Juvenile granulosa cell tumors have been found in undescended testes with abnormal sex chromosomes and ambiguous genitalia for references see Testicular tumors do not show endocrine hyperactivity, in contrast to ovarian juvenile granulosa cell tumors.
Aberrant WNT signaling and stimulatory G-protein mediated signaling have been linked with juvenile granulosa cell tumors. Adult-type granulosa cell tumors are comparable to the ovarian tumors, but are extremely rare 2, , These tumors occur in adults at an average age of 42 years. Twenty percent of the patients have shown gynecomastia due to the hormonal activity of the tumor. Most of the tumors are benign, but some malignant cases have also been reported 2.
Mutations in FOXL2 have been reported in adult ovarian granulosa cell tumors but only few secondary mutations have been found in testicular granulosa cell tumors , These exceedingly rare neoplasms are composed of fibroblastic cells of testicular stroma or tunica albuginea 2.
These tumors are reported to be benign. Tumors consisting of more than one stromal or tubular component or have indeterminate morphology are classified as mixed and unclassified sex cord-stromal tumors 2, Sex cord-stromal tumors can contain combinations of Leydig, Sertoli, granulosa, and theca cells, and are therefore called mixed tumors Leydig cells can be difficult to recognize in these tumors.
These tumors are rare and can occur at any age. Depending on the predominant cell type the tumors may behave differently. Gynecomastia, as a sign of endocrine activity, can be found in ten percent of patients 2. These tumors are always benign in children, but in adults malignancy can be found Thus, most of the patients can be treated by orchidectomy, and lymph node dissection is indicated only in cases with overt malignant features on microscopic examination.
Other tumors occurring in the testis are divided into miscellaneous and hematolymphoid tumors 2, The first group includes ovarian epithelial-type tumors, serous or mucinous cystadenomas, adenocarcinomas, Brenner tumor, xantogranuloma and hemangioma. In addition, testicular spread of malignant acute leukemia is common in young boys, and metastases from other solid tumors including the prostate gland, colon, kidney, stomach, pancreas, and malignant melanoma can be found in the testis of adults.
Relative imbalance of androgen signaling excess or deficiency causes the most pronounced secondary endocrine symptoms associated with testicular tumors. Testosterone is produced by tumors, such as Leydig cell tumors, or by normal Leydig cells stimulated by large amounts of hCG from some germ cell tumors. Excess of androgens would lead to precocious puberty in children , , In addition, aromatisation of androgens leads to a relative excess of estrogens, which causes impairment of spermatogenesis in adults and gynecomastia at any age , Testicular dysfunction in young adult patients with testicular cancer, who usually are in their best reproductive age, is a serious clinical problem.
Patients with testicular tumors have poor spermatogenesis and decreased fertility even before the overt tumor has developed 66, 67, 68, and before cytotoxic treatment Features include oligozoospermia, elevated LH levels, and a variable degree of testicular dysgenesis or atrophy in the biopsy, in some cases further complicated by the presence of GCNIS.
Testicular function is further disturbed by treatment of neoplasm. In recent years there is growing concern about adverse late effects of irradiation and chemotherapy 1, , , , Refinement of the dosage must be considered in each patient individually, to eradicate the neoplasm with least possible damage to the endocrine function. The eradication of GCNIS or a tumor by irradiation in bilateral cancer cases leads also invariably to the disappearance of all germ cells and sterility.
This underlines the importance of semen analysis and cryopreservation before treatment which will allow assisted reproduction treatment, if needed , , It is also important to perform semen analysis in all patients interested in fertility before the treatment.
TESE and subsequent intracytoplasmic sperm injection ICSI may be also an option for fertility treatment in some cases of post-chemotherapy azoospermia All patients treated for testicular cancer require careful assessment of their reproductive hormones and spermatogenic capacity with respect to their future fertility, sexual potency, possible need for androgen replacement therapy and general well-being.
In long-term survivors fertility is impaired and signs of Leydig dysfunction manifested as low testosterone and high LH levels are common , , The authors thank the research and clinical teams at their departments for the contribution to the studied summarized in this review.
The authors are also grateful to Prof. McLachlan for the critical review of the chapter. Turn recording back on. National Center for Biotechnology Information , U. Contents www. Search term. Abstract Testicular cancer comprises different neoplasms, depending on the cell of origin and the typical age at presentation, but germ cell-derived tumors constitute the vast majority of cases. Figure 1. Figure 2. Histology of main types of testicular germ cell tumors.
Figure 3. Global incidence rates of testicular cancer. Semen Analysis Semen analysis cannot as yet be used alone for detection of early stages of testicular cancer. Scrotal Imaging Ultrasonography Scrotal ultrasonography has been increasingly popular for assessment of the testicles and should be performed routinely if there is a suspicion of testicular malignancy, even if there is no history of cryptorchidism or fertility problems.
Serum Tumor Markers, Detection and Monitoring of Overt Tumors In the vast majority of cases a scrotal mass is usually the first presentation of testicular cancer, with tenderness reported by only few patients.
The stage grouping recently updated by WHO 2 , is shown in Table 2. Radiotherapy - low dose radiotherapy is a good alternative to orchiectomy in some cases, for example when GCNIS is present in the contralateral testis, so the patient can be spared a total castration and lifelong androgen replacement therapy. The efficacy of radiotherapy with doses as low as 16 Gy was demonstrated in the early studies Even though the lower dose better preserves the function of Leydig cells, more recent studies and current EAU guidelines recommend a dose of 20 Gy, given in fractions of 2Gy , This dose of radiation will almost always destroy also normal germ cells, so radiotherapy may be delayed in patients who wish to secure natural conception of a child.
Chemotherapy - is not an option to treat GCNIS, because a persistence or relapse has been reported in a high proportion of patients , Furthermore, in some cases of extragonadal germ cell tumors treated with chemotherapy, testicular GCNIS progressed to metachronous overt testicular tumors However, if a patient with disseminated disease receives a chemotherapy, he will have a lower risk of metachronous bilateral TGCT.
Surveillance - is potentially hazardous since GCNIS may progress to invasive cancer at any time, but may be an option after careful informed discussion of risks and monitoring with ultrasound examinations, especially if the patient wishes to defer treatment temporarily for the purpose of paternity.
Table 3 Sex cord stromal tumors of the testis adapted from ref. Leydig cell tumors benign or malignant. Leydig Cell Hyperplasia and Tumors Leydig cells are located in the interstitial compartment of the testis and are involved in the development of secondary male characteristics and maintenance of spermatogenesis.
Figure 5. Histology of a Leydig cell tumor. Testicular Adrenal Rest Tumors Excessive secretion of adrenocorticotropin ACTH in poorly controlled hydroxylase deficiency congenital adrenal hyperplasia, CAH or Nelson syndrome postadrenalectomy status may lead to development of hyperplastic interstitial nodules called adrenal rests in the testis resembling Leydig cell tumor or hyperplasia , , Sertoli Cell Tumors Sertoli cells are the somatic cells in the seminiferous epithelium giving structural, metabolic and hormonal support to spermatogenic cells.
Granulosa Cell Tumors Juvenile-type granulosa cell tumors are the most common somatic testicular tumors in infants and occur during the first 6 months after birth 2, , , Fibroma-Thecoma Tumors These exceedingly rare neoplasms are composed of fibroblastic cells of testicular stroma or tunica albuginea 2.
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Some Leydig cell tumors can make estrogens female sex hormones , which can cause breast growth or loss of sexual desire. Some Leydig cell tumors can make androgens male sex hormones. Androgen-producing tumors may not cause any symptoms in men, but in boys they can cause signs of puberty at an abnormally early age, such as a deepening voice and the growth of facial and body hair.
Even if testicular cancer has spread to other parts of the body, many men might not have symptoms right away. But some men might have some of the following:. But if you have any of these signs or symptoms, see your doctor right away. Lump or swelling in the testicle Most often, the first symptom of testicular cancer is a lump on the testicle, or the testicle becomes swollen or larger.
Breast growth or soreness In rare cases, germ cell tumors can make breasts grow or become sore. Early puberty in boys Some Leydig cell tumors can make androgens male sex hormones. Symptoms of advanced testicular cancer Even if testicular cancer has spread to other parts of the body, many men might not have symptoms right away. But some men might have some of the following: Low back pain , from cancer spread to the lymph nodes bean-sized collections of immune cells in back of the belly.
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