02). Among upper tract lesions, UP2 staining showed greater intensity and proportion than UP3 (both P < 0.001), including improved sensitivity (68% versus 23%) and equal specificity (both 100%) for UC (P = 0.006). Among UC metastases, UP2 staining showed greater intensity and proportion (both P < 0.001) with higher sensitivity (73% versus 37%, respectively, P = 0.001). Of 88 additional cases tested, no non-urothelial cases stained for either UP., Conclusions: The UP2 antibody outperforms the UP3 antibody, including in diagnostically challenging settings, and is a useful addition to the armamentarium of biomarkers for UC., (© 2014 John Wiley & Sons Ltd.)

Identification of new molecular markers has led to the molecular classification of prostate cancer based on driving genetic lesions. The translation of these discoveries for clinical use necessitates the development of simple, reliable and rapid detection systems to screen patients for specific molecular aberrations. We developed two dual-color immunohistochemistry-based assays for the simultaneous assessment of ERG-PTEN and ERG-SPINK1 in prostate cancer. A total of 232 cases from 184 localized and 48 metastatic prostate cancers were evaluated for ERG-PTEN and 284 cases from 228 localized and 56 metastatic prostate cancers were evaluated for ERG-SPINK1. Of the 232 cases evaluated for ERG-PTEN, 81 (35%) ERG-positive and 77 (33%) PTEN-deleted cases were identified. Of the 81 ERG-positive cases, PTEN loss was confirmed in 35 (15%) cases by fluorescence in situ hybridization (FISH). PTEN status was concordant in 203 cases (sensitivity 90% and specificity 87%; P<0.0001) by both immunohistochemisty and FISH; however, immunohistochemisty could not distinguish between heterozygous and homozygous deletion status of PTEN. Of the 284 cases evaluated for ERG-SPINK1, 111 (39%) cases were positive for ERG. In the remaining 173 ERG-negative cases, SPINK1 was positive in 26 (9%) cases. SPINK1 expression was found to be mutually exclusive with ERG expression; however, we identified two cases, of which one showed concomitant expression of ERG and SPINK1 in the same tumor foci, and in the second case ERG and SPINK1 were seen in two independent foci of the same tumor nodule. Unlike the homogenous ERG staining in cancer tissues, heterogeneous SPINK1 staining was observed in the majority of the cases. Further studies are required to understand the molecular heterogeneity of cases with concomitant ERG-SPINK1 expression. Automated dual ERG-PTEN and ERG-SPINK1 immunohistochemisty assays are simple, reliable and portable across study sites for the simultaneous assessment of these proteins in prostate cancer.

We report the case of a high-grade carcinoma involving the kidney in a young male with renal vein thrombosis and review the differential diagnosis and immunohistochemical workup. High-grade neoplasms involving the renal sinus include collecting duct carcinomas (CDCs), renal medullary carcinomas (RMCs), invasive high-grade urothelial carcinoma (UC) of the upper urinary tract, clear cell renal cell carcinoma, and type 2 papillary renal cell carcinoma. Distinguishing UC from CDC and RMC is problematic in small biopsy samples. The diagnosis of CDC (a rare, aggressive subtype of renal cell carcinoma) is challenging and requires the exclusion of UC. Renal medullary carcinoma is characterized by an appropriate clinical setting and consistent loss of nuclear expression of integrase interactor 1 (INI-1). A panel consisting of p63, paired box gene 8 (PAX8), and INI-1 is most optimal in distinguishing UC from CDC and RMC. A subset of urothelial carcinoma of upper urinary tract may be positive with PAX8.

We evaluated the diagnostic usefulness of the 34betaE12-p63 cocktail, compared with 34betaE12 and p63 used alone, in 34 prostate needle biopsy (NBXs) and 3 transurethral resection specimens containing atypical glandular proliferations and in 18 NBXs containing unequivocal prostate carcinoma (PCa). Staining intensity; percentage of basal cells staining in benign, atypical, and malignant glands; number of benign glands lacking basal cell staining; and staining variance were analyzed. All NBXs with unequivocal PCa were negative with all 3 markers. Diagnoses were as follows for the atypical cases after staining for the 3 markers: PCa, 9; postatrophic hyperplasia, 12; high-grade prostatic intraepithelial neoplasia (HGPIN), 5; atypical adenomatous hyperplasia, 6; benign atypical proliferations, 4; and HGPIN with adjacent small atypical acinar proliferation suggestive of PCa, 1. The cocktail demonstrated consistently strong staining intensity and improved basal cell staining in morphologically benign and benign atypical glands compared with p63 and 34betaE12 alone; it had the smallest staining variance compared with 34betaE12 (F < 0.0001) and p63 (F = 0.31), although its advantage for resolving individual atypical cases was limited compared with 34betaE12 and p63 alone. Of 37 atypical cases, 1 (3%) additionally was resolved as benign using the cocktail and p63. Because the diagnosis of PCa is supported by lack of basal cell staining, the immunohistochemical analysis with highest possible sensitivity and lowest possible variability is critical to ensure that a negative reaction is true. The cocktail provides a simple, cost-effective improvement in basal cell immunohistochemical analysis of difficult prostate lesions.

Aims: Renal cell carcinoma (RCC) with clear cells and psammoma‐like calcifications would often raise suspicion for MITF family translocation RCC. However, we have rarely encountered tumours consistent with clear cell RCC that contain focal psammomatous calcifications. Methods and results: We identified clear cell RCCs with psammomatous calcifications from multiple institutions and performed immunohistochemistry and fluorescence and RNA in‐situ hybridisation (FISH and RNA ISH). Twenty‐one tumours were identified: 12 men, nine women, aged 45–83 years. Tumour size was 2.3–14.0 cm (median = 6.75 cm). Nucleolar grade was 3 (n = 14), 2 (n = 4) or 4 (n = 3). In addition to clear cell pattern, morphology included eosinophilic (n = 12), syncytial giant cell (n = 4), rhabdoid (n = 2), branched glandular (n = 1), early spindle cell (n = 1) and poorly differentiated components (n = 1). Labelling for CA9 was usually 80–100% of the tumour cells (n = 17 of 21), but was sometimes decreased in areas of eosinophilic cells (n = 4). All (19 of 19) were positive for CD10. Most (19 of 20) were positive for AMACR (variable staining = 20–100%). Staining was negative for keratin 7, although four showed rare positive cells (four of 20). Results were negative for cathepsin K (none of 19), melan A (none of 17), HMB45 (none of 17), TFE3 (none of 5), TRIM63 RNA ISH (none of 13), and TFE3 (none of 19) and TFEB rearrangements (none of 12). Seven of 19 (37%) showed chromosome 3p deletion. One (one of 19) showed trisomy 7 and 17 without papillary features. Conclusions: Psammomatous calcifications in RCC with a clear cell pattern suggests a diagnosis of MITF family translocation RCC; however, psammomatous calcifications can rarely be found in true clear cell RCC. [ABSTRACT FROM AUTHOR]

The distinction between tubular carcinomas (TC) and invasive well-differentiated (grade 1) ductal carcinoma (IDC) is important given treatment and prognostic differences. Studies have described a strong association between flat epithelial atypia (FEA) and TC. The incidence of FEA associated with grade 1 IDC is not well established. The aim of the present study was to assess morphology and intra-epithelial lesions between 14 TC and 18 grade 1 IDC matched for size. Of 14 TC, eight (57%) had associated FEA, seven (50%) had micropapillary atypical ductal hyperplasia (ADH), three (21%) had low nuclear grade ductal carcinoma in situ (DCIS), and four (29%) had lobular neoplasia. Notably, only two of 18 (11%) grade 1 IDC had associated FEA. Three of 18 (16%) grade 1 IDC had ADH, two (11%) had lobular neoplasia, and seven (39%) had DCIS. All tubular carcinomas were estrogen receptor (ER) positive and negative for Her-2/neu overexpression. All grade 1 IDC were ER positive but 5% also overexpressed Her-2/neu. Axillary lymph node metastasis was present in 11% of grade 1 IDC and absent in TC. A strong association was found between TC, FEA, and micropapillary ADH, which may reflect a biological progression. Despite matching for tumor size, grade 1 IDC have a higher incidence of lymph node metastasis and may have Her-2-neu overexpression compared to TC. [ABSTRACT FROM AUTHOR]