Normal urothelial cells possess the capacity to produce mucoid substances [4
]. Diffuse and globular mucoprotein deposits in urothelial cells have also been described [5
]. The ability of urothelial cells to secrete mucin in chronic urocystitis with and without glandular metaplasia and in adenocarcinomas or signet-ring cell carcinomas of the urinary bladder is well-known [6
]. On the other hand, urothelial bladder carcinoma exhibits diverse microscopic appearances. Foci of glandular metaplasia are common, usually in the form of intracytoplasmic mucin-containing vacuoles [7
Tumor cells in our case expressed the apomucins MUC1 and MUC2 Several mucin genes designated MUC genes have been identified [8
]. Previous studies have shown that MUC1 mucin protein is strongly expressed by urothelial cells. Walsh et al. examined the presence of MUC1 and -2 in normal and malignant urothelium and found that MUC1 was expressed by both normal and malignant epithelium, whereas MUC2 expression was found only in urothelial carcinomas [7
]. In colon carcinomas with MUC1, gene products have been correlated with advanced disease stage [9
]; on the other hand, in bladder carcinomas there is no significant association between high expression of MUC1 and histologic grade and also disease stage [7
]. MUC1 and -2 expression in our case was not correlated with poor prognosis, because both primary and recidiving tumors were low-grade superficial urothelial carcinomas.
Among a total of 100 cases of urothelial carcinomas, Donhuijsen et al. found that 37 tumors revealed periodic-acid Schiff-positive cytoplasmic inclusions [5
]. These inclusions were histochemically, immunohistochemically, and ultrastructurally identified as cytoplasmic deposits of mucoid materials, similar to our case.
There are several entities that should be considered in differential diagnosis. The most important reactive cystic change within the urothelium is the formation of von Brunn nests. In so-called florid Brunneriosis [10
] cyst formation is more pronounced and involves a large number of nest structures. Apical glandular differentiation and eosinophilic secretion are also common, acquiring features of cystitis cystica and cystitis glandularis. The case we have described herein may show numerous cysts with mucin secretion similar to cystitis cystica.
Several overlapping morphologic variants of urothelial carcinoma with glandular appearance exist. The so-called urothelial carcinoma with tubules is composed of small- to medium-size urothelial cell-lined tubules. The growth pattern of this tumor is mainly infiltrative; moreover, it lacks the signet-ring elements and larger cystic spaces present in our case [11
Another very similar entity comprises microcystic urothelial carcinoma. This type demonstrates cystic changes within an otherwise typical urothelial carcinoma, or urothelial carcinoma with glandular differentiation. Cysts were rarely be filled with eosinophilic secretion similar to our case. The cyst lining may be absent, flattened, urothelial, or differentiated toward mucinous cells. Cysts in our case were lined with urothelial cells; in addition, signet-ring cells were present in the walls of cysts [11
Urothelial carcinoma with gland-like lumina represents another microcystic change within an otherwise typical urothelial carcinoma. These luminal structures may contain mucin [13
]. We have found areas identical to this type of urothelial carcinoma within the main tumor mass of our case.
In conclusion, we present a case of superficial papillary urothelial carcinoma with striking multicystic architecture, with a combination of features of urothelial carcinoma with gland-like lumina, with signet-ring cell differentiation and microcystic pattern.