A retrospective study of 83 women with sex cord–stromal tumours (73 with granulosa cell tumour and 10 with Sertoli-Leydig cell tumour), all diagnosed between 1975 and 2003, reported that survival was higher with age under 50, smaller tumour size, and absence of residual disease. The study found no effect of chemotherapy. A retrospective study of 67 children and adolescents reported some benefit of cisplatin-based chemotherapy.

A prospective study of ovarian sex cord–stromal tumours in children and adolescents began enrolling participants in 2005.

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

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.

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.

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.

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).

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.

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.

A pelvic examination may detect an adnexal mass. A CA-125 blood test is a nonspecific test that tends to be elevated in patients with tubal cancer. More specific tests are a gynecologic ultrasound examination, a CT scan, or an MRI of the pelvis.

Occasionally, an early fallopian tube cancer may be detected serendipitously during pelvic surgery.

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.

Prognosis depends to a large degree on the stage of the condition. In 1991 it was reported that about half of the patients with advanced stage disease survived 5 years with a surgical approach followed by cisplatinum-based chemotherapy.

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.

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.

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.

Regardless of location, all rhabdoid tumours are highly aggressive, have a poor prognosis, and tend to occur in children less than two years of age.

Diagnosis of EIN lesions is of clinical importance because of the increased risk of coexisting (39% of women with EIN will be diagnosed with carcinoma within one year) or future (the long term endometrial cancer risk is 45 times greater for a woman with EIN compared to one with only a benign endometrial histology) endometrial cancer. Diagnostic terminology is that used by pathologists, physicians who diagnose human disease by examination of histologic preparations of excised tissues. Critical distinctions in EIN diagnosis are separation from benign conditions such as benign endometrial hyperplasia (a field effect in endometrial tissue caused by excessive stimulation by the hormone estrogen), and cancer.

The spectrum of disease which must be distinguished from EIN (Table II) includes benign endometrial hyperplasia and carcinoma:

Table II: Disease classes that need to be distinguished from EIN.

EIN may be diagnosed by a trained pathologist by examination of tissue sections of the endometrium. All of the following diagnostic criteria must be met in a single area of one tissue fragment to make the diagnosis (Table III).

Table III: EIN diagnosis.

It is important to exclude a tumor which is directly extending into the ear canal from the parotid salivary gland, especially when dealing with an adenoid cystic or mucoepidermoid carcinoma. This can be eliminated by clinical or imaging studies. Otherwise, the histologic differential diagnosis includes a ceruminous adenoma (a benign ceruminous gland tumor) or a neuroendocrine adenoma of the middle ear (middle ear adenoma).

PUNLMPs are exophytic lesions that appear friable to the naked eye and when imaged during cystoscopy.

They are definitively diagnosed after removal by microscopic examination by pathologists.

Histologically, they have a papillary architecture with slender fibrovascular cores and rare basal mitoses. The papillae rarely fuse and uncommonly branch. Cytologically, they have uniform nuclear enlargement.

They cannot be reliably differentiated from low grade papillary urothelial carcinomas using cytology, and their diagnosis (vis-a-vis low grade papillary urothelial carcinoma) has a poor inter-rater reliability.

Pathologic grading and staging tumors are:

graded by the degree of cellular atypia (G1->G3), and

staged:

Inhibin, a hormone, has been used as tumor marker for granulosa cell tumor.

PUNLMPs are treated like non-invasive low grade papillary urothelial carcinomas, excision and regular follow-up cystoscopies.

There is a rare occurrence of a pelvic recurrence of a low-grade superficial TCC after cystectomy. Delayed presentation with recurrent low-grade urothelial carcinoma is an unusual entity and potential mechanism of traumatic implantation should be considered. Characteristically low-grade tumors are resistant to systemic chemotherapy and curative-intent surgical resection of the tumor should be considered.

The histology of EST is variable, but usually includes malignant endodermal cells. These cells secrete alpha-fetoprotein (AFP), which can be detected in tumor tissue, serum, cerebrospinal fluid, urine and, in the rare case of fetal EST, in amniotic fluid. When there is incongruence between biopsy and AFP test results for EST, the result indicating presence of EST dictates treatment. This is because EST often occurs as small "malignant foci" within a larger tumor, usually teratoma, and biopsy is a sampling method; biopsy of the tumor may reveal only teratoma, whereas elevated AFP reveals that EST is also present. GATA-4, a transcription factor, also may be useful in the diagnosis of EST.

Diagnosis of EST in pregnant women and in infants is complicated by the extremely high levels of AFP in those two groups. Tumor surveillance by monitoring AFP requires accurate correction for gestational age in pregnant women, and age in infants. In pregnant women, this can be achieved simply by testing maternal serum AFP rather than tumor marker AFP. In infants, the tumor marker test is used, but must be interpreted using a reference table or graph of normal AFP in infants.

Serous cystic neoplasms can come to clinical attention in a variety of ways. The most common symptoms are very non-specific and include abdominal pain, nausea and vomiting. In contrast to many of the other tumors of the pancreas, patients rarely develop jaundice (a yellowing of the skin and eyes caused by obstruction of the bile duct), or weight loss. These signs and symptoms are not specific for a serous cystic neoplasm, making it more difficult to establish a diagnosis. Doctors will therefore often order additional tests.

Once a doctor has reason to believe that a patient may have serous cystic neoplasm, he or she can confirm that suspicion using one of a number of imaging techniques. These include computerized tomography (CT), endoscopic ultrasound (EUS), and magnetic resonance cholangiopancreatography (MRCP). These tests will reveal a cystic mass within the pancreas. The cysts do not communicate with the larger pancreatic ducts. In some cases a fine needle aspiration (FNA) biopsy can be obtained to confirm the diagnosis. Fine needle aspiration biopsy can be performed through an endoscope at the time of endoscopic ultrasound, or it can be performed through the skin using a needle guided by ultrasound or CT scanning.

A growing number of patients are now being diagnosed before they develop symptoms (asymptomatic patients). In these cases, the lesion in the pancreas is discovered accidentally (by chance) when the patient is being scanned (x-rayed) for another reason.

The diagnosis of salivary gland tumors utilize both tissue sampling and radiographic studies. Tissue sampling procedures include fine needle aspiration (FNA) and core needle biopsy (bigger needle comparing to FNA). Both of these procedures can be done in an outpatient setting. Diagnostic imaging techniques for salivary gland tumors include ultrasound, computer tomography (CT) and magnetic resonance imaging (MRI).

Fine needle aspiration biopsy (FNA), operated in experienced hands, can determine whether the tumor is malignant in nature with sensitivity around 90%. FNA can also distinguish primary salivary tumor from metastatic disease.

Core needle biopsy can also be done in outpatient setting. It is more invasive but is more accurate compared to FNA with diagnostic accuracy greater than 97%. Furthermore, core needle biopsy allows more accurate histological typing of the tumor.

In terms of imaging studies, ultrasound can determine and characterize superficial parotid tumors. Certain types of salivary gland tumors have certain sonographic characteristics on ultrasound. Ultrasound is also frequently used to guide FNA or core needle biopsy.

CT allows direct, bilateral visualization of the salivary gland tumor and provides information about overall dimension and tissue invasion. CT is excellent for demonstrating bony invasion. MRI provides superior soft tissue delineation such as perineural invasion when compared to CT only.