Approach

Early diagnosis is associated with better long-term prognosis; diagnostic delay may result in progression and the need for more intensive treatment.[2]​ Any intratesticular mass should be considered a testicular cancer until demonstrated otherwise. Age of the patient, family history of testicular cancer, previous diagnosis of testicular cancer, and, most important, history of undescended testis should alert the physician to a possible diagnosis. In addition, awareness of the differential diagnostic possibilities based on routine light microscopic features and further directed observations or serologic studies may help to achieve an accurate diagnosis.[40]

Clinical evaluation

The typical patient is between 20 to 34 years of age.[13] He may report nonspecific testicular discomfort and the feeling of a mass in the testis. Symptom onset is usually more than 2 weeks but patients may present with painful swelling of sudden onset (due to associated hemorrhage or infection) in 10% of cases.[41]

Examination of the testis is essential for detecting this condition early. Genital exam is a relatively quick and simple clinical assessment, and should be carried out when a male patient presents with genital symptoms.[42] The exam should first be performed with the patient standing to assess asymmetry of a low-riding testis. The location of the mass can be palpated by gently rolling the testicle between thumb and fingers. The mass should be firmly attached to the testis (intratesticular) on the side or the lower pole of the testis. Special attention should be given to the shape and consistency of the mass. The mass is usually smooth, firm, and nonfluctuating. However, on occasions it presents as an uneven distortion of the contour of the testis or as homogeneous enlargement. Palpation of the spermatic cord for thickness and mobility, and presence of inguinal swelling should be noted. If there is any doubt, an ultrasound of the testis is mandatory. A urologist should evaluate every testicular mass.

A full systemic exam should be performed, as around 5% to 10% of patients have extratesticular manifestations at the time of presentation with or without apparent primary tumor in the testes.[43]

Investigations

Ultrasound of the testis is the preferred initial imaging modality and has high sensitivity for testicular malignancy.[2][44]​​​​​​​​​[45][Figure caption and citation for the preceding image starts]: Ultrasonographic picture of testicular mass as hypoechoic lesionBMJ Case Reports 2011; doi:10.1136/bcr.12.2010.3565 [Citation ends].com.bmj.content.model.Caption@24484fa​​​​ ​​​​​​However, a negative ultrasound does not exclude the presence of cancer and should be repeated in 6 to 8 weeks in patients with indeterminate findings on ultrasound or physical exam and normal serum tumor markers.[2] Ultrasound should be carried out with color Doppler assessment to confirm the presence of a testicular mass before orchiectomy.[46] Use of color Doppler can help to distinguish tumors from other scrotal swellings (e.g., varicocele).[47] The contralateral testis should also be evaluated for the presence of synchronous tumors and microcalcifications, and to measure the testicular volume.[46]​ Biopsy of the contralateral testis may be indicated if a suspicious mass is identified, the testis is atrophied, or there is a history of cryptorchidism. It is not recommended for testicular microcalcifications alone.[45][48]​​[49]​ Clusters of microcalcifications may be associated with increased risk of testicular cancer in the presence of other risk factors, although the clinical significance of this remains controversial.[50]

Computed tomography (CT) scan of the pelvis and abdomen with contrast is used to assess the stage of cancer spread.[2][48][51]​​​​​​​ Magnetic resonance imaging (MRI) may be useful as an alternative modality, if CT is inconclusive or the contrast media is contraindicated due to patient allergy or renal insufficiency.[2] Chest imaging is mandatory to assess for the presence of lung metastases.[2][51]​​​​​ Chest x-ray is advised as first-line chest imaging for clinical stage I seminoma only. CT chest is recommended as first-line for other tumor types, or those with rising postorchiectomy serum tumor markers, or with evidence of metastases on abdominal/pelvic imaging, chest x-ray or physical exam.[2] CT-positron emission tomography (PET) scanning has not been shown to be superior to CT alone and is not recommended for staging.[2]

Serum tumor markers should be obtained before and after orchiectomy, with staging based on postorchiectomy nadir values.[2][48]​ The combination of elevated beta-human chorionic gonadotropin (beta-hCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH) is diagnostic of the disease. AFP can be elevated by embryonal carcinoma, teratoma, yolk sac tumors, or mixed tumors. Pure choriocarcinomas and seminomas are not associated with elevated AFP levels. If histology shows pure seminoma but serum AFP is elevated without other identifiable cause, the tumor should be reclassified and treated as nonseminomatous. Seminomas may present with modest elevations of beta-hCG due to the presence of syncytiotrophoblasts in the tumor. LDH is raised in 40% to 60% of all patients with seminoma or nonseminomatous germ cell tumors.[52] In 10% of persistent or recurrent nonseminomas, LDH is the sole elevated marker.[53]​ However, it has a high false-positive rate and should be used mainly to assess tumor burden. Approximately 80% of nonseminomatous tumors have elevated serum markers. Both AFP and beta-hCG are increased in 44% of cases, AFP alone is elevated in 26% of cases, and beta-hCG alone is elevated in 9% of cases.[52]

Placental alkaline phosphatase is elevated in up to 40% of cases with advanced disease.[52]​​​ However, placental alkaline phosphatase is not used in routine clinical practice and should be limited to experimental or clinical trial settings. Serum microRNA-371a-3p (M371) has emerged as a potential biomarker for both seminomatous and nonseminomatous germ cell tumors, with improved sensitivity and specificity compared to conventional tumor markers.[54] Further prospective studies are needed to guide implementation of M371 into routine clinical practice.[55]

The diagnosis of testicular cancer is generally established by removing and examining the involved testicle (orchiectomy) after obtaining serum tumor markers.

[Figure caption and citation for the preceding image starts]: Metastatic seminoma. Left image: H&E stain low power. Right image placental alkaline phosphatase (PLAP) stain high power. The H&E image shows nests of malignant cells with clear cytoplasm; the tumour cells are strongly positive for PLAP confirming the diagnosisLaw C et al. BMJ Case Rep. 2020 Apr 22;13(4):e233368. doi: 10.1136/bcr-2019-233368; used with permission [Citation ends].com.bmj.content.model.Caption@590e745d​​​​[Figure caption and citation for the preceding image starts]: NonseminomaFrom the collection of Dr Francisco G. La Rosa; used with permission [Citation ends].com.bmj.content.model.Caption@b54784a​​ At all stages of disease, orchiectomy is essential.[2] Radical inguinal orchiectomy should be performed early in the evaluation of a suspicious testicular mass. In early-stage disease, an orchiectomy is often curative.

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