Testis and scrotum: cytology of testicular and scrotal masses and male infertility

CHAPTER 20 Testis and scrotum

cytology of testicular and scrotal masses and male infertility

Ika Kardum-Skelin, Paul J. Turek

To Iva, Matko, Vlado, Ashley, Sophia and Vanessa. We would like to acknowledge the help of Professor I Crepinko and all the staff of the Laboratory of Cytology and Hematology, Merkur University Hospital in Zagreb and The Turek Clinic in San Francisco.

Introduction

Enlargement of the male external genitalia implies any one of various events within and around the scrotum, while the testes themselves may or may not be enlarged. The condition occurs in all age groups, is usually associated with pain, as with haematocele after surgical procedures, testicular torsion and similar events and may be accompanied by other local or general symptoms. A number of causes may lead to either unilateral or bilateral scrotal enlargement. Any testicular enlargement, oedema or pain requires a thorough diagnostic work-up to exclude the possibility of carcinoma of the testis.

Diagnostic work-up of testicular and scrotal masses

Inspection and palpation

The appearance, size and symmetry of the scrotum and contents are determined by inspection. This may reveal the hypoplastic appearance of an undescended testicle. Consistency of the scrotum is determined by palpation: a ‘bag of worms’ sensation signifies a varicocele and when the patient assumes a supine position, venous blood flows out, thus reducing the swelling; palpable enlargement caused by a testicular mass; the findings typical of torsion of the spermatic cord, or the ‘blue dot’ sign, which indicates torsion of the appendix testis or appendix of epididymis.¹

Transillumination

Transillumination is performed in a dark room using a light source. If the light passes through the scrotum, it is very probably filled with fluid. Unlike spermatocele and hydrocele both of which can generally be transilluminated, light passage through a haematocele is not possible due to the dark colour of the blood.

Ultrasound

Ultrasound is a proven and safe diagnostic procedure. Ultrasound showed 100% accuracy in the evaluation of hydroceles, haematoceles and paratesticular masses, but was less informative in testicular abscesses (80%) and epididymo-orchitis (77%).² Ultrasound was able to distinguish accurately between the normal and a pathological scrotum. Extratesticular lesions were readily differentiated from testicular lesions. Abnormal testicular echo patterns were usually associated with tumours, whereas orchitis, granulomas and haematomas were found to have a similar appearance. Ultrasound may also be useful in post-orchiectomy follow-up examinations to exclude tumour in the contralateral testis.³

Advances in ultrasound technology in recent years have made ultrasound the examination of choice for imaging scrotal pathology, whether acute or chronic in nature. Doppler technology has increased the radiologist’s ability to assess flow within the prepubertal testicle, thus allowing for assessment of viability in the undescended testis as well as in neonatal torsion. Ultrasound is a readily available, non-invasive examination without radiation exposure, which provides excellent anatomical detail and serves as an important and very helpful imaging modality in all types of paediatric scrotal pathology.⁴

Fine needle aspiration cytology

Fine needle aspiration (FNA) of the testis and scrotum is a simple, rapid, minimally invasive and painless out-patient procedure. The sample obtained is more representative than biopsy as several separate punctures can be made, and there is no local scarring.⁵ FNA has become increasingly popular for evaluating both superficial and deep-seated lesions.⁶ Testicular FNA offers valuable prognostic parameters in selected patients with varicocele scheduled for sclerotherapy.⁷ The cytopathological pattern of neoplasia is highly characteristic, indicating the diagnosis with high precision. FNA is the technique of choice for the study of the pathology of scrotal contents, and it should be employed on the patient’s very first visit. The main advantage of FNA is avoiding delay in the diagnosis.⁸ No local seeding of tumour has been observed by the FNA procedure.⁹ FNA can also be a useful method to evaluate clinically suspect testicular infiltration in children with acute lymphoblastic leukaemia, and can be considered as an alternative procedure to surgical biopsy for screening testicular recurrence of childhood acute lymphoblastic leukaemia.¹⁰

Biopsy

Testis biopsy was first reported by Hotchkiss and Engle at the New York Hospital, Cornell Medical Center in the late 1930s. The primary purposes of testicular biopsy are to distinguish between obstructive azoospermia and primary seminiferous tubular failure and to differentiate malignant from benign testicular lesions. Until standards for the evaluation of aspirated material are well established, open testis biopsy is the diagnostic procedure of choice.¹¹ The procedure can be performed as core needle biopsy (CNB), testis-sparing biopsy, or open surgical biopsy. There are four main clinical scenarios when CNB testicular biopsy is performed: (1) lesions with equivocal malignant ultrasound features; (2) discrepancy between radiological and clinical findings; (3) suspected malignant process where orchiectomy is unnecessary, e.g. lymphoma; and (4) atrophic testes, where it is frequently difficult to differentiate malignancy from the heterogeneous echo pattern.¹² Testis-sparing surgery may be required if a benign lesion is considered highly likely. If frozen section analysis is equivocal, then radical orchiectomy is required. Testis-sparing surgery proved feasible in highly selected cases.¹³

Tumour markers

Determination of tumour markers in the blood can be useful in the diagnosis of testicular tumours. Proteins secreted by particular tumours of the testis, such as alpha-fetoprotein (AFP) or beta-human chorionic gonadotrophin (β-hCG), can be demonstrated in 90% of patients with embryonal carcinoma of the testis and 10% of patients with seminoma.¹⁴

Benign lesions of the scrotum

Pathological processes of the scrotum are numerous. They include a few common and well-known diseases and a large spectrum of rare lesions. The testis may also be involved by some systemic diseases (Table 20.1).¹⁵

Table 20.1 Conditions leading to scrotal enlargement

Non-neoplastic disorders	Inflammation and systemic diseases	Orchitis
		Epididymitis
		Retention lesions
	Cystic lesions	Hydrocele
		Varicocele
		Spermatocele
		Haematocele
	Trauma and surgical procedure sequels	Torsion
		Trauma
		Surgical procedure of the testis
		Surgical procedure in the inguinal region
	Hernia
Testicular tumours	Germ cell tumours	Seminoma
		Embryonal carcinoma
		Yolk sac tumour
		Teratoma
		Choriocarcinoma
	Sex cord stromal cell tumours	Granulosa cell tumour
		Sertoli cell tumour
		Leydig cell tumour
		Androblastoma
		Gynandroblastoma

Epididymal nodules are not infrequently encountered in surgical practice. These are generally small and slippery and FNA is not easy. But as it is rapid and less traumatic than a biopsy, FNA has an important role in the differential diagnosis of epididymal nodules because it can detect malignancy and benign conditions such as tuberculosis and acute and chronic epididymo-orchitis. Gupta et al. found that the lesions most commonly diagnosed by FNA were as follows: tuberculous epididymitis (30.7%), non-specific inflammation (4.4%), microfilaria (0.9%), hydrocele (11.4%), spermatocele (18.4%), spermatic granulomas (5.3%), adenomatoid tumour (1.3%), leiomyosarcoma (0.4%) and lipoma (0.4%).¹⁶ They found FNA to be useful in the diagnosis of 90.3% of cases, thereby avoiding surgical biopsy and other investigations.

Symptoms such as a ‘pulling’ sensation in the testis, oedema, painful ejaculation, blood in the semen, palpable nodules, or change in the colour or structure of the scrotal skin may also occur due to a number of other benign diseases and conditions.

Cystic lesions

Cystic lesions include hydrocele, haematocele and spermatocele.⁵ Testicular enlargement due to the accumulation of fluid, blood or seminal fluid may mimic tumour findings.

Hydrocele and haematocele

Accumulation of fluid or blood in the scrotum occurs due to trauma, surgical procedures of the testis or inguinal region associated with compromised testicular supply with blood and/or increased vascular permeability. Any systemic disorder leading to impaired regulation of body fluid may also lead to oedema in the scrotal region. The nature of the disorder determines whether testicular enlargement will be bilateral (e.g. heart failure, liver decompensation, anasarca), or unilateral.

Cytological findings: hydrocele and haematocele

In hydrocele cases, fluid is obtained by cytological puncture, yielding scant cellularity in the sediment, consisting of some mesothelial cells and lymphocytes (Fig. 20.1A). In addition to previously described cellular elements, polymorphonuclear granulocytes, typical and reactive mesothelial cells, histiocytes and cellular detritus are found in persistent hydroceles. Microbiological cultures are sterile. In haematocele, the specimen contains blood and/or phagocytosed erythrocytes and siderophages, depending on the duration of haematocele (Fig. 20.1B).

Fig. 20.1 Cystic lesions (MGG): (A) hydrocele – sparse cellularity with a few histiocytes and erythrocytes; (B) haematocele – note the background of erythrocytes and fibrin; (C) spermatocele with numerous spermatozoids.

Spermatocele

A cystic growth in the epididymal region occurs due to seminal duct distension caused by inflammation or some other disorder (obstruction by adhesions, tumour, etc.), and is mostly painless (Fig. 20.1C).

Cytological findings: spermatocele

Milky fluid is obtained by puncture, and spermatozoa lacking motility are found in the smear. Histiocytes and epididymal lining cells are found in persistent spermatoceles.⁵

Varicocele

Varicocele occurs due to varicosity of the vascular plexus conveying venous blood from the testis. The condition develops as a consequence of pressure upon outflow veins, for example by a kidney tumour. The cause, however, usually remains unknown, and it has not yet clear why it more frequently occurs on the left side. On palpation, the scrotum feels like a ‘bag of worms’. The diagnosis is generally made by ultrasound, while cytological puncture is not indicated.

Epidermal cysts

Epidermal cysts are located intradermally; they can be small yet they may cause great enlargement of the scrotum.

Cytological findings: epidermal cysts

Hernia

This disorder is characterised by impaired communication between the abdominal cavity and scrotum, when a segment of the omentum or intestine slips into the scrotal sac. History data reveal the enlargement to be more pronounced on standing, coughing, carrying heavy objects, or with strain on examination.

Cytological findings: hernia

Cytological puncture is not indicated in unambiguous cases. However, when cytological puncture is performed in unrecognised cases, besides adipose tissue elements the samples contain mesothelial cells or intestinal epithelium, and occasionally even intestinal content (faeces or microbiological intestinal flora).

Tumours of the testis

The histopathology of testicular tumours, emphasising new, unusual, or underemphasised aspects is presented in an excellent review by Young.¹⁹ Because of the good prognosis for some testicular tumours and early detection of the disease, any scrotal enlargement should be considered a tumour until proved otherwise. The pathogenesis of testicular tumours is unknown. A higher incidence of testicular tumours has been reported in patients with cryptorchidism or Klinefelter’s syndrome, as a post-traumatic condition or based on a positive family history. In spite of numerous studies demonstrating the usefulness of FNA cytology in the diagnosis of testicular enlargement, both for differentiation between non-neoplastic and malignant tumours and for tumour typing, there remains a dose of scepticism among urologists as to whether to approach a primary tumour by FNA or orchiectomy followed by histopathology. However, the wisdom of removing the testis for what may turn out to be a benign lesion has to be questioned. Therefore, FNA testis as a minimally invasive procedure should be the first diagnostic method following imaging techniques (mostly ultrasound, and less frequently computed tomography or magnetic resonance imaging).

Tumours of the germinal epithelium account for 95% of all malignant tumours of the testis; sex cord stromal tumours are very rare, generally are Sertoli cell or Leydig cell tumours, and are usually benign.