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[edit | edit source]

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

Differentiating Testicular cancer from other Diseases[edit | edit source]

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	Physical examination	AFP	Beta hCG	p-ALP	Imaging	Histopathology
Germ Cell tumors
Seminoma^[1]^[2]	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^[3]	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^[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	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^[6]^[7]	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^[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	+	±	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^[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	±	+	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 )^[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	-	-	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^[15]	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)^[16]^[17]^[18]	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^[19]^[20]^[21]	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^[22]^[23]	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[edit | edit source]

↑ 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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