CHAPTER 19 Prostate gland
Chapter contents
Introduction
Transrectal fine needle aspiration biopsy (FNA) was introduced in Sweden in 1960 by Franzén, Giertz and Zajicek as a minimally invasive cytological method to confirm a clinical diagnosis of carcinoma of the prostate. It has now been in use for nearly 50 years and has proved to be a simple, safe and accurate method of investigation of palpable lesions in the prostate gland.1,2
Epidemiology of prostatic cancer
Prostate cancer accounts for 9.7% of malignant tumours in men and is the most common cancer among males in the Western world.3 It is one of the leading causes of cancer death in men, second only to lung cancer, and an increasing number of men are being diagnosed with prostate cancer worldwide. Autopsy studies have shown invasive carcinoma in 8% of men in their 20s, rising to 80% for men in their 70s.4 It has been estimated that four-fifths of these cancers are truly occult but that one-fifth have the potential to become clinically manifest and eventually lethal. This malignancy is, however, not invariably lethal and may have a prolonged natural history, being now diagnosed at earlier stages due to widespread serum prostate-specific antigen (PSA) testing.
Thus, a large proportion of clinically significant cancers remain undetected. At the time of diagnosis, almost half of the cancers are advanced and a little over half are localised and potentially curable. These data emphasise the need for improvement in the diagnosis and detection of prostatic cancer. Some improvement may already have occurred. Rietbergen et al. found that among cancers detected by screening, 78% had organ-confined disease.5
Aetiology and pathogenesis
The aetiology and pathogenesis of prostatic cancer are not known. The majority of prostate cancers are sporadic, and only 5–15% of cases are hereditary.6
Clinical features
Clinical symptoms develop only late in the disease. They are mainly related to bladder outlet obstruction. Such symptoms are non-specific and may be caused by prostatic enlargement of whatever nature, including benign prostatic hyperplasia and some forms of prostatitis. Haematuria or haemospermia are sometimes the first symptoms. However, most cancers are asymptomatic and detected by routine rectal palpation, abnormal transrectal ultrasound examination or by a raised serum PSA. Not infrequently, secondary deposits cause the presenting symptoms, for example, supraclavicular lymph node enlargement or pain from bone secondaries, while the primary tumour is silent.
Diagnostic procedure
Three clinical methods are currently available for the detection and diagnosis of carcinoma of the prostate: digital rectal examination (DRE), measurement of serum PSA levels and transrectal ultrasonography (TRUS). Each method alone has limited sensitivity and specificity, but combination of the three has significantly improved the cancer detection rate. If there is no palpable abnormality, a serum PSA level over 4 ng/mL in combination with an abnormal TRUS, or a PSA level over 10 ng/mL alone, are highly suggestive of clinically significant cancer.3,7 If cancer is suggested by one or more of these diagnostic methods, preoperative morphological confirmation of the diagnosis is the next step. Other indications are palpable abnormality in a patient who is not a candidate for radical surgery; patients with disseminated disease and long waiting lists for core needle biopsy (CNB). This can be done by needle biopsy, either by transrectal FNA for cytological diagnosis, or by transrectal or transperineal CNB for histological examination. The diagnostic accuracy of FNA is comparable with that of CNB.2,8
CNB needles in use today are usually 18 gauge or less. Some workers claim that with needles of this size, the complication rate is similar to that of FNA.9 Others find that the risk of complications is higher and patient discomfort is greater with CNB and recommend it be used selectively.10 Tumour implantation in the needle track has not been reported for prostatic FNA but does occur, albeit rarely, following transrectal CNB.11 Transrectal FNA remains the simplest, quickest and least expensive method to confirm clinically palpable cancer.1,3 Ultrasound directed CNB is more appropriate in the investigation of non-palpable malignancy suggested by either a high serum PSA or by an abnormal transrectal ultrasonogram.12–14
Technique of transrectal FNA of prostate
FNA is guided by transrectal palpation. The Franzén guide cannula was designed to make it possible to position the needle accurately in the abnormal area felt with the fingertip. It is secured by a metal ring fixed to the fingertip and a plate in the palm of the hand. A rubber fingerstall is pulled over it. The needles are 23 gauge or 25 gauge and the results are comparable with CNB of the prostate.8,15,16 Up to six passes can be made in one session but two to four are usually sufficient.
FNA of the prostate is an out-patient procedure that needs no patient preparation. Prophylactic administration of antibiotics should be considered in patients at increased risk of infection since septic reactions can occur. Post biopsy haematuria is a not infrequent occurrence but significant haemorrhagic complications do not occur even in patients on anticoagulant treatment.17
Special stains are rarely used in prostatic cytology. Staining for PSA and for prostate-specific acid phosphatase (PSAP) is helpful in confirming a primary prostatic adenocarcinoma and in the distinction between adenocarcinoma and transitional cell carcinoma. Staining for high-molecular-weight cytokeratins, which are present in the prostate only in basal cells, has been found helpful in differentiating benign proliferative processes from well-differentiated adenocarcinoma.18,19 A recent study has shown that detection of p504S is a sensitive and specific marker for prostatic carcinoma.20 Immunohistochemical analysis is essential in the recognition of small cell carcinoma of neuroendocrine type. Finally, macrophage markers and PSA/PSAP can be used in distinguishing granulomatous prostatitis from poorly differentiated carcinoma, which is occasionally also a problem histologically.
Causes of prostatic enlargement
The purpose of FNA is to confirm a clinical suspicion of cancer and to decide the nature of a palpable abnormality. Any condition that can cause prostatic enlargement, firmness and irregularity therefore enters the differential diagnosis. The most common cause is nodular benign prostatic hyperplasia. Prostatitis may also cause a palpable abnormality, in particular granulomatous prostatitis can clinically mimic cancer. An enlarged seminal vesicle can occasionally feel suspicious.
Most prostatic neoplasms are adenocarcinomas. A few uncommon types such as prostatic duct (endometrioid) adenocarcinoma and mucinous adenocarcinoma can be separated from the usual acinar adenocarcinoma. Neuroendocrine tumours and transitional cell carcinomas are uncommon and so are mesenchymal tumours. A classification of prostatic tumours modified from Murphy21 is presented in Box 19.1.
Benign prostatic hyperplasia
It is usually not difficult to obtain cellular material from a case of benign prostatic hyperplasia (BPH). However, the cells may be diluted by a large amount of thin secretion and may need to be concentrated by two-step smearing. Admixture with blood is rarely a problem. In general, smears of BPH aspirates contain many fewer cells than smears from adenocarcinoma.
Cytological findings: benign prostatic hyperplasia
Benign glandular epithelial cells are cohesive without overlapping or crowding and occur mainly as large monolayered sheets, reflecting the relatively large size of the glands in BPH. The cells are polygonal with central round nuclei and abundant pale cytoplasm, and cell membranes are distinctly visible, giving the epithelial sheets a honeycomb pattern. Single cells are uncommon unless too much pressure at smearing has caused the sheets to break up. However, it has been pointed out that small groups of cells suggestive of loss of cohesion occur in prostatic smears from men younger than 40 years.22
The nuclei of benign epithelial cells have inconspicuous nucleoli and finely granular chromatin (Fig. 19.1). In MGG-stained smears, coarse dark red cytoplasmic granules are commonly present (Fig. 19.1A). The granules are a strong indicator of benignity, although they can occasionally be found also in well-differentiated carcinoma.

Fig. 19.1 Benign prostatic glandular epithelium. Monolayered sheets with regular distribution of nuclei, visible cell membranes and coarse red cytoplasmic granules visible in (A) (A: MGG; B: PAP).
Smears may have a thin and watery background of secretion, with a high protein content condensed to dark staining clumps, amyloid bodies or concretions. A small number of histiocytes, lymphocytes and neutrophils are frequently seen in the absence of prostatitis. Fragments of spindle smooth muscle cells and stroma are rarely seen (Fig. 19.2).
Other elements that may be found in BPH are metaplastic or mature squamous epithelial cells from the mucosa of the bladder neck or urethra, and mucin-secreting columnar cells from the rectal mucosa, and cells from the seminal vesicles. The metaplastic cells are cytologically bland and should not raise a suspicion of malignancy.
Prostatitis
Cytological findings: prostatitis
Inflammatory cells should be present in large numbers before a cytological diagnosis of prostatitis is made. The glandular epithelial cells may appear mildly atypical. The nuclei may be irregularly distributed, cell membranes may be less distinct and there may be a slight reduction in cell cohesion with more frequent single cells. No multilayering of cells in aggregates or microacinar groupings of epithelial cells are seen, the chromatin is bland and nucleoli remain inconspicuous (Fig. 19.3).
Granulomatous prostatitis
Cytological findings: granulomatous prostatitis
When present, large multinucleated histiocytic giant cells, which often contain clumps of phagocytosed secretion, render the diagnosis of granulomatous prostatitis obvious. Cytological diagnosis is important since there is often a high level of suspicion of cancer clinically. Histiocytes are frequent, most are of epithelioid type and may form granulomatous clusters. There is a dirty background of secretion, debris and various inflammatory cells.
The diagnosis may be less obvious if spindled histiocytes predominate and giant cells are absent (Fig. 19.4). In the presence of granulomatous prostatitis, mild epithelial atypia should not be a cause for concern. Histiocytes may sometimes appear atypical, particularly in MGG smears. If this causes diagnostic problems, immunocytochemical staining for macrophage markers are helpful.

Fig. 19.4 Granulomatous prostatitis. Characteristic large multinucleated giant cells not shown; note epithelioid histiocytes, inflammatory cells in background and fragment of mildly atypical glandular epithelium (MGG).

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