Definition/General

Introduction:
-Cervical mucinous carcinoma is a rare subtype of cervical adenocarcinoma characterized by abundant intracytoplasmic mucin production
-Accounts for 10-15% of all cervical adenocarcinomas
-Includes gastric-type, intestinal-type, and signet-ring cell carcinoma variants.
Origin:
-Originates from endocervical glandular epithelium with divergent differentiation pathways
-Gastric-type shows pyloric/foveolar differentiation
-Intestinal-type exhibits enteric features
-Signet-ring variant demonstrates extreme mucin accumulation
-Most cases are HPV-independent, particularly gastric-type adenocarcinoma.
Classification:
-WHO classification recognizes three main subtypes
-Gastric-type (most common, 45-50%)
-Intestinal-type (25-30%)
-Signet-ring cell type (10-15%)
-Mixed mucinous patterns (10-15%)
-Minimal deviation adenocarcinoma (adenoma malignum) represents well-differentiated gastric-type variant.
Epidemiology:
-Accounts for 1-3% of all cervical cancers
-Peak incidence in 5th-6th decade
-Higher prevalence in Japan for gastric-type
-Associated with Peutz-Jeghers syndrome in 15% of minimal deviation adenocarcinoma cases
-HPV-independent in 70-80% of gastric-type cases.

Clinical Features

Presentation:
-Watery vaginal discharge (70-80%)
-Abnormal vaginal bleeding (60%)
-Pelvic pain or pressure (40%)
-Cervical mass or barrel-shaped cervix (35%)
-Often presents at advanced stage due to deep infiltration.
Symptoms:
-Profuse mucoid discharge characteristic of gastric-type
-Postcoital bleeding in 45% cases
-Lower abdominal discomfort
-Constitutional symptoms in advanced disease
-Urinary symptoms from bladder involvement.
Risk Factors:
-Peutz-Jeghers syndrome for minimal deviation adenocarcinoma
-Prior pelvic radiation (rare)
-Chronic cervicitis
-No strong HPV association for gastric-type
-Immunosuppression for HPV-associated intestinal-type.
Screening:
-Pap smear has low sensitivity (30-40%)
-HPV testing negative in gastric-type
-Endocervical curettage more sensitive
-MRI useful for deep cervical involvement
-Gastroscopy-type endoscopic examination beneficial.

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Gross Description

Appearance:
-Firm, tan-white mass with mucoid cut surface
-Infiltrative growth pattern with irregular borders
-Barrel-shaped cervix in advanced cases
-Mucin pools visible on sectioning.
Characteristics:
-Size ranges from microscopic to >5 cm
-Deep stromal infiltration common
-Extension to parametrium frequent
-May involve lower uterine segment
-Surface ulceration in 30% cases.
Size Location:
-Endocervical location predominant (80%)
-May extend to vaginal fornices
-Parametrial involvement in 40-50%
-Lower uterine segment extension in 25%
-Multifocal disease in 15%.
Multifocality:
-Skip lesions reported in gastric-type
-Multicentric disease in 10-15%
-Discontinuous spread pattern
-Associated with ovarian metastases (20%)
-Peritoneal dissemination possible.

Microscopic Description

Histological Features:
-Abundant intracellular and extracellular mucin
-Gastric-type shows pyloric gland differentiation
-Intestinal-type exhibits goblet cells and enterocyte-like cells
-Complex glandular architecture with cribriform patterns.
Cellular Characteristics:
-Columnar cells with apical mucin caps
-Clear to pale eosinophilic cytoplasm
-Mild to moderate nuclear atypia in well-differentiated cases
-High-grade nuclear features in poorly differentiated tumors.
Architectural Patterns:
-Complex branching glands
-Cribriform and papillary patterns
-Solid areas in high-grade tumors
-Desmoplastic stromal reaction
-Perineural invasion common (40%).
Grading Criteria:
-Well-differentiated: minimal atypia, complex glands
-Moderately differentiated: moderate atypia, solid areas <50%
-Poorly differentiated: marked atypia, solid areas >50%
-Signet-ring variant considered high-grade.

Immunohistochemistry

Positive Markers:
-MUC6 positive in gastric-type (90%)
-HIK1083 positive in gastric-type (85%)
-CK7 positive (95%)
-CEA positive (80%)
-CA125 positive (60%)
-PAX8 positive (70%)
-MUC5AC positive in gastric-type (75%).
Negative Markers:
-p16 negative in HPV-independent cases (80%)
-ER negative (90%)
-PR negative (85%)
-CK20 usually negative
-CDX2 negative except intestinal-type
-Vimentin negative.
Diagnostic Utility:
-MUC6 and HIK1083 specific for gastric-type
-p16 negativity distinguishes from usual adenocarcinoma
-PAX8 confirms Müllerian origin
-CDX2 positive in intestinal-type (70%).
Molecular Subtypes:
-HPV-independent gastric-type most common
-HPV-associated intestinal-type
-Mixed immunophenotypes exist
-Molecular profiling shows distinct signatures.

Molecular/Genetic

Genetic Mutations:
-STK11 mutations in Peutz-Jeghers associated cases (95%)
-KRAS mutations in 30%
-TP53 mutations in 40%
-GNAS mutations in gastric-type (30%)
-PIK3CA mutations in 25%.
Molecular Markers:
-HPV DNA negative in gastric-type
-Microsatellite stable in most cases
-HER2 amplification rare (5%)
-PDL1 expression in 20%
-High tumor mutational burden uncommon.
Prognostic Significance:
-STK11 mutations associated with aggressive behavior
-KRAS mutations correlate with poor prognosis
-HPV-negative status indicates worse outcome
-High-grade histology predicts rapid progression.
Therapeutic Targets:
-Limited targeted therapy options
-Anti-angiogenic agents under investigation
-Immunotherapy for PDL1-positive cases
-KRAS inhibitors in clinical trials
-MEK inhibitors showing promise.

Differential Diagnosis

Similar Entities:
-Endometrial mucinous carcinoma: involves corpus primarily
-Metastatic gastric carcinoma: CK7-/CK20+ pattern
-Metastatic colorectal carcinoma: CDX2+/PAX8-
-Clear cell carcinoma: clear cytoplasm without mucin.
Distinguishing Features:
-Gastric-type: MUC6+/HIK1083+, p16-
-Usual endocervical adenocarcinoma: p16+, HPV+
-Mesonephric carcinoma: GATA3+, mucicarmine-
-Endometrioid carcinoma: ER+/PR+, squamous differentiation.
Diagnostic Challenges:
-Minimal deviation adenocarcinoma mimics benign glands
-Gastric-type missed on Pap smears
-Distinction from metastases requires clinical correlation
-Deep biopsies needed for diagnosis.
Rare Variants:
-Adenoma malignum (minimal deviation adenocarcinoma)
-Colloid carcinoma variant
-Mucinous carcinoma with neuroendocrine differentiation
-Mixed adenoneuroendocrine carcinoma.

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

Radical hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection, received [fresh/in formalin]

Diagnosis

Cervical mucinous carcinoma, [gastric-type/intestinal-type/signet-ring cell type]

Histological Features

[Well/Moderately/Poorly] differentiated mucinous adenocarcinoma with [abundant intracellular and extracellular mucin/goblet cell differentiation/signet-ring cell morphology]

Tumor Size

Greatest dimension: [X] cm; Additional dimensions: [X] × [X] cm; Gross tumor volume: [X] cm³

Depth of Invasion

Depth of stromal invasion: [X] mm; Cervical wall thickness: [X] mm; Percentage of wall invasion: [X]%

Margins

Ectocervical margin: [Negative/Positive] ([X] mm); Endocervical margin: [Negative/Positive] ([X] mm); Deep stromal margin: [Negative/Positive] ([X] mm); Vaginal cuff margin: [Negative/Positive] ([X] mm)

Lymphovascular Invasion

[Present, extensive (>10 foci)/Present, focal/Not identified]; [Small vessel/Large vessel] involvement

Parametrial Involvement

Right parametrium: [Involved/Not involved]; Left parametrium: [Involved/Not involved]; Extent of involvement: [X] mm

Lymph Nodes

Total nodes examined: [X]; Positive nodes: [X]; Largest metastatic deposit: [X] mm; Extranodal extension: [Present/Absent]

Immunohistochemistry

MUC6: [Positive/Negative]; HIK1083: [Positive/Negative]; p16: [Negative/Positive]; PAX8: [Positive/Negative]; CDX2: [Negative/Positive]

Molecular Testing

HPV ISH: [Negative/Positive]; STK11 mutation: [Not detected/Detected]; Additional findings: [specify]

Pathological Stage

FIGO Stage (2018): [stage]; TNM Stage (8th edition): pT[X]N[X]M[X]

Additional Findings

[Cervical intraepithelial neoplasia/Endometriosis/Nabothian cysts/Other findings]