Intracaval and intracardiac metastatic nonseminomatous germ cell tumor: a rare cause of hemolytic anemia and thrombocytopenia

Intracaval and intracardiac nonseminomatous germ cell tumor metastases although rare have been previously reported in the literature. Most cases arise as a result of direct hematogenous spread via invasion of the internal spermatic vein, or from lymphatic venous shunting. We report a unique case of disseminated testicular germ cell tumor that presented with extensive intracaval and intracardiac metastatic teratoma and with valvular involvement. These findings were heralded by the presence of a new cardiac murmur, anemia, and severe thrombocytopenia. Resection of the intracardiac mass, prompted by rapid tumor progression despite treatment with systemic chemotherapy, demonstrated mature teratoma and resulted in prompt normalization of the patients hematologic profile.     

Mixed germ cell tumors with abundant sarcomatous component in the temporal lobe after radiochemotherapy of neurohypophyseal germinoma: a case report

We report a case of intracranial germ cell tumor that showed pathological changes from neurohypophyseal germinoma to mixed germ cell tumors consisting exclusively of undifferentiated sarcomatous component after radiochemotherapy. Three surgical specimens and autopsied brain from the patient were histologically examined. An initial specimen from the neurohypophyseal tumor was diagnosed as germinoma with a two-cell pattern. Five years later, after repeated radiochemotherapy, the second specimen resected from the right temporal lobe showed mixed germ cell tumors consisting of the three components of germinoma, choriocarcinoma, and immature teratoma. Six months later after intensive radiotherapy, the right temporal tumor recurred and was surgically removed. The histological diagnosis was mixed germ cell tumors with abundant immature teratoma component. The patient died of uncontrollable tumor growth with repeated intratumoral hemorrhages. The autopsied brain showed sarcoma with angionecrosis. This pathological alteration indicated an increase in the sarcomatous component after undergoing various treatments. We discuss the histological changes of intracranial germ cell tumor modified by treatment.     

Transformation of ovarian yolk sac tumor to immature teratoma following chemotherapy

The patient, a 28-year-old woman, in her ninth week of pregnancy, was operated on for stage Ia, mixed germ cell tumor (grade 3 immature teratoma + yolk sac tumor) of AFP decreased to the normal level. Eight months later, an intrapelvic mass and raised AFP were found. The extirpated recurrent tumor in the pouch of Douglas was a grade 2 immature teratoma with no yolk sac element. FAM chemotherapy was given again, and the patient is alive and well after taking oral UFT. As in testicular germ cell tumors, ovarian germ cell tumors can be converted to a more differentiated tumor following chemotherapy.     

Telomerase activity in germ cell cancers and mature teratomas.

BACKGROUND: An inverse relationship has been reported between the presence of telomerase enzymatic activity and the induction of differentiation in human tumor cell lines. Male germ cell tumors represent an attractive clinical model to assess this relationship further because high telomerase activity is present in normal germ cell progenitors and in embryonal carcinomas that can differentiate into mature teratomas. To investigate how telomerase activity and the differentiation state of germ cell tumors are related, telomerase activities and telomere lengths were measured in benign testicular tissues, germ cell cancers, and mature or immature teratomas. METHODS: By use of a modified telomeric repeat amplification protocol (TRAP) assay, telomerase activity was measured in four specimens of benign testicular tissue, in 27 germ cell cancers, in seven mature teratomas, and in one immature teratoma. Telomere lengths were measured in all specimens by restriction digestion of genomic DNA and Southern blot hybridization analysis. Associations between telomerase activity and tissue histopathology were assessed with two-sided Fisher's exact tests. RESULTS: Telomerase activity was detected in all examined germ cell cancers and in the benign testicular tissue specimens. In marked contrast, telomerase activity was not detected in any mature teratoma (P<.0001). Very long telomeres were detected in some mature teratomas, consistent with telomerase repression as a late event in teratoma formation. The immature teratoma, with malignant transformation, had high telomerase activity. CONCLUSION: Telomerase is active in germ cell cancers and repressed in mature teratomas. The absence of telomerase activity may contribute to the limited proliferative capacity of mature teratomas. These findings support the existence of an inverse relationship between telomerase activity and the differentiation state of clinical germ cell tumors.     

The first case of primary testicular germ cell tumor containing nephroblastoma as the only one non-germ cell component

Adult extrarenal nephroblastomas (Wilms' tumor) are extremely rare tumors. They show a higher incidence of non-seminomatous elements and these so-called 'teratoid' Wilms' tumors are suggested to be of germ cell origin. To date, however, the number of reported cases with gonadal teratoma containing nephroblastoma is very low, and due to this reason, there are no standardized criteria for the categorization and treatment of these lesions. To our knowledge, the first case of nephroblastoma arising in a non-atrophic testis has been reported and it is associated with a teratoma as morphologically identifiable germ cell tumor and rhabdomyosarcoma as a second non-germ cell element. We report the second case of an adult nephroblastoma that arose within the primary testicular teratoma in a non-atrophic testis. Teratoma and nephroblastoma within the same testis may have an important point to clarify the developmental mechanism in nephroblastomatous differentiation of germ cell tumors.     

Vincristine, dactinomycin, and cyclophosphamide in the treatment of malignant germ cell tumors of the ovary. A Gynecologic Oncology Group Study (a final report)

Seventy-six patients with malignant germ cell tumors of the ovary received vincristine, dactinomycin, and cyclophosphamide (VAC) postoperatively. Fifty-four were treated after removal of all gross disease. The majority of these remain disease-free. Indeed, only 15 (28%) have failed, including 11 of 24 with pure endodermal sinus tumor, 3 of 11 (27%) with mixed germ cell tumor containing endodermal sinus elements, and only 1 of 20 with immature teratoma grade 2 or 3, a patient seen initially with recurrent disease. Postoperative VAC therapy, however, did not appear to be effective in patients with unresectable or incompletely resected germ cell tumors of the ovary. Fifteen of 22 patients (68%) with incompletely resected germ cell tumors failed VAC therapy, including 4 of 7 with pure endodermal sinus tumor, 5 of 5 with mixed germ cell tumors containing endodermal sinus elements, 2 of 2 with embryonal carcinoma, and 4 of 8 with immature teratoma. In failing, patients' median time to progression was 8 months. Dose-limiting toxicity was seen in 30% of the entire group. Combined cisplatin, vinblastine and bleomycin therapy now is being tested in this group of tumors.     

Recurrence of a germ cell tumor 12 years after initial treatment: a case report

Patients with testicular germ cell tumors who have disease-free remission for more than 2 years are usually considered to be cured of their disease. This report describes a case of a germ cell tumor recurring 12 years after initial diagnosis and its treatment in a 35-year-old man who developed a retroperitoneal mass adhering to the abdominal aorta with a bout of severe colic in the left flank. Although tumor markers were not elevated and histology of the biopsy specimen was initially diagnosed as adenocarcinoma, we finally concluded that the retroperitoneal tumor was teratoma developing as a recurrence of the germ cell tumor for the following reasons: (1) the histology of the specimen was similar to an epithelial component of teratoma found in the tissue resected 12 years before; (2) systemic survey failed to detect any other primary site; (3) the young age of this patient was consistent with germ cell tumor rather than adenocarcinoma; and (4) the retroperitoneum is the most frequent site of late recurrences of testicular cancer. He was treated successfully with combination chemotherapy of cisplatin, etoposide and bleomycin followed by surgery. It is important to differentiate this treatable disease from metastasis from an unknown primary, because the latter responds poorly to therapy and survival is usually short.      

Intracranial growing teratoma syndrome (iGTS): an international case series and review of the literature

Journal of Neuro-Oncology - Intracranial growing teratoma syndrome (iGTS) is a rare phenomenon of paradoxical growth of a germ cell tumor (GCT) during treatment despite normalization of tumor...     

Germ cell origin of testicular carcinoid tumors.

PURPOSE: Carcinoids are neuroendocrine tumors and most frequently occur within tissues derived from the embryonic gut. These tumors can occur in any organ site but are rare in the testis. The cell type giving rise to testicular carcinoid is unknown. We hypothesized that testicular carcinoid may have a germ cell origin. EXPERIMENTAL DESIGN: We describe our analysis of protein and genetic markers of germ cell neoplasia, using immunohistochemistry and fluorescence in situ hybridization, in four testicular carcinoid tumors. RESULTS: All four cases of testicular carcinoid tumor arose in a background of mature teratoma. Isochromosome 12p was identified in carcinoid tumor cells in all four samples. 12p overrepresentation was also observed in three cases. Isochromosome 12p and 12p overrepresentation were present in cells of coexisting mature teratoma in three cases. Carcinoid tumors showed strong immunoreactivity for synaptophysin and chromogranin, but no immunoreactivity for OCT4, CD30, c-kit, TTF-1, and CDX2. Membranous and cytoplasmic staining for beta-catenin was detected in three cases. CONCLUSION: Our findings suggest that testicular carcinoid represents a phenotypic expression of testicular teratoma and is of germ cell origin.     

Primary mediastinal germ cell tumors. Histologic patterns of treatment failures at autopsy

Twenty-five patients presented with primary mediastinal germ cell tumors at Roswell Park Memorial Institute between 1959 and 1984. All patients were treated by surgery and chemotherapy with or without radiotherapy. Four patients are still alive, and 21 patients died of mediastinal germ cell tumor and its sequelae. Two patients were found to have testicular scars and were dropped from the study. Nongerm cell malignant transformation of a teratoma occurred in five of the remaining 17 patients (29%), resulting in three adenocarcinomas and two sarcomas. Another patient developed leukemia. Metastatic disease most commonly involved the lungs, mediastinal lymph nodes, liver, bone, retroperitoneum, and heart. Respiratory failure was the cause of death in 12 patients. Of the possible mechanisms of germ cell transformation into malignant nongerm cell tumors discussed, this study suggests that chemotherapy alone is unlikely to induce stem cell differentiation. The presence of mature, differentiated teratoma within the primary lesion may be indicative of a poorer prognosis.     

Three cases of primary lung and mediastinal malignant germ cell tumors --clinical and pathological studies

This is a clinical and pathological study of malignant germ tumors in the lung or mediastinum. Germ cell tumors may be considered to originate from primitive germ cells with totipotency. One of 3 cases showed clinical and pathological findings suggesting that a part of the tumor differentiated into many kinds of tissue, such as growing and metastasizing. Initial diagnosis was performed radiographically and pathologically with difficulty. But finally, the first patient was diagnosed as malignant teratoma, the second as yolk sac tumor and the third as choriocarcinoma, in consideration of the tumor markers and clinical process.     

Neuroendocrine Tumor Arising within Mature Cystic Teratoma of the Pancreas: Literature Review and Case Report

Cystic teratomas are germ cell tumors most commonly found in the ovaries and testes. The pancreas, however, is very rare as a site of occurrence. Moreover, only two cases of cystic teratoma with concomitant neuroendocrine tumor have been reported to date. We report the case of a 33-year-old female who presented with abdominal pain. Computed tomography and magnetic resonance imaging of the upper abdomen revealed an 85 mm cystic tumor in the head of the pancreas. Cystic teratoma and mucinous cystadenoma were suggested as differential diagnoses. Cytopathologic analysis of endoscopic ultrasound-guided fine needle aspiration was consistent with mucinous cystadenoma. Therefore, the patient underwent surgical resection. Histologic analysis revealed a mature cystic teratoma of the pancreas with a concomitant neuroendocrine tumor. The patient is in great condition at 8 months follow-up. Cystic teratoma of the pancreas with a concomitant neuroendocrine tumor is an extremely rare condition. Surgical resection remains the mainstay of treatment as it provides a definitive diagnosis and no recurrences have been reported to date.     

Growing Teratoma Syndrome of the Ovary Showing Three Patterns of Metastasis: A Case Report

Growing teratoma syndrome (GTS) is defined as metastatic masses during or after chemotherapy for germ cell tumors, which contain only mature teratoma components. The peritoneum of the pelvis and abdomen and the retroperitoneum are the most frequent sites of metastasis. We report a case of GTS of the ovary showing three patterns of metastasis: dissemination, lymphogenous metastasis, and hematogenous metastasis. The patient initially presented 5 years ago with a mixed germ cell tumor of the left ovary and positive cytology of ascites. After surgery and chemotherapy, mature teratomas recurred as pelvic peritoneal dissemination, a para-aortic lymph node mass, and a lung mass. Our case highlights the importance of long-term follow-up and a whole-body search. We think that our case is suggestive regarding the mechanism of critical GTS.Key Words: Growing teratoma syndrome, Immature teratoma, Three patterns of metastasis     

Glutathione sulfhydryl transferase-pi expression in testicular germ-cell tumors - an immunohistochemical study of 30 cases

Glutathione sulfhydryl transferase (GST) is believed to play a major role in the detoxification of chemotherapeutic agents and therefore is thought to be important in chemoresistance. Thirty primary testicular germ cell tumors were stained immunohistochemically for GST pi using a rabbit polyclonal antibody and formalin-fixed paraffin-embedded tissue. There were 12 pure seminomas and 18 mixed germ cell tumors (GCTs). Immunostaining of each element present was graded as negative (-), weakly positive (+), or strongly positive (++). The results were as follows: seminoma (8/17 +, 9/17 ++); embryonal carcinoma (1/13 -, 7/13 +, 5/13 ++); mature teratoma (9/9 ++); immature teratoma (7/7 +); endodermal sinus tumor (7/8 +, 1/8 ++); and choriocarcinoma (1/1 -). These results show that variability exists in the expression of GST pi between different tumor types and between different examples of the same tumor type. Strongest expression was seen in seminomas and mature teratomas while other germ cell elements tended to show weaker staining. The staining patterns showed no apparent correlation with stage or response to therapy.     

Long-term survival and morbidity in patients with metastatic malignant germ cell tumors treated with cisplatin-based combination chemotherapy

Forty-three of 79 patients treated for clinically metastatic germ cell cancer survived for a median of 66 months (range, 52-83). In patients without previous chemotherapy the 5-year survival rate was 69%, whereas only 32% of patients with prior chemotherapy survived for 5 years. Limited disease, complete clinical response, histopathologically proven postchemotherapy tumor necrosis or complete resectability of a posttreatment mature teratoma indicated a favorable prognosis in patients without prior chemotherapy. Only 20% to 30% of the patients with less than a clinical complete response or with posttreatment residual malignant tumor can be salvaged by second line therapy. Posttreatment mature teratoma should be resected completely whenever possible, as this condition may lead to reactivation of the malignancy even after several years. Raynaud-like phenomena and/or gastrointestinal problems are the main long-term sequel (10%-15%) after modern multimodality treatment of advanced germ cell cancer (fertility-related problems are not considered here). In the majority of surviving patients, the lifestyle seems unaffected by the previous intensive treatment, evaluated about 5 years after discontinuation of all therapy.     

Sarcoma arising in a residual testicular teratoma after cytoreductive chemotherapy

A case of testicular teratoma metastasized to the retroperitoneum and after cytoreductive chemotherapy was noted to contain areas of frank sarcoma. Sarcomatous areas included embryonal rhabdomyosarcoma with a pattern of sarcoma botyroides, alveolar rhabdomyosarcoma, and fibrosarcoma. These areas differed markedly from areas of immature teratoma, which composed the remainder of the retroperitoneal lesion and which also characterized the primary tumor. These sarcomatous areas were characterized by numerous mitoses, marked cellular pleomorphism and diagnostic histologic, ultrastructural, and immunocytochemical features. Residual germ cell tumors following cytoreductive chemotherapy are traditionally categorized as teratoma only or teratoma with embryonal carcinoma or choriocarcinoma for therapeutic and prognostic reasons. This case does not conform to this simple categorization and raises serious questions concerning subsequent therapeutic decisions.     

Expression of a specific mouse germ cell nuclear antigen (GCNA1) by early embryonic testicular teratoma cells in 129/Sv-Sl/+ mice

Spontaneous testicular teratomas which develop at a high rate in 129/Sv-Sl/+ mice are thought to be derived from germ cells. The teratomas present initially as groups of atypical germ-like cells within seminiferous cords of the 15.5 days post coitum (dpc) embryonic testes. These pluripotent teratoma stem cells are capable of differentiating into many kinds of tissues in adult mice. In this immunohistochemical study, we have examined the testes of 129/Sv-Sl/+ mice to determine whether the teratoma cells which developed in these gonads retain the nuclear antigen GCNA1. GCNA1 is a 110 kDa mouse Germ Cell Nuclear Antigen recognized by a rat monoclonal antibody 10D9G11. GCNA1 is expressed in mouse germ cells after they migrate into the genital ridge (11.5 dpc), throughout embryonic development until postnatally germ cells arrive at the diplotene/dictyate stage of the first meiotic division, when it is no longer expressed. Early foci (16.5 dpc) of teratoma stem cells in 129/Sv-Sl/+ mice strongly express GCNA1, but down regulate GCNA1 expression by 19.5 dpc. The loss of GCNA1 expression from teratoma stem cells late in embryonic development is in contrast to embryonic gonocytes which retain GCNA1 expression throughout fetal development. All postnatal undifferentiated and differentiated teratoma cells did not appear to express GCNA1. The expression of the germ cell specific nuclear antigen GCNA1 in early teratoma stem cells further demonstrated that the testicular teratomas originate from early germ cells. The stronger reaction of monoclonal antibody 10D9G11 to GCNA1 within early teratoma cells compared to normal germ cells makes GCNA1 useful in identifying early embryonic tumor foci.     

Ovarian tumor complicated by a colo-ovarian fistula

Although a fistula is a rare complication of ovarian tumor, we encountered four patients with cole-ovarian fistulas in three years. The first case was demonstrated by following barium enema by the extravasation of barium from the sigmoid colon, and by a gas-containing lesion in the tumor observed on computed tomography. Mature cystic teratoma was the pathological diagnosis in two cases. A mixed germ cell tumor and a serous cystadenoma of low malignant potential were diagnosed in the other two cases. The etiology and differential diagnosis of cole-ovarian fistula are reviewed.     

Correlation of endoscopic biopsy with tumor marker status in primary intracranial germ cell tumors

Summary We retrospectively analyzed the results of eight patients who underwent endoscopic biopsy of a newly diagnosed primary intracranial germ cell tumor (GCT), and correlated tumor pathology with serum and cerebrospinal fluid (CSF) tumor markers and treatment outcome in order to determine the reliability of GCT sampling by this method. A biopsy diagnosis was made in each patient, and the tumor histology correlated with tumor marker measurements for all six patients diagnosed with germinoma and for one with a yolk sac tumor. One biopsy revealed only mature teratoma, an inconclusive result since the patient’s serum and CSF tumor markers were elevated. No morbidity was experienced as a result of the operative procedure. Five of six patients diagnosed with germinoma responded completely to radiation therapy and are without evidence of disease, while one suffered a likely germinoma recurrence and was subsequently successfully retreated. We conclude that endoscopic biopsy of marker-negative germ cell tumors is a safe, reliable method of establishing a diagnosis of germinoma. However, endoscopic biopsy may fail to yield an accurate diagnosis in cases of malignant non-germinomatous tumor. We would thus conclude that when primary germ cell tumor is considered, endoscopic tumor biopsy is recommended in patients with a negative biochemical analysis, but not suggested for patients presenting with elevated tumor markers.