Scrotal mass differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]

Differential Diagnosis

The table below summarizes the findings that differentiates scrotal mass according to the clinical features, laboratory findings, imaging features, histological features, and genetic studies.

Disease Name	History and Symptoms	Physical Examination	Lab Findings	Imaging Findings	Gross and Histologic Findings	Genetic Studies / Immunohistochemistry
Germ Cell Tumors
Seminoma	Most common 30-50 year-old with painless unilateral testicular mass or mild discomfort	Palpable, nontender unilateral testicular mass Usually homogeneous enlargement	Elevated serum placental ALP (PALP)	Hypoechogenic intratesticular well-defined mass on ultrasound with internal blood flow on Doppler ultrasound Cysts and calcificications are uncommon Hypointense lesion with inhomogeneous enhancement on MRI Homogeneous when small and heterogeneous when large	Grey-white homogeneous mass with a lobular appearance Fried egg appearance on histopathology (large cells and clear cytoplasm) Prominent lymphocytic infiltration and less commonly, granulomatous formation	Stains positively for ALP, c-KIT, CD30, EMA, and glycogen
Embryonal cell carcinoma	Young adults Painful testicular mass Manifests with early mestastasis (bone, lung, CNS)	Often unremarkable (small primary tumor)	Elevated serum hCG Elevated serum AFP, when mixed	Variable echogenicity (usually hypoechoic on ultrasound) No differentiating features on imaging Commonly invade the surrounding structures (tunica albuginea) Irregular calcifications	Pale-grey mass with areas of hemorrhagic and necrosis Often mixed histopathological features (solid, papillary, tubular, pseudoglandular)	Stains positively for CD30 and hCG stain May stain positively for AFP, when mixed
Yolk sac tumor	Most common testicular cancer in children less than 3 years of age Rapidly growing unilateral mass in an infant or a young child	Palpable, nontender unilateral testicular mass Usually heterogeneous enlargement	Elevated serum AFP	Diffuse enlargement of the testis with a heterogeneous appearance on ultrasound Areas of hemorrhage and necrosis on MRI	Yellow, mucinous, non-encapsulated, heterogeneous mass with areas of necrosis and hemorrhage Patterns that resemble embryonal structures (yolk sac, allantois) with reticular, papillary, or elongated forms Schiller-Duval bodies (perivascular structures)	Stains positively for AFP, alpha-1-antitrypsin, PAS diastase
Teratoma	Bimodal distribution of age (infants and middle aged adults) Painless tumor History of congenital disease (Down syndrome, klinefelter, spina bifida)	Palpable, nontender unilateral testicular mass Usually heterogeneous enlargement	Elevated serum hCG Elevated serum AFP	Heterogeneous, cystic appearance with mucinous or sebaceous depositions Variable echogenicity on ultrasound Calcifications usually irregular	Large, heterogeneous appearance with solid, cystic, mucoid, and/or cartilageanous components Presence of at least 2 germ layers	Chromosome 12p mutations Stains positively for cytokeratin. hCG, and AFP
Teratocarcinoma	Middle aged adult with painless testicular mass of mild discomfort May manifest with features of metastasis	Palpable, nontender unilateral testicular mass Usually heterogeneous enlargement	Elevated serum hCG Elevated serum AFP	Variable echogenicity on ultrasound	Features of both teratoma and embryonal carcinoma (more common) or both teratoma and choriocarcinoma (less common) Solid and cystic components with mucoid, cartilagenous, sebaceous gland, myxoid stroma components Additional features of underlying embryonal carcinoma or choriocarcinoma	Stains positively for cytokeratin. hCG, AFP, and CD30
Choriocarcinoma	Adolescent or young adult with extratesticular symptoms Mass is small and locally asymptomatic Manifests with early metastasis and signs of hemorrhage (hemorrhagic stroke, hyperthyroidism, cannon-ball metastasis in lung, liver involvement, neurological deficits)	Often unremarkable (small primary tumor)	Elevated serum hCG	Variable echogenicity No differentiating features on imaging Commonly invade the surrounding structures (tunica albuginea)	Prominent areas of hemorrhage and necrosis Nest and sheet pattern that simultaneously includes both cytotrophoblast and syncytiotrophoblast (rarely pure) Paucity of intermediate trophoblasts (unlike placental site trophoblastic tumor)	Stains positively for hCG
Diffuse embryoma	20-25 yo man with painful testicular mass	Tender testicular mass	Elevated serum hCG Elevated serum AFP	Poorly-defined, heterogeneous hyperechoic mass on ultrasound	Non-encapsulated mass Intermingled (lace-like) embryonal carcinoma and yolk sac components in equal proportions, but no discrete embyoid bodies Scattered trophoblastic components Necklace-like arrangement of cells	Stains positively for cytokeratin, AFP (yolk sac component), and CD30 (embyonal component)
Polyembryoma	20-25 yo man with painful testicular mass	Tender testicular mass	Elevated serum AFP Elevated serum hCG	Poorly-defined, heterogeneous hyperechoic mass on ultrasound	Multiple discrete embyoid bodies (combination of both embryonal carcinoma and yolk sac components)	Stains positively for cytokeratin, AFP (yolk sac component), and CD30 (embyonal component)
Placental site trophoblastic tumor	Infant or young adult Painful small testicular mass	Small nontender or minimally painful testicular mass	Elevated serum hCG	Variable echogenicity No differentiating features on imaging May have vascular flow	Solid yellowish mass that resembles uterine tissue Less prominent foci of hemorrhage and ncerosis Predominance of intermediate trophoblast cells (implantation-site type) that invade surrounding blood vessels Paucity of cytotrophoblast and syncytiotrophoblast cells (unlike choriocarcinoma)	Stains positively for hPL (diffuse), p63, cytokeratin, AFP, and hCG (patchy) Negative p63 staining
Epithelioid trophoblastic tumor
B
C
D