Testicular cancer differential diagnosis

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

Overview

Testicular cancer must be differentiated from epididymitis, hematocele, hydrocele, spermatocele, granulomatous orchitis, and varicocele.

Differentiating Testicular cancer from other Diseases

Testicular cancer must be differentiated from:

Diseases		Benign/ Malignant	Unilateral/Bilateral	History	Demography	Metastasis	Genetics	Histopathology	Clinical manifestations			Para-clinical findings
									Pain	Mass	Physical examination
												Lab findings	Imaging
Germ Cell tumors	Seminoma	Malignant	Unilateral	History of cryptorchidism Excellent prognosis	Most common among age of 15-35 years old Does not occur during infancy	Late metastasis	Stains positively for: ALP C-KIT CD30 EMA Glycogen	Large cells wit watery cytoplasm Fried egg appearance	-	+	Palpable, nontender unilateral testicular mass Usually homogeneous enlargement	Elevated serum placental ALP (PALP)	Ultrasound: Homogeneous hypoechoic intratesticular mass Cysts and calcificications are uncommon Inhomogenous feature in larger mass
	Embryonal carcinoma	Malignant	Usually located in parenchyma of testis May be nonpalpable	Hemorrhagic mass with necrosis Worse prognosis than seminoma	Rare type Peak incidence at the age of 30 years old Usually mixed with other types	Early metastasis to: retroperitoneum Lung Liver	Stains positively for: CD30 HCG May stain positively for : AFP, when mixed with other tumors	Primitive epithelial cells with marked pleomorphism Often mixed histopathological features (solid, papillary, tubular, pseudoglandular)	+	±	Unremarkable May present with abdominal/ pelvic mass Abdominal pain may be present Metastatic findings	Elevated serum hCG Elevated serum AFP, when mixed with other tumor types	Ultrasound: Usually hypoechoic mass Invasion to tunica albuginea Irregular calcifications
	Yolk sac tumor	Malignant	Unilateral	Known as a endodermal sinus tumor History of undescended testes in youth	Most common prepubertal testicular cancer in children < 3 years of age Common among Asian	Uncommon	Stains positively for: AFP Alpha-1-antitrypsin PAS diastase	Yellow, mucinous, encapsulated mass Schiller-Duval bodies (perivascular structures) Hyaline-type globules	+	+	Palpable mass Nontender mass Unilateral mass	Elevated serum AFP	Ultrasound: Diffuse enlargement of the testis with a heterogeneous appearance MRI: Areas of hemorrhage and necrosis
	Teratoma	Benign Malignant	Unilateral	History of congenital disease such as: Klinefelter's syndrome Down syndrome Spina bifida	May present in both prepubertal and adult men Benign form in children under 4 years old	Uncommon in benign ones among prepubertal men Common in malignant ones among postpubertal ones Metastasis may be teratomatous	Chromosome 12p mutations Stains positively for: Cytokeratin HCG AFP	Large, heterogeneous appearance Presence of at least 2 germ layers	-	+	Palpable mass Nontender mass Unilateral mass	Elevated serum hCG Elevated serum AFP	Ultrasound: Heterogeneous, cystic appearance Irregular calcifications
	Choriocarcinoma	Malignant	Testicular mass may be small/ asymptomatic	History of cryptorchidism Abdominal undescended testis	Most aggressive type	Early metastasis: Liver Brain Lung	Stains positively for: hCG Genetic changes of 12p11.2-p12.1 chromosomal region	Characterized by hemorrhagic and necrotic areas Disordered syncytiotrophoblastic and cytotrophoblastic elements	+	±	Nonpalpable or small mass Painless or radiating pain to groin/ abdomen Metastatic findings Gynecomastia Hyperthyroidism symptoms	Elevated serum hCG	Ultrasound: Hemorrhage and necrosis May appear more cystic inhomogeneous, and calcified
	Mixed germ cell tumors	Malignant	Unilateral	Two or more germ cell tumors present as a single mass Depends on underlying components	Average age about 30 years old Rare in prepubertal age Include one-third of all testicular gem cell tumors	Metastasis depends on tumors types Metastasis to lung, liver, brain, skin	May stain positive based on underlying components	Variable components depends on tumor Accompanied with necrosis and hemorrhages	±	+	Physical exam findings based on underlying components	Elevations in: AFP Beta-hCG	Imaging findings based on underlying components
	Carcinoma in situ (intratubular germ cell neoplasia )	Malignant	Unilateral Bilateral	Cryptorchid testes Previous testicular cancer Abnormal sexual differentiation	A precursor of most testicular germ cell tumors Adjacent to a other testicular germ cell tumors > 90% of all	Common: Lymph nodes Any other organs	Stain positively for: PALP Genetic changes in chromosome 12	Proliferation of neoplastic germ cells in seminiferous tubules	-	-	N/A	Elevated for: PALP	N/A
Diseases		Benign/ Malignant	Unilateral/Bilateral	History	Demography	Metastasis	Genetics	Histopathology	Pain	Mass	Physical exam	Lab Findings	Imaging
Non- germ cell tumors	Leydig cell tumor	Malignant in up to 20% of adult cases Benign among children	Unilateral	Slowly enlarging painless unilateral mass Based on large size, vascular invasion, and mitotic activity classify into benign / malignant	Bimodal age distribution in both adults and children Considered as stromal tumors	Uncommon metastasis	Mutation in fumarate hydratase Stains positively for: inhibin-A Calretinin WT-1 SALL-4	Golden brown color May have cystic, hemorrhagic, or necrotic areas Eosinophilic crystals of Reinke	-	+	Palpable mass Unilateral mass Nontender Gynecomastia	N/A	Ultrasound: Well-defined, hypoechoic solid mass Cystic component Irregular calcifications
	Sertoli cell tumor	Usually Benign	Unilateral Bilateral	Classified as large cell calcifying or sclerosing types Androblastoma from sex cord stroma History of peutz-Jeghers syndrome and Carney complex Gradually enlarging testicular mass	Occur in any ages (infancy to elderly) Average age of 45 years Mean age for large cell calcifying variant is 21 years old 0.1% of testicular tumors Considered as stromal tumors	Uncommon metastasis	Stain positively for: Inhibin Cytokeratin	Solid or hollow tubules divided by basement membrane Pale eosinophilic cytoplasm	-	+	Palpable and painless mass Hyperestrinism is noted in syndromic cases Gynecomastia	N/A	Ultrasound: Large cell calcifying variant Hypoechoic
	Testicular lymphoma	Malignant	Unilateral Bilateral ( mostly up to 35% of cases)	Aggressive extranodal non-Hodgkin lymphoma Large cell diffuse B-cell lymphoma is responsible for most cases	The most common in men older than 50 years old	Common metastasis to : Skin Subcutaneous tissue Bone marrow Central nervous system Lung	Stains positively for: CD45 Depends on lymphoma subtype	Pleomorphic malignant cells Large irregular nuclei Vascular invasion Seminiferous tubules	-	+	Palpable mass Nontender mass	Depends on lymphoma subtype	Ultrasound: Diffuse testicular infiltration and enlargement Hypervascularity Hypoechoic and solid lesion
	Granulosa cell tumors	Malignant	Unilateral	Juvenile type associated with: Sex chromosome abnormalities Ambiguous genitalia Cryptorchidism	Similar to ovarian counterparts Occur in both adult and juvenile Juvenile type in children less than 2 years old ( the most common infancy tumor) Adult type with average age of 44 years old ( rare)	Metastasis occur in 10%-20% of cases	Stains positively for: Calretinin Inhibin Vimentin, Actin MIC2	Common features are microfollicular and diffuse Call-Exner bodies in adult type ( eosinophillic material) In juvenile type: Solid sheets or nodules and form ectatic spaces	-	+	Palpable mass Nontender mass	Elevated serum: Inhibin Müllerian inhibiting hormone	Ultrasound: Hypoechoic mass Solid and cystic appearance

References

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