Infratentorial Glioblastoma Metastasis to Bone.

BACKGROUND: Glioblastoma multiforme (GBM) is a rapid-growing central nervous system neoplasm. We report a case of GBM with extensive intramedullary lumbar drop metastasis and highly unusual osseous spine metastasis from a primary infratentorial GBM occurring 10 years after the initial diagnosis, which to our knowledge has not been described previously. CASE DESCRIPTION: This 37-year-old man presented with new-onset headaches of increasing severity. Brain magnetic resonance imaging (MRI) demonstrated a heterogeneously enhancing mass in the left superior temporal lobe with adjacent edema. The lesion was initially biopsied in December 2006 and diagnosed as GBM (World Health Organization grade IV) with characteristic features of a highly cellular infiltrating glial neoplasm with nuclear pleomorphism, abundant microvascular proliferation, and abundant necrosis with pseudopalisading nuclei. Ki-67 immunostaining revealed that 15%-20% tumor cell nuclei were positive, indicating a high proliferative index. Histologically, this neoplasm demonstrated characteristic "cell wrapping." Immunoreactivity was variably but strongly positive for glial fibrillary acidic protein in neoplastic cells. In 2018, additional MRI revealed disease throughout the spine and bone biopsy of the thoracic spine showed the same glial neoplasm with primitive neuroectodermal tumor-like components (GBM-PNET). CONCLUSIONS: This case is meant to highlight that, although rare, infratentorial GBM-PNET has a higher frequency of isocitrate dehydrogenase 1 (IDH1) mutation and may metastasize to the spine years after the initial diagnosis despite the likely better prognosis.

Primitive neuroectodermal tumor arising from an untreated congenital undescended testicle.

A 26-year-old male with a personal history of schizophrenia initially presented with a 13 cm pelvic mass corresponding to a cryptorchidic testis. The patient was treated with primary and second-line chemotherapy for metastatic germ-cell tumor followed by surgical consolidation. Final pathology revealed a primitive neuroectodermal tumor (PNET) mixed with mature teratoma. Despite multidisciplinary management, significant patient non-compliance led to inadequate follow up and treatment delays ultimately resulting in death. To our knowledge, this is the only reported case of teratoma with malignant transformation arising from an untreated congenital undescended testicle.

Intracranial Peripheral Primitive Neuroectodermal Tumor Arising from the Clivus with Intracranial Metastasis in an Elderly Woman: Case Report and Review of the Literature.

BACKGROUND: Intracranial peripheral primitive neuroectodermal tumors (pPNETs) are rare lesions, accounting for only 1% of all pPNETs, and usually arise from bone and soft tissue. These tumors primarily affect young patients (<30 years old) and rarely affect older patients. The common intracranial locations of these lesions are frontal dura and tentorium. These lesions rarely may involve the cerebellopontine angle, cavernous sinus, and jugular foramen. Involvement of clivus has not been reported to date. Intracranial metastasis from primary intracranial pPNET is a further rare occurrence. CASE DESCRIPTION: A 74-year-old woman presented with gradually progressive painless diminution of vision in both eyes alongwith headache for 6 months duration. Radiology demonstrated a clival mass as well as a suspected intracranial metastasis. Histopathology was suggestive of pPNET. We also present a brief review of the literature on pPNETs. CONCLUSIONS: pPNETs of the clival region are exceptionally rare. In elderly patients with clival mass lesions, the rare possibility of pPNET should be kept in mind.

Management of patients with metastatic teratoma with malignant somatic transformation.

PURPOSE OF REVIEW: The purpose of this review is to examine the historical context alongside contemporary studies in order to provide the most current recommendations for the management of patients with metastatic teratoma with malignant somatic transformation (MST). RECENT FINDINGS: The main themes in the recent literature covered herein include prognostic features, the management of early-stage disease, recommended chemotherapeutic and surgical strategies as well as recognized patterns of late relapse. SUMMARY: Recent literature, combined with a significant contribution from historical studies, suggests that while MST is uncommon, its aggressive nature coupled with its resistance with traditional germ cell tumor chemotherapies makes it very difficult to manage. The key message is that surgery is recommended in all resectable MST from primary retroperitoneal lymph node dissection for clinical stage I, to radical removal of disease after chemotherapy and when chemotherapy fails. In advanced cases with documented spread of the transformed histologic subtype, systemic therapies targeted to the identified tumor type should be considered.

Metastatic malignant transformation of teratoma to primitive neuroectodermal tumor (PNET): results with PNET-based chemotherapy.

BACKGROUND: Metastatic germ cell cancers are highly chemosensitive and have 80% cure rate with cisplatin-based chemotherapy. Postchemotherapy teratoma can usually be surgically resected. However, teratoma, which is pluripotent tissue, can undergo malignant transformation along mesodermal elements to primitive neuroectodermal tumor (PNET). Unlike teratoma, PNET can metastasize and render a patient unresectable and incurable. We report the results of treatment of patients with malignant transformation to PNET with cyclophosphamide+doxorubicin+vincristine (CAV) alternating with ifosfamide+etoposide (IE). METHODS: We reviewed 86 patients with histologically confirmed PNET transformed from testicular teratoma at Indiana University from 1998 to 2012. We identified 18 patients who were treated with chemotherapy comprising cyclophosphamide (1000 to 1200 mg/m), doxorubicin (50 to 75 mg/m), and vincristine (2 mg) alternating with ifosfamide (1.8 g/m) plus etoposide (100 mg/m) for 5 consecutive days. Treatment was given every 3 weeks with a maximum of 6 cycles or until progression or undue toxicity. Hematopoietic growth factors were usually incorporated. The remaining 68 patients underwent surgical resection. RESULTS: Twelve patients had unresectable disease and 6 were treated in an adjuvant setting. Median age was 29 years (range, 20 to 53 y). Nine of the 12 metastatic patients achieved objective response by RECIST criteria. Six of those were rendered with no evidence of disease (NED) with further surgery. Although 4 of the 6 patients subsequently relapsed, 1 patient remains alive and NED at 78 months. The 6 patients who received adjuvant treatment are alive with NED at 9 to 90 months with a median duration of 32.7 months. CONCLUSIONS: CAV and IE alternating chemotherapy has high objective response rate for PNET transformed from teratoma and results in occasional long-term disease-free survival when combined with subsequent resection. We recommend adjuvant CAV alternating with IE chemotherapy for patients with PNET after RPLND due to the high probability of recurrent disease and their high chemosensitivity to this regimen.

Clinical and pathological features of primary neuroectodermal tumor/Ewing sarcoma of the kidney.

OBJECTIVE: To collect and analyze clinical and pathological features of primitive neuroectodermal tumor (PNET)/Ewing sarcoma (EWS), a rare tumor occurring most commonly in bone and soft tissues of young people, which rarely occurs as a primary renal neoplasm and exhibits highly aggressive biological behavior. METHODS: All cases of PNET/EWS published from 1975 to February 2012 were collected. When available, clinical and pathological data were extracted for each case. Survivals were estimated with the Kaplan-Meier method and compared with the log-rank test with 95% confidence interval (CI). RESULTS: A total of 116 cases were found. All patients had clinical symptoms as first presentation of disease such as pain (54%), hematuria (29%), and bulky renal mass (28%). Sixty-six percent of patients had stage IV disease at diagnosis. Median disease-free survival (DFS) was 5.0 months (95% CI 2.4-7.6). The probability to be alive at 18 months was 60% and 85% for patients with metastatic disease (M1) or not (M0) at diagnosis, respectively. Median overall survival (OS) was 24 months (95% CI 4.5-15.1) in patients with M1 disease, whereas it was not reached in patients with M0 disease (P <.001). In patients with M0 disease, 50% received neoadjuvant chemotherapy and the 12-month OS was 93% compared to 75% of untreated patients (P = .092). In patients with M1 disease who underwent treatment, the median progression-free survival (PFS) was 22.0 months (95% CI 17.9-26.1) with a clinical benefit in 74% of cases. CONCLUSION: Our findings suggest that PNET/EWS is a rare aggressive tumor affecting principally young people, with a poor prognosis for patients with M1 disease; chemotherapy is an effective strategy in M1 disease and probably also in M0 disease.

Treatment outcomes in 23 thoracic primitive neuroectodermal tumours: a retrospective study.

OBJECTIVES: Thoracic primitive neuroectodermal tumour is an aggressive malignancy with poor survival despite multimodality treatment regimens. Early diagnosis of the tumour by histological, immunohistochemical, ultrastructural and cytogenetic techniques and early total surgical resection of the tumour with intensive chemoradiation may improve outcomes. METHODS: Over 30 years, 23 patients (median age 29.5) with primitive neuroectodermal tumours (15 chest wall, 4 lung, 3 costovertebral sulcus and 1 anterior mediastinum) were diagnosed by transthoracic needle biopsy (43%) or excisional biopsy (57%). Treatment of a localized disease (Stage I and II) in 19 patients included surgery (wide excision of chest lesions in 11, 4 lung resections, excision of 3 costovertebral sulcus and 1 anterior mediastinal tumours, and resection of adjacent tissues involved by tumour en bloc) with adjuvant chemoradiation. Four metastatic chest wall tumours (Stage III) had chemotherapy and radiation alone. RESULTS: Tumour recurred in 5 (2 chest wall, 2 costovertebral sulcus and 1 lung) requiring further chemotherapy, radiation and completion pneumonectomy for a lung recurrence. The incidence of recurrent tumour in 7 years for Stage I was 21 vs 40% (P=0.4) for Stage II lesions and 16% after the neoadjuvant chemotherapy vs 30% (P=0.4) after adjuvant chemoradiation. Four with recurrence, except one with a chest recurrence, succumbed to second relapse (78-96 months). All four Stage III chest tumours succumbed to advanced disease (30 months). The Kaplan-Meier disease-free survival of the overall group (23 patients) was 82±2% at 5 years and 64±3% at 10 years. The 10-year disease-free survival of 19 patients with localized tumours was 76%, but was high at 90% for chest wall tumours and low 33% for costovertebral sulcus tumours (P≤0.01). The 10-year disease-free survival was 86% for Stage I vs 60% (P=0.02) for Stage II tumours; and 83% for neoadjuvant vs 76% (P=0.06) for adjuvant chemotherapy and radiation. CONCLUSIONS: The primitive neuroectodermal tumours are aggressive neoplasms with poor prognosis. Early diagnosis and total surgical excision of localized tumours with neoadjuvant or adjuvant chemotherapy and radiation improved disease-free survival.

Extraosseous Ewing sarcoma and peripheral primitive neuroectodermal tumor of the thyroid gland: Case report and review.

The Ewing family of tumors and peripheral primitive neuroectodermal tumor (pPNET) represent different manifestations of the same entity. Immunohistochemical and cytogenetic studies suggest that these tumors have a common origin. Ewing sarcoma is more common in bone, while pPNET is more common in soft tissues. Extraosseous Ewing sarcoma (EoES) is rare. We present the case of a 48-year-old man who presented with acute obstructive respiratory failure secondary to a large thyroid swelling. The patient was initially diagnosed with giant B-cell non-Hodgkin lymphoma and treated with chemotherapy. However, subsequent immunohistochemical staining of biopsy specimens revealed that the patient actually had EoES/pPNET of the thyroid gland. We performed a nearly complete surgical resection of the tumor plus a total laryngectomy and resection of five tracheal rings. However, the patient died of a cerebral metastasis 1 month later after he had completed one cycle of postoperative chemotherapy.

Primary pulmonary primitive neuroectodermal tumor metastasis to the pancreas: a rare case with seven-year follow-up.

There are only nine primitive neuroectodermal tumor (PNET) cases that have arisen in lung parenchyma without pleural or chest wall involvement in the literature. Here, we present a long-term survival case of pulmonary PNET. A pulmonary mass was detected in a 19-year-old man on a chest radiograph and computed tomography image. At the three-year follow-up, the mass had enlarged in diameter by two-fold. The lesion was resected via lower left lobectomy. Histologically, the tumor was composed of uniform cells with round nuclei and scanty cytoplasm arranged in lobules with rosettes and pseudorosettes formation. Immunohistochemically, the tumor was positive for CD99, vimentin, neuron specific enolase and chromogranin A, and negative for cytokeratins, CD3, desmin, and leukocyte common antigen. Pancreatic metastasis occurred sixteen months after the first surgery, which was managed by pancreatectomy. The patient has survived seven years after the mass was initially detected, and four years after the first lobectomy. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1500847644913244.

Askin tumour: a rare thoracopulmonary tumour in adults.

Askin tumour, a primitive neuroectodermal tumour of the thoracopulmonary region, is a rare tumour presenting in childhood. Its presentation in adults is rare. We report a case of an Askin tumour in an adult patient who presented to us with worsening breathlessness and vague chest pain. Investigations including immunohistochemistry confirmed the diagnosis of Askin tumour.

Glucagon receptor is required for long-term survival: a natural history study of the Mahvash disease in a murine model.

BACKGROUND AND AIM: We have described a novel Mahvash disease of hyperglucagonemia and pancreatic neuroendocrine tumors (PNETs) associated with an inactivating glucagon receptor mutation, and identified the glucagon receptor-deficient (Gcgr(-/-)) mice as its murine model. We aim to elucidate the natural history of the rare Mahvash disease by long-term observation of the Gcgr(-/-) mice. MATERIALS AND METHOD: Wild type (WT) (n=52), heterozygous (n=127), and Gcgr(-/-) (n=56) mice living under standard vivarium conditions were observed without specific treatments over 22 months. Autopsy was performed on dead animals. RESULTS: The WT and heterozygous mice did not exhibit any measurable differences. The Gcgr(-/-) mice became progressively lethargic and cachexic after 12 months. Random glucose levels were stable in WT and heterozygous mice but decreased with age in the Gcgr(-/-) mice. At the end of observation, 28/56 Gcgr(-/-), 7/52 WT, and 24/127 heterozygous mice died. The survival curve of Gcgr(-/-) mice began to separate from those of WT and heterozygous mice at 12 months and the survival difference widened with age. At 18 months, survival probability was 17% for Gcgr(-/-) mice but 77% for WT and 81% for heterozygous mice. Autopsy revealed numerous PNETs up to 15 mm in diameter in most well-preserved Gcgr(-/-) pancreata (17/20) but none in WT or heterozygous ones. Four Gcgr(-/-) mice developed liver or subcutaneous metastasis. CONCLUSION: The untreated Mahvash disease may cause cachexia, severe hypoglycemia, and early death. Patients with Mahvash disease need to undergo life-long surveillance for PNETs. Functional glucagon receptor is thus required for long-term survival.

Extra-osseous Ewing sarcoma of the thyroid gland mimicking lymphoma recurrence: a case report.

Extra-osseous Ewing sarcomas/peripheral primitive neuroectodermal tumors (EOES/pPNETs) are high-grade malignant tumors found in various organs, such as the lung, skin, intestine, kidney and female genital tract; however, to the best of our knowledge, only two cases have previously been identified in the thyroid gland. We describe a case of primary EOES/PNET of the thyroid gland in a 66-year-old man with a previous history of large B cell lymphoma. During a routine follow-up examination, the patient underwent an ultrasound cervical scan showing a solid nodule of the left thyroid lobe. The fine-needle aspiration biopsy of the nodule suggested a neuroendocrine tumor. Histological and immunohistochemical examination of the surgical specimen supported a diagnosis of EOES/PNET, which was further confirmed by the demonstration of EWSR1 gene translocation by means of fluorescent in situ hybridization and by the detection of glycogen particles and neurosecretory granules by means of electron microscopy. Total body computed tomography and magnetic resonance imaging excluded the involvement of other sites, and therefore a diagnosis of primary EOES/PNET of the thyroid gland was made.This paper also discusses the main differential diagnoses, including lymphoma recurrence, other small round cell tumors (primary or metastatic), and a thyroid localization of an EWS/PNET from another organ.

Primitive chest wall neuroectodermal tumor in a pediatric patient.

A 13-year-old boy with a primitive neuroectodermal tumor of the chest wall is presented. After four cycles of chemotherapy, a computed tomography scan of his chest showed a larger mass invading the left upper lobe of the lung. He underwent resection of the left chest wall from the left fourth to sixth ribs, including the tumor, combined with left upper lobectomy and lymph node dissection. A diagnosis of primitive neuroectodermal tumor was confirmed histopathologically and immunohistochemically. After surgery, four cycles of chemotherapy with ifosfamide and etoposide were given. One year after treatment, the patient is currently doing well without evidence of recurrence.

Prognostic factors and outcome in Askin-Rosai tumor: a review of 104 patients.

PURPOSE: To evaluate the prognostic factors and treatment outcome of patients with Askin-Rosai tumor of the chest wall treated at a single institution. METHODS AND MATERIALS: Treatment comprised multiagent chemotherapy and local therapy, which was either in the form of surgery alone, radical external-beam radiotherapy (EBRT) alone, or a combination of surgery and EBRT. Thirty-two patients (40%) were treated with all three modalities, 21 (27%) received chemotherapy and radical EBRT, and 19 (24%) underwent chemotherapy followed by surgery only. RESULTS: One hundred four consecutive patients aged 3-60 years were treated at the Tata Memorial Hospital from January 1995 to October 2003. Most (70%) were male (male/female ratio, 2.3:1). Asymptomatic swelling (43%) was the most common presenting symptom, and 25% of patients presented with distant metastasis. After a median follow-up of 28 months, local control, disease-free survival, and overall survival rates were 67%, 36%, and 45%, respectively. Median time to relapse was 25 months, and the median survival was 76 months. Multivariate analysis revealed age ≥18 years, poor response to induction chemotherapy, and presence of pleural effusion as indicators of inferior survival. Fifty-six percent of patients with metastatic disease at presentation died within 1 month of diagnosis, with 6-month and 5-year actuarial survival of 14% and 4%, respectively. CONCLUSION: Primary tumor size, pleural effusion, response to chemotherapy, and optimal radiotherapy were important prognostic factors influencing outcome. The combination of neoadjuvant chemotherapy, surgery, and radiotherapy resulted in optimal outcome.

Unusual presentation of peripheral primitive neuroectodermal tumor of the maxilla.

The peripheral primitive neuroectodermal tumor (pPNET) is a rare and highly malignant soft tissue neoplasm in children and young adults. Fewer than 10 reported cases of pPNET of maxilla are available in the English literature. A 28-year-old woman was presented with the pPNET of the maxilla and metastasis. Two years after diagnosis, she experienced diplopia, and then magnetic resonance imaging was done, which showed a mass in the optic chiasma and parasellar region. The typical appearance resembled large noncalcified soft tissue masses in the magnetic resonance image and computed tomographic scan of the maxilla. Diagnosis was established by immunohistochemical features. She was treated with surgery, chemotherapy, radiation therapy, and gamma knife. She was under close observation since then (approximately 8 mo), and there has been no recurrence of tumor up to now.

Supratentorial primitive neuroectodermal tumor metastasis to the abdomen via a ventriculoperitoneal shunt.

Primitive neuroectodermal tumors (PNETs) include a heterogeneous group that originate from primitive neuroepithelial cells. PNETs are prone to cerebrospinal fluid seeding and central nervous system spread. Infratentorial PNET, or medulloblastoma, is a common brain tumor in children and metastatic spread to the abdomen via a ventriculoperitoneal (VP) shunt has been described. Supratentorial PNETs are much less common. We present a rare case of a predominantly supratentorial PNET metastasizing to the abdomen via a VP shunt and discuss the radiological findings. This case demonstrates the small but real risk of metastatic spread, which should be weighed when considering VP shunt placement.

Primitive neuroectodermal tumors in patients with testicular germ cell tumors usually resemble pediatric-type central nervous system embryonal neoplasms and lack chromosome 22 rearrangements.

Primitive neuroectodermal tumors (PNETs) are one of the most frequent types of 'non-germ cell' tumor in patients with testicular germ cell tumors and have a guarded prognosis when present in metastatic sites after cisplatin-based chemotherapy. Improved treatments, including targeted therapy, require understanding the biology of these neoplasms. We therefore analyzed the morphologic, immunohistochemical and molecular biologic features of 14 PNETs from 14 patients with concurrent or previous testicular germ cell tumors; 12 tumors were from metastatic sites and 2 were primary in the testis. Using standard light microscopic criteria for central nervous system and peripheral PNETs, we classified nine tumors as medulloepithelioma, three as medulloblastoma/supratentorial PNET, one as neuroblastic tumor with abundant neuropil and true rosettes and one as small cell embryonal tumor/PNET (Ewing sarcoma-like). Immunostains directed against INI1, CD57, S-100 protein, NeuN, WT1, neurofilament, CD99, GFAP, synaptophysin, chromogranin, AE1/AE3 cytokeratin, Fli-1 and collagen IV were performed for each case. INI1 was diffusely and strongly positive in all tumors whereas the other stains, except for cytoplasmic WT1 (which showed substantial reactivity in most tumors), were mostly focal to negative, including CD99 (eight negative, six focal) and Fli-1 (all negative). The most consistently reactive 'neuroendocrine' marker was CD57. Each case was also analyzed for chromosome 22 rearrangements using a FISH-based break-apart probe method. Only 1 tumor, classified as medulloepithelioma, was scored positive for chromosome 22 translocation (22% rearranged cells) and the remaining 13 were negative, including the one case that resembled peripheral PNET. We conclude that PNETs derived from testicular germ cell tumors mostly resemble central nervous system PNETs and generally lack the chromosome 22 translocation of peripheral PNETs. Future treatment strategies should take these findings into account.

Peripheral neuroectodermal tumor of the vulva: a case report.

BACKGROUND: Peripheral neuroectodermal tumors arising from vulva are extremely rare; only 12 cases have been reported so far. These tumors belong to the Ewing sarcoma family of tumors. They occur in bones and variety of soft tissues of chest wall, pelvis, paravertebral region, and lower extremities. Being aggressive tumors, they have poor prognosis. CASE: We report a case of a 20-year-old woman who presented with a 20 x 15 x 10-cm pedunculated mass arising from the right labium majus. Judicious use of a panel of markers led to diagnosis of peripheral neuroectodermal tumor. The patient died of metastatic disease. CONCLUSIONS: Judicious use of a panel of markers and a molecular test, if necessary, helps in confirming the diagnosis. Surgery followed by chemotherapy with or without radiation is the treatment of choice.

Peripheral primitive neuroectodermal tumour of the chest wall invading lung with regional lymph node metastasis.

Here we present the case of a 26-year-old man in whom peripheral primitive neuroectodermal tumour of chest wall origin invaded the left lung with regional lymph node metastasis. He underwent initial resection of the left chest wall tumour with combined left lower lobectomy, left S5 segmentectomy, and lymph node dissection in order to facilitate a definitive diagnosis and also to obviate the risk of fatal bleeding due to tumour invasion of the pulmonary artery. Histological examination of the resected sample revealed small round cell proliferation with neural differentiation, and confirmed lymph node involvement within the left lower lobe. EWS/FLI-1 fusion gene transcripts were detected by the reverse-transcription polymerase-chain reaction. Diagnosis of peripheral primitive neuroectodermal tumour was confirmed. After surgery, combination chemotherapy with cyclophosphamide, vincristine, doxorubicin, ifosphamide, and etoposide was given. Five years after resection, the patient remains alive and well, with no signs of recurrence.