Pathology of Testicular Choriocarcinoma
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Choriocarcinoma of the testis is a germ cell tumor that is rarely identified in its pure form; it is more often seen as a component of a nonseminomatous germ cell tumor. [1, 2] Choriocarcinoma is defined by the presence of 2 cellular components, both syncytiotrophoblasts—which often show bizarre, atypical nuclei—and cytotrophoblasts, arranged in solid nests and sheets. Intermediate trophoblasts are also often present. [3] See the image below.
Choriocarcinoma is extremely rare in its pure form, constituting less than 1% of testicular tumors. [4] More frequently, this tumor is seen as a component of mixed germ cell tumors in approximately 8-10% of such cases. [5] The overall incidence of choriocarcinoma of the testis is approximately 0.8 cases per year per 100,000 male population in countries with the highest frequency of testicular cancer. [6] This tumor most is often found in males between the ages of 15 and 30 years but may be seen from puberty to old age. [7]
Although there is no known specific etiology of choriocarcinoma, germ cell tumors in general are believed to originate from malignant intratubular germ cells. Choriocarcinoma occurs within the testicular parenchyma, with no predilection to a particular site. Vascular invasion is common and the high metastatic potential of this tumor allows for it to travel throughout the body.
Choriocarcinoma of the testis presents most commonly in 15- to 30-year-old patients with hormonal symptoms such as gynecomastia and an elevated human chorionic gonadotropin (hCG) level. The hCG level is elevated due to an increase in production by the syncytiotrophoblastic component of the tumor. Other features may include mild testicular enlargement and evidence of metastatic disease due to the high incidence of vascular invasion. [5]
The most common sites of metastasis include the lungs, retroperitoneum, gastrointestinal tract, liver, and central nervous system. [8] Oftentimes, the metastatic tumor is discovered first only to unveil the primary tumor in the testis afterward. This occurs because of the rapid malignant potential of this tumor. In certain cases in which metastatic disease is uncovered, the primary tumor may no longer be visible and only a scar is seen within the testis. Thyrotoxicosis is a rare symptom that occurs due to the structural similarities between hCG and thyroid-stimulating hormone (TSH).
The following conditions should be considered in the differential diagnosis of testicular choriocarcinomas:
Imaging plays a vital role in the assessment of germ cell tumors in general. Tumor bulk, sites of metastases, and response to treatment can all be assessed by various imaging techniques. The most commonly used imaging modality is computed tomography (CT) scanning, but plain film radiography, ultrasonography, and magnetic resonance imaging (MRI) are used as well. [9]
Primary testicular disease often shows a hypoechoic pattern on ultrasonograms. CT scanning has been shown to be the most sensitive method of assessing metastatic disease within the thorax, abdomen, and pelvis.
Positron emission tomography (PET) scanning is an emerging diagnostic imaging technique used to assess for metastatic disease. However, its optimal role is yet to be agreed upon. [9]
Typically, the testis is normal in size but may show mild enlargement. The tumor displays abundant hemorrhage and necrosis, usually with poorly defined, grayish viable tissue at the periphery. [5]
Histologically, choriocarcinoma is composed of syncytiotrophoblasts and cytotrophoblasts, of which the presence of both is required for diagnosis. These cells are typically intermingled together in solid nests or sheets, occasionally in a villuslike arrangement. [5, 7] The syncytiotrophoblasts are large, multinucleated cells with vacuolization and amphophilic cytoplasm. They typically have multiple large, pleomorphic, smudged-appearing nuclei. The cytotrophoblasts are small to medium in size, with clear cytoplasm and mild to moderate nuclear pleomorphism. Mitotic activity is oftentimes abundant. The background shows extensive hemorrhage and necrosis. See the following images.
Cytotrophoblasts may be indistinct, and it is often difficult to discern them from other seminoma or embryonal carcinoma cells, aside from their close concurrence with syncytiotrophoblasts. Commonly, the syncytiotrophoblasts surround the cytotrophoblasts creating a “cap.” [5] See the images below.
Rare variants of choriocarcinoma have been described. Two of these are grouped under the term choriocarcinomalike lesion (CCLL). [10] The first variant shows an unusual proliferation of teratomatous epithelium and is known as teratomatous CCLL. The second variant is a cystic, nonbiphasic form.
Another variant is known as placental-site trophoblastic tumor (PSTT). This is a well-known entity within the female reproductive tract. However, in males, only 2 cases have been reported. [11] The first case involved an adult male patient whose tumor showed a predominant component of cytotrophoblastic nodules with only rare syncytiotrophoblastic cells. The second case involved a 16-month-old boy whose tumor consisted of only mononuclear, intermediate trophoblast cells and was identical to the more common PSTT of the uterus.
Very rarely, a monophasic variant has been described, in which the syncytiotrophoblasts are very infrequent, and the tumor is composed almost exclusively of cytotrophoblasts. [11, 12]
A single case of choriocarcinoma was reported with an angiosarcomatous component. This phenomenon, although rare, portends a poor clinical outcome with a decreased life expectancy. [13]
These infrequent variants highlight the importance that trophoblastic tumors other than classic choriocarcinoma can occur in the testis.
Syncytiotrophoblasts are positive for human chorionic gonadotropin (hCG), human placental lactogen (HPL), and pregnancy-specific beta-1 glycoprotein (SP1), whereas cytotrophoblasts are negative for all of these markers. [14] Low–molecular-weight keratins such as Cam 5.2 are positive in both syncytiotrophoblasts and cytotrophoblasts. Placental alkaline phosphatase (PLAP) is positive in about 50% of choriocarcinomas, whereas carcinoembryonic antigen (CEA) is positive in about 25%. [15, 16] Vimentin is negative. Inhibin is typically positive in syncytiotrophoblasts and negative in cytotrophoblasts. [17] Immunohistochemical stains may also play an important role in differentiating choriocarcinoma from other germ cell tumors with syncytiotrophoblastic cells. OCT 3/4 will be negative in syncytiotrophoblastic components of choriocarcinoma but positive in those of seminoma or embryonal carcinoma. [18]
Choriocarcinoma of the testis shares similar genetic features of other malignant germ cell testicular neoplasms. The most recent developments show that the most common genetic abnormality is the formation of an isochromosome 12p [i(12p)]. The i(12p) occurs in both primary and metastatic disease sites. [19] Currently, no specific gene on i(12p) involved with the development of germ cell tumors is known.
Choriocarcinoma spreads through both lymphatic and hematogenous routes. The most commonly involved lymph nodes are the retroperitoneal. Other common sites of involvement include the lungs, liver, gastrointestinal tract, spleen, brain, and adrenal glands.
Tumor staging of choriocarcinoma is similar to that of all testicular germ cell neoplasms. It is typically determined after the orchiectomy is performed and the diagnosis is made. The tumor classification is as follows [20] :
The primary tumor is classified as pT1 if it is limited to the testis and does not invade the tunica vaginalis.
The tumor is classified as pT2 if it shows vascular or lymphatic invasion or it invades the tunica vaginalis.
The tumor is classified pT3 if it invades the spermatic cord.
The tumor is classified as pT4 if it invades the scrotum.
Regional lymph node metastasis is staged depending on the size and number of metastases, as follows [20] :
Stage N0 is reserved for no metastases.
Stage N1 is refers to a metastasis within any number of lymph node with the mass(es) measuring no greater than 2 cm in its greatest dimension.
Stage N2 refers to a metastasis within any number of lymph node with the mass(es) measuring greater than 2 but less than 5 cm in its greatest dimension.
Stage N3 refers to a lymph node metastasis greater than 5 cm in its greatest dimension.
Distant metastases are staged based on their location within the body, as follows [20] :
Stage M0 is reserved for no distant metastasis.
Stage M1a is refers to a nonregional nodal or pulmonary metastasis.
Stage M1b refers to a distant metastasis other than to nonregional lymph nodes or lungs.
Serum tumor markers including lactate dehydrogenase (LDH), human chorionic gonadotropin (hCG), and alpha-fetoprotein (AFP) also play a role in the staging of testicular tumors.
The natural history of choriocarcinoma is similar to the adult type of embryonal carcinoma. It presents with advanced-stage disease in a majority of cases. The ability of choriocarcinoma to rapidly invade blood vessels allows for rapid dissemination of the tumor. In addition, increasing levels of human chorionic gonadotropin (hCG) correspond to a worse prognosis. [6] There are currently no predictive factors for this tumor.
Mostofi FK, Price EB. Tumors of the Male Genital System: Atlas of Tumor Pathology. 2nd ed. Washington, DC: Armed Forces Institute of Pathology; 1973.
Ulbright TM. Germ cell neoplasms of the testis. Am J Surg Pathol. 1993 Nov. 17(11):1075-91. [Medline].
Alvarado-Cabrero I, Hernandez-Toriz N, Paner GP. Clinicopathologic analysis of choriocarcinoma as a pure or predominant component of germ cell tumor of the testis. Am J Surg Pathol. 2014 Jan. 38(1):111-8. [Medline].
Ramon y Cajal S, Pinango L, Barat A, Moldenhauer F, Oliva H. Metastatic pure choriocarcinoma of the testis in an elderly man. J Urol. 1987 Mar. 137(3):516-9. [Medline].
Ro JY, Amin MB, Kim K-R, Ayala AG. Tumors of the male genital tract. Fletcher CDM, ed. Diagnostic Histopathology of Tumors. 3rd ed. Philadelphia, Pa: Elsevier; 2007. 827-8.
Ebele JN, Sauter G, Epstein JI, Sesterhenn IA, eds. WHO Classification of Tumors: 2004 Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon, France: International Agency for Research on Cancer; 2004.
Tannenbaum M, Madden JF, eds. Testicular tumors. Diagnostic Atlas of Genitourinary Pathology. Philadelphia, Pa: Churchill Livingstone Elsevier; 2006. 95.
Ouarssani A, Asseban M, Ftouhi M, Rguibi MI. [Hemoptysis revealing an endobronchial metastasis of testicular choriocarcinoma]. Rev Mal Respir. 2013 Jan. 30(1):81-3. [Medline].
Dalal PU, Sohaib SA, Huddart R. Imaging of testicular germ cell tumours. Cancer Imaging. 2006 Sep 7. 6:124-34. [Medline]. [Full Text].
Ulbright TM, Loehrer PJ. Choriocarcinoma-like lesions in patients with testicular germ cell tumors. Two histologic variants. Am J Surg Pathol. 1988 Jul. 12(7):531-41. [Medline].
Ulbright TM, Young RH, Scully RE. Trophoblastic tumors of the testis other than classic choriocarcinoma: “monophasic” choriocarcinoma and placental site trophoblastic tumor: a report of two cases. Am J Surg Pathol. 1997 Mar. 21(3):282-8. [Medline].
Young RH. Testicular tumors—some new and a few perennial problems. Arch Pathol Lab Med. Apr 2008. 132:548-64. [Full Text].
Contreras AL, Punar M, Tamboli P, et al. Mediastinal germ cell tumors with an angiosarcomatous component: a report of 12 cases. Hum Pathol. 2010 Jun. 41(6):832-7. [Medline].
Ulbright TM, Amin MB, Young RH. Tumors of the Testis, Adnexa, Spermatic Cord, and Scrotum. Atlas of Tumor Pathology. Fasc 25; ser 3. Washington, DC: Armed Forces Institute of Pathology; 1999. 1-334.
Niehans GA, Manivel JC, Copland GT, Scheithauer BW, Wick MR. Immunohistochemistry of germ cell and trophoblastic neoplasms. Cancer. 1988 Sep 15. 62(6):1113-23. [Medline].
Lind HM, Haghighi P. Carcinoembryonic antigen staining in choriocarcinoma. Am J Clin Pathol. 1986 Oct. 86(4):538-40. [Medline].
Shih IM, Kurman RJ. Immunohistochemical localization of inhibin-alpha in the placenta and gestational trophoblastic lesions. Int J Gynecol Pathol. 1999 Apr. 18(2):144-50. [Medline].
Harik LR, Ulbright TM. The testis, paratesticular structures, and male external genitalia. Silverburg SG, Delellis RA, Frable WJ, eds. Principles and Practice of Surgical Pathology and Cytopathology. 4th ed. Elsevier; 2006. 1753-4.
Reuter VE. Origins and molecular biology of testicular germ cell tumors. Mod Pathol. 2005 Feb. 18 Suppl 2:S51-60. [Medline].
Testis. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, eds. AJCC Cancer Staging Manual. 7th ED. New York, NY: Springer Verlag; 2009. 469-73.
Alvarado-Cabrero I, Hernandez-Toriz N, Paner GP. Clinicopathologic analysis of choriocarcinoma as a pure or predominant component of germ cell tumor of the testis. Am J Surg Pathol. 2014 Jan. 38(1):111-8. [Medline].
Chieffi P, Chieffi S. An update on newly discovered immunohistochemical biomarkers for the diagnosis of human testicular germ cell tumors. Histol Histopathol. 2014 Aug. 29(8):999-1006. [Medline].
Michael Gilger, MD Gastrointestinal Pathologist, Colorado GI Pathology, Centennial Pathologists
Michael Gilger, MD is a member of the following medical societies: American Society for Clinical Pathology, College of American Pathologists, United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.
Thomas M Wheeler, MD Chairman, Department of Pathology and Immunology, WL Moody, Jr, Professor of Pathology, Professor of Urology, Baylor College of Medicine
Thomas M Wheeler, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Medical Association, American Society for Clinical Pathology, American Society of Cytopathology, American Thyroid Association, American Urological Association, College of American Pathologists, United States and Canadian Academy of Pathology, International Society of Urological Pathology, Harris County Medical Society
Disclosure: Received stock from PathXL for medical advisory board. for: PathXL, Inc.
Liang Cheng, MD Professor of Pathology and Urology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine; Chief, Genitourinary Pathology Service, Indiana University Health
Liang Cheng, MD is a member of the following medical societies: American Association for Cancer Research, American Urological Association, College of American Pathologists, United States and Canadian Academy of Pathology, International Society of Urological Pathology, Arthur Purdy Stout Society
Disclosure: Nothing to disclose.
Pathology of Testicular Choriocarcinoma
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