Definition/General

Introduction:
-Ovarian cystadenomas represent the most common benign epithelial tumors of the ovary
-They constitute 60-70% of all benign ovarian neoplasms
-These tumors are characterized by cystic architecture lined by non-proliferative epithelium
-They show no atypia and have excellent prognosis with complete surgical excision.
Origin:
-Originate from the surface epithelium of the ovary or inclusion cysts
-Develop from invagination of surface epithelium into ovarian stroma
-The epithelium undergoes müllerian differentiation
-No malignant potential when truly benign
-Represent the benign end of the adenoma-borderline-carcinoma sequence.
Classification:
-Classified by WHO 2020 guidelines based on epithelial type
-Serous cystadenoma (most common, 60%)
-Mucinous cystadenoma (25-30%)
-Endometrioid cystadenoma (rare)
-Clear cell cystadenoma (rare)
-Brenner tumor (transitional cell type)
-Mixed types possible.
Epidemiology:
-Peak incidence in reproductive years (20-50 years)
-Younger age than borderline and malignant tumors
-Serous cystadenoma: 4th-5th decades
-Mucinous cystadenoma: 3rd-4th decades
-No specific ethnic predilection
-Indian population shows similar age distribution with excellent outcomes.

Clinical Features

Presentation:
-Asymptomatic in many cases (incidental finding)
-Pelvic mass on examination
-Abdominal distension (large tumors)
-Pelvic pain (mild, intermittent)
-Urinary symptoms (pressure effects)
-No constitutional symptoms
-Normal performance status
-Fertility preserved.
Symptoms:
-Pelvic discomfort or fullness
-Mild abdominal pain
-Urinary frequency (large masses)
-Early satiety (very large tumors)
-Bloating sensation
-No weight loss or systemic symptoms
-Regular menstrual cycles usually maintained
-No hormonal effects.
Risk Factors:
-No specific known risk factors
-Reproductive age
-Nulliparity (slight association)
-Infertility treatment (ovulation induction)
-Family history (minimal association)
-Genetic factors (unclear significance)
-Environmental factors (no clear association).
Screening:
-No specific screening recommended
-Routine pelvic examination
-Transvaginal ultrasound for evaluation
-CA-125 (usually normal, <35 U/mL)
-Simple cyst criteria on ultrasound
-Follow-up imaging for size monitoring
-MRI for complex cases.

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Gross Description

Appearance:
-Unilocular or multilocular cystic masses
-Smooth external surface
-Thin-walled cysts with clear or serous fluid
-Serous cystadenoma: Clear, straw-colored fluid
-Mucinous cystadenoma: Thick, viscous, mucoid content
-No solid areas or papillary projections
-Intact capsule.
Characteristics:
-Size varies from 2-30 cm (average 10-15 cm)
-Smooth, glistening surface
-Translucent wall in serous type
-Thicker wall in mucinous type
-No excrescences or surface irregularities
-Homogeneous fluid content
-No areas of hemorrhage or necrosis.
Size Location:
-Size typically 5-20 cm in diameter
-Unilateral in majority (85-90%)
-Bilateral occurrence: Serous (10-15%), Mucinous (<5%)
-Mobile masses (not adherent)
-Smooth contour
-No ascites typically
-Ovarian surface usually intact.
Multifocality:
-Bilateral involvement uncommon
-Multiple cysts within same ovary possible
-No peritoneal involvement
-No lymph node involvement
-Contralateral ovary usually normal
-Uterus and tubes typically uninvolved
-No implants or seeding.

Microscopic Description

Histological Features:
-Single layer of epithelial cells lining cyst wall
-Bland cytology with no atypia
-Uniform nuclei with regular contours
-No mitotic activity
-Serous type: Ciliated columnar epithelium
-Mucinous type: Mucin-containing columnar cells
-Fibrous stroma without proliferation.
Cellular Characteristics:
-Epithelial cells show minimal variation in size and shape
-Basally located nuclei
-Abundant cytoplasm (mucinous type)
-Cilia present (serous type)
-No nuclear enlargement
-No prominent nucleoli
-No loss of polarity
-Regular cell borders.
Architectural Patterns:
-Simple cystic architecture
-Single epithelial layer
-No papillary formations
-No solid areas
-Smooth internal surface
-Fibrous cyst wall
-No complex branching
-Uniform lining throughout.
Grading Criteria:
-Cystadenomas are not graded as they are benign by definition
-Assessment focuses on confirming benign features
-Absence of atypia
-No proliferative activity
-Simple architecture
-Exclusion of borderline features
-No areas of concern requiring additional sampling.

Immunohistochemistry

Positive Markers:
-CK7 (cytokeratin 7, positive)
-PAX8 (müllerian origin marker)
-WT1 (serous type, nuclear staining)
-ER/PR (hormone receptors, variable)
-CA-125 (serous type)
-Calretinin (mesothelial marker, may be positive)
-CK19 (cytokeratin 19).
Negative Markers:
-CK20 (negative in serous, may be positive in mucinous)
-CDX2 (negative in serous)
-TTF-1 (thyroid transcription factor)
-p53 (wild-type, scattered cells)
-Ki-67 (very low proliferation index)
-Inhibin (sex cord-stromal marker)
-Chromogranin (neuroendocrine).
Diagnostic Utility:
-PAX8 and WT1 confirm müllerian origin
-CK7/CK20 profile helps in subtyping
-Low Ki-67 confirms benign nature
-p53 wild-type pattern
-Negative sex cord markers exclude other tumors
-Usually not necessary for straightforward cases
-Helpful in differential diagnosis.
Molecular Subtypes:
-Wild-type p53 (no mutations)
-KRAS mutations (rare in benign cystadenomas)
-BRAF mutations (absent)
-PIK3CA mutations (rare)
-Microsatellite stable
-No significant mutations in most cases
-Stable genome overall.

Molecular/Genetic

Genetic Mutations:
-Very few mutations in benign cystadenomas
-Wild-type p53 (>95% cases)
-KRAS mutations (rare, <5%)
-PIK3CA mutations (rare, <5%)
-BRAF mutations (absent)
-ARID1A mutations (rare)
-Stable karyotype
-No oncogene amplifications.
Molecular Markers:
-p53 expression (wild-type pattern)
-Ki-67 proliferation index (very low, <2%)
-PTEN expression (intact)
-MLH1/MSH2/MSH6/PMS2 (intact)
-β-catenin (membranous pattern)
-Cyclin D1 (low expression)
-p16 (negative or weak).
Prognostic Significance:
-Excellent prognosis (100% cure with complete excision)
-No malignant potential when truly benign
-No recurrence after complete removal
-No impact on survival
-Fertility preservation possible
-No genetic counseling required
-Routine follow-up sufficient.
Therapeutic Targets:
-Surgical excision is curative
-Conservative surgery (cystectomy) preferred in young patients
-No adjuvant therapy required
-No targeted therapy needed
-Hormone therapy not indicated
-Fertility-sparing surgery appropriate
-Complete excision prevents recurrence.

Differential Diagnosis

Similar Entities:
-Functional ovarian cysts (follicular, corpus luteum)
-Borderline tumor
-Invasive carcinoma
-Endometriotic cyst
-Tubo-ovarian abscess
-Paraovarian cyst
-Hydrosalpinx
-Urachal cyst (rare).
Distinguishing Features:
-Cystadenoma: Epithelial lining present
-Cystadenoma: No atypia
-Functional cyst: No epithelial lining or luteinized cells
-Borderline: Epithelial proliferation and atypia
-Endometriotic: Chocolate-colored content, hemosiderin
-Abscess: Clinical signs of infection
-Paraovarian: Separate from ovary.
Diagnostic Challenges:
-Distinguishing from functional cysts (clinical correlation, follow-up)
-Ruling out malignancy (imaging, tumor markers)
-Bilateral vs unilateral disease assessment
-Size criteria for surgical intervention
-Age considerations (functional cysts more common in reproductive age)
-Imaging characteristics crucial.
Rare Variants:
-Papillary cystadenoma (benign papillary projections)
-Adenofibroma (prominent fibrous component)
-Cystadenofibroma (mixed cystic-solid)
-Brenner tumor (transitional epithelium)
-Clear cell cystadenoma (very rare)
-Mixed müllerian cystadenoma.

Sample Pathology Report

Template Format

Sample Pathology Report

Complete Report: This is an example of how the final pathology report should be structured for this condition.

Specimen Information

Ovarian cyst, [left/right], measuring [size] cm

Diagnosis

Ovarian cystadenoma, [subtype]

Classification

WHO 2020: Benign epithelial tumor, [specific subtype]

Histological Features

Benign cystic tumor lined by [epithelial type] without atypia

Size and Extent

Size: [X] cm, confined to ovary

Margins

Surgical margins: [clear/involved]

Prognostic Factors

Excellent prognosis with complete excision

Final Diagnosis

Benign ovarian cystadenoma, [complete subtype]