Fase I de las observaciones práctica III

The direct smears that were Giemsa stained revealed bloody and moderately cellular sample, composed predominantly of normal renal tubular epithelium. A few small tissue fragments with nests of atypical cells partly embedded in eosinophilic fibrous stroma were observed (Fig. 3). In some small open groups, medium sized cells showed enlarged nuclei with slight variation of size and shape, even chromatin and poorly defined pale cytoplasm. Some atypical naked nuclei were also found. There was no cellular material available for immunocytochemical staining. Cyto-

pathological diagnosis was atypical cells - malignancy could not be excluded - with a recommendation to repeat US-FNAB of the renal tumor which was per- formed a month later.

Cytomorphology of the second US-FNAB sample was the same as was the cytopathological diagnosis, because again there was no cellular material for immunocytochemistry.

Figure 3. Juxtaglomerular cell tumor. A small tissue frag-

ment with nests of atypical cells partly embedded in eosi- nophilic fibrous stroma with blood in the background in ultrasound guided fine-needle aspirate (Giemsa, x400).

Histopathology

The patient was operated 6 months later and partial resection of the left kidney was performed. On gross examination the resection specimen measured 2×2.5 cm. A tumor measuring 2 cm on the greatest diameter was found on the cut surface. The tumor was well demarcated, cystic and hemorrhagic. The cyst wall was 2 mm thick. Histologically, the tumor was com- posed of sheets of polygonal cells with central round nuclei showing some atypia and with abundant gra- nular eosinophilic cytoplasm. Tumor showed complex vascular hemangiopericytic pattern with remnants of tubular elements (Fig. 4). Many different antibodies were used for immunhistochemical assessment of the tumor with the following results: EMA-, CD10-, RCC-, HHF-35-, SMA-, CD117-, S-100-, desmin-, CD31-, synaptophysin-, chromogranin-, calponin-, calcitonin-.

Finally, after obtaining clinical data on high blood pressure, immunohistochemical staining for diagnostic antigens was performed with positive staining for renin, vimentin and CD34. The diagnosis of juxtaglo- merular cell tumor (JGCT) was definitely confirmed by electron microscopy which revealed rhomboid shaped renin protogranules.

Cyto‐ and histopathology of rare kidney tumors 

Figure 4. Juxtaglomerular cell tumor. Sheets of polygonal

cells with central round nuclei showing atypia and with abundant granular eosinophilic cytoplasm. Hemorrhage between sheets of tumor cells resembles hemangiopericytic pattern (H&E, x200).

Discussion

JGCT is a very rare benign renin-secreting tumor occurring in younger patients, mostly between 20 and 30 years of age. It arises from specialized smooth muscle cells of the juxtaglomerular apparatus. Patients usually present with severe poorly controlled hyper- tension accompanied by hyperkalemia and secondary aldosteronism which resolve after surgical removal of tumor. JGCT can present with variable histolo- gical patterns therefore immunohistochemical staining for renin, vimentin, CD34 and electron microscopy revealing renin protogranules significantly contribute to correct final diagnosis (15).

Cytomophology of JGCT has been reported in a few cases with only one case assessed preoperatively and interpreted as papillary renal cell carcinoma due to papillary-like structures, mild nuclear pleomorphism and hyperchromasia. The authors concluded that FNA is not sensitive enough for reliable diagnosis (16). However with the knowledge of this rare entity combined with appropriate clinical data on high blood pressure in a young patient the diagnosis of JGCT might at least be suggested among differential diag- noses in US-FNAB sample.

Case 3

A 34-year old patient presented with nephrolithiasis and spontaneous stone elimination. The abdominal ultrasound (US) examination revealed hepatorenal polycystic disease, consistent with adult type poly-

cystic kidney disease (ATPKD). Additionally, a hy- perechogenic cyst was detected in his left kidney, measuring 4 to 5 cm in greatest diameter. US-FNAB of the lesion followed.

Cytomorphology

Direct smear was highly cellular with predominant tri-dimensional tissue fragments. Papillary-like struc- tures and nucler pallisading were noted at the edges of many fragments, while some exhibited cribriform- like pattern. All fragments contained numerous deep pink stained globules of different sizes (Fig. 5). Calcifications were noted on top of some clusters. Cells were rather uniform, medium sized, mainly organized around pink globules. Nuclei were oval with slight variation in size, bland chromatin, with small nucleoli, some exhibiting grooves. The cyto- plasm was moderate to abundant, vacuolated, cell borders could be appreciated in Papanicolaou stained cytopins. Single cells were very rare, however some round naked nuclei were found. Abundant granulated pink material, numerous macrophages and erythro- cytes were present in the background. Tumor cells were negative for RCC and CD10 and positive for P504S, vimentin and CK7.

The cytopathological diagnosis suggested papillary renal cell neoplasm, morphologically corresponding to MiTF/TFE family translocation-associated renal carcinoma.

Figure 5. Thyroid-like follicular carcinoma of the kidney.

Tri-dimensional tissue fragments with papillary-like struc- tures and nuclear pallisading or cribriform-like pattern with deep pink stained globules of different sizes in ultrasound guided fine-needle aspirate (Giemsa, x100).

Histopathology

Left nephrectomy was performed. The resection spe- cimen weighted 720 g and measured 18×13 cm in

Cyto‐ and histopathology of rare kidney tumors 

greatest diameters, the kidney measured 13×7 cm. The renal parenchyma was mostly polycystic. The sharply circumscribed incapsulated solid grey tan tumor was found in the lower pole of the kidney and measured 5.5×4.8 cm. Centrally, it was partially haemorrhagic and cystically degenerated.

Histologically, the tumor was incapsulated and con- sisted of tubular and cystic structures resembling thyroid follicular carcinoma. The follicular structures were of various sizes, lined mostly by cuboidal cells and filled with amorphous eosinophillic / basophillic material reminiscent of coloid or mucus (Fig. 6). The nuclei were round to oval with evenly distributed chromatin, the nucleoli were inconspicuous. Occa- sionally, nucleoli were more prominent, with nuclear features corresponding mostly to Fuhrman grade 2, focally even grade 3. Similarly to FNAB nuclear grooves could be detected in some areas, but there were no calcifications. Invasion into the tumor capsule was found on multiple locations. There was no mi- totic activity. Focally, the tumor showed papillary or even solid growth with higher nuclear grade. Wide panel of antibodies was used for immunohisto- chemistry with the following results: CAM5.2+, CD10-, CD15-, CD56-, CD117-, CEA-, CK7+, CK20-, CK34βe12+, CK AE1/AE3+, EMA+, P504S+, RCC+, TFE3-, thyroglobulin-, TTF-1-, vimentin-, WT-1-.

Final histopathological diagnosis was thyroid-like follicular carcinoma of the kidney.

Figure 6. Thyroid-like follicular carcinoma of the kidney.

Tubular and cystic structures resembling thyroid follicu- lar carcinoma (H&E, x100).

Discussion

New rare renal tumor entities have been described in the last decade among them the thyroid-like folli- cular carcinoma (TLFC) of the kidney which is not

yet included in the current WHO cleassification. Histologically it shares similarities to primary thyroid follicular carcinoma, but is negative for thyroid immunohistochemical markers (16,17). TLFC is presumed to have low malignant potential, however analysis of further cases is needed to acquire addi- tional knowledge on clinical characteristics and bio- logical behavior.

Only one case of cytological features of renal TLFC was reported retrospectively on the sample prepared by intraoperatiove smear (18). They observed a hyper- cellular smear with cells arranged in sheets but with- out any follicular, papillary, or acinar arrangement and eosinophilic material associated with the neo- plastic epithelial cells in the background of the smear. Their differential diagnoses included a primary renal- cell carcinoma versus a metastatic tumor. On the review, our case contained tissue fragments with folli- cular structures and eosinophilic coloid-like material that were misinterpreted as papillary structures sug- gesting papillary renal cell neoplasm, probably MiTF/ TFE family translocation-associated renal carcinoma (17). Also immunoprofile was suggestive of papillary type of renal cell carcinoma. Awareness of the new entity could give broader range of differential diag- noses in US-FNAB specimen.

Conclusion

In our previous study we have shown that US-FNA can accurately classify major subtypes of RCC in routine clinical setting when sufficient cellular ma- terial is obtained and cytomorphology was supple- mented by immunocytochemical staining (19). How- ever, unusual or rarely observed cytomorphology of renal neoplasms accompanied by unusual immuno- phenotype were prone to misdiagnosis. Specifically atypical cells in a poorly cellular sample suggested possible malignancy in JGCT while papillary-like structures proposed diagnosis of papillary type of renal cell carcinoma as in MEST and TLFC. Additio- nally, immunocytochemical reactions can be mislea- ding because the positivity for some markers over- laps with papillary type of renal cell carcinoma. Therefore outmost caution is advised in assessing US- FNAB samples of renal lesions with unusual cytomor- phology to avoid misdiagnosis.

References

1. Orell SR, Langlois SL, Marshall VR. Fine needle as- piration cytology in the diagnosis of solid renal and adrenal masses. Scan J Urol Nephrol 1985; 19: 211–6.

Cyto‐ and histopathology of rare kidney tumors 

2. Pilloti S, Rilke F, Alasio L, Garbagnati F. The role of fine needle aspiration in assessment of renal masses. Acta Cytol 1988; 32: 1–9.

3. Kelley CM, Cohen MB. Raab SS. Utility of fine- needle aspiration biopsy in solid renal masses. Diagn Cytopathol 1996; 14: 14-19.

4. Renshaw AA, Granter SR, Cibas ES. Fine-needle as- piration of the adult kidney. Cancer 1997; 81: 71–88. 5. Laguna MP. Kümmerlin I, Rioja J, de la Rosette JJMCH. Biopsy of renal mass: where are we now? Curr Opin Urol 2009; 19: 447–53.

6. Kümmerlin IPED, Smedts F, ten Kate FJWHorn T, Algaba F, Trias I, Wijkstra H, et al. Cytological punc- tures in the diagnosis of renal tumors: a study on accu- racy and reproducibility. Eur Urol 2009; 55: 187–98. 7. Adeniran AJ, Al-Ahmadie HA, Iyengar P, Reuter V, Lin O. Fine needle aspiration of renal cortical lesions in adults. Diagn Cytopathol 2010; 38: 710–5. 8. Renshaw AA, Lee KR, Madge R, Granter SR. Accu-

racy of fine needle aspiration in distinguishing subtypes of renal cell carcinoma. Acta Cytol 1997; 41: 987–94. 9. Volpe A, Mattar K, Finelli A, Kachura JR, Evans AJ,

Geddie WR, et al. Contemporary results of percuta- neous biopsy of 100 small renal mases: a single center experience. J Urol 2008; 180: 2333–7.

10. Renshaw AA. Subclassification of renal cell neoplasms: an update for practicing pathologist. Histopathology 2002; 41: 283–300.

11. Skinnider BF, Amin MB. An immunohistochemical approach to the differential diagnosis of renal tumors. Semin Diagn Pathol 2005; 22: 51–68.

12. Michal M, Hes O, Bisceglia M, et al. Mixed epithelial

and stromal tumors of the kidney. A report of 22 cases. Virchows Arch 2004; 445: 359–67.

13. Turbiner J, Amin MB, Humphrey PA, et al. Cystic nephroma and mixed epithelial and stromal tumor of the kidney: a detailed clinicopathologic analysis of 34 cases and proposal for renal renal stromal and epithelial tumor (REST) as a unifying term. Am J Surg Pathol 2007; 31: 489–500.

14. DeFanti L, Nodit L. Mixed Epithelial and Stromal Tumor-Cytologic Findings of an Unusual Renal Cyst. Diagn Cytopathol 2013 Feb 27. doi: 10.1002/dc.22964. [Epub ahead of print].

15. Méndez GP, Klock C, Nosé V. Juxtaglomerular cell tumor of the kidney: Case report and differential diag- nosis with emphasis on pathologic and cytopathologic features. Int J Surg Pathol 2011; 19: 93–8.

16. Malde S, Sheikh I, Woodman I, Fish D, Bilagi P, Sheriff MKM. Primary Thyroid-Like Follicular Renal Cell Carcinoma: An Emerging Entity. Case Reports in Pathology Volume 2013, Article ID 687427, 5 p. [http://dx.doi.org/10.1155/2013/687427]

17. Volavšek M, Strojan Fležar M, Mikuz G. Thyroid- like follicular carcinoma of the kidney in a patient with nephrolithiasis and polycystic kidney disease: a case report. Diagn Pathol 2013; 8: 108. doi:10.1186/ 1746-1596-8-108.

18. Dhillon J, Mohanty SK, Krishnamurthy S. Cytologic diagnosis of thyroid-like follicular carcinoma of the kidney: A case report. Diagn Cytopathol 2012; Nov 16. doi:10.1002/dcc.22930. Epub ahead of print 19. Strojan Fležar M, Gutnik H, Jeruc J, Srebotnik-Kirbiš

I. Typing of renal tumors by morphological and immu- nocytochemical evaluation of fine needle aspirates. Virchows Arch 2011; 459: 607–14.