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Immunoprofiles of Chromophobe Renal Cell Carcinoma (RCC) and Oncocytoma
S28
Abstracts
Materials and Methods: One hundred and twenty nine patients attending the Veterans Administration Medical Center in Washington DC were studied after approval from the local Institutional Review Board. The study period was 2008 to 2011 and focused on those patients with atypical urine cytology. The UroVysion test was performed as a reflex test on the residual aliquot of the fixed urine samples with atypical cytology. The specimens included 19 voided and 110 cystoscopic urines. Results were correlated with clinical history, cytomorphological features, cystoscopic examination and, where available, bladder biopsy. Results: All patients except one were male, with an age range of 31 to 90 years (median 65 years; mean 66.7 years). Overall, 34/129 (26%) of cytologically atypical samples were UroVysion positive. These included 6/18 voided and 28/107 cystoscopic urine specimens. Four specimens were borderline or quantity insufficient by standard UroVysion manufacturer’s guidelines. Biopsies were performed on 18 UroVysion positive cases (2 voided and 16 cystoscopic urines) within 0 to 3 months of the test. Urothelial neoplasia was seen in 2/2 voided and 16/16 cystoscopic urine specimens resulting in a high specificity. On the other hand, biopsy proven urothelial carcinoma was seen in 6 of 14 UroVysion negative specimens, cases with tumor present on cystoscopic examination, resulting in low sensitivity. The most common Urovysion abnormality was gain of chromosomes 3, 7 and 17. Loss of 9p21 occurred in 6 cases and was the sole abnormality in 3. Conclusions: This study indicates that the UroVysion test could be a useful test in the diagnosis of bladder cancer in conjunction with urine cytology and cystoscopic examination, especially in cases with atypical cytology in voided urine and atypical cytology and no tumor identified on cystoscopic examination in cystoscopic urine. In our study in all UroVysion positive cases, follow up biopsy showed neoplastic changes, indicating that UroVysion has high specificity and that UroVysion positive cases need periodic further evaluation. 30 Immunoprofiles of Chromophobe Renal Cell Carcinoma (RCC) and Oncocytoma Bing Zhu, MD, PhD, Stephen Rohan, MD, Xiaoqi Lin, MD, PhD. Pathology, Northwestern University, Chicago, Illinois Introduction: Chromophobe RCC and oncocytoma share some histologic and cytologic features, which can potentially cause difficulty in diagnosis in fine needle aspiration and needle core biopsy. We aimed to study if immunohistochemistry (IHC) can help distinguish Chromophobe RCC from oncocytoma on small tissue specimens by performing IHC on tissue microarray (TMA). Materials and Methods: Duplicate TMAs (1.5 mm in diameter) were prepared from paraffin-embedded tissue blocks of histologically confirmed chromophobe RCC (36 cases) and oncocytoma (20 cases) to represent different areas of the tumors. IHC was performed on duplicate TMA sections with appropriate controls. Results: See Table 1. Table 1
IHC results of chromophobe RCC and oncocytoma
Tumor
Positivity
HP-1
CK7
CD117
PAX8
MUC1
P16
Chromophobe RCC
Diffuse Focal Total Diffuse Focal Total Diffuse Focal Total
34 2 36 17 2 19
19 (53%) 15 (42%) 34 (94%) 2 (10%) 3 (15%) 5 (25%) < 0.005 < 0.005 < 0.005
26 3 29 14 3 17
4 5 9 5 6 11
34 (94%) 2 (6%) 36 (100%) 11 (55%) 5 (25%) 16 (80%) < 0.005 < 0.005 < 0.01
25 5 30 15 4 19
Oncocytoma
P Values
(94%%) (6%) (100%) (85%) (10%) (95%)
(72%) (8%) (81%) (70%) (15%) (85%)
(11%) (14%) (25%) (25%) (30%) (55%)
< 0.025
(69%) (14%) (83%) (75%) (20%) (95%)
Chi-Square test.
Conclusions: Chromophobe RCC and oncocytoma share not only histologic and cytologic features, but also share most IHC markers, HP1, H2AFX (100% vs. 100%, totally), S100A1 (44% vs. 55%, totally),
CD117, p16, and CA-9 (0% for all). CK7 is expressed significantly more frequently in chromophobe RCC than oncocytoma, both diffusely (53% vs. 10%) and focally (42% vs. 15%). Although there is no statistically significantdifference between expression of PAX8 in chromophobe RCC and oncocytoma if counting diffuse and focal expression independently, total expression of PAX8 is more frequently seen in oncocytoma than in chromophobe RCC (55% vs. 25%). MUC1 is expressed more diffusely and frequently in chromophobe RCC than in oncocytoma (94% vs. 55%). Therefore, none of these IHC markers are specific for either chromophobe RCC or oncocytoma. Since CK7 and MUC1 are expressed more diffusely and frequently in chromophobe RCC than in oncocytoma, and PAX8 is expressed slightly more frequently in oncocytoma than in chromophobe RCC, including these markers in a IHC panel may help distinguish chromophobe from oncocytoma on small biopsy samples. However, histomorphologic and cytomorphologic features appear to be the most important criteria to distinguish chromophobe RCC from oncocytoma on biopsy samples. 31 A Retrospective Review of Atypical Clusters in Urine Cytology: Analysis of Cytologic Features and Clinical Significance Heidi Jess, MD, Alaa Afify, MD, Eric Huang, MD, PhD. Department of Pathology and Laboratory Medicine, University of California, Davis Medical Center, Sacramento, California Introduction: Urine cytology has been the mainstay for surveillance in patients with a history of urothelial carcinoma (UC) and also to evaluate patients with hematuria. Common urine specimens received in cytology laboratories include voided urine, catheterized urine and bladder washings. While clusters of urothelial cells in instrumented urine samples are considered effects secondary to the procedure, clusters in voided urine are traditionally regarded as uncommon and should be interpreted as atypical. In the present study, we performed a blinded review of atypical clusters in urine cytology and analyzed its cytologic features and clinical significance. Materials and Methods: A retrospective review of all voided urine samples and randomly selected instrumented urine samples from 2007 to 2012 with an interpretation of atypia were identified by the Pathology Laboratory Information System and retrieved at our institution. Urine samples with atypical clusters were independently and blindly re-evaluated by two cytopathologists for features including: cluster type (loose vs. tight), cluster border (smooth vs. irregular), nuclear to cytoplasmic ratio (low vs. high), nuclear contour (smooth vs. irregular), chromatin texture (normochromatic vs. hyperchromatic), and cytoplasmic feature (vacuolated vs. homogenous). Clinical outcomes were correlated with surgical and/or clinical follow-up. Results: During the five year period, a total number of 877 urine specimens were available on file, of which 12 (1%) cases of voided urine were interpreted as atypical. Of the 31 cases reviewed, 22 (71%) cases had a benign outcome (9 voided and 13 instrumented), while 9 (29%) cases had a more significant underlying lesion in follow-up (3 voided and 6 instrumented). Of these, clinical outcomes of low-grade UC, high-grade UC, or papillary lesion not otherwise specified were seen in 3 (33%), 3 (33%) and 3 (33%) cases, respectively. Cytologic evaluation showed moderate to good inter-observer variability with percent agreement between 58-100%. There was significant overlap in all of the cytologic features analyzed between benign and neoplastic cases. In addition, the results were heterogeneous within a single case. Conclusions: Traditionally, urothelial clusters in voided urine are considered uncommon in urine cytology and should render a diagnosis of atypical urothelial cells by cytologists. In the present series, only 9 (29%) cases of atypical clusters had a neoplastic clinical course. The overlapping cytologic features between benign and neoplastic urothelial cell clusters make it difficult to differentiate between these two based on cytologic features alone. Thus, combination testing by urine cytology and cystoscopy is the optimal method for detecting urothelial lesions.
Abstracts
Materials and Methods: One hundred and twenty nine patients attending the Veterans Administration Medical Center in Washington DC were studied after approval from the local Institutional Review Board. The study period was 2008 to 2011 and focused on those patients with atypical urine cytology. The UroVysion test was performed as a reflex test on the residual aliquot of the fixed urine samples with atypical cytology. The specimens included 19 voided and 110 cystoscopic urines. Results were correlated with clinical history, cytomorphological features, cystoscopic examination and, where available, bladder biopsy. Results: All patients except one were male, with an age range of 31 to 90 years (median 65 years; mean 66.7 years). Overall, 34/129 (26%) of cytologically atypical samples were UroVysion positive. These included 6/18 voided and 28/107 cystoscopic urine specimens. Four specimens were borderline or quantity insufficient by standard UroVysion manufacturer’s guidelines. Biopsies were performed on 18 UroVysion positive cases (2 voided and 16 cystoscopic urines) within 0 to 3 months of the test. Urothelial neoplasia was seen in 2/2 voided and 16/16 cystoscopic urine specimens resulting in a high specificity. On the other hand, biopsy proven urothelial carcinoma was seen in 6 of 14 UroVysion negative specimens, cases with tumor present on cystoscopic examination, resulting in low sensitivity. The most common Urovysion abnormality was gain of chromosomes 3, 7 and 17. Loss of 9p21 occurred in 6 cases and was the sole abnormality in 3. Conclusions: This study indicates that the UroVysion test could be a useful test in the diagnosis of bladder cancer in conjunction with urine cytology and cystoscopic examination, especially in cases with atypical cytology in voided urine and atypical cytology and no tumor identified on cystoscopic examination in cystoscopic urine. In our study in all UroVysion positive cases, follow up biopsy showed neoplastic changes, indicating that UroVysion has high specificity and that UroVysion positive cases need periodic further evaluation. 30 Immunoprofiles of Chromophobe Renal Cell Carcinoma (RCC) and Oncocytoma Bing Zhu, MD, PhD, Stephen Rohan, MD, Xiaoqi Lin, MD, PhD. Pathology, Northwestern University, Chicago, Illinois Introduction: Chromophobe RCC and oncocytoma share some histologic and cytologic features, which can potentially cause difficulty in diagnosis in fine needle aspiration and needle core biopsy. We aimed to study if immunohistochemistry (IHC) can help distinguish Chromophobe RCC from oncocytoma on small tissue specimens by performing IHC on tissue microarray (TMA). Materials and Methods: Duplicate TMAs (1.5 mm in diameter) were prepared from paraffin-embedded tissue blocks of histologically confirmed chromophobe RCC (36 cases) and oncocytoma (20 cases) to represent different areas of the tumors. IHC was performed on duplicate TMA sections with appropriate controls. Results: See Table 1. Table 1
IHC results of chromophobe RCC and oncocytoma
Tumor
Positivity
HP-1
CK7
CD117
PAX8
MUC1
P16
Chromophobe RCC
Diffuse Focal Total Diffuse Focal Total Diffuse Focal Total
34 2 36 17 2 19
19 (53%) 15 (42%) 34 (94%) 2 (10%) 3 (15%) 5 (25%) < 0.005 < 0.005 < 0.005
26 3 29 14 3 17
4 5 9 5 6 11
34 (94%) 2 (6%) 36 (100%) 11 (55%) 5 (25%) 16 (80%) < 0.005 < 0.005 < 0.01
25 5 30 15 4 19
Oncocytoma
P Values
(94%%) (6%) (100%) (85%) (10%) (95%)
(72%) (8%) (81%) (70%) (15%) (85%)
(11%) (14%) (25%) (25%) (30%) (55%)
< 0.025
(69%) (14%) (83%) (75%) (20%) (95%)
Chi-Square test.
Conclusions: Chromophobe RCC and oncocytoma share not only histologic and cytologic features, but also share most IHC markers, HP1, H2AFX (100% vs. 100%, totally), S100A1 (44% vs. 55%, totally),
CD117, p16, and CA-9 (0% for all). CK7 is expressed significantly more frequently in chromophobe RCC than oncocytoma, both diffusely (53% vs. 10%) and focally (42% vs. 15%). Although there is no statistically significantdifference between expression of PAX8 in chromophobe RCC and oncocytoma if counting diffuse and focal expression independently, total expression of PAX8 is more frequently seen in oncocytoma than in chromophobe RCC (55% vs. 25%). MUC1 is expressed more diffusely and frequently in chromophobe RCC than in oncocytoma (94% vs. 55%). Therefore, none of these IHC markers are specific for either chromophobe RCC or oncocytoma. Since CK7 and MUC1 are expressed more diffusely and frequently in chromophobe RCC than in oncocytoma, and PAX8 is expressed slightly more frequently in oncocytoma than in chromophobe RCC, including these markers in a IHC panel may help distinguish chromophobe from oncocytoma on small biopsy samples. However, histomorphologic and cytomorphologic features appear to be the most important criteria to distinguish chromophobe RCC from oncocytoma on biopsy samples. 31 A Retrospective Review of Atypical Clusters in Urine Cytology: Analysis of Cytologic Features and Clinical Significance Heidi Jess, MD, Alaa Afify, MD, Eric Huang, MD, PhD. Department of Pathology and Laboratory Medicine, University of California, Davis Medical Center, Sacramento, California Introduction: Urine cytology has been the mainstay for surveillance in patients with a history of urothelial carcinoma (UC) and also to evaluate patients with hematuria. Common urine specimens received in cytology laboratories include voided urine, catheterized urine and bladder washings. While clusters of urothelial cells in instrumented urine samples are considered effects secondary to the procedure, clusters in voided urine are traditionally regarded as uncommon and should be interpreted as atypical. In the present study, we performed a blinded review of atypical clusters in urine cytology and analyzed its cytologic features and clinical significance. Materials and Methods: A retrospective review of all voided urine samples and randomly selected instrumented urine samples from 2007 to 2012 with an interpretation of atypia were identified by the Pathology Laboratory Information System and retrieved at our institution. Urine samples with atypical clusters were independently and blindly re-evaluated by two cytopathologists for features including: cluster type (loose vs. tight), cluster border (smooth vs. irregular), nuclear to cytoplasmic ratio (low vs. high), nuclear contour (smooth vs. irregular), chromatin texture (normochromatic vs. hyperchromatic), and cytoplasmic feature (vacuolated vs. homogenous). Clinical outcomes were correlated with surgical and/or clinical follow-up. Results: During the five year period, a total number of 877 urine specimens were available on file, of which 12 (1%) cases of voided urine were interpreted as atypical. Of the 31 cases reviewed, 22 (71%) cases had a benign outcome (9 voided and 13 instrumented), while 9 (29%) cases had a more significant underlying lesion in follow-up (3 voided and 6 instrumented). Of these, clinical outcomes of low-grade UC, high-grade UC, or papillary lesion not otherwise specified were seen in 3 (33%), 3 (33%) and 3 (33%) cases, respectively. Cytologic evaluation showed moderate to good inter-observer variability with percent agreement between 58-100%. There was significant overlap in all of the cytologic features analyzed between benign and neoplastic cases. In addition, the results were heterogeneous within a single case. Conclusions: Traditionally, urothelial clusters in voided urine are considered uncommon in urine cytology and should render a diagnosis of atypical urothelial cells by cytologists. In the present series, only 9 (29%) cases of atypical clusters had a neoplastic clinical course. The overlapping cytologic features between benign and neoplastic urothelial cell clusters make it difficult to differentiate between these two based on cytologic features alone. Thus, combination testing by urine cytology and cystoscopy is the optimal method for detecting urothelial lesions.