What are the other Names for this Condition? (Also known as/Synonyms)

• Carcinoma-In-Situ of the Testis
• Intratubular Atypical Germ Cells of Testis
• Testicular Intratubular Germ Cell Neoplasia 

What is Intratubular Germ Cell Neoplasm of Testis? (Definition/Background Information)

• Intratubular Germ Cell Neoplasia of Testis (ITGCN) belongs to a category of germ cell neoplasm (tumors) that is not palpable or seen with the naked eyes. ITGCN is not associated with spermatocytic seminoma or endodermal sinus tumor. It is also rarely associated with teratomas
• The risk factors for Intratubular Germ Cell Neoplasia of Testis are mainly undescended testicles and the presence of germ cell tumors
• The cause of the condition is usually unknown; but, it has been widely accepted that it is caused by unknown events resulting in fetal germ cells undergoing abnormal cell division
• It is usually asymptomatic, or sometimes, the symptoms involve infertility, undescended testis, or intersex features. The complications of Testicular Intratubular Germ Cell Neoplasia of Testis include infertility and imbalance in the production of male sex hormones leading in the absence of secondary sexual characteristics
• The prognosis of Intratubular Germ Cell Neoplasia of Testis is excellent with surgical excision of the testis. If not treated, nearly 50% of the cases progress to germ cell tumors within 5 years

Who gets Intratubular Germ Cell Neoplasm of Testis? (Age and Sex Distribution)

• Intratubular Germ Cell Neoplasia of Testis is seen to occur in males worldwide. It can occur at any age including in children, but is common in adults
• Individuals of all racial and ethnic background can be affected. But, it is more commonly seen in the Caucasian population of Denmark, Switzerland, Norway, and other European nations, than the African American population

What are the Risk Factors for Intratubular Germ Cell Neoplasm of Testis? (Predisposing Factors)

The risk factors for Intratubular Germ Cell Neoplasia of Testis are mostly unknown.

• However, the most important known risk factor is a condition called cryptorchidism, or undescended testicle(s). In this condition, one or both the testicles fail to descend into the scrotum from the abdomen
• Normally, the testicles descend into the scrotum, either before birth or within few months after birth. In some cases, the testis never descends and this causes the testicles to remain in the abdomen, even after a year of birth

Other risk factors may include:

• Infertility
• Presence of hypospadias (birth defect involving the urethra)
• Presence of inguinal hernia
• Atrophy of testis due to variety of causes
• Gonadal dysgenesis: An abnormal development of the testicle that increases the risk for Intratubular Germ Cell Neoplasia of Testis. Individuals with low birth weight may have increased risk of developing these tumors
• Family or personal history: Men with a family history of testicular cancer may have an increased risk. Though Intratubular Germ Cell Neoplasia of Testis do not usually run within families, rare cases of increased incidence within families have been reported
• HIV infection and decreased immunity (due to factors such as a kidney transplant) has been shown to increase risk for some testicular cancers
• Smoking: Some studies have shown that longstanding smoking increase the risk
• Prior history of chemotherapy for different malignancy
• It is common in testis harboring germ cell tumors

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider. 

What are the Causes of Intratubular Germ Cell Neoplasm of Testis? (Etiology)

The causes of Intratubular Germ Cell Neoplasia of Testis are mostly unknown. It does not involve amplification or deletion in the short arm or chromosome 12, indicating that changes in 12p are not the initiating event for the formation of germ cell tumors.

Testicular Intratubular Germ Cell Neoplasia is mostly believed to occur due to some of the following factors:

• Genetic defects, such as aneuploidy ranging from hypotriploidy to hypopentaploidy, which are commonly observed
• There is an association with chromosomal abnormalities in chromosome 2, 4, and 13
• Smoking
• A weakened immune system (immune-compromised)
• Family history of testicular cancers
• Exposure to radiation, chemicals, and pesticides
• Prior history of chemotherapy for a different malignancy (cancer)

Currently, research is underway to improve our understanding of these cancers.

What are the Signs and Symptoms of Intratubular Germ Cell Neoplasm of Testis?

Intratubular Germ Cell Neoplasia of Testis is mainly asymptomatic, with no observable macroscopic lesions and the absence of palpable lesions. It may present with the following conditions:

• Undescended testis
• Symptoms secondary to testicular dysfunction may be observed such as:
  • Infertility
  • Dysfunction in the production of male gonadal hormones leading to changes in sexual characteristics      

How is Intratubular Germ Cell Neoplasm of Testis Diagnosed?

Intratubular Germ Cell Neoplasia of Testis is mainly asymptomatic and diagnosed through a testicular tissue biopsy. However, in order to identify the candidates for testicular biopsy, the healthcare provider will undertake a thorough physical examination and a complete medical history. Additionally, the following examinations and diagnostic tests are helpful:

• Testicular examination
• Complete blood count (CBC) with differential of white blood cells
• Liver function test (LFT)
• Blood tests called serum tumor markers:
  • Alkaline phosphatase
  • Alpha-fetoprotein (AFP)   
  • Human chorionic gonadotropin (hCG)
  • Lactate dehydrogenase (LDH)
  • Testosterone levels
• Radiological imaging studies, such as testicular ultrasound, to rule out any testicular tumors
• Tissue biopsy of the tumor: A tissue biopsy is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis
• Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, histochemical stains, molecular testing and very rarely electron microscopic studies. Examination of the biopsy under a microscope by a pathologist is considered to be gold-standard in not only arriving at diagnosis, but also helpful in predicting prognosis based on various components present in the tumor

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Intratubular Germ Cell Neoplasm of Testis?

The complications due to Intratubular Germ Cell Neoplasia of Testis may include:

• Infertility
• Eventual progression of the condition to testicular germ cell tumors

How is Intratubular Germ Cell Neoplasm of Testis Treated?

• Intratubular Germ Cell Neoplasia of Testis is mainly treated by ablation using radiation, such that the radiation is sufficient to destroy carcinoma in situ cells, while preserving most of the normal testicular cells
• Chemotherapy can be used to ablate the lesion, but sometimes the lesions are resistant to chemotherapy and may persist and progress into chemotherapy-resistant malignant testicular tumors
• Surgical removal of testis, known as orchidectomy, is a definitive treatment for Intratubular Germ Cell Neoplasia of Testis. But since all the lesions do not progress to germ cell tumors, sometimes it can be an ‘over-treatment’ and not recommended as a first choice, especially in young males who want to have a family
• If the lesion persists, then there is a very high possibility of it progressing into malignant germ cell tumors of the testis. In such cases, the individuals have to be regularly screened for the development of testicular tumors

How can Intratubular Germ Cell Neoplasm of Testis be Prevented?

The cause of Intratubular Germ Cell Neoplasia of Testis is unknown; hence, there are no known methods to prevent the tumor occurrence.

• Since, it is mainly associated with undescended testis, it is imperative to either treat undescended testis within a year of birth, or surgically remove the undescended testis afterwards
• Regularly performing self-examination of the testicles may help detect any tumor and associated carcinoma (in situ) surrounding the tumor
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Eliminating the modifiable risk factors can help avoid Testicular Intratubular Germ Cell Neoplasia

What is the Prognosis of Intratubular Germ Cell Neoplasm of Testis? (Outcomes/Resolutions)

• The prognosis of Intratubular Germ Cell Neoplasia of Testis is excellent
• Individuals can be completely cured by radiation ablation or surgical removal of the testis

Additional and Relevant Useful Information for Intratubular Germ Cell Neoplasm of Testis:

• Intratubular Germ Cell Neoplasia of Testis (ITGCN) has to be distinguished from spermatocytic seminoma, where the tumor cells completely obliterates and fills the lumen of the seminiferous tubules
• ITGCN is described as the presence of atypical germ cells within the seminiferous tubules characterized by abundant vacuolated cytoplasm, large, irregular nuclei, and prominent nucleoli.
• There are many online groups available for individuals diagnosed with Germ Cell Neoplasia of Testis that provide supportive care, encouragement, and bring a measure of relief to the affected individuals and their families