BACKGROUND: Pulmonary primitive neuroectodermal tumor (PNET), a member of the Ewing sarcoma family of tumors, is a rare malignancy that is associated with a grim prognosis. To date, fewer than 30 cases of pulmonary PNET have been reported. In this case report, we present the clinical details of a 12-year-old girl with pulmonary PNET who underwent surgical treatment. We also conducted an analysis and summary of other relevant studies and the surgical outcomes.
METHODS: In May 2018, a 12-year-old girl was admitted with symptoms of cough and blood-tinged phlegm. A computed tomography scan revealed a large mass, measuring 12.9 cm × 8.1 cm, in the right middle and lower lungs. A percutaneous lung biopsy confirmed poorly differentiated tumor cells with a nested growth pattern. Immunohistochemical staining demonstrated positive expression of CD99, CD56, Vimentin, and Synaptophysin. The patient was diagnosed with pulmonary PNET. Following three cycles of neoadjuvant chemotherapy, a substantial reduction in tumor volume was observed. Subsequently, the patient underwent a surgical procedure involving pneumonectomy and partial resection of the left atrium with the assistance of cardiopulmonary bypass. The patient was discharged 37 days after surgery. During a three-year follow-up period, she exhibited no signs of tumor recurrence and has successfully returned to school.
CONCLUSIONS: This case highlights the successful management of an advanced PNET with neoadjuvant chemotherapy, pneumonectomy, and partial resection of the left atrium employing cardiopulmonary bypass. The patient remained disease-free after three years. Our analysis of surgically treated cases indicates that neoadjuvant chemotherapy can contribute to improved prognoses for PNET patients. It is crucial to emphasize that complete surgical excision remains the cornerstone of treatment, underscoring the importance of surgeons considering radical surgical approaches whenever feasible for patients with pulmonary PNETs.

Pancreatic neuroendocrine neoplasms (pNENs) are relatively rare epithelial malignancies originating from pancreatic neuroendocrine cells, pathologically classified into well-differentiated pancreatic neuroendocrine tumors (pNETs) and poorly-differentiated pancreatic neuroendocrine carcinoma (pNECs). Although they also fall under the category of pNENs, the almost entirely distinct biological characteristics and survival prognosis have caused debate among surgeons when it comes to the development of surgical intervention options, particularly for locally advanced G3 pNETs and pNECs. We present a case of 66-year-old male with nonfunctional G3 pNET, invasion of five nearby pancreatic organs and type II liver metastases. The patient achieved good outcomes after undergoing multivisceral resection and postoperative adjuvant chemotherapy. This finding helps surgeons better understand locally advanced pNENs, formulate treatment decisions systematically and confidently, and balance patient benefits and risks of surgery.

Somatostatin receptors are commonly expressed in most pancreatic neuroendocrine tumors (pNETs), a rare type of pancreatic tumors with high heterogeneity. However, the role of somatostatin receptor 2 (SSTR2) has seldom been investigated separately in pNET. This retrospective study aims to evaluate the role of SSTR2 in the clinicopathological features and genomic background of nonfunctional and well-differentiated pNET.
A total of 223 cases of nonfunctional well-differentiated pNET were included, and the correlation between SSTR2 status and clinicopathological outcome was evaluated. In addition, we performed whole exome sequencing in SSTR2-positive and SSTR2-negative pNETs and identified that the 2 lesions harbored different mutational landscapes.
Negative SSTR2 immunochemistry staining was significantly related to an earlier onset of disease, larger tumor size, advanced stage of American Joint Committee on Cancer, and tumor metastasis in lymph nodes and liver. Under pathological assessment, positive peripheral aggression, vascular invasion, and perineural invasion were markedly increased in SSTR2-negative cases. Moreover, SSTR2-negative patients exhibited significantly worse progression-free survival than SSTR2-positive patients (hazard ratio, 0.23; 95% confidence interval, 0.10-0.53; P = 0.001).
Somatostatin receptor 2-negative nonfunctional pNET might represent a subtype of pNET with poor outcomes and evolve from a different genomic background.

Central Nervous System (CNS) embryonal tumors represent a heterogeneous group of highly aggressive tumors occurring preferentially in children but also described in adolescents and adults. In 2021, the CNS World Health Organization (WHO) classification drastically changed the diagnosis of the other CNS embryonal tumors including new histo-molecular tumor types. Here, we report a pediatric case of a novel tumor type among the other CNS embryonal tumors classified within the methylation class \"CNS Embryonal Tumor with BRD4-LEUTX Fusion\". The patient was a 4-year girl with no previous history of disease. For a few weeks, she suffered from headaches, vomiting and mild fever associated with increasing asthenia and loss of weight leading to a global deterioration of health. MRI brain examination revealed a large, grossly well-circumscribed tumoral mass lesion located in the left parietal lobe, contralateral hydrocephalus and midline shift. Microscopic examination showed a highly cellular tumor with a polymorphic aspect. The majority of the tumor harbored neuroectodermal features composed of small cells with scant cytoplasm and hyperchromatic nuclei associated with small \"medulloblastoma-like\" cells characterized by syncytial arrangement and focally a streaming pattern. Tumor cells were diffusely positive for Synaptophysin, CD56, INI1 and SMARCA4 associated with negativity for GFAP, OLIG-2, EMA, BCOR, LIN28A and MIC-2. Additional IHC features included p53 protein expression in more than 10% of the tumor\'s cells and very interestingly, loss of H3K27me3 expression. The Heidelberg DNA-methylation classifier classified this case as \"CNS Embryonal Tumor with BRD4:LEUTX Fusion\". RNA-sequencing analyses confirmed the BRD4 (exon 13)-LEUTX (exon 2) fusion with no other molecular alterations found by DNA sequencing. Our case report confirmed that a new subgroup of CNS embryonal tumor with high aggressive potential, loss of H3K27me3 protein expression, BRDA4-LEUTX fusion, named \"Embryonal CNS tumor with BRD4-LEUTX fusion\", has to be considered into the new CNS WHO classification.

Splanchnic vein thrombosis due to co-existing metastatic pancreatic neuroendocrine tumour (pNET) and JAK2V617F mutation is a rare condition.
Here we present a case of a young woman with complete remission of a non-functioning grade 2 pNET with unresectable liver metastases, coexisting with JAK2V617F mutation. Splenectomy and distal pancreatectomy were performed. Neither surgical removal, nor radiofrequency ablation of the liver metastases was possible. Therefore, somatostatin analogue (SSA) and enoxaparine were started. Peptide receptor radionuclide therapy (PRRT) was given in 3 cycles 6-8 weeks apart. Genetic testing revealed no multiple endocrine neoplasia type 1 (MEN-1) gene mutations. After shared decision making with the patient, she gave birth to two healthy children, currently 2 and 4 years old. On pregnancy confirmation, SSA treatment was interrupted and resumed after each delivery. Ten years after the diagnosis of pNET, no tumour is detectable by MRI or somatostatin receptor scintigraphy. PRRT followed by continuous SSA therapy, interrupted only during pregnancies, resulted in complete remission and enabled the patient to complete two successful pregnancies.

Primitive neuroectodermal tumor (PNET) of the lung is rare in adults, and treatment options vary. We herein describe the disease course and follow-up of PNET in an adult. A 27-year-old man was admitted to our hospital because of cough and headache, and whole-exome sequencing revealed positive expression of the EWSR1-FLI1 fusion gene and amplification of the APC gene. Although the patient received multidisciplinary treatment including chemotherapy regimens of etoposide plus cisplatin; focal radiotherapy focusing on the cerebrum, lung, and kidneys; and a subsequent palliative gastrointestinal operation, he eventually died of multiple organ functional failure. His overall survival period was 18 months, and his progression-free survival period was 4 months. During the treatment, the patient showed remarkable sensitivity to radiotherapy. In conclusion, PNET of the lung in adult patients is extremely rare, and the prognosis is very poor. Involvement of a multidisciplinary team in the development of personalized therapeutic strategies is essential. This patient with APC gene amplification showed excellent sensitivity to radiotherapy for intrapulmonary and intracranial lesions, suggesting that APC gene amplification may be related to radiotherapy sensitivity. However, further clinical research is needed.

Von Hippel-Lindau disease (VHL) is frequently associated with pancreatic neuroendocrine tumors (PNETs). Here, we report a case of tumor-to-tumor metastasis in a VHL patient in whom colon cancer metastasized to the interior of a PNET. A 65-year-old man had undergone bilateral adrenalectomy for pheochromocytomas in both adrenal glands in his 50 s. Genetic screening was performed considering his family history of pheochromocytoma, and he was diagnosed with VHL. PNET was detected, for which the patient was regularly monitored by follow-up imaging. One year ago, the patient underwent right hemicolectomy to remove a tumor in the ascending colon (pT3N0M0, pStage IIA). He was admitted to our department for detailed examination because the pancreatic tumor had grown, and thus, pancreaticoduodenectomy was performed. Diagnostic imaging and histological findings indicated tumor-to-tumor metastasis, in which the patient\'s previous colon cancer had metastasized to and proliferated within the PNET. Colon cancer metastasizing to a PNET is extraordinarily rare and has never been reported in the literature. Thus, practitioners should be vigilant for tumor-to-tumor metastasis when performing imaging surveillance of PNETs.

BACKGROUND: Ewing sarcoma/primitive neuroectodermal tumor (PNET) of the renal is extremely rare. The common cause of ectopic ACTH syndrome is pulmonary neuroendocrine tumors, such as small cell carcinomas and carcinoid tumors. Here, we present an unusual case of ectopic ACTH syndrome and hypothyroidism caused by Ewing sarcoma/PNET of the right kidney.
METHODS: A 19-year-old girl presented with a history of right lumbar pain and discomfort for 2 months, aggravated for 2 days. Abdominal contrast-enhanced computed tomography and computed tomography angiography showed an upper pole occupancy of the right kidney occupancy with subepithelial hemorrhage. Preoperative hormone levels including plasma total cortisol (PTC), adrenocorticotrophic hormone (ACTH) and thyroid hormone measurements were abnormal, indicating that the patient had Cushing syndrome and hypothyroidism. The patient underwent right radical nephrectomy. Histopathological analysis revealed a renal small round blue cell tumor (consistent with a primitive neuroectodermal tumor), with positive immunohistochemistry for CD99 and Ki67 (about 10%) and molecular pathology for EWSR1 gene fusions. PTC, ACTH and thyroid hormone returned to normal after surgery.
CONCLUSIONS: We report a rare ectopic ACTH syndrome and hypothyroidism due to renal Ewing sarcoma/PNET. The clinical manifestation of renal Ewing sarcoma/PNET is non-specific and the diagnosis relies on pathological morphology, immunohistochemistry and fusion gene detection. At present, surgery combined with radiotherapy and chemotherapy is used in the treatment, but the prognosis is still not optimistic.

Embryonal tumor with multilayered rosettes (ETMR) is a rare and highly malignant brain tumor that develops in children younger 4 years old. This neoplasm is characterized by extremely aggressive course, low sensitivity to chemotherapy and radiotherapy. Thanks to the progress of pathologists, diagnosis of ETMR is now available using immunohistochemical examination with LIN28A and SALL4 antibodies. Moreover, detection of microRNA amplification in the 19q13.42 locus by fluorescent hybridization in situ allows an unmistakable diagnosis.
The authors describe clinical course and treatment outcome in a 2-year-old patient with a giant tumor of the right parietotemporal region. Postoperative histological examination verified ETMR. Despite adjuvant treatment, we observed fast progression of disease and unfavorable outcome after 5 months. Case report is supplemented by literature review.
CONCLUSIONS: ETMR is very rare and poorly understood neoplasm. The authors present a giant hemispheric ETMR in a 2-year-old boy with an extremely aggressive course of disease. Despite the advances in diagnosis and treatment of CNS tumors in children, there are currently more questions than answers regarding ETMR. Pooled analysis of all available data with large-scale studies is needed. It is necessary to emphasize an exceptional role of each clinical case for global study of this tumor. Timely adjuvant/neoadjuvant therapy in highly specialized centers is also essential.
Эмбриональная опухоль с многослойными розетками (embryonal tumor with multilayered rosettes — ETMR) — редкая и высокозлокачественная опухоль головного мозга, развивающаяся у детей преимущественно до 4-летнего возраста и характеризующаяся крайне агрессивным течением, а также весьма низкой чувствительностью к химиотерапии и лучевому лечению. Благодаря успехам патоморфологов диагностика ETMR в настоящее время доступна за счет применения иммуногистохимического исследования с антителами к LIN28A и SALL4, кроме того, выявление амплификации микроРНК в локусе 19q13.42 методом флюоресцентной гибридизации in situ позволяет безошибочно поставить диагноз. Приведено описание клинического течения и исхода лечения пациента 2 лет с гигантской опухолью правой теменно-височной области, при гистологическом исследовании которой после операции верифицирована ETMR. Была осуществлена попытка адъювантного лечения, однако отмечена очень быстрая прогрессия заболевания, смерть пациента наступила через 5 мес. Описание клинического случая дополнено обзором литературы. Несмотря на достижения в диагностике и лечении опухолей центральной нервной системы у детей, при обнаружении ETMR — больше вопросов, чем ответов, и необходимо проведение масштабных исследований с анализом всех имеющихся данных. Следует подчеркнуть исключительную роль каждого диагностированного случая в контексте глобального изучения данной опухоли и значение своевременного начала адъювантного и неоадъювантного лечения в условиях высокоспециализированных центров.

Primitive neuroectodermal tumour is a poorly differentiated small round cell neoplasm that primarily affects children and is very rarely seen in adults. Peripheral primitive neuroectodermal tumours are rare compared to the central type and resemble soft tissue sarcoma. Primitive neuroectodermal tumours involving the subcutaneous tissue are rare and only a few cases involving the subcutaneous tissue of the anterior abdominal wall have been reported. However, no cases involving the subcutaneous tissue of the shoulder region have been reported. We report the case of a peripheral primitive neuroectodermal tumour arising from subcutaneous tissue of the right shoulder in a young adult.
UNASSIGNED: case report; magnetic resonance imaging; neuroectodermal tumour; neuron-specific enolase; subcutaneous tissue.