2021-20/ May 17
Contributors: Renier Cruz Baca and Lourdes Huanca Amesquita

A man in his 20s with a left testicular mass underwent radical orchiectomy. Serum AFP: 3.2 ng/mL, βHCG: 6059 mUI/mL, LDH: 353 U/L


1. What is the correct diagnosis?

a. Choriocarcinoma with teratoma

b. Epithelioid trophoblastic tumor and teratoma

c. Placental site trophoblastic tumor and teratoma

d. Teratoma with somatic-type malignancy

e. Regressed choriocarcinoma

1. Placental site trophoblastic tumor and teratoma

Placental site trophoblastic tumour (PSTT), first described in the uterus by Kurman in 1976, is a rare neoplasm that shows, together with epithelioid trophoblastic tumor (ETT), a predominantly intermediate trophoblastic differentiation. Although PSTT occurs mainly in women of reproductive age, it is also encountered in men as an exceptional entity recognized in the last WHO classification as part of the non-choriocarcinomatous trophoblastic tumors of the testis. According to a literature review, six cases of testicular PSTT have been reported, the great majority encountered in post-pubertal men, mixed with another germ cell tumor such as teratoma, yolk sac tumor or embryonal carcinoma.

PSTT consists typically of a relatively monotonous population of polygonal intermediate trophoblastic cells with moderate amounts of amphophilic or eosinophilic cytoplasm. Most of the cells are mononucleate but some are binucleate or multinucleate. The variably atypical nuclei are commonly convoluted, dense, and smudged and have cytoplasmic inclusions and occasionally, large nucleoli. Atypical mitosis is common. Fibrinoid material may surround groups of tumor cells and replace vessel walls. A distinctive pattern of vascular invasion in which tumor cells infiltrate and replace vessel walls and fill their lumina is observed. Necrosis is common and may be extensive.

Immunohistochemical stains are positive for HSD3B1, inhibin, GATA3, HPL, PLAP, CD146 (Mel-Cam) and low weight cytokeratins (CK18) and negative for p63. Our case was positive for inhibin, GATA3, HPL, CK18 and negative for p63. Proliferative index with ki67 is usually 10-30% (our case had 30% of proliferative index).

Differential diagnosis include: Epithelioid trophoblastic tumour which has a more squamoid appearance, apoptotic hyaline cellular debris and usually lacks vascular involvement. ETT similarly to PSTT is positive for GATA3 and inhibin (as was our case) but unlike PSTT is diffusely positive for p63 and negative for HPL. Choriocarcinoma (CCA) forms a hemorrhagic mass with biphasic growth composed of cytotrophoblast and syncytiotrophoblast as well as intermediate trophoblast. CCA usually lacks the fibrinoid material and distinctive pattern of vascular invasion of PSTT and its Ki67 proliferative index is much higher. CCA stains for hCG and SALL4, our case was SALL4 negative and lacked the trimorphic trophoblastic population. Carcinoma of teratomatous origin (somatic-type malignancy) is another possible differential diagnosis, particularly squamous or poorly differentiated carcinoma with a polygonal cell morphology. The presence of distinct keratin, intercellular bridges and negativity for trophoblastic markers are of aid in recognizing a somatic-type carcinoma of teratomatous derivation. Regressed choriocarcinoma could be a reasonable differential diagnosis, especially tumors that have partially regressed, thus one can encounter any number of syncytiotrophoblast, cytotrophoblast or intermediate trophoblast accompanied by the typical scarring with areas of dense collagen, hyalinized remnants of seminiferous tubules, prominent lymphoplasmacytic infiltrate and hemosiderin-containing macrophages as well as coarse intratubular calcifications.

Studies have indicated that ERK, MAPK, mTOR signaling pathway, transcription factor NF-kB, Kiss-1 and GATA3 may play key roles in the invasion and metastasis of PSTT. In regards of the genetic mechanism, a study analized the status of X chromosome inactivation of PSTT and found that PSTT present a unique genetic mode, requiring the presence of a paternal X (Xp) chromosome. Duplication of Xp chromosome is considered to cause abnormal genetic overdosing and plays a role in trophoblastic proliferation. The hypotheses is that Xp harbors a dominant oncogene or tumorigenesis results from abnormal dosage of functional X chromosomes.

PSTT constitutes an aggressive, chemo-resistant malignancy with unpredictable evolution and undefined prognosis. Its pathogenesis is not known, although Idrees et. al have proposed that a possible scenario would be the initial development of the most primitive of trophoblastic tumors, choriocarcinoma, which progresses to form a spectrum of trophoblastic cell types. In many cases the less proliferative trophoblast cells are subsumed by the rapidly growing dominant cytotrophoblasts of the CCA but in others the highly proliferative elements regress and allows progression of the intermediate cell types.

1. Idrees MT, Kao Ch-S, Epstein JI, Ulbright TM, Nonchoriocarcinomatous Trophoblastic Tumors of the Testis The Widening Spectrum of Trophoblastic Neoplasia, Am J Surg Pathol, 2015 November; 39(11) DOI: 10.1097/PAS.0000000000000509

2. Razafimahefa J, Gosset C, Culine S, Mongiat-Artus P., Verine Jerome, Placental site trophoblastic tumor in nonseminomatous mixed germ cell tumors of the testis: A case report and review of the literature, Clinical Genitourinary Cancer, 2018 April ;16(2):e349-e354. DOI: 10.1016/j.clgc.2017.12.010

3. Petersson F, Grossmann P, Vanecek T, Coric M, Cacic M, Hes O, Michal M, Testicular germ cell tumor composed of placental site trophoblastic tumor and teratoma, Hum Pathol 2010 Jul;41(7):1046-50. DOI: 10.1016/j.humpath.2009.10.026.

4. Feng X, Wei Z, Zhang S, Du Y, Zhao H, A Review on the Pathogenesis and Clinical Management of Placental Site Trophoblastic Tumors, Front. Oncol, 2019, November;9(937). DOI: 10.3389/fonc.2019.00937

5. Clement, P. B., Stall, J. N., & Young, R. H. 1. (2020). Atlas of gynecologic surgical pathology (Fourth edition.). Edinburgh: Elsevier. Trophoblatic Lesions, Miscellaneous Primary Uterine Neoplasms, Uterine Hematolymphoid Neoplasms, and Metastatic Neoplasms to the Uterus (pp. 312-314)

6. Kurman, R. J., Ellenson, L. H., & Ronnett, B. M. (2019). Blaustein’s pathology of the female genital tract. New York: Springer. Shih I-M, Ronnett BM, Mazur M, Kurman RJ Gestational Trophoblastic Tumors and Related Tumorlike Lesions (pp. 1368-1371) DOI: 10.1007/978-3-319-46334-6

7. Moch H, Humphrey PA, Ulbright TM, Reuter VE (2016). WHO Classification of Tumours of the Urinary System and Male Genital Organs 4th ed. Lyon: IARC. Ulbright TM, Amin MB, Balzer B, Berney DM, Epstein JI, Guo C, Idrees MT, Looijenga LHJ, Paner G, Rajpert-De Meyts E, Skakkebaek NE, Tickoo SK, Yilmaz A, Oosterhuis JW Germ cell tumours (p. 210)

8. Ulbright TM, Young RH (2013). Tumors of the testis and adjacent structures 4th series, Silver Spring, Maryland: American Registry of Pathology (pp. 221-224)

Renier Cruz Baca
National Institute of Neoplastic Diseases of Peru (INEN),

Lourdes Huanca Amesquita
National Institute of Neoplastic Diseases of Peru (INEN),


Trophoblastic neoplasia; non-choriocarcinomatous trophoblastic tumor, placental site trophoblastic tumor