Definition/General
Introduction:
Ovarian apocrine carcinoma is an extremely rare malignant tumor showing apocrine differentiation with characteristic morphology
Represents less than 0.1% of all ovarian malignancies
More commonly seen in breast, salivary glands, and skin
Shows abundant eosinophilic cytoplasm with apical snouts
Contains apocrine secretion in cytoplasm.
Origin:
Arises from surface epithelium or inclusion cysts of the ovary with apocrine metaplasia
May arise from pre-existing endometriosis with apocrine change
Results from hormonal influences leading to apocrine differentiation
Shows similar morphology to apocrine carcinoma of breast
Represents rare variant of ovarian adenocarcinoma.
Classification:
Classified under WHO 2020 as variant of surface epithelial tumor
Grade I-III based on nuclear features and architecture
Most cases are Grade II-III (intermediate to high grade)
FIGO staging follows standard ovarian cancer protocols
TNM classification applies with detailed staging criteria.
Epidemiology:
Peak incidence in 5th-7th decades (45-70 years)
Postmenopausal women predominantly affected (80-90%)
Unilateral presentation typical (85-90%)
Associated with endometriosis in 30-40% cases
Indian population shows similar demographics
Hormonal factors may play a role.
Clinical Features
Presentation:
Pelvic mass (most common presentation in 85-90% cases)
Abdominal distension due to tumor mass
Pelvic pain and discomfort
Unilateral presentation typical (85-90%)
Often early stage at presentation (60-70% Stage I-II)
May present as incidental finding.
Symptoms:
Pelvic pain (60-70% cases)
Abdominal bloating and fullness
Urinary frequency due to mass effect
Menstrual irregularities (premenopausal women)
Postmenopausal bleeding occasionally
Constitutional symptoms uncommon unless advanced.
Risk Factors:
Age >45 years (primary risk factor)
Personal history of endometriosis (30-40% association)
Nulliparity or low parity
Hormone replacement therapy
Family history of breast/ovarian cancer
Late menopause (>52 years).
Screening:
Transvaginal ultrasound shows solid-cystic mass
CA-125 may be mildly elevated
CT/MRI pelvis for characterization
PET-CT in advanced cases
Tissue biopsy required for definitive diagnosis
Genetic counseling if family history positive.
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Gross Description
Appearance:
Solid-cystic tumor with well-defined margins
Gray-white to tan cut surface with cystic areas
Smooth external surface typically
May show papillary projections in cystic areas
Hemorrhage and necrosis uncommon unless high-grade.
Characteristics:
Firm consistency with cystic components
Gray-white to yellow-tan coloration
Well-circumscribed in most cases
Cystic fluid may be serous or mucinous
Calcifications rare
Surface involvement uncommon (10-15%).
Size Location:
Size ranges from 3-12 cm (median 6 cm)
Unilateral involvement in 85-90% cases
Can arise from any part of ovary
Surface involvement uncommon
Bilateral disease rare (<15%)
Usually confined to ovary at presentation.
Multifocality:
Unifocal presentation typical (90-95% cases)
Multifocal disease rare within same ovary
Bilateral involvement in <15% cases
Extraovarian spread uncommon at presentation
Peritoneal implants rare in early-stage disease
Lymph node involvement uncommon.
Microscopic Description
Histological Features:
Malignant epithelial cells with apocrine differentiation
Abundant eosinophilic cytoplasm with apical snouts
Decapitation secretion (apocrine secretion) visible
Large, vesicular nuclei with prominent nucleoli
Mitotic activity variable (5-20/10 HPF)
Desmoplastic stroma may be present.
Cellular Characteristics:
Large epithelial cells with abundant eosinophilic cytoplasm
Apical cytoplasmic blebs (apocrine snouts)
Large, round to oval nuclei with vesicular chromatin
Prominent nucleoli typically present
Intracytoplasmic vacuoles may be seen
Nuclear pleomorphism variable.
Architectural Patterns:
Glandular architecture predominates
Papillary pattern may be present
Solid areas in high-grade tumors
Cystic spaces lined by apocrine cells
Infiltrative growth pattern in invasive areas
Fibrous stroma separating tumor nests.
Grading Criteria:
Grade I (well-differentiated): Well-formed glands, minimal nuclear pleomorphism
Grade II (moderately differentiated): Moderate nuclear pleomorphism, some solid areas
Grade III (poorly differentiated): Marked nuclear pleomorphism, predominantly solid growth
Mitotic count and nuclear features important for grading.
Immunohistochemistry
Positive Markers:
CK7 (95-100% cases)
PAX8 (90-95% cases - ovarian origin)
Androgen receptor (AR) (80-90% cases - characteristic)
GCDFP15 (70-80% cases - apocrine marker)
Mammaglobin (40-50% cases)
GATA3 (60-70% cases)
CA125 (50-60% cases).
Negative Markers:
CK20 (negative)
CDX2 (negative - excludes GI origin)
TTF1 (negative - excludes lung primary)
WT1 (usually negative)
Calretinin (negative - excludes sex cord stromal tumor)
Inhibin (negative)
p63 (negative in most cases).
Diagnostic Utility:
PAX8 positivity confirms ovarian epithelial origin
Androgen receptor positivity supports apocrine differentiation
GCDFP15 positivity confirms apocrine phenotype
CK7+/CK20- pattern typical
Mammaglobin positivity may cause confusion with breast primary
Clinical correlation essential.
Molecular Subtypes:
Hormone receptor positive subtype (AR positive in 80-90%)
Apocrine-like molecular profile
Low to intermediate Ki-67 proliferation index
p53 wild-type pattern in most cases
PIK3CA pathway alterations may be present
Androgen-driven phenotype predominates.
Molecular/Genetic
Genetic Mutations:
PIK3CA mutations (30-40% cases)
ARID1A mutations (20-25% cases)
KRAS mutations (15-20% cases)
TP53 mutations uncommon (<10% - typically wild-type)
PTEN mutations (10-15% cases)
Androgen receptor amplification (20-30% cases).
Molecular Markers:
Androgen receptor expression (80-90% cases)
GCDFP15 expression (70-80% cases)
p53 wild-type pattern (>90% cases)
Low to intermediate Ki-67 (<30% typically)
PIK3CA pathway activation
Hormone receptor status variable.
Prognostic Significance:
Stage at presentation most important prognostic factor
Grade correlates with prognosis
Early-stage disease has favorable prognosis (>80% 5-year survival)
Androgen receptor positivity may predict better outcomes
PIK3CA mutations may have prognostic implications
Lower grade tumors have excellent prognosis.
Therapeutic Targets:
Androgen receptor (anti-androgen therapy potential)
PIK3CA inhibitors for mutated cases
mTOR inhibitors (investigational)
Anti-angiogenic agents (bevacizumab)
Hormone therapy (limited role)
CDK4/6 inhibitors (investigational).
Differential Diagnosis
Similar Entities:
Metastatic breast apocrine carcinoma (morphologically identical)
Endometrioid adenocarcinoma with apocrine features
Clear cell carcinoma (may have eosinophilic cytoplasm)
High-grade serous carcinoma with eosinophilic areas
Sertoli cell tumor (may have eosinophilic cytoplasm)
Steroid cell tumor.
Distinguishing Features:
vs Breast metastasis: Clinical history crucial
PAX8 positive in ovarian
Mammography/breast imaging negative
vs Endometrioid: Lacks squamous differentiation
GCDFP15 positive in apocrine
vs Clear cell: Lacks hobnail morphology
Different IHC profile
vs Sertoli cell: Inhibin/calretinin negative
EMA positive.
Diagnostic Challenges:
Distinguishing from breast metastasis most challenging
Morphological overlap with other eosinophilic tumors
Clinical correlation essential
IHC panel required (PAX8, AR, GCDFP15, mammaglobin)
Small biopsy samples may be insufficient
Frozen section diagnosis difficult.
Rare Variants:
Apocrine carcinoma with endometrioid features
Mixed apocrine-serous carcinoma
Apocrine carcinoma with clear cell areas
Cystic apocrine carcinoma
Apocrine carcinoma with squamous differentiation
Each variant requires comprehensive IHC workup.
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
Right/Left ovary and fallopian tube, measuring [X x Y x Z] cm and weighing [X] grams
Gross Description
The ovary shows a [X] cm solid-cystic mass with gray-white cut surface. Surface appears [smooth/irregular]. Fallopian tube appears [normal/abnormal].
Microscopic Description
Malignant epithelial tumor with apocrine differentiation showing [features]. Nuclear grade [I/II/III] with [mitotic activity].
Immunohistochemistry
CK7: Positive, PAX8: Positive, AR: Positive, GCDFP15: Positive, CK20: Negative, TTF1: Negative, Mammaglobin: [Positive/Negative]
Diagnosis
Ovarian Apocrine Carcinoma, Grade [I/II/III], FIGO Stage [stage]
Staging (FIGO 2014)
T[X]N[X]M[X], Stage [I/II/III/IV] with detailed staging criteria
Final Diagnosis
Right/Left Ovarian Apocrine Carcinoma, Grade [X], FIGO Stage [X], with prognostic factors