Definition/General
Introduction:
Primary large cell neuroendocrine carcinoma (LCNEC) of the breast is an extremely rare and aggressive malignancy
It is a type of poorly differentiated neuroendocrine carcinoma, histologically similar to LCNEC of the lung
The diagnosis requires the exclusion of a metastasis from another primary site.
Origin:
It is thought to arise from the neuroendocrine differentiation of a ductal carcinoma or from pre-existing neuroendocrine cells in the breast.
Classification:
It is classified as a subtype of poorly differentiated neuroendocrine carcinoma of the breast.
Epidemiology:
Extremely rare, with only a few case reports in the literature
It typically affects older women.
Clinical Features
Presentation:
Presents as a large, rapidly growing, palpable breast mass
Axillary lymph node metastasis is common.
Symptoms:
A painless breast lump is the most common symptom.
Risk Factors:
No specific risk factors are known.
Screening:
Usually presents as a palpable mass
Mammographic and ultrasound findings are non-specific.
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Gross Description
Appearance:
A large, fleshy, tan-white mass with infiltrative borders
Necrosis is a prominent feature.
Characteristics:
The tumor is typically large and may have a soft or firm consistency.
Size Location:
Can occur anywhere in the breast.
Multifocality:
Rare.
Microscopic Description
Histological Features:
The tumor is composed of sheets and nests of large polygonal cells with abundant eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli
It is characterized by a high mitotic rate and extensive necrosis
An organoid or trabecular growth pattern may be seen.
Cellular Characteristics:
The cells are large with a low N/C ratio
The nuclei are large and vesicular with prominent eosinophilic nucleoli.
Architectural Patterns:
Solid sheets, nests, and trabeculae are common.
Grading Criteria:
This is a high-grade carcinoma by definition.
Immunohistochemistry
Positive Markers:
The tumor cells are positive for neuroendocrine markers such as synaptophysin and chromogranin A
They are also positive for cytokeratins.
Negative Markers:
Typically triple-negative (ER, PR, and HER2 negative).
Diagnostic Utility:
IHC is essential for diagnosis and to differentiate from other high-grade carcinomas
The main challenge is excluding a lung primary.
Molecular Subtypes:
Classified as triple-negative.
Molecular/Genetic
Genetic Mutations:
The molecular genetics are not well characterized but may involve mutations in TP53 and RB1, similar to LCNEC of the lung.
Molecular Markers:
No specific molecular markers are routinely used for diagnosis.
Prognostic Significance:
The prognosis is very poor, with a high rate of early and widespread metastasis.
Therapeutic Targets:
Treatment is primarily with platinum-based chemotherapy, similar to LCNEC of the lung
The role of surgery and radiation is less clear.
Differential Diagnosis
Similar Entities:
Metastatic LCNEC from the lung
Poorly differentiated adenocarcinoma NST
Apocrine carcinoma.
Distinguishing Features:
Excluding a lung primary is crucial
Poorly differentiated adenocarcinoma NST will be negative for neuroendocrine markers
Apocrine carcinoma has more granular cytoplasm and is positive for AR and GCDFP-15.
Diagnostic Challenges:
The main challenge is confirming a primary breast origin
A co-existing DCIS component is the best evidence but is rare.
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]