THE NESTED VARIANT OF UROTHELIAL CARCINOMA: A CLINICOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL STUDY OF ONE CASE AND COMPA

1. THE NESTED VARIANT OF UROTHELIAL CARCINOMA: A CLINICOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL STUDY OF ONE CASE AND COMPARISON TO FLORID VONN BRUNN’S NESTS RITA PASSANTINO - LORENZO MARASA’ DEPARTMENT OF PATHOLOGY, A.R.N.A.S. CIVICO, PALERMO

2. INTRODUCTION • Urothelial Carcinoma-Nested Variant (UC-NV) was described as a malignant entity by Talbert and Young in 1989. • Despite its deceptively bland histomorphological appearance, the lesion is reported to have an aggressive behaviour. • So far, in the international literature, less than 10 groups have reported their experience with this variant, suggesting that this lesion is either rare or underrecognized. • A case of this tumour is presented in this report.

3. CASE REPORT • On June 2007, a 73-year-old sicilian man was referred to our department because of two episodes of gross hematuria. • Computed tomography imaging studies showed a moderate bilateral hydronephrosis and a diffuse thickening of the bladder wall. • Lymphadenopathy or metastatic disease was not identified. • A biopsy of the bladder showed muscle-invasive urothelial carcinoma involving the trigone. Three weeks later, a radical cystoprostatectomy was performed.

4. GROSS EXAMINATION • Edematous urinary bladder mucosa and a markedly and diffusely thickened bladder wall with pronounced involvement of the trigone region and obstruction of the ureteral orifices.

5. HISTOLOGICAL EXAMINATION • This lesion had a deceptive benign appearance: except for the surface mucosa, the bladder wall was extensively infiltrated by neoplastic cells, which were arranged in a diffuse pattern of relatively ill-defined and variably sized nests. • The neoplastic cells were characterized by clear/pale cytoplasm with poorly defined borders and rounded nuclei with inconspicuous nucleoli. The chromatin was finely gra-nular and evenly distributed. There was generally no signi-ficant nuclear pleomorphism, and mitoses were rare. • UC-NV was the only type of urothelial carcinoma present in this case. Focal conventional flat overlying in situ urothelial carcinoma was identifiedwithout any direct connection with below UC-NV.

6. HISTOLOGICAL EXAMINATION

7. HISTOLOGICAL EXAMINATION

8. HISTOLOGICAL EXAMINATION

9. IMMMUNOHISTOCHEMICAL EXAMINATION • UC-NV had a high p53 and Ki-67 expression which correlates with the aggressiveness of this subtype, a strong staining for p63 wich supports the urothelial nature of this neoplasm, while CK20 was not discriminatory. p63 p53

10. CONCLUSIONS • UC-NV is a rare but important histopathologic entity. • It is a deceptively bland-appearing neoplasm with potential of deep invasion and metastases that should not go unrecognized because of its poor prognosis. • At early stage, this tumour, in fact, might be difficult to differentiate from benign conditions such as florid von Brunn’s nests, so the awareness of this condition is of outermost importance. There isn’t a specific cutoff value with regard to immunohistochemical features between UC-NV and florid vonn Brunn’s nests, so the morphologic assessment is very important in the distinction between these entities.

11. MAIN REFERENCES Volmar KE et al. Florid vonn Brunn nests mimicking urothelial carcinoma: a morphologic and immunohistochemical comparison to the nested variant of urothelial carcinoma. Am J Surg Pathol. 2003 Sep; 27(9): 1243-52. Lin O et al. Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 12 cases. Modern Pathology 2003; 16(12): 1289-1298.