Roni M. Cox

The Utility of Pax-2 and Renal Cell Carcinoma Marker Immunohistochemistry in Distinguishing Papillary Renal Cell Carcinoma From Nonrenal Cell Neoplasms With Papillary Features

PAX-2, a homeogene expressed during kidney development, has been studied as a marker of renal origin in both primary and metastatic clear cell renal cell carcinoma (RCC), but not in papillary neoplasms or in comparison with RCC marker (RCCma). We studied immunohistochemical expression of PAX-2 and RCCma in 24 papillary RCC (PRCC) and 66 nonrenal cell papillary neoplasms (NRCPN) from a variety of organs. Of the PRCC, 16/24 (67%) were positive for PAX-2; 23/24 (96%) were positive for RCCma. Of the NRCPN, 9/66 (14%) is positive for PAX-2 [4/10 (40%) ovarian papillary serous carcinomas, 5/9 (56%) uterine papillary serous carcinomas]; RCCma was positive in 28/66 (42%), including 9/9 (100%) papillary thyroid carcinomas, 8/10 (80%) ovarian papillary serous carcinomas, 4/9 (44%) uterine papillary serous carcinomas, 1/10 (10%) papillary urothelial carcinomas, 1/2 (50%) intraductal papillary mucinous carcinomas of the pancreas, 3/3 (100%) choroid plexus papillomas, 1/1 (100%) pituitary adenoma with papillary features, and 1/2 (50%) lung adenocarcinomas with papillary features. The sensitivity of PAX-2+/RCCma+ immunophenotype for PRCC was 58% with a specificity of 54%. There is significant overlap between the expressions of these markers in PRCC and NRCPN; however, the positivity of RCCma and/or PAX-2 is 100% sensitive for PRCC and may prove useful in the initial work up of metastases of unknown primary. PAX-2 and RCCma immunohistochemistry should be interpreted with caution in papillary neoplasms, with particular attention to the possibility of ovarian and uterine papillary serous carcinomas, which can express both PAX-2 and RCCma.

Pseudoangiosarcomatous urothelial carcinoma of the urinary bladder.

The pseudoangiosarcomatous pattern has been described mostly in cutaneous and some visceral squamous cell carcinomas and is unique for its striking morphologic resemblance to angiosarcoma. Herein, we describe the clinicopathologic features of 7 pseudoangiosarcomatous urothelial carcinomas that occurred in the urinary bladder. The patients included 6 men and 1 woman ranging in age from 47 to 87 years (median 70 y). The pseudoangiosarcomatous morphology was observed in 7 urothelial carcinomas including 3 with squamous differentiation and comprised 35% to 85% of the invasive tumor. Histologically, the pseudoangiosarcomatous carcinomas were characterized by tumor cell discohesion and lysis that created pseudolumina formations surrounded by attached residual tumor cells. Detached degenerating tumor cells variably admixed with inflammatory cells were common in the false lumina. Partly intact urothelial carcinoma nests contained irregular or cleft-like spaces and disintegrating tumor cells with stretched intercellular bridges. The tumor was commonly associated with a dense collagenous matrix, often surrounding the lytic nests. Similar tumor cell discohesion and breakdown were observed in 3 tumors with foci of squamous cell differentiation, distinguished by the presence of dyskeratosis and keratin formation. All 7 tumors contained other nonpseudoangiosarcomatous carcinoma components such as conventional urothelial carcinoma (5), squamous differentiation (4), sarcomatoid spindle cell carcinoma (2), small cell carcinoma (1), micropapillary carcinoma (1), and glandular differentiation (1). The pseudoangiosarcomatous urothelial carcinomas were all (7/7) diffusely CK7 positive, most (6/7) were GATA3 positive, and none (0/7) expressed vascular-associated markers. There was no evidence to suggest that apoptosis (by TUNEL assay and cleaved caspase-3 immunostaining) or loss of the adhesion molecules CD138 and e-cadherin were possible causes for the tumor cell discohesion and breakdown. All 7 tumors were high stage at cystectomy and included 1 pT3a, 2 pT3b, and 4 pT4a tumors, and 3 had pelvic lymph node involvement. Follow-up data available in 6 cases revealed a poor outcome with an overall median survival of 8.5 months. In conclusion, we present an unusual morphology of bladder carcinoma that has a striking resemblance to a malignant vasoformative tumor. Our series showed that bladder pseudoangiosarcomatous carcinoma morphology is associated with a higher tumor stage at cystectomy, commonly admixed with other aggressive carcinoma variant morphologies, and portend a poorer outcome. Knowledge of this pattern is also important to avoid misdiagnosis, particularly in limited tissue samples.

Should hilar lymph nodes be expected in radical nephrectomy specimens

Lymph node (LN) status is essential in staging both renal cell carcinoma (RCC) and pelvic urothelial carcinoma (PUC). The rate of regional LN involvement is influenced by pathologic tumor stage, extent of the surgical resection, and accuracy of pathologic gross examination. In this study, we assess the presence of hilar LNs in radical nephrectomies (RN) by entirely submitting the hilar fat region (HFR) for microscopic evaluation (ME). Fifty consecutive RNs from 2006 to 2008 were evaluated by a standard gross examination protocol (SGEP) which consisted of palpation and sectioning of the HFR with submission of grossly identified LNs. Subsequently, the entire HFR was re-evaluated and submitted as studys total submission protocol (TSP). The number and disease status of hilar LNs identified by the SGEP and TSP were compared. Fifty RNs (37 clear cell RCC, 6 papillary RCC, 7 PUC) were studied prospectively. Ten of the 50 RNs had LNs identified (20%) with both protocols. Four of the 50 RNs had nodal metastases (8%) with the LN sizes ranging between 1.3 and 2.5 cm (mean 1.8 cm). All nodal metastases were identified by the SGEP. In three RNs (6%), additional minute (mean 0.12 cm) negative LNs not seen by the SGEP were identified by the TSP. LNs are present in only 20% of RNs, even after complete ME of the HFR. The SGEP for identifying hilar LNs in RNs is sufficient for staging and did not lead to underreporting of LN metastases.

Metastatic melanoma with dedifferentiation and extensive rhabdomyosarcomatous heterologous component

Melanoma may undergo dedifferentiation and sarcomatous transformation with loss of melanocytic markers. Dedifferentiated melanoma rarely forms true rhabdomyoblasts with skeletal muscle immunophenotype (rhabdomyosarcomatous heterologous component). A 52‐year‐old woman was diagnosed with invasive melanoma (Breslow thickness 0.83 mm) of the upper back in 2012, treated by wide local excision only. In 2013, an axillary mass was excised to show metastatic melanoma with 2 morphologies: an epithelioid morphology expressing S100 and MART‐1 and a spindled morphology with loss of melanocytic markers but strong expression of desmin. This metastasis was found to have BRAF V600E mutation. In 2015, a thoracic epidural mass biopsy showed atypical spindle cells with focal HMB‐45 but essentially no S100 expression. Numerous rhabdomyoblasts, some with striations that were strongly positive for desmin and myogenin, were present. In 2016, a right nephrectomy was performed for metastasis to the kidney, and showed sheets of spindle cells and rhabdomyoblasts expressing desmin and myogenin but not S100. Only focal areas demonstrated expression of HMB‐45 and SOX‐10, supporting the melanocytic origin of the tumor. The numerous rhabdomyoblasts and the loss of S100 expression in the metastatic lesions in this case could have easily led to misdiagnosis if the clinical history was not known.

Enucleation/partial nephrectomy for large mixed epithelial stromal tumor and herniating into the pelvicalyceal system

Objectives: Mixed Epithelial and Stromal Tumor of the kidney is an adult renal neoplasm. It is mostly benign in nature. Typically it is composed of a mixture of epithelial and mesenchymal components. We hereby report on the feasibility of performing partial nephrectomy/enucleation for Huge Mixed Epithelial Stromal Tumor of the kidney without sacrificing the involved renal unit even in the tumors herniating into the collecting system. Methods: Two female patients on long term hormonal therapy developed large enhancing multiloculated and septated renal masses. Kidney mass size was 18.5 cms in one patient and 11.5 in the second. In one patient, the mass was herniating into the collecting system. Both patients had enucleation/partial nephrectomy. Results: Enucleation and partial nephrectomy were successfully performed in both patients. In the patient with the mass herniating into the collecting system, the horns of the mass herniating into the collecting system were easily enucleated with repair of the collecting system and salvage of the involved renal unit. Post op pathology revealed MEST in both patients. There were no intraoperative or postoperative complications. Conclusions: Enucleation and partial nephrectomy for huge MEST is feasible. Mixed Epithelial Stromal Tumor herniating into the pelvicalyceal system may not warrant nephroureterectomy as previously reported.

Wilms Tumor: An Uncommon Entity in the Adult Patient.

Wilms tumor, the most common kidney tumor in children, is rarely seen in adults, making it a challenge for the adult oncologist to diagnose and treat. Unlike with renal cell carcinoma, patients with Wilms tumor should receive adjuvant chemotherapy with or without radiation therapy. Adult oncologists may not be familiar with pediatric oncology protocols, so it is important to consult with pediatric oncologists who have more experience in this disease. Multimodal therapy based on pediatric protocols improved the outcomes of adults with Wilms tumor worldwide. We report a rare case of a 24-year-old woman with a slow-growing mass of the left kidney during a 4-year period. The mass was surgically removed and final diagnosis confirmed by pathology to be Wilms tumor. The patient received adjuvant chemotherapy and has been free of disease since 2014.

Composite Paraganglioma and Neuroblastoma of the Urinary Bladder: A Rare Histopathological Entity

Paraganglioma of the urinary bladder is an uncommon clinical entity. Neuroblastoma of the urinary bladder is another rare tumor with only 7 reported cases, all in children. This report presents the case of a composite paraganglioma and neuroblastoma in a 45 year-old male who presented with dysuria and flank pain. On the computerized tomography scan, the bladder wall overlying the tumor was smooth and the mass had a large exophytic component. The initial diagnosis was paraganglioma on transurethral resection. Following partial cystectomy and bilateral pelvic lymph node dissection, pathology confirmed a composite tumor consisting of paraganglioma and neuroblastoma. To our knowledge, this is the first report of such a composite tumor involving the bladder.