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Presented by Dr. Jonathan Epstein and prepared by Dr. Sintawat Wangsiricharoen
A 65 year-old woman underwent a TURB showing an invasive tumor in the bladder.
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Question 1 of 1
1. Question
A 65 year-old woman underwent a TURB showing an invasive tumor in the bladder.
Choose the correct diagnosis:
Correct
Answer: A. Uterine cervical cancer invading the bladder
Histological Description: There are variably sized invasive nests of basaloid carcinoma with a non-keratinizing squamous appearance undermining normal urothelium. There is moderate-marked cytological pleomorphism.
Discussion: The morphology of cervical carcinoma can mimic the often variable and non-specific histologic appearance of urothelial carcinoma. Urothelial carcinoma can appear similar to squamous cell carcinoma as it can demonstrate a squamoid appearance as well as a nested appearance. Further, cervical carcinoma involving the bladder can colonize surface urothelium mimicking urothelial carcinoma in situ. The lack of surface involvement and/or nests of tumor cells involving deep muscular tissue can provide a clue that the tumor is secondarily involving the bladder rather than a primary, although this histology can occasionally be seen in a primary urothelial carcinoma. Uterine cervical squamous carcinoma can be negative for GATA3, though some cases can exhibit moderate to strong staining. p16 overexpression and positive p16 immunohistochemical staining in primary bladder neoplasms, including urothelial carcinoma with squamous differentiation, primary bladder squamous cell carcinoma, and primary bladder adenocarcinoma demonstrates that p16 in general does not act as a surrogate marker for HPV infection and does not rule out a bladder primary. The main utility of p16 immunohistochemistry in this differential diagnosis is that negative and patchy results argue against a cervical primary, although in a minority of cervical squamous carcinomas there may be non-diffuse p16 staining. A more definitive test where cervical carcinoma involving the bladder is in the differential, is to perform ISH for high risk HPV, as bladder urothelial carcinomas are negative. In the current case, RNA ISH was diffusely positive for high risk HPV proving the tumor was uterine cervical carcinoma invading the bladder. Given the critical distinction in treatment and prognosis, there should be a low threshold for performing ISH for high risk HPV in a woman with a non-keratinizing squamous cell carcinoma involving the bladder in the absence of an in-situ urothelial carcinoma component.
Reference:
Carcinoma of the Uterine Cervix Involving the Genitourinary Tract: A Potential Diagnostic Dilemma. Schwartz LE, Khani F, Bishop JA, Vang R, Epstein JI. Am J Surg Pathol. 2016;40:27-35Incorrect
Answer: A. Uterine cervical cancer invading the bladder
Histological Description: There are variably sized invasive nests of basaloid carcinoma with a non-keratinizing squamous appearance undermining normal urothelium. There is moderate-marked cytological pleomorphism.
Discussion: The morphology of cervical carcinoma can mimic the often variable and non-specific histologic appearance of urothelial carcinoma. Urothelial carcinoma can appear similar to squamous cell carcinoma as it can demonstrate a squamoid appearance as well as a nested appearance. Further, cervical carcinoma involving the bladder can colonize surface urothelium mimicking urothelial carcinoma in situ. The lack of surface involvement and/or nests of tumor cells involving deep muscular tissue can provide a clue that the tumor is secondarily involving the bladder rather than a primary, although this histology can occasionally be seen in a primary urothelial carcinoma. Uterine cervical squamous carcinoma can be negative for GATA3, though some cases can exhibit moderate to strong staining. p16 overexpression and positive p16 immunohistochemical staining in primary bladder neoplasms, including urothelial carcinoma with squamous differentiation, primary bladder squamous cell carcinoma, and primary bladder adenocarcinoma demonstrates that p16 in general does not act as a surrogate marker for HPV infection and does not rule out a bladder primary. The main utility of p16 immunohistochemistry in this differential diagnosis is that negative and patchy results argue against a cervical primary, although in a minority of cervical squamous carcinomas there may be non-diffuse p16 staining. A more definitive test where cervical carcinoma involving the bladder is in the differential, is to perform ISH for high risk HPV, as bladder urothelial carcinomas are negative. In the current case, RNA ISH was diffusely positive for high risk HPV proving the tumor was uterine cervical carcinoma invading the bladder. Given the critical distinction in treatment and prognosis, there should be a low threshold for performing ISH for high risk HPV in a woman with a non-keratinizing squamous cell carcinoma involving the bladder in the absence of an in-situ urothelial carcinoma component.
Reference:
Carcinoma of the Uterine Cervix Involving the Genitourinary Tract: A Potential Diagnostic Dilemma. Schwartz LE, Khani F, Bishop JA, Vang R, Epstein JI. Am J Surg Pathol. 2016;40:27-35
