The role of chemotherapy in intracranial germinoma: A case report

Background: The case of a 29-year-old man with histologically proven simultaneous germinoma (seminoma) of the pineal gland and a stage I embryonal carcinoma of the testis is reported. An intradural metastatic lesion from the pineal germinoma was diagnosed at the level of the first thoracic vertebra. Treatment, after inguinal orchiectomy, was chemotherapy only, rather than conventional radiotherapy for the pineal germinoma.Methods: Therapy consisted of bleomycin (B), etoposide (E) and cisplatin (P). MRI was used to assess the effectiveness of BEP chemotherapy.Results: A complete remission of the pineal gland germinoma and the epidural metastasis was documented after two cycles of BEP chemotherapy and after 15 months of follow-up the patient remains free of relapse.Discussion: The pathogenesis of simultaneously occurring germinoma of the pineal gland and embryonal cell carcinoma of the testis is discussed.The choice of therapy in these circumstances is a matter of debate and the good result of chemotherapy alone in this patient suggest that primary chemotherapy may be the therapy of choice in patients with pineal germinomas.     

The blood-brain barrier and response of C.N.S. metastases to chemotherapy

Summary A case demonstrating a differential effect of chemotherapy on a pineal metastasis and parenchymal cerebral metastases is described. At presentation, extensive metastatic small cell carcinoma of the lung was present and CT scanning showed an apparently solitary metastasis in the pineal. The clinical course and serial CT scans showed significant improvement of the pineal tumor and simultaneous development of multiple intra-cerebral metastases. This case confirms that the pineal gland is excluded from the blood-brain barrier, and indicates the clinical importance of the effect of the blood-brain barrier in the responsiveness of CNS metastases to chemotherapy.     

Differential neurooncogenicity of strains of JC virus, a human polyoma virus, in newborn Syrian hamsters.

The neurooncogenicity recently isolated strains of the human polyoma virus, JC virus, was determined by intracerebral inoculation of newborn Syrian golden hamsters. All three strains produced malignant brain tumors in a majority of inoculated animals during a 6.5-month observation period. The results obtained with the MAD-2 strain, 19 of 20 animals with cerebellar medulloblastomas and 0 of 20 animals with pineal gland tumors, were quite similar to those observed previously with the prototypic strain of JC virus, MAD-1. Inoculation of the MAD-4 strain, however, resulted in 10 of 22 animals with pineal gland tumors and only 10 of 22 animals with tumors in the cerebellum. The MAD-3 strain was neurooncogenic, but too few animals lived to be weaned to provide significant additional information. The basis for the apparent predilection of the MAD-4 strain for the pineal gland is unknown. Two hamsters in the experiment developed extracranial neuroblastomas.     

A study on the relationship between the pineal gland and the opioid system in patients with cancer. Preliminary considerations

Recent studies showed that both the pineal gland and the endogenous opioid system are involved in the modulation of the immune system and in the regulation of tumor growth. Moreover, a relationship between pineal and opioid system has been demonstrated. In order get an overall view of the psychoneuroendocrine interactions in cancer patients, the levels of melatonin, the most important pineal hormone, and of beta-endorphin have been measured on blood samples collected during the morning. The study was carried out on 54 patients, 42 healthy subjects, and in 34 patients having illnesses other than cancer. Breast cancer, lung carcinoma, and colorectum cancer were the three neoplasms detected in the patients investigated. Growth hormone (GH), somatomedin-C and prolactin (PRL) levels were also determined. beta-endorphin levels were found to be substantially within the normal range in patients with cancer, whereas those of melatonin were raised in several cases. The beta-endorphin/melatonin ratio was higher than 2 in normal subjects, in non-neoplastic patients and in most cancer patients without metastases, whereas this ratio was lower than 2 in almost all patients in a metastatic stage of the disease. Neither melatonin levels nor those of beta-endorphin appeared to be significantly correlated with GH, somatomedin-C, and PRL concentrations. The low beta-endorphin/melatonin ratio observed in metastatic patients suggests the presence of an unbalanced relation between the pineal and the opioid system in those subjects. Therefore, an anomalous relationship between pineal function and opioid activity might play a role in the clinical course of neoplastic disease.     

Glioblastoma multiforme of the pineal region

Glioblastoma multiforme (GBMs) tumors are exceedingly rare tumors in the pineal region. We present three cases in which patients presented with a pineal/posterior third ventricular region mass and review all the previously reported cases in the literature. Pineal region GBM seems to be a very aggressive tumor with a high rate of leptomeningeal and ependymal metastatic disease. Patients usually present with signs and symptoms of hydrocephalus and Parinaud’s syndrome. The clinical and radiological characteristics of pineal GBM do not differentiate it from other malignancies of this region, thus surgical biopsy is generally required for definitive diagnosis. Glioblastoma should be considered in the differential diagnosis of the pineal region tumors, especially when evidence of leptomeningeal or ependymal metastatic disease is present.     

Pleomorphic granular cell astrocytoma of the pineal gland.

BACKGROUND. Primary neoplasms of the pineal gland are uncommon. Two patients with unusual primary pineal tumors that had similar distinctive histologic features are reported. METHODS. The surgically resected neoplastic pineal tissue from these patients were examined by light microscopy, immunohistochemistry, and electron microscopy and correlated with the patients' clinical course. RESULTS. These pineal tumors consisted of a mixture of spindle-shaped cells with fibrillated cell processes and many large lipidized and/or granular pleomorphic cells, some of which were multinucleated. These two tumors superficially resembled pleomorphic xanthoastrocytoma and granular cell tumors of the central nervous system. The pleomorphic tumor cells expressed glial fibrillary acidic protein and some also produced retinal S-antigen, a marker for retinal photoreceptor cells. Long-term follow-up (8 years) on one of these patients suggested a relatively "benign" clinical course. CONCLUSIONS. It is possible that this newly described tumor may be a distinct subset of pineal gland neoplasias with a favorable biologic behavior despite the histologic features that would suggest otherwise.     

Primary intracranial yolk sac tumor: immunofluorescent demonstration of alpha-fetoprotein synthesis.

An autopsy case of 20-year-old male with primary intracranial yolk sac tumor (endodermal sinus tumor) is reported. Whereas the biopsy specimen obtained from the pineal region showed diffuse proliferation of atypical tumor cells, the metastatic subdural tumor removed from lumbar spinal region had the characteristic histologic appearance of yolk sac tumor. The histologic diagnosis was intracranial yolk sac tumor originating in the pineal gland. The elevated amount of alpha-fetoprotein in the cerebrospinal fluid and in the serum further supported the diagnosis. At autopsy, only metastatic tumor was present in the posterior fossa. The immunofluorescence study demonstrated the presence of intra- and extracellular alpha-fetoprotein globules in the tumor tissue. The intra- and extracellular distribution of alpha-fetoprotein, in general, appeared to coincide with that of the PAS-positive hyaline globules in the tumor.     

Pineal parenchymal tumor of intermediate differentiation with papillary features: a continuum of primary pineal tumors?

Pineal parenchymal tumors comprise a rare group of primary neoplasms of the pineal gland. We describe a case involving a 29-year-old woman who presented with signs and symptoms of hydrocephalus secondary to a pineal region tumor obstructing the third ventricle. Surgical resection was performed and pathological analysis revealed a novel diagnosis consistent with a pineal parenchymal tumor of intermediate differentiation (PPTID) with transition to a papillary tumor of the pineal region (PTPR). To our knowledge, this particular pineal region tumor pathology has not yet been reported in the literature and highlights the continuum with which primary pineal tumors exist. We provide a review of the existing literature on pineal region tumors, specifically PTPR and PPTID, and offer insight into the management of these rare neoplasms.     

An adrenal gland nodule presenting as an early sign of metastatic spread from colorectal cancer: report of two cases

The presence of an adrenal gland nodule may be an early or late sign of metastatic spread from colorectal cancer. It usually appears when the internal malignancy is widely disseminated and has been previously diagnosed. Adrenal insufficiency can be compatible with bilateral and diffuse involvement of this uncommon site of disease. Although a surgical approach can be proposed in some circumstances, chemotherapy is usually the only therapeutic option. We present 2 cases that document examples of both events, so as to illustrate the most relevant aspects of this condition.     

Sarcoidosis of the pineal gland: an unusual presentation of neurosarcoidosis

Introduction Sarcoidosis is an inflammatory disease characterized by noncaseating granulomas that is rarely found as primary CNS pathology. We report an unusual case of sarcoidosis involving the pineal gland with radiographic, histopathology, and clinical data. Case report A 45-year-old man without evidence of systemic sarcoidosis presented with a history of gradual onset of blurry vision and diplopia that progressed over 3 months. MR imaging demonstrated an enhancing mass in the pineal region. A suboccipital craniotomy was performed with resection of the mass through a supra-cerebellar infratentorial approach. Histopathologic analysis did not reveal a pineoblastoma but instead revealed noncaseating granulomas within the pineal gland. Extensive hematologic laboratory examinations, cerebral spinal fluid studies, and cultures for infection were all negative. This mass lesion was diagnosed as solitary neurosarcoidosis of the pineal gland, without dissemination. The patient was treated with steroids and at 4-year follow-up is asymptomatic with an unremarkable MRI scan. Conclusion This is an unusual case of pineal sarcoidosis mimicking a tumor with associated MRI, CT and histopathologic findings reported together. Although rare, sarcoidosis of the pineal gland should not be excluded from a comprehensive differential diagnosis of an enhancing pineal region mass.     

Gastrointestinal metastases from malignant tumors of the lung

Autopsy data of 423 cases of primary tumor of the lung over a 36-year period were evaluated for the presence of gastrointestinal tract metastases. Fifty-eight cases (14%) were found and were analyzed for histologic nature of tumor, anatomic location, symptomatology and complications. The most common histologic type of lung tumor causing gastrointestinal tract metastasis was squamous cell (19 cases, 33%), followed by large cell (17 cases, 29%), and oat cell (11 cases, 19%). The esophagus was the most common site of involvement (33 cases). Fourteen of the 33 cases were involved by direct extension of the tumor. The middle third of the esophagus had metastases more commonly (16/33, 49%) than the other two sites. Most patients with gastrointestinal metastases had no symptoms. In those patients with symptoms, dysphagia was most common when the tumor involved the proximal gastrointestinal tract (esophagus, stomach), whereas, pain was most commonly seen with involvement of the distal gastrointestinal tract (small bowel, large bowel). Six of 20 patients (30%) with small bowel involvement experienced perforation and peritonitis as complications of metastatic involvement and two patients with large bowel metastasis had obstruction; a third had dehiscence of a previous anastomotic site. Gastrointestinal tract metastases from primary carcinoma of the lung are more common than previously thought and may be associated with serious clinical complications.     

Central nervous system progression among patients with metastatic breast cancer responding to trastuzumab treatment

Central nervous system (CNS) metastases from breast cancer are common and can present as the first or solitary site of disease progression. The CNS has been reported to act as a sanctuary site that denies access to many chemotherapeutic agents. We present here, a series of 10 metastatic breast cancer patients who developed CNS metastases after an initial response to trastuzumab treatment. Forty one patients with metastatic HER2-overexpressing breast cancer, without evidence of CNS involvement prior to the initiation of trastuzumab treatment, were followed during trastuzumab treatment. A neurological evaluation was performed in those patients who developed neurological signs or symptoms during the course of treatment. The clinical course and pattern of CNS involvement in these patients are discussed. Thirty two patients (78%) showed an initial response to trastuzumab treatment. Ten (31%) of the responding patients developed either isolated CNS relapse or concurrent CNS and systemic progression at a median of 43 weeks after the initiation of trastuzumab treatment. Trastuzumab as a single agent was continued following control of brain symptoms in three patients, two showed signs of systemic disease progression at 11 and 15 weeks following the diagnosis of CNS metastases, respectively. In two other patients, trastuzumab in combination with weekly chemotherapy was continued for more than 20 weeks after CNS relapse without evidence of disease progression. The incidence of CNS involvement in our group of patients was higher than expected. With more successful and prolonged systemic anti-tumour effects achieved by novel drug combinations, the risk of developing CNS metastases might be even greater. Evaluation of prophylactic cranial irradiation strategies might be studied for high-risk patients.     

MRI of pineal region tumors

The pineal region is a heterogeneous area that includes the pineal gland and several parapineal structures. Pineal region masses include germ cell tumors (GCTs), pineal parenchymal cell tumors, glioma, meningioma, metastases, and non-neoplastic masses such as pineal cysts, lipoma, epidermoid, vascular malformations. Although MRI has allowed an improvement in distinguishing true pineal masses from parapineal masses impinging into the region of the gland, it is still difficult to differentiate the pineal GCTs from pineal parenchymal tumors with only images, and the clinical informations such as age, sex, and the tumor markers are very important.     

Metastasis of murine mammary tumour lines from the mammary gland and ectopic sites.

A murine model of spontaneous metastasis of mammary adenocarcinomas in mice was developed by serial transplantation of spontaneous BALB/cfC3H/ Crgl tumours into the mammary gland. Through 8 transplant generations, 5 lines demonstrated maintenance of metastatic phenotype and consistent gross and histological morphology and growth properties. Tumour lines M12, M35 , and M51 metastasized from the mammary gland with overall frequencies of 53, 80, and 85%, respectively. Line T5 was weakly metastatic, capable of a minor degree of lung colonization in 8% of hosts, while line WT2 failed to establish any grossly or histologically detectable pulmonary foci. The significance of the mammary gland as transplant site was shown by comparing the growth and metastasis of these lines in mammary gland with that observed upon subcutaneous transplantation. Subcutaneous metastatic frequency of one tumour line was significantly reduced from that obtained when grown in the mammary gland while histological organization differed markedly in 2 of the tumours. Furthermore, while tumours implanted into the gland grew as well encapsulated masses, the same tumours grown subcutaneously frequently invaded the body wall and occasionally colonized adjacent peritoneal organs and, more often, mesenteries. Intravenous injection of dissociated tumours further emphasized the importance of events that occur at the primary site. There was no correlation between spontaneous metastatic ability and the capacity to colonize the lung following i.v. inoculation. This study demonstrates the importance of transplant site in the assessment of metastasis in experimental systems.     

Metastatic adenocarcinoma to the cervical lymph node: a significant proportion of cholangiocarcinoma in thai patients.

Objective: To determine distribution of the primary site of metastatic adenocarcinoma to the cervical lymph node in Thai population with histological correlation. Materials and Methods: 72 Thai patients with metastatic adenocarcinoma to the cervical lymph node were retrospectively analyzed. Results: Thyroid gland (papillary carcinoma) was the commonest source of tumor (41%), followed by lung (25%), bile duct (17%) and breast (7%). Metastatic cholangiocarcinoma typically produced distinct glandular pattern, and frequently involved the right supraclavicular lymph node. Brush border of the gland-forming tumor cells was a consistent finding in metastatic cholangiocarcinoma, with 100% sensitivity and 97% specificity. Conclusions: Cholangiocarcinoma represents a significant portion of primary tumor in Thai patients with cervical nodal metastasis. This figure may hold true for countries where bile duct malignancy is endemic, and may be of clinical usefulness in identification of primary cancer.     

Radiation therapy for metastatic disease involving the orbit

A series of 47 patients with clinically demonstrated metastatic disease to the eye were evaluated for treatment with radiation therapy. Of the 37 patients who completed treatment, 88.9% responded with demonstrated tumor regression and improvement of symptoms. The breast and lung remain the two most common sites of origin for metastatic disease involving the orbit although the reason for this remains undetermined. The most common site of orbital involvement is the posterior choroid and no predilection for involvement of either the right or left eye could be determined. Radiation doses in the range of 3000-4000 rad delivered over a 3- to 4-week period of time, with care being taken to spare the lens, is recommended. Aggressive radiation therapy is indicated when the eye metastasis occurs without systemic disease or with stable systemic disease. The median survival in this group of patients was 8.5 months in those patients in whom adequate follow-up information was available.     

The clinicopathologic characteristics of colorectal cancer in patients under 50 years of age: experience of an oncology center

BACKGROUND/AIM: Colorectal cancer is seen mostly among patients older than 50 years of age. An aggressive behavior is a frequently cited as characteristic of colorectal cancer in young patients. The purpose of the present study was to reveal the clinicopathologic characteristics of colorectal cancer among patients under 50 years of age. METHODS: Two hundred and seventy-one patients with colorectal cancer admitted to our oncology center were evaluated, and clinicopathologic findings of the young and old patients were compared. Patient gender, site distribution, tumor stage classification, lymph node involvement, metastatic site, histologic classification, histologic differentiation, family history of malignant tumors, presenting symptoms and survival rates were compared. RESULTS: One hundred patients were 50 years of age or under. Clinical, histopathologic characteristics and overall survival of the two groups did not differ. A higher rate of familial cancer syndromes was detected among young patients. CONCLUSIONS: The presentation and outcome of the disease in young patients do not differ from those of older patients. A significant family history of colorectal cancer in the young patients showed the need for screening whereas the outcome of metastatic disease was poor. In order to anticipate long survival, early detection and aggressive treatment is necessary.     

Metastatic rhabdomyosarcoma of the thyroid gland, a case report

The thyroid gland is a known but an unusual site for metastatic tumors from various primary sites. Despite the fact that it is one of the largest vascular organs in the body, clinical and surgical cases have given an incidence of 3?% of secondary malignances of the organ. Nevertheless, thyroid metastases are not an exceptional finding at autopsy, they are encountered in 2?% to 24?% of the patients with malignant neoplasm. Soft tissue sarcomas metastatic to the thyroid are extremely rare as the majority of thyroid metastasis are caused by tumors of the kidneys, lungs, mammary glands, ovaries , and colon or by melanomas. We report a case of 22-years-old woman with right leg rhabdomyosarcoma metastatic to the thyroid gland.     

Successful treatment of extracranially metastasized pineal gland germinoma with high-dose methotrexate.

Germinoma of the pineal gland is a rare disease usually confined to the brain which responds well to radiotherapy. Spinal seeding occurs in approximately 4% of cases and distant metastases are extremely rare. We report on a 27-year-old female with an intracranially metastasized pineal gland germinoma, meningeal carcinomatosis and distant bone metastases. Treatment was initiated with intrathecal methotrexate (MTX) and continued with high-dose intravenous MTX. The therapy was very well tolerated apart from reversible hepatic toxicity requiring a dose reduction. The patient was in complete remission after three courses followed by two consolidation cycles; the patient has now been in continuous complete remission for more than 22 months. This is the first report to show that MTX is a potent drug in treating pineal gland germinoma. Long-term side effects of radiotherapy such as reduced mental function or hypopituitarism can probably be avoided. Single-agent high-dose MTX may provide high efficacy with limited adverse effects, especially at a more advanced tumor stage with spinal seeding and extracranial disease.     

Metastases to pineal gland

Metastases to the pineal gland is an uncommon event. Bronchogenic carcinomas are the most frequent source of the primary lesion. A case of small cell carcinoma of the lung with solitary metastases to the pineal gland is reported; the literature is reviewed.