The 1997 International Germ Cell Consensus Classification is a tool for estimating the risk of relapse after treatment of malignant germ cell tumor.

A small study of ovarian tumors in girls reports a correlation between cystic and benign tumors and, conversely, solid and malignant tumors. Because the cystic extent of a tumor can be estimated by ultrasound, MRI, or CT scan before surgery, this permits selection of the most appropriate surgical plan to minimize risk of spillage of a malignant tumor.

Access to appropriate treatment has a large effect on outcome. A 1993 study of outcomes in Scotland found that for 454 men with non-seminomatous (non-germinomatous) germ cell tumors diagnosed between 1975 and 1989, 5-year survival increased over time and with earlier diagnosis. Adjusting for these and other factors, survival was 60% higher for men treated in a cancer unit that treated the majority of these men, even though the unit treated more men with the worst prognosis.

Choriocarcinoma of the testicles has the worst prognosis of all germ cell cancers

Presence of an ovarian tumour plus hormonal disturbances suggests a Leydig cell tumour, granulosa cell tumour or thecoma. However, hormonal disturbances, in Leydig tumours, is present in only 2/3 of cases. Testicular Leydig cell tumours can be detected sonographically, ultrasound examinations may be ordered in the event of a palpable scrotal lump, however incidental identification of these lesions is also possible.

A conclusive diagnosis is made via histology, as part of a pathology report made during or after surgery. Reinke crystals are classically found in these tumours and help confirm the diagnosis, although they are seen in less than half of all Leydig cell tumours. See also Sex cord-stromal tumour. Immunohistochemical markers of Leydig cell tumours include inhibin-alpha, calretinin, and melan-A.

On ultrasound, a sertoli cell tumour appears as a hypoechoic intratesticular lesion which is usually solitary. However, the large cell subtype might present as multiple and bilateral masses with large areas of calcification. An MRI may also be conducted, but this typically is undefinitive.

Microscopy and immunohistochemistry are the only way to give a definitive diagnosis, especially when there is a suspected seminoma.

Blood tests may detect the presence of placental alkaline phosphatase (PLAP) in fifty percent of cases. However, PLAP cannot usefully stand alone as a marker for seminoma and contributes little to follow-up, due to its rise with smoking. Human chorionic gonadotropin (hCG) may be elevated in some cases, but this correlates more to the presence of trophoblast cells within the tumour than to the stage of the tumour. A classical or pure seminoma by definition do not cause an elevated serum alpha fetoprotein . Lactate dehydrogenase (LDH) may be the only marker that is elevated in some seminomas. The degree of elevation in the serum LDH has prognostic value in advanced seminoma.

The cut surface of the tumour is fleshy and lobulated, and varies in colour from cream to tan to pink. The tumour tends to bulge from the cut surface, and small areas of hemorrhage may be seen. These areas of hemorrhage usually correspond to trophoblastic cell clusters within the tumour.

Microscopic examination shows that seminomas are usually composed of either a sheet-like or lobular pattern of cells with a fibrous stromal network. The fibrous septa almost always contain focal lymphocyte inclusions, and granulomas are sometimes seen. The tumour cells themselves typically have abundant clear to pale pink cytoplasm containing abundant glycogen, which is demonstrable with a periodic acid-Schiff (PAS) stain. The nuclei are prominent and usually contain one or two large nucleoli, and have prominent nuclear membranes. Foci of syncytiotrophoblastic cells may be present in varied amounts. The adjacent testicular tissue commonly shows intratubular germ cell neoplasia, and may also show variable spermatocytic maturation arrest.

POU2AF1 and PROM1 have been proposed as possible markers.

Intratesticular masses that appear suspicious on an ultrasound should be treated with an inguinal orchiectomy. The pathology of the removed testicle and spermatic cord indicate the presence of the seminoma and assist in the staging. Tumors with both seminoma and nonseminoma elements or that occur with the presence of AFP should be treated as nonseminomas. Abdominal CT or MRI scans as well as chest imaging are done to detect for metastasis. The analysis of tumor markers also helps in staging.

The preferred treatment for most forms of stage 1 seminoma is active surveillance. Stage 1 seminoma is characterized by the absence of clinical evidence of metastasis. Active surveillance consists of periodic history and physical examinations, tumor marker analysis, and radiographic imaging. Around 85-95% of these cases will require no further treatment. Modern radiotherapy techniques as well as one or two cycles of single-agent carboplatin have been shown to reduce the risk of relapse, but carry the potential of causing delayed side effects. Regardless of treatment strategy, stage 1 seminoma has nearly a 100% cure rate.

Stage 2 seminoma is indicated by the presence of retroperitoneal metastasis. Cases require radiotherapy or, in advanced cases, combination chemotherapy. Large residual masses found after chemotherapy may require surgical resection. Second-line treatment is the same as for nonseminomas.

Stage 3 seminoma is characterized by the presence of metastasis outside the retroperitoneum—the lungs in "good risk" cases or elsewhere in "intermediate risk" cases. This is treated with combination chemotherapy. Second-line treatment follows nonseminoma protocols.

Due to the difficulty in identifying the tumour using imaging techniques, an orchiectomy is often performed. The majority of sertoli cell tumours are benign, so this is sufficient. There is no documented benefit of chemotherapy or radiotherapy.

GCNIS is not palpable, and not visible on macroscopic examination of testicular tissue. Microscopic examination of affected testicular tissue most commonly shows germ cells with enlarged hyperchromatic nuclei with prominent nucleoli and clear cytoplasm. These cells are typically arranged along the basement membrane of the tubule, and mitotic figures are frequently seen. The sertoli cells are pushed toward the lumen by the neoplastic germ cells, and spermatogenesis is almost always absent in the affected tubules. Pagetoid spread of GCNIS into the rete testis is common. Immunostaining with placental alkaline phosphatase (PLAP) highlights GCNIS cell membranes in 95 percent of cases. OCT3/4 is a sensitive and specific nuclear stain of GCNIS.

The usual chemotherapy regimen has limited efficacy in tumours of this type, although Imatinib has shown some promise. There is no current role for radiotherapy.

The usual treatment is surgery. The surgery for females usually is a fertility-sparing unilateral salpingo-oophorectomy. For malignant tumours, the surgery may be radical and usually is followed by adjuvant chemotherapy, sometimes by radiation therapy. In all cases, initial treatment is followed by surveillance. Because in many cases Leydig cell tumour does not produce elevated tumour markers, the focus of surveillance is on repeated physical examination and imaging.

In males, a radical inguinal orchiectomy is typically performed. However, testes-sparing surgery can be used to maintain fertility in children and young adults. This approach involves an inguinal or scrotal incision and ultrasound guidance if the tumour is non-palpable. This can be done because the tumour is typically unifocal, not associated with precancerous lesions, and is unlikely to recur.

The prognosis is generally good as the tumour tends to grow slowly and usually is benign: 10% are malignant. For malignant tumours with undifferentiated histology, prognosis is poor.

Women with benign germ cell tumors such as mature teratomas (dermoid cysts) are cured by ovarian cystectomy or oophorectomy. In general, all patients with malignant germ cell tumors will have the same staging surgery that is done for epithelial ovarian cancer. If the patient is in her reproductive years, an alternative is unilateral salpingoophorectomy, while the uterus, the ovary, and the fallopian tube on the opposite side can be left behind. This isn't an option when the cancer is in both ovaries. If the patient has finished having children, the surgery involves complete staging including salpingoophorectomy on both sides as well as hysterectomy.

Most patients with germ cell cancer will need to be treated with combination chemotherapy for at least 3 cycles. The chemotherapy regimen most commonly used in germ cell tumors is called PEB (or BEP), and consists of bleomycin, etoposide, a platinum-based antineoplastic (cisplatin).

Spermatocytic seminomas are diagnosed based on tissue from orchiectomy (or partial orchiectomy), done for a lesion suspicious for cancer on medical imaging.

The macroscopic appearance of the tumour is of a mutinodular grey-white to tan coloured mass with gelatinous, haemorrhagic and necrotic areas. The tumour may extend beyond the testis.

GCNIS is generally treated by radiation therapy and/or orchiectomy. Chemotherapy used for metastatic germ cell tumours may also eradicate GCNIS.

Although often described as benign, a teratoma does have malignant potential. In a UK study of 351 infants and children diagnosed with "benign" teratoma reported 227 with MT, 124 with IT. Five years after surgery, event-free survival was 92.2% and 85.9%, respectively, and overall survival was 99% and 95.1%. A similar study in Italy reported on 183 infants and children diagnosed with teratoma. At 10 years after surgery, event free and overall survival were 90.4% and 98%, respectively.

Depending on which tissue(s) it contains, a teratoma may secrete a variety of chemicals with systemic effects. Some teratomas secrete the "pregnancy hormone" human chorionic gonadotropin (βhCG), which can be used in clinical practice to monitor the successful treatment or relapse in patients with a known HCG-secreting teratoma. This hormone is not recommended as a diagnostic marker, because most teratomas do not secrete it. Some teratomas secrete thyroxine, in some cases to such a degree that it can lead to clinical hyperthyroidism in the patient. Of special concern is the secretion of alpha-fetoprotein (AFP); under some circumstances AFP can be used as a diagnostic marker specific for the presence of yolk sac cells within the teratoma. These cells can develop into a frankly malignant tumor known as yolk sac tumor or endodermal sinus tumor.

Adequate follow-up requires close observation, involving repeated physical examination, scanning (ultrasound, MRI, or CT), and measurement of AFP and/or βhCG.

The presenting features may be a palpable testicular mass or asymmetric testicular enlargement in some cases. The tumour may present as signs and symptoms relating to the presence of widespread metastases, without any palpable lump in the testis. The clinical features associated with metastasising embryonal carcinoma may include low back pain, dyspnoea, cough, haemoptysis, haematemesis and neurologic abnormalities.

Males with embryonal carcinoma tend to have a normal range serum AFP. The finding of elevated AFP is more suggestive of a mixed germ cell tumour, with the AFP being released by a yolk sac tumour component.

Unlike classical seminoma, spermatocytic seminomas rarely metastasise, so radical orchidectomy alone is sufficient treatment, and retroperitoneal lymph node dissection and adjuvant chemotherapy or radiotherapy are generally not required.

Dysgerminomas, like other seminomatous germ cell tumors, are very sensitive to both chemotherapy and radiotherapy. For this reason, with treatment patients' chances of long-term survival, even cure, is excellent.

After removal, the testicle is fixed with Bouin's solution because it better conserves some morphological details such as nuclear conformation. Then the testicular tumor is staged by a pathologist according to the TNM Classification of Malignant Tumors as published in the AJCC Cancer Staging Manual. Testicular cancer is categorized as being in one of three stages (which have subclassifications). The size of the tumor in the testis is irrelevant to staging. In broad terms, testicular cancer is staged as follows:

- Stage I: the cancer remains localized to the testis.

- Stage II: the cancer involves the testis and metastasis to retroperitoneal and/or paraaortic lymph nodes (lymph nodes below the diaphragm).

- Stage III: the cancer involves the testis and metastasis beyond the retroperitoneal and paraaortic lymph nodes. Stage 3 is further subdivided into non-bulky stage 3 and bulky stage 3.

Further information on the detailed staging system is available on the website of the American Cancer Society.

Regardless of location in the body, a teratoma is classified according to a cancer staging system. This indicates whether chemotherapy or radiation therapy may be needed in addition to surgery. Teratomas commonly are classified using the Gonzalez-Crussi grading system: 0 or mature (benign); 1 or immature, probably benign; 2 or immature, possibly malignant (cancerous); and 3 or frankly malignant. If frankly malignant, the tumor is a cancer for which additional cancer staging applies.

Teratomas are also classified by their content: a solid teratoma contains only tissues (perhaps including more complex structures); a cystic teratoma contains only pockets of fluid or semi-fluid such as cerebrospinal fluid, sebum, or fat; a mixed teratoma contains both solid and cystic parts. Cystic teratomas usually are grade 0 and, conversely, grade 0 teratomas usually are cystic.

Grade 0, 1 and 2 pure teratomas have the potential to become malignant (grade 3), and malignant pure teratomas have the potential to metastasize. These rare forms of teratoma with malignant transformation may contain elements of somatic (non germ cell) malignancy such as leukemia, carcinoma or sarcoma.

A teratoma may contain elements of other germ cell tumors, in which case it is not a pure teratoma but rather is a mixed germ cell tumor and is malignant. In infants and young children, these elements usually are endodermal sinus tumor, followed by choriocarcinoma. Finally, a teratoma can be pure and not malignant yet highly aggressive: this is exemplified by growing teratoma syndrome, in which chemotherapy eliminates the malignant elements of a mixed tumor, leaving pure teratoma which paradoxically begins to grow very rapidly.

The main way testicular cancer is diagnosed is via a lump or mass inside a testis. More generally, if a young adult or adolescent has a single enlarged testicle, which may or may not be painful, this should give doctors reason to suspect testicular cancer.

Other conditions may also have symptoms similar to testicular cancer:

- Epididymitis or epididymoorchitis

- Hematocele

- Varicocele

- Orchitis

- Prostate infections or inflammations (prostatitis), bladder infections or inflammations (cystitis), or kidney (renal) infections (nephritis) or inflammations which have spread to and caused swelling in the vessels of the testicles or scrotum

- Testicular torsion or a hernia

- Infection, inflammation, retro-peritonitis, or other conditions of the lymph nodes or vessels near the scrotum, testicles, pubis, anorectal area, and groin

- Benign tumors or lesions of the testicles

- Metastasis to the testicles from another, primary tumor site(s)

The nature of any palpated lump in the scrotum is often evaluated by scrotal ultrasound, which can determine exact location, size, and some characteristics of the lump, such as cystic vs solid, uniform vs heterogeneous, sharply circumscribed or poorly defined. The extent of the disease is evaluated by CT scans, which are used to locate metastases.

The differential diagnosis of testicular cancer requires examining the histology of tissue obtained from an inguinal orchiectomy - that is, surgical excision of the entire testis along with attached structures (epididymis and spermatic cord). A biopsy should not be performed, as it raises the risk of spreading cancer cells into the scrotum.

Inguinal orchiectomy is the preferred method because it lowers the risk of cancer cells escaping. This is because the lymphatic system of the scrotum, through which white blood cells (and, potentially, cancer cells) flow in and out, links to the lower extremities, while that of the testicle links to the back of the abdominal cavity (the retroperitoneum). A transscrotal biopsy or orchiectomy will potentially leave cancer cells in the scrotum and create two routes for cancer cells to spread, while in an inguinal orchiectomy only the retroperitoneal route exists.

Blood tests are also used to identify and measure tumor markers (usually proteins present in the bloodstream) that are specific to testicular cancer. Alpha-fetoprotein, human chorionic gonadotropin (the "pregnancy hormone"), and LDH-1 are the typical tumor markers used to spot testicular germ cell tumors.

A pregnancy test may be used to detect high levels of chorionic gonadotropin; however, the first sign of testicular cancer is usually a painless lump. Note that only about 25% of seminomas have elevated chorionic gonadotropin, so a pregnancy test is not very sensitive for making out testicular cancer.

In the testis pure embryonal carcinoma is also uncommon, and accounts for approximately ten percent of testicular germ cell tumours. However, it is present as a component of almost ninety percent of mixed nonseminomatous germ cell tumours. The average age at diagnosis is 31 years, and typically presents as a testicular lump which may be painful. One fifth to two thirds of patients with tumours composed predominantly of embryonal carcinoma have metastases at diagnosis.

Since gestational choriocarcinoma (which arises from a hydatidiform mole) contains paternal DNA (and thus paternal antigens), it is exquisitely sensitive to chemotherapy. The cure rate, even for metastatic gestational choriocarcinoma, is around 90–95%.

At present, treatment with single-agent methotrexate is recommended for low-risk disease, while intense combination regimens including EMACO (etoposide, methotrexate, actinomycin D, cyclosphosphamide and vincristine (Oncovin) are recommended for intermediate or high-risk disease.

Hysterectomy (surgical removal of the uterus) can also be offered to patients > 40 years of age or those for whom sterilisation is not an obstacle. It may be required for those with severe infection and uncontrolled bleeding.

Choriocarcinoma arising in the testicle is rare, malignant and highly resistant to chemotherapy. The same is true of choriocarcinoma arising in the ovary. Testicular choriocarcinoma has the worst prognosis of all germ-cell cancers.

Testicular microlithiasis is an unusual condition diagnosed on testicular ultrasound. It is found in between 1.5 to 5% of normal males, and may be found in up to 20% of individuals with subfertility. It is an asymptomatic, non-progressive disease. The cause is unknown, but this condition has been associated with testicular cancer in a small group of individuals, cryptorchidism, mumps, infertility and intraepithelial germ cell neoplasia. Classic testicular microlithiasis is defined as five or more echogenic foci per view in either or both testes, and limited testicular microlithiasis defined as one or more echogenic foci that do not satisfy the criteria for classic testicular microlithiasis. In 80% of cases, both testicles are affected.

Testicular microlithiasis is not associated with risk of testicular cancer in asymptomatic individuals with no risk factors for testicular germ cell tumor. However, a large meta-analysis has shown that in individuals with associated risk factors for testicular germ cell tumor, the increase in risk of concurrent diagnosis of testicular germ cell tumor, or testicular carcinoma-in-situ upon biopsy is approximately eight to ten-fold.

There is extensive controversy over whether testicular microlithiasis in individuals with testicular germ cell tumor, or risk factors for such, should undergo testicular biopsy to exclude the presence of testicular carcinoma-in-situ, also known as intratubular germ cell neoplasia of unclassified type. Additionally, whether the presence of testicular microlithiasis should influence decision for adjuvant chemotherapy or surveillance in individuals with testicular germ cell tumor remains unclear. A recent review in Nature Reviews Urology has comprehensively evaluated these topics.

There is no cure or treatment for testicular microlithiasis, however, patients may be monitored via ultrasound to make sure that other conditions do not develop. Emphasis on testicular examination is the recommended follow up for asymptomatic men incidentally identified with testicular microlithiasis. For men with risk factors for testicular germ cell tumor such as subfertility however, individualized discussion with their urologists is necessary.

Germinomas, like several other types of germ cell tumor, are sensitive to both chemotherapy and radiotherapy. For this reason, treatment with these methods can offer excellent chances of longterm survival, even cure.

Although chemotherapy can shrink germinomas, it is not generally recommended alone unless there are contraindications to radiation. In a study in the early 1990s, carboplatinum, etoposide and bleomycin were given to 45 germinoma patients, and about half the patients relapsed. Most of these relapsed patients were then recovered with radiation or additional chemotherapy.

A dysgerminoma is a type of germ cell tumor; it usually is malignant and usually occurs in the ovary.

A tumor of the identical histology but not occurring in the ovary may be described by an alternate name: seminoma in the testis or germinoma in the central nervous system or other parts of the body.

Dysgerminoma accounts for less than 1% of ovarian tumors overall. Dysgerminoma usually occurs in adolescence and early adult life; about 5% occur in pre-pubertal children. Dysgerminoma is extremely rare after age 50. Dysgerminoma occurs in both ovaries in 10% of patients and, in a further 10%, there is microscopic tumor in the other ovary.

Abnormal gonads (due to gonadal dysgenesis and androgen insensitivity syndrome) have a high risk of developing a dysgerminoma. Most dysgerminomas are associated with elevated serum lactic dehydrogenase (LDH), which is sometimes used as a tumor marker.

Intracranial germinoma occurs in 0.7 per million children. As with other germ cell tumors (GCTs) occurring outside the gonads, the most common location of intracranial germinoma is on or near the midline, often in the pineal or suprasellar areas; in 5-10% of patients with germinoma in either area, the tumor is in both areas. Like other (GCTs), germinomas can occur in other parts of the brain. Within the brain, this tumor is most common in the hypothalamic or hypophyseal regions. In the thalamus and basal ganglia, germinoma is the most common GCT.

The diagnosis of an intracranial germinoma usually is based on biopsy, as the features on neuroimaging appear similar to other tumors.

Cytology of the CSF often is studied to detect metastasis into the spine. This is important for staging and radiotherapy planning.

Intracranial germinomas have a reported 90% survival to five years after diagnosis. Near total resection does not seem to influence the cure rate, so gross total resection is not necessary and can increase the risk of complications from surgery. The best results have been reported from craniospinal radiation with local tumor boost of greater than 4,000 cGy.

Testicular biopsy would confirm the absence of spermatozoa. Seminal plasma protein TEX101 was proposed for differentiation of Sertoli cell-only syndrome from maturation arrest and hypospermatogenesis. And a clinical trial at Mount Sinai Hospital, Canada started testing this hypothesis in 2016.