Bladder, ureter & renal pelvis
Neuroendocrine neoplasms
Paraganglioma
Author: Gillian Levy, M.D.
Last author update: 1 December 2014
Last staff update: 27 December 2021
Copyright: 2003-2023, PathologyOutlines.com, Inc.
PubMed Search: Bladder paraganglioma [title]
Table of Contents
Definition / general | Terminology | Epidemiology | Sites | Etiology | Clinical features | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Differential diagnosis | Additional referencesCite this page: Levy G. Paraganglioma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bladderparaganglioma.html. Accessed March 22nd, 2023.
Definition / general
- Tumor derived from paraganglion cells, similar to counterpart at other sites
Terminology
- Also called extra-adrenal pheochromocytoma
Epidemiology
- Uncommon in bladder (0.06% to 0.1% of all bladder tumors)
- Median age 41 years vs. 70 years for urothelial carcinoma
- Often young women
- Age range 10-88 years
- Male to female ratio 2:3
Sites
- All sites in bladder; at any level of bladder wall
- Muscularis propria is the most common location
Etiology
- Derives from paraganglion cells in bladder wall
Clinical features
- Many cases are hereditary and associated with familial paraganglioma, neurofibromatosis Type 1, von Hippel-Lindau disease, Carney triad or rarely MEN2 (Ann N Y Acad Sci 2006;1073:21)
- 50% have “micturition attack” during urination with full bladder, consisting of bursting headache, pounding sensation, anxiety, sweating, syncope, hypertension or hematuria
- 50% have positive urinary VMA
- Malignant behavior in 5-15%; cannot be predicted from histology
- 50% have hematuria
Prognostic factors
- High stage tumors (pT3) have poorer outcomes (Cancer 2000;88:844)
- Distant metastasis are rare and can occur many years later
Case reports
- 25 year old man with tumor exhibiting malignant features (Internet Journal of Surgery 2008;15:1)
- 55 year old man (Internet Journal of Urology 2009;6:1)
- 64 year old man with composite paraganglioma-ganglioneuroma (Can Urol Assoc J 2009;3:E45)
Treatment
- TUR (transurethral resection), wedge resection or partial cystectomy
- Malignant paraganglioma: radical cystectomy with removal of metastasis if possible
Gross description
- Usually single, small (2-3 mm), lobulated, well circumscribed, anywhere in bladder (not just base)
- Positive chromaffin reaction (tumor turns dark brown after placement in Zenker's fixative)
Gross images
Contributed by Debra Zynger, M.D.
Bladder paraganglioma
Microscopic (histologic) description
- Resembles paragangliomas elsewhere, with zellballen (diffuse patterns of large polygonal cells in clusters separated by a delicate fibrovascular stroma); cells have abundant eosinophilic granular cytoplasm, fairly uniform nuclei with smooth chromatin
- Frequently involves muscularis propria but without a desmoplastic reaction
- Occasionally has degenerative type nuclei
- Rarely has clear cells, tumor necrosis or mitotic figures
- May be oncocytic or mixed with ganglioneuroma
Microscopic (histologic) images
Contributed by Debra Zynger, M.D.
Nested architecture
Amphophilic cytoplasm
Pseudopapillae
Cellular spindling
Mitotic activity
Muscularis propria invasion
Synaptophysin
GATA3
Contributed by David Cohen, M.B.B.Ch., M.D.
40 year old woman with bladder tumor
ChromograninA
Synaptophysin
NSE
S100
HMB45
Positive stains
- Chromogranin, synaptophysin, neuron specific enolase
- S100: sustentacular cells
- GATA3: important pitfall as this overlaps with urothelial carcinoma
Electron microscopy description
- Neurosecretory granules
Molecular / cytogenetics description
- Often not diploid (Hum Pathol 1991;22:1162)
Differential diagnosis
- Carcinoid tumor:
- May have focal nesting pattern, keratin+
- Melanoma:
- Usually not a defined nesting pattern; is spindled or epithelioid, has prominent nucleoli
- S100+, HMB45+, MelanA+
- Normal paraganglia
- Urothelial carcinoma:
- May have nesting pattern but more atypia; lacks prominent vascular network of paraganglioma
- Keratin+, neuroendocrine markers negative (Am J Surg Pathol 2004;28:94)
- Usually associated with carcinoma in situ or noninvasive papillary carcinoma
Additional references
