Table of Contents
Definition / general | Essential features | Terminology | Epidemiology | Sites | Clinical features | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Electron microscopy description | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Gellert LL, Pernick N, Zynger D. Paraganglioma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/adrenalparaganglioma.html. Accessed January 22nd, 2021.
Definition / general
- Tumors of paraganglia, regardless of location (although tumor of adrenal medulla is termed pheochromocytoma)
- Histologically similar, regardless of location
- 2 categories:
- Parasympathetic: arise predominately in the head and neck; usually nonfuctional
- Sympathetic: arise in the retroperitoneum, thorax and pelvis; usually functional
Essential features
- Nested tumor with neuroendocrine expression
- Often associated with various syndromes and familial conditions, including Succinate dehydrogenase / B mutations, von Hippel Lindau (VHL), Carney triad, Neurofibromatosis type 1 (NF1), MEN 2A and 2B
- 20% are multiple
- Determined to be malignant only when metastases are present
Terminology
- Head and neck: named according to location they arise
- Carotid body paraganglioma
- Jugulotympanic paraganglioma (previously called glomus jugulare tumors)
- Vagal paraganglioma
- Laryngeal paraganglioma
- Chemodectoma refers to carotid and aortic body paraganglioma (tumors of paraganglia with a chemoreceptor function)
Epidemiology
- Average patient age is fourth and fifth decade
- Distribution by gender is almost equal
Sites
- Head and neck: along parasympathetic nerves near carotid body, jugulotympanicum, vagus nerve and larynx
- Carotid body most common site
- Sympathetic chains: 42% adrenal / periadrenal / perirenal, 28% organ of Zuckerlandl / near abdominal aorta, 10% bladder, 12% thorax, 2% cardiac
- Rarely in ovary (Am J Surg Pathol 2006;30:600)
Clinical features
- Nonsymptomatic, hypertension or local compression
- Carotid body:
- Present at angle of mandible / bifurcation of common carotid artery as a slow growing painless mass
- May represent hyperplasia due to hypoxia, particularly at high altitudes
- Also associated with hepatic cirrhosis, Carney triad (epithelioid leiomyosarcoma, pulmonary chondroma, functioning extra-adrenal paragangliomas)
- May cause cranial nerve palsy, dysphagia or carotid sinus syndrome (bradycardia and syncope)
- Rarely produces catecholamines
- 90% benign, 90 - 95% solitary
- May invade locally or spread to lymph nodes or lung (must rule out multicentric tumor)
- Adhere to carotid bifurcation but this does not represent malignant infiltration
- May be familial (Arch Pathol Lab Med 1990;114:1272)
- Jugulotympanic:
- Usually arise lateral in temporal bone (glomus tympanicum tumor) or jugular bulb (glomus jugulare tumor), erode through floor and present as mass of external auditory canal or middle ear; also mass at base of skull, middle ear "polyps"
- 40% extend into cranial cavity
- Usually adults, almost always women
- Often misidentified as hemangiomas due to fragmented specimens
- Malignant cases often involve bone
- Laryngeal:
- Rare
- Usually arise from superior paraganglia
- Hoarseness and dysphagia
- 25% mortality
- Often tender subcutaneous metastases
- Aorticopulmonary:
- May cause hoarseness, dysphagia or chest pain / discomfort
- Rarely hemoptysis or superior vena cava syndrome
Prognostic factors
- Determined to be malignant only when metastases are present
- Site: organ of Zuckerkandl (22 - 50% malignant versus 10%+ in adrenal gland)
Case reports
- 25 year old woman with left malignant vagal paraganglioma (Head Neck Pathol 2016;10:201)
- 30 year old man with succinate dehydrogenase B gene mutation and left atrial and carotid body paraganglioma (Ann Thorac Surg 2017;103:e323)
- 44 year old woman with norepinephrine secreting paraganglioma of organ of Zuckerkandl (Arch Pathol Lab Med 2001;125:1387)
- 52 year old man with aorticopulmonary paraganglioma (Jpn J Thorac Cardiovasc Surg 2006;54:212)
- 54 year old woman with large paraganglioma in left paraaortic area (Asian Cardiovasc Thorac Ann 2012;20:482)
- 61 year old postmenopausal woman with ovarian carcinoma and paraaortic paraganglioma mimicking lymph node metastasis (J Obstet Gynaecol Res 2010;36:204)
- 68 year old woman with retroperitoneal tumor and liver metastases 23 years after resection (Arch Pathol Lab Med 1985;109:373)
- 75 year old woman with paraganglioma of orbit and regression (Orbit 2015;34:99)
- 76 year old man with mesenteric paraganglioma (Arch Pathol Lab Med 2002;126:362)
- Young man with extra-adrenal sympathetic paraganglioma of organ of Zuckerkandl (J La State Med Soc 2012;164:26)
- 10 patients with carotid body tumors (Ann Vasc Surg 2017;43:265)
Treatment
- Surgical excision
Gross description
- Rubbery, firm, may have pseudocapsule
- Brown cut surface; variable central scar
Gross images
Microscopic (histologic) description
- Similar to pheochromocytoma
- Nesting (Zellballen) or trabecular pattern of cells within a prominent vascular network
- Zellballen pattern may be obscured by anastomosing bands
- Round / oval cells and giant multinucleated cells with abundant granular eosinophilic or basophilic cytoplasm
- May have nuclear atypia and vascular invasion (does not indicate malignancy)
- May have dysmorphic vessels, melanin-like pigment ("pigmented paraganglioma"), abundant stroma and osseous metaplasia
- Intracytoplasmic hyaline globules are present in sympathoadrenal paragangliomas
- No or rare mitotic figures except in obviously malignant tumors; no rosettes or acini
- Usually no chronic inflammatory infiltrate, no necrosis (unless preoperative tumor embolization)
Microscopic (histologic) images
Cytology description
- Irregular clusters of tumor cells with eosinophilic finely granular cytoplasm and mildly irregular nuclei
- May have marked cytologic atypia
- Fine needle aspiration not recommended for carotid body paragangliomas due to high likelihood of misinterpretation and risk for catecholamine crisis and hemorrhage
Positive stains
- Same as pheochromocytoma: chromogranin, synaptophysin, S100 (sustentacular cells)
- Reticulin highlights nesting pattern
Electron microscopy description
- Chief cells have abundant cytoplasmic neurosecretory granules
- May have giant mitochondria with paracrystalline inclusions
- Sustentacular cells wrap around chief cells and lack neurosecretory granules
- No desmosomes
Differential diagnosis
Board review style question #1
Which of the following histologic features of paraganglioma is predictive of malignant behavior?
- Capsular invasion
- Cytologic atypia
- Increased mitosis
- The only predictor of malignant behavior is metastatic disease.
Board review style answer #1
Board review style question #2
The genetic mutation most commonly associated with benign paragangliomas of the head and neck is:
- NF1
- RET oncogene
- Succinate dehydrogenase (SDH) mitochondrial complex
- THEM127 and VHL
Board review style answer #2