Paragangliomas of the head and neck region. A pathologic study of tumors from 71 patients.

The histopathology of 72 paragangliomas originating in the head and neck region of 71 patients is presented. There were 45 carotid body, 13 vagal body, eight jugulotympanic, and three nasal paragangliomas. In addition, two arose in the larynx and one in the area of the aortic arch. Tumors occurred in four unrelated families. The two most important histologic features leading to a diagnosis of paraganglioma were zellballen and the presence of cytoplasmic argyrophil granules in all cases in which staining with the Grimelius technique was carried out. Ultrastructural study of three carotid body and two vagal body paragangliomas revealed both light and dark chief cells. Tumor cells contained membrane bound, electron dense neurosecretory types of granules, which usually ranged in diameter from 120 to 200 nm. Follow-up information was available for 67 patients (94 per cent). Two of the three nasal paragangliomas, 50 per cent of the jugulotympanic paragangliomas, 17 per cent of the vagal body paragangliomas, and 10 per cent of those of the carotid body recurred locally following attempted surgical resection. All patients treated with radiation had persistent tumor. Four (9 per cent) of the carotid body paragangliomas were malignant, all four patients dying with widespread metastases. One vagal body paragangliomas metastasized to regional lymph nodes (the patient was alive and well at five years), and another caused death by direct intracranial extension. In contrast to the benign tumors, malignant paragangliomas tended to show foci of necrosis and vascular invasion. Mitotic figures, which usually were not identified in the benign cases, were seen in all malignant tumors.     

Paraganglioma (chemodectoma) of the larynx. Presentation of 2 cases

Two rare cases of laryngeal paraganglioma are reported. The first patient was a 14-year-old girl, that had a new laterocervical paraganglioma, 4 years after the excision of a laryngeal tumor. The other patient was a 33-year-old man. In both the cases, the diagnosis was made on histopathological ground and the tumors displayed the typical histological pattern of paragangliomas: epithelioid tumor cell arranged in nests (Zell-ballen) in a vascular stroma. Neoplastic cells were found to contain argyrophil granules and chromogranin. Laryngeal paragangliomas reported in the literature are 73, they generally are supraglottic, show no sex predilection and prefer the V-VII decades of age.     

Paraganglioma of the mesenterium: a case report

Extra-adrenal paragangliomas constitute 10 % or less of phaeochromocytomas/paragangliomas. Even rarer is the occurrence of paragangliomas outside the usual distribution of paraganglionic tissue. We report a case of extra-adrenal paraganglioma occurring in the small intestine mesentery in a 65-year-old man. To our knowledge, there are only seven case reports of paraganglioma occurring in this non-typical site. Computed tomography showed a solid expansive non-homogenously enhancing mesenteric mass, measuring 10 x 8 cm with peripheral cystic component. Histologically, the tumour had a typical organoid "zellballen" pattern, showed immunohistochemical positivity for synaptophysin, neuron specific enolase, CD-56, chromogranin, and focally vimentin, and was cytokeratin and EMA negative. S-100 protein stained few sustentacular cells. The patient was free from recurrence or metastasis three months after tumour resection. Although rare, paraganglioma should be included in the preoperative differential diagnosis of solid mesenteric tumours, to prevent any potential life-threatening event peroperatively in the case of a catecholamines-producing tumour.     

Gangliocytic paraganglioma of the appendix

AIMS: A case of gangliocytic paraganglioma is reported in the appendix which, to the best of our knowledge, is the first case at this particular site to be described in modern literature. METHODS AND RESULTS: A 47-year-old man with signs and symptoms of acute appendicitis underwent appendectomy. In the resected specimen a tumour with a diameter of 9 mm was found, which microscopically consisted of three different cell types: (a) epithelioid cells lying in a trabecular pattern and in formations reminiscent of 'Zellballen' as seen in paragangliomas (b) spindle cells and (c) ganglion-like cells. A diagnosis of 'gangliocytic paraganglioma' was made and confirmed by immunohistochemical and ultrastructural examination. CONCLUSION: Gangliocytic paragangliomas are rare tumours of uncertain histogenesis. More than 40 years ago a tumour in the appendix with features similar to our case was described by Masson as 'neuro-carcino?de'. Concerning its origin, Masson, as well as other authors describing gangliocytic paragangliomas decades later, referred to the endodermal-neuroecto dermal complexes found by Van Campenhout. It is felt that the current finding of a gangliocytic paraganglioma in the appendix supports the hypothesis that gangliocytic paragangliomas arise from these embryonal structures.     

Duodenal gangliocytic paraganglioma: a radiological-pathological correlation

Duodenal gangliocytic paraganglioma is a rare tumor that characteristically occurs in the second portion of the duodenum and typically presents with gastrointestinal bleeding. Gangliocytic paragangliomas have a characteristic triphasic microscopic appearance with epithelioid cells, spindle cells, and ganglion cells, resulting in a complex histology with features of paraganglioma, carcinoid, and ganglioneuroma. Duodenal gangliocytic paragangliomas have an excellent prognosis after surgical resection but metastatic spread to regional lymph nodes and recurrence may rarely occur. We report a case of duodenal gangliocytic paraganglioma and discuss the radiological and pathological differential diagnosis of this rare entity.     

Nonchromaffin paraganglioma in the nose and paranasal sinuses

Nonchromaffin paraganglioma occurring in the nose and paranasal sinuses are extremely rare. The authors have experienced a case of nonchromaffin paraganglioma of nasal cavity which extended to the epipharynx. To our knowledge, this reported case is the fourth case that has appeared in the world literature. The patient, a 31-year-old female, had complained of a right nasal obstruction and mucopurulent rhinorrhea for two years. The right nasal cavity was filled with a polypoid mass showing no bleeding tendency or necrosis. Radiographs revealed a homogeneous shadow which occupied the entire nasal cavity and paranasal sinuses. Histopathological studies revealed that the tumor showed typical findings of nonchromaffin paraganglioma and neurosecretory granules in cytoplasm were observed by electron microscopic study. Subsequently, the tumor recurred at on the posterior epipharyngeal wall after a duration of one year and three months, and was removed completely. Since then, there was no recurrence of the tumor until the present time.     

Gangliocytic paraganglioma: a rare case with metastases of all 3 elements to liver and lymph nodes

Gangliocytic paragangliomas are a rare but well-described neuroendocrine tumor with a proclivity for the duodenal area. It is usually a locally infiltrative lesion with a good prognosis. Rare cases that spread to lymph nodes have been documented. A 52-year-old female was found to have a duodenal tumor, enlarged regional lymph nodes, and multiple small nodules in the liver. The duodenal tumor was a classic triphasic gangliocytic paraganglioma. Two regional lymph nodes and one of the nodules in the liver were noted to contain all 3 elements constituting a gangliocytic paraganglioma. This is the second case of gangliocytic paraganglioma with liver spread and is also noteworthy because of the presence of all 3 elements in the metastases. The presence of lymph node and liver metastases should not result in overtreatment as such behavior is not necessarily fraught with a bad clinical outcome. It is probably best to regard such cases as having “uncertain malignant potential” and advocate careful follow-up.     

NONCHROMAFFIN PARAGANGLIOMA IN THE NOSE and PARANASAL SINUSES

Nonchromaffin paraganglioma occurring in the nose and paranasal sinuses are extremely rare. The authors have experienced a case of nonchromaffin paraganglioma of nasal cavity which extended to the epiphar-ynx. To our knowledge, this reported case is the fourth case that has appeared in the world literature.
The patient, a 31-year-old female, had complained of a right nasal obstruction and mucopurulent rhinorrhea for two years. The right nasal cavity was filled with a polypoid mass showing no bleeding tendency or necrosis. Radiographs revealed a homogeneous shadow which occupied the entire nasal cavity and paranasal sinuses. Histopathological studies revealed that the tumor showed typical findings of nonchromaffin paraganglioma and neurosecretory ganules in cytoplasm were observed by electron microscopic study. Subsequently, the tumor recurred at on the posterior epipharyngeal wall after a duration of one year and three months, and was removed completely. Since then, there was no recurrence of the tumor until the present time. ACTA PATHOL. JPN. 35: 489–495, 1985.     

February 2004: a 44-year-old man with a 2-year history of epistaxis

A 44-year old man presented with a 2-year history of epistaxis and a nodular lesion in the nasopharyngeal mucosa. Neuroimaging revealed a midline nasopharyngeal tumor extending through the skull base to the clivus. Following surgical resection, histological studies showed a paraganglioma, a tumor with a typical nesting pattern, abundant capillary network, and strong immunoreactivity for neuroendocrine markers. Paragangliomas of the head and neck are rare tumors, which may come to the neuropathologist's attention because of their propensity for intracranial spread. In particular, paragangliomas located in the nasopharynx may generate diagnostic difficulties, as they appear to have no connection with major paraganglia in the region. Morphologic criteria do not allow distinguishing between benign and malignant forms.     

The cytologic diagnosis of gangliocytic paraganglioma: A case report

Gangliocytic paragangliomas are rare tumors primarily found in the duodenum. We report a case of a woman who presented with a retroperitoneal lymph node involved by metastatic gangliocytic paraganglioma. Subsequently, fine‐needle aspiration (FNA) cytology was used to identify the primary duodenal gangliocytic paraganglioma. The smears of the aspirate material were highly cellular and contained a dominant population of epithelioid cells, a second population of ganglion cells and a third population of small, bland spindled cells. To our knowledge, the cytologic features of gangliocytic paraganglioma have not previously been documented. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Multicentric metachronous pulmonary and intravagal paraganglioma: a case report with immunohistochemical findings

An unprecedented presentation of multicentric paraganglioma in a 48-year-old man is described. One of the paragangliomas, originally diagnosed as a carcinoid tumor, presented as a lung mass and was removed. Four years later, an intravagal paraganglioma was discovered. The lung and intravagal tumors had identical morphologic and immunoreactive characteristics. Both tumors consisted of chief cells (type 1) and sustentacular cells (type 2). The chief cells were immunoreactive with neuroendocrine markers (synaptophysin and chromogranin), but nonreactive with epithelial markers (CAM 5.2, high- and low-molecular-weight keratins, epithelial membrane antigen, and carcinoembryonic antigen). The sustentacular cells were positive for S100 protein. Although pulmonary carcinoids may mimic paragangliomas and occasionally contain sustentacular cells, the diagnosis was rejected because the tumor cells did not demonstrate reactivity with epithelial markers.     

Paraganglioma of the vagina: report of a case

To date, only four paragangliomas have been described in the vagina. Due to their rare occurrence in this region, they may pose diagnostic difficulties clinically and pathologically. This case study reports on an endocrinologically inactive vaginal paraganglioma, emphasizing the morphological and immunohistochemical differential diagnoses.     

The Dutch founder mutation SDHD.D92Y shows a reduced penetrance for the development of paragangliomas in a large multigenerational family

Germline mutations in SDHD predispose to the development of head and neck paragangliomas, and phaeochromocytomas. The risk of developing a tumor depends on the sex of the parent who transmits the mutation: paragangliomas only arise upon paternal transmission. In this study, both the risk of paraganglioma and phaeochromocytoma formation, and the risk of developing associated symptoms were investigated in 243 family members with the SDHD.D92Y founder mutation. By using the Kaplan–Meier method, age-specific penetrance was calculated separately for paraganglioma formation as defined by magnetic resonance imaging (MRI) and for paraganglioma-related signs and symptoms. Evaluating clinical signs and symptoms alone, the penetrance reached a maximum of 57% by the age of 47 years. When MRI detection of occult paragangliomas was included, penetrance was estimated to be 54% by the age of 40 years, 68% by the age of 60 years and 87% by the age of 70 years. Multiple tumors were found in 65% and phaeochromocytomas were diagnosed in 8% of paraganglioma patients. Malignant paraganglioma was diagnosed in one patient (3%). Although the majority of carriers of a paternally inherited SDHD mutation will eventually develop head and neck paragangliomas, we find a lower penetrance than previous estimates from studies based on predominantly index cases. The family-based study described here emphasizes the importance of the identification and inclusion of clinically unaffected mutation carriers in all estimates of penetrance. This finding will allow a more accurate genetic counseling and warrants a ‘wait and scan'' policy for asymptomatic paragangliomas, combined with biochemical screening for catecholamine excess in SDHD-linked patients.     

Malignant paraganglioma

A case of malignant paraganglioma of the right carotid bifurcation with metastases in the vertebral bodies in a 63-year-old man is reported. The criteria for malignancy in paragangliomas are discussed and special attention is paid to the difficult morphological differential diagnosis of these tumors and their metastases as illustrated by the present case.     

Metastatic carotid body paraganglioma detected during evaluation for biliary stone disease

Carotid body paragangliomas are neuroendocrine cell tumors. Most invade locally to surrounding tissues with metastases being less commonly encountered than with other tumors: a minority of tumors metastasizes to distal sites. Spread is more unusual after surgical removal of the primary tumor. Hepatic spread is very rare but has been documented. We report a case of a clinically silent metastatic paraganglioma identified during an evaluation for choledocholithiasis. We describe a 70‐year‐old female presenting with symptoms of abdominal pain who was found to have cholelithiasis and choledocholithiasis. MRI imaging performed during evaluation revealed enhancing liver and lung lesions suspicious for metastasis. FNA of a hepatic lesion showed paraganglioma. She had a remote history of bilateral carotid body tumors, of which the left tumor was resected in 2005. This is a rare case of metastatic carotid body paraganglioma. Primary tumor source was a resected tumor or a smaller sized nodule that was managed with serial imaging. The subject's lack of symptoms and her disease extent with confirmed hepatic and presumed pulmonary spread is unique. Diagn. Cytopathol. 2014;42:868–871. © 2014 Wiley Periodicals, Inc.     

Tumoren des Nebennierenmarks und der Paraganglien

The sympathetic and parasympathetic paraganglia are the site of pheochromocytomas and paragangliomas. The adrenal pheochromocytoma and the abdominal paraganglioma derive from the sympathetic nervous system. The parasympathetic paragangliomas are predominantly localized in the head and neck region. Most pheochromocytomas are hormonally active and benign. The abdominal paragangliomas usually correspond to adrenal pheochromocytomas, but are more commonly malignant. The parasympathetic paragangliomas are usually benign, hormonally inactive and are most commonly located in the bifurcation of the carotid artery.     

Primary paraganglioma of the lung

There are few reported cases of primary pulmonary paraganglioma in the pathology literature. Given the historical confusion surrounding bronchial tumors, widespread use of the term "chemodectoma" and classification of these lesions as paraganglioma in an outdated World Health Organization classification of lung tumors, the recognition of tumors arising from paraganglia within the lung has not been accepted by leading authorities. We present a well-documented case of a primary pulmonary paraganglioma with typical morphologic features and a supporting immunohistochemical profile. The 0.9 cm endobronchial tumor was submucosal and composed of nests of ovoid cells with abundant eosinophilic cytoplasm, cytoplasmic vacuoles, round to oval nuclei with speckled chromatin, and occasional conspicuous nucleoli. The nests of cells were surrounded by thin-walled vascular channels and stellate spindle cells. The ovoid cells showed strong diffuse staining for chromogranin A, synaptophysin, and faint staining for S-100; they were negative for cytokeratin AE1/AE3, Cam 5.2, and epithelial membrane antigen. The stellate spindle cells stained intensely positive for S-100 protein. A critical review of reported cases of pulmonary chemodectomas and paragangliomas in the English literature features few, if any, well-documented examples. While this exceedingly rare tumor should be discerned from carcinoid tumor, it remains unknown if primary pulmonary paragangliomas behave aggressively like intra-abdominal extra-adrenal paragangliomas, or in a more indolent manner observed with extra-adrenal paragangliomas in other locations.     

Update on tumours of the adrenal cortex,phaeochromocytoma and extra‐adrenal paraganglioma

McNicol A M
(2011) Histopathology  58, 155–168
Update on tumours of the adrenal cortex, phaeochromocytoma and extra‐adrenal paraganglioma This review covers aspects of adrenal cortical tumours, phaeochromocytoma and extra‐adrenal paragangliomas. Relevant clinical and epidemiological information is included. It is now known that about 30% of paragangliomas occur in a familial setting and these new aspects of the genetic background are presented. The main diagnostic problem in both groups of tumours is the recognition of malignant potential. The uses and limitations of multifactorial histological assessment in diagnosis and prognosis are discussed. Finally, data on the molecular changes associated with tumorigenesis and tumour progression are highlighted, and how this information may contribute in future to diagnosis and prognosis.     

Giant Mitochondria with Paracrystalline Inclusions in Paraganglioma of the Urinary Bladder: Correlation with Mitochondrial Abnormalities in Paragangliomas of Other Sites

Mitochondrial abnormalities have received relatively little attention in the ultrastructural evaluation of paragangliomas. Review of the few literature references dealing with this issue, however, reveals that quantitative and qualitative changes of these organelles occur in that context. A bladder paraganglioma is described that was characterized by numerous mitochondria, which in addition displayed giant forms along with matrical paracrystalline inclusions. Upon retrospective review of 12 archival cases of paragangliomas, enlarged and structurally abnormal mitochondria were found in all of them. Although various speculations can be made, the mechanism of formation and the pathophysiologic significance of these abnormal mitochondria remain unknown. From a morphologic diagnostic point of view, however, these abnormalities, which in this case of bladder paraganglioma were also light microscopically evident, can be of significant help in establishing the correct diagnosis.