Diagnosis Of Germinoma Research Articles

Primary medulla oblongata germinomas: two case reports and review of the literature

An intracranial germinoma is a tumor that is sensitive to radiotherapy. As medulla oblongata germinomas are extremely rare, determining an accurate preoperative diagnosis is challenging. Two cases of medulla oblongata lesions were surgically treated, and a postoperative diagnosis of germinoma was determined in both of the cases. The tumor in one patient completely resolved after a treatment course consisting of surgical intervention, radiotherapy and chemotherapy; the other patient, who did not receive any type of adjuvant treatment after surgery, suffered from tumor relapse and died from pneumonia 8 months following surgery. A preoperative diagnosis of medulla oblongata germinoma is difficult because of the lack of specific clinical signs and symptoms. If the correct diagnosis is reached, patients can have a favorable prognosis with proper evaluation and treatment. An invasive operation can potentially lesion and impair the function of the medulla oblongata, which is fatal to the patient.

Intracranial Germinoma Manifesting as Cavernous Sinus Syndrome

An 11-year-old girl presented with a rare case of neurohypophyseal germinoma manifesting as cavernous sinus syndrome with left abducens nerve palsy. Magnetic resonance (MR) imaging showed a mass located in the left cavernous sinus. Biopsy revealed an inflammatory reaction with lymphocytic infiltration. Postoperative MR imaging showed regression of the mass. Her eye movements were also restored. However, after 5 months, she developed right oculomotor and abducens nerve palsy, and MR imaging showed a large suprasellar mass invading the bilateral cavernous sinuses. The transcranial biopsy sample showed positive staining for placental alkaline phosphatase and c-kit, and the diagnosis of germinoma was confirmed. Chemotherapy and radiotherapy were administered, and the patient has been in complete remission for over 4 years.

Childhood intracranial germinoma with granulomatous reaction

Central nervous system tumors are the second most common type of childhood cancer in Turkey. Germinomas constitute two thirds of intracranial germ cell tumors. The granulomatous inflammation occurring around germinomas can cause histological diagnostic difficulty. We present a 12-year-old girl with a diagnosis of germinoma in the corpus callosum associated with granulomatous reaction to emphasize the diagnostic challenge which may occur during stereotactic biopsy interpretation or intraoperative consultation.

Intracranial Germinoma Presenting With Hemiatrophy- Follow-up Results and Literature Review -Two Case Reports-

Two boys aged 8 and 12 years presented with intracranial germinoma manifesting as cerebral hemispheric atrophy, hemiparesis, and decline in academic performance. First magnetic resonance (MR) imaging showed no enhanced lesions, but follow-up MR imaging obtained 12 or 23 months after the first visit showed new mass lesions in the temporal lobe or pituitary gland. Biopsy of these lesions resulted in a histological diagnosis of germinoma. Chemoradiation therapy produced complete remission but both patients continued to manifest mild hemiparesis and impaired cognitive function. Review of 18 previous and our 2 patients presenting with hemispheric atrophy revealed strong male predominance (18:2), mean age of 12.8 ± 5.2 (standard deviation) years, hemiparesis in all patients, and cognitive decline in 9 patients. Initial MR imaging detected mass lesions in only 9 patients, but follow-up MR imaging performed 10-38 months later detected new mass lesions in 5 patients. Radiation with/without chemotherapy provided good tumor control in all patients, but none of the 9 patients with cognitive dysfunction recovered their intellectual ability. We recommend early diagnosis based on biopsy of the atrophic site and timely treatment to improve the quality of life in these patients.

Primary cystic germinoma originating from the midbrain

A primary intracranial germinoma that involves the midbrain is rare. We describe an unusual case of primary cystic germinoma originating from the midbrain. A 29-year-old man presented with diplopia, and his MRI showed a cystic, ring-like enhanced lesion in the thalamo–mesencephalic junction. Open biopsy was performed and the diagnosis of germinoma was based upon the histopathological findings. Following chemotherapy and radiotherapy, the symptoms improved and the tumor disappeared. We propose that primary intracranial germinoma should be included in the differential diagnosis of midbrain tumors, because early diagnosis and appropriate treatment for midbrain germinoma improves clinical outcome.

Intracranial Germinoma as a Very Rare Cause of Panhypopituitarism in a 23-year Old Man

A 23 year-old patient was referred to the endocrine outpatient clinic with the suspicion of diabetes insipidus as he complained of nycturia and polydipsia since 2-3 months. Further he presented with nausea, vomiting, loss of appetite, rapid weight loss, diffuse body pain and fatigue. No headache, blurred vision, or fever were reported. The clinical examination showed sexual infantilism (poor beard, pubic and axillary hair growth, small testis). The patient's skin was strikingly pale as well as dry and scaly. Lymph node palpation was unremarkable. Endocrine evaluation revealed diabetes insipidus as well as complete anterior pituitary insufficiency. MR imaging demonstrated contrast-enhancing mass lesions at the pineal gland, hypothalamus, and anterior horn of lateral ventricles bilaterally. The localization pattern deemed to be highly suspicious for intracranial germinoma. As beta-HCG and AFP were negative in serum and cerebrospinal fluid the diagnosis of germinoma was confirmed histologically. After radiotherapy with cranio-spinal radiation therapy with 24 Gy followed by two weeks of local tumor boost with 16 Gy, the posttherapy MRI scan indicated complete tumor removal. This case demonstrates a very rare and potentially curable tumor as the cause of panhypopituitarism in adults.

Basal ganglia germinoma: Diagnostic value of MR spectroscopy and 11C-methionine positron emission tomography

We herein report a 12-year-old girl with a basal ganglia germinoma who presented with right-sided hemiparesis after a minor head trauma. Magnetic resonance (MR) imaging revealed a minimally enhanced lesion involving the left putamen, thalamus, and corona radiata. The lesion showed low-signal intensity on T1-, and high intensity on T2- and diffusion-weighted imaging. The MR signal in the adjacent globus pallidum was also low on T2-weighted imaging. MR spectroscopy on the lesion showed a large lactate/lipid/macromolecule peak with a decreased NAA/Cr ratio, but no increase in the Cho/Cr ratio. However, posttraumatic infarction at the territory of lateral lenticulostriate artery was ruled out 1 month later. This was based on progression of the hemiparesis and neuroimaging results, including an increased Cho/Cr ratio and weak uptake on (11)C-methionine positron emission tomography of the basal ganglia lesion. Stereotaxic brain biopsy confirmed the diagnosis of germinoma.

Pineal Germinoma With a Prominent Epithelioid Cell Granuloma Component -Case Report-

A 20-year-old man presented with a rare case of germinoma with a large component of epithelioid cell granuloma manifesting as oscillopsia. Magnetic resonance imaging demonstrated a mass in the pineal region with homogeneous enhancement with gadolinium. Craniotomy was performed, ending in biopsy. The initial histological diagnosis was epithelioid cell granuloma, but systemic investigation detected no evidence of granulomatous disorder. A revised diagnosis of germinoma was based on positive immunohistochemical staining for placental alkaline phosphatase (PLAP) and c-kit. Histological diagnosis is sometimes incorrect if granulomatous reaction is dominant. Immunohistochemical staining for PLAP and c-kit should be performed if germinoma is clinically suspected.

Granulomatous tissue response in germinoma, a diagnostic pitfall in endoscopic biopsy

We report a case of a 24-year-old man with a right thalamic germinoma that initially mimicked a granulomatous inflammation, compatible with neurosarcoidosis based on clinical symptoms, imaging results and histology of an endoscopically navigated biopsy. A second biopsy, prompted by clinical course, and performed openly from parieto-lateral revealed the underlying germinoma, obscured in the first biopsy by a granulomatous tissue response, particularly at the tumor edge. The present case highlights granulomatous inflammatory tissue response on the tumor edge of germinoma as a tumor-immanent diagnostic challenge. This diagnostic problem is aggravated by stereotactic and endoscopic approaches. We conclude that granulomatous inflammation in a specimen obtained by biopsy of a midline lesion should always be considered for the differential diagnosis of germinoma. Stereotactic and endoscopic surgery should sample several different target points within the lesion. Because of tumor heterogeneity of germinoma, the open biopsy approach is advantageous compared to endoscopic or stereotactic techniques for germinoma and should be considered if a germinoma is in the differential diagnosis and if allowed by the clinical situation.

Podoplanin expression in primary central nervous system germ cell tumors: a useful histological marker for the diagnosis of germinoma

Podoplanin, a mucin-like transmembrane sialoglycoprotein, promotes platelet aggregation and may be involved in cancer cell migration, invasion, metastasis, and malignant progression. Podoplanin/aggrus is highly expressed in testicular seminoma, suggesting that it may be a sensitive marker for testicular seminomas. Here we investigated the expression of podoplanin in central nervous system (CNS) germ cell tumors (GCTs) by immunohistochemical staining of tumor samples from 62 patients. In 40 of 41 (98%) germinomas (including germinomatous components in mixed GCTs), podoplanin was diffusely expressed on the surface of germinoma cells; lymphocytes, interstitial cells, and syncytiotrophoblastic giant cells were negative for podoplanin. Except for immature teratomas (12/17; 71%), podoplanin expression was absent in non-germinomatous GCTs, including seven teratomas, seven embryonal carcinomas, seven yolk sac tumors, and seven choriocarcinomas. In immature teratomas, focal podoplanin staining was observed in fewer than 10% of immature squamous and columnar epithelial cells. Thus, podoplanin expression may be a sensitive immunohistochemical marker for germinoma in CNS GCTs. As such, it may be useful for diagnosis, for monitoring the efficacy of treatment, and as a potential target for antibody-based therapy.

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

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.

Primary midbrain cystic germinoma mimicking glioma: a case with neuroendoscopic biopsy

Intracranial germinoma arising primarily in the midbrain is extremely rare. We present the first reported case of cystic midbrain germinoma that lacked evident solid components and mimicked a midbrain glioma. In a 22-year-old man with headache and diplopia, magnetic resonance imaging showed a ring-enhancing lesion in the midbrain. The preoperative diagnosis included brain stem glioma, metastasis, and neuroepithelial cyst. A neuroendoscopic biopsy specimen provided a histologic diagnosis of germinoma. The patient responded well to chemotherapy and radiotherapy. The case illustrates the diagnostic value of neuroendoscopic biopsy in the differential diagnosis of brainstem lesions in adult. The possibilities considered should now include germinoma.

C-kitgene mutation: common and widely distributed in intracranial germinomas

Of the intracranial germ cell tumors (IGCTs), 10% of germinomas and most nongerminomatous tumors remain refractory to multimodality therapy. The authors investigated the mutation of c-kit and the expression of its product KIT in IGCTs to identify tumors susceptible to imatinib mesylate, a synthetic agent targeting KIT. The authors investigated 26 IGCTs, including 13 germinomas, five mixed germ cell tumors (MGCTs), four immature teratomas (ITs), and two each of yolk sac tumors and choriocarcinomas. These tumors were examined for the expression of KIT and CD34 by immunohistochemical analysis, and for mutations in exons 2, 8 to 11, 13, and 17 of c-kit. Strong KIT expression was found in the cell membrane of germinomas (100%) and germinomatous cells of MGCTs (80%), as well as in the cytoplasm of epithelial and smooth-muscle cells of ITs. The membranous expression of CD34 was found in the nongerminomatous tumor cells and the chondrocytes of MGCTs (60%), ITs (100%), and a choriocarcinoma (50%), but not in germinomas and germinomatous cells. A total of five missense mutations distributed in exons 2, 11, 13, and 17 of c-kit were detected in three (23%) of the 13 germinomas. The novel mutations E73K, T96M (both in exon 2), and A636V (in exon 13) were detected in a single tumor. The presence or type of c-kit mutation was not correlated with patient prognosis. Immunohistochemical analysis of KIT expression is useful for the diagnosis of germinoma. This study may help in clarifying the pathogenesis of IGCTs and in identifying tumors susceptible to drugs targeting KIT.

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Expression and distribution of c-kit receptor and its ligand in human CNS germ cell tumors: A useful histological marker for the diagnosis of germinoma

We previously reported the expression of protooncogene c-kit in CNS germ cell tumors and suggested that the soluble form of c-kit (s-kit) may represent a specific clinical marker for germinoma-containing tumors. Here we investigated the expression of stem cell factor (SCF), a specific ligand of c-kit, in CNS germ cell tumor samples from 16 patients, using immunohistochemical methods to assay the expression of c-kit and SCF protein. The immunostaining patterns of c-kit and SCF were almost identical. In all germinoma-containing tumors, c-kit and SCF were diffusely expressed on the surface of germinoma cells; lymphocytes and interstitial cells were negatively stained. In immature teratomas, only some mature components, e.g., cartilage and gland, were immunoreactive for c-kit and SCF. Syncytiotrophoblastic giant cells (STGCs) were negative for both SCF and c-kit, suggesting that germinoma cells primarily coexpress SCF and c-kit. The coexpression of c-kit and SCF may be an important immunohistochemical marker for the diagnosis of CNS germinoma, and the SCF/c-kit pathway may be an alternative molecular target for the treatment of human CNS germinomas.

Primary midbrain germinoma

Intracranial germinomas arising primarily in the midbrain are extremely rare and only one case has been reported in the literature. A 15-year-old boy presented with headache, diplopia, unsteadiness and personality changes. Brain MRI showed a heterogeneous lesion in the midbrain. The pineal body region was free. The preoperative diagnosis included brain-stem glioma, metastasis and lymphoma. Stereotactic biopsy was permitted in order to take a specimen and the diagnosis of germinoma was established. The patient responded well to chemotherapy and radiotherapy. Germinoma should be included in the differential diagnosis of midbrain lesions. Preoperative diagnosis is difficult and biopsy is still needed for such lesions.

Stereotactic radiotherapy for pediatric intracranial germ cell tumors

Purpose: Intracranial germ cell tumors are rare, radiosensitive tumors seen most commonly in the second and third decades of life. Radiotherapy alone has been the primary treatment modality for germinomas, and is used with chemotherapy for nongerminomatous tumors. Stereotactic radiotherapy techniques minimize the volume of surrounding normal tissue irradiated and, hence, the late radiation morbidity. This study reports our experience with stereotactic radiotherapy in this group of tumors. Methods and Materials: Between December 1992 and December 1998, 18 patients with intracranial germ cell tumors were treated with stereotactic radiotherapy. A total of 23 histologically proven tumors were treated. Thirteen patients had a histologic diagnosis of germinoma, and 5 patients had germinoma with nongerminomatous elements. Of those patients with a histologic diagnosis of germinoma, 5 had multiple midline tumors. The median age of the patients was 12.9 years (range, 5.6–17.5 years). Results: A boost using stereotactic radiotherapy was delivered to 19 tumors following whole-brain radiation in 8 cases and craniospinal radiation in 11 cases. Three tumors were treated with stereotactic radiotherapy to the tumor volume alone following chemotherapy, and 1 tumor received a boost using stereotactic radiosurgery following craniospinal radiation. A median dose of 2520 cGy (range, 1500–3600) cGy was given to the whole brain, and a median dose of 2160 (range, 2100–2600) cGy was given to the spinal field. The median boost dose to the tumor was 2600 (range, 2160–3600) cGy, given by stereotactic radiotherapy delivered to the 95% isodose line. At a median follow-up time of 40 (range, 12–73) months, no local or marginal recurrences were reported in patients with germinoma. Two patients with nongerminomatous tumors have relapsed. One had elevation of tumor markers only at 37 months following treatment, and the other had persistent disease following chemotherapy and radiation therapy. Eight patients documented pituitary-hypothalamic dysfunction; in 7 (87.5%) of these patients, the dysfunction was present before commencing radiotherapy. Four patients (22%) developed newly diagnosed diabetes insipidus following surgery. Three patients (17%) received antidepressant medication at follow-up. Conclusion: Our series shows that stereotactic radiotherapy is achievable and well tolerated in this group of patients. Longer follow-up is required to fully assess the impact on long-term toxicity. Psychologic assessment of mood and affect should be performed as part of routine follow-up in this group of adolescent children.

Thickened Pituitary Stalk on Magnetic Resonance Imaging in Children with Central Diabetes insipidus

Magnetic resonance imaging (MRI) has revealed isolated pituitary stalk thickening (PST) in certain cases of idiopathic or secondary central diabetes insipidus (DI) due to infiltrative processes. Twenty-six children with DI and PST underwent cerebral MRI at the age of 8 ± 4 years and were followed (n = 25) by clinical and MRI evaluation for 5.5 ± 3.6 and 3.0 ± 2 years, respectively, but given no treatment other than hormonal substitutive therapy. Patients were subdivided into groups according to the etiology of the DI: germinoma (n = 4), Langerhans’ histiocytosis (n = 5) or ‘idiopathic’ DI with PST (n = 17). Complete anterior pituitary evaluation in 24 of the 26 patients revealed that 14 children were suffering from associated growth hormone deficiency and 7 had multiple hormone deficiencies. At the first MRI evaluation, pituitary stalk enlargement varied from 2.2 to 9.0 mm. The anterior pituitary gland was found to be normal (n = 12), small (n = 8) or enlarged (n = 6). At the final evaluation, a change in MRI features had occurred in 16 patients: morphological and/or signal changes in the PST (n = 16; 6 of whom showed an increase in PST) and changes in anterior pituitary gland size (n = 8; 3 of whom had increased and 5 had decreased). The presence of a growing suprasellar mass with a progressively enlarging pituitary stalk was demonstrated in the 6 patients who had shown increased pituitary stalk enlargement 1.8 ± 1.6 years after the first MRI. In 4 of these patients, a diagnosis of germinoma was made 1.3 ± 0.6 years after PST identification by MRI at the onset of DI, but the other 2 patients showing a suprasellar mass were still categorized as ‘idiopathic’ at the final clinical evaluation performed 7.8 and 12.3 years after DI onset. In 10 patients (all but 1 with Langerhans’ histiocytosis, showing ‘idiopathic’ DI) the pituitary stalk enlargement was diminished after 2.0 ± 1.9 years of MRI follow-up, and there was a complete reversal of pituitary stalk enlargement in 5 patients. We conclude that the natural history of ‘idiopathic’ isolated central DI with PST is unpredictable. Although germinoma should always be considered during the first 3 years of follow-up in patients presenting isolated DI with PST by repeated investigations every 3–6 months, it remains an infrequent etiology, affecting only 15% of cases in our study.

Prognosis of intracranial germinoma with syncytiotrophoblastic giant cells treated by radiation therapy

Purpose : The limited information in the literature suggests that intracranial germinoma with syncytiotrophoblastic giant cells (STGC) producing human chorionic gonadotropin (HCG) is associated with a higher recurrence rate compared with pure germinoma producing no HCG. To determine whether the poorer prognosis for germinoma with STGC is an inevitable finding, we retrospectively analyzed data for our patients. Methods and Materials : Data were analyzed for 44 patients who had pretreatment examination of HCG titers in the serum and/or cerebrospinal fluid (CSF) and underwent radiotherapy between 1978 and 1993. The diagnosis of germinoma was made histologically in 19 patients and clinically in 25 according to the established criteria. The treatment volume was the primary tumor site in 9 patients, the cerebrospinal axis in 29, and other in 6. The median follow-up period was 90 months. Results : Twenty (45%) of the 44 patients had elevated HCG titer. The abnormal HCG levels ranged from 4.9 to 189 mIU/ml (median: 18 mIU/ml) in serum and 8.2 to 660 mIU/ml (median: 26 mIU/ml) in CSF. No difference was found between the two groups in any patient or treatment characteristics including tumor size and incidence of CSF dissemination. The mean radiation dose to the primary tumor site was 46.4 Gy for pure germinoma and 47.5 Gy for germinoma with STGC and both 89% for those with pure germinoma. Among these patients, only two with pure germinoma developed recurrence. Conclusions : Our data suggest that the prognosis of intracranial germinoma with STGC treated with adequate radiation therapy does not differ from that of pure germinoma. Our current policy of delivering 40–45 Gy for tumors < 4 cm in diameter seems to be a reasonable treatment for germinoma with STGC.