Case # 4. 52 year old man with a 2 cm right kidney mass
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Diagnosis: Negative/Non-diagnostic Normal kidney tissue
Fine needle aspiration (FNA) of the kidney is performed in patients with renal lesions that are not candidates for immediate resection. Most commonly these are patients who are unresectable due to tumor stage or medical conditions, patients who may have metastatic disease to the kidney, or patients with indeterminant (usually cystic) lesions.
Increasingly young patients with small lesions who may be candidates for nephron sparing surgery (partial nephrectomy) ) are being aspirated (1). Although large lesions are usually straightforward, obtaining an adequate sample for evaluation may be difficult with cystic or small lesions.
Adequacy Criteria Unfortunately, there are no good adequacy criteria for renal FNA. Although it is reported that as many as 30% of aspirates are inadequate and a repeat aspiration remains unhelpful in over 40% of these cases (2-4), the criteria for this decision are not identified. In general, an FNA is adequate when a specific or differential diagnosis can be made.
Although there were many cells in the aspirate illustrated here, they were all normal elements, and would not account for the patient s mass. Normal elements are not uncommonly aspirated when an FNA is performed, especially when the lesion is small. These normal elements have been a source of false positive diagnoses in the College of American Pathologist s Non-Gynecologic Cytology Program. While there are only three normal elements in the kidney, each can be confused with different types of tumors.
Figure 5. Normal glomeruli
Glomeruli (Figs 1 and 5) are cellular globular structures which may mimic papillae of papillary renal cell carcinoma. These structures lack significant atypia, but so do low grade papillary renal cell carcinomas. In contrast to papillary renal cell carcinoma, however, the cellularity in a glomerulus is not evenly distributed, being much more dense in the center than at the periphery, and the endothelial cells lining the capillary loops can be seen at the extreme edge of many glomeruli.
In renal cell carcinomas, the nuclei may be peripheral, but the cytoplasm almost always extends even more peripherally, and the nucleus is never as flat as an endothelial cell.
Figure 6. Normal proximal tubular cells
Proximal tubular cells present as large isolated cells with round bland nuclei, small but easily seen nucleoli, and abundant, granular cytoplasm (Figure 2 and 6). The granularity is more easily appreciated on alcohol fixed preparations (Figure 6). Since the cells usually lack a well defined cell border, the granules often appear to be spilling out of the cell. These cells are very similar if not identical to those seen in oncocytoma.
FNAs of oncocytoma should be cellular and proximal tubular cells should be relatively scant. Cells in oncocytomas are not infrequently binucleate and proximal tubular cells are not. Often there will be some variation in cell and nuclear size in oncocytomas which are not seen in proximal tubular cells.
Usually the cell borders of oncocytoma cells are well defined while those of proximal tubular cells are torn and irregular. When the cells are stripped of their cytoplasm, the naked nuclei may resemble those of a clear cell renal cell carcinoma, but it is unusual for a clear cell tumor to be stripped of its cytoplasm and a diagnosis should not be made on naked nuclei alone.
Figure 7, Distal tubular cells
Distal tubular cells are small isolated or cohesive cells, with scant clear to slightly granular cytoplasm and small round nuclei without nucleoli (Figures 3, 4, and 7). Occasionally intact tubules will be seen (Figure 4). The cell borders are well defined, and the cytoplasm is not vacuolated although it may be clear (5). These cells can be identical to those seen in either a low grade clear cell or papillary renal cell carcinoma.
However: - distal tubular cells are rare and in diagnostic aspirates of renal cell carcinoma the cells should be abundant - distal tubular cells do not form the papillae and spherules that are seen in low grade papillary renal cell carcinoma - while the cytoplasm can appear clear it is almost always scant and is not as abundant as is seen in renal cell carcinomas.
How can pathologists avoid over-diagnosing normal elements as renal cell carcinoma? First, know what normal elements look like, and remember that these cells can closely mimic the cells of a low grade renal cell carcinoma. Second, most hypocellular specimens should be diagnosed as suspicious rather than positive. It is very unusual in a true FNA (rather than a direct smear or bench FNA) for there to be many normal elements.
While it is certainly true that some tumors are diagnosable on very limited material, most tumors are hypercellular,, and most of the benign lesions that can mimic a tumor (normal elements, atypical cyst lining cells, infarcts) are characteristically hypocellular. In most settings a suspicious diagnosis is sufficient to proceed with surgery.
Third, it is possible to get both proximal and distal tubular cells in the same aspirate, and the identification of two types of cells, one much larger and than the other should not be used as a criteria for malignancy. Finally, interpreting renal FNA is easier with experience. Since most pathologists see very few cases, a low threshold for obtaining additional consultation is prudent.
References 1.Renshaw AA, Granter SR, Cibas ES. Fine needle aspiration of the adult kidney. Cancer Cytopathol 1997;81:71-88. 2.Murphy WM, Zambroni BR, Emerson LD, Moinuddin S, Lee LH. Aspiration biopsy of the kidney. Cancer 1985;56:200-205. 3.Nguyen GK. Percutaneous fine-needle aspiration biopsy cytology of the kidney and adrenal. Pathol Annu 1987;22(1):163-191. 4.Cristallini EG, Paganelli C, Bolis GB. Role of fine-needle aspiration biopsy in the assessment of renal masses. Diagn Cytopathol 1991;7:32-35. 5.Linsk JA, Franzen S. Aspiration cytology of metastatic hypernephroma. Acta Cytol 1984;28:250-260.