Zuckerkandl's Organ Research Articles

Laparoscopic removal of a large pheochromocytoma-paraganglioma of the Zuckerkandl organ

Paragangliomas represent 15 to 20% of all chromaffin tissue tumors. Most often, paragangliomas are located in the abdominal cavity along the large vessels — in the para-aortic region from the diaphragm to the aortic bifurcation. One of the most common extra-adrenal pheochromocytomas is the Zuckerkandl tumor, originating from the para-aortic accumulation of sympathetic tissue located in the area of the inferior mesenteric artery’s origine or in the zone of the aortic bifurcation itself. Due to the technical difficulty in performing laparoscopic removal of paragangliomas, conversion to laparotomy is frequent and reaches 80%. The article describes a clinical case of a patient suffering from this type of neoplasm, with diagnosis details and treatment by a successful radical laparoscopic intervention with a large chromaffinnoma located in a difficult anatomical zone removal.

Pigmented Renal Paraganglioma: A Case Report and Review of the Literature

Aim: Paragangliomas are rare non-epithelial tumors originating from paraganglia cells in various anatomical regions. Pigmented paragangliomas are more rare. We present the second reported case of kidney-induced pigmented paraganglioma in conjunction with literature. Case Report: A 44-year-old female patient with no known systemic disease was evaluated due to palpitations and a mass detected in the right kidney. Surgically, a 6 cm mass localized between kidney middle pol and vena cava inferior was separated from the surrounding tissues. In the sections prepared from the lesion, there were organoid patterned cell islands separated by fibrovascular septa. Brown pigment was evident in most of the tumor cells. Immunohistochemically, tumor cells expressed synaptophysin, chromogranine, NSE. In tumor cells, Mart1 and HMB45 were negative. In the light of all these findings, the case was diagnosed as ‘pigmented paraganglioma’. Discussion: The most common localizations of paragangliomas are carotid body, vagal body, middle ear, Zuckerkandl organ, mediastinum and retroperitoneum. There are 12 cases of intrarenal paraganglioma reported in the literature. Pigmented paraganglioma originating from the kidney has been reported only once. Conclusions: By presenting the second kidney-derived pigmented paraganglioma reported in the literature, we emphasize that the morphological and geographic spectra of these tumors may be large.

Laparoscopic resection of a large clinically silent paraganglioma at the organ of Zuckerkandl: a rare case report and review of the literature

BackgroundLarge paraganglioma of the Zuckerkandl organ (POZ) is extremely rare. The patient can occasionally be paucisymptomatic, further obscuring the diagnosis and carrying high mortality. Recommended treatment for large paraganglioma (PGL) is open surgical removal. We report a case of successful laparoscopic resection of a large POZ with normal blood pressure in a 45-year-old man.Case presentationA 45-year-old man was hospitalized because of hyperglycemia. Computed tomography of the abdomen and the serum and urinary catecholamine levels confirmed the diagnosis of large POZ. But his blood pressure was normal and he underwent laparoscopic tumor excision successfully. During 6 months follow-up after laparoscopy, serum and urinary catecholamines were normal but glycaemia remained high level. DNA analysis of the succinate dehydrogenase complex subunits B (SDHB) and SDHD revealed no mutation.ConclusionsPOZ is an unusual mass and preoperative diagnosis can be difficult in clinically silent cases. PGL cannot be excluded in patients with normal blood pressure. Even a large POZ can be excised laparoscopically by following proper techniques.

Schwann Cell Precursors Generate the Majority of Chromaffin Cells in Zuckerkandl Organ and Some Sympathetic Neurons in Paraganglia

In humans, neurosecretory chromaffin cells control a number of important bodily functions, including those related to stress response. Chromaffin cells appear as a distinct cell type at the beginning of midgestation and are the main cellular source of adrenalin and noradrenalin released into the blood stream. In mammals, two different chromaffin organs emerge at a close distance to each other, the adrenal gland and Zuckerkandl organ (ZO). These two structures are found in close proximity to the kidneys and dorsal aorta, in a region where paraganglioma, pheochromocytoma and neuroblastoma originate in the majority of clinical cases. Recent studies showed that the chromaffin cells comprising the adrenal medulla are largely derived from nerve-associated multipotent Schwann cell precursors (SCPs) arriving at the adrenal anlage with the preganglionic nerve fibers, whereas the migratory neural crest cells provide only minor contribution. However, the embryonic origin of the ZO, which differs from the adrenal medulla in a number of aspects, has not been studied in detail. The ZO is composed of chromaffin cells in direct contact with the dorsal aorta and the intraperitoneal cavity and disappears through an autophagy-mediated mechanism after birth. In contrast, the adrenal medulla remains throughout the entire life and furthermore, is covered by the adrenal cortex. Using a combination of lineage tracing strategies with nerve- and cell type-specific ablations, we reveal that the ZO is largely SCP-derived and forms in synchrony with progressively increasing innervation. Moreover, the ZO develops hand-in-hand with the adjacent sympathetic ganglia that coalesce around the dorsal aorta. Finally, we were able to provide evidence for a SCP-contribution to a small but significant proportion of sympathetic neurons of the posterior paraganglia. Thus, this cellular source complements the neural crest, which acts as a main source of sympathetic neurons. Our discovery of a nerve-dependent origin of chromaffin cells and some sympathoblasts may help to understand the origin of pheochromocytoma, paraganglioma and neuroblastoma, all of which are currently thought to be derived from the neural crest or committed sympathoadrenal precursors.

Composite paraganglioma and ganglioneuroma in the retroperitoneum: a case report

Reports of a composite paraganglioma (PG) and ganglioneuroma (GN) in the retroperitoneum are rare. In the present case, dynamic computed tomographic (CT) findings showed a 30 × 22 × 20 mm tumor that was located in the retroperitoneum and which was dissociated from pancreatic tissue and the left adrenal gland. The markedly reddish tumor showed a clear margin and central multicystic changes on the cut surface. The tumor was composed of two major components, the PG and the GN. The paraganglionic cells in the PG component, which were arranged in a nested pattern, occupied the main and central part of the tumor. Both ganglionic cells and Schwann cells in the GN were located in a unorganized pattern in the periphery. The paraganglionic cells exhibited a Zellballen pattern, which consisted of an association of edematous vascular-rich stroma and focal hemorrhage, resulting in multicystic changes. These centrally located tumor cells were pleomorphic in part and did not have mitotic figures. In the periphery, Schwann cells, which were arranged in an obscure and fascicular pattern that was intermingled with large ganglionic cells, were located adjacent to the PG component with a mostly sharp margin. With higher magnification, the border was not as sharp, as revealed especially with chromogranin-A immunostain, in which both the PG and GN components were focally intermingled with each other. The histogenesis of the composite PG and GN was thought to be extraadrenal neural crest cells in the retroperitoneum because the tumor was not located in the adrenal gland or the Zuckerkandl organ, according to the CT findings. The immunohistochemical findings of this rare case of a composite PG and GN in the retroperitoneum are reported with a focus on the peculiar arrangement of these two components.

Extra-adrenal Pheochromocytoma in the Organ of Zuckerkandl: Diagnosis and Treatment Strategies

Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare catecholamine-secreting neuroendocrine tumors arising from chromaffin tissue and can occur within the adrenal medulla (PHEO) or extra-adrenal sites (PGL). The most common site for PGL is the organ of Zuckerkandl, extra-adrenal chromaffin tissue near the origin of the inferior mesenteric artery.We here present 2 patients with extra-adrenal PGL in the organ of Zuckerkandl, located by iodine-123-metaiodobenzylguanadine ( (123)I-MIBG) scintigraphy and thereafter treated surgically or with iodine-131-metaiodobenzylguanadine ( (131)I-MIBG). First, in a 15-year-old boy with clinical suspicion of PHEO, the diagnosis was established by biochemical evaluation and confirmed by further imaging studies, including CT and (123)I-MIBG, as PGL in the Zuckerkandl organ. The tumor was completely resected by laparotomy. Second, in a 70-year-old woman presenting with progressive hypertension and palpitations, MR and (123)I-MIBG revealed a singular tumor lesion with abnormal (123)I-MIBG uptake in the Zuckerkandl organ. Due to severe general vascular disease, surgery was not performed and instead the patient underwent (131)I-MIBG therapy. The patient showed a good symptomatic response with improvement of symptoms and no relevant side-effects of therapy.

Zuckerkandl's organ improves long-term survival and function of neural stem cell derived dopaminergic neurons in Parkinsonian rats

Transplantation of neural stem cells (NSC) derived dopamine (DA) neurons has emerged as an alternative approach to fetal neural cell transplantation in Parkinson's disease (PD). However, similar to fetal neural cell, survival of these neurons following transplantation is also limited due to limited striatal reinnervation (graft with dense neuronal core), limited host–graft interaction, poor axonal outgrowth, lack of continuous neurotrophic factors supply and principally an absence of cell adhesion molecules mediated appropriate developmental cues. In the present study, an attempt has been made to increase survival and function of NSC derived DA neurons, by co-grafting with Zuckerkandl's organ (a paraneural organ that expresses neurotrophic factors as well as cell adhesion molecules); to provide continuous NTF support and developmental cues to transplanted DA neurons in the rat model of PD. 24 weeks post transplantation, a significant number of surviving functional NSC derived DA neurons were observed in the co-transplanted group as evident by an increase in the number of tyrosine hydroxylase immunoreactive (TH-IR) neurons, TH-IR fiber density, TH-mRNA expression and TH-protein level at the transplantation site (striatum). Significant behavioral recovery (amphetamine induced stereotypy and locomotor activity) and neurochemical recovery (DA-D2 receptor binding and DA and DOPAC levels at the transplant site) were also observed in the NSC + ZKO co-transplanted group as compared to the NSC or ZKO alone transplanted group. In vivo results were further substantiated by in vitro studies, which suggest that ZKO increases the NSC derived DA neuronal survival, differentiation, DA release and neurite outgrowth as well as protects against 6-OHDA toxicity in co-culture condition. The present study suggests that long-term and continuous NTF support provided by ZKO to the transplanted NSC derived DA neurons, helped in their better survival, axonal arborization and integration with host cells, leading to long-term functional restoration in the rat model of PD.

3.204 Zuckerkandl's organ improves long-term survival and function of neural stem cells derived dopaminergic neurons in Parkinsonian rats

3.204 Zuckerkandl's organ improves long-term survival and function of neural stem cells derived dopaminergic neurons in Parkinsonian rats

3.017 Zuckerkandl's organ improves long-term survival and function of neural stem cells derived dopaminergic neurons in Parkinsonian rats

3.017 Zuckerkandl's organ improves long-term survival and function of neural stem cells derived dopaminergic neurons in Parkinsonian rats

Pathogenesis of Parkinson's disease: prospects of neuroprotective and restorative therapies.

Parkinson's disease (PD) is caused by the degeneration of dopaminergic neurons of substantia nigra projecting to striatum. The cause of idiopathic PD is obscure, and most cases are sporadic. It is widely accepted that there is a genetic component of the disease, and the earlier the age of onset, the greater the likelihood that genetic factors play a dominant role. Oxidative stress of the substantia nigra seems to contain the driving force for neurodegeneration, leading to a destructive "toxic cycle." The most prevalent therapy is levodopa administration, but it is not efficacious after several years of treatment. Several alternative therapies are currently being explored, such as neuroprotective approaches. Compounds with potentially neuroprotective efficacy such as selegiline, dopamine agonists, riluzole, creatine, and coenzyme Q10 are currently being tested. Trophic factors represent another class of neuroprotective compounds, but their intracerebral administration is difficult to achieve. In this respect, a potentially useful therapeutic approach is grafting cell vectors that release trophic molecules that stimulate regeneration in the damaged nigrostriatal system. Promising results have been obtained with fibroblasts engineered to secrete glial cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) or viral vectors expressing GDNF. We have tested the suitability of intrastriatal grafts of chromaffin cells obtained from the Zuckerkandl's organ, which exert beneficial effects in parkinsonian rats, and release trophic factors such as GDNF and transforming growth factor-beta1 (TGF-beta1).

Functional Regeneration in a Rat Parkinson's Model after Intrastriatal Grafts of Glial Cell Line-Derived Neurotrophic Factor and Transforming Growth Factor β1-Expressing Extra-Adrenal Chromaffin Cells of the Zuckerkandl's Organ

Intrabrain transplantation of chromaffin cell aggregates of the Zuckerkandl's organ, an extra-adrenal paraganglion that has never been tested for antiparkinsonian treatment, induced gradual improvement of functional deficits in parkinsonian rats. These beneficial effects were related to long survival of grafted cells, striatal reinnervation, and enhancement of dopamine levels in grafted striatum. Grafted cells were not dopaminergics, but they expressed glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor-beta(1). These factors were detected in the host striatal tissue, indicating that chromaffin cells secreted them after grafting. Because glial cell line-derived neurotrophic factor possesses neurorestorative properties over dopaminergic neurons, and transforming growth factor-beta(1) is a cofactor that potentiates the neurotrophic actions of GDNF, functional regeneration was likely caused by the chronic trophic action of neurotrophic factors delivered by long-surviving grafted cells. This work should stimulate research on the clinical applicability of transplants of the Zuckerkandl's organ in Parkinson's disease.

A Case of Extra-adrenal Pheochromocytoma Producing Epinephrine

We reported a case of a 72-year-old man with an extra-adrenal pheochromocytoma secreting excessive epinephrine (E). He had been treated for diabetes mellitus and essential hypertension. His diabetes was controlled poorly, but his blood pressure was controlled well. He was admitted to our hospital for weight loss evaluation. An upper gastrointestinal series and computed tomography of the abdomen revealed an ovoid mass (diameter, approximately 5×6 cm) overlying the abdominal aorta and the inferior vena cava between the second and the third lumbar vertebra. Aortography showed a hypervascular mass. Analysis of catecholamine (CA) and its metabolites showed elevations in plasma norepinephrine (NE, 3850 pg/ml) and E (560 pg/ml) levels as well as the urinary NE (1200-1400μg/day), E (310-350μg/day) and vanillylmandelic acid (26.8 mg/day) levels. Vena caval CA sampling indicated that the peak levels for both NE and E were at the third lumbar vertebra. The tumor (104 g) was removed in April 1991. Histological analysis revealed a typical pheochromocytoma with paraganglia adjacent to the tumor. The tumor cells were immunoreacted to phenylethanolamine-N-methyltransferase (PNMT). NE and E granules appeared on electron microscopy, and the urinary NE and E were normalized by the surgery. These findings suggest that our case may be an E-secreting extra-adrenal pheochromocytoma.The conversion of NE to E is catalyzed by PNMT found primarily in the adrenal medulla and the organ of Zuckerkandl. An E-secreting pheochromocytoma is generally located at either of these two sites. The classic location of the tumor to the Zuckerkandl organ is in the retroperitoneal tissue lateral to or overlying the lower portion of the abdominal aorta in the vicinity of the inferior mesenteric artery. Our case was at the typical location and had a microscopic pattern of paraganglia adjacent to the tumor. In our case, the pheochromocytoma appears to have originated in the Zuckerkandl.

Observations on the anatomy and amine histochemistry of the nerves and ganglia which supply the pelvic viscera and on the associated chromaffin tissue in the guinea-pig

The organs of the lower abdominal and pelvic regions of the guinea-pig receive nerves from the inferior mesenteric ganglia and pelvic plexuses. The inferior mesenteric ganglia connect with the sympathetic chains, the superior mesenteric ganglia, the pelvic plexuses via the hypogastric nerves, and with the gut. Each pelvic plexus consists of anterior and posterior parts which send filaments to the internal generative organs and to the rectum, internal anal sphincter and other pelvic organs. The pelvic nerves enter the posterior plexuses, which also receive rami from the sacral sympathetic chains. The adrenergic neurons of the pelvic plexuses are monopolar, do not have dendrites and are supplied by few varicose adrenergic axons. Nearly all the nerves contain adrenergic fibres. After exposure to formaldehyde vapour the chromaffin cells appear brightly fluorescent with one or two long, often varicose, processes. Most of the chromaffin cells are in Zuckerkandl's organ or in chromaffin bodies associated with the inferior mesenteric ganglia. Groups of chromaffin cells are found along the hypogastric nerves and in the pelvic plexuses; they become smaller and fewer as regions more posterior to Zuckerkandl's organ are approached.

GANGLIONEUROMA OF THE OVARY

Tumors composed of such highly specialized tissue as adult ganglion cells and their processes are comparatively rare. McFarland,¹who reported a case in 1931, was able to find reference in the literature to ninety-three similar tumors. The literature was likewise reviewed in 1932 by Bigler and Hoyne,2who added two cases of their own. Loretz³reported the first instance in 1870. Since then ganglioneuromas have been reported as arising in the central nervous system, cranial nerve roots and their associated ganglions and the sympathetic ganglions of the neck, thorax and abdomen. They also may arise in the adrenal medulla, the carotid gland, the coccygeal gland and Zuckerkandl's organ. No previous report has been found of a ganglioneuroma arising in the ovary. Ganglioneuromas appear to arise chiefly from the sympathetic nervous system. In the ovary, groups of sympathetic ganglion cells occur normally in the medulla near the hilus.