Testis & epididymis
Nonseminomatous germ cell tumors-general
Topic Completed: 1 January 2013
Minor changes: 6 July 2020
Copyright: 2002-2019, PathologyOutlines.com, Inc.
PubMed Search: Nonseminomatous germ cell tumors [title] (NSGCT)
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Etiology and Pathophysiology | Clinical features | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Asadbeigi S, Hassan O. Nonseminomatous germ cell tumors-general. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/testisnsgctgeneral0.html. Accessed January 23rd, 2021.
Definition / general
- A group of germ cell tumors different than seminoma
- More aggressive than seminoma
- It is recommended to list components with percentage involvement
- Do not overlook yolk sac tumor (YST) foci or nongerm cell component
Essential features
- Modal age of NSGCT is a decade earlier than seminoma
- More aggressive than seminoma
- Variegated appearance grossly, since usually a mixture of different components
- Differential diagnosis includes: seminoma, sex cord stromal tumor, lymphoma and metastatic carcinoma
Terminology
- Malignant mixed germ cell tumor, embryonal carcinoma, yolk sac tumor (YST), teratoma postpubertal type, choriocarcinoma, nonchoriocarcinomatous trophoblastic tumors
ICD coding
- ICD-10: C62.90 - malignant neoplasm of unspecified testis, unspecified whether descended or undescended
Epidemiology
- Testicular germ cell tumors account for 1% of all male cancers worldwide (Andrology 2015;3:4)
- Majority of male GCT are seminomas and mixed seminoma and NSGCT
- Modal age of NSGCT is a decade earlier than seminoma
- Nonseminomatous germ cell tumors constitutes slightly less than half of testicular germ cell tumors (Andrology 2015;3:4)
- Embryonal carcinoma (EC) is the second most common pure testicular GCT, represent 10.8% of pure germ cell tumors (Andrology 2018 Dec 21 [Epub ahead of print])
- YST 75% to 80% of all childhood testicular neoplasms
- In adults, pure form is exceedingly rare, representing 0.6% of pure germ cell tumors (Andrology 2018 Dec 21 [Epub ahead of print])
- Choriocarcinoma present in 7 - 8% of mixed GCT
- Very rare in pure form (0.2 - 0.6 % of GCT) (Am J Surg Pathol 2018;42:1113)
Sites
- Testis, ovaries, mediastinum and brain
Etiology and Pathophysiology
- NSGCT develops when a germ cell neoplasia is situ or a seminoma cell becomes reprogrammed (Eur Urol 1993;23:245, Proc Natl Acad Sci U S A 2003;100:13350)
Clinical features
- NSGCT tends to be more aggressive than seminoma (Iran J Radiol 2016;13:e27812)
- 60% present with stage I disease (Clin Cancer Res 2016;22:1265)
- Less responsive to radiation therapy and chemotherapeutic agents (Iran J Radiol 2016;13:e27812)
- Embryonal carcinoma (EC): most patients present with a testicular mass which can be painful due to rapid growth
- 10% of patients present with metastatic disease (J Urol 1986;136:604)
- Yolk sac tumor (YST): most patients present with painless testicular mass
- YST has a higher proportion of local disease when compared to other NSGCT (Lancet 1987;2:294)
- Choriocarcinoma: tend to present with distant metastasis such as lung metastasis (Am J Surg Pathol 2018;42:1113)
- Teratoma, postpubertal type: tend to present with a testicular mass or with metastasis (IARC: WHO classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016)
Laboratory
- Elevated LDH, α Fetoprotein and β HCG
Radiology description
- Cystic and solid intratesticular mass
- Teratoma tend to be well circumscribed with complex architecture due to different components
Prognostic factors
- Poor prognostic factors include: higher age, retroperitoneal primary disease, mediastinal primary disease, bone metastases, liver metastases, pulmonary metastases and increased levels of tumor markers (Eur Urol 2017;71:290)
Case reports
- 22 year old man with a history of testicular NSGCT presents with progressive swelling over right scapular region (Case Rep Urol 2015;2015:205297)
- 26 year old man with a well defined mass between the rectum and the urinary bladder (J Coll Physicians Surg Pak 2018;28:S2)
- 34 year old man presenting with low back pain was found to have a retroperitoneal mass (J Surg Case Rep 2019;2019:rjy358)
- 36 year old man presenting with benign looking gingival mass (J Oral Pathol Med 2006;35:579)
- 37 year old man with testicular tumor with metastasis into lung, liver, adrenal gland and retroperitoneum (Cureus 2018;10:e2329)
Treatment
- Surgery plus chemotherapy
Gross description
- Variegated appearance since usually a mixture of different components
- May have areas of hemorrhage and necrosis in choriocarcinoma
- May be focally cystic and may have mucinous cut surface in YST
Gross images
Images hosted on other servers:
Embryonal carcinoma and mature teratoma
Seminoma and immature teratoma
Mixed germ cell tumor
Large areas of necrosis
Soft yellow areas
Microscopic (histologic) description
- Embryonal carcinoma: solid sheets, tubular papillary architecture, primitive cells with indistinct cell borders, marked nuclear atypia
- Yolk sac tumor: simultaneous presence of a myriad of histologic patterns, microcystic / reticular pattern is the most common, myxoid stroma, Schiller-Duval bodies, extracellular and intracellular hyaline globules
- Choriocarcinoma: plexiform admixture of syncitiotrophoblasts, cytotrophoblasts and intermediate trophoblasts
- Teratoma, postpubertal type: virtually any epithelial or mesenchymal component can be seen; degrees of cytologic atypia is allowed in both epithelial and mesenchymal component and does not mean somatic malignant transformation
Microscopic (histologic) images
Contributed by Oudai Hassan, M.D.
Teratoma, postpubertal type
YST, microcystic pattern
Embryonal carcinoma (EC) intermixed with YST
YST, reticular and microcystic patterns
Choriocarcinoma
Positive stains
- Embryonal carcinoma: SALL4, AE1 / AE3, CD30, OCT 3/4, PLAP, alpha feto-protein (AFP) (+/-) (Am J Surg Pathol 2014;38:e50)
- Yolk sac tumor: SALL4, alpha feto-protein (AFP), glypican 3, cytokeratin, PLAP (+/-) (Am J Surg Pathol 2014;38:e50)
- Choriocarcinoma: SALL4, hCG, cytokeratin, EMA (+/-), PLAP (+/-) intermediate cells human placental lactogen (+), GATA3+ in cytotrophoblasts (Am J Surg Pathol 2014;38:e50)
Negative stains
- CD117, podoplanin, SOX17, CD45, PAX5, CK20, CD3, inhibin, calretinin (Am J Surg Pathol 2014;38:e50)
Molecular / cytogenetics description
- I (12p): present in up to 80% of male germ cell tumors (J Natl Cancer Inst 1994;86:349)
- Recent studies have showed TGCT associated genetic mutations (i.e. KIT and KRAS) and also identified new mutations (Curr Opin Urol 2017;27:41)
- High rates of alterations within the TP53-MDM2 axis are seen in patients with platinum resistant disease (Curr Opin Urol 2017;27:41)
- Amplification of 12p11.2-p12.1 region is preferentially found in seminomas lacking I (12p) (Oncogene 2003;22:1880, Am J Pathol 2000;157:1155, Cancer Res 2002;62:1822, Oncogene 2003;22:7695)
Sample pathology report
- Testes, right, orcchiectomy:
- Malignant mixed germ cell tumor, consisting of teratoma (70%), yolk sac tumor(20%) and embryonal carcinoma (10%).
- Tumor measures 5 cm in greatest dimension.
- Surgical resection margins are negative.
- The tumor is organ confined.
- No lymph-vascular space invasion is identified.
- Gem cell neoplasia in situ.
- Please see cancer checklist below for more details.
Differential diagnosis
- Seminoma: presents one decade later than NSGCT
- Sheets of clear cells, well defined cytoplasmic borders and granulomatous-lymphocytic host reaction
- Positive for OCT 3/4, CD117 and podoplanin
- Sex cord stromal tumors: more common in children, mostly nonfunctional and the vast majority are benign
- Positive for Inhibin, calretinin and negative for SALL4 and OCT 3/4
- Lymphoma: most common testicular neoplasm in men over 50 years old, about 80 - 90% of testicular lymphoma is diffuse large B cell lymphoma
- Metastatic carcinoma: most common tumor to metastasize to the testis is prostate cancer
Board review style question #1
- A 26 year old man presents with hemoptysis. A physical examination highlights the presence of a right testicular mass. Serum Β-HCG titer was 4650 mIU/mL. The orchiectomy specimen shows a hemorrhagic tumor which consists of a mixture of multinucleated cells and small mononuclear cuboidal cells. Which marker highlights the mononuclear cells?
- CD30
- GATA3
- OCT 3/4
- P63
Board review style answer #1
Board review style question #2
- Invasion of which of the following structures is compatible with pathologic stage 1 in germ cell tumors?
- Epididymis
- Hilar soft tissue
- Lymph vascular spaces
- Rete testis
Board review style answer #2
