Definition/General
Introduction:
Primary neuroendocrine carcinoma (NEC) of the breast is a rare tumor type, characterized by the expression of neuroendocrine markers in more than 50% of the tumor cells
It is a heterogeneous group of tumors with varying prognoses.
Origin:
The origin is thought to be from neuroendocrine cells that are occasionally found in the normal breast epithelium, or from the neuroendocrine differentiation of a conventional adenocarcinoma.
Classification:
According to the WHO, breast NECs are classified into well-differentiated neuroendocrine tumor (NET), poorly differentiated neuroendocrine carcinoma (NEC) (which includes small cell and large cell types), and invasive carcinoma with neuroendocrine differentiation.
Epidemiology:
These tumors are rare, accounting for less than 1% of all breast cancers
They are more common in older women.
Clinical Features
Presentation:
Presents as a palpable breast mass, similar to adenocarcinoma NST
Carcinoid syndrome is extremely rare.
Symptoms:
A painless breast lump is the most common symptom.
Risk Factors:
The risk factors are similar to those for conventional breast cancer.
Screening:
Mammographic and ultrasound findings are non-specific.
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Gross Description
Appearance:
A well-circumscribed, firm, tan-yellow mass.
Characteristics:
Size is variable
Necrosis can be present in high-grade tumors.
Size Location:
Can occur anywhere in the breast.
Multifocality:
Uncommon.
Microscopic Description
Histological Features:
Well-differentiated NETs show organoid patterns like nests and trabeculae, with cells having "salt-and-pepper" chromatin
Poorly differentiated NECs (small cell or large cell) show sheets of highly atypical cells with high mitotic activity and necrosis.
Cellular Characteristics:
The tumor cells are monotonous with scant cytoplasm and granular chromatin
In high-grade tumors, the cells are pleomorphic with high N/C ratios.
Architectural Patterns:
Nesting, trabecular, and solid patterns are common
Rosette formation can be seen.
Grading Criteria:
Grading is based on mitotic count and Ki-67 index, similar to neuroendocrine tumors elsewhere.
Immunohistochemistry
Positive Markers:
The diagnosis requires positivity for neuroendocrine markers such as synaptophysin and chromogranin A in >50% of cells
Most tumors are ER-positive.
Negative Markers:
HER2 is usually negative.
Diagnostic Utility:
IHC is essential for diagnosis
It is also important to exclude a metastasis from a neuroendocrine tumor elsewhere (e.g., lung, GI tract).
Molecular Subtypes:
Most are of the Luminal A or B molecular subtype.
Molecular/Genetic
Genetic Mutations:
The molecular profile is similar to that of ER-positive breast cancer, with frequent mutations in PIK3CA and GATA3.
Molecular Markers:
No specific molecular markers are routinely used for diagnosis.
Prognostic Significance:
The prognosis is variable
Well-differentiated NETs have a relatively good prognosis, similar to grade-matched adenocarcinoma NST
Poorly differentiated NECs have a poor prognosis.
Therapeutic Targets:
Treatment is similar to that of conventional breast cancer, based on ER and HER2 status
Endocrine therapy is often used
Somatostatin analogues can be used in some cases.
Differential Diagnosis
Similar Entities:
Metastatic neuroendocrine tumor
Adenocarcinoma NST with focal neuroendocrine differentiation
Solid papillary carcinoma.
Distinguishing Features:
Excluding a metastasis is crucial
Adenocarcinoma with focal neuroendocrine differentiation has <50% of cells positive for neuroendocrine markers
Solid papillary carcinoma can have neuroendocrine features but has a characteristic papillary architecture.
Diagnostic Challenges:
The main challenge is to distinguish primary from metastatic neuroendocrine tumors
The >50% cutoff for neuroendocrine marker expression is key for diagnosis.
Rare Variants:
Small cell carcinoma of the breast is a very rare and aggressive 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]