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Tumor-like lesions

Follicle cyst


Editorial Board Member: Ricardo R. Lastra, M.D.
Deputy Editor-in-Chief: Jennifer A. Bennett, M.D.
Gulisa Turashvili, M.D., Ph.D.

Last author update: 12 July 2021
Last staff update: 14 July 2023

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PubMed Search: Ovarian follicular cysts [title]

Gulisa Turashvili, M.D., Ph.D.
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Frozen section description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2
Cite this page: Turashvili G. Follicle cyst. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/ovarynontumorfollicularcysts.html. Accessed December 22nd, 2024.
Definition / general
  • Benign cyst measuring at least 3 cm and lined by an inner layer of granulosa cells with an outer layer of theca cells
Essential features
  • Benign cyst lined by an inner layer of granulosa cells with an outer layer of theca cells
  • Measures ≥ 3 cm, as opposed to cystic follicle, which measures < 3 cm
  • Should be differentiated from cystic granulosa cell tumor
  • May occur at any age, with a variable clinical presentation depending on age and etiology
Terminology
  • Follicular cyst
ICD coding
  • ICD-10: N83.0 - cyst, follicular (atretic) (hemorrhagic) (ovarian)
  • ICD-11: GA18.0 - follicular cyst of ovary
Epidemiology
Sites
  • Ovary
Pathophysiology
  • Physiologically:
    • Ovarian follicle matures during proliferative phase of menstrual cycle, mature oocyte gets released due to luteinizing hormone (LH) surge at midcycle and follicle transforms to corpus luteum
    • If no fertilization, corpus luteum atrophies and forms corpus albicans
  • Follicle may become cystic via 2 mechanisms:
    • Gonadotropin independent:
      • McCune-Albright syndrome (N Engl J Med 1985;312:65)
      • Primary hypothyroidism
      • Isosexual pseudoprecocity
      • Idiopathic central precocious puberty
    • Gonadotropin dependent due to hypothalamic pituitary gonadal axis dysfunction:
  • Cyst usually disappears within 2 - 3 menstrual cycles but may persist
Clinical features
  • Usually asymptomatic and incidental
  • May form adnexal or pelvic mass
  • Pelvic / abdominal pain, rarely hemoperitoneum, due to rupture or torsion (Am J Obstet Gynecol 1984;149:5)
  • May be multiple or bilateral and present with symptoms related to hyperestrogenism (isosexual precocity, pseudoprecocity, menstrual disturbances including amenorrhea and postmenopausal bleeding, endometrial hyperplasia) when associated with McCune-Albright syndrome
  • Rarely, central precocious puberty or isosexual precocity not related to McCune-Albright syndrome (Arch Dis Child 1999;81:53)
  • Most cysts regress during the first 4 months of life but may undergo torsion, hemorrhage and rupture during the neonatal period or in utero
  • May be associated with symptoms of primary hypothyroidism, including Van Wyk-Grumbach syndrome (juvenile hypothyroidism, precocious puberty with delayed bone age and ovarian cysts)
  • May be associated with FSH secreting pituitary adenoma and sometimes precedes clinical presentation of adenoma (Int J Gynecol Pathol 2019;38:562)
  • May be associated with ovarian remnant syndrome in 7% of cases (Acta Obstet Gynecol Scand 2012;91:965)
  • May be associated with autoimmune oophoritis (Obstet Gynecol 1989;74:492)
Diagnosis
  • Histologic examination of tissue
Radiology description
  • Ultrasound examination (J Ultrasound Med 1988;7:597):
    • Thin walled unilocular cyst measuring at least 3 cm
    • Posterior acoustic enhancement
    • Absence of internal echoes
    • No color flow, nodules or any solid components
    • Fluid debris level or internal echoes, if torsion
Radiology images

Images hosted on other servers:
Follicle cyst on ultrasound

Follicle cyst on ultrasound

Prognostic factors
Case reports
Treatment
  • Observation
  • High dose, combined estrogen progestogen preparations
  • LH releasing hormone agonists
  • Excision if symptomatic or persistent (Arch Pediatr 1994;1:903)
  • Cyst puncture if associated with isosexual pseudoprecocity
Gross description
  • Usually solitary
  • Ranging from at least 3 cm to up to 18.5 cm (Int J Gynecol Pathol 2021;40:359)
  • Larger size during pregnancy and puerperium
  • Thin walled cyst with smooth inner surface
  • Usually unilocular
  • No solid component
  • Clear to straw colored fluid contents
  • Serosanguinous or hemorrhagic fluid contents or clotted blood if torsion
  • Multiple or bilateral if associated with McCune-Albright syndrome
Gross images

AFIP images
Unilocular cyst with smooth lining

Unilocular cyst with smooth lining



Images hosted on other servers:
   

Large follicle cysts

Frozen section description
  • Benign cystic structure lined by an inner layer of granulosa cells with an outer layer of theca cells
  • Either cell type may be luteinized
Microscopic (histologic) description
  • Inner layer (1 to several) of granulosa cells with or without luteinization
  • Outer layer of theca cells with or without luteinization
    • Dense reticulum on reticulin stain
  • Luteinized cells have eosinophilic to clear cytoplasm and round nuclei with central nucleoli
  • Nonluteinized cysts are more common in patients with precocious puberty (Int J Gynecol Pathol 2021;40:359)
  • Dystrophic calcifications in neonatal cysts (Int J Gynecol Pathol 2021;40:359)
  • Multiple follicle cysts may be associated with eosinophil rich infiltrate (so called eosinophilic perifolliculitis) in autoimmune oophoritis (J Reprod Med 2006;51:141, Int J Gynecol Pathol 2021;40:359)
Microscopic (histologic) images

Contributed by Gulisa Turashvili, M.D., Ph.D.
Cyst wall

Cyst wall

Cyst lining   Cyst lining

Cyst lining

Luteinized theca cells

Luteinized theca cells

Reticulin stain

Reticulin stain

Positive stains
Negative stains
Sample pathology report
  • Right ovary, cystectomy:
    • Follicle cyst
Differential diagnosis
  • Cystic adult type granulosa cell tumor:
    • May be virilizing
    • Usually larger than follicular cysts
    • Multiple layers of granulosa cells
    • Typical architectural patterns within cyst wall (Call-Exner bodies, trabecular, corded)
    • With or without invagination of granulosa cells into cyst wall (Int J Gynecol Pathol 2021;40:359)
    • Nuclear grooves (may be inconspicuous in luteinized forms)
    • Extensive sampling may be required
  • Cystic juvenile granulosa cell tumor:
    • Pale to vacuolated cytoplasm
    • Typical noncystic foci usually present
  • Cystadenoma:
  • Endometriotic cyst:
    • At least focally lined by endometrial-type epithelium
    • Surrounded by endometrial stroma with or without hemorrhage or hemosiderin laden macrophages within wall
  • Cystic follicle:
    • Considered physiologic
    • Morphology identical to follicle cyst but measuring < 3 cm
  • Simple cyst:
    • Denuded cyst without obvious lining or flattened lining
    • No theca cells
  • Large solitary luteinized follicle cyst (Am J Surg Pathol 1980;4:431):
    • Occurs during pregnancy or puerperium
    • Larger than follicular cyst (median size 25 cm)
    • 1 to several layers of markedly luteinized granulosa cells and theca cells that are usually indistinguishable
    • Variable nuclear atypia ranging from small round nuclei with single nucleolus to enlarged nuclei with focal marked pleomorphism, hyperchromasia and smudgy chromatin (degenerative)
    • Absent or rare mitotic figures
  • Hyperreactio luteinalis:
    • Secondary to elevated human chorionic gonadotropin (hCG) levels due to gestational trophoblastic disease, fetal hydrops, multiple gestations, ovarian hyperstimulation syndrome
    • Hyperandrogenism in 15%
    • Bilateral, multiple, thin walled follicle cysts with distinct granulosa and theca cells
    • More extensive luteinization in theca cells compared with granulosa cells
    • Markedly edematous ovarian stroma and groups of luteinized stromal cells between cysts
    • Corpora lutea in ovarian hyperstimulation syndrome
  • Corpus luteum cyst:
    • Undulating border and inner fibrous lining with a zone of small blood vessels with involution (Int J Gynecol Pathol 2021;40:359)
    • Markedly luteinized polygonal shaped granulosa cells with abundant eosinophilic cytoplasm
  • Cortical inclusion cyst:
    • < 1 cm
    • Lined by serous type ciliated epithelium or nonciliated nonmucinous flat epithelium
Additional references
Board review style question #1
Follicular cyst


What entities are included in the differential diagnosis of this cystic lesion of the ovary?

  1. Clear cell carcinoma, cystic follicle and cystic corpus luteum
  2. Corpus luteum cyst, endometriotic cyst and endometrioid borderline tumor
  3. Cystic adult type granulosa cell tumor, cystic follicle and corpus luteum cyst
  4. Endometriotic cyst, corpus luteum cyst and clear cell carcinoma
  5. Serous borderline tumor, cystic adult type granulosa cell tumor and cystic follicle
Board review style answer #1
C. Cystic adult type granulosa cell tumor, cystic follicle and corpus luteum cyst

Comment Here

Reference: Follicular cyst
Board review style question #2
What features would favor a cystic adult type granulosa cell tumor over a follicle cyst?

  1. Large size (> 10 cm), 1 - 2 layers of granulosa cells with readily identifiable mitotic figures and without invagination into cyst wall or nuclear grooves
  2. Large size (> 10 cm), markedly luteinized granulosa cell layer with readily identifiable mitotic figures
  3. Large size (> 10 cm), thick granulosa cell layer with multiple architectural patterns, invagination into cyst wall and nuclear grooves
  4. Small size (< 10 cm), 1 - 2 layers of granulosa cells without invagination into cyst wall or nuclear grooves
  5. Small size (< 10 cm), 1 - 2 layers of granulosa cells without invagination into cyst wall or nuclear grooves and with external layer of luteinized theca cells
Board review style answer #2
C. Large size (> 10 cm), thick granulosa cell layer with multiple architectural patterns, invagination into cyst wall and nuclear grooves

Comment Here

Reference: Follicular cyst
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