In the past, nephrogenic adenoma was thought to arise from the remnant of embryogenic mesonephric tissue in the urinary tract, or from metaplastic change of urothelium due to inflammation or injury. In 1981, Bhagavan et al. examined nephrogenic adenoma morphologically with electron microscopy and found the presence of Tamm-Horsfall protein [
15]. They revealed that this lesion was of mesonephric origin rather than of metanephric. Based on the fact that the nephrogenic adenoma often occurs in patients who received kidney transplantation, Mazal et al. in 2002 [
3] made a research into the origin of nephrogenic adenoma. They analyzed X and Y chromosomes employing fluorescence in situ hybridization. In the cases of male recipients from female donors, the cells of nephrogenic adenoma had XX chromosome pattern, On the contrary, in the cases of female recipients from male donors, the cells had XY chromosome pattern. These results indicated that origin of nephrogenic adenoma was donor-derived renal cells [
3]. Moreover they thought nephrogenic adenoma in extrarenal organs like urinary bladder was caused by proliferation of cells of renal origin, and showed positive immunostaining of PAX2 [
16]. PAX2 is a transcriptional factor in development and expressed in renal tubular cells and parietal cells of the Bowman’s capsule of gromerulus [
16]. PAX2 has recently been considered to be one of the useful markers for nephrogenic adenoma [
16]. “ PAX8, another transcriptional factor, expressed in renal cells is also positive in nephrogenic adenoma [
17]. It is currently thought that dislodged renal tubular epithelial cells are transplanted into the urinary tract mucosa and engraftment occurs, resulting in the disease [
3]. In the present case, repeated urinary tract infection might have contributed to the development of nephrogenic adenoma. We consider that occurrence of the tumor in renal pelvis of both sides after bladder extraction supported this hypothesis.
About 10 % of the cases with nephrogenic adenoma occur in pediatric age [
1], and show the same morphological and immunohistochemical features as adult cases [
18]. They occur under the specific pathological conditions such as Turner's syndrome [
4] or prune belly syndrome [
5]. Multifocal [
6] and/or diffuse [
7] lesions have also been reported. FMF is known to cause inflammatory conditions such as peritonitis, pleurisy, arthritis, erysipelas-like erythema and pericarditis. Responsible gene of FMF located at chromosome 16p13.3 encodes a pyrin/marenostrin protein composed of 781 amino acids and consists of 10 exons [
11,
12]. Usually, pyrin has N-terminal PYRIN domain and C-terminal B30.2 domain. Activity of caspase-1 is regulated by ASC (apotosis-associated speck-like protein which contains a caspase recruitment domain) which bound to PYRIN domain and, B30.2 domain also regulates activity of IL-1β by directely inhibition of caspase-1 activation [
19,
20]. Major mutations of FMF are found in E148Q in exon 2, and M894V, M694I, V726A, and M680I in exon 10 of
PYD [
21,
22]. If there is a mutation in exon 10, the diagnosis of FMF can be confirmed. Additionally, if mutations in the other exons, including heterozygous mutation are detected, colchicine can be utilized not only for a treatment, but also for a diagnosis of FMF variant [
23]. In FMF variants, mutations in exon 1 (E84K), exon 2 (L110P, E148Q, R202Q, G304R), exon 3 (P369S, R408Q) and exon5 (S503C) are known. It is believed that inflammation is provoked by missense mutations of
PYRIN gene which result in loss of suppressive function of inflammasome and increase of IL-1β production [
19,
20]. In our case, only one heterozygous mutation of E148Q (exon2) was observed. There is a report that this mutation was seen in 20 % of Japanese patients [
24], but the present case was diagnosable as FMF variant, because treatment with colchicine was very effective. We did not search for other mutations on the chromosome, because most of them are limited at E148Q (exon2) and, M694I (exon 10) in the Japanese patients. Pyrin, located in microtubules and actin [
25], is a protein highly expressed in white blood cells. They are coded by MEFV gene which regulates inflammatory response by interacting with the cytoskeletons and mutation of this gene probably decreased or deleted its function [
25]. Colchicine also has a function to inhibit the polymerization of microtubules (tubulin). In the present case, not only white blood cells but also the tumor cells of nephrogenic adenoma were positive for vimentin. This suggests the possibility of expression of tubulin (component of cytokelaton). Many of the FMF cases are autosomal recessive, and the symptoms are less likely to occur in heterozygous mutation of E148Q (exon 2), so that the patient might have different mutations to cause the symptoms.