Kidney and retroperitoneal tissues

CHAPTER 11 Kidney and retroperitoneal tissues

Beatrix Cochand-Priollet

Introduction

As is apparent throughout this third edition of Diagnostic Cytopathology, fine needle aspiration (FNA) cytology of deep-seated organs is an extremely useful technique, widely used especially preoperatively to ensure that the patient is given the most appropriate treatment. However, long-term results over a number of years show that FNA has been less successful for the kidney than for other organs.

About 20 years ago, renal FNA was rarely considered worthwhile because tumours were very large when discovered, requiring total nephrectomy whatever the final diagnosis. Preoperative diagnoses are more frequently required now, as many renal tumours are incidental, discovered on ultrasound or CT scan (Fig. 11.1) and usually detected as small masses in asymptomatic patients.^1,² Even so, microbiopsies are often preferred to FNA, as highlighted by a number of recently published series,³^–¹¹ sometimes associated with cytological analysis, but more often not.

Fig. 11.1 Tumour 1.4 cm in diameter discovered incidentally on CT scan.

However, renal FNA is a safe method, providing accurate results with high levels of sensitivity and specificity when performed by well-trained, skilled cytopathologists.¹²^–¹⁴ The diagnostic accuracy of FNA has been shown to range from 70% to 100%,^12,¹³ whereas its specificity ranges from 91.9% to 99% and its sensitivity from 80% to 94%.^12,¹⁴ Only a few series of renal FNA analyses have been published over the last 10 years, the largest of which include 180 and 108 cases,^13,¹⁴ with most consisting of less than 20 cases or even of reports of single cases.

We have chosen to follow the 2004 World Health Organization classification for the cytological description of the different tumours (see Box 11.1). This classification is based on the correlation between results for morphological analysis, immunohistochemistry, electron microscopy, cytogenetics and molecular genetics.¹⁵ Some of the tumours are quite rare and have not yet been described cytologically, although illustrated in histological textbooks. these tumours will not be discussed in this chapter.

Indications and contraindications for FNA of kidney

For solid renal masses, the indications include:

• To establish the diagnosis, and especially the malignant potential, of a renal tumour that cannot be resected due to its size or the patient’s inability to tolerate surgery, or because there are already metastases at the time of diagnosis

• To make a diagnosis of a metastasis or diagnose a second primary renal tumour in the presence of an already known cancer

• To decide on the surgical strategy in cases of small tumours located at the upper or lower poles of the kidney (whether partial or total nephrectomy or non-surgical treatment)²

• To select small benign renal neoplasms in order to facilitate optimal patient management.¹⁶

For cystic lesions of the kidney, FNA is virtually always indicated in order to eliminate or confirm malignancy.¹⁷

Contraindications are in general the same as those for FNA of other deep-seated organs. In addition though, FNA is contraindicated in patients with only one kidney.

FNA technique

In the past, radiological investigations included intravenous pyelography, angiography, ultrasonography, computed tomography and magnetic resonance imaging. Nowadays, contrast enhanced sonography and PET/computed tomography are likely to be used as they are more efficient techniques.¹⁸^–²⁰ Renal arteriography is no longer the procedure of choice for the evaluation of renal masses. These investigations are very useful for detecting renal masses, to appreciate their solid or cystic/partially cystic appearance, to detect an extension into the surrounding adipose tissue or renal pelvis as well as extension into the renal vein. However, there are very few cases where radiological techniques can specify the histological type of the tumour, apart from angiomyolipoma if this mixed tumour includes a substantial component of adipose tissue. In order to determine the histological type of a renal tumour, cytological or histological material has to be available.

Renal FNAs are usually performed with a 23–25-gauge needle attached to a 20 mL syringe. When aspiration is completed the cytological material is usually expelled directly onto slides in order to obtain air-dried smears for staining with Diff-Quik or May–Grünwald Giemsa (MGG) and some alcohol-fixed smears to be stained by the Papanicolaou (PAP) method. Liquid-based preparation is also widely used, rinsing the needle directly into an appropriate preservative (Hologic® or Tripath Imaging®). For cystic lesions, centrifugation is recommended with cytospin slides then prepared for both Diff-Quik and PAP staining.

Cell block preparation is a valuable technique for FNA of deep-seated organs. It offers the opportunity to obtain some embedded cytological material previously fixed with formalin and recovered after centrifugation or to include some very small hardly discernible fragments of tissue. Tissue sections obtained from these cell blocks may be stained by haematoxylin and eosin or may be used for histochemistry as well as immunohistochemistry. These ancillary techniques are useful in selected cases and may replace core biopsy material.

Complications that may occur include transient haematuria, haemorrhage with pain, pneumothorax or infection. Some cases of cutaneous seeding have been reported in the past but none have been published recently, probably due to improvements in FNA technique. Very rare cases of massive tumour infarction have also been reported.²¹

The unsatisfactory specimen

This category has rarely been described in detail and even though most articles give a percentage of unsatisfactory specimens, ranging from 5% to 21%, yet the criteria used are not adequately reported. A few authors have tried to validate some criteria considered as helpful guidelines.¹³ These are summarised as follows:

• An adequate sample from a solid mass has to contain ‘representative material,’ that is a large number of well-preserved cells, but they should not be normal cells and must present the characteristics and features of a diagnostic category

• A cyst fluid aspirate, even if devoid of cells, is not necessarily unsatisfactory

• Normal cells are quite often observed in kidney FNAs and these must be identified in order to avoid any confusion with abnormal or tumour cells. These normal cells are described in Table 11.1 (Fig. 11.2).

Table 11.1 Cytological features of normal renal cells

Fig. 11.2 FNA: Kidney. Normal cells from the tubules. Notice the regular round nuclei (MGG).

Malignant tumours of kidney

Renal cell carcinomas (RCC) represent over 90% of all malignancies in the kidney that occur in adults of both sexes, but are two to three times more frequent in men than in women.¹⁵ These carcinomas account for 3% of adult malignancies overall (Box 11.1).²² Tobacco smoking is one of the major aetiological factors. Workers in the rubber industry also have a higher incidence of RCC. Nephroblastoma, the most frequent malignant tumour in infancy, affects about one child in every 8000.¹⁵

Clear cell renal cell carcinoma (CCRCC)

As the commonest histological type, this tumour is found in about 70% of all adult renal carcinomas.²² CCRCCs are very rare in infancy.²³ The tumour is randomly distributed in the cortex and occurs with equal frequency in either kidney, usually as a solitary tumour but sometimes multiple.¹⁵ CCRCCs may occur in patients with von Hippel–Lindau disease, which is inherited through an autosomal dominant trait and caused by germine mutations of the VHL tumour suppressor gene, located on chromosome 3p25-26. Recently, 3p deletions have also been described for the sporadic CCRCCs (3p25.1-25.3, 3p21.3-22.3; 3p14.1-14.2). They underline the role of chromosome 3 in renal cancer development, and are frequently associated with a trisomy 5q.²⁴ The mean age for sporadic CCRCCs is 61 years versus 37 years for CCRCCs in von Hippel–Lindau disease.

Macroscopically, these tumours are typically golden yellow with haemorrhagic and necrotic areas as well as patchy calcification (Fig. 11.3). Histologically, CCRCCs are composed of cells with clear cytoplasm filled with lipid and glycogen which are dissolved during routine histological processing. The cells show solid or acinar or more rarely papillary patterns with a thin network of small blood vessels between the cells groups.

Fig. 11.3 Large tumour with necrosis and haemorrhagic areas, very suggestive of a clear cell renal cell carcinoma (CCRCC).

Cytological findings: CCRCC (Figs 11.4, 11.5)

• Isolated cells in association with some clusters of cells, rarely with papillary clusters

• Cells with irregular borders

• Nuclear atypia ranging from small to large nuclei with regular or irregular borders

• Abundant cytoplasm, either vacuolated or granular

• Many naked nuclei, but usually without necrosis.

Fig. 11.4 FNA: CCRCC; clusters of cells with microvacuolated cytoplasm and both regular and irregular nuclei (MGG).

Fig. 11.5 FNA: CCRCC; same type of clusters as previously but note a macrophage with cellular debris from necrosis (MGG).

Diagnostic pitfalls: CCRCC

Problems may occur in cases of chromophobe renal cell carcinoma with a clear component when the perinuclear clear rim of the chromophobe cells is enlarged. CCRCCs may also be misdiagnosed for xanthogranulomatous pyelonephritis but xanthoma cells are more foamy than clear;²⁵ however, when xanthogranulomatous pyelonephritis is associated with keratinising squamous metaplasia, the risk of misdiagnosing malignancy is higher.²⁶ Adrenocortical carcinomas may also be hard to differentiate from CCRCCs but the radiological findings should be helpful.

Chromophobe renal cell carcinoma (CRCC)

This carcinoma represents approximately 5% of all renal carcinomas.¹⁵ The mean age of incidence is in the sixth decade. Only a few cases of metastases have been described. Extensive chromosomal losses have been shown, especially -1,-2,-6,-10,-13,-17,-21.²⁷ In addition, mutations in BHD and TP53 genes have been described.²⁸

Macroscopically, these tumours are typically light brown when fresh and light grey after formalin fixation, with no or few haemorrhagic areas (Fig. 11.6). Histologically, CRCCs are composed of cells with polygonal, transparent usually microvacuolated cytoplasm. A perinuclear clear rim is often observed. The cytoplasmic borders are clearly defined, making the cells appear to be framed. The nuclei are often irregular and wrinkled; bi- or multinucleated cells are common. These cells show an essentially solid pattern with a network of thick-walled blood vessels between the cells groups. In fact, there are two types of chromophobe cell carcinoma: one composed of relatively clear cells, the other of large eosinophilic cells mimicking oncocytomas. Mixed types have been described.

Fig. 11.6 Light grey tumour suggestive for a chromophobe renal cell carcinoma (CRCC).

Cytological findings: CRCC (Figs 11.7, 11.8)^13,^29,³⁰

• Isolated cells in association with some small clusters of cells

• Variable-sized tumour cells

• Cells with well-defined borders or even thickened cell membranes

• Nuclei often have irregular borders, sometimes with cytoplasmic nuclear inclusions or grooves

• Binucleation

• Abundant cytoplasm, either clear but microvacuolated or eosinophilic and granular

• Perinuclear clearing of the cytoplasm.

Fig. 11.7 FNA: CRCC-clear cell variant; cells with well-defined borders and microvacuolated cytoplasm (cell block, H&E).

Fig. 11.8 FNA: CRCC-oncocytic variant; cells with well-defined borders but granular eosinophilic cytoplasm and irregular nuclei. Note a nuclear cytoplasmic inclusion (cell block, H&E).

Diagnostic pitfalls: CRCC

Problems may occur in cases of CRCC-eosinophilic variant when the cytoplasm is granular and eosinophilic, resembling that of oncocytic cells. It is then necessary to be cautious and to look for the nuclear irregularities not usually seen in oncocytoma. Difficulties may also arise between CCRCCs and chromophobe cell carcinomas in cases of chromophobe cell carcinoma-clear variant (Fig. 11.9). Cytochemistry and/or immunocytochemistry can then be helpful.

Fig. 11.9 FNA: CRCC–CCRCC variant. Note the few cells with well-defined borders and binucleation (MGG).

Papillary renal cell carcinoma (PRCC)

This carcinoma represents approximately 10% of all renal carcinomas.¹⁵ As with the chromophobe renal cell carcinoma, the mean age of incidence is in the sixth decade. Five-year survival for all stages ranges from 49% to 84%. Two types of PRCC have been described. Type 1 is usually a low-grade tumour with a favourable clinical outcome and type 2 a high-grade tumour with a poor prognosis. Trisomy or tetrasomy 7, trisomy 17 and loss of chromosome Y are the usual karyotypic changes in type 1 PRCC. Additional trisomies may be observed, most frequently trisomies 16, 12 and 20.³¹ These abnormalities are not observed in type 2, which seems to be more heterogeneous. Recently, MYC activation has been revealed in these high-grade papillary carcinomas.³²

Macroscopically the type 1 PRCC tumours are well-circumscribed, partially cystic with some haemorrhagic and necrotic areas. Bilaterality and multifocality are more often encountered than with the other primitive renal tumours. Histologically, the type I PRCC are characterised by a papillary and tubular architecture. Foamy macrophages are often observed within the fibrovascular core of the papillae, as well as some microcalcifications. The haemorraghic and necrotic areas include some cholesterol crystals. In type 1 tumours the papillae are covered by small, regular, sometimes clear or eosinophilic cells (Fig. 11.10) whereas in type 2 PRCCs the papillary architecture is often not obvious and the cells are tall with eosinophilic cytoplasm and enlarged nuclei including prominent nucleoli. Hyperexpression of Topo II has been described.