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]