Definition/General

Introduction: Phyllodes tumor with signet ring cell carcinoma is an exceptionally rare malignant phyllodes tumor where the stromal component contains signet ring cell carcinoma characterized by cells with intracytoplasmic mucin displacing the nucleus to the periphery.
Origin:
-Develops from intralobular breast stroma with differentiation toward signet ring cell carcinoma
-May arise through mucin-producing transformation of stromal cells with characteristic signet ring morphology.
Classification:
-WHO Classification categorizes this as malignant phyllodes tumor with heterologous elements
-Signet ring cell carcinoma component shows characteristic mucin-filled cells.
Epidemiology:
-Exceptionally rare with fewer than 5 cases reported worldwide
-Peak age 40-65 years
-Female predominance
-Associated with aggressive behavior and poor prognosis.

Clinical Features

Presentation:
-Large, rapidly growing breast mass
-May present with skin changes including peau d'orange
-Often associated with inflammatory signs
-Advanced stage at presentation.
Symptoms:
-Rapid breast enlargement over weeks to months
-Breast skin thickening
-Peau d'orange appearance
-Breast pain and tenderness
-Constitutional symptoms possible.
Risk Factors:
-Previous phyllodes tumor history
-Middle to older age
-Family history of gastric cancer
-Genetic predisposition to signet ring cell carcinoma.
Screening:
-No specific screening available
-Clinical examination for masses and skin changes
-Imaging with mammography, ultrasound, and MRI
-Urgent tissue diagnosis.

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Gross Description

Appearance:
-Large, ill-defined mass with firm to hard consistency
-Cut surface shows gray-white areas with possible gelatinous appearance
-Extensive infiltration.
Characteristics:
-Size typically >5 cm (range 3-15 cm)
-Firm to hard consistency
-Ill-defined borders
-Gelatinous or mucoid areas
-Extensive local invasion.
Size Location:
-Can occur in any breast region
-Usually involves extensive breast tissue
-Unilateral presentation
-Extension to skin and chest wall common.
Multifocality:
-Often multifocal or diffuse involvement
-Extensive signet ring cell infiltration
-Lymphatic involvement common
-Widespread distribution.

Microscopic Description

Histological Features:
-Biphasic tumor with epithelial and mesenchymal components
-Signet ring cell carcinoma areas show individual cells with intracytoplasmic mucin displacing nuclei peripherally.
Cellular Characteristics:
-Signet ring cells with large mucin vacuoles displacing nuclei
-Crescent-shaped nuclei at cell periphery
-Abundant intracytoplasmic mucin
-High nuclear-cytoplasmic ratio.
Architectural Patterns:
-Single-file growth pattern typical
-Targetoid pattern around ducts
-Extensive stromal infiltration
-Lakes of extracellular mucin.
Grading Criteria:
-High-grade carcinoma by definition
-Poorly cohesive growth pattern
-Extensive mucin production
-High metastatic potential.

Immunohistochemistry

Positive Markers:
-Cytokeratins positive (CK7, CK20 variable)
-EMA positive
-CEA positive
-Mucin stains strongly positive
-CDX2 may be positive
-Epithelial component: CK7+, EMA+.
Negative Markers:
-E-cadherin negative or decreased
-TTF-1 negative
-PAX8 negative
-Estrogen receptor usually negative
-Progesterone receptor usually negative.
Diagnostic Utility:
-Strong mucin stains characteristic
-Loss of E-cadherin typical
-CDX2 positivity may suggest gastric-type differentiation.
Molecular Subtypes:
-Gastric-type signet ring cell carcinoma
-Lobular carcinoma-like signet ring cells
-Mixed signet ring and conventional adenocarcinoma.

Molecular/Genetic

Genetic Mutations:
-CDH1 mutations (E-cadherin gene)
-TP53 mutations
-PIK3CA alterations
-KRAS mutations possible
-Microsatellite instability rare.
Molecular Markers:
-Loss of E-cadherin expression
-High mucin gene expression (MUC1, MUC2)
-Low hormone receptor expression
-High Ki-67 index.
Prognostic Significance:
-CDH1 mutations predict poor prognosis
-Loss of E-cadherin associated with invasiveness
-High grade indicates aggressive behavior.
Therapeutic Targets:
-HER2-targeted therapy if positive
-Immune checkpoint inhibitors
-Anti-mucin therapies under development
-Chemotherapy combinations.

Differential Diagnosis

Similar Entities:
-Primary signet ring cell carcinoma of breast
-Metastatic signet ring cell carcinoma from stomach
-Invasive lobular carcinoma
-Mucinous carcinoma.
Distinguishing Features:
-Phyllodes with signet ring: Leaf-like areas, mucin+
-Primary signet ring: No phyllodes component
-Metastatic: Clinical history, imaging.
Diagnostic Challenges:
-Recognition of signet ring cell features
-Distinction from metastatic gastric carcinoma
-Assessment of phyllodes components
-E-cadherin interpretation.
Rare Variants:
-Signet ring cell carcinoma with neuroendocrine features
-Mixed signet ring and ductal carcinoma
-Signet ring with squamous differentiation.

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]