Thyroidization of the kidney is a well known phenomenon, where dilated tubular structures with atrophic epithelium containing colloid-like material imitate the usual structure of the thyroid gland. Usually, thyroidization occurs as a process secondary to chronic pyelonephritis and is a habitual characteristic of an end stage kidney disease. But the similarities between the kidney and the thyroid gland do not end up here. In the last years, a unique tumor type, primary to the kidney, but essentially looking as a thyroid lesion has been described, being named TLFC of the kidney. The first and by now the only real series consisted of 6 cases , 4 of those tumors being described for the second time by the same author. The well circumscribed neoplasms histologically resembling follicular carcinoma of the thyroid gland, but lacking typical thyroid markers, were reported to have favorable prognosis. Only one of the patients from that series, with tumors measuring up to 11.8 cm in greatest diameter, developed a metastasis in the renal hilar lymph node. The other patients were disease free in the follow up period from 7 to 84 months .
Additional case reports appeared in the literature [6–10], all but one describing tumors with follicular morphology, composed of cells with moderate amphophilic to slightly eosinophilic cytoplasm creating macro and microfollicles containing inspissated colloid-like material, with only small amount of packed follicles devoid of secretions. One of two cases described by Alessandrini et al. , however showed focal papillary arhitecture, without nuclear grooving or optical clearing. In our case, nuclear grooves have been visible in both specimens. In FNAB, focal calcifications were additionally noted on top of some fragments, which was not the case in histological samples, where they were absent. Analogous to our case, nuclear grooves in FNAB of TFLC have been noted by Dhillon et al. . The authors retrospectively described FNAB results after already publishing histologic and clinical characteristics of the same TFLC, unique for the presence of lung and retroperitoneal lymph nodes metastases . This was also the only case of TFLC with distant metastases, as these tumors generally have low malignant potential .
Concerning the tumor growth pattern in our case, although predominantly macrofollicular in HE slides, the papillary tumor growth could be observed focally in the histology, as well as in FNAB. This, in addition to calcifications present in FNAB, has led to the cytological diagnosis of papillary renal cell neoplasm, morphologically corresponding to MiTF/TFE family translocation-associated renal carcinoma, which was subsequently excluded by morphology of the nephrectomy specimen and negative TFE3 immunohistochemistry.
Marked lymphocytic infitration may be present in cases of TFLC, mostly as prominent intratumoral collections, but sometimes it is seen at the periphery, surrounding the tumor. These collections may occasionally contain lymphoid follicles with reactive germinal centers . Our case was devoid of inflammation. Due to the presence of calcium oxalate crystals, only mild lymphocytic infiltrate was present around focally disrupted tubuli in the medulla.
Immunohistochemically, the TFLCs described in the literature showed variable, although relatively consistent negativity for Pax-2, RCC, CD10, WT-1, P504S, vimentin, CD56 and CD57 , and typical (but not obligate) negativity for CK7. For the diagnosis of TFLC all cases should be negative for thyroid markers such as TTF-1, thyroglobulin and galectin-3. In one reported case  the tumor was thyroglobulin positive, but the authors did not test TTF-1 or galectin-3. The exclusion of a metastazing thyroid carcinoma was carried out merely with clinical methods therefore one can argue, that the kidney tumor was a metastasis. However, the uneventful follow up of 18 months is a strong argument against a metastasizing thyroid carcinoma.
Although very rare, metastases to the kidney from the thyroid have been reported. Due to typical follicular morphology of the FTCL the metastasis of follicular thyroid carcinoma should be excluded in the first place. Metastatic follicular and papillary thyroid carcinoma in the kidney usually occur in patients with disseminated disease [14, 15], sometimes even long after the primary tumor has been treated [16, 17]. Another possible origin of a TTF-1 positive follicular tumor metastatis is struma ovarii, which is a very remote possibility, as are other follicular neoplasms, entering differential diagnosis such as serous and small cell carcinoma of the ovary, intrahepatic cholangiocarcinoma or breast tumors with follicular morphology [5, 9]. Other rare primary tumors of the kidney with follicular growth pattern include carcinoid of the kidney (our case was CD56 negative) and, due to thyroidization-like appearance, the acquired cystic-disease associated RCC, which will be discussed later.
Returning to discussion on immunohistochemistry, the present TTF-1 and thyroglobulin negative case fits into the criteria for TLFC. However, diffuse positivity for CK7 and P504S was detected. Since in the literature variable staining results for those two markers were reported, they do not exclude our diagnosis «per se«. Nevertheless, our immunohistochemical results open the question whether or not this tumor could be a variant of papillary RCC. The only FISH analysis , which was performed on this tumor, did not show the clasical aberrations of the papillary carcinoma (trisomy 3q, 7, 8, 12, 16, 17 and loss of Y chromosome) but completely unspecific aberrations (loss of chromosomes 1, 3, 7, 9p21, 12, 17, and X). Genetic profiling of RCCs generally helps defining renal cell tumor subtypes in cases with inconclusive morphology, as shown in a report of synchronous clear cell RCC and tubulocystic carcinoma . However, more data on genetic changes are needed to draw conclusions and clarify differential diagnosis in cases of TFLC.
Due to thyroidization like appearance of TFLC, the acquired cystic-disease associated RCC is another differential diagnosis. However, our patient did not suffer from an acquired but a hereditary renal cystic disease, which is the most common hereditary renal cystic disease. The clinical deterioration of the renal function can go unnoticed and the disease is diagnosed as an incidental finding at autopsy. Mostly, the end stage kidney disease appears at the age of 40 years. In our patient the polycystic disease has been diagnosed incidentally at the US examination due to persistent pain after spontaneous renal stone elimination. Although the patient is not an at-risk individual (no ADPKD familal history) the diagnosis of ADPKD was made clinically according to US criteria, since it is well known, that the family history may be absent in 20-40% patients . Molecular analysis for determination of patient's genetic status was not performed, neither was it required for the diagnosis. As already mentioned, the patient's kidney function has not yet deteriorated, his blood pressure is normal.
Cystic appearance of the kidney containing solid tumor leads to differential diagnostic consideration of another rare primary renal neoplasm with favourable prognosis, namely mixed epithelial stromal tumor of the kidney (MEST), tumor with morphological similarities to cystic nephroma. However, MEST contains ovarian type stroma positive for estrogen and progesterone receptors and is predominantly observed in middle aged women .
The association between polycystic kidney disease and RCC has been well documented [20–22], as well as the association of acquired polycytic kidney disease with renal tumors, which now represent a special type of tumor, already included into the WHO classification . One of the characteristics of those tumors, in addition to the end stage kidney disease, is the abundance of calcium oxalate crystals. Similar calculi, although not so abundant, have been found also in the kidney of our patient. In the first place, they were the reason for the diagnosis of ADPKD as well as of renal tumor, since the presenting symptom in our patient has been nephrolithasis with spontaneous stone elimination. However, no specific type of neoplasm has been descibed to occur in ADPKD. Most common histological subtypes assocated with ADPKD were clear cell RCC, followed by papillary and tubulocystic carcinoma [20–22]. Primary neuroendocrine tumors of the kidney, although rare, have also been reported to most commonly arise in the setting of acquired and congenital abnormalities, including polycystic kidney disease in 2% . We are not aware of any published case of FTLC occuring in association with ADPKD. Our case, however shares some characteristics of papillary RCC, for instance CK7 and P504S positivity as well as focal papillary growth. Clinicaly, the association to ADPKD would also make more sense if the diagnosis in our case would be papillary RCC. However, the macrofollicular morphology, inspissated material, RCC and CD10 negativity as well as CK34βe12 positivity are the hallmarks of TLFC. There was no difference between follicular and papillary areas in the immunostaining patterns. Thyroid like kidney tumors with both, follicular and papillary features have been described also by other authors [24–26].