Between 2% and 5% of malignant germ-cell tumors in men arise at extragonadal sites. Of extragonadal germ cell tumors, testicular carcinoma in situ (CIS) are present in 31–42% of cases, and CIS are reported to have low sensitivity to chemotherapy in spite of the various morphology and to have a high likelihood of developing into testicular tumors. A testicular biopsy may thus be highly advisable when evaluating an extragonadal germ cell tumor.
A 36-year-old man was diagnosed as having an extragonadal non-seminomatous germ cell tumor, that was treated by cisplatin-based chemotherapy, leading to a complete remission. In the meantime, testicular tumors were not detected by means of ultrasonography. About 4 years later, a right testicular tumor was found, and orchiectomy was carried out. Microscopically, the tumor was composed of seminoma.
We herein report a case of metachronous occurrence of an extragonadal and gonadal germ cell tumor. In the evaluation of an extragonadal germ cell tumor, a histological examination should be included since ultrasonography is not sufficient to detect CIS or minute lesions of the testis.
Pediatric germ cell tumors (GCT) are rare tumors: 80% are benign, 20% malignant (2-3% of all malignant pediatric tumors). The gonadal sites (ovary and testis) account for 40% of cases.
Represent 30% of GCTs and 70% of neoplastic ovarian masses, being the most common ovarian neoplasms in children and teenagers. Benign and immature forms (teratomas) constitute about 80% of all ovarian GCTs, malignant forms represent 20% increasing during adolescence. The most common malignant entity in children is the yolk sac tumors (YST); dysgerminoma is frequent during adolescence and being bilateral in 10% of cases. Presentation is similar in malignant and benign lesions; abdominal pain (70-80%) and lower abdominal mass are common symptoms. Evaluation of alpha-fetoprotein (αFP) or beta subunit of human chorionic gonadotropin (βHCG) is essential to address the nature of the tumors: Their elevation means presence of malignancy. Surgery includes intraoperative staging procedures and requires ovariectomy or ovarosalpingectomy for malignant lesions, but may be conservative in selected benign tumors. Since malignant GCTs are very chemosensitive, primary chemotherapy is recommended in metastatic or locally advanced tumors.
Represent 10% of pediatric GCT, and about 30% of malignant GCT with two age peaks: Children <3 years may experience mature teratoma and malignant GCTs, represented almost exclusively by YST, while adolescents may also show seminomas or other mixed tumors. The main clinical feature is a painless scrotal mass. Surgery represents the cornerstone of the management of testicular GCTs, with an inguinal approach and a primary high orchidectomy for malignant tumors, while a testis-sparing surgery can be considered for benign lesions. A retroperitoneal lymph node (LN) biopsy may be necessary to define the staging when the involvement of retroperitoneal LN is uncertain at imaging investigations.
Patients with gonadal malignant GCTs fare better than those with extragonadal mediastinal germ cell tumors (MGCTs) and survival rate exceeds 90% in localized forms. Chemotherapy has significantly improved the outcome of malignant forms since the introduction of platinum based regimens. The surgical procedure has to be performed in agreement with the ongoing protocols.
Children; germ cell tumors; gonadal
While testicular germ cell tumors (TGCTs) are the most common malignancy in young men, germ cell tumors in women are uncommon. Familial clustering, epidemiologic evidence of increased risk with family or personal history of TGCT, and associations with genitourinary tract anomalies suggest an underlying genetic predisposition to TGCT, but traditional linkage studies have yet to identify a highlypenetrant TGCT cancer susceptibility gene. In this paper, we investigate the familial occurrence of testicular and ovarian germ cell tumors.
We report a family in which a TGCT and an ovarian germ cell tumor (OGCT) occurred in two siblings, summarize the existing literature on familial occurrences of OGCT, either alone or in combination with extragonadal or TGCTs, and compare the incidence of familial and sporadic testicular and ovarian GCTs. Sporadic GCT data were obtained from the US Surveillance Epidemiology and End Results (SEER) registry.
We identified 16 reports of OGCT occurring in conjunction with either ovarian, testicular or extragonadal GCT. In these familial cases, the mean age at onset of female dysgerminoma was younger than that noted in the general population (age 17 vs age 24, p=0.01). In SEER, the incidence of TGCT was 15 times higher than that of OGCT. Histologic distributions in males and females showed distinctly different patterns.
Although the incidence of OGCTs in the general population is quite low, its occurrence in multiple members of the same family and in families with TGCT suggests that a gene conferring susceptibility to GCTs may exist in some families.
ovarian germ cell tumor; familial; epidemiology; testicular germ cell tumor; genetic predisposition; SEER
Seminomatous and non-seminomatous Germ Cell Tumors (GCT) of the testis are a rare cancer, with an estimated incidence of 56.3 per million white males and 10 per million black males in the United States.
The association between non-seminomatous GCT and horseshoe kidney is a rare event and is seen in about 1.3% of patients requiring retroperitoneal lymph node dissection. To our knowledge, no cases have been reported in which replacement of the IVC was also necessary.
We report the case of a 22-year-old man with horseshoe kidney and metastatic non-seminomatous germ cell tumor involving the wall of the inferior vena cava.
Following post-chemotherapy retroperitonal lymph node dissection, the inferior vena cava was replaced with an expanded polytetrafluoroethylene graft.
At 2-years follow-up, the patient was in good health and the graft was patent. No clinical or diagnostic signs of renal impairment or recurrence of neoplastic disease were noted.
Radical surgery is warranted in patients with non-seminomatous germ cell tumor metastasizing to the retroperitoneal lymph nodes. When vena cava replacement is required, and the situation is further complicated by horseshoe kidney, as in this case, surgical technique will rely on multidisciplinary surgical treatment planning by a team composed of urologists, vascular surgeons and oncologists.
Testis; Neoplasm GCT; PTFE
About 3 – 5% of all patients with testicular germ cell tumour (GCT) develop a contralateral cancer, the majority of which arise within 10–15 years. Little is known about the risk of second GCTs after more than two decades. Here we present 3 cases with very late presenting contralateral GCT and provide a summary of similar cases reported previously.
(1) This white Caucasian man underwent right-sided orchiectomy for a nonseminomatous GCT at the age of 22 years. Additional treatment consisted of retroperitoneal lymph node dissection (RPLND) and chemotherapy with 4 cycles of vinblastin / bleomycin. 36 years later, contralateral seminoma clinical stage 1 developed. Cure was achieved by orchiectomy. Histologically, testicular intraepithelial neoplasia (TIN; intratubular germ cell neoplasia) was detected in the tumour-surrounding tissue.
(2) This white Caucasian male had right-sided orchiectomy for nonseminomatous GCT at the age of 29 years. Pathological stage 1 was confirmed by RPLND. 25 years later, he received left sided orchiectomy for seminoma stage 1. Histologically, TIN was found in the tissue adjacent to seminoma. Two brothers had testicular GCT, too, one with bilateral GCT. (3) This 21 year old white Caucasian man underwent left-sided orchiectomy for nonseminomatous GCT. Pathological stage 1 was confirmed by RPLND. 21 years later, he received organ-preserving excision of a right-sided seminoma, followed by BEP chemotherapy for stage 3 disease. Histologically, TIN was found in the surrounding testicular tissue.
22 cases of bilateral GCT with intervals of 20 or more years have previously been reported, thereof three with intervals of more than 30 years, the longest interval being 40 years.
Apart from increased risks of cardiovascular diseases and non-testicular malignancies, patients with GCT face the specific probability of a second GCT in the long run. This risk persists life-long and is not eliminated by chemotherapy. Contralateral testicular biopsy can identify patients at risk by revealing precursor cells of GCT though false-negative biopsies may occur sporadically. However, in view of the multi-facetted late hazards of GCT patients, this minor surgical procedure might somewhat simplify the long-time care of these patients.
Testicular germ cell neoplasms; Bilateral tumours; Testicular biopsy; Seminoma; Familial germ cell tumours
Giant cell tumor (GCT) is usually a benign but locally aggressive primary bone neoplasm in which monocytic macrophage/osteoclast precursor cells and multinucleated osteoclast-like giant cells infiltrate the tumor. The etiology of GCT is unknown, however the tumor cells of GCT have been reported to produce chemoattractants that can attract osteoclasts and osteoclast precursors. Rarely, GCT can originate at extraosseous sites. More rarely, GCT may exhibit a much more aggressive phenotype. The role of chemotherapy in metastatic GCT is not well defined.
We report a case of an aggressive GCT of the uterus with rapidly growing lung metastases, and its response to chemotherapy with pegylated-liposomal doxorubicin, ifosfamide, and bevacizumab, along with a review of the literature.
Aggressive metastasizing GCT may arise in the uterus, and may respond to combination chemotherapy.
Tumour lysis syndrome (TLS) and choriocarcinoma syndrome (CS) are severe complications of chemotherapy for testicular cancer. They are rare, but can be life-threatening. A 37-year-old man complaining of persisting cough was referred to our hospital. A computed tomography (CT) scan revealed huge tumours that occupied the peritoneal cavity, with multiple lung, liver, and para-aortic metastases. Although there was no abnormal finding in the testes, serum testicular tumor markers showed marked elevation. A CT-guided biopsy for the peritoneal tumours revealed extragonadal germ cell tumour (GCT), including yolk sac tumour and choriocarcinoma. Chemotherapy with bleomycin, etoposide, and cisplatin (BEP) was started after admission. The morning after the beginning of BEP, the patient developed hemorrhagic shock, in addition to acute pulmonary and renal failure, because of TLS and massive hemorrhage at bilateral lung metastases. He was intubated and resuscitated. Despite appropriate therapy, his renal function did not recover and hemodialysis was started. The patient eventually died of severe respiratory distress syndrome and infection. To our knowledge, this is the first case report of TLS and CS as complications of hemorrhage at the lung metastases of advanced testicular cancer leading to death.
We previously reported a dose-finding and phase II trial of the TI-CE regimen (paclitaxel [T] plus ifosfamide [I] followed by high-dose carboplatin [C] plus etoposide [E] with stem-cell support) in germ cell tumor (GCT) patients predicted to have a poor prognosis with conventional-dose salvage therapy. We now report the efficacy of TI-CE with prognostic factors for disease-free survival (DFS) and overall survival (OS) in our full data set of 107 patients.
Patients and Methods
Eligible patients had advanced GCTs with progressive disease following chemotherapy and unfavorable prognostic features (extragonadal primary site, incomplete response [IR] to first-line therapy, or relapse/IR to ifosfamide-cisplatin–based conventional-dose salvage). Univariate and multivariate analyses (MVAs) of prognostic factors were performed. The predictive ability of the Einhorn and Beyer prognostic models was assessed.
Most patients were platinum refractory and had an IR to first-line chemotherapy. There were 54 (5%) complete and eight (8%) partial responses with negative markers; 5-year DFS was 47% and OS was 52% (median follow-up, 61 months). No relapses occurred after 2 years. Five (24%) of 21 primary mediastinal nonseminomatous GCTs are continuously disease free. On MVA, primary mediastinal site (P < .001), two or more lines of prior therapy (P < .001), baseline human chorionic gonadotropin ≥ 1,000 U/L (P = .01), and lung metastases (P = .02) significantly predicted adverse DFS. Poor-risk patients did worse than good- or intermediate-risk patients according to both Beyer (P < .002) and Einhorn (P < .05) models.
TI-CE is effective salvage therapy for GCT patients with poor prognostic features. Mediastinal primary site and two or more lines of prior therapy were most predictive of adverse DFS. Beyer and Einhorn models can assist in predicting outcome.
To review the experience with the diagnosis and management of extragonadal germ cell tumors (GCT) with a subset analysis of those with atypical features.
Materials and Methods:
A retrospective chart review of patients of extragonadal germ cell tumors between 2000 and 2010 was carried out.
Fifteen children aged 7 days to 15 years (median, 1.5 years) were included. Three had an antenatal diagnosis (one sacrococcygeal, one retrobulbar, one retroperitoneal tumor) and were operated in the neonatal period. The locations were distributed between the retrobulbar area (1), anterior neck-thyroid gland (1), mediastinum (4), abdominothoracic extending through the esophageal hiatus (1), retroperitoneal (4) and sacrococcygeal (4). On histological examination, five harbored immature elements while two were malignant; the latter children received postexcision adjuvant chemotherapy. There was no mortality. At a median follow-up of 4.5 years (6 months to 8 years), 14/15 have had an event-free survival. One immature mediastinal teratoma that recurred locally 7.5 years after the initial operation was excised and adjuvant chemotherapy instituted.
Extragonadal GCTs in children are uncommon and occasionally present with atypical clinical, radiological and histological features resulting in diagnostic and therapeutic dilemmas.
Extragonadal; germ cell tumor; atypical
•5% of extragonadal germ cell tumours are currently considered to be of primary retroperitoneal origin.•Retroperitoneal EGGCTs are assumed to a poor prognosis group even if they fulfill the IGCCCG criteria for good, or intermediate prognosis.•The combination of radical surgery and chemotherapy may prolong disease-free survival even in a second- or third-line treatment.
Primary retroperitoneal extragonadal tumours relapsing after initial chemotherapy have a poor prognosis.
Presentation of the case
We report a case of primary retroperitoneal embryonal carcinoma in a patient with negative open testes biopsy. After the first line of chemotherapy (4 cycles BEP) secondary surgery with extirpation of a retroperitoneal residual mass was performed. The residuum proved histologically to be a mature teratoma, and no adjuvant treatment was given according to current recommendations. The patient had regular follow-up. 3.5 years later, patient developed recurrence in the ipsilateral adrenal gland, which was treated with surgery and 4 cycles of salvage VeIP chemotherapy. Seven months after the second surgical intervention the patient underwent multivisceral “desperation surgery” for early metastatic disease progression followed by 2 cycles of salvage TIP chemotherapy. The patient is currently disease-free at 34 months.
Initial postchemotherapy retroperitoneal lymph node dissection is crucial for local retroperitoneal disease control. Aggressively treated metastatic recurrent disease does not preclude prolonged survival. Despite a generally poor prognosis, repeated complex oncosurgical therapy for retroperitoneal extragonadal tumours may be worthwhile.
GGCT, gonadal germ cell tumour; EGGCT, extragonadal germ cell tumour; IGCCCG, International Germ Cell Cancer Collaborative Group; MDT, multidisciplinary team; BEP chemotherapy, chemotherapy with bleomycin, etoposid and cisplatin; G-CSF prophylaxis, granulocyte-colony stimulating factor profylaxis; VeIP chemotherapy, chemotherapy with vinblastine, ifosfamide and cisplatin; TIP chemotherapy, chemotherapy with paclitaxel, ifosfamid and cisplatin; EORTC, European Organisation for Research and Treatment of Cancer; PET/CT, positron emission tomography–computed tomography; RPLND, retroperitoneal lymphadenectomy; Germ cell tumour; Extragonadal; Relapse; Recurrence; Surgery; Adjuvant therapy
We retrospectively evaluated long-term oncological outcomes in patients with germ cell tumors (GCTs) primarily treated at our institution and assessed late recurrence and second primary malignancies.
This study included a total of 139 males with newly diagnosed GCTs of the testis or extragonadal origin who received treatment, including surgery, chemotherapy and radiation therapy, at our hospital between 1980 and 2005. We reviewed late recurrence that occurred at least 2 years after the initial disease-free status and secondary malignancies as well as oncological outcomes.
In patients with seminoma, 5-year progression-free survival and cause-specific survival rates were 87.2% and 100% for Stage I, 88.9% and 100% for Stage II, and 50.0% and 50.0% for Stage III, respectively, whereas in those with non-seminomatous GCTs, they were 79.1% and 96.3% for Stage I, 89.5% and 89.4% for Stage II, and 85.7% and 78.4% for Stage III, respectively. Late recurrence was found in five (3.6%) patients and all of them responded to salvage treatment and achieved disease-free status. Second primary hematological neoplasms occurred in three (2.2%), although they had a long-term free of the primary disease. All died of the second primary disease.
Late recurrence was successfully managed with appropriate treatments, although its incidence was not negligible. Periodic follow-up may be necessary for >5 years in patients with GCTs for early detection of late recurrence. In addition, care should be taken to watch for the development of life-threatening second primary malignant disease during long-term follow-up.
urology; urologic-med; urologic-radOncol
Of 297 patients with metastatic testicular and extragonadal germ cell tumours (GCT), bone involvement was detected clinically in 3% (7/251) of those at first presentation and in 9% (4/46) of relapsed cases. This difference was not statistically significant (95% confidence limits -2%; +14%). Concurrent systemic metastases, commonly involving lung (7/11 cases) and para-aortic lymph nodes (6/11), were present in all patients with bone disease. All affected patients had localized bone pain and lumbar spine was the most frequent site involved (9/11). Spinal cord compression occurred in two patients while a third developed progressive vertebral collapse after chemotherapy and required extensive surgical reconstruction. At median follow-up of 4 years, survival among patients presenting with bone disease (6/7) was similar to overall survival in the whole group (84%) and appeared better than in those with liver (18/26, 69%) or central nervous system (6/9) metastases at presentation. Back pain in metastatic germ cell tumours is often due to retroperitoneal lymphadenopathy but lumbar spine osseus metastases must be recognized early if severe potential complications, such as spinal cord compression, are to be avoided. In this series, bone metastases were not seen in the absence of widespread systemic disease suggesting all solitary bony lesions in GCT patients should be biopsied.
Evaluation of utility of fluorine-18 fludeoxyglucose (18F-FDG) positron emission tomography/CT (PET/CT) for restaging patients with primary malignant germ cell tumours (GCTs).
Data of 92 patients (age, 31.94 ± 10.1 years; male/female, 86/6) with histopathologically confirmed malignant GCTs (gonadal, 88; mediastinal, 4; seminomatous, 47 and non-seminomatous, 45) who underwent 18F-FDG PET/CT for restaging (suspected recurrence/post-therapy evaluation) were retrospectively analysed. Two experienced nuclear medicine physicians reviewed the PET/CT images in consensus, qualitatively and semi-quantitatively [maximum standardized uptake value (SUVmax)]. Histopathology (if available) and clinical/imaging/biochemical follow-up (minimum of 6 months) were employed as the reference standard.
18F-FDG PET/CT was interpreted as positive in 59 and negative in 33 patients. Local disease was seen in 5, nodal disease in 50 and distant metastasis in 22 patients. PET/CT was true positive in 49, false positive in 10, true negative in 30 and false negative in 3 patients. 18F-FDG PET/CT showed sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 94.2%, 75.0%, 83.0%, 90.9% and 85.8% overall; 90.0%, 74.0%, 72.0%, 90.9% and 80.8% in seminomatous GCT; and 96.8%, 76.9%, 91.1%, 90.9% and 91.1% in non-seminomatous GCT, respectively. Difference in PET/CT accuracy for seminomatous and non-seminomatous GCTs was not significant (p = 0.263). PET/CT demonstrated disease in 13 patients with negative/equivocal conventional imaging findings and in 9 patients with normal tumour markers. No site- or histology-based difference was seen in SUVmax.
18F-FDG PET/CT demonstrates high diagnostic accuracy for restaging patients with malignant GCTs. It has comparable diagnostic performance in both seminomatous and non-seminomatous malignant GCTs.
Advances in knowledge:
The present article demonstrates high diagnostic accuracy of 18F-FDG PET/CT for restaging both seminomatous and non-seminomatous malignant GCTs in a large patient population.
We reviewed the European Group for Blood and Marrow Transplantation (EBMT) experience with salvage high-dose chemotherapy (HDC) in paediatric patients with extragonadal germ-cell tumour (GCT). A total of 23 children with extragonadal GCT, median age 12 years (range 1–20), were treated with salvage HDC with haematopoietic progenitor cell support. The GCT primary location was intracranial site in nine cases, sacrococcyx in eight, retroperitoneum in four, and mediastinum in two. In all, 22 patients had a nongerminomatous GCT and one germinoma. Nine patients received HDC in first- and 14 in second- or third-relapse situation. No toxic deaths occurred. Overall, 16 of 23 patients (70%) achieved a complete remission. With a median follow-up of 66 months (range 31–173 months), 10 (43%) are continuously disease-free. Of six patients who had a disease recurrence after HDC, one achieved a disease-free status with surgical resection followed by chemotherapy and radiotherapy. In total, 11 patients (48%) are currently disease-free. Eight of 14 patients (57%) with extracranial primary and three of nine patients (33%) with intracranial primary GCT are currently disease-free. HDC induced impressive long-term remissions as salvage treatment in children with extragonadal extracranial GCTs. Salvage HDC should be investigated in prospective trials in these patients.
extragonadal germ cell tumour; high-dose chemotherapy; salvage therapy; children
Most bone tumors that occur in the clavicle are malignant. A few giant cell tumors (GCTs) of the clavicle have been reported; however, the most appropriate operative method for this tumor has never been discussed.
A 54-year-old man noticed enlargement of the proximal aspect of the right clavicle. A plain X-ray revealed lytic change and ballooning of the proximal end of the right clavicle. The tumor was isointense on T1-weighted magnetic resonance images and showed a mixture of low- and high-intensity areas on T2-weighted images without extension to the surrounding soft tissues. Bone scintigraphy showed strong accumulation (normal/tumor ratio, 2.31), and positron emission tomography revealed strong uptake of fluorine-18-2-fluoro-2-deoxy-d-glucose (SUVmax, 6.0) in the proximal part of the right clavicle. Because we could not completely exclude malignancy, an open biopsy was performed. Pathologically, the tumor comprised mononuclear stromal cells and multinuclear giant cells, resulting in a diagnosis of a GCT of the bone. Although curettage may be considered for such lesions (Campanacci grade II), we chose resection to minimize the chance of recurrence. The tumor was resected en-bloc with the proximal half of the clavicle. No postoperative shoulder disproportion was observed, and full range of motion of the right shoulder was maintained. The patient was satisfied with the surgical outcome (Musculoskeletal Tumor Society score of 96 %). He returned to his original job as a land and house investigator without any signs of recurrence for 1 year after surgery.
Although GCT of the bone rarely occurs in the clavicle, the typical X-ray findings demonstrated in the present case are helpful for a correct diagnosis. Although en-bloc resection without reconstruction is appropriate for GCTs in expendable bones, there has been much discussion about shoulder function after total claviculectomy. Considering the importance of the function of the clavicle, which is to support the scapula through the acromioclavicular joint, we preserved the muscle attachments of the deltoid, trapezius, and pectoralis major. Because both the oncological and functional outcomes were satisfactory, we recommend preservation of as much of the clavicle as possible in patients with clavicular bone tumors.
Giant cell tumor; Claviculectomy; Pathology; Shoulder function
Testicular tumors are a heterogeneous group of neoplasms exhibiting diverse histopathology and can be classified as seminomatous and non-seminomatous germ cell tumor types. Mixed germ cell tumors contain more than one germ cell component and various combinations have been reported. Here, we present a rare case of a mixed germ cell tumor composed of seminoma, choriocarcinoma and teratoma with a secondary somatic malignancy.
A 31-year-old Caucasian man presented with splenic rupture to our hospital. A right-sided testicular swelling had been present for 6 months and his alpha-fetoprotein, beta-human chorionic gonadotropin, and lactose dehydrogenase were increased. An ultrasound of his scrotum revealed an enlarged right testis with heterogeneous echogenicity. Multiple hypervascular lesions were noted in his liver and spleen. He underwent transcatheter embolization therapy of his splenic artery followed by splenectomy and right-sided orchiectomy. A computed tomography scan also showed metastasis to both lungs. During his last follow up after four cycles of cisplatin-based chemotherapy, the level of tumor markers had decreased, decreases in the size of his liver and pulmonary lesions were noted but new sclerotic lesions were evident in his thoracolumbar region raising concern for bony metastasis.
Prognosis of testicular tumor depends mainly on the clinical stage, but emergence of a sarcomatous component presents a challenge in the treatment of germ cell tumors and the histological subtype of this component can be used as a guide to specific chemotherapy in these patients.
Mixed germ cell tumors; Rhabdomyosarcoma; Sarcomatous component
This report reviews 48 patients who from 1979 to 1994 were treated at the Norwegian Radium Hospital for newly diagnosed noncerebral extragonadal malignant germ cell tumour (EGGCT). Based on histology and/or serum tumour markers, 12 patients had a seminoma and 36 a non-seminoma. At diagnosis, 33 and 15 patients were classified as having abdominal and mediastinal EGGCT respectively. At the time of diagnosis 13 patients, all with non-seminomatous tumours, had metastases to bone, liver or brain. One patient with abdominal seminoma was cured by radiotherapy alone, whereas cisplatin-based chemotherapy (with or without surgery) was planned in the 47 remaining patients. Twenty-seven out of 42 patients receiving four or more chemotherapy cycles were rendered tumour free by induction chemotherapy, including 5 of the 13 patients with extralymphatic non-pulmonal disease. An additional tumour-free patient died of septicaemia after only two cycles of chemotherapy. Late relapses (after > 2 years) were observed in three patients, and a testicular primary was diagnosed during follow-up in three cases. Seven patients died of treatment-related complications, five of these because of neutropenic septicaemia. The median age of these patients was 52 years compared with 35 years in the remaining 41 patients (P < 0.05). The 5-year overall survival for all 48 patients was 60% (95% CI 46-74%) [cancer-specific 5-year survival 71% (95% CI 50-92%)]. EGGCT is a potentially curable disease, even in patients with very advanced disease. Special attention should, however, be devoted to patients above the age of 40 years because of an increased risk of treatment-related side-effects. Late relapses and the subsequent development of testicular tumours indicate the need for long-term follow-up.
Germ cell tumors (GCTs) most often arise in the gonads but some develop extragonadally. The aim of this study was to examine sex- and race-specific trends in incidence and survival of gonadal (GGCTs) and extragonadal GCTs (EGCTs) in the US from 1973 to 2007. We also examined the topographic distribution of EGCTs by race and sex.
We estimated age-specific and age-standardized incidence rates and 5-year relative survival rates (RSR) of GCTs using the Surveillance, Epidemiology, and End Results (SEER) Program (SEER 9 registries). GCTs and their topographic sites were identified using ICD-O morphology and topography codes.
Of 21,170 GCTs among males, 5.7% were extragonadal (whites 5.5%; blacks 16.3%). Of 2,093 GCTs among females, 39.3% were extragonadal (whites, 36.9%; blacks 51.0%). The incidence of GGCT was much higher among white (56.3/1,000,000) than black males (10.0/1,000,000) while there was no difference in incidence between white and black females (3.2/1,000,000). The rates of EGCT among men and women of both races were similar (range:1.9 – 3.4/1,000,000). The most frequent extragonadal sites were mediastinum among males and placenta among females. The 5-year RSR of testicular GCT was higher among whites (97%) than blacks (90%), as was the 5-year RSR of ovarian GCT (whites, 92%; blacks 85%). In general, the 5-year RSRs of EGCTs were lower than the 5-year RSRs of GGCTs.
The different incidence trends of GGCTs and EGCTs and distinct age-specific incidence patterns by anatomic site of EGCTs suggests that GGCTs and EGCTs may have different etiologies.
testicular neoplasms; ovarian neoplasms; incidence; time trends; germ cell tumors; extragonadal germ cell tumors
Malignant giant cell tumor (GCT) of bone is a rare tumor with debilitating consequences. Patients with GCT of bone typically present with mechanical difficulty and pain as a result of bone destruction and are at an increased risk for fracture. Because of its unusual occurrence, little is known about the epidemiology of malignant GCT of bone. This report offers the first reliable population-based estimates of incidence, patient demographics, treatment course and survival for malignancy in GCT of bone in the United States. Using data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program, we estimated the overall incidence and determinants of survival among patients diagnosed with malignant GCT of bone from 1975–2004. Cox proportional hazards regression was used to evaluate demographic and clinical determinants of survival among malignant GCT cases. Based on analyses of 117 malignant GCT cases, the estimated annual incidence in the United States was 1.6 per 10,000,000 persons per year. Incidence was highest among adults aged 20 to 44 years (2.4 per 10,000,000 per year) and most patients were diagnosed with localized (31.6%) or regional (29.9%) disease compared to distant disease (16.2%). Approximately 85% of patients survived at least 5 years, with survival poorest among older patients and those with evidence of distant metastases at time of diagnosis. The current study represents the largest systematic investigation examining the occurrence and distribution of malignancy in GCT of bone in the general U.S. population. We confirm its rare occurrence and suggest that age and stage at diagnosis are strongly associated with long-term survival.
giant cell tumor of bone; surveillance; epidemiology and end results; descriptive epidemiology; incidence; survival; osteosarcoma.
Primary central nervous system germ cell tumors (CNS-GCTs) in children and adolescents have unique clinical features and methods of treatment compared with those in adults. There is little information about Chinese children and adolescents with CNS-GCTs. Therefore, in this study we retrospectively analyzed the clinical features and treatment outcome of Chinese children and adolescents with primary CNS-GCTs. Between January 2002 and December 2012, 57 untreated patients from a single institution were enrolled. They were diagnosed with CNS-GCTs after pathologic or clinical assessment. Of the 57 patients, 41 were males and 16 were females, with a median age of 12.8 years (range, 2.7 to 18.0 years) at diagnosis; 43 (75.4%) had non-germinomatous germ cell tumors (NGGCTs) and 14 (24.6%) had germinomas; 44 (77.2%) had localized disease and 13 (22.8%) had extensive lesions. Fifty-three patients completed the prescribed treatment, of which 18 underwent monotherapy of surgery, radiotherapy, or chemotherapy, and 35 underwent multimodality therapies that included radiotherapy combined with chemotherapy or surgery combined with chemotherapy and/or radiotherapy. PEB (cisplatin, etoposide, and bleomycin) protocol was the major chemotherapy regimen. The median follow-up time was 32.3 months (range, 1.2 to 139 months). Fourteen patients died of relapse or disease progression. The 3-year event-free survival (EFS) and overall survival rates for all patients were 72.2% and 73.8%, respectively. The 3-year EFS was 92.9% for germinomas and 64.8% for NGGCTs (P = 0.064). The 3-year EFS rates for patients with NGGCTs who underwent monotherapy and multimodality therapies were 50.6% and 73.5%, respectively (P = 0.042). Our results indicate that multimodality therapies including chemotherapy plus radiotherapy were better treatment option for children and adolescents with CNS-GCTs.
Primary central nervous system germ cell tumors; chemotherapy; radiotherapy; survival rate; children
•We experienced a rare case of lately recurrent granulosa cell tumors.•Granulosa cell tumors rarely metastasize to the liver.•Diagnostic laparoscopy is useful for definitive diagnosis.•Aggressive therapy may contribute of the patient’s long-term prognosis.
Granulosa cell tumors (GCTs) are rare functional sex-cord-stromal ovarian neoplasms characterized by low malignancy potential and late relapse, which rarely metastasize to the liver.
Presentation of case
A 43-year-old female, who had undergone surgery to treat a GCT of the left ovary in 1976, complained of abdominal distention in May 2001. Imaging studies demonstrated masses in the right lobe of the liver, together with massive ascites. The patient’s bloody ascites showed no cytological evidence of malignancy. A diagnostic laparoscopy was performed, and the biopsy specimen was histologically proven to be a recurrent granulosa cell tumor. The patient was successfully treated surgery followed by systemic chemotherapy. Her postoperative course was uneventful and systemic chemotherapy was repeated due to the suspicion of a recurrence in the pelvic cavity.
GCTs which are rare malignant tumors of the ovary, tend to be associated with late recurrence. Although most recurrences occur within 10 years after the initial diagnosis, there are occasional reports of recurrences after 10 years have been. We experienced the rare case of a patient who relapsed 25 years after the initial diagnosis.
The long natural history of this disease highlights the importance of extended follow up for GCT patients. In addition, aggressive therapy including surgery and chemotherapy may contribute to a patient’s long-term prognosis.
Granulosa cell tumor; Metastatic liver tumor; Diagnostic laparoscopy; Recurrence
Malignant mediastinal germ cell tumors are a rare disease and represent only 1% to 4% of all mediastinal tumors. Gonadal germ cell tumors are generally the most common type and constitute 90% of germ cell tumors. The mediastinum is the second most frequently affected area ahead of other extragonadal areas, which include the retroperitoneum, the sacrococcygeal area, and the central nervous system. We report on the case of a mediastinal yolk sac tumor with a complete histological response to chemotherapy.
A 26-year-old Moroccan man, without a medical or surgical history, presented with a four-month history of chest distress, dyspnea, and a frequent dry cough for the previous month. A computed tomographic scan of the chest revealed a bulky mediastinal mass, which was biopsied. Histologically, the tumoral mass proved to be a yolk sac tumor. The serum level of alpha-fetoprotein of this patient was elevated to 19052 ng/ml.
After 4 courses of preoperative chemotherapy, the patient underwent a surgical resection of the tumor, with a complete pathologic response.
At the time of writing, the patient is alive with complete remission without any evidence of recurrence.
Primary mediastinal Yolk sac neoplasm represent a unique entity, and as such require specialized management. The diagnosis should be made not only by morphological studies but the patient’s age and the elevation of serum alpha-fetoprotein should also be considered. The utilization of cisplatin-based chemotherapy is associated with the best chance of a cure for this disease. This should be followed by surgical resection of the residual tumor in the nonseminomatous germ cell tumor.
Mediastinal nonseminomatous germ cell tumors; Complete pathologic response; Cisplatin-based chemotherapy
Germ cell tumors (GCT) are the most common solid tumors in adolescent and young adult males (age 15 and 35 years) and remain one of the most curable of all solid malignancies. However a subset of patients will have tumors that are refractory to standard chemotherapy agents. The management of this refractory population remains challenging and approximately 400 patients continue to die every year of this refractory disease in the United States.
Given the preclinical evidence implicating vascular endothelial growth factor (VEGF) signaling in the biology of germ cell tumors, we hypothesized that the vascular endothelial growth factor receptor (VEGFR) inhibitor sunitinib (Sutent) may possess important clinical activity in the treatment of this refractory disease. We proposed a Phase II efficacy study of sunitinib in seminomatous and non-seminomatous metastatic GCT’s refractory to first line chemotherapy treatment (ClinicalTrials.gov Identifier: NCT00912912). Next generation targeted exome sequencing using HiSeq 2000 (Illumina Inc., San Diego, CA, USA) was performed on the tumor sample of the unusual responder.
Five patients are enrolled into this Phase II study. Among them we report here the clinical course of a patient (Patient # 5) who had an exceptional response to sunitinib. Next generation sequencing to understand this patient’s response to sunitinib revealed RET amplification, EGFR and KRAS amplification as relevant aberrations. Oncoscan MIP array were employed to validate the copy number analysis that confirmed RET gene amplification.
Sunitinib conferred clinical benefit to this heavily pre-treated patient. Next generation sequencing of this ‘exceptional responder’ identified the first reported case of a RET amplification as a potential basis of sensitivity to sunitinib (VEGFR2/PDGFRβ/c-kit/ FLT3/RET/CSF1R inhibitor) in a patient with refractory germ cell tumor. Further characterization of GCT patients using biomarkers for clinical response and patient selection is warranted.
ClinicalTrials.gov Identifier: NCT00912912
Sunitinib; Germ cell tumor; Phase II trials; Targeted therapy; RET; EGFR; Next generation sequencing; Adolescent and young adult; Vascular endothelial growth factor receptor; VEGF; Unusual responder; Exceptional responder; Outlier responder
Giant cell tumors (GCTs) mainly occur in metaphyses of long bones and are generally considered histologically benign; however, GCTs may be locally aggressive with a high rate of local recurrence and exhibit the potential for distant metastasis. Primary GCT of the clivus is extremely rare and is easily misdiagnosed and, thus, treatment remains controversial. The present report describes the case of a 22-year-old male with GCT located in the skull base originating from the clivus, with the involvement of multiple cranial nerves, which was successfully treated with transnasal transsphenoidal surgery following adjuvant radiotherapy and intravenous bisphosphonate administration. The patient remains symptom free at two years of follow-up. This report contributes to the limited literature regarding GCTs of the skull.
giant cell tumor; clivus; trigeminal nerve; abducens nerve; radiotherapy; bisphosphonate
The development of sarcomatous component (SC) in testicular germ cell tumor (GCT) is an uncommon phenomenon. We searched our surgical pathology files from 1985 to 2007 and identified 33 cases of testicular GCTs with SC. The average age of patients was 31 years. All patients underwent radical orchiectomy, which demonstrated a GCT in all patients except for 3 patients who had received neoadjuvant chemotherapy. All testicular GCTs contained a teratomatous component. The GCTs were pure teratomas in 3 cases, and were mixed GCTs in the other cases. The SC was observed in primary testicular tumor (n = 19), in metastasis (n = 11), or in both primary testicular tumor and metastasis (n=3). The average percentage of the SC in the primary testicular GCT was 32% (range, 5% to 99%). The most common histologic type of SC was rhabdomyosarcoma (n = 24), followed by high-grade unclassified sarcoma (n = 5), rhabdomyosarcoma admixed with high-grade unclassified sarcoma (n = 2), angiosarcoma (n = 1), and low-grade myxoid sarcoma (n = 1). Clinical follow-up information was available for 27 patients. Of the 13 patients whose SC was limited to the testicular GCT, 2 died of GCT not otherwise specified (NOS) at 37 and 68 months, respectively; and 11 patients were free of disease at a mean of 46 months. Of the 14 patients with a SC in the metastasis, 7 patients died of GCT NOS at a mean of 95 months, and 7 patients were free of disease at a mean of 104 months. These results suggest that patients with a SC confined to the primary testicular GCT may not have a higher risk of mortality than those at a comparable stage without a SC. However, patients with a SC in the metastasis have an increased risk of mortality.
testicular germ cell tumor; sarcomatous component; rhabdomyosarcoma