Introduction
Cells that form sperm in males and eggs in females are called germ cells. Abnormal cells are found in the tiny tubes where sperm develop. These abnormal cells can develop into cancer and invade nearby normal tissue. It is also referred to as stage 0 testicular carcinoma in situ or testicular intraepithelial neoplasia. In patients with testicular germ cell tumors, the risk of contralateral germ cell neoplasia in situ is four to eight percent, with a greater risk in patients with testicular atrophy.
Which Are the Germ Cells Tumors That Do Not Arise From Intratubular Germ Cell Neoplasm?
The germ cell tumors that are not arising from intratubular germ cell neoplasia include
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Spermatocytic tumors (malignant but rare growth of testes).
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Yolk sac tumors (metastatic tumor of the ovary and test primarily but also be found in other areas of the body).
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Mature teratomas (a type of tumor of the germ cell) in infants.
What Are the Classifications of Intratubular Germ Cell Neoplasia?
Intratubular germ cell neoplasia is classified based on the presence of germ cell neoplasia in situ in the adjacent parenchyma. The classification is as follows:
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Intratubular Seminoma: Morphologically (form and structure) similar cells that completely fill the tubules and replace normal sertoli (striated elongated cells lining the seminiferous tubules) and germ cells.
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Intratubular Nonseminoma: Embryonal carcinoma cells with compaction, overlap, pleomorphism, and necrotic foci.
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Intratubular yolk sac tumor.
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Intratubular teratoma.
What Is the Pathogenesis of Intratubular Germ Cell Neoplasia?
Seminoma (a type of cancer that begins in male germ cells and usually occurs in the testicle but can also be seen in other areas like the brain, chest, or abdomen) and non-seminoma can co-exist in the same tumor. Seminomas are sensitive to radiation therapy.
Several stable gene modifications involved in modulating the common mechanism of single germ cells, such as DNA hypomethylation and histone arginine dimethylation, are shared by gonocytes and intratubular germ cell neoplasia. This leads to two possible mechanisms of intratubular germ cell neoplasia development: either regression of spermatogonia to a primordial germ cell phenotype or abnormal persistence of gonocytes beyond the neonatal period.
Testicular germ cell tumors arise from intratubular germ cell neoplasia. Intratubular germ cell neoplasia is closely associated with fetal gonocytes. Events in the prenatal and perinatal periods can lead to abnormal persistence of fetal gonocytes resulting in intratubular germ cell neoplasia and subsequent testicular germ cell tumor.
Testicular germ cell tumors represent the vast majority of malignant testicular tumors, divided into seminomas and nonseminomas according to histologic findings. Both seminoma and non-seminoma are seen in young men.
Intratubular germ cell neoplasia is a precursor for most testicular germ cell tumors except pediatric germ cell tumors (yolk sac, mature teratoma) and spermatocyte seminoma.
What Is the Diagnosis of Intratubular Germ Cell Neoplasia?
Testicular biopsy is done to diagnose intratubular germ cell neoplasia. The appearance resembles a seminoma. Seminomas tend to grow and spread slowly. Non-seminoma, a more common testicular cancer, grows more than seminomas.
The abnormal germ cells are larger than normal spermatogonia, have large hyperchromatic nuclei with prominent nucleoli, and contain abundant cytoplasm with conspicuous cell margins. The tubular basement membrane is often thickened, and the tubules vary from accommodating adjacent normal sertoli cells and spermatogonia to being completely filled with intratubular germ cell neoplasm cells.
Intratubular neoplasms occurring in the absence of testicular enlargement have been found in cryptorchidism (undescended testes), in the testes of some infertile males, dysgenic testes (underdeveloped testes), and the contralateral testes (volume or length is greater than 2 cm with palpable or nonpalpable testes) after orchiectomy in germ cell cases.
What Are the Histologic or Microscopic Findings?
There can be abnormalities within the seminiferous tubules. The cells are large and atypical, with clear cytoplasm, angulated nuclei with wavy chromatin, prominent nucleoli, and cell borders resembling fried egg seminoma cells. The basement membrane is hyalinized or thickened with atrophic seminiferous tubules arranged like a string of beads which displace the sertoli cells towards the lumen. They will have immunohistochemical characters of spermatogenic precursor cells in the fetal and post-natal testis. Patchy involvement throughout the testis can be seen. Spermatogenesis is usually absent. And maybe having microliths (calcifications).
What Is the Treatment for Intratubular Germ Cell Neoplasia?
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Chemotherapy was used to treat intratubular germ cell neoplasia initially. But later modern studies showed that chemotherapy alone could not treat intratubular germ cell neoplasm.
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Platinum-based chemotherapy is used for bilateral testicular cancer.
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The treatment is orchiectomy (surgical removal of one or both the testis), surveillance, and radiation to the affected testicle.
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In cases where orchiectomy is not performed, there will be a recurrence and subsequent development of a typical invasive tumor.
What Are the Risk Factors for Intratubular Germ Cell Neoplasia?
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Intratubular and testicular germ cell tumors have common risk factors.
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Personal history: The contralateral testicle is at 25 times higher risk if there is a personal history of testicular germ cell tumor.
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Infertility risk is three times higher than non-fertile men.
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In the case of cryptorchidism (it is when one or both the testis do not descend from the abdomen to the scrotum).
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Testicular microlithiasis (a condition in which small clusters of calcium crystals are found in the testicles).
What Is Bilateral Testicular Cancer ?
Bilateral testicular cancer is closely linked with intratubular germ cell neoplasia. Thirty-five percent of testicular cancer cases are bilateral. Bilateral testicular cancers generally have the same histological features. It contains seminomas most frequently, followed by non-seminomas and non-germinal tumors. Bilateral testicular tumors are either synchronous (occurring at the same point) or metachronous (occurring at different points). Bilateral testicular cancers are usually diagnosed early and have a good prognosis.
Conclusion
Testicular cancer is most commonly seen in young men. Non-seminomas are common in the age group of the thirties, whereas seminoma in the age group of the forties. In situ stage of germ cell neoplasia is the common precursor of seminomas and nonseminomas. Intratubular germ cell neoplasia is formerly known as carcinoma in situ of the testis. Patients with testicular cancer should be monitored regularly. Self-examination helps in preventing secondary cancers. Hormone replacement therapy should be given in cases of orchiectomy to treat potential androgen deficiency.
