Peripheral PNET Research Articles

A Rare Case of Primitive Neuroectodermal Tumor of Tongue.

Primitive neuroectodermal tumor of the periphery is a rare entity and belongs to Ewing sarcoma family of tumors. It comprises 1% of all sarcomas and majority of these cases occur in the age group of less than 35 years. It is highly aggressive and patient often presents with distant metastasis leading to poor prognosis. Its characteristic features include t(11:22) translocation. A young female patient presented with growth in the tip of the tongue. Biopsy was done and histopathology using H&E and PAS staining revealed primitive neuroectodermal tumor. Immunohistochemistry helped to confirm the diagnosis. There was no evidence of distant metastasis at the time of presentation. The most accepted modality of treatment is wide surgical excision followed by chemoradiotherapy. The growth was excised and patient was treated with radiotherapy. The patient succumbed to liver metastasis following 10 months of treatment. Peripheral PNET usually affects the long bones like femur and in head and neck region, mandible is most frequently involved. This is a rare case of PNET of tongue with very few references from literature and hence makes it an interesting read.

Primary spinal extradural extraosseous primitive neuroectodermal tumor/Ewing's sarcoma: A critical analysis and review

Primary spinal extradural Ewing's sarcoma/primitive neuroectodermal tumor (PNET) is rare malignant tumor of childhood and early adulthood. The World Health Organization classifies PNET as an undifferentiated round cell tumor arising from primitive neuroepithelial cell. It can be central or peripheral PNET depending on site of presentation. Usually, the presenting symptoms are chronic back pain and myelopathy. Overall prognosis and survival are dismal in spite of total surgical resection and adjuvant therapy. Because of the rarity and malignant behavior, definite management of spinal PNET has never been described. After review of medical record at Acharaya Vinoba Bhave Rural Hospital, Sawangi, India, we identified four patients of spinal PNET and were included in our study. Age at diagnosis ranging from 15 to 26 years old with mean age of 20 years old. All four cases were epidural in location, two of which were of Askin type tumor with spinal cord compression. Rural population with low literacy and financial constraints were the key reasons of late presentations at our hospital. Counseling and proper education regarding the disease are a must for early case detection and early treatment of those living in rural areas and suffers from financial constraints. Due to rarity of the disease and its poor prognosis, a well-organized multicentric controlled trial is required to formulate a standard guidelines in the management of this disease.

Radiation diagnostics of peripheral primitive
 neuroectodermal tumors (PNET)
 in children at the Scientific Center
 of Pediatrics and Pediatric Surgery
 (Almaty, Kazakhstan)

Relevance: Peripheral primitive neuroectodermal tumor (primitive neuroectodermal tumor – PNET) belongs to the group
 of malignant tumors that develop from migrating embryonic neural crest cells. PNET includes several nosological forms: Askin’s
 tumor, esthesioneuroblastoma, the very peripheral primitive neuroectodermal tumor, and Ewing’s sarcoma. PNET accounts for
 3–9% of all soft tissue tumors and 19% of all soft tissue sarcomas in children. In Europe and the US, PNETs account for 3.4 cases
 per year per 1 million children below 15 years; in Kazakhstan – 0.6-1.2 cases per 1 million child population. Rapid tumor growth,
 malignancy, and early metastasis to other organs and systems predetermine the PNET’s specific role in oncology.
 The purpose of the study was to improve the quality and availability of early sarcoma diagnostics in children at medical
 institutions of the general medical network.
 Results: 35 cases of peripheral PNET in children were analyzed. The age of the patients was 1.5 to 17 years, the average age –
 9.3 years. Boys were 1.3 times more than girls. One patient (3.6%) had extra-skeletal tumor localization. Children with stage IIB
 prevailed – 46.4% of cases (13 children).
 Radiographical differentiation between Ewing’s sarcoma and primary chronic or “healed” (antibiotic) acute hematogenous
 osteomyelitis in the initial phase of the process is almost impossible before the extraosseous soft tissue component is formed.
 The bone damage process is more often localized in the bone diaphysis and subsequently spreads to its metaphyses.
 Conclusion: PNET is more likely to come from the chest wall, so it is advisable to start the X-ray examination from the chest.
 In terms of radiation semiotics, PNET is similar to Ewing’s sarcoma and Askin’s tumor; therefore, an additional immunohistochemical study of the tumor tissue is required. An important indirect diagnostic criterion in Ewing’s sarcoma is the predominance of the soft tissue component over the bone manifestations. Extended CT and MRI studies with contrast enhancement
 (chest, abdominal cavity, pelvis, and the primary lesion area) and skeletal scintigraphy are required to clarify the extent of
 changes, stage the tumor accurately, and assess the tumor dynamics after treatment. The above conclusions generally confirm
 the available literature data.

Tumors With Neuroectodermal Differentiation of the Uterus and Ovary: A Series of 12 Cases and Review of the Literature

Abstract Objectives Primitive neuroectodermal tumors (PNETs) are a group of small round cell tumors most commonly found in the central nervous system, soft tissue, or bone. Such tumors arising in the uterus or ovary are rare. In this study, we describe the clinicopathologic features from a series of gynecological tumors with neuroectodermal differentiation. Methods In a retrospective review, 5 years of departmental archives were searched for gynecological tumors diagnosed at Orlando Health’s Department of Pathology. Clinicopathological information was analyzed, including age at diagnosis, tumor size, depth of invasion, other component, pathologic stage, FIGO stage, immunohistochemical stains, months of follow-up, and current disease status. Results Twelve fully staged tumors with neuroectodermal differentiation were identified. Eleven were of uterine origin and one was of ovarian origin. Ages at diagnosis ranged from 38 to 78 years (median 65). Neuroectodermal component was variable in morphology, including lymphocyte-like small cells in sheets, perivascular pseudorosettes, or cords; larger cells with prominent nucleoli with or without cystic change; and giant cells resembling megakaryocytes. Components other than neuroectodermal differentiation included carcinosarcoma, dedifferentiated endometrioid carcinoma, and high-grade serous carcinoma. Membranous and/or paranuclear dot-like CD99 immunoreactivity were in all cases. Ten patients were deceased due to disease at 1 to 33 months follow-up, while one patient was alive without evidence of disease after 61 months follow-up, possibly due to being able to tolerate a different therapeutic protocol for peripheral PNET. Conclusion Neuroectodermal differentiation may be found as components of other gynecological tumors, especially those with an aggressive phenotype and high-stage disease. The neuroectodermal component comprises a spectrum of cytohistological features. Because of its presentation in the shadow of other components, it may be more common than is generally assumed. Mortality remains high, but recognition of neuroectodermal differentiation in gynecologic tumors might introduce a different therapeutic approach and potentially improve clinical outcomes.

Extraosseous Primary Intracranial Ewing Sarcoma/peripheral Primitive Neuroectodermal Tumor: Series of Seven Cases and Review of Literature.

Background:The Ewing sarcoma peripheral PNET (ES-pPNET) is very rare small round cell tumour that involves the CNS as either a primary dural neoplasm or by direct extension from contiguous bone or soft tissue.Materials and Methods:Biopsy proven cases of intracranial ES/pPNET with orbital involvement operated during Jan 2010-Jan 2014 were retrospectively included and their clinical data, operative and histological findings were reviewed from institutional oncology register.Results:seven patients (4 males; 3 female) were studied with mean age at presentation of 13 years. Six patients had orbital involvement in one or other form. Surgical excision was gross total in five, near total in one, and subtotal in one patient. All patients received adjuvant therapy, only chemotherapy in 2, only Radiotherapy in four, both in one. MRI characteristics were studied in six patients. Four patients died with average survival of 33.2 months and three patients are having Progression free survival of average 23.3 months.Conclusions:The EWS-pPNET is very rare tumour and very poorly described in literature. These tumours are showing special predilection for the frontotemporal dura and erode through the flat bone of cranium like orbital roof and lateral wall of the orbit. These tumours are aggressive, multi compartmental, vascular and very rapidly growing, so missing or overlooking the primary symptoms of dural stretching/bony involvement leads to delay in management and poor outcome.

A Rare Case of Peripheral PNET with A Rare Presentation

A Rare Case of Peripheral PNET with A Rare Presentation

A rare case of extraskeletal Ewing's sarcoma/primitive neuroectodermal tumor developing in maxillary sinus of an old patient

Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) family of tumors is an uncommon group of malignant neoplasms that may present in both skeletal and extraskeletal sites. PNET outside the central nervous system is called peripheral PNET (pPNET) developing from migrating embryonal cells of the neural crest. Very few cases of pPNET of the maxilla are reported in English literature. These tumors may be difficult to diagnose due to their primitive morphology. These tumors occur predominantly in infancy or early childhood. The occurrence of extraskeletal ES/PNET in the maxillary sinus in an old age is very rare. We report a case of extraskeletal ES/PNET developing in maxillary sinus in a 60-year-old woman. The ES/PNET should be included in the differential diagnosis of a small round cell tumor and immunohistochemical analysis with a panel of immunomarkers should be done for correct diagnosis and proper treatment.

Comparison of Primary Spinal Central and Peripheral Primitive Neuroectodermal Tumors in Clinical and Imaging Characteristics and Long-Term Outcome

ObjectivePrimary spinal primitive neuroectodermal tumors are extremely rare entities. The purpose of this study was to analyze the differences in clinical and imaging characteristics and outcomes between primary spinal central PNETs (cPNETs) and peripheral PNETs (pPNETs). MethodsThere were 25 consecutive patients with primary spinal primitive neuroectodermal tumors enrolled. The diagnosis was cPNET in 6 patients with negative CD99 expression and pPNET in 19 patients with positive CD99 expression. Gross total resection (GTR) was achieved in 12 patients, subtotal resection was performed in 9 patients, and partial resection was performed in 4 patients. Postoperative chemotherapy was given to 14 patients, and radiotherapy was given to 16 patients. ResultsThe age at diagnosis was significantly younger in the cPNET group (mean 12.8 years) compared with the pPNET group (mean 22.5 years) (P = 0.040); the 2 pathologies did not show a significant difference in prognosis. GTR (P = 0.041), radiotherapy (P = 0.008), and GTR with radiotherapy (P = 0.009) were significant factors leading to a higher 2-year survival rate. Kaplan-Meier analysis showed that radiotherapy (P < 0.001) and GTR with radiotherapy (P = 0.040) resulted in a longer median survival time. Patients who underwent GTR, chemotherapy, and radiotherapy all together had the highest 1-year (100.0%) and 2-year (71.4%) survival rates and the longest median survival time (32 months). ConclusionsPatients with spinal cPNETs were younger compared with patients with pPNETs. The prognosis of spinal cPNETs and pPNETs was poor with no significant difference between the entities. The most beneficial treatment modality is GTR combined with adjuvant radiotherapy and chemotherapy.

Fine Needle Aspiration of Metastatic Central-Type Primitive Neuroectodermal Tumor in Patients With History of Germ Cell Tumor: A Retrospective Study of 5 Cases

Central-type primitive neuroectodermal tumors (c-PNETs) are uncommon somatic malignancies arising in germ cell tumors (GCTs). They display different histologic features, immunostaining profile and lack of chromosome 22 translocation, compared to peripheral PNETs. In this study, we are describing cytomorphologic features of metastatic c-PNET by fine needle aspiration (FNA). A computerized search of our laboratory information …

Rare presentation of peripheral primitive neuroectodermal tumor in the maxilla and mandible: A report of two cases.

Peripheral primitive neuroectodermal tumor (pPNET) is a rare and highly malignant undifferentiated tumor, which presents in infants and young adults. pPNETs in the head and neck region are uncommon and have a varying incidence of occurrence. Peripheral PNETs of the maxilla and mandible are particularly rare. At present, only 16 cases of pPNET of the maxilla and 13 cases of pPNET of the mandible have been reported. The present study describes a case of pPNET of the maxilla in a 16-year-old male and a case of pPNET of the mandible in another 16-year-old male. The present study reports the radiological findings and the clinical courses of the two patients.

Computed tomography and magnetic resonance imaging findings of peripheral primitive neuroectodermal tumors of the head and neck

We aimed to analyze the computed tomography (CT) and magnetic resonance imaging (MRI) findings of peripheral primitive neuroectodermal tumor (pPNET) of the head and neck. Eight patients with pPNET of the head and neck confirmed by histopathological examination were analyzed retrospectively. The average patient age was 8 years. The tumor location in the 8 patients was as follows: maxillofacial region (right, 2; left, 1), left maxillary sinus (1), right masticator space (1), left carotid space (1), right infratemporal fossa (1), and left parotid gland (1). All 5 patients who underwent CT demonstrated ill-defined soft masses and no calcification. Three patients with tumors in the maxillofacial region showed homogeneous small masses and a mild enhancement. The patient with left maxillary sinus tumor showed a heterogeneous mass with patchy, necrotic foci and mild heterogeneous enhancement. The patient with right masticator space tumor showed a heterogeneous mass, and marked heterogeneous enhancement. The T1-weighted images of the patients with right infratemporal fossa, left carotid space, and left parotid gland tumors were isointense. The T2-weighted images were heterogeneous and mildly hyperintense in 2 patients and hyperintense in 1 patient. Heterogeneous intermediate enhancement was demonstrated in 2 patients and mild ring enhancement in 1 patient. The imaging features of pPNET of the head and neck are non-specific. An ill-defined, aggressive mass and variable enhancement on CT and MR images may suggest the diagnosis of pPNET. Peripheral PNET should be included in the differential diagnosis of children and adolescents' regional tumors.

Primitive Neuroectodermal Tumor of Maxilla: A Rare Case

ABSTRACT Primitive neuroectodermal tumor (PNET) is an aggressive round cell malignancy of presumed neural crest origin belonging to Ewing's sarcoma family of tumors. Peripheral PNET is less common in head and neck region and only eight cases of primary PNET of maxilla have been reported. We report a case of 3-year-old boy diagnosed with PNET of maxilla based on detailed radiologic, histopathologic, and immunohistochemical studies. Though the imaging features of PNET are nonspecific and definitive diagnosis is only by immunohistochemistry, PNET should be included in the differential diagnoses of fast growing soft tissue tumors of children and young adolescents. We emphasize the need for its early diagnosis and prompt management owing to its aggressive nature and high mortality rate.

KIT expression and methylation in medulloblastoma and PNET cell lines and tumors

The stem cell factor/kit tyrosine kinase receptor pathway is related to tumor growth and progression in several cancers including Ewing sarcoma, a peripheral PNET (pPNET). Identifying additional groups of tumors that may use the pathway is important as they might be responsive to imatinib mesylate treatment. MB and central PNET (cPNET) are embryonal tumors of the CNS that share similar undifferentiated morphology with Ewing sarcomas and display aggressive clinical behavior. cPNET outcome is significantly lower than MB outcome, even for localized tumors treated with high-risk MB therapy. The elucidation of signaling pathways involved in MB and cPNET pathogenesis, and the discovery of new therapeutic targets is necessary to improve the treatment of these neoplasms. We analyzed KIT expression in 2MB, one pPNET, one cPNET and 2 rhabdomyosarcoma (RMS) cell lines. Also, in 13 tumor samples (12MB and one cPNET), we found KIT overexpression in the most aggressive cell lines (metastatic MB and pPNET). Hypermethylation of KIT was clear in the RMS non-expressing cell lines. Among MB tumors, we could see variable levels of KIT expression; a subset of them (25%) might be related in its growth pattern to KIT up-regulation. No methylated KIT was detected in the tumors expressing the lowest levels of KIT. Our results point to methylation as an epigenetic regulatory mechanism for KIT inhibition only in the KIT non-expressing RMS cell lines, and neither in the rest of the cell lines nor in the tumor samples.

Phase II trial of pemetrexed in children with refractory solid tumors: A Children's Oncology Group study.

9535 Background: Pemetrexed is a multi-targeted antifol that inhibits key enzymes involved in nucleotide biosynthesis. We performed a phase 2 trial of pemetrexed in children with refractory or recurrent solid tumors to estimate the response rate and further define its toxicity profile. Methods: Pemetrexed, at a dose of 1,910 mg/m2, was administered as a 10-minute intravenous infusion every 21 days. Patients also received vitamin B12 (500–1,000 mcg IM, q 3 courses), daily multivitamin supplementation and dexamethasone (0.1 mg/kg/dose bid × 3 days q course). A two-stage design (10 + 10) was employed for each of the following disease strata: osteosarcoma, Ewing sarcoma/ peripheral PNET, rhabdomyosarcoma, neuroblastoma, ependymoma, medulloblastoma/ supratentorial PNET and non-brainstem high-grade glioma. Results: Of 72 eligible subjects (39 males), 68 were evaluable for response. No complete or partial responses were observed. Stable disease, for a median (range) of 5 (4- 8+) cycles, was observed in 5 patients: ependymoma, Ewing sarcoma, medulloblastoma, neuroblastoma, osteosarcoma (n=1 each); one patient with Ewing sarcoma is still on study after 8 cycles. Seventy patients fully evaluable for toxicity received 112 treatment cycles. Rash, a DLT in the phase I study, was generally < grade 2 and occurred in 23% of patients. Other toxicities occurring in >10% of patients overall included: elevated ALT (40%) and AST (36%), fatigue (33%), itching (15%), nausea (24%), vomiting (20%), hypophosphatemia (20%), and hyperglycemia (24%), anemia (40%), and neutropenia (47%), and thrombocytopenia (40%). Neutropenia and elevated ALT were the most commonly recurring toxicities observed in patients receiving multiple cycles. One patient discontinued protocol therapy because of persistently elevated ALT. Two allergic reactions occurred, each with the first dose. Conclusions: Although reasonably well tolerated, pemetrexed as administered in this study has no significant activity in a broad spectrum of refractory pediatric solid tumors. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Lilly Lilly

Uterine Tumors with Neuroectodermal Differentiation. A Report of 4 Cases

We report four cases of uterine tumors with neuroectodermal differentiation. One tumor had neuroectodermal component only; in the three other tumors, the neuroectodermal component was admixed with another component, namely rhabdomyosarcoma (1 case), and endometrioid adenocarcinoma (2 cases). Histologically, the neuroectodermal component consisted of small to medium sized cells arranged in diffuse sheets. The tumor cells had round nuclei with stippled to coarsely granular chromatin, mostly with non-prominent nucleoli, and scant eosinophilic or amphophilic cytoplasm. Immunohistochemically, 4/4 tumors showed expression of vimentin, synaptophysin and CD56; 3/4 tumors were CD99 and NSE positive; 2/4 tumors showed focal expression of S-100 protein; and 1/4 tumors had focal dot-like cytoplasmic positivity for cytokeratin AE1/AE3. FLI-1 was negative in all cases. FISH examination was performed and none of the tumors showed rearrangement of EWSR1 gene. Uterine tumors with neuroectodermal differentiation are rare; to the best of our knowledge only 44 cases have been reported in the literature to date, referred to as Ewing sarcoma, peripheral PNET (pPNET), PNET (not otherwise specified) and uterine tumors with neuroendocrine differentiation.

Peripheral Primitive Neuroectodermal Tumor of the Stomach: A Case Report

Peripheral primitive neuroectodermal tumors (peripheral PNETs) are very rare and highly aggressive softtissue malignancies originating from the neural crest. To the best of our knowledge, only a few cases of peripheral PNETs of the stomach have been reported in the literature. We report a case of large peripheral primitive neuroectodermal tumor of the stomach with MDCT findings in a 22-year-old man presenting epigastric pain and vomiting.

Imaging findings of abdominal peripheral primitive neuroectodermal tumor: report of four cases with pathological correlation

Peripheral primitive neuroectodermal tumors (peripheral PNETs) are rare in the abdomen. We report the imaging findings of four peripheral PNETs arising in the abdomen. Three were ill-demarcated tumors and one was a well-demarcated tumor, with extensive local invasion and lymph node metastasis in two cases, respectively. The tumors are of inhomogeneous attenuation and heterogeneous enhancement after intravenous administration of contrast materials. Although their imaging manifestations cannot distinguish them from other sarcomas, recognition of these imaging features may be helpful in suggesting the possibility of peripheral PNETs in some cases.

Radiological evaluation of peripheral primitive neuroectodermal tumor arising in abdomen-pelvis region

To analyze the CT and MRI features of peripheral primitive neuroectodermal tumor (pPNET) arising in abdomen-pelvis region, and to improve the radiological diagnostic ability of this tumor. The CT and MRI appearances of thirteen abdomen-pelvis region pPNET patients proved pathologically were reviewed retrospectively. The age of diagnosis ranged from 2 years to 72 years (median, 30 years). The tumors were located in the abdomen and pelvic cavity (nine patients), retroperitoneal tissues (two patients), right kidney (one patient) and liver (one patient). The radiological appearances of the tumors resembled heterogeneous soft tissue masses, eight masses with cystic or necrotic areas. Masses in abdomen and pelvic cavity and kidney were well-defined; while masses in retroperitoneal tissue and liver were ill-defined. Heterogeneous enhancement with intravenous contrast agents was evident. There are speckled, patching and irregular calcifications in four patients, one of them with calcification after treatment. Five patients died, and eight patients remiss on clinical follow-up. The radiological features of peripheral PNET are non-specific. CT and MRI are useful in delineating the extent, finding distant metastasis, predicting respectability and monitoring treatment.

Dumbbell-shaped peripheral primitive neuroectodermal tumor of the spine—case report and review of the literature

Primary spinal peripheral primitive neuroectodermal tumors (pPNETs) are extremely rare. Here, we present a case study of a 29-year-old male with a dumbbell-shaped pPNET at the T9-10 spine level, including details of his examination, surgical procedures applied, histological and genetic findings, and his subsequent treatment. We discuss the clinical course, the pathology and treatment for this disease, the surgical approach to thoracic dumbbell tumors and we review the literature. To our knowledge, this is the first report of a case of a dumbbell-shaped intradural and spinal peripheral PNET.

Primary peripheral primitive neuroectodermal tumors of the spinal cord: report of two cases and review of the literature

Primary intraspinal peripheral primitive neuroectodermal tumors (pPNETs) are extremely rare tumors with only seven reported cases in the literature. The histopathologic diagnosis of this tumor is complex and has led to a variety of treatment approaches. The distinction between central and peripheral type primary spinal cord PNETs has not always been made in the literature, leading to a paucity of data in this disease. We present here two young patients with primary intraspinal pPNET, their treatment and outcome. The first patient, a 27 year old male, presented with an intradural mass extending from L2 through L5, after multiple relapses, he is currently alive with disease after 72 months, the longest survival yet reported. The second patient, a 16 year old female, presented with an intradural mass at the cauda equina from L2 through L5, and is currently alive with responsive disease at 5 months after initial diagnosis. Here, we discuss the clinical course, the pathology and treatment for this disease and review the literature.