Low-Grade Serous Adenocarcinoma
Martin Köbel, MD
Esther Oliva, MD
Key Facts
Etiology/Pathogenesis
Association with serous borderline tumor
KRAS, BRAF, NRAS mutations (MAPK pathway alterations)
Clinical Issues
Usually high stage
Low response rate to platinum/Taxol chemotherapy
Long-term outcomes similar to high-grade serous carcinoma
Microscopic Pathology
Spectrum from noninvasive to invasive neoplasia
Noninvasive patterns: Tall and slender to rounded bud-like papillae with variable cellularity; solid, fenestrated or cribriform (sometimes microcystic) growth
Patterns of invasion (> 5 mm): Micropapillae, small papillae, small or large nests, or macropapillae (with broad fibrovascular cores) in cleft-like spaces
Low-grade nuclear atypia with < 3x variation in size with visible nucleoli
≤ 12 mitoses/10 HPF (cutoff used as secondary diagnostic criterion to confirm grading)
Ancillary Tests
p53 wild-type pattern, p16 negative or patchy
pax-8, pax-2, and WT1 positive
ER/PR positive (only minority strong and diffuse)
Top Differential Diagnoses
High-grade serous carcinoma
Serous borderline tumor
 Low-grade serous papillary carcinoma of the ovary may show striking, almost confluent, growth of micropapillae (slender papillae) or small papillae occupying > 5 mm. |
 Elongated micropapillae free-floating within nonepithelial-lined cleft-like spaces  are characteristic of low-grade serous carcinoma. Note the focal presence of psammoma bodies  . |
TERMINOLOGY
Abbreviations
Low-grade serous adenocarcinoma (LGSC)
Synonyms
Well-differentiated serous carcinoma, invasive micropapillary carcinoma, serous psammocarcinoma
Definitions
Malignant epithelial neoplasm of serous cell lineage with micropapillary architecture, low-grade nuclear atypia, and destructive invasion
ETIOLOGY/PATHOGENESIS
Neoplastic Progression
Association with serous borderline tumor (biological continuum)
Low-grade serous carcinoma and serous borderline tumor often coexist (in up to 75%) in variable combinations
Synchronous or metachronous (serous borderline tumor occasionally recurs as low-grade carcinoma)
May be seen at same location or different sites (e.g., ovary and peritoneum or lymph node)
KRAS, BRAF, NRAS mutations (MAPK pathway alterations) in both
CLINICAL ISSUES
Epidemiology
