Definition/General

Introduction:
-Primary signet ring cell carcinoma of the breast is a rare type of mucin-producing adenocarcinoma
-It is defined by the presence of more than 20% of tumor cells being signet ring cells
-It is most often a variant of invasive lobular carcinoma.
Origin:
-It arises from the terminal duct-lobular unit (TDLU)
-The signet ring cells are characterized by large intracytoplasmic mucin vacuoles that push the nucleus to the periphery.
Classification:
-It can be seen in both ductal and lobular carcinomas, but it is much more common in the lobular type
-The diagnosis requires a significant component of signet ring cells.
Epidemiology:
-It is rare, accounting for about 1% of all breast cancers
-It typically affects postmenopausal women.

Clinical Features

Presentation:
-Presents as a palpable breast mass or as a diffuse thickening of the breast
-The clinical and radiological features are often non-specific.
Symptoms: A painless breast lump is the most common symptom.
Risk Factors: The risk factors are similar to those for invasive lobular carcinoma.
Screening:
-Mammography may show a spiculated mass or architectural distortion
-It can be difficult to detect mammographically.

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Gross Description

Appearance:
-An ill-defined, firm, white-tan mass
-It may have a gelatinous appearance if there is abundant extracellular mucin.
Characteristics: The tumor is often infiltrative.
Size Location: Can occur anywhere in the breast.
Multifocality:
-Can be multifocal, similar to invasive lobular carcinoma.

Microscopic Description

Histological Features:
-The tumor is composed of infiltrating signet ring cells, either individually or in small clusters
-The cells have a large, clear, mucin-filled cytoplasm that displaces the nucleus to the periphery, creating the characteristic signet ring shape.
Cellular Characteristics:
-The signet ring cells contain intracytoplasmic mucin, which can be demonstrated with a mucicarmine or PAS stain.
Architectural Patterns:
-The growth pattern is typically infiltrative, with single cells and linear cords, similar to invasive lobular carcinoma.
Grading Criteria: These tumors are generally considered high-grade.

Immunohistochemistry

Positive Markers:
-The IHC profile is usually that of invasive lobular carcinoma, with positivity for ER and PR
-They are positive for cytokeratins.
Negative Markers:
-They are typically E-cadherin negative
-HER2 is usually negative.
Diagnostic Utility:
-IHC is used to confirm the diagnosis and to differentiate from metastatic signet ring cell carcinoma (e.g., from the stomach)
-GATA3 and mammaglobin are useful for confirming breast origin.
Molecular Subtypes: Most are of the Luminal A or B molecular subtype.

Molecular/Genetic

Genetic Mutations:
-Loss of CDH1 (E-cadherin) is a key genetic event, similar to invasive lobular carcinoma.
Molecular Markers: No specific molecular markers are routinely used for diagnosis beyond CDH1.
Prognostic Significance:
-The prognosis is generally considered to be poor, worse than that of conventional invasive lobular carcinoma
-There is a high rate of lymph node and distant metastasis.
Therapeutic Targets:
-Treatment is similar to that of invasive lobular carcinoma, based on hormone receptor status
-Endocrine therapy is the mainstay of treatment.

Differential Diagnosis

Similar Entities:
-Metastatic signet ring cell carcinoma (stomach, colon)
-Mucinous carcinoma
-Lipid-rich carcinoma.
Distinguishing Features:
-Metastatic gastric signet ring cell carcinoma is often positive for CK20 and CDX2
-Mucinous carcinoma has abundant extracellular mucin
-Lipid-rich carcinoma has clear vacuoles that are lipid, not mucin.
Diagnostic Challenges:
-The main challenge is excluding a metastasis from the gastrointestinal tract
-A panel of IHC including breast-specific and GI-specific markers is essential.
Rare Variants: The entire entity is a rare variant.

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]

Final Diagnosis

Final diagnosis: [complete diagnosis]