Editor: Mahmut Akgul (

2022-36/September 19

Contributors: Alicia Kenyon, Li Li

A man in his 30s presents with a left testicular 2.3 cm cystic mass with marked heterogeneity, concerning for a malignant neoplasm. The patient had a left testicular surgery performed in childhood with unclear indication. Serological studies include: LDH 140, AFP 5.3, and beta-HCG < 3.



a) Embryonal carcinoma and hydrocele

b) Yolk sack tumor and epidermoid cyst

c) Seminoma and epidermoid cyst

d) Lymphoma and hydrocele

e) Choriocarcinoma and epidermoid cyst

Seminoma and epidermoid cyst

Grossly, the cut surface of the testicular lesion revealed a yellow-to-white, irregular, friable, soft mass with cystic changes measuring 2.8 x 2.8 x 2.7 cm.

Microscopic examination demonstrated a seminoma (*) adjacent to an epidermoid cyst (arrow) (Image 1A), H&E, 20x. The epidermoid cyst (H&E, 40x) has a keratinized squamous epithelial lining (Image 1B) containing a granular cell layer (inset). The lumen of the cyst is filled with keratinaceous debris (*).

A classic type seminoma (H&E, 200x) demonstrating diffuse nests of tumor cells separated by fibrous septa with infiltrating small lymphocytes is shown (Image 2A). The tumor cells have ample clear cytoplasm, large nuclei, prominent nucleoli, and distinct cell membranes (1). Germ cell neoplasia in situ (GCNIS) is in the center of the field (Image 2A, arrow), surrounded by the invasive seminoma. GCNIS is characterized by large atypical cells with abundant clear cytoplasm, large nuclei, and prominent nucleoli within the spermatogonial niche of the seminiferous tubule (Image 2A)(2). Immunohistochemical stain shows that the seminoma tumor cells are positive for germ cell marker OCT3/4 (nuclear, Image 2B), and CD117 and D2-40 (membranous, Image C-D), 200x.

Epidermoid cyst of the testis is a rare lesion accounting for ~1% of all adult testicular tumors, and 3% of pediatric testicular tumors. Some authors maintain that these tumors originate from squamous metaplasia of either the mesothelium or the rete testis epithelium while others consider them to be monodermal teratoma as their occurrence overlaps with that of recognized germ cell tumors (GCTs). Epidermoid cysts have also been identified as components of classic teratomas (3). Epidermoid cysts of the testis may be histologically subcategorized as prepubertal or postpubertal-type teratoma (4, 5). Anheuser et al. defines postpubertal-type teratomas as “complex” epidermoid cysts since they are associated with an ipsilateral GCT as opposed to the prepubertal-type teratoma or “simple” epidermoid cyst (4). The postpubertal-type is a malignant GCT arising from GCNIS whereas the prepubertal-type is a benign lesion with no GCNIS association (4, 5) GCNIS is also a recognized precursor for other adult malignant GCTs, such as seminoma and teratoma (6, 7). The prepubertal-type teratoma uniformly demonstrates unremarkable clinical behavior. Therefore, differentiating prepubertal-type from the malignant postpubertal-type testicular teratoma is important as the treatment strategies differ in these two entities (8)

Of note, our patient had a left testicular surgery performed in childhood for an unknown indication, suggesting the epidermoid cyst may be a preexisting lesion, a prepubertal-type teratoma, as opposed to an adult onset postpubertal-type teratoma (monodermal type). However, the patient also had GCNIS in addition to a seminoma and epidermoid cyst. Given the presence of GCNIS, we cannot rule out that this epidermoid cyst is a postpubertal-type monodermal teratoma mixed with classic type seminoma. Chromosome 12p abnormalities (isochromosome 12p [i(12p)] and 12p overrepresentation) by fluorescence in situ hybridization (FISH) analysis are hallmark genetic markers for adult testicular GCTs. These markers are seen in the vast majority of testicular GCTs of adults, including postpubertal-type teratomas but are absent in prepubertal-type teratomas (3, 5, 9, 10).

1. Berney DM, Moch H, Srigley JR, Looijenga LH. Germ cell neoplasia in situ. In: WHO Classification of Tumours Editorial Board. Urinary and male genital tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2022 [cited 2022 Aug 20]. (WHO classification of tumours series, 5th ed.; vol. 8). Available from:

2. Idrees MT, Raspollini MR, Looijenga LH, Daugaard G, Verrill C, Yilmaz A. Seminoma. In: WHO Classification of Tumours Editorial Board. Urinary and male genital tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2022 [cited 2022 Aug 20]. (WHO classification of tumours series, 5th ed.; vol. 8). Available from:

3. Cheng L, Zhang S, MacLennan GT, Poulos CK, Sung MT, Beck SD, Foster RS. Interphase fluorescence in situ hybridization analysis of chromosome 12p abnormalities is useful for distinguishing epidermoid cysts of the testis from pure mature teratoma. Clin Cancer Res. 2006;12(19):5668-5672. doi:10.1158/1078-0432.CCR-06-0976

4. Anheuser P, Kranz J, Stolle E, Höflmayer D, Büscheck F, Mühlstädt S, Lock G, Dieckmann KP. Testicular epidermoid cysts: A reevaluation. BMC Urology. 2019 June; 19 (52).

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6. Berney DM, Looijenga LH, Idrees M, Oosterhuis JW, Rajpert-De Meyts E, Ulbright TM, Skakkebaek NE. Germ cell neoplasia in situ (GCNIS): evolution of the current nomenclature for testicular pre-invasive germ cell malignancy. Histopathology. 2016 Jul;69(1):7-10. doi: 10.1111/his.12958. Epub 2016 Apr 12. PMID: 26918959.

7. Coffin CM, Ewing S, Dehner LP. Frequency of intratubular germ cell neoplasia with invasive testicular germ cell tumors. Histologic and immunocytochemical features. Arch Pathol Lab Med. 1985;109(6):555-559.

8. Ulbright TM. Gonadal teratomas: a review and speculation. Adv Anat Pathol. 2004;11(1):10-23. doi:10.1097/00125480-200401000-00002

9. Bosl GJ, Ilson DH, Rodriguez E, Motzer RJ, Reuter VE, Chaganti RSK, Clinical Relevance of the i(12p) Chromosome in Germ cell Tumors. JNCI: Journal of the National Cancer Institute, 1994 March ; 86(5): 349–355.

10. Rodriguez E, Mathew S, Mukherjee AB, Reuter VE, Bosl GJ, Chaganti RS. Analysis of chromosome 12 aneuploidy in interphase cells from human male germ cell tumors by fluorescence in situ hybridization. Genes Chromosomes Cancer, 1992 July;5(1):21-9. doi: 10.1002/gcc.2870050104. PMID: 1384658.

Alicia Kenyon
Sidney Kimmel Medical College at Thomas Jefferson University
Philadelphia, PA Li Li
Department of Pathology, Anatomy, and Cell Biology
Thomas Jefferson University Hospital
Philadelphia, PA


Testicle; seminoma; epidermoid cyst; germ cell neoplasia in situ (GCNIS); mixed germ cell tumor