Ganglioneuroma : primary tumor or maturation of a suspected neuroblastoma?

Ganglioneuroma is a benign neurogenic tumor. These tumors are originating from neuroepithelium along sympathetic ganglia. Main localization is the mediastinum in children older than 10 years. An association with malignant neuroblastoma is rarely observed and it still remains a topic under current discussion. We describe the clincal course of a 17 year-old female patient with a large presacral mass causing amenorrhoea and weight loss. Eleven years before presentation, an incidental urine test showed an elevation of vanillylmandelic acid (VMA) and homovanillic acid (HMA) and a neuroblastoma was suspected. However, further investigations showed no tumor and the test results turned out to be normal within 1 year. Now, a malignant neurogenic tumor was again suspected, but a CT-guided biopsy revealed a benign tumor. The mass was originating from the left sacral nerve roots. A tumor resection via a dorsal approach was performed. Final histology showed a differentiated ganglioneuroma. This is, to our knowledge, the first report describing a patient with elevated VMA/HMA and suspected neuroblastoma who developed a ganglioneuroma 11 years later. The association of ganglioneuroma and neuroblastoma and the abnormal urine tests pointing toward a neuroblastoma 11 years ago remains unclear and the possible answers are discussed in our report.     

Thoracoscopic removal of neurogenic mediastinal tumors: technical aspects

Background: Thoracoscopy is fast becoming the standard approach for the removal of neurogenic mediastinal tumors. However, there are risks for adjacent nervous structures (stellate ganglion, spinal cord). The aim of this study was to review the technical features of this approach.Methods: Between December 1999 and January 2003, nine patients underwent thoracoscopic resection of a mediastinal neurogenic tumor at our hospital. Five of these patients were asymptomatic with incidentally found tumor; the other four patients had compression-related syndromes. Two tumors had developed in the superior sulcus, and one had a spinal canal component (dumbell-type tumor).Results: Thoracoscopic dissection was possible in all cases. In one patient, resection of the tumor was performed via a combined neurosurgical and thoracoscopic approach. Seven tumors were benign nerve sheath tumors (schwannoma), and 2 were nerve cell tumors (ganglioneuroma). The postoperative course was uncomplicated in all patients.Conclusion: The thoracoscopic resection of mediastinal neurogenic tumors is technically easy, except for bulky tumors of the superior sulcus and dumbbell tumors, which require a combined thoracoscopic and neurosurgical approach.     

Adult-Type Ganglioneuroblastoma in the Adrenal Gland Treated by a Laparoscopic Resection: Report of a Case

A case of ganglioneuroblastoma in the adrenal gland of a 50-year-old man is reported. The patient was incidentally found to have a nonfunctioning tumor in the right adrenal gland. The tumor, measuring 4.5cm, was successfully removed using laparoscopy. Histologically, the tumor was diagnosed to be a ganglioneuroblastoma. Immunohistochemically, a few MIB-1-positive cells and no S-100 protein-positive cells were observed. There has been no evidence of recurrence for 2.5 years to date after the operation. Adrenal ganglioneuroblastoma is extremely rare in adults, and only seven such cases have been previously reported in the literature.     

Polysialylated neural cell adhesion molecule in childhood ganglioneuroma and neuroblastoma of different histological grade and clinical stage

Background and aims: Neuroblastoma cells express the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), which normally becomes restricted to a few neural regions after embryogenesis. The aim of the present study was to evaluate PSA-NCAM as a marker in childhood neuroblastoma. Patients/methods: We studied the expression of PSA-NCAM on tumor specimens and in sera of 27 children, altogether, with ganglioneuroma and neuroblastoma of different histological grades and clinical stages. For both methods, immunohistochemistry on 5-μm frozen sections and immunoluminescence serum assay, the polysialic-acid-specific monoclonal antibody 735 was used. Results: PSA-NCAM expression was highest in patients with undifferentiated neuroblastoma and advanced stages of disease, whereas children with differentiated tumor types and low clinical stages had distinctly reduced or no reactivity in immunohistochemistry and, simultaneously, normal serum levels. PSA-NCAM expression correlated with other prognostic and diagnostic markers, such as MYCN gene amplification, and serum concentrations decreased during successful treatment. Conclusions: We conclude that PSA-NCAM, both immunohistochemically and in the serum, is a promising candidate for another useful diagnostic and prognostic tumor marker in childhood neuroblastoma. Received: 25 February 1998 / Accepted: 23 June 1998     

A case report: Adrenal ganglioneuroblastoma in a 59-year old man

Ganglioneuroblastoma is a common type of tumor in children, but is rarely seen in adults. We present here a case of adrenal ganglioneuroblastoma in a 59-year old man.     

A ganglioneuroma of the sigmoid colon presenting as leading point of intussusception in a child: a case report

We present a case of intestinal ganglioneuroma (GN) of the sigmoid colon in a 5-year-old girl, which caused intermittent colocolic intussusception. Ganglioneuromas are rare benign tumors of the autonomic nervous system composed of mature ganglion cells and satellite cells. Colonic GNs are uncommon. The unusual intramural proliferation of neural elements in this case resembled the diffuse intestinal ganglioneuromatosis, which is known to be associated with multiple endocrine neoplasia type 2B. However, the specific mutations of multiple endocrine neoplasia type 2B were not found by genetic sequencing. This is the first pediatric case described in the literature of a solitary polypoid GN presenting as a colocolic intussusception. We present a brief overview of intestinal ganglioneuromatous lesions and associated conditions.     

Arterial constriction after resection of neuroblastic tumors in children: Two-center retrospective study

Background/purposeNeuroblastic tumors are the most common pediatric extracranial solid tumors in infants and very young children. Although, especially in newborns, there is an increasing number of situations in which observation alone is used, surgery remains an important step in the treatment of neuroblastoma but can be complicated by arterial vasospasm in the surgical field. The aim of this two-center retrospective study was to analyze the occurrence of arterial constriction as a complication of neuroblastic tumors resection.MethodsMedical records of patients who were treated surgically for neuroblastic tumors in the years 2012–2019 were reviewed.ResultsFor 8 years, 113 children were treated for neuroblastic tumors. The treatment included both primary and delayed surgery after initial chemotherapy carried out according to SIOPEN protocols. In 11 out of 113 cases (9.7%) local arterial constriction was observed. In 6 out of 11 cases an attempt was made to save the organ, however, two patients suffered from kidney atrophy, two other partial kidney infarctions, one child suffered from partial limb paresis, and another from brain ischemia and death.ConclusionsLocal arterial constriction constitutes a relatively common (10% of cases) and severe complication of neuroblastic tumors resection. Efficacy of local application of papaverine based on our experience remains unproven hence further research is warranted.     

膀胱移行细胞癌脂肪细胞型脂肪酸结合蛋白的表达及其意义

目的:探讨脂肪细胞型脂肪酸结合蛋白(A-FABP)在膀胱癌组织中的表达及其与膀胱癌的病理分级和临床分期的关系.方法:应用免疫组织化学方法检测A-FABP在43例膀胱癌组织和9例正常膀胱组织中的表达.结果:43例膀胱癌组织中A-FABP阳性表达率为72.1%,A-FABP在浸润型膀胱癌与浅表型膀胱癌组织中的表达差异有统计学意义(P<0.05).其表达与肿瘤的临床分期及病理分化程度有较好的对应关系.结论:A-FABP蛋白的表达特征可以作为反映膀胱癌的生物学行为和预后的参考指标.     

Successful management of presacral ganglioneuroma: A case report and a review of the literature

INTRODUCTIONPresacral ganglioneuromas are rare, usually benign lesions. Patients typically present when the mass is very large and becomes symptomatic.PRESENTATION OF CASEThis report describes the case of a 42 year old lady presenting with back pain who was subsequently diagnosed with a presacral ganglioneuroma based on MR imaging and a CT guided biopsy of the lesion.DISCUSSIONAfter counselling regarding nonoperative management, the patient opted for surgical resection. Open resection was performed with preservation of the neurovascular pelvic anatomy and an uneventful postoperative recovery. A review of the relevant literature was also performed using a search strategy in the online literature databases PUBMED and EMBASE.CONCLUSIONSurgical resection of a presacral ganglioneuroma is reasonable given their propensity for local effects and reported potential malignant transformation.     

Multiple synchronous tumors in a child with Fanconi anemia

Fanconi anemia (FA) is an autosomal recessive inherited syndrome characterized by congenital abnormalities, aplastic anemia, and a high likelihood of developing cancer. We describe a child who presented with 2 synchronous solid tumors (Wilms tumor and neuroblastoma), later found to have FA, who developed severe toxicity and died after a first cycle of chemotherapy. Our experience emphasizes that a predisposing genetic condition should be sought in cases of multiple tumors and that managing FA patients with cancer can be particularly difficult.     

E-cadherin: a marker for differentiation and invasiveness in prostatic carcinoma

Summary Considerable controversy exists concerning the value of histomorphological data in the assessment of the malignant potential of prostatic carcinomas. We investigated the expression pattern of E-cadherin in human prostate at the translational level. E-cadherin is a specific epithelial cell-cell adhesion molecule which has previously been found to be expressed in well-differentiated non-invasive carcinoma cell lines but is lost in many poorly differentiated invasive cell lines. The E-cadherin expression pattern in the prostate samples was correlated with histopathological findings in the same specimens. We found strong E-cadherin expression in normal prostate and benign prostatic hyperplasia. A decrease in or loss of E-cadherin was seen in 13 of 14 locally advanced and in 8 of 9 poorly differentiated prostatic carcinomas. We conclude that downregulation of E-cadherin expression plays a role in prostate carcinogenesis and invasiveness.     

Glypican 3: a novel marker in testicular germ cell tumors

Glypican 3 (GPC3), a membrane-bound heparin sulfate proteoglycan, may play a role in promoting embryonic cell growth and differentiation. GPC3 is mutated in Simpson-Golabi-Behmel syndrome, characterized by tissue overgrowth and an increased risk of embryonal malignancies. Recently, GPC3 was reported to be one of the over-expressed genes in testicular yolk sac tumors by gene expression microarray analysis. However, the presence of the GPC3 protein in germ cell tumors has never been investigated. The purpose of the study was to investigate the GPC3 expression in various histologic components of testicular germ cell tumors using immunohistochemistry and to assess its possible utility as a diagnostic marker. Tumors from 71 patients were examined, including components of 42 seminomas, 37 embryonal carcinomas, 24 yolk sac tumors, 20 teratomas with mature elements, 16 teratomas with immature elements, and 7 choriocarcinomas. Cytoplasmic and membranous immunoreactivity was semiquantitatively evaluated. All yolk sac tumor (24/24) and choriocarcinoma (7/7) components were immunoreactive for GPC3, whereas only 38% of teratomas with immature elements and 8% of embryonal carcinomas expressed GPC3. There was no immunoreactivity in benign testicular tissue, intratubular germ cell neoplasia, seminomas (0/42), or teratomas with mature elements (0/20). We conclude that the oncofetal protein GPC3 is a novel immunohistochemical marker in testicular germ cell tumors with differential expression in defined histologic subtypes. Our findings suggest a possible role of GPC3 in tumor cell differentiation. Furthermore, GPC immunostaining may be useful in the pathologic diagnosis of nonseminomatous germ cell tumors, particularly yolk sac tumor, and choriocarcinoma.     

TCL1 in B-cell tumors retains its normal b-cell pattern of regulation and is a marker of differentiation stage

The high expression of the T-cell oncogene TCL1 in B-cell tumors and the emergence of B-cell lymphomas in TCL1-transgenic mice suggest a pathogenetic role for this kinase coregulator in B-cell malignancies. We compared the expression of TCL1 in B-cell tumors with their differentiation stage. As with normal B-cell subsets, uniform TCL1 expression was characteristic of tumors of pregerminal center derivation such as precursor B-cell lymphoblastic leukemia/lymphoma (85%, 47/55) and mantle cell lymphoma (84%, 49/58), and was more variable in follicular lymphoma (57%, 28/49). Large B-cell lymphoma was less frequently positive for TCL1 (36%, 18/50), especially among cases of the activated B-cell type. All types of Hodgkin lymphoma, splenic marginal zone lymphoma, and post-germinal center-derived tumors, including plasma cell myeloma and MALT lymphoma, were negative for TCL1, except for 1 case. In nearly all TCL1-expressing tumors, as with normal B cells, variations in cellular TCL1 levels were related to the proliferation and microenvironmental factors. In normal B cells, cell lines and primary B-cell tumor samples, TCL1 downmodulation occurred after prolonged cytokine treatment and/or B-cell receptor stimulation. In contrast to mature T-cell tumors where TCL1 expression is always indicative of an activating TCL1 gene translocation, TCL1 expression in B-cell tumors parallels its regulation in non-neoplastic B cells. Therefore, TCL1 expression can be used diagnostically as an indicator of the differentiation stage of a given B-cell tumor.     

Immunoreactive S-antigen in cerebrospinal fluid: a marker of pineal parenchymal tumors?

This investigation evaluated the possibility that the occurrence of S-antigen in cerebrospinal fluid (CSF) might be used as a preoperative marker of pineal parenchymal tumors (pineoblastoma and pineocytoma). Such a marker could provide a means of preoperatively differentiating these neoplasms from pineal region tumors of other origin. The S-antigen, also known as the 48-kD protein or arrestin, is a highly antigenic protein originally found in the retina and pineal gland. In the retinal photoreceptors and submammalian pineal photoreceptors the protein is thought to be involved in phototransduction; its function in the mammalian pinealocyte is unknown. S-Antigen immunoreactivity also occurs in certain neoplastic cells of retinoblastomas, pineocytomas, pineoblastomas, and cerebellar medulloblastomas. This study included a group of 13 patients with tumors of the pineal region. Samples of CSF were obtained preoperatively and analyzed for the S-antigen using western blot technology. Tumor biopsy material was classified according to conventional neurohistological criteria and was also examined by immunocytochemical techniques for the presence of the S-antigen. S-Antigen immunoreactivity was found in the preoperative CSF of the one patient found to have pineocytoma; tumor tissue removed from this patient was the only neoplastic tissue examined in this study which contained S-Antigen immunoreactive tumor cells. Furthermore, hydroxyindole-O-methyltransferase activity was detectable in the pineocytoma but not in three other pineal tumors, and melatonin levels in the CSF of the pineocytoma patient were the highest in the patient group examined. These preliminary results suggest that testing for S-antigen in CSF might be useful in characterizing and treating tumors of the pineal region and, when identified in conjunction with other markers, it might also help to better define pineal parenchymal tumors. This study needs confirmation with a larger number of patients. If this approach is eventually found to be a reliable predictor of pineal cell tumors, it may supplant the need for surgical biopsies before initiating appropriate adjunctive therapy.     

Adrenal Neuroblastoma in an Adult: Report of a Case

Neuroblastomas comprise a major part of adrenal tumors in children. However, they are seldom reported in adults. In this report we present the case of a 30-year-old woman who was operated on for an incidentaloma. Following an adrenalectomy, she was put on a chemoradiotherapy regimen. A histopathologic assessment of the specimen revealed Homer-Wright rosettes against a background of fibrillary matrix, which indicated a diagnosis of a neuroblastoma. In spite of a low incidence in adulthood, it should be emphasized that all adrenal tumors without any particular characteristics may be a neuroblastoma, which tends to show a very poor prognosis. Hence, such patients should undergo postoperative chemoradiotherapy, which may improve both the remission rates and survival.     

The use of spinal angiography in the management of posterior mediastinal tumors: Case series and review of the literature

Introduction

Resection of inferiorly located posterior mediastinal tumors can be complicated by their proximity to the artery of Adamkiewicz (AKA). Although uncommon, intraoperative injury to the AKA may result in paraparesis or paralysis secondary to spinal cord ischemia. The use of preoperative spinal angiography may serve as a useful adjunct to the surgeon in guiding extent of resection of the tumor to avoid injury to this critical artery.

Methods

After IRB approval (H-31712), three patients, from 2008 to 2011, with lower posterior mediastinal tumors were identified. Their charts were reviewed for information concerning preoperative imaging, operative details, and postoperative neurologic complications. The literature regarding imaging of the AKA, cases of injury in pediatric patients, and recommendations for treatment after its injury were reviewed.

Results

One patient, who did not have preoperative spinal angiography, developed transient paresis lasting 6 weeks after posterior mediastinal tumor resection. Two patients underwent preoperative spinal angiography with successful localization of the AKA. In both cases, the patients subsequently underwent posterior mediastinal tumor resection without injury to the artery and without postoperative neurologic sequelae.

Conclusions

Preoperative spinal angiography may serve as a useful adjunct in the evaluation of children with inferior posterior mediastinal tumors in order to delineate the relationship of the artery of Adamkiewicz to the tumor for the purpose of guiding surgical resection.     

Apo D in soft tissue tumors: a novel marker for dermatofibrosarcoma protuberans

Using gene microarray expression profiling, we previously found that apolipoprotein D (Apo D) was highly expressed in dermatofibrosarcoma protuberans (DFSP). In this study, we confirm that Apo D is highly and relatively specifically expressed in DFSP using immunohistochemistry. A tissue microarray containing 421 soft tissue tumors was constructed and stained with antibodies against Apo D and CD34. Cytoplasmic immunostaining for Apo D was found in 9 of 10 typical DFSPs. In addition, 3 of 3 Bednar tumors and 2 of 3 giant cell fibroblastomas stained in conventional sections. In contrast, Apo D was immunoreactive in only a very small subset of a diverse collection of other soft tissue tumors, including Malignant Fibrous Histiocytoma (MFH), glomus tumor, neurofibroma, and malignant peripheral nerve sheath tumors. Immunostains for Apo D were negative in conventional sections of 16 fibrous histiocytomas, and an additional 12 variants of fibrous histiocytoma. Digital images of all immunohistochemical and hematoxylin and eosin tissue microarray stains are available at the accompanying website (http://microarray-pubs.stanford.edu/tma_portal/apod/). We conclude that Apo D is strongly expressed in DFSPs and neural lesions and may be useful in differentiating DFSP from fibrous histiocytoma.     

CDX-2 homeobox gene product expression in neuroendocrine tumors: its role as a marker of intestinal neuroendocrine tumors

CDX-2 is a homeobox gene product essential for intestinal development and differentiation. It can be used as a specific marker of colorectal adenocarcinomas and other tumors with intestinal differentiation, but little is known about its expression in endocrine and neuroendocrine (NE) cells and NE primary and metastatic tumors. Using the Cdx-2-88 monoclonal antibody, we evaluated CDX-2 expression in routine samples of 20 normal endocrine/NE tissues and of 299 samples of well-differentiated NE tumors (WDNET) and high-grade NE carcinomas (NEC) from different sites. For 17 cases, we examined primary and corresponding metastatic lesions. We also examined 8 cytologic samples of liver metastases derived from 4 ileal WDNETs, 1 lung WDNET, and 3 pancreatic endocrine tumors. CDX-2 mRNA expression with RT-PCR technique on frozen material was evaluated in 5 WDNETs. CDX-2 was expressed in normal NE cells of the intestine and gastric fundus. High CDX-2 expression was seen in all ileal and appendiceal WDNET, while low levels were seen in WDNETs from stomach, duodenum, and rectum; no reactivity was seen in other WDNETs. Low levels of CDX-2 expression were seen in one third of nonfunctioning pancreatic WDNET where it was more frequently observed in cases with metastatic disease (P = 0.002). CDX-2 was identified in all cytologic specimens of metastatic ileal WDNETs. CDX-2 mRNA analysis confirmed immunohistochemical results. CDX-2 was expressed at high levels in 81% of intestinal NEC. Unexpectedly, variable levels of expression of CDX-2 were seen also in 39% of NEC of other sites, without any relation with the site of origin. This reactivity frequently overlapped TTF-1 expression, suggesting deregulated expression of homeobox genes in NEC. The restricted pattern of CDX-2 expression may have diagnostic value in the identification of the primary site of a metastatic WDNET. Conversely, a limited diagnostic role is suggested for CDX-2 in NEC because of its frequent expression in nongastrointestinal tumors.