Introduction

Paragangliomas are the tumors of the paraganglionic tissue in our body. Depending upon their size and and anatomic location, paragangliomas can cause a variety of signs and symptoms but their morphology alone is almost the same. Paragangliomas represent an uncommon neoplasms of the urinary bladder (1). Their origin is uncertain but they are tought to arise from the paraganglionic tissue that can be found in the wall of the urinary bladder (2). Although the most common clinical presentation is hematuria, bladder paragangliomas may cause voiding-associated or voiding exacerbated symptoms of hypertension, headache, palpitations, blurred vision and/or sweating due to their hormonally active status. The tumors may arise at any age, occur more or less equally in both sexes and rarely may be associated with neurofibromatosis, multipl endocrine neoplasia type 2 and von Hippel-Lindau disease (3). Although most paragangliomas are sporadic, germline mutations in the succinate dehydrogenase family of genes encoding subunit A, B, C and D (SDHA, SDHB, SDHC, SDHD) of the mitochondrial respiratory chain complex II are one of the genetic causes of hereditary cases (3). Macroscopically, the tumors are typically lobulated, solid, submucosal or intramural dome-shaped masses covered by intact urothelium. Their size may vary from a few cm to 10 cm in diameter, but most are small. Light microscopy usually shows discrete nests of neoplastic chief cells in the characteristic Zellballen pattern with intervening vascular septa (Figure 1), but this feature is not always conspicuous and some tumors grow diffusely. The neoplastic cells are round or polygonal epitheloid cells with abundant eosinophilic or granular cytoplasm. Tumor cell nuclei are centrally located and are vesicular with finely granular chromatin. The cell nests are surrounded by S-100 (+) sustentacular cells (Figure 2) (4). Morphological featureas such as nuclear pleomorphism, mitotic figures, atypical mitosis or presence of necrosis are not a reliable predictor for malignant behaviour. Approximately 10% of the neoplasms are malignant and this is best predicted by depth of invasion into the bladder wall and confirmed by the presence of regional or distant metastasis (1). If present, the metastases mostly involve regional lymph nodes, lung, liver and skeleton. The neoplastic chief cells are argyrophilic and positive for neuroendocrine markers including neuron-specific enolase, chromogranin and synaptophysin (Figure 3). A variety of hormonal substances, including serotonin, vasoactive intestinal polypeptide, gastrin, substance P, somatostatin, and bombesin may also be found to be positive immunohistochemically in the chief cell cytoplasms. For bladder paragangliomas, the most important differential diagnosis is urothelial carcinoma. Based on a series of Zhou et al. (5), 20% of the tumors were initially misdiagnosed as carcinoma. In the context of a muscle invasive nested lesion, paraganglioma may be interpreted erroneously as invasive nests of urothelial carcinoma. However, the infiltrative nests of urothelial carcinoma lack the prominent vascular network of paraganglioma and are usually seperated by variable amounts of stromal tissue and do not form a circumscribed mass. Other tumors which may mimic paraganglioma are prostatic adenocarcinoma, metastatic large cell neuroendocrine carcinoma, granular cell tumor, alveolar soft part sarcoma, metastatic renal cell carcinoma, carcinoid tumors and malignant melanomas. All of these tumors have their characteristic morphology and immune profile (4). Therefore, the differential diagnosis may easily be made. Treatment of urinary bladder paraganglioma is primarily surgical by transurethral resection, partial cystectomy, or radical cystectomy (4). Concept: Ipek Isik Gönül, Design: Ipek Isik Gönül, Data Collection or Processing: Ipek Isik Gönül, Analysis or Interpretation: Ipek Isik Gönül, Literature Search: Ipek Isik Gönül, Writing: Ipek Isik Gönül, Peer-review: Internal peer-reviewed, Conflict of Interest: No conflict of interest was declared by the authors, Financial Disclosure: The authors declared that this study has received no financial support.