Varying numbers of renal tubules and glomeruli may be found in fine needle aspirations. Glomeruli appear as thick, rounded structures with dense centers (Fig. 5.1). Renal tubules are seen as small monolayer tissue fragments, groups, or tubular structures (Figs. 5.2 and 5.3). They may be mistaken for well-differentiated renal cell carcinoma in limited specimens.

Kidney cancers usually occur in older people. They may be sporadic or hereditary. The latter comprise about 4 % of kidney tumors. The majority of these primary malignant neoplasms of kidney are carcinomas arising from renal parenchyma. Primary tumors arising from the renal pelvis are rare. They are mostly urothelial, but squamous cell and adenocarcinomas may also occur.

Renal cell carcinomas make up a small percentage (~3 %) of adult malignancies. They have multiple chromosomal abnormalities which differ among the types of RCCs. Some of these are shown in Table 5.1 Three major types, conventional (clear cell), papillary, and chromophobe, comprise 85–90 % of RCCs. There is limited information about FNA findings in the remaining rare types, some of which will be covered in addition to the major types (Table 5.2).

Clear cell (conventional) is the most common subtype, comprising 70 % of renal cell carcinomas. Sporadic CRCCs are usually solitary tumors. Multiple, bilateral tumors are rare in sporadic CRCC, but they are typical of hereditary forms such as Von Hippel–Lindau syndrome.

Histologically, the tumor is comprised of polygonal or cuboidal cells with clear or granular cytoplasm and distinct cytoplasmic borders surrounded by a thin-walled vascular network. Cytoplasm of clear cells contains lipid and glycogen. Various architectural patterns, including pseudopapillary forms, can be seen. Cystic changes, hemorrhage, and necrosis are common.

Cytomorphology:

Ultrasound- or CT-guided FNAs with on-site evaluation yield cellular material composed predominantly of tissue fragments and cell clusters (Fig. 5.10a, b). Tumor cells have clear or finely vacuolated cytoplasm with distinct cellular cytoplasmic borders (Fig. 5.11a, b). Most of the tumors have small round nuclei with inconspicuous or small nucleoli which correspond to Fuhrman Grade 2 (Fig. 5.11b). Higher grade tumors have larger nuclei with prominent nucleoli (Fig. 5.11c). One of the characteristic cytopathologic features of this tumor is crossing delicate vasculature in the tissue fragments (Fig. 5.12). Pseudopapillary fragments may be seen. They lack the fibrovascular stalk of the true papillary formations found in papillary renal cell carcinomas.

Immunohistochemistry:

CRCC is usually positive for AE1/AE3 keratins, vimentin, RCC, CD10, CAIX, PAX-8, PAX-2 and negative for CD117, Ksp-cadherin, and parvalbumin.

Key features:

Differential diagnosis:

The most important differential diagnosis is the differentiation of CRCC from metastatic tumors with clear cell features. Adrenal cortical carcinoma and hepatocellular carcinoma are among these neoplasms. Papillary carcinomas with focal clear cell changes should also be considered. In the absence of clear cell changes, oncocytoma and chromophobe RCC may enter into the differential diagnoses.

Papillary renal cell carcinoma comprises 10–15 % of renal parenchymal neoplasms. They are three times more common in men than in women. More than half of these neoplasms are discovered incidentally by abdominal ultrasound or computed tomography performed for other purposes. Multiple tumors are more common than conventional type. The survival rate, generally, is better than for conventional RCCs. The application of Fuhrman grading for prognoses is controversial. Genetically they show trisomy of chromosomes 7 and 17, with loss of the Y chromosome.

Characteristic histological features are papillary structures lined with neoplastic cells. Solid papillary and tubulopapillary forms are common. Aggregates of foamy histiocytes in the fibrovascular cores and hemosiderin pigment in the tumor cells and histiocytes are typically found. Two types have been classified: Type 1, the most common, composed of a single layer of neoplastic cells with scant, eosinophilic cytoplasm, small ovoid nuclei, and inconspicuous nucleoli. Abundant psammoma bodies may be seen. Type 2 tumors are composed of tumor cells with abundant eosinophilic cytoplasm with higher grade nuclei.

Cytomorphology:

Diagnostic FNA specimens are hypercellular, comprised predominantly of tissue fragments, cellular aggregates, and some single cells. There are usually some tissue fragments with characteristic papillary formation (Fig. 5.13), fibrovascular core surrounded by neoplastic cells which exhibit scant to moderate amounts of cytoplasm and round or ovoid nuclei with inconspicuous or small nucleoli (Fig. 5.14). Varying proportions of neoplastic cells may have clear cell features. Globular forms and loose cellular aggregates can be the predominant component (Fig. 5.15). The presence of abundant psammoma bodies is one of the characteristic features of these neoplasms (Fig. 5.14). Foamy histiocytes and hemosiderin pigment in tumor cells and histiocytes (Fig. 5.16a–c) are characteristic features of papillary RCC which help to differentiate this tumor from other types of RCCs. Clear cell features, focally or predominantly, could be present.

Immunohistochemistry (IHC):

IHC is performed on the cell blocks or core biopsies. Papillary RCCs are strongly and diffusely positive for CK7 and AMACR (cytoplasmic, granular) and also positive for RCC, PAX-2, PAX-8, and CD10 (Fig. 5.17a–c).

Key features:

Differential diagnosis:

The characteristic cytomorphology includes papillary structures with foamy hemosiderin-laden histiocytes and hemosiderin pigment in the tumor cells. When the papillary tumor is composed of predominantly clear cells, the differential diagnosis includes mainly clear cell RCC and other rare subtypes, clear cell papillary RCC, and Xp11.2 translocation RCC. The presence of hemosiderin pigment in tumor cells, hemosiderin-laden histiocytes, and psammoma bodies are helpful features in differentiating PRCC from other renal neoplasms with clear cell features. Immunohistochemical and genetic profiles of these neoplasms are also different from PRCC.

Chromophobe renal cell carcinoma (CRRCC) is a rare tumor comprising only about 5 % of renal cell carcinomas. Histologically, the tumor has two cell types: one has abundant clear to pale cytoplasm and the other granular, eosinophilic cytoplasm with thick cytoplasmic borders (eosinophilic type). Nuclei with wrinkled borders (raisinoid nuclei) and perinuclear clearing are characteristic features. Binucleation is common (Fig. 5.18).

Cytomorphology:

FNA specimens are cellular with cohesive aggregates and single tumor cells (Fig. 5.19a). The latter have large pale or dense granular cytoplasm (Fig. 5.19b). Frequent binucleation and variation in nuclear size are characteristic features. Irregular nuclear borders and occasional intranuclear pseudoinclusions are also seen (Fig. 5.19c). The perinuclear clearing seen in histologic preparations is less apparent in cytologic preparations (Fig. 5.18).