Definition/General

Introduction:
-Minimal deviation adenocarcinoma (MDA) of the breast is an extremely rare variant of well-differentiated adenocarcinoma, analogous to adenoma malignum of the cervix
-It is characterized by deceptively bland, well-formed glands that deeply infiltrate the stroma.
Origin: It is thought to arise from the terminal duct-lobular unit (TDLU).
Classification: It is a rare variant of well-differentiated invasive ductal carcinoma.
Epidemiology:
-Extremely rare, with only a few case reports in the literature
-It can be associated with Peutz-Jeghers syndrome.

Clinical Features

Presentation:
-Presents as a palpable breast mass
-The clinical and radiological features are non-specific.
Symptoms: A painless breast lump is the most common symptom.
Risk Factors: Association with Peutz-Jeghers syndrome has been reported.
Screening:
-Usually diagnosed after investigation of a palpable mass
-Mammographic and ultrasound findings are non-specific.

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Gross Description

Appearance:
-A firm, ill-defined, gray-white mass.
Characteristics: The tumor may have a rubbery or firm consistency.
Size Location: Can occur anywhere in the breast.
Multifocality: Rare.

Microscopic Description

Histological Features:
-The tumor is composed of haphazardly arranged, well-formed glands that deeply infiltrate the stroma
-The glands are lined by a single layer of deceptively bland cuboidal or columnar cells
-There is a prominent desmoplastic stromal reaction.
Cellular Characteristics:
-The tumor cells show minimal cytological atypia, with small, uniform nuclei and inconspicuous nucleoli
-Mitotic activity is low
-Despite the bland appearance, the infiltrative nature and absence of a myoepithelial layer are key to the diagnosis.
Architectural Patterns:
-The key feature is the deep, infiltrative growth of bland-looking glands.
Grading Criteria: This is a well-differentiated (Grade 1) carcinoma.

Immunohistochemistry

Positive Markers:
-The tumor cells are positive for cytokeratins (e.g., CK7)
-They are typically ER and PR positive.
Negative Markers:
-HER2 is usually negative
-Myoepithelial markers (e.g., p63, calponin) are absent around the infiltrating glands.
Diagnostic Utility:
-IHC is crucial to demonstrate the absence of a myoepithelial layer to confirm invasion
-Hormone receptor status is important for therapy.
Molecular Subtypes: Most are of the Luminal A molecular subtype.

Molecular/Genetic

Genetic Mutations: Association with germline mutations in the STK11 gene (Peutz-Jeghers syndrome) has been reported.
Molecular Markers: No specific molecular markers are routinely used for diagnosis.
Prognostic Significance:
-Despite its well-differentiated appearance, MDA can have an aggressive course with a risk of lymph node and distant metastasis
-The prognosis is better than for high-grade carcinomas but worse than for tubular carcinoma.
Therapeutic Targets:
-Treatment is primarily surgical
-Endocrine therapy is often used due to the high rate of ER positivity.

Differential Diagnosis

Similar Entities:
-Tubular carcinoma
-Sclerosing adenosis
-Radial scar
-Microglandular adenosis.
Distinguishing Features:
-Tubular carcinoma has more angulated tubules and apical snouts
-Sclerosing adenosis and radial scar are benign lesions that retain a myoepithelial layer
-Microglandular adenosis is ER-negative and S100-positive.
Diagnostic Challenges:
-The main challenge is distinguishing MDA from benign sclerosing lesions due to its bland cytology
-The deep infiltrative pattern and absence of myoepithelial cells are key distinguishing features.
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]