Benign paraspinal ganglioneuroma with paraneoplastic opsoclonus myoclonus syndrome.

Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare immune-mediated movement disorder occurring as a paraneoplastic manifestation of neuroblastic tumours (NTs), especially neuroblastoma in infancy. Ganglioneuroma (GN), the benign tumour in the spectrum, is rarely associated with OMAS. We report the case of a child in her second year of life presenting with acute onset of progressive paraplegia and OMAS. MRI showed diffuse and infiltrating left paraspinal mass from T3-T9 levels with differentials of neuroblastoma or ganglioneuroblastoma. Histopathological and immunohistochemistry examination of the excised tumour showed maturing GN. The OMAS was managed with intravenous immunoglobulin and steroids. In the 6-month follow-up, the child has a residual motor weakness with myelomalacia in neuroimaging. The case report substantiates the occurrence of OMAS as paraneoplastic manifestation in NTs, including benign, in children younger than 2 years with a female predilection.

Ganglioneuroma Arising in Congenital Melanocytic Nevus in a Patient with Cardiac Anomalies: A Case Report.

A congenital melanocytic nevus is a benign melanocyte proliferation, that may be complicated by malignant transformation. We are reporting a three-year-old girl, who had a giant congenital melanocytic nevus on her back, that was treated by serial surgical excisions with tissue expander insertion. Histopathological examination confirmed the diagnosis of congenital melanocytic nevus with ganglioneuroma. Out of approximately 250 case reports on congenital melanocytic nevus, we identified only two reports of medium/large congenital melanocytic nevus with cutaneous ganglioneuroma. Due to the potential malignant transformation of congenital melanocytic nevus, reporting the features and characteristics of such rare findings may help in further understanding congenital melanocytic nevus, its associations, and prognosis.

Composite paraganglioma-ganglioneuroma with atypical catecholamine profile and phenylethanolamine N-methyltransferase expression: a case report and literature review.

Pheochromocytomas and paragangliomas (PPGLs) are rare tumors that secrete catecholamines and arise from the adrenal medulla or extra-adrenal sympathetic ganglia. These tumors secrete adrenaline and noradrenaline, but paragangliomas usually produce only noradrenaline because of the lack of phenylethanolamine N-methyltransferase (PNMT) expression. Composite paragangliomas, which are complex tumors consisting of multiple types of neuroblastic cells, are extremely rare. We present the case of a 46-year-old woman with an atypical catecholamine profile who was preoperatively diagnosed with pheochromocytoma. However, postoperative pathology revealed that the patient had an extra-adrenal paraganglioma accompanied by a ganglioneuroma, which led to the diagnosis of a composite tumor. Interestingly, PNMT is expressed in both paragangliomas and ganglioneuromas. In addition, we reviewed reported composite paragangliomas and compared their clinical features with those of composite pheochromocytomas. We also discuss various aspects of the etiology of composite paragangliomas and the mechanism by which PNMT is expressed in tumors.

[Peripheral neuroblastic tumors in childhood]. / Periphere neuroblastische Tumoren im Kindesalter.

Peripheral neuroblastic tumors represent the fourth-largest group of malignant tumors in childhood. The majority of these tumors are neuroblastomas, which can be classified into undifferentiated, poorly differentiated, and differentiating subtypes. In addition, peripheral neuroblastic tumors include ganglioneuroblastoma, a composite tumor composed of Schwannian cell stroma and neuroblasts as well as benign ganglioneuroma. In this overview, histopathological diagnostic criteria and grading systems, as well as common molecular alterations that are of prognostic and therapeutic significance, are discussed.

Extra-adrenal peripheral neuroblastic tumors: A clinicopathological study of 18 cases.

Background: Peripheral neuroblastic tumors arise from the sympathoadrenal lineage of the neural crest. They have been classified according to the International Neuroblastoma Pathology Committee (INPC) into Four categories according to International Neuroblastoma Pathology Committee (INPC): a) Neuroblastoma (NB) b) Ganglioneuroblastoma (GNB), nodular c) Ganglioneuroblastoma, intermixed, and d) Ganglioneuroma (GN). Because of the rarity of extra-adrenal peripheral neuroblastic tumors, limited information is available regarding the chemotherapy of NB and GNB. A few case reports or case series with a small number of patients have been documented in the literature. Aim: To describe the clinicopathological characteristics of extra-adrenal peripheral neuroblastic tumors. Materials and. Methods: Clinical, histopathological, and immunohistochemistry (IHC) findings of 18 cases were retrieved. Immunohistochemistry at the time of diagnosis was performed using Ventana Benchmark XT. The mean value was calculated using the Microsoft Office Excel 2019 software. Results: The posterior mediastinum was the most commonly affected extra-adrenal site in our study. Neuroblastoma consisted of eight cases (six in children, two in adults), of which four cases were poorly differentiated and the other four cases were differentiating. Two cases had favorable histology. The bone marrow and cervical lymph node metastasis were documented. Of the four GNB cases, one patient developed bone metastasis. All patients of NB and GNB received combination chemotherapy. One out of six GN patients presented with a large retroperitoneal mass encasing the aorta and renal vessels, mimicking a sarcoma. Conclusion: Extra-adrenal peripheral neuroblastic tumors do not pose any diagnostic issue in adequate tissue sampling. In limited material, immunohistochemistry is needed. The chemotherapy regimen has not been standardized due to rarity. Further molecular testing and targeted therapy may be of help in the future.

Diverse imaging findings of Lhermitte-Duclos disease.

AIM: To evaluate the diverse clinical and imaging features of Lhermitte-Duclos disease (LDD) and its subgroup comparison. MATERIALS AND METHODS: Clinical data from 21 patients with LDD were collected, including eight patients with LDD without other tumours and 13 LDD with other tumours. Redefined diagnostic criteria are used to evaluate Cowden Syndrome. Imaging indicators were analysed retrospectively to extract typical and atypical features. Imaging findings and preoperative diagnostic accuracy were compared between the subgroups. RESULTS: None of these patients met the redefined diagnostic criteria. The typical "tiger stripe sign" was seen in most LDD lesions (13/29, 61.9%), with lower density (29.66 ± 2.51 versus 37.81 ± 2.76 HU, p<0.001) and higher apparent diffusion coefficient (ADC) value (1.04 ± 0.05 × 10-3 versus 0.74 ± 0.03 × 10-3 mm2/s, p<0.001) than that of the normal cerebellum. Atypically, some lesions showed abnormal vessels (8/21, 38.1%), intratumoural calcification (3/21, 14.29%), intratumoural haemorrhage (4/21, 19.05%), peritumoural oedema (6/21, 28.57%), and heterogeneous enhancement (5/21, 23.81%). The typical "tiger stripe sign" was more common in LDD with other tumours (84.62% versus 25%, p=0.018). Although LDD without other tumours was more common with abnormal vessels (75% versus 15.38%, p=0.018), intratumoural calcification (37.5% versus 0, p=0.042), intratumoural haemorrhage (50% versus 0, p=0.012), peritumoural oedema (62.5% versus 7.69%, p=0.014) and heterogeneous enhancement (50% versus 7.69%, p=0.047). Preoperative diagnostic accuracy was higher in LDD with other tumours than LDD without other tumours (76.92% versus 25%, p=0.032). CONCLUSION: The "tiger stripe sign" of LDD is characteristic, but not unique. With or without other tumours, it may be associated with the imaging diversity. Combining typical and atypical signs can improve the imaging assessment of LDD.

Parapharyngeal Space Ganglioneuroma: Clinical Experience and Review of the Literature.

Ganglioneuroma is a rare benign tumor originating in the sympathetic ganglia, composed of differentiated ganglion cells, nerve sheath cells, and nerve fibers, which tend to occur in the posterior mediastinum, adrenal gland, retroperitoneal, and other locations, occurring in the head and neck is relatively rare, and parapharyngeal space involvement is extremely rare. In our report, we present 2 adult male patients whose preoperative imaging and fine needle cytology did not confirm the diagnosis of a parapharyngeal space mass and who completely resected the tumor through a combined cervical and oral approach. Finally, pathology confirmed ganglioneuroma; we also reviewed the English articles on parapharyngeal ganglioneuroma over the past 40 years, and summarized the diagnostic and treatment characteristics of parapharyngeal ganglioneuroma in combination with our cases to improve understanding of the disease.

[Intestinal ganglioneuromatosis as an early extra-endocrine manifestation of type 2B multiple endocrine neoplasia].

Multiple endocrine neoplasia type 2B (MEN 2B) is a rare variant of hereditary tumor syndromes caused by germinal mutations in the proto-oncogene RET. One of the components of the syndrome is multiple neurinomas, the early detection of  which is not always given due attention. We present a description of the case of MEN 2B, manifested in the first months of life by intestinal ganglioneuromatosis. The disease presented with chronic constipation, including episodes of intestinal obstruction that required repeated surgical interventions. MEN 2B was suspected at the age of 15. At the time of diagnosis, an increase in serum calcitonin levels was noted (1041 pg/ml, norm <9.5 pg/ml), and a node in the thyroid gland was also determined (1,3*1,0*1,2 see, TIRADS 5), subsequently verified as a neoplasm of C-cells. By DNA analysis, a pathogenic variant p.Met918Thr, typical for MEN2 B, was detected in the RET gene. No signs of pheochromocytoma were found at the time of investigation. The patient underwent a thyroidectomy with lymphadenectomy. The difficulties of early diagnosis of sporadic cases of MEN 2B due to the nonspecificity of gastrointestinal manifestations of the disease are discussed.

Mixed ganglioneuroma and cortical adenoma in adrenal gland: A case report.

RATIONALE: Adrenal mixed corticomedullary tumors (MCMTs) are single tumor masses composed of an intimately admixed population of both adrenal cortical cells and medullary components. Most medullary tumor components are pheochromocytomas; however, MCMTs composed of ganglioneuroma and adrenal cortical adenoma are extremely rare. The current case is a rare case of adrenal MCMT composed of ganglioneuroma and adrenal cortical adenoma with primary aldosteronism. PATIENT CONCERNS: A 49-year-old male was admitted because of hypokalemia and an adrenal mass. He was diagnosed with hypertension in his 20s and was taking blood pressure medications. DIAGNOSIS: Plasma aldosterone concentration 376.5 pg/dL (normal 37.8~233.0 pg/mL) and potassium 2.8 mmol/L (normal 3.4~4.9 mmol/L) were detected. The aldosterone-to-renin ratio [the ratio of plasma aldosterone concentration (ng/dL) to PRA (ng/mL/hour)] was 38. The saline loading test showed that serum aldosterone (49.4 ng/dL) was not suppressed, compared with the basal level (28.4 ng/dL). The adrenal venous sampling test showed that the aldosterone level markedly increased to 1521.2 pg/mL. Abdominal computed tomography revealed an enlarged relatively well-circumscribed multinodular mass (35 × 13 × 30 mm) in the right adrenal gland. INTERVENTIONS: Laparoscopic right adrenalectomy was performed under the clinical diagnosis of a functioning adrenal cortical adenoma. OUTCOMES: After laparoscopic right adrenalectomy, the serum aldosterone and renin levels returned to normal. The patient maintained a normal aldosterone level without recurrence for 16 months. LESSONS: Adrenal MCMTs of the ganglioneuroma and cortical adenomas in the ipsilateral adrenal gland are extremely rare. Adrenal MCMTs exhibit benign clinical behavior, with no metastasis or death due to the tumor. With the development of diagnostic imaging technology, it is possible to identify mixed tumors. However, surgical resection of adrenal gland is a common treatment and a final diagnosis should be made based on the pathological results after surgery. Because this is to rule out the occurrence of rare malignant tumors and confirm the pattern of mixed tumors.

Ganglioneuromatosis intestinal difusa a lo largo del tubo digestivo.

BACKGROUND: Ganglioneuromas are histologically benign neoplasms derived from the sympathetic nervous system, whose occurrence in the gastrointestinal tract is rare and often syndromic. According to the injury pattern and extension, lesions are divided into polypoid ganglioneuroma, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. This work aimed to present the incidental post mortem finding of diffuse ganglioneuromatosis of the gastrointestinal tract in a patient without syndromic involvement. CASE REPORT: We describe the case of a two-year-old female patient with surgically corrected type III tracheoesophageal atresia and fistulous recanalization, multiple episodes of aspiration pneumonia, and septic shock. During the last admission, she developed massive pulmonary hemorrhage and multi-organ failure. Post mortem histopathological study identified hypertrophy of the pylorus and enlarged enteric nerve trunks and plexuses with intermingled mature ganglion cells. We identified ganglioneuromatosis affecting all gastrointestinal tract segments with the predominance of the myenteric plexuses. CONCLUSIONS: Intestinal ganglioneuromatosis is a rare disease with a spectrum of lesions ranging from isolated to syndromic with high morbidity and mortality. Therefore, it is necessary to know the condition, investigate systematically when it is suspected, and rely on genetic studies to confirm or rule out any syndromic association.

INTRODUCCIÓN: Los ganglioneuromas son neoplasias histológicamente benignas derivadas del sistema nervioso simpático, cuya ocurrencia en el tubo digestivo es rara y comúnmente sindromática. De acuerdo con el patrón de la lesión y la extensión se dividen en ganglioneuroma polipoide, poliposis ganglioneuromatosa y ganglioneuromatosis difusa. El objetivo de este trabajo es presentar el hallazgo incidental post mortem de ganglioneuromatosis difusa del tubo digestivo en una paciente sin afectación sindromática. CASO CLÍNICO: Se describe el caso de un paciente de sexo femenino de 2 años con atresia traqueoesofágica tipo III corregida quirúrgicamente que cursó con recanalización fistulosa, múltiples episodios de neumonía por aspiración y choque séptico. Durante el último ingreso cursó con hemorragia pulmonar masiva y falla multiorgánica. En el estudio post mortem se identificó hipertrofia del píloro y de los troncos y plexos nerviosos entéricos con células ganglionares maduras entremezcladas. Se identificó ganglioneuromatosis que afectaba todos los segmentos del tubo digestivo, con predominio de los plexos mientéricos. CONCLUSIONES: La ganglioneuromatosis intestinal es una rara enfermedad que presenta un espectro de lesiones desde una forma aislada hasta sindromática con morbimortalidad elevada. Por ello, es necesario conocer la enfermedad, indagar sistemáticamente cuando se sospeche y apoyarse de estudios genéticos que confirmen o descarten alguna asociación sindromática.

Case Report: Composite pheochromocytoma with ganglioneuroma component: A report of three cases.

Composite pheochromocytoma (CP) is a very rare tumor originating from neural crest cells, predominantly composed of pheochromocytoma (PCC), a chromaffin cell tumor arising in adrenal medulla, and ganglioneuroma, a tumor derived from autonomic ganglion cells of the nervous system. Moreover, CP may be present in the hereditary syndromes of which pheochromocytoma is part. Literature offers scarce data on this subject, and particularly about its biological behavior, clinical evolution, and molecular profile. We report the phenotype and outcome of three cases of CP (PCC and ganglioneuroma components), followed up at the Endocrine Service of the Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil. Two nonsyndromic patients (cases 1 and 2) were negative to germline mutations in genes VHL, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and MAX, while the third case (case 3) had clinical diagnosis of neurofibromatosis syndrome. Cases 1, 2, and 3 were diagnosed at 29, 39, and 47 years old, respectively, and were followed up for 3, 17, and 9 years without no CP recurrence. All cases had apparent symptoms of catecholaminergic excess secreted by PCC. Ganglioneuroma, the neurogenic component present in all three cases, had a percentage representation ranging from 5% to 15%. Tumors were unilateral and large, measuring 7.0 cm × 6.0 cm × 6.0 cm, 6.0 cm × 4.0 cm × 3.2 cm, and 7.5 cm × 6.0 cm × 4.5 cm, respectively. All cases underwent adrenalectomy with no recurrence, metastasis, or development of contralateral tumor during follow-up. Genetic testing has been scarcely offered to CP cases. However, a similar frequency of genetic background is found when compared with classic PCC, mainly by the overrepresentation of NF1 cases in the CP subset. By literature review, we identified a notorious increase in cases reported with CP in the last decade, especially in the last 3 years, indicating a recent improvement in the diagnosis of this rare disorder in clinical practice.

Comparison of two Schwann Cell-Containing Orbital Tumors: Schwannoma and Ganglioneuroma. / Gegenüberstellung zweier Schwann-Zell-haltiger orbitaler Tumoren: Schwannom und Ganglioneurom.

Orbital tumors comprise a variety of diseases, although tumors of the peripheral nerves are rare. Of these, schwannoma is considered the most common entity, consisting histopathologically almost exclusively of Schwann cells. Another benign tumor containing Schwann cells is ganglioneuroma. Here, ganglion cells are histopathologically apparent in addition to the Schwann cell-containing stroma. Ganglioneuroma belongs to the group of neuroblastic tumors and can occur anywhere in the pathway of sympathetic ganglion cells. In this report, we present the disease courses as well as the findings of two patients with different orbital tumors. In both cases, the diagnosis was only confirmed by histopathological examination. The first patient had a schwannoma with cystic degeneration and the second patient had a ganglioneuroma, both tumor entities which occur only rarely in the orbit. Commonalities and differences are discussed.

Choroidal ganglioneuromas in Francois variant neurofibromatosis-1: A rare retinoblastoma mimic.

Neurofibromtosis-1 (NF-1) is the commonest oculo-neuro-cutaneous syndrome with multiple ocular manifestations. Reporting three children who presented with unilateral glaucoma (buphthalmos), ipsilateral facial hemihypertrophy, and eyelid plexiform neurofibroma: completing the triad of François syndrome, a rare NF1 variant. Two presented with leukocoria and were referred to as retinoblastoma suspects. Histopathology showed ganglioneuroma, a benign choroidal tumor, associated with NF-1, which does not need treatment. Knowledge of this rare condition avoids misdiagnosis of retinoblastoma, prevents aggressive management, and the associated psychological impact.

Rare Case of Large Catecholamine Secreting Ganglioneuroma in an Asymptomatic Elderly Male.

Ganglioneuromas (GNs) are benign tumors that originate from neural crest cells, composed mainly of mature ganglion cells. These tumors, which are usually hormonally silent, tend to be discovered incidentally on imaging tests and occur along the paravertebral sympathetic chain, from the neck to the pelvis and occasionally in the adrenal medulla. Rarely, GNs secrete catecholamines.1 Adrenal GNs occur most frequently in the fourth and fifth decades of life, whereas GNs of the retroperitoneum and posterior mediastinum are usually encountered in younger adults.2 Adrenal GNs are commonly hormonally silent and asymptomatic; even when the lesion is of substantial size.3 We report an incidentally detected asymptomatic case of an adrenal ganglioneuroma with mildly elevated urinary catecholamine levels in an elderly male. After preoperative alpha blockade, the patient underwent open right adrenalectomy. Upon microscopic examination, the right adrenal mass proved to be a ganglioneuroma, maturing type and the immunohistochemistry examination showed immunoreactivity to synaptophysin, chromogranin, and CD 56, while S100 was strongly positive at the Schwannian stroma. Following resection, catecholamine levels normalized, confirming the resected right adrenal ganglioneuroma as the source of the catecholamine excess. This case represents a rare presentation of catecholamine-secreting adrenal ganglioneuroma in the elderly.

Dysplastic gangliocytoma of the cerebellum in a cat.

A 2.5-year-old cat presented with progressive ataxia and lethargy. Magnetic resonance imaging (MRI) showed enlargement of the cerebellum and herniation of cerebellar vermis. Postmortem examination confirmed the MRI findings, and histopathology showed numerous large dysplastic neurons populating and displacing the Purkinje cell layer and extending into the molecular and granular layers of the cerebellum. The lesion was diagnosed as dysplastic gangliocytoma of the cerebellum. In humans, this tumor is often associated with Cowden syndrome, a genetic disorder characterized by multiple hamartomas and an increased risk of developing certain neoplasms, known to be linked to a germline mutation of the phosphatase and tensin homolog (PTEN) gene. Reduction in PTEN nuclear and cytoplasmic immunohistochemical labeling of dysplastic neurons in this case suggested a possible PTEN mutation involved in the tumorigenesis. This report provides a detailed pathology description of the tumor and the use of neuronal and PTEN markers which will help guide pathologists presented with this rare condition in the future.

Ganglioneuroma on fine needle aspiration cytology: Case series and review of the literature.

We report two cases of an uncommon benign lesion, retroperitoneal ganglioneuroma, first diagnosed on fine needle aspiration (FNA) cytology. Our first case presented with nausea, constipation, vomiting, and neutropenia after three cycles of chemotherapy for breast cancer treatment, while our second patient presented with seemingly unprovoked abdominal pain and progressive neuropathy. Both underwent computed tomography (CT) scans, in which a soft tissue mass was found in the retroperitoneal space in each patient. An endoscopic ultrasound guided (EUS) FNA was performed on both patients, and as a result, the masses were diagnosed as retroperitoneal ganglioneuromas. As retroperitoneal ganglioneuromas have low incidence of proliferation, invasive surgery was avoided in favor of routine follow-up imaging. Cytologically, both masses showed large, scattered ganglion cells with abundant cytoplasm and large nuclei against a background of wavy spindle cells with elongated nuclei. Histologically, both were positive for S-100. When an EUSFNA is performed and quality material is collected, a diagnosis of retroperitoneal ganglioneuroma may be established, preventing invasive surgery and its accompanying risks in favor of routine follow-up imaging.

Diffuse Ganglioneuromatosis of the Colon in a Patient with Neurofibromatosis 1.

Ganglioneuromas are rare, benign neurogenic tumors characterized by a proliferation of ganglion cells, nerve fibers, and support cells of the nervous system. They have been classified into three groups: solitary, polyposis, and diffuse. The diffuse type has several syndromic associations including multiple endocrine neoplasia syndrome type 2B and, less commonly, neurofibromatosis type 1. We report a case of diffuse ganglioneuromatosis in the colon of a 49-yearold male with a history of neurofibromatosis type 1. Gastrointestinal neoplasms associated with neurofibromatosis type 1 are reviewed.