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1.  Testicular seminoma after the complete remission of extragonadal yolk sac tumor : a case report 
BMC Urology  2004;4:13.
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.
Case presentation
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.
PMCID: PMC535804  PMID: 15546481
2.  Giant cell tumor of the uterus: case report and response to chemotherapy 
BMC Cancer  2007;7:46.
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.
Case presentation
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.
PMCID: PMC1832205  PMID: 17359524
3.  A Mini-Review of Familial Ovarian Germ Cell Tumors: An Additional Manifestation of the Familial Testicular Germ Cell Tumor Syndrome 
Cancer epidemiology  2009;33(1):31-36.
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.
PMCID: PMC2735217  PMID: 19679044
ovarian germ cell tumor; familial; epidemiology; testicular germ cell tumor; genetic predisposition; SEER
4.  Bone disease in testicular and extragonadal germ cell tumours. 
British Journal of Cancer  1988;58(6):793-796.
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.
PMCID: PMC2246879  PMID: 3224081
5.  TI-CE High-Dose Chemotherapy for Patients With Previously Treated Germ Cell Tumors: Results and Prognostic Factor Analysis 
Journal of Clinical Oncology  2010;28(10):1706-1713.
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.
PMCID: PMC3651604  PMID: 20194867
6.  Treatment and outcome of patients with extragonadal germ cell tumours--the Norwegian Radium Hospital's experience 1979-94. 
British Journal of Cancer  1998;77(2):329-335.
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.
PMCID: PMC2151244  PMID: 9461006
7.  Salvage high-dose chemotherapy for children with extragonadal germ-cell tumours 
British Journal of Cancer  2005;93(4):412-417.
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.
PMCID: PMC2361583  PMID: 16106248
extragonadal germ cell tumour; high-dose chemotherapy; salvage therapy; children
8.  Gonadal and extragonadal germ cell tumors in the United States, 1973–2007 
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.
PMCID: PMC3631107  PMID: 22320869
testicular neoplasms; ovarian neoplasms; incidence; time trends; germ cell tumors; extragonadal germ cell tumors
9.  Primary yolk sac tumor of seminal vesicle: a case report and literature review 
Yolk sac tumor (endodermal sinus tumor) is a rare malignant germ cell tumor arising in the testis or ovary. Extragonadal yolk sac tumor is even rarer and has only been described in case reports. Due to the rarity of the tumors, the appropriately optimal treatment remains unclear. We report a case of yolk sac tumor in the seminal vesicle.
A 38-year-old Asian male presented with gross hematuria and hemospermia. Transrectal ultrasound scan showed a solid mass in the left seminal vesicle and the scrotal sonography showed no abnormalities. Bilateral seminal vesicles were resected, and histopathological examination showed a typical pattern of yolk sac tumor (YST). The patient responded poorly to comprehensive treatment of radiotherapy, chemotherapy and surgeries, developed systemic multiple metastases, and died of cachexia one and half years after diagnosis.
PMCID: PMC3499222  PMID: 22978485
Yolk sac tumor; Seminal vesicle; Extragonadal
10.  Atypical extragonadal germ cell tumors 
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.
PMCID: PMC3263044  PMID: 22279357
Extragonadal; germ cell tumor; atypical
11.  Retroperitoneal Extragonadal Nonseminomatous Germ Cell Tumor with Synchronous Orbital Metastasis 
Advances in Urology  2009;2009:419059.
A huge retroperitoneal tumor with a right orbital mass was detected and proved to be an extragonadal nonseminomatous germ cell tumor on biopsy. BEP chemotherapy caused some regression in orbital mass however no change in retroperitoneal tumor size as well as serum tumor marker levels occurred. Herein, we present a rarely seen entity of extragonadal retroperitoneal nonseminomatous germ cell tumor with synchronous orbital metastases and discuss its diagnosis and management.
PMCID: PMC2633450  PMID: 19197374
12.  Late Recurrence and Second Primary Malignancy among 139 Patients with Germ Cell Tumors: Long-term Outcome of the Disease in a Single-center Experience 
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.
PMCID: PMC2813544  PMID: 19906660
urology; urologic-med; urologic-radOncol
13.  Post-orchidectomy retroperitoneal seminoma: A case report 
Oncology Letters  2013;5(4):1240-1242.
Between 2 and 5% of malignant germ cell tumors in males arise at extragonadal sites. The origin of extragonadal retroperitoneal germ cell tumors remains controversial. Whether these develop primarily in the retroperitoneum or are metastases of a primary testicular tumor has long been debated. We report a 38-year-old male who presented with abdominal pain and was diagnosed with retroperitoneal seminoma. The patient gave a history of having undergone a right orchidectomy for an undescended testis via the inguinal route 10 years previously with a reported histology of benign inflammatory mass.
PMCID: PMC3629255  PMID: 23599771
retroperitoneal seminoma; orchidectomy; late relapse
14.  Testicular Germ Cell Tumors with Sarcomatous Components: An Analysis of 33 Cases 
The American journal of surgical pathology  2009;33(8):10.1097/PAS.0b013e3181adb9d7.
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.
PMCID: PMC3812063  PMID: 19561445
testicular germ cell tumor; sarcomatous component; rhabdomyosarcoma
15.  Leptomeningeal Metastases in a Patient with an Extragonadal Germ Cell Tumor 
Clinical Medicine. Oncology  2008;2:371-374.
We present a case of leptomeningeal metastases in a 30-year-old man with an extragonadal germ cell tumor. The patient was referred to our hospital for treatment of an occipital brain metastasis. This lesion was resected, followed by whole brain radiotherapy and further chemotherapy, and a temporary complete remission was achieved. However, leptomeningeal recurrence developed, and despite salvage chemotherapy, the patient died of disease. Although multidisciplinary treatment is given to treat brain metastases of germ cell tumors, the patients’ prognosis has been unsatisfactory. The identification of a standard/effective treatment is required.
PMCID: PMC3161680  PMID: 21892301
leptomeningeal metastasis; brain metastasis; germ cell tumor; surgery; chemotherapy
16.  Spinal Cord Injury due to the Giant Cell Tumor of the Second Thoracic Vertebra: A Case Report 
Annals of Rehabilitation Medicine  2013;37(2):269-273.
Giant cell tumor (GCT) is a relatively rare neoplasm. In GCT, the bone affection of the axial skeleton is extremely rare. Most GCT arises in the meta-epiphyseal ends of the long bones. Its peak incidence is between 30 to 40 years of age. GCT is usually classified as benign, but shows locally aggressive behavior and may occasionally undergo a malignant transformation. The patients with GCT in the spine often complain of the lower back pains, as the tumors primarily involve the sacrum. We report a case of an adolescent female complaining of the upper back pain with a sudden weakness of the lower extremities, later diagnosed with the GCT of the T2 vertebra. The present patient showed American Spinal Injury Association Impairment Scale (AIS) D before the surgery, which changed to AIS E after the treatments including the surgery, radiation therapy and rehabilitation.
PMCID: PMC3660490  PMID: 23705124
Giant cell tumor; Spinal cord injuries
17.  Testicular seminomatous mixed germ cell tumor with choriocarcinoma and teratoma with secondary somatic malignancy: a case report 
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.
Case presentation
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.
PMCID: PMC3917416  PMID: 24380446
Mixed germ cell tumors; Rhabdomyosarcoma; Sarcomatous component
18.  Granular cell tumor of hand presenting as subcutaneous nodule mimicking dermal adnexal tumor: A diagnosis by cytology 
Granular cell tumor (GCT) is an uncommon tumor and is believed to be of schwannian origin. GCT is benign but rare malignant cases are recorded. GCT occurs in almost any part of the body. The common sites are the tongue, skin, and subcutaneous tissue. GCT of hand is an extremely rare. Till date only 17 cases are reported in the literature. Preoperative diagnosis of GCT is important, because GCT mimics dermal adnexal tumor in subcutaneous tissue, other soft tissue tumor or inflammatory lesions. GCT is composed of large polygonal cells with eosinophilic granular cytoplasm and these cells are often immunoreactive for the S-100 protein. Fine-needle aspiration cytology has been suggested to be diagnostic modality of choice and this would undoubtedly aid the correct diagnosis. Excision with wide surgical margins is curative for benign GCT. Recurrence and malignant transformation requires regular follow-up. Here, this communication documents a case of cytological diagnosis of the granular cell tumor of hand in a 21-year-old female, clinically suspected to be a dermal adnexal tumor.
PMCID: PMC3573450  PMID: 23439997
Fine-needle aspiration cytology; granular cell tumor; hand; histology; immunohistochemistry
19.  Fulminant hepatic failure in a patient with advanced extragonadal germ cell tumour 
BMJ Case Reports  2010;2010:bcr0120102661.
Fulminant hepatic failure (FHF) in association with metastatic cancer, without evidence of liver metastases, has not been previously reported in the literature. This report concerns a case of FHF in a 36-year-old man with advanced germ cell tumour arising from an extragonadal (retroperitoneal) primary. Liver function and encephalopathy improved following chemotherapy, suggesting prompt diagnosis and treatment may have cured the patient. Following completion of chemotherapy, he developed spontaneous bacterial endocarditis, requiring aortic valve replacement, a rare complication of curative chemotherapy. At 44 months post completion of chemotherapy, he has regained his premorbid performance status and has returned to work.
PMCID: PMC3027936  PMID: 22778367
20.  Presentation of two patients with malignant granulosa cell tumors, with a review of the literature 
Granulosa cell tumors (GCTs) of the ovary account for 2 to 5 of ovarian malignancies. We present two patients with malignant ovarian adult GCT. In one patient, a combination of bleomycin, etoposide, and cisplatin was effective after initial surgery for malignant GCT. In the other, an aromatase inhibitor was effective for recurrent malignant GCT. We also review the literature for further management of this tumor. Because GCT of the ovary is rare, it will be necessary to elucidate the clinical phenotype and establish treatment protocols by accumulating and analyzing more patients.
PMCID: PMC3490972  PMID: 22963202
Ovarian malignant granulosa cell tumor; BEP combination therapy; Aromatase inhibitor
21.  Incidental Discovery of Testicular Microlithiasis: What Is the Importance of Ultrasound Surveillance? Two Case Reports 
Case Reports in Oncology  2013;6(3):520-525.
Many studies have demonstrated an association between diffuse bilateral testicular microlithiasis (TM) and gonadal and extragonadal germ cell tumors. Nevertheless, it is still uncertain whether ultrasound surveillance is really necessary in patients with TM in the absence of other risk factors such as previous testicular cancer, a history of cryptorchidism or testicular atrophy. We report the cases of a 33- and a 39-year-old man presenting with a retroperitoneal extragonadal tumor. The first patient underwent an MRI examination in order to rule out a lumbosacral hernia: MRI images showed no slipped disks but a voluminous retroperitoneal solid mass. The histological analysis revealed an immature teratoma. The second patient came to the emergency department complaining of abdominal pain, vomiting, weight loss and mild jaundice: ultrasound examination showed a large, ill-defined heterogeneous abdominal mass, confirmed by CT and MRI examination. The histology diagnosed a yolk sac tumor. In both patients, the testicular sonography was performed to rule out a focal lesion, but it displayed bilateral TM without a focal testicular mass. Based on our direct experience, we highlight the importance of annual ultrasonographic surveillance of the testis and the retroperitoneal space in patients with occasionally detected TM.
PMCID: PMC3843917  PMID: 24348387
Testicular microlithiasis; Germ cell tumors; Testicular ultrasound
22.  Nonurological malignancies in children 
Nonurological malignancies in children include a wide variety of tumors. These tumors include primary tumors of the liver, thyroid, lung, gastrointestinal tract (GIT), and adrenals; soft tissue sarcomas (STSs) like rhabdomyosarcoma (RMS) and non-RMS; and finally extragonadal germ cell tumors (GCT).
This article aims at describing the current thinking in the management of these childhood solid tumors. This is critical in view of the recent advances in the elucidation of the molecular, genetic, and biologic behavior of these tumors and how these factors are getting integrated not only in the staging but also in developing a risk-based approach towards the management of these tumors.
Materials and Methods:
Reference was made to recently published literature from the leading pediatric cancer centers of the world to make a sense of things of the most current thinking in this rapidly expanding field. This will provide surgeons and physicians taking care of these children with a working knowledge in this somewhat challenging field.
Treatment results vary from center to center depending on access to resources and following different management protocols. Results have improved for these tumors with the advent of newer chemotherapeutic agents, novel delivery methods of radiation therapy (RT), and improvement in surgical technique. Due to the limited number of patients presenting with these tumors, national and international collaboration of data is critical for all and beneficial to individual treatment centers. This has resulted in better results in the past and will definitely result in still better results in the future.
PMCID: PMC3935298  PMID: 24604982
Childhood; nonurological malignancies; hepatoblastoma; rhabdomyosarcoma; extragonadal germ cell tumor; pediatric solid tumor
23.  Alternating dose-dense chemotherapy in patients with high volume disseminated non-seminomatous germ cell tumours 
British Journal of Cancer  2002;86(10):1555-1560.
Only about half of patients with a poor-prognosis non-seminomatous germ-cell tumours can achieve a cure. The aim of this phase II study was to assess the efficacy and toxicity of a dose-dense alternating chemotherapy regimen in this subset of patients. High volume non-seminomatous germ-cell tumours was defined as follows: at least two sites of non pulmonary metastases, an extragonadal primary tumour, a serum human chorionic gonadotropin level higher than 10 000 mIU ml−1, or a alpha-foetoprotein level higher than 2000 mIU ml−1. Patients who fulfilled these criteria were treated with the so-called BOP-CISCA-POMB-ACE regimen (bleomycin, vincristine, and cisplatin; cisplatin, cyclophosphamide, and doxorubicin; cisplatin, vincristine, methotrexate, and bleomycin; etoposide, dactinomycin, and cyclophosphamide) plus granulocyte colony-stimulating factor. A total of 58 patients were enrolled. Patients were retrospectively classified according to the International Germ-Cell Cancer Consensus Group classification; 38 patients (66%) had poor-prognosis disease and 19 patients (33%) had intermediate-prognosis. Patients received a median of 2.5 courses (range 0.25 to five courses) of the BOP-CISCA-POMB-ACE regimen. Forty-two patients (72.4%) had a complete response to therapy. With a median follow-up time of 31 months, the 3-year progression-free survival rate was 71% (95% confidence interval, 60 to 84%) and the 3-year overall survival rate was 73% (95% confidence interval: 62 to 86%). The 3-year PFS rates were 83% (95% confidence interval: 68 to 100%) in the intermediate-prognosis group and 65% (95% confidence interval: 51 to 82%) in the poor-prognosis group. Early side effects included mainly grade 4 haematologic toxicity (neutropaenia in 79% of patients, thrombocytopaenia in 69%, anaemia in 22%), grade 4 stomatitis (19%), and four early deaths (7% of patients), at least partially related to toxicity. The dose-dense BOP-CISCA-POMB-ACE regimen is highly active in patients with non-seminomatous germ-cell tumours classified as intermediate-prognosis or poor-prognosis according to the International Germ-Cell Cancer Consensus Group. Because outcomes with this regimen compare favourably with outcome after standard therapy, dose-dense chemotherapy should be further investigated in this subset of patients.
British Journal of Cancer (2002) 86, 1555–1560. DOI: 10.1038/sj/bjc/6600272
© 2002 Cancer Research UK
PMCID: PMC2746595  PMID: 12085204
chemotherapy; dose-dense chemotherapy; germ-cell tumours; International Germ-Cell Cancer Consensus Group; non-seminomatous germ cell-tumours
24.  Case report: Malignant teratoma of the uterine corpus 
BMC Cancer  2009;9:195.
Teratomas are the commonest germ cell tumours and are most frequently found in the testes and ovary. Extragonadal teratomas are rare and mainly occur in midline structures. Uterine teratomas are extremely rare with only a few previous case reports, usually involving mature teratomas of the uterine cervix.
Case Presentation
We report an 82-year-old lady presenting with post-menopausal bleeding. Initial investigations revealed a benign teratoma of the uterus which was removed. Her symptoms persisted and a recurrent, now malignant, teratoma of the uterine corpus was resected at hysterectomy. Six months after surgery she relapsed with para-aortic lymphadenopathy and was treated with a taxane, etoposide and cisplatin-containing chemotherapy regimen followed by retroperitoneal lymph node dissection.
In this report we discuss the aetiology, diagnosis and management of uterine teratomas, and review previous case studies.
PMCID: PMC2709639  PMID: 19538751
25.  Fine-needle aspiration cytology of granular cell tumor: A report of two cases 
Granular cell tumors (GCTs) are uncommon soft tissue tumors, which are difficult to diagnose merely on clinical examination. Being an effective first-line investigation, the fine-needle aspiration cytology (FNAC) plays a significant role in its pre-operative recognition. However, as the tumor is likely to mimic certain other lesions, a cytopathologist needs to be aware of its characteristic cytomorphology. We report two cases of GCT who presented with subcutaneous swellings in the left lower back and the right-sided anterior abdominal wall for 6 and 2 months, respectively. Both the patients had a clinical diagnosis of lipoma/neurofibroma. FNAC was done in both. In the first case a cytodiagnosis of xanthogranuloma was suggested and GCT in the second. Subsequent histologic examination of both showed features of GCT. FNAC would aid in presumptive diagnosis of GCT.
PMCID: PMC3793358  PMID: 24130413
Fine-needle aspiration cytology; granular cell; preoperative diagnosis; tumor; xanthogranuloma

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