What causes cysts to form?

Why Cysts Form

Cysts form through multiple distinct mechanisms depending on their location and underlying cause, but fundamentally result from epithelial cell proliferation combined with fluid accumulation within an enclosed space, often triggered by genetic mutations, hormonal influences, inflammation, or developmental abnormalities.

Genetic and Developmental Mechanisms

Polycystic Kidney Disease

• In autosomal dominant polycystic kidney disease (ADPKD), cysts develop from genetic mutations in PKD1 or PKD2 genes, which encode proteins localized to the cilia-centrosome complex 1.
• These mutations disrupt normal tubular epithelial cell function, leading to increased epithelial cell proliferation and progressive fluid accumulation within nephron segments 2.
• Cysts develop slowly over time, with children having fewer cysts initially and later onset of complications compared to adults 1.
• The "cilia hypothesis" suggests that dysfunction of the cilia-centrosome complex is central to cyst formation in many genetic cystic diseases, though non-ciliary proteins also contribute 2.

Hormonal Influences on Cyst Growth

• Estrogen exposure is the most important driver of cyst growth in polycystic liver disease (PLD), explaining why women typically have more severe disease 1.
• In rare cases, elevated gonadotrophin levels (FSH and LH) can stimulate ovarian cyst growth, particularly when there is deficiency of sex steroid synthesis 3.
• The hormonal mechanism involves increased cellular proliferation in response to hormonal stimulation of cyst-lining epithelium 3.

Acquired Cyst Formation

Renal Cysts in End-Stage Disease

• Acquired cystic disease develops in end-stage renal disease, with duration of hemodialysis and male gender increasing occurrence 1.
• These cysts arise from atypical renal cysts with multilayered epithelium that serve as precursor lesions, eventually developing solid nodular growth within the cyst 1.
• The mechanism involves epithelial proliferation in terminally differentiated tubular epithelium combined with fluid accumulation and extracellular matrix remodeling 4.

Cellular Mechanisms of Cyst Expansion

• Cyst formation requires coordinated interplay between cellular proliferation and fluid secretion 4.
• Growth factors like EGF or TGF-alpha are required to initiate cyst development from individual epithelial cells, with insulin as a necessary co-factor 4.
• Agonists of adenylate cyclase (including PGE1, vasopressin, and forskolin) enhance both cyst initiation and progression by stimulating net fluid secretion from cells into the cyst lumen 4.

Inflammatory and Obstructive Causes

Ganglion Cysts

• Most current theories hold that extra-articular mucin "droplets" coalesce to form the main body of ganglion cysts, with the cyst wall and pedicle forming subsequently 5.
• The exact mechanism remains unknown, but these cysts connect to nearby synovial joints through a pedicle 5.

Pericardial Cysts

• Pericardial cysts represent congenital diverticulae or cystic formations, while inflammatory cysts comprise pseudo-cysts or encapsulated effusions caused by rheumatic disorders, infection, trauma, or cardiac surgery 1, 6.
• In pulmonary arterial hypertension, pericardial effusions form due to right ventricular failure with increased right-sided filling pressures, leading to increased filtration and lymphatic obstruction 1.

Skin and Soft Tissue Cysts

General Skin Cyst Formation

• Skin cysts form due to genetic problems, errors in embryonic development, cellular defects, chronic inflammation, infections, blockages of ducts, or injuries 7.
• The common structure includes an outside cyst wall that engulfs differentiated suprabasal layers and keratins 7.
• Cysts result from degradation of skin epithelium and appendages while retaining certain characteristics of multipotency 7.

Key Clinical Pitfalls

• Don't assume a normal ultrasound in childhood excludes ADPKD, as cysts develop slowly and diagnostic sensitivity is better in older children 1.
• Multiple kidney cysts in childhood are highly suggestive of genetic cystic disease and require clinical work-up, as simple cysts are very rare in children 1.
• In acquired cystic disease of the kidney, distinguish between atypical renal cysts (precursor lesions) and early ACD-RCC by requiring solid nodular growth within the cyst for cancer diagnosis 1.