Mucinous Borderline Tumour / Atypical Proliferative Mucinous Tumour (MBT/APMT)

Epidemiology and Etiology:

• Most common borderline ovarian tumour in Asia
• 30-50% of borderline ovarian tumours in North America and Europe
• Wide age range (mean 40-49 y)
• Appear to arise from mucinous cystadenomas

Common sites:

• Confined to the ovary (nearly always)
• No well-documented cases of a mucinous borderline / atypical proliferative mucinous tumour associated with peritoneal implants (all are stage 1)
• Acellular mucin may sometimes be detected on peritoneal surfaces

Gross features:

• Unilateral (nearly always)
• Bilaterality should prompt consideration of metastatic carcinoma
• Several cm to up to 50 cm (mean 21.5 cm)
• Smooth external surface
• Small to large cysts containing mucin
• Solid areas maybe
• Smooth inner walled cysts usually
• Some ulcerated
• Some have areas of solid growth
• Adequate sampling is crucial (typically heterogenous and can harbor occult foci of carcinoma)
• 1 section per cm of greatest tumour dimension for tumours < 10 cm, focusing on solid or grossly unusual areas
• 2 sections per cm of greatest tumour dimension for tumours > 10 cm or if microinvasion or intraepithelial CA is seen

Histologic features:

• Adequate sampling is crucial (typically heterogenous and can harbor occult foci of carcinoma)
• GI type epithelium:
• Gastric pyloric-type
• Goblet cells
• Neuroendocrine cells
• Paneth cells occasionally
• Proliferative areas > 10% of the epithelial volume, varying degrees of:
• Stratification
• tufting
• villous or slender filiform papillae
• Nuclear changes (mild to moderate):
• enlargement
• hyperchromasia
• pseudostratification (sometimes)
• ABSENT high-grade nuclear features
• Mitoses vary from slight to brisk
• Pseudomyxoma ovarii (acellular pools of mucin in the stroma) (20%)
• Granulomatous stromal response common
• MBT/APMT with intraepithelial carcinoma:
• Marked nuclear atypia (foci) confined to the epithelium
• Loss of polarity
• Architectural proliferation is usually appreciable
• Cribriform pattern on its own, or epithelial stratification of > 3 cell layers on its own, without severe atypia, does not qualify
• MBT/APMT with microinvasion:
• Stromal invasion (small foci < 5 mm in greatest linear extent)
• No requirement regarding the number of such foci allowed
• Single cells, glands, clusters/nests, small foci of confluent glandular or cribriform growth within the stroma
• Mild to moderate atypical mucinous epithelial cells
• More marked cytological atypia should be classified as “microinvasive carcinoma”
• Mural nodules:
• Microscopic to about 10 cm
• Single or multiple
• Sharply demarcated from the adjacent mucinous epithelium
• 3 varieties:
• Reactive sarcoma-like
• Typically hemorrhagic
• Heterogeneous cell population

• Numerous multinucleated cells of the epulis type
• Atypical spindle cells
• Moderate size
• Hyperchromatic nuclei
• Pleomorphic mononucleated or binucleated giant cells
• Inflammatory cells
• Mitotic index often brisk in most cellular areas
• Weak-focal cytokeratin staining
• Circumscribed
• Benign clinical course

• Foci of anaplastic carcinoma (see mucinous carcinoma)
• Sarcomatous nodules (see mucinous carcinoma)

Immunophenotype:

Marker:	Sensitivity:	Specificity:
CK7 (diffusely positive)	Typically
CK20 (variable / less extensive)
CDX2	Variable
ER/PR (neg)	Almost always
PAX8	50-60%

Molecular features:

• KRAS mutation (30-75%) (early event)

Other features:

• No well-documented cases of a mucinous borderline / atypical proliferative mucinous tumour associated with peritoneal implants (all are stage 1)
• Appear to arise from cystadenoma, and may progress to carcinoma
• Excellent prognosis (with adequate sampling to rule out carcinoma)
• Only a few cases of progression to carcinoma and these were not adequately sampled
• MBT/APMT with intraepithelial carcinoma:
• 95-100% OS
• MBT/APMT with microinvasion:
• 5% recurrence rate (limited data)
• < 5% tumour-related death rate (FIGO stage IC tumours only)
• Microinvasive carcinoma:
• Insufficient data
• Surgical removal of the entire ovary is preferred treatment (some with cystectomy recur)

References:

• Kurman RJ, Carcangiu ML, Herringotn S, Young RH. WHO Classification of Tumours of Female Reproductive Organs (2014)