Adrenal gland & paraganglia
Pheochromocytoma / paraganglioma
Paraganglioma
Editorial Board Member: Debra Zynger, M.D.
Topic Completed: 1 August 2018
Minor changes: 4 July 2020
Copyright: 2002-2020, PathologyOutlines.com, Inc.
PubMed Search: Paraganglioma [title]
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 answer #1 | Board review style question #2 | Board review answer #2Cite this page: Gellert LL, Pernick N, Zynger D. Paraganglioma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/adrenalparaganglioma.html. Accessed August 8th, 2020.
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
Contributed by Debra Zynger, M.D.
Parapharyngeal paraganglioma
Bladder paraganglioma
Retroperitoneal paraganglioma
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
Contributed by Lan L. Gellert, M.D., Ph.D.
Abdominal paraganglioma
Ear paraganglioma
Contributed by Dr. Ayesha Azam, University Hospital Coventry & Warwickshire (UK), Case of the Week #456
Carotid body paraganglioma
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 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 answer #2
