Malignant Gastrointestinal Neuroectodermal Tumor: A New Kid on the Block?

ABSTRACT: Also referred to as "osteoclast-rich, clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT)," malignant gastrointestinal neuroectodermal tumor is a newly described, rare, aggressive sarcoma that commonly arises in the small bowel, stomach, and colon. Histogenesis is likely from an autonomous nervous system-related primitive cell of neural crest origin. The hallmark genetic finding of EWS-CREB1 or EWS-ATF1 fusion transcripts clinches the diagnosis. Annular constrictive lesions tend to be smaller, show homogenous contrast enhancement on computed tomography, and may present with bowel obstruction. Larger, expansile masses tend to be exophytic and show heterogeneous contrast enhancement. Surgical resection is the mainstay of treatment. Frequent recurrences, metastases, and death from disease in 75% of patients portend a poor prognosis. Targeted chemotherapy based on specific tumor pathways is being developed.

Primary Ewing Sarcoma/Primitive Neuroectodermal Tumor of Kidney With Inferior Vena Cava Thrombus: Findings on 18F-FDG PET/CT.

Primary Ewing sarcoma/primitive neuroectodermal tumor is a group of rare aggressive tumors in adults derived from neuroectoderm, and primary renal involvement is extremely rare. We describe an F-FDG PET/CT findings of a 28-year-old man who presented with left renal mass with inferior vena cava thrombus, which turned out to be primary Ewing sarcoma on histopathology specimen post left nephrectomy.

A rare case of paediatric primary central nervous system lymphoma treated with high-dose methotrexate and rituximab-based chemoimmunotherapy and whole brain radiotherapy followed by tumour bed boost with three-dimensional conformal radiation technique.

BACKGROUND: Primary central nervous system lymphomas (PCNSL) are rare in the paediatric population. CLINICAL CASE: A 12-year-old boy presented to our clinic with complaints of multiple episodes of generalised tonic-clonic seizures for 1 year and gradual loss of vision in both eyes for 3 months. Baseline magnetic resonance imaging (MRI) of the brain showed a large (7.2 × 7 cm) enhancing soft tissue lesion in the right frontal lobe causing mass effect and midline shift. With a radiological diagnosis of supratentorial primitive neuroectodermal tumour, he underwent subtotal resection of tumour. The post-operative histopathology revealed diffuse large B cell lymphoma (DLBCL). Systemic lymphoma workup was essentially normal. He received five cycles of chemoimmunotherapy with rituximab, high-dose methotrexate (HDMTX), vincristine and procarbazine and had complete radiological response (CR). This was followed by whole brain radiotherapy (WBRT) to a dose of 36 Gy in 20 fractions and sequential tumour bed boost to a dose of 9 Gy in 5 fractions by three-dimensional conformal technique. Subsequently, he received two cycles of consolidation chemotherapy with high-dose cytarabine. At completion of treatment, 3 and 6 months thereafter, MRI brain showed CR. At last follow-up visit, 13 months from the date of diagnosis, he was disease-free and asymptomatic with the exception of dimness of vision in both eyes due to long-standing bilateral optic atrophy. CONCLUSION: This report highlights the fact that paediatric PCNSL may be effectively treated by a combination of HDMTX and rituximab-based chemoimmunotherapy followed by consolidation with conformal WBRT and tumour bed boost. Lack of awareness of this rare entity may lead to diagnostic delay and potential ramifications as exemplified by chronic atrophic papilloedema and visual loss in the illustrative case.

PET/TC con 18F-FDG en metástasis cardíaca en un paciente con antecedente de tumor neuroectodérmico maligno de la pared torácica (tumor de Askin): caso clínico y revisión de la literatura / 18F-FDG PET/CT in a cardiac metastasis in a patient with history of malignant neuroectodermal tumour of the chest wall: case report and review of the literature

Presentamos el caso de un varón de 25 años con tumor neuroectodérmico maligno de la pared torácica izquierda (tumor de Askin), tratado con cirugía después de tratamiento quimioterápico neoadyuvante y seguido por quimioterapia de consolidación. Después de 9 años libre de enfermedad, el paciente presenta un episodio de tromboembolismo pulmonar agudo. El ecocardiograma, la tomografía computarizada de tórax y la resonancia magnética cardíaca evidencian una masa en la aurícula derecha. Se sospechó recidiva del tumor de Askin versus mixoma auricular. La PET/TC con 18F-FDG mostró una masa hipermetabólica en la aurícula derecha con extensión a la cavidad ventricular derecha, altamente sugestiva de malignidad. El resultado del examen anatomopatológico después de la biopsia y posteriormente a la exéresis de la masa auricular derecha fue compatible con metástasis del tumor primario (AU)

The case presented is a 25-year-old male with a malignant neuroectodermal tumour on the left chest wall (Askin tumour), treated with surgery after neoadyuvant chemotherapy and followed by consolidation chemotherapy. After 9 years of disease free survival, the patient developed an acute pulmonary embolism. The echocardiogram, thoracic CT, and cardiac MRI scans revealed a mass in the right atrium. Recurrence of an Askin tumour versus an atrium myxoma was suspected. 18F-FDG PET/CT showed an intense hypermetabolic right atrium mass with extension to the right ventricle highly suggestive of malignancy. The result of the histopathology examination after biopsy and subsequently exeresis of the right atrium mass was consistent with a metastasis of the primary tumour (AU)

68Ga-labelled peptides in the management of neuroectodermal tumours.

Neuroectodermal tumours arise from chromaffin cells and possess the ability to secrete catecholamines. They are generally rare and may occur in association with a variety of hereditary syndromes such as MEN-2A and 2B, neurofibromatosis type 1 and von Hippel-Lindau disease. The most common types are phaeochromocytoma arising from the adrenal medulla and paraganglioma of extra-adrenal origin. Phaeochromocytomas tend to be benign and are often associated with a gene mutation if the disease is bilateral, while paragangliomas are often malignant, have a more aggressive nature and tend to metastasize. There are no specific histological or immunohistochemical features that indicate the malignant potential and the diagnosis of malignancy can only be established by the presence of distant metastases. Therefore, imaging can play a vital role in the diagnosis, localization, staging and assessment of spread. Traditionally, this is achieved with a combination of cross-sectional (CT and MRI) and functional ((123)I-MIBG or (111)In-octreotide) imaging. However, these modalities are not adequate and achieve moderate sensitivity. The introduction of (68)Ga-DOTA peptide in PET/CT imaging has led to improved receptor targeting and superb PET resolution, as well as accurate localization of lesions. The use of this technique in neuroectodermal tumours has been shown to be superior to all available modalities, but the available data are limited and larger studies are awaited to establish its role in the management of these tumours.

Inhomogeneous activity distribution of 177Lu-DOTA0-Tyr3-octreotate and effects on somatostatin receptor expression in human carcinoid GOT1 tumors in nude mice.

The aim of this study was to investigate the activity distribution in neouroendocrine tumors after diagnostic, or therapeutic, amounts of [(177)Lu-DOTA(0)-Tyr(3)]-octreotate and to investigate how the activity distribution influences the absorbed dose. Furthermore, the activity distribution of a second administration of radiolabeled octreotate was studied. Nude mice with subcutaneously grown human midgut carcinoid (GOT1) were injected intravenously with different amounts of (177)Lu-octreotate. At different time points thereafter (4 h to 13 days), a second injection of [(111)In-DOTA(0)-Tyr(3)]-octreotate was given to estimate the somatostatin receptor (sstr) expression. The activity distribution in the tumors was then determined. Monte Carlo simulations with PENELOPE were performed for dosimetry. Fifty-one out of 58 investigated tumors showed a lower activity concentration in the peripheral part than in the central part of the tumor. The amount of activity injected, or time after administration, did neither influence the relative activity nor the sstr distribution in the tumor. After an initial down-regulation (at 4-24 h), there was an up-regulation of sstr (1.5-2 times, at 7-14 days). Monte Carlo simulations demonstrated an inhomogeneous absorbed dose distribution in the tumor using (177)Lu, with twice as high absorbed dose centrally than peripherally. The high activity concentration centrally and the up-regulation of sstr demonstrated will facilitate fractionated therapy using radiolabeled somatostatin analogues if similar results will be obtained also in patients. The inhomogeneous activity distribution in the tumor has to be taken into account when the absorbed dose distribution in tumor is calculated.

Imaging of primary malignant bone tumors (nonhematological).

Primary malignant bone tumors are uncommon and are diagnosed typically based on radiographic and microscopic findings combined with clinical and demographic features. CT and MR imaging scans are useful in further staging the tumors by determining intraosseous and extraosseous spread.

Imaging of parotid gland primitive neuroectodermal tumor.

A seven-years-old boy presented with recurrent episodes of right parotid gland swelling that was presumptively being treated as sialoadenitis. Interrogation with ultrasonography, computerized tomography and magnetic resonance imaging revealed a heterogeneous mass occupying the right parapharyngeal space, imperceptibly merging with adjoining parotid gland, scalloping the vertical ramus of the mandible and involving the base skull with widening of the foramen ovale. The findings at surgery and histopathology provided a final diagnosis of parotid gland primitive neuroectodermal tumor. This report emphasizes on the imaging findings of this rare tumor occurring in such an unusual location.

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.

Renal peripheral neuroectodermal tumor presenting at age 78: case report.

Primitive neuroectodermal tumor (PNET) of the kidney is a rare and aggressive tumor, often presenting in advanced stages and progressing rapidly. Renal PNET (rPNET) may affect a wide age spectrum, but the majority of cases are in young adults. We present a case of advanced rPNET in a 78-year-old woman. To our knowledge, this is the most advanced age of presentation of this neoplasm to date. We report on her presentation and management, and discuss the current clinical management of this tumor.

Clinical CT-based calculations of dose and positron emitter distributions in proton therapy using the FLUKA Monte Carlo code.

Clinical investigations on post-irradiation PET/CT (positron emission tomography/computed tomography) imaging for in vivo verification of treatment delivery and, in particular, beam range in proton therapy are underway at Massachusetts General Hospital (MGH). Within this project, we have developed a Monte Carlo framework for CT-based calculation of dose and irradiation-induced positron emitter distributions. Initial proton beam information is provided by a separate Geant4 Monte Carlo simulation modelling the treatment head. Particle transport in the patient is performed in the CT voxel geometry using the FLUKA Monte Carlo code. The implementation uses a discrete number of different tissue types with composition and mean density deduced from the CT scan. Scaling factors are introduced to account for the continuous Hounsfield unit dependence of the mass density and of the relative stopping power ratio to water used by the treatment planning system (XiO (Computerized Medical Systems Inc.)). Resulting Monte Carlo dose distributions are generally found in good correspondence with calculations of the treatment planning program, except a few cases (e.g. in the presence of air/tissue interfaces). Whereas dose is computed using standard FLUKA utilities, positron emitter distributions are calculated by internally combining proton fluence with experimental and evaluated cross-sections yielding 11C, 15O, 14O, 13N, 38K and 30P. Simulated positron emitter distributions yield PET images in good agreement with measurements. In this paper, we describe in detail the specific implementation of the FLUKA calculation framework, which may be easily adapted to handle arbitrary phase spaces of proton beams delivered by other facilities or include more reaction channels based on additional cross-section data. Further, we demonstrate the effects of different acquisition time regimes (e.g., PET imaging during or after irradiation) on the intensity and spatial distribution of the irradiation-induced beta+-activity signal for the cases of head and neck and para-spinal tumour sites.

Characterisation of the lung toxicity of the cell cycle inhibitor temsirolimus.

The aims of this study were reviewing our experience regarding the pulmonary toxicity of the mammalian target of rapamycin (mTOR) inhibitor temsirolimus, discussing potential pathogenic mechanisms and proposing management strategies. Medical records and radiological reports of 22 patients treated with weekly doses of temsirolimus 25 mg were reviewed. Eight (36%) out of 22 patients developed pulmonary abnormalities compatible with drug-induced pneumonitis. Half were asymptomatic and in those with symptoms, dyspnea and dry cough were the most common. Radiologically two different patterns, ground glass opacities and lung parenchymal consolidation, were described. The management of this toxicity was variable, ranging from no intervention to discontinuation of the drug. In our experience temsirolimus may cause drug-induced pneumonitis at a higher incidence than that previously reported. The presentation and its severity are variable. The risk of developing this toxicity may be increased among subjects with abnormal pre-treatment pulmonary functions or history of lung disease.

Impact of FDG PET for staging of Ewing sarcomas and primitive neuroectodermal tumours.

AIM: High-grade Ewing sarcomas and Primitive neuroectodermal tumours (PNET) make up the tumours of the Ewing family. Our purpose was to evaluate the value of [18F]fluorodeoxyglucose positron emission tomography (FDG PET) in patients with Ewing tumours. PATIENTS AND METHODS: Twenty-four patients who had PET because of a suspected Ewing tumour during a 5-year period were included in this retrospective study. The images of 33 whole-body FDG PET investigations performed in primary or secondary diagnostics were analysed visually and semi-quantitatively by using standardized uptake values (SUVs). In 14 cases, PET was compared to bone scintigraphy regarding bone lesions. The final diagnosis was based on histology, imaging and follow-up. RESULTS: Histologically, the primary lesions were 10 Ewing sarcoma, 13 PNET and one osteomyelitis. The sensitivity and specificity of an examination-based analysis (presence of Ewing tumour and/or its metastases) were 96 and 78%, respectively. Altogether, 163 focal lesions were evaluated. Sensitivity and specificity regarding individual lesions were 73 and 78%. This lower sensitivity is mainly due to small lesions. In true-positive cases, the mean SUV was 4.54+/-2.79, and the SUVs in two false-positive cases were 4.66 and 1.60. True-positive and false-positive cases could not be differentiated definitively based on SUVs because of overlap and low values in true-positive lesions. In four cases, PET depicted 70 while bone scintigraphy depicted only eight bone metastases. CONCLUSION: An FDG PET investigation is a valuable method in the case of Ewing tumours. PET is superior to bone scintigraphy in the detection of bone metastases of Ewing tumours. For the depiction of small lesions, mainly represented by pulmonary metastases, PET is less sensitive than helical computed tomography. Determination of the role of whole-body FDG PET in diagnostic algorithm needs further investigation.

Multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia-1 (MEN-1) is an autosomal dominant inherited syndrome that occurs due to inactivating mutations of the MEN1 gene locus, coding for a tumor-suppressor protein, menin. The components of MEN-1 are hyperparathyroidism due to multiple parathyroid adenomas, pancreatic neuroendocrine tumors, and pituitary adenomas, in addition to some less common neoplastic manifestations. Care of people with MEN-1 requires knowledge of the problems that may arise, and the best approaches to detect and care for the manifestations of this incurable, but manageable, disease.