Biopsy Specimens Of Carcinoma Research Articles

Human epidermal growth factor receptor 2/neu expression in urothelial carcinomas.

Urothelial carcinomas of the bladder are more common in males, making them the sixth-most common cancer in men and the tenth-most common cancer overall, worldwide. Current guidelines do not recommend routine testing for human epidermal growth factor receptor (HER2/neu) expression on the biopsy specimens of patients with urothelial carcinoma. This study was aimed at determining the expression pattern of HER2/neu and its usefulness in muscle-invasive and nonmuscle-invasive urothelial carcinoma. HER2/neu expression was assessed in 89 specimens of urothelial cancer by immunohistochemistry (IHC), and equivocal cases were subjected to fluorescent in situ hybridization (FISH). On IHC for HER2/neu, 17.9% (7/39) of the muscle-invasive bladder cancers (MIBCs) showed a 3+ expression, whereas 22% (11/50) of the non-muscle invasive cancers were positive with a score of 3+. A significant correlation between HER2/neu status and muscle invasion could not be established in the current study (P = 0.74, Fisher's exact test). Three cases of muscle-invasive (7.7%) and 2 cases (4%) among nonmuscle invasive cancers showed equivocal expression. All the cases with equivocal (2+) expression on IHC were subjected to FISH and none showed gene amplification on hybridization and were considered as negative. Overexpression of HER-2/neu was seen in 17.9% of MIBCs and 22% of non-MIBCs. There are no norms for routine testing of HER2/neu expression in the biopsy specimens of urothelial carcinoma. There is an unmet need to establish guidelines for HER2/neu scoring, similar to that for breast and gastric cancers, to determine the proportion of positive cases and help in identification of those who may benefit from targeted therapies.

Isovalerylglycine and α-Ketobutyrate are novel biomarkers that discriminate clear cell renal cell carcinoma in biopsy specimens using two-dimensional magnetic resonance spectroscopy

Tumor heterogeneity and lack of pre-operative diagnostic biomarkers are key topics in the field of renal cell carcinoma (RCC) identification. Clear cell RCC (ccRCC) is an aggressive cancer subtype which accounts for most RCC related deaths. The capacity to monitor changes at a molecular or biochemical level using two-dimensional (2D) correlated magnetic resonance spectroscopy of human kidney cancer biopsies, offers an insight into how ccRCC differs from other kidney cancer subtypes (termed here, non-ccRCC). Using this technology, two new spectral assignments, isovalerylglycine and α-ketobutyrate, were elevated in the potentially aggressive ccRCC cancer subtype. The crosspeak at F2: 0.95 ppm, F1: 2.05 ppm was assigned to isovalerylglycine and the diagonal resonance at 2.77 ppm to α-ketobutyrate. Isovalerylglycine, an amino acid leucine catabolite, was 55% higher (p = 0.004) and α-ketobutyrate 108% higher (p < 0.001) in ccRCC compared with non-ccRCC tissue biopsies. They were also elevated compared with non-cancer kidney. The increase in α-ketobutyrate in ccRCC compared with non-ccRCC also provides further insight into the role of homocysteine metabolism in kidney cancer. These biomarkers provide metabolic insight that could have future diagnostic or clinical value. They may help develop a spectral signature that, preoperatively, improves distinction between life-threatening ccRCC, non-ccRCC and non-cancer kidney.

435. A DIAGNOSTIC PITFALL; SMALL CELL CARCINOMA-LIKE FEATURES IN BASALOID SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS

Abstract Esophageal basaloid squamous cell carcinoma may resemble small cell carcinoma biopsy specimens and cause difficulties in pathology diagnosis. We aimed to explore the pathological features of basaloid squamous cell carcinomas in biopsy specimens that mimic small cell carcinoma and to clarify their diagnostic and prognostic features. This study will contribute to draw attention to an important pitfall in pathology diagnosis in endoscopic biopsy specimens of the esophagus. Thirty biopsy specimens of esophageal basaloid squamous cell carcinoma were reviewed and compared with 13 matched surgical specimens. A small cell carcinoma-like feature was defined as, when at least one of the three following findings was observed: 1) diffuse growth pattern, 2) nuclear molding and 3) nuclear crush artifact. Immunohistochemistry of synaptophysin, chromogranin A, CD56 (neuroendocrine markers) and p16 were performed in all cases. Small cell carcinoma-like features, such as diffuse growth, nuclear molding, or nuclear crush artifact, were identified in 80% (24/30) of the biopsies and in 77% (10/13) of the surgery specimens, but in a proportionally much smaller area in the surgical specimens than in the biopsy samples. The presence of a small cell carcinoma-like feature had no impact on patients´ outcome. Immunohistochemically, synaptophysin and chromogranin A were consistently negative, while CD56 was expressed in 42% (10/24) basaloid squamous cell carcinomas with small cell carcinoma-like features. p16, a highly sensitive marker for small cell carcinoma, was also expressed in 8% (2/24). In conclusion, small cell carcinoma-like features are frequent and conspicuous in biopsies, which may probably be caused by exogenous factors such as friction and external pressure that occur in biopsy procedure and in the tumor environment. Small cell carcinoma-like features may lead to a misinterpretation of a true small cell carcinoma, if CD56 is an only neuroendocrine marker expressed. p16 expression may be also detected in basaloid squamous cell carcinoma.

A diagnostic pitfall; Small cell carcinoma-like features in basaloid squamous cell carcinoma of the esophagus.

Esophageal basaloid squamous cell carcinoma may resemble small cell carcinoma biopsy specimens and cause difficulties in pathology diagnosis. We aimed to clarify the clinicopathological significance of small cell carcinoma-like morphologies in basaloid squamous cell carcinoma. Thirty biopsy specimens of esophageal basaloid squamous cell carcinoma were reviewed and compared with 13 matched surgical specimens. Small cell carcinoma-like features, such as diffuse growth, nuclear molding, or nuclear crush artifact, were identified in 80% (24/30) of the biopsies and in 77% (10/13) of the surgery specimens, but in a proportionally much smaller area in the surgical specimens than in the biopsy samples. The presence of a small cell carcinoma-like feature had no impact on patients´ outcome. Immunohistochemically, synaptophysin and chromogranin A were consistently negative, while CD56 was expressed in 42% (10/24) of basaloid squamous cell carcinomas with small cell carcinoma-like features. p16, a highly sensitive marker for small cell carcinoma, was also expressed in 8% (2/24). p40 was expressed in all cases of basaloid squamous cell carcinoma. In conclusion, small cell carcinoma-like features are frequent and conspicuous in biopsies, which are probably caused by exogenous factors such as friction and external pressure that occur in biopsy procedure and in the tumor environment. Small cell carcinoma-like features may lead to a misinterpretation of a true small cell carcinoma, if CD56 is the only neuroendocrine marker expressed. p16 expression may also be detected in basaloid squamous cell carcinoma.

Tumor-stroma ratio, neoangiogenesis and prognosis in laryngeal carcinoma. A pilot study on preoperative biopsies and matched surgical specimens

ObjectivesThe interaction between tumor cells and stroma is critical in tumorigenesis, tumor neo–angiogenesis and cancer progression. The aims of this study were to: (i) evaluate the concordance between tumor-stroma ratio (TSR) and microvascular density (MVD) on paired biopsy and surgical specimens of laryngeal carcinoma (LSCC); (ii) investigate the association of TSR with angiogenesis (CD105- and CD31-assessed MVD); (iii) assess the prognostic role of TSR and MVD evaluated on preoperative biopsies and paired surgical specimens. MethodsTSR, CD105- and CD31-assessed MVD were analyzed in paired biopsies and surgical specimens of 43 consecutive cases. ResultsTSR showed good agreement between biopsies and surgical specimens (AC1 statistic: 0.7957). In biopsies, TSR low/stroma-rich cases showed higher CD105-assessed MVD (p = 0.0380). In surgical specimens both median CD105- and CD31-assessed MVD were significantly higher in TSR low/stroma-rich than in TSR high/stroma-poor patients (p = 0.0089 and p = 0.0391). In the univariate Cox’s model, TSR predicted disease-free survival (DFS) in both biopsies and surgical specimens (p = 0.0003 and p = 0.0002). DFS was associated with CD105- and CD31-assessed MVD in biopsies (p < 0.0001 for both) and surgical specimens (p < 0.0001 for both). Considering biopsies, the multivariate analysis found both TSR (p = 0.0032; HR = 6.112, 95%CI: 1.833–20.378) and CD105-assessed MVD (p = 0.0002; HR = 1.201, 95%CI: 1.090–1.322) as DFS predictor. In paired surgical specimens, both TSR (p = 0.0074; HR = 6.137, 95%CI: 1.626–23.172) and CD105-assessed MVD (p = 0.0005; HR = 1.172 95 %CI 1.071–1.282) retained their significance in multivariate analysis. ConclusionsIf confirmed by large prospective studies, TSR and MVD could be proposed as prognostic biomarkers of LSCC for a possible treatment intensification or targeted therapy.

Clinicopathological features and prognosis of 56 small biopsy specimens of pulmonary metastatic thyroid carcinoma

Clinicopathological features and prognosis of 56 small biopsy specimens of pulmonary metastatic thyroid carcinoma

Broder versus Bryne's histologic grading parameters on incision biopsy specimens: A comparative study with P53 and KI67 expression.

Objective:Various histological grading of oral squamous cell carcinoma has been contributed to the literature at different periods, but the reliability of such grading systems is controversial. This study attempted to measure the efficacy of Bryne's parameters on the full thickness of incisional biopsies which are representative of the original lesion with the proven molecular malignancy markers P53 and Ki67.Materials and Methods:One hundred incisional biopsy specimens of oral squamous cell carcinoma were obtained and histologically graded according to Broder's grading system. The same was graded using Bryne's parameters on full thickness of obtained incision sample. Immunohistochemistry was carried out for both p53 and Ki67.Results:We found a high discrepancy in the grading of lesions with Broader as well as Bryne grading parameters within the same lesion. When compared with the molecular expression percentages of p53 and Ki67, highly significant correlation was found in Bryne's parameters (Pearson Chi-square, P value 0.000) in incisional biopsies than Broder's.Conclusion:The use of parameters by Bryne on invasive front of excision biopsies can provide significant grading on incisional biopsies which are more comparable to the molecular behavior of tumor given by the p53 and Ki67 expression.

Human Papillomavirus Testing in Head and Neck Squamous Cell Carcinoma: Impact of the 2018 College of American Pathologists Guideline Among Referral Cases at a Large Academic Institution.

Given the growing clinical significance of human papillomavirus status in oropharyngeal squamous cell carcinoma, the College of American Pathologists established a set of evidence-based recommendations for high-risk human papillomavirus testing for publication in a guideline. To evaluate the impact of the recommendations on human papillomavirus ancillary test ordering habits by comparing compliance before and after the guideline was published. We retrospectively reviewed head and neck squamous cell carcinoma biopsy or resection specimens from outside institutions during a 2.5-year period around guideline publication to determine whether human papillomavirus testing was performed in accordance with the guideline. Human papillomavirus testing deviated from the guideline in 45 of 107 cases (42.1%) before and 93 of 258 cases (36.0%) after its publication (P = .29). This included 6 of 26 cases of oropharyngeal squamous cell carcinoma (23.1%) before and 5 of 55 cases (9.1%) after (P = .16), with 5 of 5 (100.0%) after due to not performing p16 immunohistochemistry. This also included 30 of 68 cases of nonoropharyngeal carcinoma (44.1%) before and 69 of 163 (42.3%) after the guideline was published (P = .88), with 29 of 30 (96.7%) before and 67 of 69 (97.1%) after due to unnecessary use of p16 immunohistochemistry. Nodal metastasis testing deviated in 9 of 13 cases (69.2%) before and 19 of 40 cases (47.5%) after (P = .21) with marked variability in testing, including 3 of 9 (33.3%) before and 8 of 19 (42.1%) after, for not confirming certain p16 immunohistochemistry-positive tumors with human papillomavirus-specific testing. Pathologists continue to deviate from the testing guideline significantly in everyday practice. Further education and discussion about the appropriate handling of head and neck cancer specimens may be needed.

Expression of Cyclin D1 in oral squamous cell carcinoma and its correlation with histopathological differentiation

Cyclin D1 is a vital protein that has a widespread role in cell cycle regulations, providing control over G1 to S Phase transition and governing cell proliferation rates.Cyclin D1 overexpression has been reported in variety of tumors. Present study was carried out to the study the expression of cyclin D1 and its association with histopathological differentiation and stage of oral squamous cell carcinoma.48 formalin fixed paraffin embedded tissue blocks of biopsy specimens of oral squamous cell carcinoma were immunohistochemically evaluated for expression of cyclinD1.CyclinD1 expression was seen in 98.5% (46) cases of OSCC. It did not correlate with site and staging. CyclinD1 expression was seen in 94.6% of well differentiated tumor,100% in moderately differentiated and 100% in poorly differentiated oral squamous cell carcinoma, but it was not statistically significant(p=0.065).Relatively higher frequency of Cyclin D1 immuno-reactivity observed in patients with less differentiated tumours suggest inverse correlation of Cyclin D1 expression with histological differentiation of tumour.

Expression and Significance of CK5/6, P63, P40, CK7, TTF-1, NapsinA, CD56, Syn and CgA in Biopsy Specimen of Squamous Cell Carcinoma, Adenocarcinoma and Small Cell Lung Carcinoma

Expression and Significance of CK5/6, P63, P40, CK7, TTF-1, NapsinA, CD56, Syn and CgA in Biopsy Specimen of Squamous Cell Carcinoma, Adenocarcinoma and Small Cell Lung Carcinoma

Expression pattern of p-Smad2/Smad4 as a predictor of survival in invasive breast ductal carcinoma.

The present study examined SMAD family member 4 (Smad4), SMAD family member 2 (Smad2) and phosphorylated (p-)Smad2 expression in biopsy specimens from patients with invasive breast ductal carcinoma, in order to assess their abilities as prognostic markers. A total of 126 tissue samples were selected, and the expression of Smad2, p-Smad2 and Smad4 in carcinoma tissues was detected by immunostaining, and the association between protein expression and clinicopathological variables was analyzed. Smad4 expression was negatively correlated with human epidermal growth factor receptor 2 in carcinoma tissues, and Smad4 expression was consistent with that of p-Smad2. Although multivariate analysis revealed that Smad2, p-Smad2 and Smad4 were not independent predictors, Kaplan-Meier curves demonstrated that Smad4 positivity was correlated with a longer overall survival (OS) and progression-free survival (PFS) time. However, upon analysis of combined markers, there was a significant difference between the p-Smad2/Smad4 co-positive and co-negative patients; the latter tended to exhibit a shorter OS and PFS time, and multivariate analysis revealed that the combined expression of p-Smad2 and Smad4 may be used as an independent prognostic factor. These results suggested that the assessment of p-Smad2 and Smad4 protein expression in breast ductal carcinoma biopsy specimens may provide additional prognostic information.

Napsin A expression is a valuable marker in small biopsy specimens of nonsmall cell lung carcinoma

Napsin A expression is a valuable marker in small biopsy specimens of nonsmall cell lung carcinoma

Relationship between supernatant cytokines and expression of markers of epitelial-mesenchymal transition of invasive breast carcinoma of non-specific lymphynosis type

The relationship between the content of supernatant cytokines and the expression of non-specific type of markers of epithelial-mesenchymal transition markers in the presence (group II) and the absence of lymphogenous metastasis (group I) were studied in biopsy specimens of mammary invasive breast carcinoma. The concentrations of TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, MCP-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β and IL-1Ra, as well as the expression of immunohistochemical (IHC) markers of the epithelial-mesenchymal transition - cadherin-E (CDH1), β-1 integrin (CD29) and type II collagen (CII) were assayed. Results have shown that patients of these groups statistically significantly differed in spontaneous production of IL-18 and G-CSF, in terms of the index of the effect of the polyclonal activator on G-CSF production. There was a correlation between the parameter of CII expression in tumor tissue and the production of cytokines by tumor biopsy specimens; it was characteristic of all patients with invasive carcinoma of a non-specific type, and correlations, both direct and reverse between the expression indices of CDH1, CD29 and cytokine production varied depending on the presence or the absence of lymphogenous metastasis. The study revealed the features of the correlation between the production of cytokines by the tumor, its microenvironment and the expression of IHC markers of the epithelial-mesenchymal transition in patients with invasive non-specific breast carcinoma in the presence and absence of lymphogenous metastasis.

Proteins and immunohistochemical markers of breast diseases

In this work, we have compared malignant and non-malignant diseases of the mammary gland using 8 proteins: HRG, MUC1, PAI-1, HSP90αA1, CDH1, ERα, PGR and IL-12. Their concentrations in the supernatants of blood cells and breast biopsies were compared in terms of spontaneous production, induced by a polyclonal activator and after exposure to biopsy samples of the HLDF differentiation factor, as well as the indices of the effect of the polyclonal activator and HLDF on the protein production. In addition, the correlation relationships of the above indicators with the expression of markers of the epithelial-mesenchymal transition: collagen type II (CII), β-1 integrin (CD29) and cadherin-E (CDH1) were studied. The study revealed statistically significant differences in the concentration of HRG in the supernatant of blood cells, IL-12 during spontaneous production by biopsy specimens, PGR production of biopsy specimens induced by the polyclonal activator, CDH1 and IL-12 production biopsy specimens exposed to HLDF. According to the influence index of the polyclonal activator and HLDF, statistically significant differences were found for CDH1production. Comparison of non-specific invasive carcinoma biopsy specimens and non-malignant breast diseases by means of the markers of the epithelial-mesenchymal transition revealed statistically significant differences in CD29 expression and the lack of differences in the expression of CDH1 and CII. This indicates the presence of cell atypia in samples of non-malignant breast diseases; it is confirmed by the recognized correlation between the production of certain proteins and the expression of the epithelial-mesenchymal transition markers.

Assessment of PD-L1 expression using the neural network analysis algorithm in non-small cell lung carcinoma biopsy specimens

To quantify PD-L1 biomarker expression in non-small cell lung carcinomas using the neural network analysis of digital copies of histological micropreparations. Immunohistochemical study of PD-L1 (22C3) expression was performed on 96 non-small cell lung carcinoma biopsy specimens. The digital copies of histological micropreparations were processed by the QuPath software neural network analysis module. The neural network analysis module segmented tumor, stroma, and artifacts in the micropreparations, showing a sufficient level of agreement with a visual assessment. Digital image analysis quantified stained tumor cells in the high PD-L1 expression group and showed 96% agreement rate versus visual assessment. However, the group of tumors without PD-L1 expression versus visual assessment showed a low (58%) agreement rate. The neural network analysis algorithm is applicable to the study of digital copies of histological micropreparations containing tumor, stroma, and artifacts. The algorithm allows for quantitative immunohistochemical assessment of PD-L1 expression in tumor cells. The algorithm can quantify the immunohistochemically detected expression of PD-L1 in tumor cells.

The Presence of Cyclooxygenase 2, Tumor-Associated Macrophages, and Collagen Alignment as Prognostic Markers for Invasive Breast Carcinoma Patients

Inflammation, and the organization of collagen in the breast tumor microenvironment, is an important mediator of breast tumor progression. However, a direct link between markers of inflammation, collagen organization, and patient outcome has yet to be established. A tumor microarray of 371 invasive breast carcinoma biopsy specimens was analyzed for expression of inflammatory markers, including cyclooxygenase 2 (COX-2), macrophages, and several collagen features in the tumor nest (TN) or the tumor-associated stroma (TS). The tumor microarray cohort included females, aged 18 to 80 years, with a median follow-up of 8.4 years. High expression of COX-2 (TN), CD68 (TS), and CD163 (TN and TS) predicted worse patient overall survival (OS). This notion was strengthened by the finding from the multivariate analysis that high numbers of CD163+ macrophages in the TS is an independent prognostic factor. Overall collagen deposition was associated with high stromal expression of COX-2 and CD163; however, total collagen deposition was not a predictor for OS. Conversely, local collagen density, alignment and perpendicular alignment to the tumor boundary (tumor-associated collagen signature-3) were predictors of OS. These results suggest that in invasive carcinoma, the localization of inflammatory cells and aligned collagen orientation predict poor patient survival. Additional clinical studies may help validate whether therapy with selective COX-2 inhibitors alters expression of CD68 and CD163 inflammatory markers.

Dual Stain With SATB2 and CK20/Villin Is Useful to Distinguish Colorectal Carcinomas From Other Tumors.

Small sample size limits the number of immunostains that may be attempted in colorectal carcinoma (CRC) biopsy specimens. We investigated the utility of dual stain with special AT-rich sequence binding protein 2 (SATB2) or caudal-type homeobox 2 (CDX2) and cytokeratin 20 (CK20) or villin in identifying CRC. Tissue microarrays with 222 CRCs and 375 other carcinomas were built. Dual stain was performed pairing nuclear stains CDX2 or SATB2 with CK20 or villin. All four single stains showed excellent sensitivity (93%-99%) but variable specificity (56%-88%) for CRC. All four dual stains also showed excellent sensitivity (90%-96%) while much improved specificity (88%-98%) compared with single stains. SATB2 dual stain (with CK20 or villin) showed a higher specificity than CDX2 dual stain (with CK20 or villin) with a comparable sensitivity. SATB2 dual stain shows the greatest potential clinical utility in identifying CRC and is superior to CDX2 dual stain. More important, SATB2 dual stain could be helpful for specimens with limited tissues or those having a nonclassic staining pattern.

Synchronous primary lung cancers: a multidisciplinary approach in diagnosis.

BACKGROUND. For patients with two or more primary cancers a correct diagnosis is critically important because prognosis and treatment vary considerably between multiple primary cancers and metastatic disease. Two bilateral synchronous primary lung malignancies of different histological types were diagnosed and immunohistochemically confirmed in a 60-year-old woman. In biopsy specimens of the right lung pure squamous cell carcinoma was detected (stage IIIa). The tumor expressed AE1/AE3, cytokeratin 5 and 34βE12. In biopsy specimens of the left lung small cell carcinoma was detected (stage IIIa). The small cells expressed synaptophysin, chromogranin A and CD56. DNA was extracted from paraffin-embedded tissue of both tumors. Exons 5-9 of the TP53 gene were examined for genetic mutations by polymerase chain reaction and DNA sequencing analysis. Direct sequencing of DNA isolated from the small cell carcinoma revealed a TGC to TTC mutation at codon 404 of TP53 exon 5. In DNA isolated from the squamous cell carcinoma no TP53 mutation was found. The tumors' different response to chemotherapy also suggested that they belonged to different histological types. The patient lived 24 months after the diagnosis, which is more typical for stage III than for stage IV lung carcinoma. Discrimination of synchronous primary lung cancers from intrapulmonary metastases based only on clinical findings can be very difficult. Multidisciplinary diagnostic evaluation is therefore very helpful in cases like this, because a correct diagnosis will determine the best treatment for the patient and consequently a better prognosis.

Review: Anal Intraepithelial Neoplasia in HIV-Infected Men Who Have Sex with Men: Is Screening and Treatment Justified?

Anal squamous cell carcinoma (SCC) is the fourth most prevalent cancer in human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). Human papillomavirus (HPV) has been detected in over 90% of anal carcinoma biopsy specimens from MSM, and is considered a necessary, but alone, insufficient factor for carcinogenesis. Anal intraepithelial neoplasia (AIN) may be precursive for SCC, and screening cytology with referral of persons with abnormality for high-resolution anoscopy-guided biopsy, and AIN treatment, has been recommended for prevention. In the absence of either randomized controlled trials or surveillance data demonstrating a reduction in anal SCC incidence, these recommendations were based on analogy with cervical cancer. HPV-mediated genetic changes associated with cervical cancer, and aneuploidy, have been documented in AIN. However, little data exist on the rate of AIN progression to SCC. The treatment of AIN is frequently prolonged and not curative, and if routinized in the care of HIV-infected MSM, would likely be recurring well into their sixth decade of life. Clinical trials demonstrating a reduction in invasive anal carcinoma incidence, as well as acceptable morbidity with repeated AIN destruction, are needed before asking our patients to commit to routine treatment.

Urothelial carcinoma involving the ureteral orifice: a clinicopathologic analysis of 93 cases

Although tumors involving the bladder and ureter have been well described, there are only few studies in the pathology literature specifically analyzing tumors involving the ureteral orifice (UO). A search was performed for biopsy and resection specimens (transurethral resection, radical cystectomy/cystoprostatectomy, nephroureterectomy and bladder cuff resection) of urothelial carcinoma (UCa) involving the UO. Ninety-three cases were identified. Sixty-two (67%) patients were male. Mean patient age was 71 years (range, 43-91 years). Forty-two of 93 (45%) cases were invasive UCa (41 high-grade UCa; 1 low-grade UCa); 17/42 (40%) were invasive into muscularis propria. Tumor laterality was as follows: right side, 43 (46% of cases); left side, 41 (44%); bilateral, 4 (4.5%); and in 5 cases (5.5%), the laterality was not specified by the urologist. Seven cases of UCa with variant histology were also identified. Five patients had lymph node (LN) metastasis at the time of resection, and another 3 presented with LN or distant metastasis after resection (range, 4-38 months). Although this study focused primarily on the index tumor involving the UO (Group 1 cases are those with only UO involvement), in 70/93 (75%) cases (Group 2 cases), at least one other tumor was located at another site within the bladder. The fact that the majority of cases (75%) had tumors located at other sites of the bladder, emphasizes that careful examination of the UO needs to be performed by both urologists and pathologists when examining cases of UCa of the bladder.