Male Reproductive Pathology (Ch. 14)

Carcinoma of the Prostate

The significance of carcinoma of the prostate can be summarized as follows: • It is the most common cancer in males. • It is the third most common cause of cancer-related death in males. • It is a tumor of older men, and as the longevity of the population increases, there is a constant increase in the incidence of prostatic cancer. • There is still no adequate treatment for tumors that have extended beyond the confines of the prostate. More than 75% of all patients are diagnosed with such advanced tumors.

Cryptorchidism

• developmental defect that results in incomplete descent of the testis into its normal scrotal position • most important abnormality of the male reproductive system • fetal testes are originally located in the abdominal cavity → in utero, the testes slowly descend toward the inguinal canal and ultimately reaching the scrotum → the inguinal canal is then obliterated, thus preventing the testes from retracting into the abdominal cavity and permanently fixed in the scrotum. • descent of the testes is fully completed by the time of birth in most boys, however in 3% to 4% of newborn male infants the inguinal canal remains open, allowing the cremasteric muscle that is attached to the testes to pull the testes back into the inguinal canal or the abdominal cavity (retractile testes) • in most cases the inguinal canal closes, and by the end of the first year of life, less than 1% of all male infants do not have one or both testes in the scrotum → cryptorchid testes must be fixed in the scrotum surgically, and the inguinal canal must be closed surgically to prevent formation of a hernia, an outpouching of the abdominal organs (usually the intestines) into the scrotum.

Carcinoma of the Penis

• rare in the United States, where it affects only 1 to 2 men per 100,000. • much more common in parts of the world where neonatal circumcision is not practiced and genital hygiene is poor • more common in noncircumcised than circumcised men. • epidemiologic studies show that the prevalence of HPV virus induced cervical cancer parallels the prevalence of penile cancer, suggesting that the carcinogenic viruses are transmitted by sexual contact. • Almost all tumors are located on the glans of the penis → histologic examination reveals the tumors to be squamous cell carcinomas. • Tumors tend to metastasize first to inguinal lymph nodes. • Treatment includes surgical amputation combined with radiation therapy. The prognosis depends on the stage of the disease: localized lesions have a good prognosis, whereas advanced lesions are less responsive to treatment. The overall 5-year survival rate is approximately 60%.

Benign prostatic hyperplasia (BPH)

• reactive enlargement of the periurethral portion of the prostate and the so-called median bar (median lobe), a part of the prostate located at the neck of the urinary bladder • as the prostate undergoes nodular hyperplasia, it compresses the urethra, and the median lobe may even act as a valve impeding urination. • The centrally located hyperplastic nodules compress and expand the peripheral tissue. This is called the surgical capsule of the prostate, because it loosely envelopes the abnormal tissue.

Abnormalities in Testosterone Secretion

• result in incomplete development of the reproductive organs (require testosterone to develop normally) • after birth and until puberty → testes produce little testosterone • puberty → under the influence of pituitary gonadotropins, a major surge in testosterone production occurs, determining the maturation of all male sex organs and secondary sexual characteristics. • Premature activation of Leydig cells results in precocious puberty, late activation results in delayed puberty. Both conditions are usually related to hypothalamic and pituitary disturbances. • hypogonadism: puberty does not occur and the testes remain infantile → patients are infertile and have eunuchoid body features, without body or pubic hair

Other Tumors

• seminomas and malignant NSGCTs of adulthood account for 90% of all testicular tumors. • yolk sac tumors occur in infancy and childhood, typically before the end of the fourth year of life. These tumors secrete AFP. Although potentially malignant, if removed in time, the patient has an excellent prognosis. • Leydig Cell Tumors: like the normal cells from which they originate, these may be hormonally active and produce either androgens, like testosterone or estrogens • can occur at any age • although most are benign, 10% can present as low-grade malignant lesions, and some may even metastasize. • Leydig cell tumors may cause precocious puberty. In adult males, some Leydig cell tumors produce estrogen, which may cause gynecomastia, loss of libido, and feminization. • Sertoli Cell Tumors: usually benign. Although these tumors may secrete inhibin and sex hormones, the symptoms are typically related to the testicular mass rather than to the small amounts of hormones produced by the tumor.

Syphilis

• sexually acquired disease caused by the spirochete T. pallidum. • Three stages of the disease—primary, secondary, and tertiary syphilis • Primary Stage: primary lesion (a painless, indurated ulcer known as a chancre) develops 1 to 12 weeks after exposure, most often on the glans penis, but it may appear on the inner side of the prepuce in uncircumcised men or on and around the anus in male homosexuals. The ulcer is accompanied by local, usually inguinal, lymph node enlargement. The primary chancre heals spontaneously in about 4 to 6 weeks. With appropriate antibiotic treatment, it will heal in a few days. • Secondary Stage: symptoms are manifestations of systemic spread of spirochetes and an immune reaction to the pathogen. Occurs approximately 2 months to 2 years after the primary infection. Clinically, marked by systemic symptoms, such as fever, malaise, macular rash, lymph node enlargement, and the appearance of slightly elevated skin lesions (papules) called condyloma latum. Symptoms may also include mucosal ulcerations, CNS irritation (probably secondary to meningitis), hepatitis, and kidney symptoms. All symptoms have a self-limited course and disappear spontaneously. • Tertiary Stage: after remission of secondary syphilis, the disease may enter a latent phase for an extended period. The symptoms of tertiary syphilis occur in a small number of untreated or incompletely treated patients 2 to 20 years after the primary infection. The most important symptoms are related to the pathologic lesions of the cardiovascular and central nervous systems. Histologic hallmarks of tertiary syphilis include chronic perivasculitis involving the small blood vessels and typical syphilitic granulomas (gumma). Lymphocytic and plasma cellular infiltrates around the vasa vasorum of the aorta, the small nutrient arteries in the wall of the aorta, cause destruction of the arterial wall with widening of the lumen (aneurysm). Gummas of the cardiac valves also cause destruction and insufficiency of the valves, most often at the aortic orifice. Meningovascular syphilis causes destruction of the posterior columns of the spinal cord, evidenced as tabes dorsalis. As a result of destruction of the sensory nerve axons in the posterior columns, these patients lose proprioception and have difficulty coordinating their movements. In the brain the loss of neurons secondary to syphilis results in dementia, known as general paralysis of the insane → these persons lose all mental faculties and are often paralyzed because of the destruction of their motor neurons. Tertiary syphilis is incurable. • Diagnosis of syphilis is based on serologic tests, which include the detection of Treponema—specific and nontreponemal antibodies in the blood. Treponema-specific tests are more precise, but they also become positive only after a 4- to 6-week interval following infection. These tests remain positive forever and are thus useful for the diagnosis of advanced stages of syphilis.

Klinefelter's syndrome

• trisomy of sex chromosomes (47, XXY) • affected persons have atrophic testes and are infertile.

Urethritis

• urethritis with purulent exudate is typical of infection with Neisseria gonorrhoeae (diplococci that can be readily demonstrated by microscopic examination of the inflammatory cells expressed from the urethra) • nonbacterial urethritis: no bacteria evident and no purulent exudate (ureaplasma urealyticum, a bacteria-like microbe of the Mycoplasma species, accounts for about 20% of these cases.

anorchia

absence of testes

polyorchidism

three or more testes

Chlamydia trachomatis

• Chlamydia trachomatis is considered the cause of nongonococcal urethritis in about 50% of all cases. • Chlamydial infection may cause production of antibodies that cross-react with human antigens expressed on several organs, including the urethra, uvea of the eye, and the joints → Reiter's syndrome • The triad of urethritis, uveitis, and arthritis is called Reiter's syndrome. Some strains of C. trachomatis that are prevalent in tropical countries cause lymphogranuloma venereum (LGV), a disfiguring disease including suppurative inguinal lymphadenitis and multiple pus-draining sinuses in the genital area.

Cancer of the Prostate

• Histologic studies reveal that most prostatic malignant lesions are adenocarcinomas. • prostatic cells produce prostate-specific antigen (PSA), a serine protease that is secreted normally into the semen. Its physiologic role is to liquefy the coagulum that forms from ejaculated sperm. • PSA is normally present in prostatic secretions, and only a small fraction of it enters the blood. In healthy men, blood contains less than 4 ng/mL of PSA. • Prostate cancer cells also produce PSA with considerable amounts of PSA secreted by the prostate carcinoma cells entering the blood → blood levels of PSA exceeding 10 ng/mL are typically found in cancer patients. • about 30% to 40% of all patients with prostate cancer have only mild elevation of PSA levels, in the range from 4 to 6 ng/mL. Other prostatic diseases, such as prostatitis and prostatic hyperplasia, can also cause PSA elevations in the blood. • Alkaline phosphatase, another blood enzyme, is not expressed or produced by prostatic cells but is abundant in osteoblasts. When the prostatic carcinoma cells metastasize to the bone and evoke an osteoblastic reaction, the proliferation of osteoblasts results in an increase of alkaline phosphatase in the blood; therefore, any tumor that causes osteoblastic metastases will cause elevation of serum alkaline phosphatase levels. • Prostatic carcinoma originates in the peripheral parts of the prostate; therefore, it does not cause compression of the urethra or urinary problems until late in the course of the disease. • Early tumors that are limited to the prostate are the only form of prostatic cancer amenable to successful treatment → tumors are typically asymptomatic and may be detected only by measuring the serum PSA levels and taking a biopsy specimen in those men who have elevated serum PSA. • Bone metastases cause dull and persistent pain, which is often limited to the back because of the metastases in the sacrum and vertebrae • estimated that one third of all patients with tumors presumed to be confined to the prostate have lymph node metastases. • The 5-year survival of patients with tumor limited to the prostate is 75%. Patients with tumors that have spread beyond the confines of the prostate have a 35% to 50% 5-year survival rate, depending on the exact stage of the tumor.

Carcinoma in situ or Intratubular Germ Cell Neoplasia (ITGCN)

• Malignant transformation of germ cells • latent period can last 5 to 20 years → ITGCN cells then cross the basement membrane and an invasive malignant disease • seminoma: tumor cells retain the features of primitive gonocytes, forming a neoplasm composed of a single cell type, an create a tumor of seminal epithelium-like cells • embryonal carcinoma (EC): the tumor cells acquire the characteristics of embryonic cells • germ cells in the testis, like those in the ovary, are the precursors of embryonic cells. • Embryonic cells are normally formed only from zygotes (after fusion of the male and female gametes) → EC cells are descendants of spontaneously activated male germ cells that evolve into embryonic cells and can differentiate into various fetal and adult tissues and even form components that resemble extraembryonic membranes (i.e., trophoblast of the placenta and yolk sac). • malignant mixed germ cell tumor (MGCT): also known as teratocarcinoma or malignant teratoma → all the embryonic cells differentiate into mature tissues, forming a teratoma (benign tumor) composed of somatic tissues that are derived from all three embryonic germ layers: ectoderm, endoderm, and mesoderm. • Malignant mixed germ cell tumor (MGCT): also known as teratocarcinoma or malignant teratomamalignant → tumor composed of EC cells and somatic tissues • both teratoid tumors contain haphazardly arranged and intermixed tissues, such as skin, brain, muscle, and cartilage intestine. MGCTs also contain malignant stem cells (EC cells) and scattered trophoblastic and yolk sac epithelium. Trophoblastic cells, like the normal placental cells, secrete human chorionic gonadotropin (hCG) into the blood. Because hCG is not normally found in the serum or urine of males (or in females unless they are pregnant), the presence of hCG in a male is strong evidence of a germ cell tumor. Yolk sac cells secrete alpha-fetoprotein (AFP), another germ cell tumor marker of germ cell neoplasia. • ECs and MGCT have the same malignant stem cells; the only difference is that in pure EC (which is rare) these stem cells do not differentiate and are composed of monomorphic cell populations, i.e., all cells are of the same type. On the other hand, EC cells in MGCT differentiate and form various tissues. • For practical purposes, both ECs and MGCT are thus considered by clinicians under the name of nonseminomatous germ cell tumors (NSGCTs). This term distinguishes them from seminomas • In a small number of NSGCTs, the trophoblastic cells overgrow other tumor components and continue proliferating, forming highly malignant tumors equivalent to placental choriocarcinomas. Theoretically, one could predict that in some NSGCTs the yolk sac component will also acquire such highly malignant properties, as has been noted in ovarian germ cell tumors. However, pure yolk sac carcinoma rarely develops in adults. • Tumors composed of yolk sac components are confined to the testes of infants and children younger than 4 years. • Classical seminomas constitute 40% of all testicular tumors; NSGCTs account for 45%; and in 15% of the cases, the tumor is mixed seminoma and NSGCT. Sex-cord cell tumors, which includes Sertoli and Leydig cell tumors, account for 5% of all testicular tumors.

Tumors of the Testis

• Testicular tumors account for only 1% of all neoplasms in men. • peak incidence occurs in men 25 to 45 years of age • most important aspects of testicular cancer can be summarized by the "rule of nineties" • Ninety percent of tumors occur in adulthood in the age group between 25 and 45 years. These tumors are rare before puberty and in older men. • If a testicular tumor develops in an older man, most likely it represents a disseminated lymphoma or a metastasis from an abdominal primary lesion and is not a primary testicular tumor. • Ninety percent of tumors are of germ cell origin. • Ninety percent of tumors are malignant. All testicular tumors follow the same metastatic pathway → typically, the tumors spread to periaortic lymph nodes in the abdomen. From this site, the tumors metastasize to the upper abdomen and may spread hematogenously to the liver, lungs, and brain. • Ninety percent are curable with modern treatment. • Etiology and Pathogenesis: more than 90% of testicular tumors develop from germ cells. Of the remaining, 5% are derived from Sertoli and Leydig cells and 5% represent metastases. The etiology of testicular tumors is unknown but it has been noted that tumors develop more often in developmentally abnormal testes and in cryptorchid testes. Cryptorchidism is the most important predisposing condition.

Tumor Genesis

• The testis consists of spermatogenic cells, Sertoli cells, and Leydig cells, all of which can give rise to tumors. • neoplastic germ cells can differentiate into embryonic cells, as normally occurs after fertilization (the fusion of male and female germ cells). These embryonic cells can form tumors that are histologically distinct from the normal cells in the testis and consist of tissues normally found in fetal or adult organs not related to the testis. • tumors are known as benign or malignant teratomas, which are in the latter case also known as malignant mixed germ cell tumors.

BPH Patogenesis

• all theories proposed so far invoke a hormonal mechanism, implying that testosterone plays a crucial role. • development of the prostate at puberty occurs only in the presence of male sex hormones → young men who are castrated before the onset of puberty have a small, nonfunctioning prostate. • it is possible that estrogen sensitizes the prostatic cells to the action of testosterone or that the male and female hormones act synergistically → a similar interaction of estrogen and testosterone probably accounts for the BPH that occurs in older men; even though older men produce less testosterone than younger men, the relative increase of estrogen that occurs with age probably facilitates and augments the action of testosterone on the periurethral portion of the prostate. • metabolic inhibitors of testosterone, which counteract the effects of male sex hormones, are often used instead of surgery to treat prostatic hyperplasia. • on gross examination, prostates that are enlarged as a result of BPH appear nodular

Balanitis

• balanitis: inflammation of the glans penis • may present as localized or diffuse redness, swelling, or ulceration of the mucosa of the glans penis • usually caused by viruses or bacteria • herpesvirus: typically causes vesicles that rupture, giving rise to shallow ulcers. • Treponema pallidum: causes ulcerations (called syphilitic chancre) of the glans or even the skin or the shaft of the penis. • Human papilloma virus (HPV): produces genital warts, known as condyloma acuminatum.

Gonorrhea

• caused by Neisseria gonorrhoeae (also known as gonococcus) that results in purulent urethritis • typically presents with burning on urination and a yellow urethral discharge 2 to 5 days after exposure. • Gonococcus invades the mucosa of the penile urethra and the adjacent periurethral glands. The inflamed mucosa is red, moist, and covered with purulent exudate, which on microscopic examination consists predominantly of polymorphonuclear neutrophils with gonococci seen in the cytoplasm of inflammatory cells. • complications of gonococcal urethritis: ascending infection may lead to prostatitis and epididymitis. Typical consequences of inadequately treated gonorrhea include pain during urination or infertility secondary to obstructed sperm outflow. • Gonococci may also disseminate by blood to distant sites → gonococcal arthritis is the most common complication

Genital Herpes

• caused by herpes simplex virus (HSV) type 2 • virus is closely related to HSV type 1, the cause of cold sores or blisters (herpes labialis). • both viruses invade the skin and mucosal cells, disrupting the epithelial layer and producing vesicles filled with clear fluid → the genital lesions are located on the glans or the skin of the shaft of the penis or the scrotum. • the vesicles rupture and transform into shallow, painful ulcers that heal without scarring. • has a tendency to recur → following the acute disease, the HSV travels along the axons of the peripheral nerves and invades the ganglion cells that innervate the genital area. Virus remains dormant in ganglion cells, until disturbed and activated again from its latent state, it then descends along the nerves into the genital area, producing new vesicular eruptions. • individuals with active herpetic lesions are contagious, but even asymptomatic carriers or those with atypical nonvesicular lesions may transmit the disease.

BPH Clinical Features

• clinical symptoms of BPH are related to urethral compression and retention of urine • the periurethral location of hyperplastic nodules is associated with urinary symptoms early in the course of the disease, in contrast to peripherally located prostatic carcinoma, which produces such symptoms only in later stages of the disease. • BPH causes distortion and elongation of the urethra, which also affect the sphincters regulating urination. • Urinary frequency and dysuria (painful urination) are common and usually indicate a superseding infection that develops in the residual urine.

Prostate

• composed of epithelial and stromal cells that express receptors for sex hormones • the development and function of the prostate depend on male sex hormones → persons who have accidentally lost testes, or were castrated, before puberty have a very small prostate because this gland does not develop unless properly stimulated by androgens during puberty. • prostatic hyperplasia, commonly found in older men, is a hormonally induced lesion, although its pathogenesis is still unknown. It is thought to be related to an imbalance of male and female hormones that occurs as a result of a decrease in testosterone production with advancing age. • The development and function of the prostate depend on male sex hormones → losing testes before puberty results in a very small prostate because the gland does not develop unless properly stimulated by androgens during puberty. • Prostatic hyperplasia, commonly found in older men, is thought to be related to an imbalance of male and female hormones that occurs as a result of a decrease in testosterone production with advancing age.

Testes Composition

• composed of seminiferous tubules and supporting structures, which include the blood vessels, stromal cells, and connective tissue • the stroma contains hormone-secreting Leydig cells. • the seminiferous tubules are lined by germ cells in various stages of maturation and the supporting sex-cord cells, the Sertoli cells. • The epididymal ducts are lined by secretory cells that produce a protein- and carbohydrate-rich fluid → during ejaculation, the epididymal sperm enter the seminal ampule and are mixed with the seminal fluid from the seminal vesicles and the prostatic fluid (ejaculate)

Prostatic Carcinoma Etiology and Pathogenesis

• etiology and pathogenesis poorly understood • widely believed that testosterone stimulates the growth of prostatic cancer as (1) prostatic carcinoma does not develop in persons who are castrated before puberty, (2) testosterone receptors have been demonstrated on prostatic carcinoma cells, (3) castration of patients with prostatic cancer usually retards the growth of the tumor, and (4) anti-testosterone drugs retard tumor growth. • typically, patients with prostatic carcinoma do not have elevated serum testosterone levels and most of them in fact show an age-related decrease in testosterone output. • Enormous racial differences noted in the incidence of this tumor → the incidence of prostatic cancer in East Asians is more than 10 times lower than that among whites but Americans of Asian origin have a greater incidence of prostatic cancer than do their relatives living in Asia. • Carcinoma of the prostate originates in the peripheral (posterior lobe) glands. The initial tumor is limited to the glands, but it gives rise to locally invasive lesions. Cancer spreads through the lymphatics and into the adjacent organs, primarily the rectum, urinary bladder, and other pelvic structures. Perineural invasion is particularly common. Pelvic lymph nodes and, subsequently, retroperitoneal abdominal lymph nodes are involved relatively early in the course of the disease. • Distant metastases occur via the lymphatics or blood. Among the most common distant organs involved are the vertebral bones, lungs, and liver. The lumbosacral vertebral and sacral bones are most often involved, presumably as a result of retrograde spread through the vertebral venous plexus, which drains venous blood from the prostate, lower vertebrae, and the sacrum.

Nonseminomatous Germ Cell Tumors

• histologically heterogeneous group of tumors composed of malignant stem cells. • As a rule, almost all of these tumors contain EC cells, their malignant stem cell counterpart. • EC cells may form monomorphic tumors, as in pure ECs, or they may be admixed with other tissues forming the teratoma component of such a MGCT. • Approximately 15% of testicular NSGCTs also contain seminomas. Because the seminoma is the less malignant component, all of these tumors should be treated clinically as any other NSGCT. • On gross examination, NSGCTs have a variegated appearance that is partially attributable to their heterogeneous histologic composition; partially to the rapidly proliferating nature of malignant stem cells, which cause necrosis and hemorrhage; and partially to the frequent presence of trophoblastic cells that invade and destroy tissue like their normal equivalents in the placenta • On histologic examination, the tumors may be composed of EC cells only or of EC cells admixed with various other tissues and choriocarcinoma (trophoblastic) or choriocarcinoma yolk sac carcinoma-like cells. Pure choriocarcinoma occurs occasionally, but it is extremely rare. Pure yolk sac carcinoma is an almost nonexistent form of NSGCT in adults. • like all other testicular tumors, NSGCTs present as testicular masses. Affected patients tend to be somewhat younger than those with seminoma (peak incidence occurs at age of 30 years). At the time of diagnosis, many of these tumors will have already metastasized, in contrast to seminomas, most of which are still localized at the time of diagnosis. • Trophoblastic cells and yolk sac cells are found in 70% of NSGCTs → these cells produce hCG and AFP, which can be detected in the serum of tumor-bearing patients; thus, these tumors can be monitored by serologic means using AFP and hCG as tumor markers. • After removal of the tumor, the elevated serum hCG and AFP levels usually decrease to undetectable levels, as one would expect in normal males. However, if the patient has metastases that have not been removed, serum hCG and AFP levels will remain elevated. Similarly, the initial decline in serum AFP and hCG levels will be reversed if there is tumor recurrence (Figure 14-10).

Cryptorchidism Pathology

• infertility can result if both testes are cryptorchid • cryptorchid testes have a 10-fold greater risk of undergoing malignant transformation than do normal testes → surgical correction at an early age reduces this risk but does not eliminate it completely

Chlamydial Infections

• minuscule obligate intracellular pathogens that can survive only inside infected cells. • Chlamydia trachomatis, the most important of these gram negative bacteria, may be sexually transmitted and is the most common cause of bacterial urethritis in men. It can also infect women and cause urethritis, endometritis, and pelvic inflammatory disease (PID). • Chlamydial urethritis occurs most often in sexually active men → often presents with urethral pain without discharge • many infected men have no symptoms; however, they are still infectious and may transmit the infection to their sexual partners. In other men the infection may spread to the prostate and epididymis and cause chronic inflammation and pain. • treatment includes broad-spectrum antibiotics.

hypospadias

• most common abnormality of the penis • abnormal opening of the urethra on the lower side of the shaft of the penis.

Epispadia

• opening of the urethra on the posterior shaft (observing an erect penis) • may be associated with abnormal development of the anterior side of the urinary bladder (extrophy of the bladder).

Infections of the Male Reproductive Tract

• orchitis: inflammation of the testes; may occur as an isolated infection, but more often combined with epididymitis (epididymo-orchitis) → complication of lower urogenital tract infection. • Isolated orchitis: typical complication of hematogenous spread, such as occurs in secondary syphilis, or in certain viral diseases, such as mumps. • epididymitis: caused by ascending infection → usually a complication of urethritis or prostatitis. In young men it is most often a complication of sexually acquired infections caused by pathogens, such as N. gonorrhoeae and C. trachomatis. In older patients it is caused by uropathogens, and typically it is a complication of urinary obstruction or prostatic surgery. • prostatitis: disease affecting older men and is usually related to stagnation of urine. The infections are caused by uropathogens, a heterogeneous group of gram negative bacteria, such as Escherichia coli and Proteus mirabilis. The disease presents with pain during urination, urgency, and fever, and has a tendency to recur. • urethritis • balanitis: inflammation of the glans penis

Seminomas

• present as firm intratesticular masses that on cross section appear yellow and slightly lobulated • histologic examination reveals that the tumor is composed of large cells with clear, glycogen-rich cytoplasm resembling gonocytes → cells are arranged into groups separated by connective tissue septa infiltrated with lymphocytes and macrophages • peak incidence for seminomas occurs at age 40. Seminomas do not occur before puberty and are rare in persons over the age of 60 years. • Tumors cause enlargement of the testis and few other symptoms, such as discomfort or dull scrotal pain. There are no typical serologic tumor markers for seminoma → the tumor cells do not produce AFP or hCG. • Seminomas are associated with a good prognosis → tumor is radiosensitive and the cells evoke a strong immune reaction, manifested by lymphocyte and plasma cell infiltrates, which retards the growth of the tumor. • Although advanced tumors have a less favorable outcome, the overall cure rate is more than 90%.