Definition/General

Introduction: An atypical intraductal papilloma is a benign papillary lesion of the breast that contains a focus of atypical ductal hyperplasia (ADH) or low-grade ductal carcinoma in situ (DCIS).
Origin: It arises from the ductal epithelium.
Classification:
-It is classified as a benign proliferative breast lesion with atypia
-The presence of atypia within a papilloma increases the risk of subsequent breast cancer.
Epidemiology:
-They are uncommon lesions, found in a small percentage of breast biopsies.

Clinical Features

Presentation: Similar to benign papillomas, they can present with nipple discharge or as a palpable mass.
Symptoms: Nipple discharge is the most common symptom.
Risk Factors: There are no well-established risk factors.
Screening: They can be associated with mammographic abnormalities, such as a mass or calcifications.

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Gross Description

Appearance:
-A friable, polypoid mass within a dilated duct.
Characteristics: The gross appearance is indistinguishable from a benign papilloma.
Size Location: Usually small and located in the large subareolar ducts.
Multifocality: Can be multifocal.

Microscopic Description

Histological Features:
-The lesion is a papilloma with a focus of epithelial proliferation that meets the criteria for ADH or low-grade DCIS
-The atypical proliferation is typically focal and involves the epithelial component of the papilloma.
Cellular Characteristics:
-The atypical cells are monotonous, with low-grade nuclear atypia, similar to that seen in ADH or low-grade DCIS.
Architectural Patterns:
-The atypical proliferation can have cribriform, micropapillary, or solid patterns.
Grading Criteria:
-This is a lesion with atypia
-The key is to distinguish it from a papilloma completely involved by DCIS.

Immunohistochemistry

Positive Markers:
-The myoepithelial layer is preserved, which can be highlighted by myoepithelial markers
-The atypical epithelial cells are ER-positive.
Negative Markers:
-The atypical cells are negative for high molecular weight cytokeratins (e.g., CK5/6).
Diagnostic Utility:
-IHC for myoepithelial markers is essential to distinguish from invasive papillary carcinoma
-CK5/6 can help differentiate the atypical proliferation from usual ductal hyperplasia within a papilloma.
Molecular Subtypes: Molecular subtyping is not relevant for this pre-invasive lesion.

Molecular/Genetic

Genetic Mutations:
-The atypical component can show genetic alterations similar to low-grade DCIS, such as loss of heterozygosity at 16q.
Molecular Markers: No specific molecular markers are routinely used for diagnosis.
Prognostic Significance:
-Atypical papillomas are associated with a significantly increased risk of subsequent breast cancer, higher than that of a benign papilloma or ADH alone.
Therapeutic Targets: Surgical excision is the standard treatment to ensure the entire lesion is removed and to rule out an associated invasive carcinoma.

Differential Diagnosis

Similar Entities:
-Benign papilloma with UDH
-Papillary DCIS
-Invasive papillary carcinoma.
Distinguishing Features:
-UDH within a papilloma has a heterogeneous cell population and mosaic CK5/6 staining
-Papillary DCIS involves the entire papilloma and lacks a myoepithelial layer in the papillae
-Invasive papillary carcinoma shows stromal invasion.
Diagnostic Challenges:
-The main challenge is distinguishing an atypical papilloma from papillary DCIS on a core needle biopsy
-The distinction can be difficult and often requires excision for definitive diagnosis.
Rare Variants: There are no specific rare variants.

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]