DISEASES OF TESTIS AND EPIDIDYMIS

Congenital Anomalies

1. Cryptorchidism: Failure of testicular descent into the scrotal sac which occurs in 0.7% of male population. Malpositioned testis may be found any where along the normal pathway of descent from the abdominal cavity to inguinal canal.

Causes:
Most cases are idiopathic. Causes include hormonal abnormalities (e.g. deficiency of luteinizing hormone-releasing hormone), genetic abnormalities e.g. (trisomy 13), short spermatic cord, or mechanical obstruction in the inguinal canal.

Morphology: Cryptorchidism occurs

more in the right testis and may be bilateral in 25% of cases. Malpositioned testis may be of normal size in early life, but it shows some degree of atrophy at puberty

Microscopically, at the age of 6

years, there is atrophy of seminiferous tubules, associated with Leydig cell hyperplasia and interstitial fibrosis. At puberty, hyalinization of the seminiferous tubules is evident. Regressive changes may also occur in the other descended testis

Effects:

Cryptorchidism is asymptomatic. Usually discovered at the time of puberty (after testicular atrophy has occurred). If cryptorchidism is bilateral, it leads to sterility. The malpositioned testis has high incidence and tendency for development of malignancy compared to the normal positioned testis

2. Testicular atrophy

May occur as a primary developmental abnormality in patients with klinefelters' syndrome. May be secondary to cryptorchidism, vascular disease. Inflammatory disease. Hypopituitrism. Malnutrition. Obstruction of outflow of semen. Elevated level of female sex hormones, persistantly elevated level of follicle stimulating hormone. Radiation, and chemotherapy.

Inflammations

Epididymo-orchitis: Inflammatory lesions start by epididymitis with subsequent inflammation of the testis proper (orchitis). The causative organisms reach the testis by ascending infection via the vas deferens, by lymphatics of the spermatic cord, or by hematogenous spread.

Nonspecific epididymitis and orchitis: Begins as a primary infection in the urinary tract. Secondary infection of epididymis and testis occurs through ascending infection via vas deferens or lymphatics of the spermatic cord. Causative organisms are E.coli, pseudomonas, gram negative rods, and chlamydia trachomatis

Autoimmune (granulomatous) orchitis: Its origin is obscure. Trauma and autoimmune disorders have been postulated as causes of the lesion

Specific inflammation

Gonorrheal infection: It is a sexually transmitted disease caused by Neisseria gonorrhea. b. Mumps: Is a systemic viral infection that commonly affects school-age children. Testicular involvement is extremely uncommon in these age groups. When mumps occurs in postpubertal males, it is followed by orchitis in about 20%-30% of cases. The testicular involvement is unilateral in 70% of these cases.

Tuberculosis: Almost always begins in the epididymis, with secondary involvement of the testis. It results from hematogenous spread secondary to tuberculosis of the lungs and/or the kidney. d. Syphilis: It always begins as orchitis, with secondary involvement of the epididymis. In many cases orchitis is not associated with epididymitis. It may occur in both congenital and acquired syphilis. The reaction may be localized (gumma) or diffuse (diffuse syphilitic granulation tissue).

Vascular Disturbances

Torsion of the testis is due to twisting of the spermatic cord, with resultant venous obstruction. The thick-walled arteries remain opened resulting in severe venous engorgement and development of venous infarction of the testis (a sac of soft, necrotic, hemorrhagic tissue).

Cause: Occurs in patients with

incompletely descended testicles, absence of scrotal ligament, or testicular atrophy. Torsion is usually precipitated by trauma or violent movement

Miscellaneous Lesions of Tunica Vaginalis

Hydrocele: Accumulation of serous fluid within the tunica vaginalis either due to incomplete closure of processous vaginalis or secondary to generalized edema. It may be secondarily infected

Hematocele: Accumulation of blood within tunica vaginalis secondary to trauma, torsion, hemorrhage, generalized bleeding diathesis or invasion by malignancy

Chylocele: Accumulation of lymphatic fluid within the tunica vaginalis due to lymphatic obstruction, e.g. elephantiasis in filaria.

Spermatocele: Local accumulation of semen within dilated efferent ducts in the head of epididymis due to obstructive lesions in the vas deferens Varicocele: Dilated, tortuous, elongated veins in the spermatic cord.

Testicular Neoplasms

Testicular neoplasms are the most important cause of firm, painless, enlargement of the testis. Peak incidence lies between 15 to 35 years. 95% of these tumors arise from germ cells (all of them are malignant). 5% arise from Leydig cells or Sertoli cells, are more benign than germ cell tumors and are characterized by endocrine abnormalities.

WHO Classification of Testicular Neoplasms

I. Germ cell tumors A. Tumors of one histologic pattern Seminoma Embryonal carcinoma Yolk sac tumor Choriocarcinoma Teratoma a. Mature b. Immature c. Teratoma with malignant transformation of somatic elements.

B. Tumors of more than one histologic pattern Embryonal carcinoma and teratoma (teratocarcinoma). Choriocarcinoma and other types Other combinations

II. Sex cord-stromal cell tumors A. Well differentiated forms Leydig cell tumor Sertoli cell tumor Granulosa cell tumor B. Mixed forms C. Incompletely differentiated forms.

Pathogenesis: The cause for testicular tumors

remains unknown. Important risk factors include: Cryptorchidism in 10% of testicular tumors. Testicular feminization and klinefilter syndrome. Genetic factors; as evidenced by the high risk of testicular neoplasia among siblings of patients with testicular tumors. Some familial clustering are reported. Significant racial differences also occur (rare in African blacks).

I. Germ Cell Tumors A. Tumors of One Histologic Pattern

. Seminoma: It is the most common germ cell tumor in adults; it represents 30% of testicular germ cell tumors that shows a peak incidence in the fourth decade. It is the counterpart of dysgerminoma in females.

Grossly, seminoma appears as large,

soft, well demarcated, homogeneous, gray-white tumor that bulges from cut surface of the affected testis. Large tumors contain foci of coagulative necrosis. Seminomas are usually confined to the testis by an intact tunica albuginea

Microscopically, there are 3 variants

of seminoma Classic (typical) seminoma constitutes 85% of cases, Anaplastic seminoma (10%) and Spermatocytic seminoma (5%).

Classic seminoma: Composed of large cells with distinct borders, clear glycogen-rich cytoplasm, and rounded nuclei with prominent nucleoli. The cells are arranged in small lobules, separated by fibrous septae containing lymphocytic infiltrate. A granulomatous reaction containing giant cells may be seen in some cases.

Embryonal carcinoma: More aggressive than seminoma with a peak incidence between 20- 30 years.

Yolk sac tumor: (endodermal sinus tumor). The most common testicular neoplasm in infants and young children. In adults, it occurs as a component of mixed germ cell neoplasm.

Choriocarcinoma: Highly malignant testicular tumor with widespread hematogenous metastasis to the liver and lung. It occurs as a component of mixed germ cell tumor. Peak incidence between 20-30 years.

Teratomas: A group of neoplasms that show evidence of simultaneous differentiation along endodermal, mesodermal, and ectodermal lines. They may occur at any age.

Morphology: Grossly, teratomas

have variegated appearance, and are firm in consistency. Cut surface contains cysts and cartilaginous areas. Microscopically, 3 variants are recognized based on the degree of differentiation namely; mature, immature, and teratoma with malignant transformation

Mature teratomas: Contain fully differentiated tissues from the three germ cell layers in a haphazard arrangement. Structures related to ectoderm (e.g skin, neural tissue, and skin appendages), to mesoderm (e.g muscle, cartilage, adipose tissue, fatcells, lymphoid tissue, and blood cells), and to endoderm (e.g. gut, bronchial epithelium, glandular elements). Mature teratomas are more common in infants and children. In adults, it should be considered malignant.

Immature teratomas: Contain elements of the 3 germ cell layers in incomplete stages of differentiation. They should be considered malignant especially in adults.

Teratomas with malignant transformation: Characterized by frank malignancy (e.g. squamous cell carcinoma, adenocarcinoma) developing in a mature teratoma. It occurs in adult.

NB: All teratomas in adults should be considered as malignant neoplasm.

Patients with testicular germ cell tumors present mostly with painless enlargement of the testis; non-seminomatous tumors may present with widespread metastasis. Clinically, germ cell tumors are classified into two groups namely: seminomas; and

non seminomatous germ cell tumors.

The 2 groups differ in presentation as well as in prognosis and treatment.

Seminomas remain confined to testis reaching a considerable size before diagnosis. Non seminomatous germ cell neoplasms may have wide spread metastases at the time of diagnosis in the absence of a palpable testicular mass.

Seminomas metastasize by lymphatic route to the para aortic and iliac lymph nodes. Hematogenous spread is unusual in seminoma. Non seminomatous germ cell neoplasms tend to metastasize early by lymphatic; and hematogenous routes (to liver and lung). Seminomas are radiosensitive whereas nonseminomatous germ cell neoplasms are relatively radioresistant and are more aggressive, with poorer prognosis than seminomas.

Clinical staging: Is achieved by physical

examination, radiographic imaging and studies of various tumor markers. Clinical stages include: Stage I: Tumor confined to the testis. Stage II: Metastases limited to retroperitoneal nodes below diaphragm. Stage III: Metastases outside the retroperitonal nodes or above diaphragm.

Tumor markers: Serum markers are of value in; The evaluation of testicular masses. The staging of germ cell tumors. Monitoring the response of a germ cell tumor to therapy. Diagnosis of recurrence during follow up. e.g. Alfa-feto protein is elevated in germ cell neoplasms containing yolk sac elements. Human chorionic gonadotropin is elevated in germ cell neoplasms containing syncytiotrophoblastic elements.

II. Tumors of Sex CordGonadal Stroma A. Well Differentiated Forms

Leydig (Interstitial) cell tumor: Uncommon. It occurs at any age, mostly at 20-60 years. It secretes androgen, and other steroids such as estrogen and corticosteroids.

Clinical features: Presents as a

painless testicular mass with hormonal changes (gynecomastia in adults and precocious puberty in children). Prognosis: 90% are benign and have excellent prognosis; and 10% are malignant (i.e. have infiltrative and spreading tendency).

2. Sertoli cell tumor (Androblastoma): Uncommon. It is composed of Sertoli cells, or a mixture of Sertoli and granulosa cells. It secretes estrogen and/or androgen but in amounts that are insufficient to produce feminization or precocious puberty. Most tumors are benign, 10% only spread and infiltrate.

Testicular Lymphoma

It is not a primary tumor of testis. However, the affected patients may present with only a testicular mass. It constitutes 5% of all testicular neoplasms. It is the most common tumor of the testis in men over the age of 60 years. It is diffuse, large cell, non-Hodgkins lymphoma, which disseminates widely. The prognosis is extremely poor.

DISEASES OF PROSTATE

Prostatitis (Inflammation of prostate) Acute prostatitis: Usually associated with acute bacterial urinary tract infection e.g. E coli, gram negative rods, enterococci, gonococci, and staphylococcus aureus.

Clinically: There is fever, chills,

dysuria, and low backache. The prostate is enlarged, tender, spongy, and soft.

Chronic prostatitis: Bacterial or non bacterial. Occur on top of acute prostatitis, or develop insidiously without previous acute infection.

Clinically, even if asymptomatic, chronic

prostatitis may serve as a reservoir for organisms capable of causing urinary tract infection.

Senile Prostatic Hyperplasia (BPH)

Hyperplasia of both prostatic glands and its fibromuscular stroma Incidence: Present in 20% of males at the age of 40years, increasing to 70% by the age of 60 years and to 90% by the eighth decade. Aetiology: Uncertain, likely related to effects of hormonal changes. In old age, normal androgens drop, leaving action of the normally present estrogen unopposed. Estrogens may increase sensitization, mainly the central portion of the prostate, to the effect of dihydrotestosterone.

Grossly: Usually affects the periurethral glands. The prostate is enlarged, its cut

surface shows multiple well circumscribed nodules, (solid or contain cystic spaces). The urethra is compressed. Sometimes the hypertrophied gland bulge in the urinary bladder lumen as a pedunculated mass, resulting in a ball- valve type of urethral obstruction.

Hyperplastic nodules are composed of varying proportions of proliferating glands and fibromuscular stroma. The glands are lined by 2 cell layers (an inner tall columnar and a peripheral layer of flattened basal cells). Some glands show intraluminal papillae, others are cystically dilated; still others contain inspissated lamellated, proteinaceous material (corpora amylacia) in their lumina. The glands are separated from each other by proliferated fibromuscular stroma. In hugely enlarged cases, there are areas of infarcts and squamous metaplasia of some glands.

Clinical features and complications:

Frequency, urgency, and nocturia (due to urinary bladder irritation). Difficulty in starting and stopping of urinary stream. Painful distention of the urinary bladder. Infection (cystitis and / or pyelonephritis) due to residual urine in the bladder and chronic obstruction. Stone formation (due to stasis associated with infection). Hypertrophy, dilatation, and urinary bladder diverticulae. Bilateral hydronephrosis leading to chronic renal failure.

Carcinoma of the Prostate

It is the most common visceral cancer in males. It is the second most common cause of cancer-related deaths in men older than 50 years, after carcinoma of the lung. Its peak incidence is between 65-75 years. Occult cancers of the prostate are more common than those that are clinically apparent.

Pathogenesis: The cause of prostatic

carcinoma is unknown. However, clinical and experimental evidence suggest that hormonal, genetic, and environmental factors may play a role in its pathogenesis. Hormonal factors are evidenced by absence of prostatic carcinoma in males castrated before puberty. Also, its growth inhibition by orchiectomy and by administration of estrogen (eg. dihydrostilbosterol).

The role of genetic influence could be proved by increased incidence of prostatic cancer in the first degree relatives of patients with cancer of prostate. The role of environmental factors is verified by its occurrence in certain industrial settings and by the significant geographic difference in incidence of the disease.

Ill-defined masses beneath the capsule in the outer peripheral part of the prostate. Cut section shows foci of carcinoma appearing as firm, gray white-to yellow masses with ill-defined margins.

Most cases are adenocarcinoma with variable degrees of differentiation. Well differentiated carcinoma, is composed of small glands that infiltrate the adjacent stroma in an irregular haphazard fashion. These glands are not encircled by collagen or stromal cells, but they lie back-to-back, sharply dissecting through the stroma.

The malignant glands are lined by a single layer of cuboidal cells with prominent nucleoli in their nuclei. The basal cell layer seen in normal or senile hyperplastic glands is absent. The epithelial cells of adjacent glands show dysplastic changes.

The grading schema used for prostate cancer is the Gleason system. According to this system, prostate cancers are stratified into five grades on the basis of glandular patterns of differentiation. Grade 1 represents the most well-differentiated tumors, in which the neoplastic glands are uniform and round in appearance and are packed into wellcircumscribed nodules. By contrast, grade 5 tumors show no glandular differentiation, and the tumor cells infiltrate the stroma in the form of cords, sheets, and nests

Spread: by
Direct extension to seminal vesicles, wall of urinary bladder. Extension to rectum is rare. Lymphatic spread to regional lymph nodes (occurs early). Blood spread especially to bones

Staging: Staging of prostatic cancer

is important in the selection of the appropriate form of therapy. Stage T1 refers to incidentally found cancer. Stage T2 is organ-confined cancer. Stage T3show extra-prostatic extension. Stage T4 reflects direct invasion of contiguous organs.

Clinical features:
A minority of cases are asymptomatic and diagnosed at autopsy or in removal of prostate for senile hyperplasia. Locally advanced cases produce signs and symptoms of prostatism (lower urinary tract obstruction, local discomfort, dysuria, frequency, hematuria, difficulty in starting or stopping urination). Advanced cases may present with back pain. Bone osteoblastic metastases occur in late cases.

Diagnosis: More than 70% of

carcinomas are found peripherally and can be palpated through digital rectal examination. Transrectal ultra sonography, computerized tomography (CT), and magnetic resonance imaging (MRI) are useful in diagnosis and staging of prostatic carcinoma

The use of tumor markers may be beneficial in diagnosis of prostatic carcinoma. Serum acid phosphatase and prostatic specific antigen are used as markers to monitor the presence of metastases, the progress of the disease, and the effect of treatment. Immunohistochemical localization of these markers in tissue sections is helpful in verification of the prostatic origin of metastatic tumors. NB: Prostatic carcinoma may be small in size and hidden; and the patient presents for the first time by its metastases. The carcinoma in such case is called occult carcinoma.