Definition/General

Introduction: Cervical cribriform carcinoma is a rare morphological variant of cervical adenocarcinoma characterized by a cribriform (sieve-like) architectural pattern with rounded spaces within epithelial nests.
Origin:
-Arises from endocervical glandular epithelium showing cribriform growth pattern
-May develop de novo or in association with conventional adenocarcinoma components.
Classification:
-WHO Classification recognizes this as a morphological pattern within cervical adenocarcinoma rather than a distinct subtype
-May be pure or mixed with other patterns.
Epidemiology:
-Very rare variant of cervical adenocarcinoma
-Peak incidence 40-60 years
-Associated with HPV infection similar to other cervical adenocarcinomas.

Clinical Features

Presentation:
-Abnormal vaginal bleeding
-Cervical mass on examination
-May present with abnormal Pap smear showing atypical glandular cells.
Symptoms:
-Abnormal vaginal bleeding (most common)
-Vaginal discharge
-Post-coital bleeding
-Pelvic pain in advanced cases
-May be asymptomatic.
Risk Factors: Similar to cervical adenocarcinoma: HPV infection (high-risk types), smoking, immunosuppression, oral contraceptive use, DES exposure.
Screening:
-May be detected on Pap smear
-Colposcopy shows acetowhite lesions
-HPV testing typically positive for high-risk types.

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Gross Description

Appearance:
-Similar to conventional cervical adenocarcinoma
-May appear as exophytic, ulcerative, or infiltrative lesion
-Cut surface shows solid areas.
Characteristics:
-Size variable (1-8 cm)
-Firm consistency
-Gray-white to tan color
-May have areas of necrosis or hemorrhage.
Size Location:
-Can arise from any part of cervix
-Often involves endocervical canal
-May extend to ectocervix, parametrium, or corpus.
Multifocality: Usually unifocal but may be associated with other adenocarcinoma patterns within the same tumor.

Microscopic Description

Histological Features:
-Epithelial nests with cribriform (sieve-like) architecture showing rounded spaces within the epithelial mass
-Cells show varying degrees of atypia and mitotic activity.
Cellular Characteristics:
-Columnar to cuboidal epithelial cells lining the cribriform spaces
-Nuclear atypia variable
-Increased mitotic activity
-May have focal necrosis.
Architectural Patterns:
-Characteristic cribriform pattern with rounded spaces
-May be associated with solid, glandular, or papillary areas
-Invasive growth pattern.
Grading Criteria:
-Graded according to general adenocarcinoma criteria based on architectural pattern, nuclear atypia, and mitotic activity
-Usually intermediate to high grade.

Immunohistochemistry

Positive Markers:
-p16 diffusely positive (HPV-associated)
-CK7 positive
-CEA positive
-Vimentin may be positive
-PAX8 positive.
Negative Markers:
-CK20 typically negative
-TTF-1 negative
-CDX2 negative
-ER/PR variable.
Diagnostic Utility:
-p16 diffuse positivity confirms HPV association
-CK7/CK20 profile consistent with gynecologic primary
-PAX8 supports müllerian origin.
Molecular Subtypes: Associated with high-risk HPV infection similar to conventional cervical adenocarcinomas.

Molecular/Genetic

Genetic Mutations:
-Similar to conventional cervical adenocarcinomas: HPV integration, E6/E7 oncoproteins, TP53 and RB pathway inactivation.
Molecular Markers:
-p16 overexpression due to HPV integration
-High Ki-67 proliferation index
-Loss of p53 and Rb function.
Prognostic Significance:
-Prognosis similar to conventional cervical adenocarcinoma of similar stage and grade
-Stage at presentation most ímportant prognostic factor.
Therapeutic Targets:
-Standard cervical cancer treatment protocols
-Chemotherapy and radiation therapy similar to other adenocarcinomas.

Differential Diagnosis

Similar Entities:
-Metastatic cribriform carcinoma (breast, salivary gland)
-Adenoid cystic carcinoma
-Adenoid basal carcinoma
-Microcystic adnexal carcinoma.
Distinguishing Features:
-Cervical primary: p16+, HPV+
-Breast: ER+, mammaglobin+
-Adenoid cystic: dual cell population, lack of p16 expression.
Diagnostic Challenges:
-Distinction from metastatic cribriform carcinoma
-Recognition of cribriform pattern
-Differentiation from adenoid cystic carcinoma.
Rare Variants:
-Mixed cribriform and conventional adenocarcinoma
-Cribriform pattern in adenosquamous 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

[specimen type], measuring [size] cm in greatest dimension

Diagnosis

[diagnosis name]

Classification

Classification: [classification system] [grade/type]

Histological Features

Shows [architectural pattern] with [nuclear features] and [mitotic activity]

Size and Extent

Size: [X] cm, extent: [local/regional/metastatic]

Margins

Margins are [involved/uninvolved] with closest margin [X] mm

Lymphovascular Invasion

Lymphovascular invasion: [present/absent]

Lymph Node Status

Lymph nodes: [X] positive out of [X] examined

Special Studies

IHC: [marker]: [result]

Molecular: [test]: [result]

[other study]: [result]

Prognostic Factors

Prognostic factors: [list factors]

Final Diagnosis

Final diagnosis: [complete diagnosis]