We report on a very rare case of a supratentorial primitive neuroectodermal tumor in an adult, which presented with intracerebral hemorrhage, and review the relevant medical literature.
A 42-year-old Caucasian man complained of a sudden headache and nausea-vomiting. The patient rapidly deteriorated to coma. An emergency computed tomography scan showed an extensive intraparenchymal hemorrhage that caused significant mass effect and tonsilar herniation. During surgery, an increased intracranial pressure was recorded and extensive bilateral decompressive craniectomies were performed. A cherry-like intraparenchymal lesion was found in his right frontal lobe and resected. The patient died in the intensive care unit after approximately 48 hours. The resected lesion was identified as a central nervous system primitive neuroectodermal tumor.
Supratentorial primitive neuroectodermal tumors must be considered in the differential diagnosis of space-occupying lesions in adults. Spontaneous supratentorial hemorrhage due to primitive neuroectodermal tumors is an extremely rare but potentially lethal event.
We report a supratentorial primitive neuroectodermal tumor (sPNET) in 17-year-old primipara in the second trimester her pregnancy. Magnetic resonance imaging revealed a left frontoparietal mass with solid and cystic component. Gross-total resection was achieved via a left frontoparietal craniotomy. It was decided to suspend the radiotherapy and chemotherapy until the 30 weeks of gestation. But, a sudden uncal herniation was developed due to the reccurrence of the tumor and bleeding into the tumor at the 25 weeks of gestation and the patient died after urgent decompressive surgery. sPNETs is an extremely rare brain tumor in pregnancy and only two cases were reported in the literature to date. There is no universally agreed treatment protocol for sPNETs during pregnancy and a multidisciplinary approach is required in treatment. In the present study, the clinical, histopathological features and therapeutical difficulties of sPNETs diagnosed during pregnancy was discussed with the literature review.
Multidisciplinary treatment; Pregnancy; Supratentorial primitive neuroectodermal tumor
Primitive neuroectodermal tumor of the uterus is extremely rare. They occur as either pure primitive neuroectodermal tumors or admixed with neoplasms of mullerian origin.
A case of uterine primitive neuroectodermal tumor with adenosarcoma in a 50-year-old Asian Indian woman is presented. Histologically, the neoplasm displayed perivascular pseudorosettes and occasional Homer-Wright rosettes. A strong positivity for neuronspecific enolase and synaptophysin was noted, while chromogranin and CD99 were negative. Merging imperceptibly with the neuroectodermal components were the areas of adenosarcoma.
To the best of our knowledge, this report represents the second case of a uterine primitive neuroectodermal tumor with an admixed adenosarcoma.
Sinonasal teratocarcinosarcoma (SNTCS) is a rare and highly malignant tumour with combined features of a teratoma and carcinosarcoma. We report the first case of a SNTCS in 23 year old male treated with neo-adjuvant chemotherapy followed by cranio-facial resection. The resection specimen displayed cellular maturation in the neuroectodermal component. The patient presented with a short history of nasal obstruction, epistaxis and headache. On imaging, a bone destroying lesion of left paranasal sinuses and nasal cavity was identified. The diagnosis of SNTCS could be offered only on the third biopsy which showed heterogeneous admixture of primitive neuroectodermal, epithelial and mesenchymal elements. An adequate sampling with high index of suspicion is needed to catch hold this rare tumor. Tumor was excised after 4 cycles of neo-adjuvant chemotherapy. On microscopic examination, it showed similar epithelial and mesenchymal components as the pretreatment biopsies. However, the primitive neuroectodermal component displayed extensive neuronal maturation. The undifferentiated neuroectodermal cells were completely absent in the post chemotherapy specimen. This case throws light on the morphologic evidence of chemotherapy induced maturation in the neuroectodermal component within SNTCS, an event hitherto not reported in the literature in case of SNTCS.
Teratocarcinosarcoma; Sinonasal tumours; Neuronal maturation; Neo-adjuvant chemotherapy
A 16-year-old Caucasian male was diagnosed with a primitive neuroectodermal tumor (PNET) five years following the diagnosis of nonmetastatic osteosarcoma of the left proximal humerus. The patient was initially treated with standard chemotherapy and limb salvage resection for osteosarcoma. Nine months after the completion of therapy, he developed lung metastases for which he underwent surgical resection and received additional chemotherapy. Almost five years after the osteosarcoma diagnosis, the patient was diagnosed with a supratentorial PNET, which represents the first known case reported in a patient with osteosarcoma.
osteosarcoma; primitive neuroectodermal tumor; genetic predisposition syndromes
Medulloepitheliomas (WHO grade IV) are rare, malignant embryonal tumors of pediatric population, classified under the central nervous system (CNS) primitive neuroectodermal tumors (PNET). Histologically, these tumors are characterized by neoplastic neuroepithelium recapitulating the embryonic neural tube. We describe a rare case of infratentorial medulloepithelioma with divergent differentiation in a 1-year-old male child who presented with headache, vomiting, and seizures. Histopathologic examination of the excised tumor revealed the characteristic neuroepithelium, along with other areas showing primitive neuroectodermal (blastemal) cells in sheets, ependymoblastic rosettes, and nodular areas of neuronal differentiation. Possibly, this proliferating immature neuroepithelium is the cause of poor outcome in medulloepitheliomas. Due to the rarity of these tumors, it remains to be established whether infratentorial location or tumors with divergent differentiation are also predictors of adverse prognosis.
Differentiation; ependymoblastic; infratentorial; medulloepithelioma; neuronal
The occurrence of primitive neuroectodermal tumors (PNET) in patients with neurofibromatosis type 1 (NF1) has only been reported in two other cases in English-Language literature. Owing to the rarity of intraspinal PNET and the extremely high gene mutation variability in NF1, there is currently no conclusive evidence to suggest that PNET is associated with NF1. Here, we report a case of intradural PNET in a patient with NF1.
A 27-year-old male underwent a C1-C3 laminectomy for resection of an intramedullary mass. Histopathology and immunohistopathology analysis was performed. Microscopic examination and immunohistochemical staining indicated the mass was a primitive neuroectodermal tumor. Within 1 month after tumor resection, the patient developed leptomeningeal carcinomatosis. The patient was not a candidate for radiation therapy but underwent palliative systemic chemotherapy. He subsequently developed neutropenia and died 3 months after tumor resection.
To our knowledge, this is the first reported intraspinal PNET associated with NF1. Genetic analysis of CNS PNETs suggests a possible correlation, but larger case series are needed to support this theory.
Intramedullary primitive neuroectodermal tumors; neurofibromatosis type 1; primitive neuroectodermal tumor
Primary Ewing's sarcoma or primitive neuroectodermal tumor of the genital tract of women is uncommon. Rarer still is its occurrence in the vagina, with only five cases described so far. Out of these, only one case was confirmed using molecular analysis.
We present an extremely rare case of Ewing's sarcoma or primitive neuroectodermal tumor in a 17-year-old Indian girl. She presented with a vaginal mass that was initially diagnosed as a malignant round cell tumor. Immunohistochemistry showed diffuse positivity for vimentin, membranous positivity for MIC2, and positivity for BCL2 and FLI-1. On the other hand, she was negative for cytokeratin, epithelial membrane antigen, desmin, Myo D-1, myogenin and smooth muscle actin. A diagnosis of primitive neuroectodermal tumor was thus offered. Furthermore, a molecular analysis of our patient using reverse transcription-polymerase chain reaction technique showed positivity for t(11; 22) (q24; q12) (EWSR1-FLI1), thus confirming the diagnosis of a Ewing's sarcoma/primitive neuroectodermal tumor. Our patient was offered chemotherapy on Institutional protocol EFT 2001.
This is a rare case of primary vaginal Ewing's sarcoma or primitive neuroectodermal tumor, which was confirmed with molecular analysis, in the youngest patient known so far. This study reinforces the value of integrating morphological features with membranous MIC2 positivity, along with application of molecular techniques in objective identification of an Ewing's sarcoma or primitive neuroectodermal tumor at uncommon sites.
Primitive neuroectodermal tumors (PNETs) occur predominantly in childhood preferentially in the soft tissues of the lower extremity and the paraspinal region. We present here a rare case of a PNET of the kidney in an adult.
A tumor adjacent to the right kidney was detected by ultrasound coincidentally at a routine check-up in a 46-year-old woman with irritable bowel syndrome in her medical history. The patient had no clinical signs. Contrast-enhanced computerized tomography scan of the abdomen demonstrated a highly vascularized renal tumor. A retroperitonealectomy with en-bloc resection of the kidney was performed, and histopathological work-up showed a primitive neuroectodermal tumor of the kidney with the characteristic translocation t(11;22)(q24;q12).
This tumor entity must be accurately distinguished from other renal neoplasms because of the prognostic and therapeutic impact.
Primitive neuroectodermal tumor (PNET) is a rare “small round blue cell tumor” that is diagnosed by open biopsy or percutaneous biopsy of the lesion under radiologic guidance. In this case report, we present a novel approach to the diagnosis of a retroperitoneal PNET by endoscopic ultrasound- (EUS-) guided fine needle aspiration (FNA). A 35-year-old man presented with the history of left-sided flank pain and swelling of 3-weeks duration. Computerized tomography (CT) scan of his abdomen revealed a 12.8 × 13 × 12.5 cm cystic and solid mass arising from the retroperitoneum and displacing the third and fourth portions of the duodenum. He underwent EUS which revealed a well-circumscribed heterogeneous mass abutting the inferior portion of the stomach. EUS-FNA of the mass revealed malignant cells consistent with primitive neuroectodermal tumor (PNET)/Ewing's sarcoma. EUS-guided FNA is an appropriate technique for diagnosing retroperitoneal PNET/Ewing's sarcoma.
Peripheral primitive neuroectodermal tumors of the urinary bladder are rare and tend to occur in an older age group than do their counterparts in bones and soft tissue.
We report a case of peripheral primitive neuroectodermal tumor of the urinary bladder in a 67-year-old woman of Arab origin. She had undergone transurethral resection followed by chemotherapy because of pulmonary metastasized muscle-invasive squamous cell carcinoma of the bladder in 2005. One year later, she first presented with a history of repeated hematuria in our institution. Performing cystoscopy any tumor could be detected. Control cystoscopy two months later showed a tumor mass of 3 cm in diameter at another location than described for the first tumor. After perforating by transurethral resection partial bladder resection had to be done. Tissue specimen after pathological analysis revealed a peripheral primitive neuroectodermal tumor with tumor cells reactive to cluster of differentiation 99, neuron-specific enolase and S100 protein and stained negative for other markers such as cytokeratins, epithelial membrane antigen, desmin, smooth muscle actin, chromogranin and leucocyte common antigen. Staging computerized tomography was especially free from any hint on organ metastasis, but the patient died due to a cardiac problem only a few months later.
To the best of our knowledge, we report the eighth case of bladder peripheral primitive neuroectodermal tumors in literature and the first concerning an Arab patient. It is also the first presentation of a peripheral primitive neuroectodermal tumor patient with a history of squamous cell carcinoma of the bladder. As in other cases, expression of single-chain-type 1 glycoprotein and neural markers was positive and the disease was at an advanced stage at the time of diagnosis.
Medulloblastomas and supratentorial primitive neuroectodermal tumours are aggressive childhood tumours. We report our findings using array comparative genomic hybridisation (CGH) on a whole-genome BAC/PAC/cosmid array with a median clone separation of 0.97Mb to study 34 medulloblastomas and 7 supratentorial primitive neuroectodermal tumours. Array CGH allowed identification and mapping of numerous novel small regions of copy number change to genomic sequence, in addition to the large regions already known from previous studies. Novel amplifications were identified, some encompassing oncogenes, MYCL1, PDGFRA, KIT and MYB, not previously reported to show amplification in these tumours. In addition, one supratentorial primitive neuroectodermal tumour had lost both copies of the tumour suppressor genes CDKN2A & CDKN2B. Ten medulloblastomas had findings suggestive of isochromosome 17q. In contrast to previous reports using conventional CGH, array CGH identified three distinct breakpoints in these cases: Ch 17: 17940393-19251679 (17p11.2, n=6), Ch 17: 20111990-23308272 (17p11.2-17q11.2, n=4) and Ch 17: 38425359-39091575 (17q21.31, n=1). Significant differences were found in the patterns of copy number change between medulloblastomas and supratentorial primitive neuroectodermal tumours, providing further evidence that these tumours are genetically distinct despite their morphological and behavioural similarities.
Medulloblastoma; supratentorial primitive neuroectodermal tumour; array-CGH; genomic copy number
Primitive neuroectodermal tumor is a small round cell malignancy which rarely involves the orbit. We report a case of a two-year old male child presenting as unilateral eccentric proptosis with extraconal and intraconal mass, diagnosed as primary peripheral primitive neuroectodermal tumor (pPPNET) on histopathology and immunohistochemistry. There is no defined consensus in the management of these tumors due to its rare presentation. We describe its distinguishing features with emphasis on multimodal and aggressive treatment approach which ensures appropriate management of these cases.
Extraosseous Ewing's sarcoma; nonspecific enolase; primitive neuroectodermal tumor
Peripheral primitive neuroectodermal tumor of the cervix uteri is extremely rare. Between 1987 and 2010, there were only nine cases reported in the English literature, with considerably different management policies.
A 45-year-old Iranian woman presented to our facility with a primitive neuroectodermal tumor of the cervix uteri. Her clinical stage IB2 tumor was treated successfully with chemotherapy. Our patient underwent radical hysterectomy. There was no trace of the tumor after four years of follow-up.
According to current knowledge, primitive neuroectodermal tumors belong to the Ewing's sarcoma family, and the improvement of treatment outcome in our patient was due to dose-intensive neoadjuvant chemotherapy, surgery and consolidation chemotherapy in accordance with the protocol for bony Ewing's sarcoma.
Primary spinal primitive neuroectodermal tumors (PNET) are rare tumors, with only 94 cases reported till date. Metastasis to brain from a spinal PNET is even rarer. In the present report, we evaluate the pathology and treatment of solitary intracranial metastasis from spinal PNET in a 22-year-old female who presented with headache and left hemiparesis and was diagnosed to have right parietal parasagittal tumor. She has been previously diagnosed to have cervicothoracic primary spinal PNET, and was treated by surgery, radiotherapy, and chemotherapy seven years back. The intracranial tumor has been removed and pathological examination confirmed as PNET. She received radiotherapy and chemotherapy with ifosfamide and etoposide, following surgery for the right parietal PNET. At 20 months follow-up, patient is stable and has no recurrence of the disease. Critical review of reported cases of primary spinal PNET metastsising to brain was done.
CD 99; metastasis; primitive neuroectodermal tumor; spinal tumor
Brain tumors in infants present special diagnostic and therapeutic challenges. To figure out the clinical features, pathological classification of the tumors and the treatment outcome of infantile brain tumors, 458 children (age<16) with brain tumors were reviewed retrospectively. Among them 21 cases (4.6%) were diagnosed during the first 12 months of life. Two tumors were definitely of congenital origin. The majority of infants with brain tumors presented with increased intracranial pressure. Fourteen tumors were located at the supratentorial area. Sixteen cases had neuroepithelial tumors; astrocytoma (optic pathway), supratentorial primitive neuroectodermal tumor (PNET) and medulloblastoma were found in three cases each. There were two treatment-related mortalities. Compared with the outcomes in older children, the treatment outcome was poorer in medulloblastoma and the optic pathway glioma which showed a higher growth potential. Because of the limited application of postoperative adjuvant therapy, radical surgical removal played a more important role in this age group. The prognosis of patients in whom the tumors could not be totally removed, largely depended on the pathological malignancy of the tumors. Though the treatment outcome was not always dismal, immaturity of the brain, higher growth potential, perioperative risks, limitations in adjuvant therapy, and pessimistic attitude on the part of parents made management more challenging.
Renal primitive neuroectodermal tumor (rPNET) as a member of Ewing’s sarcoma family is extremely rare and usually occurs in children and young adults. Most literature about rPNET was isolated case reports.
We reported a case of 45-year-old man with the complaint of right flank pain. Computerized tomography (CT) scan demonstrated a large substantive tumor involving the lower pole of the right kidney. Then the patient underwent radical nephrectomy. Pathologic characteristics and immunohistochemical analysis confirmed the diagnosis of rPNET. Additionally, the patient received three cycles of chemotherapy, and was still alive without metastasis at 15-months follow-up.
rPNET is rare and presents aggressive clinical behavior and worse prognosis. We expect that further awareness and study of this rare tumor can be had by presenting our case.
Primitive neuroectodermal tumor; Kidney carcinoma; Ewing’s sarcoma
Rhabdoid tumors of the central nervous system are rare malignancies. Primary central nervous system atypical teratoid/rhabdoid tumors (ATT/RhTs) mostly occur during early childhood and are almost invariably fatal. These tumors show similar histological and radiological features to primitive neuroectodermal tumormedulloblastoma (PNET-MB) but have different biological behaviors. We report a case of primary intracranial ATT/RhT in the posterior cranial fossa of a child. Preoperative radiological diagnosis was PNET-MB, but pathological diagnosis is ATT/ RhT. The case involved a 16-month-old baby boy who presented with severe headache, vomiting, and gait disturbance. He was treated by surgical resection, chemotherapy, and radiotherapy. Despite aggressive therapy, he died 19 months after diagnosis. Clinical, radiological, and histopathological features of primary intracranial ATT/RhT are discussed with a special emphasis on the differential diagnosis from PNET-MB.
A 14 year old male was referred to a CT scan at our hospital for evaluation of headache. The patient was a known case of cervical soft tissue primitive neuroectodermal tumor (PNET) who has undergone surgery and radiotherapy 4 years ago. CT scan showed a large solitary extra axial, epidural lesion in the right parietal region, with mass effect and bony involvement. Subsequently, surgery was performed and the resultant biopsy was neuroepithelioma. After diagnosis the patient has undergone chemotherapy and radiotherapy. He remained symptom free, and also follow up CT scans of the brain, chest, and abdomen were normal after two years post surgery. This is the first reported case of epidural metastasis of a head and neck (peripheral) PNET.
Primitive neuroectodermal tumor (PNET) of the chest wall or Askin's tumor is a rare neoplasm of chest wall. It most often affects children and adolescents and is a very rare tumor in adults. In this case report, we present an Askin's tumor occurred in a 73-year-old male. The patient was admitted with a history of 3-month lower back pain and cough. In computed tomography, there was a lesion with dimensions of 70 × 40 × 65 mm in the superior segment of the lower lobe of the left lung. Positron emission tomography/computed tomography with 18F-flourodeoxyglucose revealed a pleural-based tumor in the left lung with a maximum standardized uptake value of 4.36. No distant or lymph node metastases were present. The patient had gone through surgery, and wedge resection of the superior segment of left lobe and partial resection of the ipsilateral ribs were performed. Pathology report with immunocytochemistry was consistent with PNET and the patient received chemotherapy after that.
Primitive neuroectodermal tumor (PNET) is a malignant neoplasm that generally arises from bone and soft tissues, with predilection for young adults. This neural crest origin tumors share biologic and histologic features with Ewing's sarcoma (ES).
We present a case of a 22-year-old woman with history of severe progressive neck pain, without radiation, associated with paresthesia in the right arm, and palpable right posterior cervical mass. Neurological examination showed increased reflexes in all four limbs, bilateral Hoffman's sign, right Babinski's sign, and right hemi-hypoesthesia. Neuroimaging revealed a right posterior cervical lesion with heterogeneous contrast enhancement extending to the neural foramina of the atlas and axis. Patient underwent microsurgical removal of the lesion, and histopathological and immunohistochemical analysis confirmed the diagnosis of peripheral primitive PNET (pPNET). The patient had adjuvant treatment with radiotherapy and chemotherapy. After twelve months, neuroimaging showed no signs of tumor regrowth and the patient had no neurological deficits. However, three months later, the patient developed hydrocephalus and cerebrospinal fluid (CSF) was positive for neoplastic cells. No other treatment was administered and the patient died.
pPNET is a rare malignant tumor with poor prognosis, although promising results with multimodal treatment-surgery, radiotherapy, and chemotherapy. Diagnosis requires immunohistochemical analysis, with identification of neuronal differentiation markers.
Cervical spine; Ewing's sarcoma; primitive neuroectodermal tumor
Ewing's sarcomas and peripheral primitive neuroectodermal tumors (ES/PNETs) are high grade malignant neoplasms. These malignancies are characterized by a chromosome 22 rearrangement, arise from bone or soft tissue, predominantly affect children and young adults, and are grouped in the Ewing family of tumors. Multimodality treatment programs are the treatment of choice. Primary localization of ES/PNET in the mediastinum is extremely rare. We describe a case of ES/PNET presenting as a mediastinal mass with tracheal compression and initial signs of superior vena cava in a 66-year-old woman.
Ewing's sarcoma; extraosseous; extraskeletal; peripheral primitive neuroectodermal tumor
Ewing's sarcoma is a malignant tumor of bones that primarily affects children and young adults. The true origin of this small round cell lesion still remains controversial. It was originally described by James Ewing in 1921 as arising from undifferentiated osseous mesenchymal cells; however, recent studies suggest that Ewing's tumor might be neuroectodermally derived from various degrees of differentiation of the primitive neural tissues. This paper reports a rare case of ES of the mandible in an 11-year-old girl, which had been previously misdiagnosed and treated as a dental abscess. In the clinical examination, a hard immobile expansive mass of 2 cm diameter was observed on the left side of the mandible. Radiographic examination revealed a diffuse radiolucent lesion with ill-defined borders and wide vestibular bone plate destruction. Microscopically, the tumor was composed by monotonous small round cells that exhibited immunoreactivity for CD99, vimentin and desmin. Surgical resection of mandible followed by mandibular reconstruction was adopted. The patient was subjected to multiagent chemotherapy with Vincristine [VC], Dactinomycin [AC], Cyclophosphamide [CP] and Doxorubicin [AD]).
Child; diagnosis; Ewing's sarcoma; immunohistochemistry; mandible
Embryonal tumors are the most common brain tumors in infants less than 36 months of age. Histologically characterized as undifferentiated small round cell tumors with divergent patterns of differentiation, these include medulloblastoma, the most common form of embryonal tumor, as well as supratentorial primitive neuroectodermal tumor, medulloepithelioma, ependymoblastoma, medullomyoblastoma, melanotic medulloblastoma, and atypical teratoid/rhabdoid tumor. All are similarly aggressive and have a tendency to disseminate throughout the central nervous system. Because of efforts to avoid craniospinal irradiation in an attempt to lessen treatment-related neurotoxicity, management of these tumors in infants is unique. Outcomes remain similarly poor among all the tumor types and, therefore, identification of specific molecular targets that have prognostic and therapeutic implications is crucial. The molecular and clinical aspects of the three most common aggressive infantile embryonal tumors, medulloblastoma, supratentorial primitive neuroectodermal tumor, and atypical teratoid/rhabdoid tumor, are the focus of this review.
Extraskeletal Ewing's sarcoma (EES) is a type of Ewing's sarcoma that arises in soft tissue and is now regarded as a member of a family of small round cell neoplasms of bone and soft tissue, including primitive neuroectodermal tumors (PNETs). EES occurs predominantly in adolescents and young adults between the ages of 10 and 30 years. The disease follows an aggressive course with a high recurrence rate. The presence of a distant metastasis is also common. EES arises in the soft tissue of either the trunk or extremities. We recently experienced two cases of EES that occurred in the chest wall. The two patients underwent wide resection and combined radiochemotherapy. There was no evidence of disease 30 and 22 months, respectively, after surgery. Although extremely rare, EES should be considered in the differential diagnosis of chest wall tumors. We report two cases of EES with a brief review of the literature.
Extraskeletal Ewing's sarcoma; Primitive neuroectodermal tumor