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:

Germ Cell tumors
Diseases	Benign/ Malignant	Unilateral/Bilateral	History	Demography	Metastasis	Genetics	Histopathology	Clinical manifestations			Para-clinical findings
								Symptoms		Physical examination	Lab findings			Imaging
								Pain	Mass	Physical examination	AFP	Beta hCG	Others
Seminoma^[1]^[2]	Malignant	Unilateral	Cryptorchidism	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 calcification are uncommon Inhomogenous feature in larger mass
Embryonal carcinoma^[3]	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 calcification
Yolk sac tumor^[4]^[5]	Malignant	Unilateral	Known as a endodermal sinus tumor 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^[6]^[7]	Benign Malignant	Unilateral	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 12 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 calcification
Choriocarcinoma^[8]^[9]	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	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^[10]^[11]	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	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 )^[12]^[13]^[14]	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	Proliferation of neoplastic germ cells in seminiferous tubules	-	-	N/A			Elevated for: Placental ALP	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^[15]	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 calcification
Sertoli cell tumor^[16]^[17]^[18]	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^[19]^[20]^[21]	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^[22]^[23]	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 factor	Ultrasound: Hypoechoic mass Solid and cystic appearance

References

↑ Siegel RL, Miller KD, Jemal A (2016). "Cancer statistics, 2016". CA Cancer J Clin. 66 (1): 7–30. doi:10.3322/caac.21332. PMID 26742998.
↑ Miller FH, Whitney WS, Fitzgerald SW, Miller EI (1999). "Seminomas complicating undescended intraabdominal testes in patients with prior negative findings from surgical exploration". AJR Am J Roentgenol. 172 (2): 425–8. doi:10.2214/ajr.172.2.9930796. PMID 9930796.
↑ Ishida M, Hasegawa M, Kanao K, Oyama M, Nakajima Y (2009). "Non-palpable testicular embryonal carcinoma diagnosed by ultrasound: a case report". Jpn J Clin Oncol. 39 (2): 124–6. doi:10.1093/jjco/hyn141. PMID 19066212.
↑ Howitt BE, Berney DM (2015). "Tumors of the Testis: Morphologic Features and Molecular Alterations". Surg Pathol Clin. 8 (4): 687–716. doi:10.1016/j.path.2015.07.007. PMID 26612222.
↑ Magers MJ, Kao CS, Cole CD, Rice KR, Foster RS, Einhorn LH; et al. (2014). ""Somatic-type" malignancies arising from testicular germ cell tumors: a clinicopathologic study of 124 cases with emphasis on glandular tumors supporting frequent yolk sac tumor origin". Am J Surg Pathol. 38 (10): 1396–409. doi:10.1097/PAS.0000000000000262. PMID 24921638.
↑ Simmonds PD, Lee AH, Theaker JM, Tung K, Smart CJ, Mead GM (1996). "Primary pure teratoma of the testis". J Urol. 155 (3): 939–42. PMID 8583612.
↑ Brosman SA (1979). "Testicular tumors in prepubertal children". Urology. 13 (6): 581–8. PMID 377749.
↑ Puri S, Sood S, Mohindroo S, Kaushal V (2015). "Cytomorphology of lung metastasis of pure choriocarcinoma of testis in a 58-year-old male". J Cancer Res Ther. 11 (4): 1035. doi:10.4103/0973-1482.154010. PMID 26881635.
↑ Wood HM, Elder JS (2009). "Cryptorchidism and testicular cancer: separating fact from fiction". J Urol. 181 (2): 452–61. doi:10.1016/j.juro.2008.10.074. PMID 19084853.
↑ Chuang KL, Liaw CC, Ueng SH, Liao SK, Pang ST, Chang YH; et al. (2010). "Mixed germ cell tumor metastatic to the skin: case report and literature review". World J Surg Oncol. 8: 21. doi:10.1186/1477-7819-8-21. PMC 2851696. PMID 20331874.
↑ Krag Jacobsen G, Barlebo H, Olsen J, Schultz HP, Starklint H, Søgaard H; et al. (1984). "Testicular germ cell tumours in Denmark 1976-1980. Pathology of 1058 consecutive cases". Acta Radiol Oncol. 23 (4): 239–47. PMID 6093440.
↑ Rajpert-De Meyts E, Skakkebaek NE (1994). "Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours". Int J Androl. 17 (2): 85–92. PMID 7517917.
↑ Jacobsen GK, Nørgaard-Pedersen B (1984). "Placental alkaline phosphatase in testicular germ cell tumours and in carcinoma-in-situ of the testis. An immunohistochemical study". Acta Pathol Microbiol Immunol Scand A. 92 (5): 323–9. PMID 6209917.
↑ Jacobsen GK, Henriksen OB, von der Maase H (1981). "Carcinoma in situ of testicular tissue adjacent to malignant germ-cell tumors: a study of 105 cases". Cancer. 47 (11): 2660–2. PMID 7260858.
↑ Cheville JC, Sebo TJ, Lager DJ, Bostwick DG, Farrow GM (1998). "Leydig cell tumor of the testis: a clinicopathologic, DNA content, and MIB-1 comparison of nonmetastasizing and metastasizing tumors". Am J Surg Pathol. 22 (11): 1361–7. PMID 9808128.
↑ Banerji JS, Odem-Davis K, Wolff EM, Nichols CR, Porter CR (2016). "Patterns of Care and Survival Outcomes for Malignant Sex Cord Stromal Testicular Cancer: Results from the National Cancer Data Base". J Urol. 196 (4): 1117–22. doi:10.1016/j.juro.2016.03.143. PMID 27036305.
↑ Young RH (2005). "Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems". Mod Pathol. 18 Suppl 2: S81–98. doi:10.1038/modpathol.3800311. PMID 15502809.
↑ Gabrilove JL, Freiberg EK, Leiter E, Nicolis GL (1980). "Feminizing and non-feminizing Sertoli cell tumors". J Urol. 124 (6): 757–67. PMID 7003168.
↑ Shahab N, Doll DC (1999). "Testicular lymphoma". Semin Oncol. 26 (3): 259–69. PMID 10375083.
↑ Kim J, Abu-Yousef M (2013). "Testicular lymphoma". Ultrasound Q. 29 (3): 247–8. doi:10.1097/RUQ.0b013e3182a0ac0e. PMID 23945480.
↑ Vega F, Medeiros LJ, Abruzzo LV (2001). "Primary paratesticular lymphoma: a report of 2 cases and review of literature". Arch Pathol Lab Med. 125 (3): 428–32. doi:10.1043/0003-9985(2001)125<0428:PPL>2.0.CO;2. PMID 11231498.
↑ Garrett JE, Cartwright PC, Snow BW, Coffin CM (2000). "Cystic testicular lesions in the pediatric population". J Urol. 163 (3): 928–36. PMID 10688023.
↑ Ditonno P, Lucarelli G, Battaglia M, Mancini V, Palazzo S, Trabucco S; et al. (2007). "Testicular granulosa cell tumor of adult type: a new case and a review of the literature". Urol Oncol. 25 (4): 322–5. doi:10.1016/j.urolonc.2006.08.019. PMID 17628299.

Template:WikiDoc Sources

[pmid26742998-1] Siegel RL, Miller KD, Jemal A (2016). "Cancer statistics, 2016". CA Cancer J Clin. 66 (1): 7–30. doi:10.3322/caac.21332. PMID 26742998.

[pmid9930796-2] Miller FH, Whitney WS, Fitzgerald SW, Miller EI (1999). "Seminomas complicating undescended intraabdominal testes in patients with prior negative findings from surgical exploration". AJR Am J Roentgenol. 172 (2): 425–8. doi:10.2214/ajr.172.2.9930796. PMID 9930796.

[pmid19066212-3] Ishida M, Hasegawa M, Kanao K, Oyama M, Nakajima Y (2009). "Non-palpable testicular embryonal carcinoma diagnosed by ultrasound: a case report". Jpn J Clin Oncol. 39 (2): 124–6. doi:10.1093/jjco/hyn141. PMID 19066212.

[pmid26612222-4] Howitt BE, Berney DM (2015). "Tumors of the Testis: Morphologic Features and Molecular Alterations". Surg Pathol Clin. 8 (4): 687–716. doi:10.1016/j.path.2015.07.007. PMID 26612222.

[pmid24921638-5] Magers MJ, Kao CS, Cole CD, Rice KR, Foster RS, Einhorn LH; et al. (2014). ""Somatic-type" malignancies arising from testicular germ cell tumors: a clinicopathologic study of 124 cases with emphasis on glandular tumors supporting frequent yolk sac tumor origin". Am J Surg Pathol. 38 (10): 1396–409. doi:10.1097/PAS.0000000000000262. PMID 24921638.

[pmid8583612-6] Simmonds PD, Lee AH, Theaker JM, Tung K, Smart CJ, Mead GM (1996). "Primary pure teratoma of the testis". J Urol. 155 (3): 939–42. PMID 8583612.

[pmid377749-7] Brosman SA (1979). "Testicular tumors in prepubertal children". Urology. 13 (6): 581–8. PMID 377749.

[pmid26881635-8] Puri S, Sood S, Mohindroo S, Kaushal V (2015). "Cytomorphology of lung metastasis of pure choriocarcinoma of testis in a 58-year-old male". J Cancer Res Ther. 11 (4): 1035. doi:10.4103/0973-1482.154010. PMID 26881635.

[pmid19084853-9] Wood HM, Elder JS (2009). "Cryptorchidism and testicular cancer: separating fact from fiction". J Urol. 181 (2): 452–61. doi:10.1016/j.juro.2008.10.074. PMID 19084853.

[pmid20331874-10] Chuang KL, Liaw CC, Ueng SH, Liao SK, Pang ST, Chang YH; et al. (2010). "Mixed germ cell tumor metastatic to the skin: case report and literature review". World J Surg Oncol. 8: 21. doi:10.1186/1477-7819-8-21. PMC 2851696. PMID 20331874.

[pmid6093440-11] Krag Jacobsen G, Barlebo H, Olsen J, Schultz HP, Starklint H, Søgaard H; et al. (1984). "Testicular germ cell tumours in Denmark 1976-1980. Pathology of 1058 consecutive cases". Acta Radiol Oncol. 23 (4): 239–47. PMID 6093440.

[pmid7517917-12] Rajpert-De Meyts E, Skakkebaek NE (1994). "Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours". Int J Androl. 17 (2): 85–92. PMID 7517917.

[pmid6209917-13] Jacobsen GK, Nørgaard-Pedersen B (1984). "Placental alkaline phosphatase in testicular germ cell tumours and in carcinoma-in-situ of the testis. An immunohistochemical study". Acta Pathol Microbiol Immunol Scand A. 92 (5): 323–9. PMID 6209917.

[pmid7260858-14] Jacobsen GK, Henriksen OB, von der Maase H (1981). "Carcinoma in situ of testicular tissue adjacent to malignant germ-cell tumors: a study of 105 cases". Cancer. 47 (11): 2660–2. PMID 7260858.

[pmid9808128-15] Cheville JC, Sebo TJ, Lager DJ, Bostwick DG, Farrow GM (1998). "Leydig cell tumor of the testis: a clinicopathologic, DNA content, and MIB-1 comparison of nonmetastasizing and metastasizing tumors". Am J Surg Pathol. 22 (11): 1361–7. PMID 9808128.

[pmid27036305-16] Banerji JS, Odem-Davis K, Wolff EM, Nichols CR, Porter CR (2016). "Patterns of Care and Survival Outcomes for Malignant Sex Cord Stromal Testicular Cancer: Results from the National Cancer Data Base". J Urol. 196 (4): 1117–22. doi:10.1016/j.juro.2016.03.143. PMID 27036305.

[pmid15502809-17] Young RH (2005). "Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems". Mod Pathol. 18 Suppl 2: S81–98. doi:10.1038/modpathol.3800311. PMID 15502809.

[pmid7003168-18] Gabrilove JL, Freiberg EK, Leiter E, Nicolis GL (1980). "Feminizing and non-feminizing Sertoli cell tumors". J Urol. 124 (6): 757–67. PMID 7003168.

[pmid10375083-19] Shahab N, Doll DC (1999). "Testicular lymphoma". Semin Oncol. 26 (3): 259–69. PMID 10375083.

[pmid23945480-20] Kim J, Abu-Yousef M (2013). "Testicular lymphoma". Ultrasound Q. 29 (3): 247–8. doi:10.1097/RUQ.0b013e3182a0ac0e. PMID 23945480.

[pmid11231498-21] Vega F, Medeiros LJ, Abruzzo LV (2001). "Primary paratesticular lymphoma: a report of 2 cases and review of literature". Arch Pathol Lab Med. 125 (3): 428–32. doi:10.1043/0003-9985(2001)125<0428:PPL>2.0.CO;2. PMID 11231498.

[pmid10688023-22] Garrett JE, Cartwright PC, Snow BW, Coffin CM (2000). "Cystic testicular lesions in the pediatric population". J Urol. 163 (3): 928–36. PMID 10688023.

[pmid17628299-23] Ditonno P, Lucarelli G, Battaglia M, Mancini V, Palazzo S, Trabucco S; et al. (2007). "Testicular granulosa cell tumor of adult type: a new case and a review of the literature". Urol Oncol. 25 (4): 322–5. doi:10.1016/j.urolonc.2006.08.019. PMID 17628299.

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Testicular cancer differential diagnosis

Overview

Differentiating Testicular cancer from other Diseases

References

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