Testicular cancer differential diagnosis

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

Abbreviations:

AFP: Alpha-fetoprotein, B-hCG: Beta-human chorionic gonadotropin, P-ALP: Placental- Alkaline phosphatase

Diseases	Benign/ Malignant	Unilateral/Bilateral	History/demography	Metastasis	Genetics	Clinical manifestations			Para-clinical findings
						Symptoms		Physical examination	Lab findings			Imaging	Histopathology
						Pain	Mass		AFP	Beta hCG	p-ALP
Germ Cell tumors
Seminoma	Malignant	Unilateral	Cryptorchidism Most common among age of 15-35 years old	Late metastasis	Stains positively for: ALP C-KIT CD30 EMA Glycogen	-	+	Palpable, nontender unilateral testicular mass Usually homogeneous enlargement	N/A	N/A	↑	Ultrasound Homogeneous hypoechoic intratesticular mass Cysts and calcification are uncommon Inhomogenous feature in larger mass	Large cells wit watery cytoplasm Fried egg appearance
Embryonal carcinoma	Malignant	Usually located in parenchyma of testis May be nonpalpable	Hemorrhagic mass with necrosis Rare type Peak incidence at the age of 30 years old	Early metastasis to: Retroperitoneum Lung Liver	Stains positively for: CD30 HCG May stain positively for : AFP, when mixed with other tumors	+	±	Unremarkable May present with abdominal/ pelvic mass Abdominal pain may be present Metastatic findings	↑*	↑	N/A	Ultrasound Usually hypoechoic mass Invasion to tunica albuginea Irregular calcification	Primitive epithelial cells with marked pleomorphism Often mixed histopathological features (solid, papillary, tubular, pseudoglandular)
Yolk sac tumor	Malignant	Unilateral	Known as a endodermal sinus tumor Undescended testes in youth Most common prepubertal testicular cancer in children < 3 years of age	Uncommon	Stains positively for: AFP Alpha-1-antitrypsin PAS diastase	+	+	Palpable mass Nontender mass Unilateral mass	↑	N/A	N/A	Ultrasound Diffuse enlargement of the testis with a heterogeneous appearance MRI Areas of hemorrhage and necrosis	Yellow, mucinous, encapsulated mass Schiller-Duval bodies (perivascular structures) Hyaline-type globules
Teratoma	Benign Malignant	Unilateral	May present in both prepubertal and adult men Benign form in children under 4 years oldCongenital disease such as: Klinefelter's syndrome Down syndrome Spina bifida	Uncommon in benign ones among prepubertal men Common in malignant ones among postpubertal ones Metastasis may be teratomatous	Chromosome 12 mutations Stains positively for: Cytokeratin HCG AFP	-	+	Palpable mass Nontender mass Unilateral mass	↑	↑	N/A	Ultrasound Heterogeneous, cystic appearance Irregular calcification	Large, heterogeneous appearance Presence of at least 2 germ layers
Choriocarcinoma	Malignant	Testicular mass may be small/ asymptomatic	Cryptorchidism Abdominal undescended testes Most aggressive type	Early metastasis: Liver Brain Lung	Stains positively for: HCG Genetic changes of 12p11.2-p12.1 chromosomal region	+	±	Nonpalpable or small mass Painless or radiating pain to groin/ abdomen Metastatic findings Gynecomastia Hyperthyroidism symptoms	N/A	↑	N/A	Ultrasound Hemorrhage and necrosis May appear more cystic inhomogeneous, and calcified	Characterized by hemorrhagic and necrotic areas Disordered syncytiotrophoblastic and cytotrophoblastic elements
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 germ cell tumors	Metastasis depends on tumors types Metastasis to lung, liver, brain, skin	May stain positive based on underlying components	±	+	Physical exam findings based on underlying components	↑	↑	N/A	Imaging findings based on underlying components	Variable components depends on tumor Accompanied with necrosis and hemorrhages
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: Placental ALP Genetic changes in chromosome 12	-	-	N/A	N/A	N/A	↑	N/A	Proliferation of neoplastic germ cells in seminiferous tubules
Diseases	Benign/ Malignant	Unilateral/Bilateral	History/Demography	Metastasis	Genetics	Pain	Mass	Physical exam	AFP	Beta hCG	p-ALP	Imaging	Histopathology
|Non-germ cell tumors
Leydig cell tumor	Malignant in up to 20% of adult cases Benign among children	Unilateral	Based on large size, vascular invasion, and mitotic activity classify into benign / malignant Bimodal age distribution in both adults and children	Uncommon metastasis	Mutation in fumarate hydratase Stains positively for: Inhibin A Calretinin WT-1 SALL-4	-	+	Palpable mass Unilateral mass Nontender Gynecomastia	N/A	N/A	N/A	Ultrasound Well-defined, hypoechoic solid mass Cystic component Irregular calcification	Golden brown color May have cystic, hemorrhagic, or necrotic areas Eosinophilic crystals of Reinke
Sertoli cell tumor ( Androblastoma)	Usually Benign	Unilateral Bilateral	Classified as large cell calcifying or sclerosing types History of peutz-Jeghers syndrome and Carney complex Occur in any ages (infancy to elderly) Average age of 45 years Mean age for large cell calcifying variant is 21 years old	Uncommon metastasis	Stain positively for: Inhibin Cytokeratin	-	+	Palpable and painless mass Hyperestrinism is noted in syndromic cases Gynecomastia	N/A	N/A	N/A	Ultrasound Large cell calcifying variant Hypoechoic	Solid or hollow tubules divided by basement membrane Pale eosinophilic cytoplasm
Testicular lymphoma	Malignant	Unilateral Bilateral ( mostly up to 35% of cases)	Aggressive extranodal non-Hodgkin lymphoma 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	-	+	Palpable mass Nontender mass	↑ or ↓	↑ or ↓	N/A	Ultrasound Diffuse testicular infiltration and enlargement Hypervascularity Hypoechoic and solid lesion	Pleomorphic malignant cells Large irregular nuclei Vascular invasion Seminiferous tubules
Granulosa cell tumors	Malignant	Unilateral	Juvenile type in children less than 2 years old ( the most common infancy tumor) Adult type with average age of 44 years old ( rare) Juvenile type associated with: Sex chromosome abnormalities Ambiguous genitalia Cryptorchidism	Metastasis occur in 10%-20% of cases	Stains positively for: Calretinin Inhibin Vimentin Actin MIC2	-	+	Palpable mass Nontender mass	N/A	N/A	N/A	Ultrasound Hypoechoic mass Solid and cystic appearance	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

* May stain positively when mixed.

References

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