Definition/General

Introduction:
-Inflammatory breast carcinoma (IBC) is a rare and very aggressive form of breast cancer that accounts for 1-5% of all breast cancers
-It is defined by clinical signs of inflammation in the breast, such as redness, swelling, and warmth, with or without an underlying palpable mass.
Origin:
-IBC is a clinical diagnosis, not a specific histological subtype
-The underlying histology is most often a high-grade invasive ductal carcinoma
-The inflammatory signs are caused by tumor emboli obstructing dermal lymphatic vessels.
Classification:
-It is classified as a clinical entity (T4d in the TNM staging system)
-The diagnosis requires the characteristic clinical presentation and pathological confirmation of dermal lymphatic invasion by tumor cells.
Epidemiology:
-It tends to affect younger women compared to other breast cancers
-It is more common in African American women
-It has a rapid onset and progression.

Clinical Features

Presentation:
-Rapid onset of breast erythema, edema, and warmth
-The breast is often tender and enlarged
-A distinct lump may or may not be present
-The skin may have a peau d'orange (orange peel) appearance.
Symptoms:
-Breast swelling, pain, tenderness, and itching
-The symptoms can be mistaken for mastitis, but they do not respond to antibiotics.
Risk Factors:
-Younger age and African American race are known risk factors
-Other general breast cancer risk factors may also apply.
Screening:
-IBC is typically not detected by screening mammography as it often does not form a distinct mass
-The diagnosis is usually made based on the acute clinical presentation.

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Gross Description

Appearance:
-There may not be a discrete tumor mass
-The breast tissue is often diffusely indurated and edematous
-The skin is thickened and erythematous.
Characteristics:
-If a mass is present, it is usually ill-defined
-The overall breast is enlarged and heavy.
Size Location: The process typically involves the entire breast.
Multifocality: IBC is considered a diffuse disease process.

Microscopic Description

Histological Features:
-The key pathological finding is the presence of tumor emboli within dermal lymphatic vessels
-The underlying invasive carcinoma is usually a high-grade ductal carcinoma, no special type
-The tumor cells are pleomorphic with high mitotic activity.
Cellular Characteristics:
-The tumor cells are large, with high-grade nuclear features, including irregular nuclear contours, coarse chromatin, and prominent nucleoli.
Architectural Patterns:
-The underlying carcinoma can have various patterns, but it is most commonly a poorly differentiated ductal carcinoma.
Grading Criteria: The underlying carcinoma is almost always high-grade (Grade 3).

Immunohistochemistry

Positive Markers:
-The IHC profile depends on the underlying carcinoma
-Many cases are ER-positive or HER2-positive
-A significant proportion are triple-negative.
Negative Markers: The IHC profile is variable.
Diagnostic Utility:
-IHC is used to characterize the underlying carcinoma (ER, PR, HER2 status) to guide therapy
-D2-40 can be used to highlight the lymphatic vessels containing tumor emboli.
Molecular Subtypes:
-IBC can be of any molecular subtype, but it is more frequently HER2-positive or triple-negative compared to non-inflammatory breast cancers.

Molecular/Genetic

Genetic Mutations:
-TP53 mutations are common
-The genomic profile is complex and heterogeneous
-Overexpression of genes involved in angiogenesis and inflammation is a feature.
Molecular Markers:
-E-cadherin is often overexpressed, which may contribute to the formation of tumor emboli
-RhoC GTPase overexpression is also implicated in the aggressive phenotype.
Prognostic Significance:
-IBC has a very poor prognosis with a high risk of early recurrence and distant metastasis
-The 5-year survival rate is significantly lower than for other types of breast cancer.
Therapeutic Targets:
-Treatment is multimodal, including neoadjuvant chemotherapy, surgery, and radiation
-HER2-targeted therapy is used for HER2-positive cases
-Hormonal therapy is used for ER-positive cases.

Differential Diagnosis

Similar Entities:
-Mastitis (infectious)
-Radiation dermatitis
-Other causes of skin inflammation
-Lymphoma or leukemia cutis.
Distinguishing Features:
-Mastitis typically responds to antibiotics and may be associated with lactation
-Radiation dermatitis has a clear history of radiation exposure
-A skin biopsy showing dermal lymphatic invasion by carcinoma is diagnostic of IBC.
Diagnostic Challenges:
-The clinical presentation can mimic infection, leading to a delay in diagnosis
-A high index of suspicion is required
-A skin punch biopsy is necessary to confirm the diagnosis.
Rare Variants: The underlying histology can be lobular carcinoma or other rare subtypes, but ductal is the most common.

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]