Fine Needle Aspiration Biopsy Cytology of Kidney: A Diagnostic Approach Based on Pattern Recognition

Cytopathology

These normal components of kidney may be found alone, raising the possibility that the lesion is normal kidney or that the FNAB has missed the target, or may be mixed with cells from a neoplastic or non-neoplastic lesion.

Clinical

These rare, benign tumors are derived from metanephric blastema; constitute 0.2% of adult renal neoplasms; and occur most commonly in adult women but also in children where the clinical and imaging DD is Wilm tumor. Occasionally, cases have been reported to metastasize. These tumors usually present incidentally on imaging but may produce abdominal or flank pain, hematuria, polycythemia, or hypertension. Imaging shows a well-circumscribed, hyperechoic mass on ultrasound and a solid homogeneous lesion on CT scan.

The histology shows a nonencapsulated, clearly demarcated tumor, up to 15 cm in size, with small acini and primitive tubules and glomeruloid structures, and in some cases a papillary component and psammoma bodies. The nuclei are round to oval, bland, and closely spaced. Minimal eosinophilic or clear cytoplasm exists in the acini, and there is scant fibrovascular hyalinized stroma.

Management is partial or, rarely, complete nephrectomy, percutaneous radiofrequency ablation, or active surveillance.

Cytopathology

There is a lack of necrosis, siderophages, papillary tissue fragments with fibrovascular cores, histiocytes, nuclear atypia, psammoma bodies and mitoses.

Differential Diagnosis

The DD includes low-grade papillary RCC, which shows a higher degree of nuclear atypia, siderophages, and a bloody, often necrotic background and is cytokeratin (CK) and epithelial membrane antigen (EMA) positive and negative in WT1 staining, and Wilm tumor with its often triphasic or biphasic pattern, frequent necrosis, larger blastema cells with a higher degree of nuclear pleomorphism, and negative CK7 in the blastema. But some regions of Wilm tumors can be similar to the microacinar pattern of metanephric adenoma. Wilm tumors have specific deletions of the short arm of chromosome 11 and long arm of chromosome 16.

Renal adenomas can be virtually indistinguishable on cytology, with their sheets and acinar tissue fragments of uniform cells with scant cytoplasm and round, small nuclei with even chromatin, but are usually less than 1 cm in size, stain with keratins and EMA, and have trisomies of chromosomes 7 and 17 on FISH.

Ancillary Diagnostic Studies

The IHC shows the tissue fragments to be AE1/AE3 pankeratin, PAX2, and CD57 positive and RCC marker, EMA, CK7, and AMACR negative, while the WT-1 is variably reported but most often negative.

Clinical

Renal cysts are frequently diagnosed incidentally by CT and ultrasound or in the workup of patients with hypertension or hematuria. Ultrasound-directed FNAB can be employed when the features are not diagnostic of a benign cyst or show a complex cystic mass. However, a significant number of cases without an epithelial component in the cyst fluid will turn out on surgical excision to be malignant lesions.

Cytopathology

Differential Diagnosis

When present in large numbers, siderophages and necrosis suggest possible RCC with cystic degeneration, as does finding clear cells or distinct papillary tissue fragments. Multilocular cystic RCC is a subtype of clear cell carcinoma and has a better prognosis. Distinction from clear cell carcinoma with cystic degeneration requires histopathology.

The DD also includes: multilocular cystic nephromas, which typically have minute epithelial tissue fragments resembling histiocytes with low N:C ratio and a hobnail placement of nuclei, which at times can show some atypia, along with minute tissue fragments of spindle cells in a cystic background; and a spectrum of lesions including mixed epithelial and stromal tumors, which show a similar bimodal pattern of hypocellular to myxoid to ovarian stroma and hobnail epithelial tissue fragments derived from the cyst lining with minimal nuclear atypia. The epithelium in these tumors is CK, vimentin, and estrogen and progesterone receptor positive, while the stroma is vimentin, smooth muscle actin, and desmin positive and HMB45 and CD117 negative. These rare tumors occur almost exclusively in women (F:M, 10:1) over a broad age range but most commonly around menopause with an average age of 56. Imaging shows a circumscribed solid or multiloculated cystic lesion in the renal cortex.

Clinical

There may be a history of trauma, or the lesion may be discovered on routine imaging. FNAB produces yellow- to brown-stained thin fluid.

Cytopathology

Differential Diagnosis

The DD is that of renal cysts with hemorrhage and renal carcinomas with hemorrhage, and correlation with history and imaging is required.

Clinical

There may be a long history of recurrent urinary tract infections, with or without urinary tract surgery for congenital abnormalities and dysfunction. The chronic infection is most commonly associated with Escherichia coli and other gram-negative bacteria but can be associated with Mycobacterium tuberculosis and schistosomiasis. The imaging is variable but can be that of a mass lesion associated with distortion of the collecting system including the renal pelvis.

Cytopathology

Differential Diagnosis

In malakoplakia the macrophages have discrete large basophilic structures (calcium and iron components) in the cytoplasm in a chronic inflammatory background of lymphocytes, plasma cells, and other histiocytes (see Plate 9-3B ; Fig. 9-12 ).

Malignant lymphomas do occur as rare primary lesions in the kidney, presenting in an older patient with flank pain or usually as a single renal mass found incidentally ( Fig. 9-13 ). However, in the majority of cases the lymphoma represents extension from other sites and renal involvement is detected during routine follow-up for lymphoma or other malignancies often as bilateral renal and adrenal masses. Lymphomas are diagnosed as primary lymphomas of the kidney if there is a dominant renal mass with or without renal failure and no history of lymphoma. Primary renal lymphomas possibly arise in a background of chronic inflammation or from the capsule or as a post-transplant lymphoproliferative disorder in a transplanted kidney. The CT features of a hypovascular mass or several masses are different to renal carcinoma, which is hypervascular in contrast-enhanced studies, but raise a DD of pyelonephritis or abscess. FNAB is required to exclude a renal carcinoma leading to nephrectomy versus lymphoma, which requires chemotherapy versus a metastasis from another site. Renal carcinomas are also increased in patients with a known history of lymphoma. FNAB with ROSE can identify the lymphoid nature of the lesion, and flow cytometry can be selected to confirm the diagnosis in almost all cases.

The lymphomas are almost always B-cell lymphomas and usually diffuse large B-cell lymphoma, Burkitt or follicular lymphoma, or acute lymphoblastic lymphoma, but CLL/small lymphocytic lymphoma and marginal zone lymphoma do occur. The commonest cytology is a monotonous large atypical lymphoid population with lymphoid cytoplasmic fragments in a background with necrosis.

Ancillary Diagnostic Studies

Although large cell lymphomas can be diagnosed on cytomorphology, flow cytometry is a useful complementary test and is generally required. FISH or gene rearrangement studies can be diagnostic in, for instance, Burkitt lymphoma or ALL, based on rinsings of the FNAB needle into saline or RPMI.

Clinical

Clear cell carcinoma comprises 70% of RCC and can be associated with chromosome 3p deletions (FISH probes or karyotyping). It also occurs in von Hippel-Lindau disease (average age 37 VS sporadic 61). There may be mutation of the VHL gene and hypermethylation of VHL promoter.

The presentation can be a renal mass on imaging workup of a patient with abdominal pain, abdominal mass, or hematuria, or as an incidental renal mass found on imaging for other reasons such as workup of a lung primary carcinoma, or as a metastasis to lymph nodes or other organs including thyroid, bone, or lung. Classically, RCC metastases can occur late, and their “clear cell” cytologic features enter the DD for “clear cell carcinomas” in many other organ sites including pancreas and thyroid.

Cytopathology

Differential Diagnosis

Low-grade clear cell carcinomas have a DD of chromophobe RCC with their more copious eosinophilic granular cytoplasm and central, round, bland nuclei lacking prominent nucleoli (see Figs. 9-52 to 9-59 ) and, to a lesser extent, oncocytomas (see Fig. 9-60 ). Xp11.2 carcinoma can have clear cells, but usually has papillary architecture, and is Xp11.2 positive. It should be noted that some clear cell renal carcinomas can be S-100 positive and, rarely, HMB-45 and melan A positive.

Multilocular cystic renal cell neoplasm of low malignant potential (multilocular cystic RCC), formed exclusively of variably sized cysts lined by attenuated and often denuded flat to cuboidal epithelium with grade 1 clear tumor cells in the intervening septa, is seen as at one end of a spectrum with cystic clear cell carcinoma at the other end and has a good prognosis.

High-grade clear cell (see Figs. 9-23 to 9-31 ), papillary type 2 (see Figs. 9-40 to 9-47 ), collecting duct (see Figs. 9-35 to 9-38 ), and urothelial cell carcinomas (see Figs. 9-75 to 9-79 ) and some metastases (see Figs. 9-61 to 7-72 ) can be hard to distinguish on cytology. IHC and cytogenetics are required.

Anaplastic tumors in the kidney include high-grade RCC, sarcomatoid carcinomas, and rhabdoid tumors. Sarcomatoid RCC (see Figs. 9-29 to 9-31 ) are regarded as the most “dedifferentiated” tumors and when detected at FNAB at ROSE should lead to a request for further passes because it is important to identify any residual, more specific renal carcinoma, most commonly a chromophobe carcinoma. FNAB offers advantages over core biopsy in this situation because it allows wider sampling of the often inoperable or metastatic carcinoma. The DD includes rare high-grade leiomyosarcomas and high-grade lymphomas. Cell block preparation with IHC is essential.

Rhabdoid tumors occur most commonly in the pediatric setting, where they form 2% of renal tumors and are highly aggressive with a poor prognosis (see Figs. 9-82 to 9-85 ). They are rare in adults, in whom rhabdoid differentiation in a RCC is more common and again signifies a poor prognosis. Electron microscopy (EM) is useful in the diagnosis of rhabdoid tumors in children.

Clear cell (tubulo) papillary RCC has recently been established as a possible separate entity with similar histology and, potentially, FNAB cytology to classic clear cell carcinoma. It is seen in end-stage renal disease, as well as sporadically, and has indolent behavior. The well-circumscribed small tumors have a variable branching tubular, acinar, cystic, or papillary pattern, separated by fibrous stroma that can have prominent myoid differentiation. The epithelial cells have clear cytoplasm, low nuclear grade, and nuclei arranged off the basement membrane in linear fashion, with no necrosis or foamy macrophages. The tumors have characteristic CK7 diffuse positivity and are CA-IX positive, as well as CD10, RCC, and AMACR negative, in distinction to clear cell carcinomas.

Juxtaglomerular body tumors are rarely reported in FNAB cytology but may have a bloody background with old blood and siderophages and enter the DD of clear cell carcinomas. These usually small tumors are found in young patients being investigated for long-standing hypertension, with high plasma renin levels, specifically on unilateral renal vein sampling, and secondary hyperaldosteronism. FNAB smears show low cellularity with small sheets of small cells with indistinct cell borders and granular cytoplasm and central minimally hyperchromatic or pleomorphic round nuclei. In some cases poorly defined connective tissue stalks containing tumor cells are seen along with calcifications, but no definite papillary structures are seen. The distinction from low-grade clear cell carcinoma is assisted by IHC, which shows the juxtaglomerular body tumors to be vimentin, renin, CD117, CD34, and neuroendocrine marker positive, and AE1/AE3 pankeratin, CK7, EMA, and S100 negative. EM shows diagnostic spherical and angulated rhomboid renin granules.