Testicular Mixed Germ Cell Tumor Research Articles

Metastatic Testicular Cancer to Left Atrium via the Left Inferior Pulmonary Vein: A Case Report

Testicular cancer is one of the most common cancers diagnosed in young men. Frequent sites of metastasis include the retroperitoneum, lungs, liver, brain, and bone. Intracardiac metastasis has also been described. An 18-year-old boy with a history of mixed testicular germ cell tumor presented to our institution for surgical resection of his metastatic disease. Intraoperative transesophageal echocardiography during his surgery confirmed a tumor thrombus into the left atrium coming from the left pulmonary vein. We report a case of metastatic testicular cancer with rare tumor extension from the left inferior pulmonary vein into the left atrium. Perioperative transesophageal echocardiography was necessary to aid intraoperative diagnosis and confirmation of the intracardiac tumor, providing data to guide surgical strategy.

Gastrointestinal hemorrhage and gynecomastia as first signs of metastatic testicular choriocarcinoma

Testicular choriocarcinoma is an infrequent non seminomatous germ cell tumor, usually presenting histologically as part of a mixed germ cell tumor, and rarely as pure form. It metastasizes early, usually along hematogenous routes, lungs being the most frequent sites of metastasis. Involvement of the gastro-intestinal tract as metastatic site is extremely uncommon and rarely described in the literature. We report the case of a 47 year-old male with gastric and pulmonary metastases from testicular mixed germ cell tumor mainly represented by choriocarcinoma as histological subtype, presenting with melena and gynecomastia as first clinical signs. Morphological and immunohistochemical analyses of biopsies taken from the endoscopically identified gastric hemorrhagic lesion and from lung nodules showed undifferentiated neoplastic epithelial cells in a necrotic and hemorrhagic background. Coexistence of gynecomastia addressed towards an hormonal-dependent tumor and prompted us to apply further morphological and immunohistochemical analyses, revealing the gonadal primary neoplasm, subsequently confirmed at surgery.

A rare case of combined placental site trophoblastic tumour with mature cystic teratoma and mixed germ cell tumour in the testis

<h3>Case report</h3> A 20-year-old male presented with persistent right testicular pain. Following ultrasound detection of testicular nodules and biopsy for intraoperative consultation which yielded germ cell tumour, he underwent radical orchidectomy. A predominantly whitish cyst and a lobulated, variegated nodule were identified. Histology showed a mature cystic teratoma with a focus of infiltrative epithelioid cells containing eosinophilic cytoplasm and pleomorphic nuclei, invading ectatic vessel wall, associated with fibrinoid change. These cells were positive for cytokeratin, human placental lactogen and inhibin, while negative for Melan-A, p63 and alpha-fetoprotein, consistent with placental site trophoblastic tumour (PSTT). The variegated nodule was a mixed germ cell tumour composed of embryonal carcinoma and immature teratoma. <h3>Discussion</h3> Aside from choriocarcinoma, primary trophoblastic tumours such as PSTT, which are derived from intermediate trophoblasts, are extremely rare in the testis. Aside from a case of pure testicular PSTT, two other cases have been described in association with germ cell tumour, of which one is a mature teratoma with PSTT that demonstrated gain of chromosome 12p. The other presented with PSTT in retroperitoneal recurrence of a testicular mixed germ cell tumour. We discuss the features of this tumour in the testis and important differentials in its diagnosis.

A Case of Gastrointestinal Bleeding due to Duodenal Metastasis from a Testicular Choriocarcinoma

Testicular cancers are the most common malignant neoplasm in men aged 15–35, but only constitute 1 % of cancers in males overall with an incidence of 2.1 cases per 100,000 males and four times greater incidence in white males than in black males [1–3]. Testicular tumors usually present as a nodule or painless swelling of one testicle, which may be noted incidentally by the patient or by his sexual partner [4]. Typically, the patient's chief complaint includes acute testicular pain or heaviness in the lower abdomen. Signs or symptoms of metastatic disease are the initial implication of testicular cancer in approximately 10 % of patients. The most common sites of extragonadal disease are the retroperitoneum, lungs, and liver [5–8]. Only rarely (5 % of cases) are metastases found in the gastrointestinal tract [9]. We report a case of testicular mixed germ cell tumor with metastasis of pure choriocarcinoma involving the small intestine.

Therapeutic Potential of SOX2 Inhibition for Embryonal Carcinoma

Some nonseminomatous germ cell tumors are resistant to any type of chemotherapy. Control of embryonal carcinoma cells is crucial to manage nonseminomatous germ cell tumors. We established SOX2 targeting therapy in an embryonal carcinoma model. SOX2 expression was evaluated in a series of testicular germ cell tumor tissue samples. The antitumor effect of SOX2 knockdown was analyzed in vitro and in vivo using an embryonal carcinoma model. In testicular germ cell tumor tissue SOX2 was expressed in the foci of embryonal carcinoma but negative in seminoma and yolk sac tumors. In an embryonal carcinoma model SOX2-siRNA induced apoptotic cell death in vitro and significant growth suppression in vivo. This study shows the therapeutic potential of SOX2 silencing for embryonal carcinoma. However, further improvements are needed in SOX2-siRNA delivery to the tumor.

A Comprehensive Analysis of PAX8 Expression in Human Epithelial Tumors

PAX8 is a paired-box gene important in embryogenesis of the thyroid, Müllerian, and renal/upper urinary tracts, and expression of PAX8 has been previously described in carcinomas from each of these sites. However, a large study including a wide variety of epithelial neoplasms from multiple organ sites other than the thyroid, kidney, or Müllerian system has not been performed. The goal of this study was to evaluate the utility of PAX8 immunostaining based on the evaluation of a wide range of epithelial tumors. PAX8 immunohistochemistry was performed on 1357 tumors (486 tumors in whole-tissue sections and 871 tumors in tissue microarrays, predominantly epithelial) from multiple organs. Only nuclear staining was scored as positive, and tumors were evaluated for the extent and intensity of staining. Western blot analysis with PAX8 was also performed on multiple tumor cell lines. Nuclear PAX8 staining was present in 91% (60 of 66) of thyroid tumors, 90% (158 of 176) of renal cell carcinomas (RCCs), 81% (13 of 16) of renal oncocytomas, 99% (164 of 165) of high-grade ovarian serous carcinomas, 71% (32 of 49) of nonserous ovarian epithelial neoplasms, 91% (10 of 11) of cervical epithelial lesions, and 98% (152 of 155) of endometrial adenocarcinomas. Of the remaining 719 evaluated tumors, only 30 cases (4%), including 12 thymic neoplasms, 3 bladder urothelial carcinomas, 4 lung squamous cell carcinomas, 2 esophageal adenocarcinomas, 1 pancreatic adenocarcinoma, 2 cholangiocarcinomas, 1 ovarian Sertoli-Leydig cell tumor, 1 ovarian sex cord stromal tumor, 3 testicular mixed germ cell tumors, and 1 acinic cell carcinoma, showed at least weak or focal PAX8 positivity. The unexpected finding was diffuse, moderate staining of PAX8 in a subset of thymomas and thymic carcinomas. The 689 remaining tumors, including but not limited to those from the prostate, colon, stomach, liver, adrenal gland, and head and neck, and small cell carcinomas from the lung, cervix, and ovary, were PAX8 negative. PAX8 specificity was confirmed by Western blot analysis, as expression was detected only in ovarian and RCC cell lines. These results show that PAX8 is a highly sensitive marker for thyroid, renal, Müllerian, and thymic tumors. Importantly, all lung adenocarcinomas, breast and adrenal neoplasms, and the majority of gastrointestinal tumors were negative for PAX8. Therefore, PAX8 is an excellent marker for confirming primary tumor site. In a subset of cases, additional markers, including but not limited to thyroid transcription factor-1, RCC, and Wilms tumor-1, may be needed to distinguish between the 3 most common PAX8-positive tumors.

Upper gastrointestinal bleeding as an initial manifestation of metastasis, secondary to a choriocarcinoma in a patient suffering from testicular mixed germ cell tumour

Upper gastrointestinal bleeding as an initial manifestation of metastasis, secondary to a choriocarcinoma in a patient suffering from testicular mixed germ cell tumour

Development of testicular germ cell cancer following successful infliximab induction therapy for ulcerative colitis

Antitumor necrosis factor alpha (anti-TNFα) agents have substantially altered the management of inflammatory bowel diseases (IBD). Their benefits must however be weighed against increased risks for infections, lymphoma, and possibly other malignancies. We report on a 27-year-old man, with a six-year history of ulcerative colitis maintained on mesalamine suppositories, presenting with clinical, radiographic and biopsy evidence of an acute colitis flare. Due to the refractory nature of his disease, infliximab was started, resulting in induction of remission within six weeks. Three months after the first dose of infliximab, the patient was diagnosed with a testicular mixed germ cell tumor requiring orchiectomy. Four cases of testicular cancer development among patients using anti-TNFα agents have been identified. Given the prevalence of IBD in young men and recent suggestions for “top–down therapy,” testicular cancer as a potential complication of anti-TNFα agents should be further explored on a population basis.

Podoplanin, a novel marker for seminoma: A comparison study evaluating immunohistochemical expression of podoplanin and OCT3/4

Podoplanin, a 38-kd membrane glycoprotein of podocytes, is the human homologue of mouse protein, aggrus, a 44-kd sialoglycoprotein; the latter has recently been reported in testicular seminomas but not in embryonal carcinomas, suggesting that it may be a specific marker for seminomas. The physiologic role of podoplanin has yet to be determined and its function in tumors is not well characterized. In this study we investigate the utility of podoplanin expression in the diagnosis of testicular germ cell tumors. Sixty-eight cases of testicular mixed germ cell tumors were analyzed using a polyclonal antibody and compared to the results for OCT3/4. Stained sections were graded semiquantitatively as follows: negative (no expression), 1+ (mild intensity), 2+ (moderate intensity), 3+ (intense staining). Diffuse cytoplasmic expression of podoplanin with membrane accentuation was seen in the seminoma component of all cases. Lymphocytes and interstitial cells were negative. In mixed germ cell tumors, podoplanin identified small clusters of seminoma cells lying adjacent to nonseminomatous components. Focal staining was present in one third of cases of choriocarcinoma. There was no significant staining of any nontrophoblastic, nonseminomatous elements. In contrast to OCT3/4, podoplanin does not stain embryonal carcinoma. The availability of a marker for seminoma will enable better recognition and distinction from embryonal carcinoma, particularly in nongonadal sites. The identification by podoplanin of seminoma cells lying adjacent to foci of embryonal carcinoma gives credence to the hypothesis that the latter arise from seminomas as part of a process of "differentiation."

Paraganglia Mimicking Metastatic Seminomatous Tumor

Two cases are presented in which microscopic groups of retroperitoneal paraganglionic cells simulated metastatic seminomatous tumor. Both patients had histories of mixed testicular germ cell tumor with abdominal metastases and had been treated with chemotherapy. Persistent retroperitoneal disease was favored on follow-up imaging studies. Subsequent retroperitoneal lymph node dissection disclosed multifocal epithelioid cell groups with clear/vacuolated cytoplasm in the fibroconnective and adipose tissue, ranging from 1.0 to 3.0 mm in size. These cell groups were initially interpreted as recurrent metastatic seminoma, but were later reinterpreted as paraganglionic cells, which were confirmed by immunohistochemical analysis. The pathologic features for distinguishing paraganglionic cells from metastatic seminoma are discussed. Awareness of the presence of paraganglia and their distinction from metastatic disease is of practical importance in avoiding an overdiagnosis of malignancy and assuring proper patient management.

Mixed germ cell tumor metastatic to the skin: Case report and literature review

BackgroundTesticular cancer is the most common cancer for males aged 15~35 years old. The initial presentation is typically an asymptomatic enlarged testicle. The retroperitoneum is the most common metastatic area. Other metastatic sites include the lung, liver, brain, adrenal glands, gastrointestinal tract and spleen. Skin metastasis is a rare event and frequently associated with poor prognosis.Case presentationA 19-year old male was diagnosed testicular mixed germ cell tumor with initial presentation of cutaneous metastasis at scalp and upper abdomen. After radical orchiectomy and four courses of cisplatin-based chemotherapy, the scalp and upper abdominal lesions regressed completely. The size of lung metastases remained unchanged.ConclusionsFor advanced stage testicular cancer, cisplatin-based chemotherapy is still effective to achieve partial response.

An unusual mixed germ cell tumor of the testis consisting of rhabdomyosarcoma, mature teratoma and yolk sac tumor

Dear Editor, We recently encountered a rare case of testicular mixed germ cell tumor (MGCT) in a 32-year-old man. The tumor was composed of a combination of a yolk sac tumor, teratoma and rhabdomyosarcomatous somatic type malignancy. The patient presented with left testicular swelling and pain. Physical examination, ultrasonography and computed tomography revealed a tumor in the left testicle. Alpha feto-protein (AFP) was elevated (720 mIU mL−1; normal reference range: 0–9 mIU mL−1). A simple orchiectomy was performed. Grossly, the tumor was tan and well circumscribed, measuring 7.0 × 6.0 × 4.5 cm3, showing a soft and yellow cut surface, with areas of cartilaginous tissue and only a slim margin of residual testicular tissue. Away from the main mass there was an additional well-circumscribed nodule (12 mm in diameter) (Figure 1A). Figure 1 Grossly, the tumor was well circumscribed, showing a soft and yellow cut surface, with areas of cartilaginous tissue and with only a slim margin of residual testicular tissue. Away from the main mass there was an additional well-circumscribed nodule (A). ... Routine formalin-fixed, paraffin-embedded tissue sections were stained with hematoxylin and eosin. An additional immunohistochemical stain for desmin, myoglobin and myogenin (DAKO, Glostrup, Denmark) was performed on a representative section of the tumor. Microscopically, the tumor was composed of a yolk sac tumor (50%) and a mature teratoma (30%) germ cell component associated with a somatic type embryonal rhabdomyosarcoma component (20%). The size of the largest focus of the rhabdomyosarcoma component is 12 mm. The yolk sac tumor showed a microcystic pattern, glandular structures, mesenchymal stroma, and partly micropapillary structures with perivascular Schiller–Duval bodies (Figure 1B). The teratoma was composed of well-differentiated cartilage and cystic formations surrounded with dense connective tissue stroma (Figure 1C). The rhabdomyosarcomatous component from a separate nodule showed sheets of atypical small cells with pleomorphic hyperchromatic nuclei and elongated cells with abundant eosinophilic cytoplasm (Figure 1D and E). The mitotic count was high (7/10 HPF). Immunohistochemically these cells strongly expressed desmin (Figure 1F), myogenin (Figure 1G) and myoglobin (Figure 1H). The adjacent testicular parenchyma contained foci of intratubular germ cell neoplasia of an unclassified type. Necrosis was observed in less than 10% of the tumor. No signs of vascular invasion and no spread to the rete testis, epididymis or beyond the tunica albuginea were found. Follow-up at 6 months after surgery did not show any recurrence or metastasis. The patient did not receive any additional therapy. In the study by Bray et al. 1, the incidence of testicular cancer has shown a consistent increase in the European countries, while at the same time there was a decline in testicular cancer mortality. Advances in the treatment of testicular cancer caused large decreases in mortality in some European countries, despite increases in incidence 1. Testicular MGCTs represent 32%–54% of all germ cell tumors 2, 3. They usually occur at the mean age of 30 years. Clinical presentation includes painless or painful enlargement of the testis. Serum levels of AFP and beta-hCG are often elevated 2. MGCTs consist of more than one histological component that may occur in any combination. Testicular germ cell tumors are omnipotent, can proliferate into homogeneous seminomas and are able to differentiate into any type of tissue, both in the embryo and outside, and form seminomas or nonseminomas (teratomas). The precursor lesion or carcinoma in situ cells show phenotypic similarity to primordial germ cells or gonocytes, which suggests that the cells were stopped at an early stage of differentiation 4. The most common combination is teratoma and embryonal carcinoma 2. A case of rhabdomyosarcoma in a mature teratoma and a case of rhabdomyosarcoma in a mediastinal teratoma have been reported 3, 5. Nongerm cell malignant tumors of somatic type malignancy may arise in primary or metastatic germ cell tumors and are most likely derived from teratomas. They are seen in 3%–6% of patients with metastatic MGCTs, suggesting a poor prognosis 2. MGCT of the testis in combination with the somatic type rhabdomyosarcoma that occurred in our patient is quite uncommon. Recognition of this variant is important because it may mimic a somatic sarcoma if inadequately sampled, and the clinical outcome may differ from the typical testicular MGCT. Therefore, correct histological analysis of testicular MGCTs and their metastases are essential parts of the diagnosis that will guide the correct therapeutic approach and give useful information on the prognosis.

Nonseminomatous Germ Cell Tumor of the Testes Metastatic to the Corpus Cavernosum of the Penis

Metastases to the penis are rare, with less than 200 cases reported. Within the genitourinary tract, advanced prostate cancer is the most common culprit. These cases typically represent widely disseminated disease and are associated with a poor prognosis. We present images of a case of a testicular nonseminomatous mixed germ cell tumor, which metastasized to the corpus cavernosum of the penis 8 months after a negative bilateral retroperitoneal lymph node dissection. The patient received chemotherapy and experienced a complete response.

Clonal evidence for the progression of a testicular germ cell tumor to angiosarcoma

Testicular germ cell tumors may have multiple histologic subtypes. Teratoma components are capable of transformation into somatic malignancies. An alternative hypothesis for the development of angiosarcoma in a patient with germ cell tumors is secondary to radiation or chemotherapy. We report a patient with a mixed testicular germ cell tumor who presented with retroperitoneal, mediastinal, and pulmonary metastases after chemotherapy. Forty months after his original diagnosis, a mediastinal angiosarcoma was diagnosed. Using tissue microdissection-loss of heterozygosity analysis and fluorescence in situ hybridization, we analyzed the clonality of the primary germ cell tumor, angiosarcoma, and metastatic teratoma. Six microsatellite polymorphic markers from 3 different chromosomes were used to examine the pattern of allelic loss; chromosome 12p alterations, including isochromosome 12p and 12p overrepresentation, were investigated. Loss of heterozygosity was demonstrated for microsatellite loci of all 3 chromosomes, and completely concordant loss of heterozygosity patterns were observed among primary germ cell tumor components, metastatic teratoma, and angiosarcoma. Isochromosome 12p and 12p overrepresentations were consistently found in the primary germ cell tumor components, metastatic teratoma, and angiosarcoma. The results indicated a clonal origin of the tumors, which supports that angiosarcoma, as well as the teratomas, arose from the testicular germ cell tumors.

Testicular mixed germ cell tumors: a morphological and immunohistochemical study using stem cell markers, OCT3/4, SOX2 and GDF3, with emphasis on morphologically difficult-to-classify areas

Stem cell markers, OCT3/4, and more recently SOX2 and growth differentiation factor 3 (GDF3), have been reported to be expressed variably in germ cell tumors. We investigated the immunohistochemical expression of these markers in different testicular germ cell tumors, and their utility in the differential diagnosis of morphologically difficult-to-classify components of these tumors. A total of 50 mixed testicular germ cell tumors, 43 also containing difficult-to-classify areas, were studied. In these areas, multiple morphological parameters were noted, and high-grade nuclear details similar to typical embryonal carcinoma were considered ‘embryonal carcinoma-like high-grade’. Immunohistochemical staining for OCT3/4, c-kit, CD30, SOX2, and GDF3 was performed and graded in each component as 0, negative; 1+, 1–25%; 2+, 26–50%; and 3+, >50% positive staining cells. The different components identified in these tumors were seminoma (8), embryonal carcinoma (50), yolk sac tumor (40), teratoma (40), choriocarcinoma (3) and intra-tubular germ cell neoplasia, unclassified (35). By immunohistochemistry, the staining patterns were OCT3/4 −3+, all seminomas, embryonal carcinomas and intra-tubular germ cell neoplasia; SOX2 −3+, all embryonal carcinomas and −2 to 3+, 11/14 (79%) primitive neuroectodermal components in immature teratomas; GDF3 −2 to 3+, all yolk sac tumors, seminomas and intra-tubular germ cell neoplasia and 1 to 2+, 40/50 embryonal carcinomas. A total of 34/43 (79%) of difficult-to-classify areas stained 3+ for OCT3/4, CD30, and SOX2, similar to embryonal carcinoma. Among these areas, only ‘embryonal carcinoma-like high-grade’ nuclear details were significantly associated with such an immunophenotype. Thus, SOX2 is expressed in embryonal carcinoma and primitive neuroectoderm of teratoma, and unlike OCT3/4, not in intra-tubular germ cell neoplasia and seminoma. Therefore, it may be useful in the distinction of seminoma from embryonal carcinoma, and potentially in diagnosing early carcinomatous differentiation in seminoma. GDF3 positivity, in the absence of OCT3/4 and CD30, combined with morphological features, is helpful in the diagnosis of yolk sac tumor. ‘Embryonal carcinoma-like high-grade’ nuclear details are the most important morphological criterion for the diagnosis of embryonal carcinoma in difficult-to-classify areas.

Pancreatitis aguda como manifestación clínica de tumor mixto de células germinales de testículo. Reporte de caso clínico

Testicular germ cell tumors are highly common in young patients and are often detected when the tumor has already metastasized, mainly to the retroperitoneum. We report the case of a young man who was diagnosed with testicular mixed germ cell tumor, which presented as acute pancreatitis. Early diagnosis and treatment with chemotherapy, resection of the testicular tumor and dissection of retroperitoneal lymph nodes is essential in these patients.

Synchronous bilateral germ-cell tumors of testis: A case report

The incidence of bilateral testicular germ-cell tumors is 3.3%. Among these, only 5-24% occur synchronously. Very few cases of synchronous tumors with different histopathology like seminoma with contralateral mixed germ-cell tumor are reported. We describe a case in a 35-year-old male who presented with right testicular swelling. Investigations revealed raised tumor markers and bilateral testicular lesions on scrotal USG. Bilateral orchidectomy with right hemiscrotectomy was done. Histopathology showed a right testicular mixed germ-cell tumor and a left testis seminoma. This case is being presented for its rarity.

Retroperitoneal hemorrhage complicating late recurrence of testicular mixed germ cell tumor

Late recurrence of testicular cancer is defined as recurrence 2 years after completion of treatment. The median time reported for this type of recurrence has been about 6 years. We report a case of hemorrhagic retroperitoneal recurrence 18 years post-treatment with description of the computed tomographic features.

Testicular mixed germ cell tumor metastasizing to skin as choriocarcinoma

Testicular mixed germ cell tumor metastasizing to skin as choriocarcinoma

Massive Upper Gastrointestinal Bleeding From Pure Metastatic Choriocarcinoma in Patient With Mixed Germ Cell Tumor With Subclinical Intestinal Metastasis

Although testicular germ cell tumors have become curable neoplasms, a better understanding of the clinicopathologic features is needed for the rare manifestations associated with treatment failure. We report a rare case of metastatic pure choriocarcinoma involving the small intestine arising from a testicular mixed germ cell tumor. In a patient who developed massive upper gastrointestinal hemorrhage during treatment, the intestinal metastases and focus of bleeding could only be determined by laparotomy. We propose an approach for the determination of subclinical intestinal metastases of testicular germ cell tumor; the case is discussed in light of similar reports in literature.