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Background: Genetic testing to identify succinate dehydrogenase (SDH) mutations in patients with head and neck paraganglioma (HNP) has been in clinical practice for more than a decade. However, the recurrence and metachronous tumor occurrence risks in surgically treated mutation-positive patients are not well studied., Methods: Clinical and procedural details of consecutive patients who underwent excision for HNP from January 1996 to October 2016 were retrospectively reviewed. End points included recurrence, metachronous tumor detection, and mortality. Germline DNA was tested to identify mutations in SDHx genes. Patients were divided into three groups on the basis of genetic testing: group I, positive; group II, negative; and group III, unknown or offered but not tested., Results: HNP was diagnosed in 268 patients, 214 (147 female; mean age, 47 years) included in this study. Directed genetic testing was performed in 68; mutations were detected in SDH in 47 (69%), a majority SDHD. In group I, 47 patients had 64 procedures for 81 tumors (52 carotid body tumors [CBTs]); 17 (36%) were bilateral, 7 (15%) multiple, 3 (6%) functional, and 7 (15%) malignant. Residual tumor in 10 was significant in 2, managed by radiation therapy and reoperation. Local recurrence was detected in 12 patients (25%) at a median of 8 years; 11 metachronous mediastinal and retroperitoneal paragangliomas were detected in 8 (17%) at a median of 13 years. Systemic metastases occurred in five (10%). Six patients (13%) had more than one recurrence. In group II, 21 patients had 22 procedures for 23 tumors, 17 CBTs. Two (9%) were bilateral and two (9%) malignant. Excision was complete in all with no recurrence or systemic metastasis at last follow-up. For group III, 146 patients underwent 153 procedures for 156 tumors, 95 CBTs; 7 (5%) were bilateral, 2 (1%) multiple, 8 (5%) functional, and 1 (0.6%) malignant. Local recurrence was detected in nine (6%) at a median of 9 years and metachronous HNP in three (2%) at a median of 5 years. Systemic metastases occurred in two (1%). Mortality was 4% in group I and 3% in group III, none procedure or tumor related. Group I (mutation positive) had 10-year overall, recurrence-free, and metachronous tumor-free survival rates of 93%, 69.4%, and 73%, respectively, lower than the other groups (P < .001)., Conclusions: Bilateral, functional, malignant, recurrent, and metachronous tumors are more common in SDH mutation-positive patients with HNP. Overall survival in patients with HNP is high. Metachronous tumors or local recurrences occur late, and long-term follow-up is necessary., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Paragangliomas are rare neoplasms that arise from chromaffin cells of the sympathetic and parasympathetic nervous system. These tumors are often cured by surgical resection but the risk for metastatic disease exists, particularly for extra-adrenal paragangliomas. The behavior of these tumors is unpredictable, and clinical and histopathological features associated with malignancy have not been determined. The most common sites of metastases include local and distant lymph nodes, bone, liver, and lung. Cutaneous metastases are exceedingly rare with only 2 reported cases, both of which presented on the scalp. Here we describe a 78-year-old woman with cutaneous metastatic paraganglioma presenting as a forehead nodule, which developed 15 years after her initial diagnosis of paraganglioma.

Metastatic extra-adrenal paragangliomas are very rare and can represent diagnostic challenges. We report a case of 69-year-old man with a tumor of the right shoulder. Histologic and immunohistochemical examinations confirmed the diagnosis of paraganglioma. Surprisingly, tumor cells were diffusely thyroid transcription factor 1 (TTF-1) positive. Succinate dehydrogenase complex subunit B (SDHB) deficiency has not been detected. Inherited syndromes associated with paragangliomas were ruled out. The primary tumor was identified in the mediastinum. This is the first report of TTF-1 expression in paraganglioma. To avoid misdiagnosis, careful clinical and pathological examination of any tumor with organoid growths pattern is necessary.

Objectives: Focal nodular hyperplasia (FNH) and peritumoral hyperplasia in the liver exhibit increased immunoreactivity for glutamine synthetase (GS). We observed FNH-like changes with map-like GS staining surrounding a metastatic paraganglioma and sought to determine how often such changes occur around primary and metastatic liver lesions., Methods: We performed GS immunohistochemistry in liver cases of 20 metastatic neuroendocrine carcinomas (NECs), 21 metastatic colon carcinomas (CCs), seven hepatocellular carcinomas (HCCs), and six FNHs and assessed lesions for size, degree of fibrosis (scored 1-3), and peritumoral hyperplasia., Results: Most NEC or CC cases had few peritumoral hyperplastic features. Three NECs, two CCs, and one HCC (13%) had patchy GS staining at the periphery of the lesions. One CC case had both histologic and immunohistochemical peritumoral hyperplasia., Conclusions: Peritumoral hyperplasia or FNH-like changes are uncommon findings around primary or metastatic lesions in the liver. GS immunohistochemistry assists in distinguishing true peritumoral hyperplasia from mass effect., (© American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Patients presenting with locally advanced, metastatic paraganglioma with life-threatening compressive symptoms of critical anatomic structure pose a significant management challenge., Methods: We present a case of a 15-year-old patient with enlarging right neck mass causing dysphagia and respiratory compromise from near complete obstruction of the oropharynx., Results: Evaluation of the patient's family history led to the identification of a mutation in the succinate dehydrogenase subunit B (SDSD) gene (G725A). Laboratory and imaging workup revealed an 8.8 × 6.6 × 4.1 cm metabolically and biochemically active right neck mass, a tumor in the left para-aortic region, and multiple bony lesions consistent with widely metastatic disease. Multidisciplinary management included preoperative clinical optimization, coil embolization, and palliative resection of the neck mass., Conclusion: Although the currently available treatment options for patients with advanced metastatic paraganglioma render no survival benefit, a multidisciplinary management approach aimed at relief of tumor-related symptoms and catecholamine excess should be undertaken., (© 2015 Wiley Periodicals, Inc.)

Head and neck paragangliomas are rare neuroendocrine tumors expressing somatostatin receptors on their cell surface, particularly subtype 2. Due to this distinctive feature, images can be obtained in Nuclear Medicine using synthetic analogues of somatostatin, mainly octreotide, which allow selective display by planar scintigraphy, SPECT-CT or PET-CT imaging after radiolabeling with (111)In or (68)Ga. Three cases have been selected and presented from a series of patients that illustrate the utility of SPECT-CT studies with (111)In-octreotide in the diagnosis and monitoring of this type of tumor. These are characterization at initial diagnosis, staging, and detection of local recurrence or metastasis, with added value with respect to anatomical images (nuclear magnetic resonance, computed axial tomography, angiography), for example in the differentiation between functional tissue or scar in patients who had previously undergone surgery., (Copyright © 2014 Elsevier España, S.L.U. y SEMNIM. All rights reserved.)

Many neuroendocrine tumors, including pheochromocytomas (PCs) and paragangliomas (PGLs), express one or more somatostatin receptors (SSTR1-5). A number of studies have reported SSTR expression in PCs and PGLs. However, receptor expression patterns have been conflicting, and until recently, specific monoclonal antibodies were not available against SSTR1-5. The aim of this study was to compare SSTR1-5 expression in succinate dehydrogenase (SDH)-deficient PCs and PGLs (defined as having absent SDHB immunostaining) to those tumors with normal SDHB staining. Immunohistochemistry for SDHB and SSTR1-5 was performed using specific monoclonal antibodies on archived formalin-fixed, paraffin-embedded tissue from patients who had undergone surgery for PC or PGLs. A total of 182 PC/PGLs were included (129 adrenal, 44 extra-adrenal, 9 metastases); 32 tumors were SDH deficient, whereas 150 tumors had positive SDHB staining. SDH-deficient tumors were more likely to demonstrate moderate or strong staining for SSTR2A and SSTR3 when compared with SDH-sufficient tumors (91% versus 49% [P < .0001] and 50% versus 21% [P = .0008], respectively). Immunostaining for the other SSTRs was not different between SDH-deficient and tumors with preserved SDHB staining. SSTR2A and SSTR3 are more likely to be expressed in SDH-deficient PC/PGLs as compared with tumors demonstrating normal SDHB staining pattern. These findings suggest that the role of somatostatin analogue therapy (unlabeled or radiolabeled) should be reexamined in the context of the underlying SDHB immunohistochemistry pattern., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The purpose of this paper is to present and discuss a new case of malignant vagal paraganglioma. A 38-year-old woman was referred for the assessment of a bilateral firm cervical mass. CT scans revealed a left cervical ovoid mass; contralaterally, a mass with a similar enhancement could be observed too. The tumor was surgically removed via a transcervical surgical approach, together with levels I to III lymph nodes. Definitive histopathological examination proved the diagnosis of malignant vagal paraganglioma with contralateral cervical lymph node metastasis. One year after surgery, a PET-CT and a scintigraphy revealed the presence of a cervical recurrence and hepatic metastasis. Three months after a second surgical intervention, the patient died. Malignant vagal paraganglioma is a rare and challenging lesion that has to be carefully assessed to plan an appropriate treatment. A strict follow-up is fundamental for an early diagnosis of eventual recurrences.

Paragangliomas typically develop in the extra-adrenal sites along the sympathetic and/or the parasympathetic chain. Occasionally, the tumors may arise in some exotic sites, including the head and neck region and the urogenital tract. Paraganglioma presenting as a primary rectal neoplasm has not been well described in the literature. Here, we report the first case of malignant paraganglioma arising in the rectum of a 37-year-old male. He presented to the clinic because of hematochezia with tenesmus. The anorectal digital examination and colonoscopic examination revealed a polypoid mass of the rectum, measuring approximately 4 cm in diameter. The overall morphology and immunophenotype were consistent with a typical paraganglioma. However, the tumor exhibited features suggestive of malignant potential, including local extension into adjacent adipose tissue, nuclear pleomorphism, confluent tumor necrosis, vascular invasion and metastases to regional lymph nodes. In conclusion, we present the first case of rectal malignant paraganglioma. Due to the unexpected occurrence in this region, malignant paraganglioma may be misdiagnosed as other tumors with overlapping features; in particular, a neuroendocrine tumor of epithelial origin. Because of the differences in treatment, separating paraganglioma from its mimics is imperative. Combination of morphology with judicious immunohistochemical study is helpful in obtaining the correct diagnosis.

Background: Extra-adrenal paraganglioma of the retroperitoneum with metastasis to the vertebra is very rare. To our knowledge this is the first report of this kind of disease in the literature., Case Presentation: Here, we present an oroginal case of paraganglioma of the retroperitoneum with metastasis to the abdominal vertebra in a 42-year-old female patient who was successfully treated by complete removal of the tumor and its metastasis. The patient was followed up for four years and remained disease-free., Conclusion: Our case demonstrated the need to consider paraganglioma of the retroperitoneum in the differential diagnosis of retroperitoneal mass, metastatic tumors to the vertebra, and the importance of radical surgery for a successful management of the disease., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1956611954880197.

This is a case report of the anesthetic management for the hepatic resection of a metastatic paraganglioma in a patient with a history of prior orthotopic liver transplantation. Of interest, the metastatic paraganglioma originated from the donor organ. The patient is an 80-year-old woman with multiple medical problems including a history of cryptogenic cirrhosis who underwent successful orthotopic liver transplantation 9 years prior. She later presented with signs and symptoms of catecholamine excess suggestive of a catecholamine-producing tumor (paraganglioma or pheochromocytoma). Elevated urine catecholamine levels and radiographic evidence of a paraganglioma in the transplanted liver metastatic from the donor organ confirmed the diagnosis. Radiofrequency ablation of the tumor and surgical resection was previously attempted without success. We describe the anesthetic management for the successful resection of the metastatic hepatic paraganglioma, which was complicated by profound intraoperative hypertension and hypotension that necessitated the use of multiple vasoactive infusions, extensive surgical blood loss requiring blood transfusion, and difficult glycemic control in an insulin-dependent diabetic patient. The postoperative course is also described. This unique case presented the anesthesia team with challenges specific to both surgery for hepatic resection as well as for catecholamine-secreting tumors. We are not aware of any reports of paragangliomas of either donor or recipient origin involving a transplanted liver, making this the first such report to the best of our knowledge., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Paragangliomas are rare neuroendocrine neoplasms arising in extra-adrenal chromaffin cells of the autonomic nervous system. In rare instances, paragangliomas present around and involve the pancreas, thereby mimicking one of the more common primary pancreatic lesions. These neoplasms present considerable diagnostic difficulty not only for the clinician and radiologist but also for the pathologist. We have collected a series of 9 peripancreatic paragangliomas clinically simulating a primary pancreatic lesion. The paragangliomas were diagnosed in 4 men and 5 women with an age range of 37 to 78 years (mean, 50 y). Patients presented clinically either with diffuse epigastric and abdominal pain (7 of 9, 78%) or with an incidental mass (2 of 9, 22%) discovered on routine radiographic imaging. All patients were found to have mass lesions suspicious for a primary pancreatic neoplasm on radiographic examination. The lesions were predominantly located in the body of the pancreas (5 of 9, 56%) and ranged in size from 5.5 to 17.0 cm (mean, 10.0 cm). Five of 9 (56%) neoplasms also demonstrated cystic change. Fine-needle aspiration (FNA) was performed on 6 cases; however, the diagnostic accuracy was low, with 3 of 6 (50%) neoplasms misdiagnosed as pancreatic neuroendocrine tumor (PanNET) (n=1), spindle cell neoplasm (n=1), or pseudocyst (n=1). In addition, 2 of 8 (25%) surgically resected tumors were misdiagnosed by the referring pathologist as a PanNET. Immunohistochemistry was performed on all cases, confirming the characteristic 2-cell populations: chief cells (synaptophysin positive and chromogranin A positive) and sustentacular cells (S-100 protein positive). Follow-up information was available for all patients and ranged from 2 months to 11.6 years (mean, 2.7 y). Three of 9 (33%) patients developed metastatic disease, and 2 of these 3 died of their disease at 2.8 and 4.6 years after diagnosis. In summary, in unsuspected cases, interpretation of FNA and surgical pathology resections can be diagnostically challenging. Awareness and proper recognition of this entity, including differential diagnosis, are imperative in establishing the correct diagnosis. Further, close follow-up of these cases should be considered because of the significant risk of metastatic disease.

Post-mortem examination was performed on a horse that died after exhibiting signs of colic. Gross findings included haemoperitoneum and a large round encapsulated mass located in the sublumbar area cranial to the left kidney. On sectioning the mass was solid red to brown and small nodules of similar tissue were noted at the periphery of the mass. The spleen was firm and three nodules were found in one thyroid gland. Microscopically, the abdominal mass, adjacent nodules, the spleen and one thyroid nodule consisted of clusters and cords of round to oval neoplastic cells, separated by a fine collagen and reticulin fibre network. Immunohistochemically, tumour cells expressed chromogranin A, synaptophysin and neuron-specific enolase, but did not express cytokeratin. The findings were consistent with a metastatic extra-adrenal sympathetic paraganglioma., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Operative excision of abdominal extra-adrenal paragangliomas (EAPs) does not preclude the late development of local-regional recurrence. We describe the incidence, characteristics, and outcome of this rarely reported feature., Methods: Retrospective analysis of local-regional recurrence that occurred during follow-up of 51 consecutive patients operated for a sporadic (n = 26) or hereditary (n = 25) EAP., Results: Seven patients with a sporadic or syndromic EAP (n = 4: von Hippel-Lindau syndrome and SDHB, SDHC, and SDHD gene mutations) underwent reoperation for a local-regional recurrence after a median time of 46 months (interquartile range [IQR], 16-100). The Kaplan-Meier estimated incidence of local-regional recurrence (+/- standard error of the mean) reached 15% +/- 7% at 5 years and 23% +/- 9% after 10 years. Recurrent EAPs were all secreting and 38% provoked clinical symptoms. New lesions were smaller than the primary EAP (P = .01) and more often associated with lymph node metastases (43% vs 4%, P = .01). Operative excision seemed complete in 5 patients. Clinical remission was maintained in 4 patients after a median follow-up of 57 months (IQR, 22-102)., Conclusion: Local-regional recurrence of sporadic and syndromic EAPs is frequent and may be delayed beyond 10 years, requiring lifelong follow-up after the initial operation. When technically feasible, operative excision can lead to prolonged remission.

A 54-year-old man underwent surgery for excision of a retroperitoneal tumor that measured 12 cm in diameter, and histopathological examination revealed the tumor was an extraadrenal retroperitoneal paraganglioma. He presented 9 years later with epigastric discomfort. Abdominal ultrasound showed a solitary liver tumor. The diagnosis, based on radiological workup, was metastatic paraganglioma. The tumor was surgically resected and the histological findings resembled those of the primary tumor. The patient has been followed up for 3 years and remains recurrence-free. Surgical resection is an effective treatment approach for primary and secondary paragangliomas, but the resectability of liver metastatic lesions is usually low, although complete resection with a wide surgical margin was possible in this patient. This case suggests that a good prognosis after the resection of hepatic metastasis depends not only on the curative resection of the metastatic lesion but also on the tumor characteristics, such as slow growth or low aggressiveness.

Mutations in succinate dehydrogense-B (SDHB) and the von Hippel-Lindau (VHL) genes result in an increased risk of developing chromaffin tumours via a common aetiological pathway. The aim of the present retrospective study was to compare the clinical phenotypes of disease in subjects developing chromaffin tumours as a result of SDHB mutations or VHL disease. Thirty-one subjects with chromaffin tumours were assessed; 16 subjects had SDHB gene mutations and 15 subjects had a diagnosis of VHL. VHL-related tumours were predominantly adrenal phaeochromocytomas (22/26; 84.6%), while SDHB-related tumours were predominantly extra-adrenal paragangliomas (19/25; 76%). Median age at onset of the first chromaffin tumour was similar in the two cohorts. Tumour size was significantly larger in the SDHB cohort in comparison with the VHL cohort (P=0.002). Multifocal disease was present in 9/15 (60%) of the VHL cohort (bilateral phaeochromocytomas) and only 3/16 (19%) of the SDHB cohort, while metastatic disease was found in 5/16 (31%) of the SDHB cohort but not in the VHL cohort to date. The frequency of symptoms, hypertension and the magnitude of catecholamine secretion appeared to be greater in the SDHB cohort. Renal cell carcinomas were a feature in 5/15 (33%) of the VHL cohort and 1/16 (6%) of the SDHB cohort. These data indicate that SDHB-related tumours are predominantly extra-adrenal in location and associated with higher catecholamine secretion and more malignant disease, in subjects who appear more symptomatic. VHL-related tumours tend to be adrenal phaeochromocytomas, frequently bilateral and associated with a milder phenotype.

We present a 23-year-old patient with extra-adrenal retroperitoneal paraganglioma with lung metastases who was successfully treated by complete removal of the tumour. Lung metastases were the first manifestation of the disease, and an abdominal computed tomography scan showed a large mass in the retroperitoneum with marked contrast enhancement. Angiography demonstrated a hypervascular mass with many feeding arteries, but vascular invasion was not apparent. The retroperitoneal tumour was resected completely followed by resection of lung metastases after 1 month of observation. The patient was disease free for 13 years after this radical surgery. The survival rate in patients with retroperitoneal paraganglioma with lung metastasis is low, and this case represents the longest surviving period reported in the literature. These tumours are usually large and located in the para-aortic region, and hence resection is sometimes challenging. We believe that a complete and meticulous surgical procedure is a prerequisite for long survival from this rare disease.

Primary and secondary neoplasms of the canine and feline heart are uncommon. During a 2-year period, 83 dogs suffering from primary cardiac (n=11), extracardiac benign (n=6) or malignant (n=66) tumours and 30 cats with primary cardiac (n=1) or extracardiac (n=29) malignant tumours were examined. Echocardiography revealed four cases of primary cardiac neoplasms in dogs, but secondary heart tumours were not detected. After necropsy, tissue samples from the heart and tumours were examined histologically and immunohistochemically. In dogs, primary neoplasms included seven haemangiosarcomas, two chemodectomas, one rhabdomyosarcoma, and one neurofibrosarcoma. In 24 of 66 dogs examined, metastases of extracardiac neoplasms were found in the heart (15 carcinomas, six malignant lymphomas, three haemangiosarcomas). In cats, one case of primary haemangiosarcoma of the pericardium and five cases of secondary cardiac tumours (two malignant lymphomas, three carcinomas) occurred. Cardiac neoplasms in cats were not identified clinically but were detected by detailed gross sectioning of the heart (n=2) or histopathological examinations (n=3). This study showed an unexpectedly high number (36%) of dogs with cardiac metastases.

Malignancy (defined as metastatic disease) has been reported in nearly 5% of head and neck paragangliomas. Metastases preferentially target the lymph nodes, lung, liver, or bone. We describe three patients with multiple silent bone metastases exhibiting a fatty halo at MRI that coexisted with expansive bone lesions. In all cases, (123)I-metaiodobenzylguanidine ((123)MIBG) scintigraphy showed no abnormal tracer uptake, whereas (111)In-pentetreotide scintigraphy visualized a few silent bone metastases. These findings indicate that MRI should be included in the staging of paraganglioma patients with risk factors for malignancy.

The incidence of paraganglioma in the paediatric population is exceedingly rare, accounting for < 0.1% of childhood cancers. We report here the response and toxicity profile in a case of malignant paraganglioma which was treated with what is currently perceived as an unconventional and non-standard approach, using three consecutive low doses of 131I-MIBG (a cumulative dose of 11 647.6 MBq). The patient had a stable disease at the end of 42 months follow-up following the first treatment with 131I-MIBG. Excellent symptomatic and hormonal responses were observed. The only adverse effect was mild nausea in the first 24 h after therapy. In addition to the potentially primary end point of radiological and biochemical response measurement, we, in this paper, endeavoured to look for a quality of life evaluation for this form of treatment. Given the rarity of this condition, the experience gained by this therapeutic approach is intriguing from response and toxicity standpoints and may be extrapolated to malignant pheochromocytoma as well. An apparent "reverse discordance" between 131I-MIBG scintigraphy and 99Tc(m)-MDP bone scan encountered during pre-therapy work up is also described with possible explanations. This draws attention to an important clinical issue in selecting patients for high dose targeted therapy.

Pheochromocytomas and extra-adrenal sympathetic paragangliomas show varied histological patterns, and it is difficult to diagnose malignancy or predict the clinical course using current histological criteria. In the present study, we reviewed 146 sympathetic paragangliomas including 116 adrenal (102 unilateral, 14 bilateral) and 30 extra-adrenal tumors including 38 metastatic tumors. We developed a scoring scale according to the following six factors: histological pattern, cellularity, coagulation necrosis, vascular/capsular invasion, Ki-67 immunoreactivity, and types of catecholamine produced. The tumors were classified as well (WD), moderately (MD), and poorly differentiated (PD) types according to their scores. The frequency of these tumor types were 113 WD (77%), 27 MD (19%), and 6 PD (4%). Metastasis was observed in 15 of 113 WD (13%), 17 of 27 MD (63%), and all 6 PD (100%). Five-year survivals of patients with metastases were 92% with WD, 69% with MD, 0% with PD. Respective 10-yr survivals were 83%, 38%, and 0%. Differences between groups were statistically significant. The data show that using this grading scoring system for sympathetic paragangliomas correlates with both metastatic potential and patient survival.

The authors report on the use of external-beam radiotherapy and octreotide in a 32-year-old woman who presented with spinal cord compression secondary to metastatic chemodectoma. Scintigraphy studies were used to confirm the presence of somatostatin receptors. Magnetic resonance imaging, and in particular spinal angiography, were performed to define the extent of spinal metastatic disease. The literature on current investigation and management of vertebral metastatic chemodectoma is reviewed.

A 70-year-old female was operated on for extradural spinal cord tumor in 1982. Microscopic examination revealed the tumor as paraganglioma. Tumor recurred at paravertebral twice in 1985 and 1989, and they were also resected. In 1995, her chest X-ray film showed round tumor in the right upper field. Exploratory open lung biopsy was performed in 1996, and right upper lobectomy was performed according to for malignant lung tumor because intra-operative microscopic findings showed carcinoid or lung metastasis of paraganglioma. Chest wall tumor at paravertebral was resected at the same time. Postoperative microscopic examination revealed the tumors were same as operated paraganglioma. The 2nd thoracotomy was done in 1999, and two chest wall tumors and a pulmonary nodule in right S8 segment were resected. They were recurrence and pulmonary metastasis of paraganglioma. Now 18 years after initial operation, she is out of hospital in tumor free.

The aim of the current report was to describe 3 cases of malignant carotid body tumor (CBT) and to review the literature. My clinical records of 87 CBTs in 81 patients (6 bilateral) were reviewed, 79 of which were operated on. Three malignant cases were found. The first was in a 40-year-old man who presented with pulmonary metastases 6 years after resection of a CBT. He was treated with chemotherapy and interferon, but died with disseminated disease 2 years later. The second case was in a 56-year-old woman who had a 5-cm, fixed, hard mass in the upper aspect of the neck and a paralysis of the left vocal cord. This lesion was completely resected, and a shunt and reconstruction with a saphenous vein graft were performed. Pathology revealed a malignant chemodectoma with invasion to 2 of the 5 lymph nodes removed. Radiotherapy (50 Gy) was given after the operation. She is well and free of disease 68 months after the resection. The third case was in a 61-year-old woman who presented with an 8-cm nontender, hard, immobile mass in the left upper neck that displaced the left wall of the oropharynx toward the midline. A carotid arteriogram showed a CBT. On computed tomography, the tumor extended to the infratemporal fossa with no bone involvement. The lesion was embolized with a 40% reduction in vascularity. At surgical exploration, the tumor involved the sternocleidomastoid muscle and the lymph nodes at levels II and III, and the internal carotid artery could not be dissected free at the skull base, so only a partial resection was performed. This patient was lost to follow-up. These 3 cases are in agreement with the literature. Locoregional control is usually obtained with complete primary tumor resection and lymphadenectomy and eventual radiotherapy. Surgery with radiotherapy seems to be effective for isolated metastases. Current multidisciplinary treatments have been unsuccessful in controlling disseminated disease.

A seven-year-old male domestic shorthaired cat was presented with persistent dyspnoea. Thoracic radiography and echocardiography revealed pulmonary oedema and a mass at the base of the heart. At necropsy the mass was found to be an aortic body chemodectoma that had metastasised to the sternal lymph node. This is a rare tumour in the cat, the third reported case where there was evidence of metastasis, and only the second reported case where there was evidence of lymphocytic infiltration of the primary tumour. Pulmonary oedema is an unusual presentation of this tumour in the cat.

This paper reports surgical treated 66 cases of parapharyngeal space neoplasms. They consist of primary 52 and secondary 14 cases, which were 59 benign and 7 malignant tumors. The surgical procedures which have been used are oral approach in 5 cases, the parotid approach in 5 cases, the cervical approach in 47 cases, the cervical approach with mandibular swing in 7 cases and the postaurical C incision approach in 2 cases. The procedures and indications of the cervical approach or (and) its combination with mandibular swing are outlined. It is considered that these two surgical procedures can provide very safe and efficacious approaches to the removal of the primary parapharyngeal space neoplasms encountered.

Iodine-131 metaiodobenzylguanidine (131I-MIBG), a radiopharmaceutical agent used for scintigraphic localization of pheochromocytomas, has been employed to treat malignant pheochromocytomas since 1983 in a few specialized centers around the world. We review our clinical experience together with the published experience of 23 other centers in 10 countries, regarding the use of 1311-MIBG for treating patients with malignant adrenal pheochromocytomas or extra-adrenal paragangliomas. There were a total of 116 evaluable patients: 3 were from our current report and another 113 were reported in the literature from 1983 to 1996. A majority of the patients were selected for treatment based upon positive tracer uptake studies. The cumulative dose of 131I-MIBG administered ranged from 96 to 2,322 mCi (3.6 to 85.9 GBq), with a mean (+/-SD) of 490+/-350 mCi (18.1+/-13.0 GBq). The subjects received a mean single therapy dose of 158 mCi (5.8 GBq) and the number of doses administered ranged from 1 to 11, with a mean of 3.3+/-2.2 doses. Initial symptomatic improvement was achieved in 76% of patients, tumor responses in 30%, and hormonal responses in 45%. Five patients had complete tumor and hormonal responses, ranging from 16 to 58 months, which were sustained at the time of reporting. Patients with metastases to soft tissue had more favorable responses to treatment than those with metastases to bone. No difference was noted in the age between the responders and non-responders. Adverse effects, recorded in 41% of the treated patients, were generally mild except for one fatality from bone marrow aplasia. Among 89 patients with follow-up data, 45% of the responders had relapsed with recurrent or progressive disease after a mean interval of 29.3+/-31.1 months (median 19 months). Of patients with an initial response to 1311-MIBG, death was reported in 33% after a mean of 23.2+/-8.1 months (median 22 months) following treatment. Of non-responders, death was reported in 45% after a mean of 14.3+/-8.3 months (median 13 months). In conclusion, this review suggests that 131I-MIBG therapy may be a useful palliative adjunct in selected patients with malignant pheochromocytoma or paraganglioma. Although controlled studies are lacking, our review raises the hope that this therapeutic modality may prolong survival with an occasional sustained complete remission or possible cure.

A case of malignant carotid body tumor with nodal, hepatic and bone metastases is reported. Carotid body chemodectomas are slow-growing tumors which invade local structures. These tumors are usually benign but can occasionally produce local and distant metastases. Development of metastatic localizations is the only formal proof of malignancy as histology cannot distinguish between benign and malignant chemodectomas. Bilateral carotid arteriography gives the diagnosis. Surgery is the basis of treatment and should be performed early in the course to limit operative complications. Radiotherapy can be given as adjuvant treatment.

Treatment with a combination chemotherapeutic regimen consisting of cyclophosphamide, vincristine, and dacarbazine for malignant paraganglioma with hepatic metastasis is reported. A 51-year-old male presented with tumors in the retroperitoneal space and liver. The patient was diagnosed as having paraganglioma based on elevated levels of serum neuron-specific enolase, urinary catecholamine and vanillylmandelic acid, and on histological findings of the liver specimen. The patient was treated with this combination chemotherapy in repeated 21-day cycles. Temporary improvement in laboratory findings and a 20% reduction in the size of the hepatic masses were observed without severe adverse effects.

Objective: To present our experience of 10 patients with extra-adrenal retroperitoneal paragangliomas, and assess prognostic tests., Design: Retrospective study of casenotes., Setting: University hospital, Italy., Subjects: 10 Patients who presented with paragangliomas between 1970 and 1991., Main Outcome Measures: Histological and immunohistochemical results, and outcome., Results: All tumours were completely resected and there was no operative mortality. Of the 8 patients who had no metastases at presentation 3 died of recurrence 3, 5, and 10 years later, respectively; 4 were alive and free of disease 2-7 years after diagnosis. The 2 patients with synchronous bone metastases at presentation died 1 and 4 years later. Immunohistochemical analysis of type I cells (chromogranin A and neurone-specific enolase) showed little correlation with progression of disease, but there was a correlation between the presence of type II cells (S100 protein) and good prognosis., Conclusions: Excision is the treatment of choice for paraganglioma. Immunohistochemical techniques may provide useful information about prognosis, in particular about those patients who are at increased risk of recurrence. Long term follow up is essential, because successful management of recurrence is dependent on early recognition.

A large primary retroperitoneal sublumbar neoplasm in a horse, with disseminated neoplastic foci in the brain, lung, kidney and spleen is described. The diagnosis was based on light microscopical studies and positive immunostaining for neuron-specific enolase. Because of the location of the primary tumour mass, the aortico-sympathetic ganglion (organ of Zukerkandl) is proposed as the origin.

Paragangliomas (carotid body tumours, chemodectomas) may arise in any area of the body where sympathetic ganglia are present, including chemoreceptors, the adrenal medulla and retroperitoneal ganglia. Increasing numbers of patients are being reported with vertebral metastases and spinal cord compression for which either decompression laminectomy or external beam radiotherapy, or both, are required. Patients with vertebral metastases may develop progression of disease after radiation therapy. There is little published information on the use of chemotherapy in this clinical situation. We report a case of metastatic paraganglioma complicated by spinal cord compression showing evidence of clinical benefit from chemotherapy after progressive disease and symptoms developed in a region previously treated by radiation therapy.

A patient with a malignant extraadrenal retroperitoneal paraganglioma had elevated levels of immunoreactive neuropeptide Y (NPY) in the peripheral blood (5988 pg/ml; normal, 123 +/- 30 pg/ml [mean +/- standard error of the mean]). A 6-month course of chemotherapy allowed surgical removal of the previously unresectable primary tumor. Postoperatively, the plasma NPY level initially fell to 1089 pg/ml; continued chemotherapy caused an additional decrease to 440 pg/ml. Four months after surgery, the plasma NPY level increased to 940 mg/ml, coincident with hepatic metastases. This case is the first report of a NPY-secreting clinically nonfunctional malignant extraadrenal paraganglioma. Determination of circulating NPY levels may be useful in the diagnosis and follow-up of patients with neuroendocrine tumors.

Paragangliomas occurring in the liver are rare. We report a patient with a history of nonfunctional paragangliomas in the head and neck who developed liver metastases years later. We discuss findings on cross-sectional imaging modalities, including magnetic resonance imaging (MRI), which demonstrate the hypervascular nature of the liver masses.

Extraadrenal retroperitoneal paragangliomas (RP) are uncommon tumors. Because of their rarity, little is known of their natural history or response to treatment. We reviewed 22 patients with RP who were seen at our center between 1949 and 1990. The distribution of male and female patients was nearly equal, and the mean age was 42. Most patients were admitted with pain or a mass, and eight of 22 tumors were functional. No significant difference was noted in duration of symptoms, size of the tumor, or survival between functional and nonfunctional tumors. Eleven of 22 (50%) RP metastasized and were therefore classified as malignant. Five-year and 10-year disease free survival rates were 19% and 19% for tumors not resected and 75% and 45% for those completely resected. Once metastases occurred, the 5-year survival rate was 36%, but no patient survived beyond 76 months. Predictors of survival included complete resection of the tumor but not size or functional status. Although some patients who received chemotherapy or radiotherapy had clinical responses, a survival benefit could not be shown. RP have a high rate of malignant behavior and should be treated aggressively with operation. Late metastases are not uncommon, and prolonged follow-up is necessary. Once metastases have occurred, some patients may have prolonged survival.

A 9-year-old sexually intact male Boxer with a history of multiple episodes of syncope and various cardiac arrhythmias was determined radiographically to have a large mass in the heart-base region and was subsequently euthanatized upon worsening of clinical signs. Histologic and ultrastructural examination of tissue from the heart-base mass indicated that the tumor was most likely a chemodectoma derived from the aortic body (aortic body tumor, extra-adrenal paraganglioma). Macroscopic and/or microscopic evidence of metastasis of the tumor was seen in the lungs, myocardium, spleen, liver, kidneys, and dura mater over the cerebellum.

Two cases of vertebral extradural metastases from paraganglionomas are presented. The significance of both is discussed with particular reference to abnormal catecholamine secretion in one and sclerotic bone metastases in the other case.

1. A pulmonary chemodectoma/glomangiosarcoma that had metastasized from the thigh was studied after removal from a 22 year old Algerian patient with hypertension, high plasma prorenin and signs of secondary aldosteronism. 2. Renin and renin mRNA were localized in sections of the tumour tissue using monoclonal anti-human renin antibody and human renin cDNA probe, respectively. 3. The cells grew prolifically in culture, but, even though their renin content was similar to that of transfected human juxtaglomerular cell tumour cells (approximately 1 pg/microgram DNA), their rate of secretion of renin was much lower (0.05-0.15 cf. 0.5-1.5 pg/h per microgram DNA). 4. Forskolin (10 mumol/l for 24 h) increased secretion of renin from 1.9 +/- 0.36 to 4.1 +/- 0.64 pg/ml per h of culture (P less than 0.001, n = 11), consistent with cAMP being a second messenger in the secretory mechanism. 5. The cells should provide valuable information about intracellular mechanisms for the regulation of renin synthesis and secretion.

A 34-year-old female who had received left hemi-thyroidectomy because of carcinoma of the thyroid complained of progressive deafness 5 years postoperatively. A red pulsating tumor was found in her mid-ear; it was removed incompletely. The tumor was diagnosed as a glomus jugulare tumor. The patient died at age 47 due to tumor progression. Autopsy revealed a temporal bone tumor with brain invasion; histological examination confirmed it to be a metastasis from the thyroid carcinoma. Clinical and histological details of this rare case are reported and the relevant literature is reviewed.

Two cases of laryngeal chemodectoma are presented. They illustrate the differences between benign and malignant varieties of this tumour. The problem of differentiating between these two types at an early stage is discussed and a possible treatment policy is presented.

A necropsy performed on an aged cat with respiratory signs revealed a large white firm mass cranioventrally to the heart, and multiple similar masses scattered throughout the lungs, diaphragm, pericardial sac and intercostal muscles. The histological examination of the primary site and the metastases are consistent with a well-differentiated aortic body carcinoma.