Definition/General

Introduction: Cervical signet ring cell carcinoma is an extremely rare variant of cervical adenocarcinoma characterized by malignant cells containing abundant intracytoplasmic mucin that displaces the nucleus to the periphery.
Origin:
-Arises from endocervical glandular epithelium with extensive mucin production
-Represents a morphological variant of adenocarcinoma rather than a distinct entity.
Classification:
-WHO Classification categorizes as a rare variant of cervical adenocarcinoma
-Defined by presence of >50% signet ring cells within the tumor.
Epidemiology:
-Extremely rare, <1% of cervical adenocarcinomas
-Peak incidence 40-60 years
-No specific risk factors beyond those for cervical adenocarcinoma.

Clinical Features

Presentation:
-Abnormal vaginal bleeding
-Cervical mass or enlargement
-May present with advanced disease due to aggressive behavior
-Often asymptomatic until advanced.
Symptoms:
-Abnormal vaginal bleeding (most common)
-Vaginal discharge
-Pelvic pain
-Urinary or bowel symptoms in advanced cases
-Weight loss.
Risk Factors: Similar to cervical adenocarcinoma: HPV infection (variable association), smoking, immunosuppression, DES exposure, oral contraceptive use.
Screening:
-May be detected on Pap smear as atypical glandular cells
-Colposcopy and biopsy required for diagnosis
-Advanced imaging for staging.

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Gross Description

Appearance:
-Poorly defined, infiltrative mass with firm consistency
-Cut surface may appear gelatinous due to mucin content
-Often associated with extensive local spread.
Characteristics:
-Size variable at presentation
-Firm to gelatinous consistency
-White to gray color
-Poorly circumscribed borders
-Extensive local infiltration common.
Size Location:
-Can arise from any part of cervix
-Often involves full thickness of cervical wall
-May extend to parametrium, vagina, or corpus early.
Multifocality:
-Usually unifocal but may show extensive local spread
-Multifocal involvement of cervical quadrants possible.

Microscopic Description

Histological Features:
-Sheets of signet ring cells with abundant intracytoplasmic mucin displacing nuclei peripherally
-Cells infiltrate cervical stroma in single-file pattern or small clusters.
Cellular Characteristics:
-Large cells with abundant clear cytoplasm filled with mucin
-Nuclei displaced to cell periphery giving signet ring appearance
-Prominent nucleoli.
Architectural Patterns:
-Infiltrative growth pattern with single cells or small clusters
-May form pools of extracellular mucin
-Desmoplastic stromal response.
Grading Criteria:
-High-grade adenocarcinoma by definition due to poor differentiation and aggressive behavior
-Nuclear features typically high-grade.

Immunohistochemistry

Positive Markers:
-CK7 positive
-CEA positive
-Mucin stains (PAS, mucicarmine) positive
-CDX2 may be positive
-CK20 variable.
Negative Markers:
-p16 variable (may be negative unlike typical cervical adenocarcinomas)
-TTF-1 negative
-Mammoglobin negative.
Diagnostic Utility:
-Mucin stains confirm intracytoplasmic mucin
-CK7/CK20 profile helps distinguish from metastatic signet ring carcinoma
-CDX2 may be positive.
Molecular Subtypes:
-Limited data on molecular profile
-HPV association variable and may be negative unlike typical cervical adenocarcinomas.

Molecular/Genetic

Genetic Mutations:
-Limited molecular data available
-May lack typical HPV-associated molecular changes
-Different molecular profile from conventional cervical adenocarcinoma.
Molecular Markers:
-p16 expression variable (may be negative)
-Ki-67 proliferation index typically high
-p53 mutations possible.
Prognostic Significance:
-Very poor prognosis due to aggressive behavior and tendency for early metastasis
-Stage at presentation most important prognostic factor.
Therapeutic Targets:
-Standard cervical cancer treatment protocols
-Chemotherapy regimens similar to other adenocarcinomas
-Limited targeted therapy options.

Differential Diagnosis

Similar Entities:
-Metastatic signet ring cell carcinoma (gastric, colorectal, breast)
-Primary cervical mucinous adenocarcinoma
-Krukenberg tumor metastatic to pelvis.
Distinguishing Features:
-Primary cervical: clinical presentation, imaging
-Metastatic gastric: CDX2+, CK20+
-Metastatic breast: mammaglobin+, GATA3+.
Diagnostic Challenges:
-Distinction from metastatic disease is crucial
-Clinical correlation and imaging essential
-Immunohistochemical profile helpful but not definitive.
Rare Variants:
-Mixed signet ring and conventional adenocarcinoma
-Signet ring features in other cervical carcinoma types.

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]