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]

Overview

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), cytokeratin, AFP, and hCG (patchy)
  • Negative p63 staining

Epithelioid 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 p63 (diffuse), p63, cytokeratin, AFP, and hCG (patchy)
  • Negative hPL staining

Mixed germ cell tumor

  • Typical age at diagnosis and other clinical features based on underlying components
  • Physical exam findings based on underlying components
  • Elevated serum hCG, AFP, and/or PALP dependeing on the underlying compoenents
  • Imaging findings based on underlying components
  • Histopathological findings based on underlying components
  • Variable proportion of choriocarcinoma, embryonal cell carcinoma, yolk sac tumor, seminoma, and/or teratoma tissue
  • May stain positively for any of CD30, hCG, AFP, ALP, c-KIT, CD30, EMA, alpha-1-antitrypsin, PAS diastase, and glycogen depending on underlying compoenents

Carcinoid
(pure neuroendocrine neoplasm)

  • Middle-aged and elderly adult
  • Manifests as a minimally painful, rapidly growing mass
  • May manifest as carcinoid syndrome
  • Tender testicular mass
  • Hydrocele or cryptorchidism
  • Elevated serum and urine 5-HIAA if carcinoid syndrome present
  • Unilateral, well-circumscribed mass without vascular invasion
  • Solid and cystic appearance
  • Mixed echogenicity on ultrasound
  • Irregular calcifications
  • Well-circumscribed, yellowish solid mass
  • Occasional cystic masses
  • Small acini, cord-forming rosettes, prominent cytoplasmic granularity
  • Salt and pepper chromatic pattern
  • Absent features of atypia
  • Neurosecretory granules on electron microscopy
  • Stains positively for cytokeratin, serotonin, chromogranin, synaptophysin, and CD56

PNET
(Ewing's tumor of the testes)

  • 30-50 yo man with rapidly enlarging mass
  • Often metastatic at presentation
  • Palpable, nontender unilateral testicular mass
  • Unremarkable
  • No differentiating features on imaging
  • Vascular flow on Doppler
  • Greyish necrotic mass of immature neural tissue
  • Sheet-like / rosette distribution of small round blue tumor cells
  • Neurosecretory granules on electron microscopy
  • Stains positively for synaptophysin, NSE, chromogranin, CD99, GFAP, FLI1
  • Split of EWS gene on chromosome 22
Sex-cord/stromal tumors
Fibroma
  • Middle-aged adult (range 20-70 years) with slowly-growing, painless testicular mass
  • History of nevoid basal cell carcinoma (Gorlin syndrome)
  • Palpable, nontender unilateral testicular mass
  • Unremarkable
  • Isoechoic mass on ultrasound with prominent acoustic shadowing (fibrous component)
  • May be homogeneous or heterogeneous
  • Margins often blended with the tunica albuginea
  • No vascular flow on Dopper
  • Well-circumscribed, often non-encapsulated solid pale yellow mass
  • No hemorrhage, no necrosis
  • Pure fibromatous features of collagenized plaques and spindle cells that synthesize collagen.
  • Low cellularity
  • Mutation in PTCH gene
  • Positive staining for calretinin, inhibin, CD56, CD34, actin, vimectin
  • Usually (but not always) negative staining for S-100, keratin, CD99/MIC-2, and desmin
Other tumors

AIDS-related testicular cancer

  • Commonly testicular lymphoma or germ cell tumor
  • Patient with history of AIDS presents with testicular swelling or pain
  • Systemic manifestations of underlying malignancy
  • Palpable testicular mass that may be tender or non-tender
  • Depends on underlying malignancy
  • Depends on underlying malignancy
  • Depends on underlying malignancy
  • Depends on underlying malignancy
Non-neoplastic mass

Brucellosis

  • Patient with history of exposure to cattle/sheep/goat/swine or animal products (milk, meat, cheese) presents with acute scrotal pain and swelling
  • Undulant fever and night sweats (characteristic wet hay odor)
  • Relapses common with similar symptoms
  • Tender testicular mass
  • Fever
  • Hydrocele
  • Elevated WBC count
  • Positive serum STA test for brucellosis
  • Elevated Brucella IgM and IgG antibodies
  • Urine PCR positive for Brucella
  • Focal/diffuse hypoechogenicity on ultrasound
  • Focal/diffusre increased blood flow on Doppler
  • Scrotal wall thickening
  • Granulomatous inflammation with lymphocytic infiltration
  • Urethral Gram stain demonstrates Gram-negative diplococci
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References

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