Definition/General
Introduction:
Ovarian acinic cell carcinoma is an extremely rare malignant epithelial tumor characterized by cells resembling serous acinar cells of salivary glands
It represents less than 0.1% of all ovarian malignancies and is typically considered a metastatic deposit from salivary gland primary.
Origin:
Primary ovarian acinic cell carcinoma is controversial, as most cases represent metastases from salivary gland primaries
True primary ovarian acinic cell carcinomas are exceptionally rare and require extensive clinical correlation to exclude extraovarian primary sites.
Classification:
According to WHO 2020 classification, acinic cell carcinoma is classified under surface epithelial tumors when primary to ovary
However, thorough investigation for salivary gland, pancreatic, or breast primaries is mandatory.
Epidemiology:
Affects women in 5th-6th decades (mean age 45-60 years)
No specific ethnic predilection reported
In Indian population, accounts for less than 0.05% of ovarian cancers
Associated with history of salivary gland tumors in 70% cases.
Clinical Features
Presentation:
Most patients present with unilateral adnexal mass (85%), abdominal distension (70%), and pelvic pain (60%)
Constitutional symptoms include weight loss (40%) and fatigue (35%)
May present as incidental finding during imaging for other conditions.
Symptoms:
Abdominal pain (75%), pelvic mass sensation (65%), bloating (55%), urinary frequency (35%), early satiety (30%)
Advanced cases may present with ascites (25%) and bowel obstruction (15%)
Rarely associated with endocrine symptoms.
Risk Factors:
Previous salivary gland malignancy (most important), age >45 years, family history of ovarian/breast cancer, BRCA mutations
No established association with reproductive factors or hormone replacement therapy.
Screening:
Transvaginal ultrasound shows solid-cystic mass with heterogeneous echogenicity
CT/MRI demonstrates enhancing soft tissue components
CA-125 elevated in 60% cases
PET-CT essential to exclude extraovarian primary sites.
Master Acinic Cell Carcinoma Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Tumors typically measure 8-15 cm in greatest dimension
Cut surface shows solid and cystic areas with tan-gray to pink coloration
Solid areas may show hemorrhage and necrosis
Cystic spaces contain serous to hemorrhagic fluid.
Characteristics:
Firm to soft consistency depending on solid/cystic ratio
Surface may be smooth or bosselated
Capsular involvement present in 70% cases
Areas of calcification may be present
Cut surface resembles salivary gland tumors with lobulated architecture.
Size Location:
Size ranges from 5-20 cm (median 12 cm)
Usually unilateral involvement (90%)
Most commonly affects right ovary (60%)
May involve ovarian surface with peritoneal implants in advanced cases.
Multifocality:
Bilateral involvement rare (10%) and suggests metastatic disease
Multifocal deposits within same ovary seen in 25% cases
Peritoneal dissemination pattern similar to serous carcinoma
Lymph node metastases common (40%).
Microscopic Description
Histological Features:
Tumor cells arranged in acinar, solid, and papillary patterns
Characteristic serous acinar cells with abundant eosinophilic cytoplasm containing PAS-positive, diastase-resistant granules
Intercalated duct-like structures may be present
Stromal desmoplasia variable.
Cellular Characteristics:
Cells show round to oval nuclei with fine to coarse chromatin and small nucleoli
Cytoplasm is abundant, eosinophilic, and granular
Nuclear pleomorphism ranges from mild to moderate
Mitotic activity typically 5-15 per 10 HPF
Clear cell change may be present.
Architectural Patterns:
Acinar pattern (60%) - cells arranged around small lumina
Solid pattern (30%) - sheets of cells with minimal stromal component
Papillary pattern (25%) - complex papillae with fibrovascular cores
Microcystic pattern may be focally present.
Grading Criteria:
Graded using modified Silverberg system: Grade I (well-differentiated) - predominant acinar pattern, minimal pleomorphism
Grade II (moderately differentiated) - mixed patterns, moderate pleomorphism
Grade III (poorly differentiated) - solid growth, marked pleomorphism, high mitotic rate.
Immunohistochemistry
Positive Markers:
Mammaglobin (95%), GCDFP-15 (90%), DOG1 (85%), SOX10 (80%), S-100 (75%)
Also positive for CK7 (90%), EMA (85%), and focally CK20 (25%)
Amylase and lipase may be positive.
Negative Markers:
TTF-1 negative, Napsin-A negative, CDX2 negative, CK19 negative, Thyroglobulin negative
ER/PR typically negative (unlike ovarian epithelial tumors)
WT1 negative, Calretinin negative.
Diagnostic Utility:
Essential IHC panel: Mammaglobin, GCDFP-15, DOG1, SOX10 for salivary gland differentiation
TTF-1, Napsin-A to exclude lung primary
CDX2, CK20 to exclude GI primary
ER/PR, WT1 to exclude typical ovarian carcinoma.
Molecular Subtypes:
Molecular classification not well-established for ovarian primaries
ARID1A mutations reported in 30% cases
PIK3CA mutations in 25%
TP53 mutations less common (15%) compared to high-grade serous carcinoma.
Molecular/Genetic
Genetic Mutations:
ARID1A mutations (30%) - associated with better response to immunotherapy
PIK3CA mutations (25%) - potential target for PI3K inhibitors
PTEN loss (20%)
TP53 mutations (15%) - associated with worse prognosis
BRCA1/2 mutations rare (5%).
Molecular Markers:
Microsatellite stability in most cases
PD-L1 expression in 40% cases (CPS ≥1)
Homologous recombination deficiency rare
KRAS mutations in 15% cases
PIK3CA amplification correlates with PI3K pathway activation.
Prognostic Significance:
TP53 mutations associated with shortened overall survival (median 24 vs 48 months)
PIK3CA mutations correlate with better response to chemotherapy
ARID1A loss predicts immunotherapy response
High tumor mutational burden (>10 mutations/Mb) in 25% cases.
Therapeutic Targets:
PI3K/AKT/mTOR pathway inhibitors for PIK3CA-mutated tumors
Immunotherapy (pembrolizumab) for MSI-high or high TMB tumors
PARP inhibitors limited efficacy due to low HRD frequency
Anti-angiogenic agents (bevacizumab) show modest activity.
Differential Diagnosis
Similar Entities:
Metastatic acinic cell carcinoma from salivary gland (most important), clear cell carcinoma of ovary, endometrioid carcinoma with secretory features, serous carcinoma with eosinophilic cytoplasm, metastatic pancreatic acinar carcinoma.
Distinguishing Features:
Salivary gland metastasis: Clinical history, bilateral involvement, multiple organ involvement
Clear cell carcinoma: Napsin-A positive, different IHC profile
Endometrioid carcinoma: ER/PR positive, different architecture
Serous carcinoma: WT1 positive, TP53 mutations common.
Diagnostic Challenges:
Distinguishing primary vs metastatic - requires extensive clinical correlation and imaging
Limited tissue sampling may not show characteristic features
Overlapping IHC profiles with some salivary gland tumors
Rare occurrence leading to underrecognition.
Rare Variants:
Acinic cell carcinoma with clear cell features - may mimic clear cell carcinoma
Papillary variant - resembles serous carcinoma
Follicular variant - shows thyroid follicle-like structures
Oncocytic variant - abundant eosinophilic cytoplasm with mitochondria.
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, total weight: __ grams. Ovary measures __ x __ x __ cm. External surface is smooth/bosselated with intact/ruptured capsule. Cut surface shows solid and cystic areas measuring __ cm, with tan-gray coloration and areas of hemorrhage/necrosis.
Diagnosis
Acinic cell carcinoma, Grade __ (WHO), with the following features: Acinar/solid/papillary growth pattern, moderate nuclear pleomorphism, mitotic rate __ per 10 HPF, lymphovascular invasion present/absent, surface involvement present/absent.
Final Diagnosis
PRIMARY OVARIAN ACINIC CELL CARCINOMA, Grade __ (WHO 2020)\n\nStaging (FIGO 2014): Stage __ \n\nIHC Profile: Mammaglobin (+), GCDFP-15 (+), DOG1 (+), SOX10 (+), TTF-1 (-), ER/PR (-)\n\nNote: Extensive clinical correlation recommended to exclude salivary gland primary. Multidisciplinary team discussion advised for treatment planning.