Bladder Case 1 SURGICAL PATHOLOGY REPORT. Procedure: Cystoscopy, transurethral resection of bladder tumor (TURBT)

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Bladder Case 1 February 17, 2007 Specimen (s) received: Bladder Tumor Pre-operative Diagnosis: Bladder Cancer Post operative Diagnosis: Bladder Cancer Procedure: Cystoscopy, transurethral resection of bladder tumor (TURBT) Gross Examination: Specimen consists of multiple irregular fragments of a gray pink soft tissue that in aggregate measure 4.5 x 4.5 x 1 cm. Many of these are soft and friable. Specimen is entirely submitted in six cassettes. Microscopic Examination: Slides examined: 6 See Diagnosis Urinary Bladder Tissues (TURBT) 1. Urothelial carcinoma, high grade, non-papillary with extensive squamous differentiation, and focal mucinous component a. Extensive tumor necrosis is present. Bacterial colonies are present. b. Extensive muscularis invasion by tumor is present. c. Vascular invasion is not identified. 2. Chronic follicularis cystitis. END Bladder Case 1

Bladder Case 2 10/25/2007 Preoperative Diagnosis: Hematuria Postoperative Diagnosis: Bladder tumor Gross Description: Received in formalin as bladder tumor are multiple pieces of firm pink-tan tissue and clotted blood, approximately 2 x 2 x 1 cm in aggregate. The specimen is entirely submitted in cassettes 1-3. Frozen Section Diagnosis: FSA: Right ureteral margin, excision: No significant dysplasia or carcinoma. FSB: Left ureteral margin, excision: No significant dysplasia or carcinoma. Microscopic Description: Sections show a high-grade carcinoma characterized by diffuse sheets and nests of malignant urothelial cells with marked nuclear pleomorphism and numerous mitoses. Many of the neoplastic cells show eccentric nuclear displacement with a signet ring appearance. These latter cells show intracytoplasmic mucin on PAS-diastase stain. The tumor cells exhibit positive staining for CEA by immunohistochemistry and are negative for PSA and PAP. The urothelium overlying the invasive carcinoma shows urothelial carcinoma in-situ. There is muscle invasion with smooth muscle bundles that are splayed and surrounded by sheets of tumor cells. Urinary bladder, transurethral resection of tumor: Invasive high-grade urothelial carcinoma with signet ring cell features. Smooth muscle invasion is present. END Bladder Case 2

Bladder Case 3 March 3, 2007 Specimen (s) received: Urinary bladder, transurethral resection (TURBT) Clinical History: Very large, necrotic infected bladder carcinoma Gross Examination: Received in formalin in one container labeled bladder tumor contains 75 grams of pink, tan and grey, irregular fragments of soft tissue. Representative sections are submitted in 10 cassettes labeled A1 through A10 Bladder tumor: high grade poorly differentiated carcinoma with squamous features, consistent with a primary bladder carcinoma. See comment. Tumor infiltrates bladder wall deep muscle tissue. Comment: This poorly differentiated carcinoma is composed of predominately diffuse sheets of undifferentiated malignant cells. In addition, there is extensive necrosis. There is notable squamous differentiation. No transitional cell differentiation is identified. Nevertheless, the features are consistent with a primary bladder carcinoma. END Bladder Case 3

Pathology Report, 06/27/2007 Clinical History: Bladder cancer Specimen: Bladder tumors Bladder Case 4 #1 Gross Description The specimen is received in B-5 fixative and labeled Bladder tumors. It consists of multiple tan-brown shaggy fragments of tissue aggregating to 7.6 x 5.5 x 1.2 cm. The specimen is entirely submitted in ten cassettes. Cystoscopy, biopsy, and transurethral resection of bladder tumors: Bladder tumors: Invasive transitional cell carcinoma with papillary and micropapillary features and squamous cell carcinoma, nuclear grade IV accompanied by extensive necrosis. The squamous cell tumor is extensively invasive and although there is extensive necrosis, invasion into muscularis propria is identified. Pathology Report, 07/28/2007 #2 Clinical Diagnosis and History: Not provided Specimen: Radical cystectomy Urinary bladder: Multifocal tumors with papillary transitional carcinoma, grade II-III of IV, with superficial invasion into bladder wall. Tumor with moderately differentiated keratinizing squamous cell carcinoma (4.0 x 3.0 x 1.8 cm), extending through the deep muscle (outer half) into perivesical fat. Surgical resection margins including ureteral margins, free of malignancy. No evidence of lymphovascular space invasion identified. END Bladder Case 4

Bladder Case 5 June 14, 2007 Specimen (s) received: Bladder, transurethral resection (TURB) Clinical History: Bladder tumor Gross Examination: Received in formalin are multiple tan, pink focally papillary, mildly cauterized tissues aggregating 12 cc. Specimen is totally submitted in cassettes 1-6. Microscopic Examination: Sections show a poorly differentiated urothelial carcinoma arising within the urothelial surface and extensively infiltrating the underlying mucosal lamina propria and muscularis propria. The in-situ component exhibits papillary and non-papillary growth patterns. The invasive component, which extensively involves virtually all of the biopsy fragments, exhibits moderate nuclear pleomorphism, increased mitotic activity and extensive involvement of the muscularis propria. Foci suggestive of lymphovascular invasion are noted. These features represent urothelial carcinoma, mixed papillary and non-papillary type; grade III/IV, with extensive invasion and involvement of the muscular wall. Bladder transurethral resection. Urothelial carcinoma, grade III/IV, with extensive involvement of the muscularis propria and foci suggestive of lymphovascular invasion. END Bladder Case 5

RP/Ureter Case 1 October 20, 2007 Specimen: A. Left ureter biopsy B. Uterus and bladder C. Right ureter A. Left ureter biopsy - invasive high grade urothelial carcinoma. B. Uterus and bladder (radical cystohysterectomy) - invasive high grade urothelial carcinoma orginating in the left ureter. Neoplasm penetrates into but not through muscularis propria of the ureter. No involvement of the urethra. Staging AJCC pathologic stage: pt2; pnx; pmx; No involvement of soft tissue margins; invasive carcinoma is present at the transected left ureteral margin. Cystic atrophy of the endometrium. Cervix, right fallopian tube and right ovary with no significant diagnostic abnormality. C. Right ureter - chronic ureteritis with reactive urothelial atypia; no dysplastic or neoplastic changes in sections examined. END RP/Ureter Case 1

July 1, 2007 RP/Ureter Case 2 #1 Right renal pelvis, biopsy: Papillary urothelial carcinoma, low grade (noninvasive) #2 July 4, 2007 A. Base of right ureter, biopsy: Papillary urothelial carcinoma, low grade (noninvasive) B. Right ureter, intramural, biopsy: Papillary urothelial carcinoma, low grade (noninvasive) C. Right ureter external to bladder wall, biopsy: Papillary urothelial carcinoma, low grade (noninvasive) D. Bladder, right trigone, biopsy: Papillary urothelial carcinoma, low grade (noninvasive) E. Right bladder neck tumor, biopsy: Papillary urothelial carcinoma, non-invasive July 20, 2007 #3 Right kidney and ureter, resection, TURB: A. Papillary urothelial carcinoma, low grade (noninvasive) B. Tumor location: Renal pelvis C. Renal ureter margin of resection uninvolved by tumor or dysplasia D. Urinary bladder, designated anterior wall tumor, transurethral resection: Low grade papillary urothelial carcinoma (noninvasive). END RP/Ureter Case 2

RP/Ureter Case 3 June 11, 2007 Gross Description: Received is a 20.0 x 9.5 x 4.0 cm, right kidney encircled by perinephric adipose tissue and Gerota's fascia, a 23.0 cm in length segment of ureter and an attached bladder cuff, 1.5 x 1.0 cm. Three separate exophytic, soft, papillary masses are noted. The first is in the ureter, 2.4 x 1.0 x 1.0 cm. Two additional masses are both located in the inferior major calyx of the renal pelvis with the larger, 1.5 x 0.9 x 0.6 cm, and the smaller adjacent mass, 0.5 cm in maximum dimension. The superior pole of kidney has two golden yellow, subcapsular nodules, 0.2 and 0.4 cm in maximum dimension. The remaining caliceal system has no additional areas of nodularity or firmness. The kidney parenchyma consists of tan tissue without additional masses. Microscopic Description: Sections of kidney and ureter demonstrate four separate urothelial tumors. The largest is located in the distal ureter, 2.4 cm in diameter and consists of a low-grade papillary transitional cell carcinoma without evidence of infiltration. Three additional tumors are noted in the caliceal system of the right kidney. These represent high grade papillary transitional cell carcinomas focally associated with infiltration of the lamina propria/submucosa but without extension into the adjacent muscle wall. Kidney focally shows subcapsular adrenal cortical rests. This is substantiated with IP studies. Multifocal papillary transitional cell carcinoma, low to high grade. Four separate tumors present, measuring 2.4 cm, 1.5 cm, 0.5 cm and 0.5 cm in maximum dimension. Largest lesion located in mid right ureter and remaining three lesions located in the inferior calyx of the right kidney. The tumors in the inferior calyx are high grade and demonstrate focal infiltration of the lamina propria/submucosa but without evidence of involvement of the underlying muscle wall. Tumor within ureter is low grade and shows no evidence of infiltration. END RP/Ureter Case 3

RP/Ureter Case 4 December 2, 2007 Specimen: Left kidney and ureter, nephroureterectomy Microscopic Examination: Sections of the renal pelvis demonstrate focal papillary urothelial carcinoma, high-grade, showing no evidence of invasion in its involvement of the renal pelvis. In these sections, tumor directly adjoins the renal medulla. In addition, sections of the ureter demonstrate focal, high-grade papillary urothelial carcinoma. A section of the proximal aspect of the detached ureter segment demonstrates a focus of hemorrhagic mucosal erosion with an associated microfocus of lamina propria microinvasion. There is no demonstrable muscular wall invasion. The distal resection margin at the ureterovesical junction shows no tumor. Other sections of the ureteral and pelvocaliceal urothelium, while showing focal urothelial dysplasia, demonstrate no urothelial carcinoma in situ. Final Dx Left kidney and ureter, nephroureterectomy: papillary urothelial carcinoma involving renal pelvis and ureter, multifocal, with the following features: high-grade papillary urothelial carcinoma with no evidence of invasion, renal pelvis; high-grade papillary urothelial carcinoma, ureter. END RP/Ureter Case 4

RP/Ureter Case 5 January 22, 2011 Clinical History: Recurrent transitional cell bladder carcinoma with first diagnosis in January 2007. Specimen: Right kidney and right ureter, nephroureterectomy A. Right kidney, nephrectomy specimen: High grade papillary transitional cell carcinoma involving the renal pelvis, with stromal but not muscular invasion. Hilar vascular and Gerota's fascia margins of resection are free of tumor. B. Right ureter and ileocolonic cutaneous reservoir, excised: segment of ureter with extensive low-grade papillary transitional cell carcinoma without clear evidence of stromal, muscular, or angiolymphatic invasion. Non-invasive carcinoma is present at the ureterocolonic anastomotic site. The colon segment shows mild acute serositis. Two small benign lymph nodes. END RP/Ureter Case 5

RP/Ureter Case 6 August 25, 2007 Specimen: A. Colonic mesentery - biopsy B. Retroperitoneal soft tissue - biopsy C. Internal ring soft tissue - biopsy Gross Description: Three specimens are received. A. Colonic mesentery consists of multiple irregular, necrotic soft tan to firm calcified tissue fragments aggregating to 1.5 cm. B. Retroperitoneal tissue consists of a membranous tan-red 1.3 cm soft tissue fragment. C. Internal ring consists of an approximately 1.5 cm firm tan lymph node. Microscopic Description: The colonic mesentery and retroperitoneal biopsies show an infiltrative high-grade carcinoma with features fully consistent with high-grade urothelial carcinoma. The internal ring soft tissue shows a benign reactive lymph node. A. Colonic mesentery, biopsy: High-grade carcinoma consistent with urothelial carcinoma. B. Retroperitoneum, biopsy: High-grade carcinoma consistent with urothelial carcinoma. C. Soft tissue, internal ring: No evidence of malignancy. END RP/Ureter Case 6

RP/Ureter Case 7 January 27, 2007 Specimen: D. Left ureter biopsy E. Right ureter biopsy D. Left ureter biopsy - invasive high grade urothelial carcinoma E. Right ureter biopsy low grade urothelial carcinoma, noninvasive END RP/Ureter Case 7

RP/Ureter Case 8 July 12, 2007 Clinical History: Bladder cancer Specimen: Radical Cystectomy A. Lymph nodes, pelvic right (resection): Two of 15 lymph nodes positive for metastatic urothelial carcinoma (largest involved lymph node is 2.6 cm in greatest diameter) (2/15) B. Lymph nodes, pelvis left (resection): Two of 13 lymph nodes positive for metastatic urothelial carcinoma (largest involved lymph node is 1.7 cm in greatest dimension) (2/13) C. Bladder and prostate (resection): Poorly differentiated transitional cell carcinoma of the bladder involving right and left ureter bladder junction, right and left bladder wall, prostate urethra. The tumor invades into the perivesicular soft tissue microscopically (pt3bstage). Carcinoma in situ associated with invasive carcinoma and also involving right and left ureters and bladder dome. D. Urethral margins are free of tumor. Right and left urethral margins show carcinoma in situ. Prostate: urothelial carcinoma in situ and invasive carcinoma involving prostatic urethra. E. Lymph nodes, sacral area (resection): Three of 10 lymph nodes positive for metastatic urothelial carcinoma (largest involved lymph node is 1 cm in greatest dimension) (3/10) END RP/Ureter Case 8