Definition/General
Introduction:
Invasive adenocarcinoma of no special type (NST), formerly known as invasive ductal carcinoma (IDC), is the most common type of invasive breast cancer, accounting for up to 75% of cases
It is a diagnosis of exclusion for tumors that do not fit into any of the specific histological subtypes.
Origin:
It arises from the terminal duct-lobular unit (TDLU)
It is characterized by the infiltration of malignant glandular epithelial cells into the surrounding stroma.
Classification:
It is the default category for invasive breast carcinomas
It is graded using the Nottingham grading system (Elston-Ellis modification of Scarff-Bloom-Richardson system), which assesses tubule formation, nuclear pleomorphism, and mitotic count.
Epidemiology:
The incidence increases with age, with a peak in postmenopausal women
The risk factors are the same as for breast cancer in general, including genetic and hormonal factors.
Clinical Features
Presentation:
Typically presents as a hard, irregular, palpable mass
It can also be detected by screening mammography as a spiculated mass with or without calcifications.
Symptoms:
A painless breast lump is the most common symptom
Nipple retraction, skin dimpling, and axillary lymphadenopathy can also be present.
Risk Factors:
General breast cancer risk factors apply, including female sex, older age, family history, BRCA mutations, and hormonal factors.
Screening:
Mammography is the primary screening tool
Ultrasound is used for further evaluation of palpable masses or mammographic abnormalities.
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Gross Description
Appearance:
A firm to hard, gray-white mass with infiltrative, spiculated borders
The cut surface is often gritty due to desmoplastic stroma and calcifications.
Characteristics:
Size is variable
Areas of necrosis and hemorrhage can be seen, especially in high-grade tumors.
Size Location:
Most common in the upper outer quadrant of the breast.
Multifocality:
Multifocality and multicentricity can occur.
Microscopic Description
Histological Features:
The tumor is composed of malignant ductal cells arranged in cords, nests, and sheets infiltrating a desmoplastic stroma
The degree of tubule formation is variable.
Cellular Characteristics:
The tumor cells show varying degrees of nuclear pleomorphism, hyperchromasia, and mitotic activity, which form the basis of the Nottingham grade.
Architectural Patterns:
The growth pattern is infiltrative
An associated ductal carcinoma in situ (DCIS) component is often present.
Grading Criteria:
The Nottingham grade (1, 2, or 3) is one of the most important prognostic factors and is based on tubule formation, nuclear pleomorphism, and mitotic rate.
Immunohistochemistry
Positive Markers:
The IHC profile is heterogeneous
About 70% are ER-positive, 60% are PR-positive, and 15-20% are HER2-positive
Positive for cytokeratins (e.g., CK7, CK8/18) and E-cadherin.
Negative Markers:
Negative for myoepithelial markers (e.g., p63) in the invasive component.
Diagnostic Utility:
IHC is essential for determining ER, PR, and HER2 status, which is crucial for guiding therapy
It also helps in the differential diagnosis with other tumor types.
Molecular Subtypes:
Adenocarcinoma NST can be of any molecular subtype: Luminal A, Luminal B, HER2-enriched, or Basal-like (triple-negative).
Molecular/Genetic
Genetic Mutations:
The genetic landscape is heterogeneous and depends on the molecular subtype
Common mutations include PIK3CA, TP53, GATA3, and MAP3K1.
Molecular Markers:
Molecular profiling assays (e.g., Oncotype DX, MammaPrint) can be used on ER-positive, HER2-negative tumors to assess the risk of recurrence and predict the benefit of chemotherapy.
Prognostic Significance:
The prognosis is determined by a combination of factors, including tumor size, Nottingham grade, lymph node status, and molecular subtype
Grade 1 tumors have a good prognosis, while Grade 3 tumors have a poorer prognosis.
Therapeutic Targets:
Therapy is guided by the ER, PR, and HER2 status
Options include endocrine therapy, HER2-targeted therapy, chemotherapy, and immunotherapy for triple-negative breast cancer.
Differential Diagnosis
Similar Entities:
Special subtypes of breast carcinoma (e.g., lobular, tubular, mucinous)
Metastatic adenocarcinoma.
Distinguishing Features:
The diagnosis of NST is made when the tumor does not meet the criteria for any of the special subtypes
For example, it lacks the single-file pattern of lobular carcinoma or the well-formed tubules of tubular carcinoma
Metastatic adenocarcinoma is excluded by clinical history and IHC (e.g., GATA3, mammaglobin are breast-specific).
Diagnostic Challenges:
The main challenge is ensuring that a tumor is not a special subtype, as this can have prognostic and therapeutic implications
Adequate sampling is important.
Rare Variants:
NST itself is the common type, not 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]