Adrenal gland and paraganglia
Pheochromocytoma / paraganglioma
Paraganglioma

Authors: Lan L. Gellert, M.D., Ph.D., Debra L. Zynger, M.D., Nat Pernick, M.D. (see Authors page)
Editorial Board Member Review: Debra L. Zynger, M.D.

Revised: 7 August 2018, last major update August 2018

Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: Paraganglioma [title]

Cite this page: Gellert, L.L., Zynger, D.L., Pernick, N. Paraganglioma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/adrenalparaganglioma.html. Accessed November 12th, 2018.
Definition / general
  • Tumors of paraganglia, regardless of location (although tumor of adrenal medulla is termed pheochromocytoma)
  • Histologically similar, regardless of location
  • 2 categories:
    1. Parasympathetic: arise predominately in the head and neck; usually nonfuctional
    2. Sympathetic: arise in the retroperitoneum, thorax and pelvis; usually functional
Essential features
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
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
Treatment
  • Surgical excision
Gross description
  • Rubbery, firm, may have pseudocapsule
  • Brown cut surface; variable central scar
Gross images

Images hosted on PathOut server:

Contributed by Dr. Debra Zynger, Ohio State University (USA):
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Parapharyngeal paraganglioma

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Bladder paraganglioma

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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

Images hosted on PathOut server:

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
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
Board review question #1
Which of the following histologic features of paraganglioma is predictive of malignant behavior?

  1. Capsular invasion
  2. Cytologic atypia
  3. Increased mitosis
  4. Lymphovascular invasion
  5. None of the above
Board review answer #1
E. Paraganglioma is determined to be malignant only when metastases are present
Board review question #2
The genetic mutation most commonly associated with benign paragangliomas of the head and neck is:

  1. NF1
  2. RET oncogene
  3. Succinate dehydrogenase (SDH) mitochondrial complex‚Ä®
  4. THEM127 and VHL
Board review answer #2
C. Succinate dehydrogenase (SDH) mitochondrial complex