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Presented by Dr. Jonathan Epstein and prepared by Dr. Yembur Ahmad
This case talks about a 45-year-old man with a bladder tumor.
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Clinical History: A 45 year-old man underwent a TUR for a bladder tumor.
Choose the correct diagnosis:
Correct
Answer: D
Histological Description: Within the lamina propria there is a proliferation of cells with amphophilic cytoplasm and overt pleomorphism. Although at a casual glance, the cells appear to grow in a diffuse sheet, upon closer inspection the cells are arranged in nests with a network of thin capillaries separating the nests. The tumor does not have prominent mitotic activity. The tumor invades muscularis propria.
Discussion: The mean age of paragangliomas in the bladder is 41 years with a broad range from 10-88 years. Although they often present with hematuria, patients may also have more specific symptoms of micturition attacks consisting of syncope, headache, hypertension, palpitation, blurred vision and/or sweating following straining when urinating. Two thirds of patients have hypertension. Most are exophytic with an intact smooth mucosa unless ulcerated. Tumors vary in size from several millimeters to 10 cm. Most are solitary. Usually, there are uniform sized and shaped nests delineated by delicate fibrovascular septae. Uncommonly, as in this case, paragangliomas can have foci of more diffuse growth where the nesting pattern is not as evident. The key to the correct diagnosis is recognizing the abundant amphophilic granular cytoplasm and also not having tunnel vision to only consider urothelial carcinoma when confronted with a nested tumor in the bladder. Another aspect of the current case that is diagnostically difficult is that in the typical case of paraganglioma involving the bladder, nuclei are typically uniform small and round with uniform chromatin. However, cases like our can have occasional scattered pleomorphic enlarged nuclei, most with a degenerative appearance consisting of smudgy indistinct chromatin. In contrast to a high grade pleomorphic urothelial carcinoma, mitotic figures are uncommon. In contrast to urothelial carcinoma, paragangliomas are cytokeratin negative and synaptophysin and chromogranin positive. In some cases, S100 highlights sustentacular cells surrounding tumor nests. An immunohistochemical pitfall is that both invasive urothelial carcinoma and paraganglioma are positive for GATA3. All paragangliomas should also be evaluated immunohistochemically for SDHB which can be lost as a result of a sporadic mutation but could also represent a germline mutation associated with the hereditary paraganglioma syndrome. Paragangliomas which show loss of SDHB have a higher risk of malignant behavior. Depending on the location and size of the tumor, final treatment could be only the initial TUR, repeat TUR, or partial or radical cystectomy. Paragangliomas can invade the muscularis propria, as seen in the current case. 10% of bladder paragangliomas are malignant, which cannot be predicted based on the morphology.
Incorrect
Answer: D
Histological Description: Within the lamina propria there is a proliferation of cells with amphophilic cytoplasm and overt pleomorphism. Although at a casual glance, the cells appear to grow in a diffuse sheet, upon closer inspection the cells are arranged in nests with a network of thin capillaries separating the nests. The tumor does not have prominent mitotic activity. The tumor invades muscularis propria.
Discussion: The mean age of paragangliomas in the bladder is 41 years with a broad range from 10-88 years. Although they often present with hematuria, patients may also have more specific symptoms of micturition attacks consisting of syncope, headache, hypertension, palpitation, blurred vision and/or sweating following straining when urinating. Two thirds of patients have hypertension. Most are exophytic with an intact smooth mucosa unless ulcerated. Tumors vary in size from several millimeters to 10 cm. Most are solitary. Usually, there are uniform sized and shaped nests delineated by delicate fibrovascular septae. Uncommonly, as in this case, paragangliomas can have foci of more diffuse growth where the nesting pattern is not as evident. The key to the correct diagnosis is recognizing the abundant amphophilic granular cytoplasm and also not having tunnel vision to only consider urothelial carcinoma when confronted with a nested tumor in the bladder. Another aspect of the current case that is diagnostically difficult is that in the typical case of paraganglioma involving the bladder, nuclei are typically uniform small and round with uniform chromatin. However, cases like our can have occasional scattered pleomorphic enlarged nuclei, most with a degenerative appearance consisting of smudgy indistinct chromatin. In contrast to a high grade pleomorphic urothelial carcinoma, mitotic figures are uncommon. In contrast to urothelial carcinoma, paragangliomas are cytokeratin negative and synaptophysin and chromogranin positive. In some cases, S100 highlights sustentacular cells surrounding tumor nests. An immunohistochemical pitfall is that both invasive urothelial carcinoma and paraganglioma are positive for GATA3. All paragangliomas should also be evaluated immunohistochemically for SDHB which can be lost as a result of a sporadic mutation but could also represent a germline mutation associated with the hereditary paraganglioma syndrome. Paragangliomas which show loss of SDHB have a higher risk of malignant behavior. Depending on the location and size of the tumor, final treatment could be only the initial TUR, repeat TUR, or partial or radical cystectomy. Paragangliomas can invade the muscularis propria, as seen in the current case. 10% of bladder paragangliomas are malignant, which cannot be predicted based on the morphology.