Definition/General
Introduction:
Primary small cell carcinoma of the breast is an extremely rare and highly aggressive malignancy
It is a type of poorly differentiated neuroendocrine carcinoma, histologically identical to small cell carcinoma of the lung
The diagnosis requires the exclusion of a metastasis from the lung or another primary site.
Origin:
It is thought to arise from neuroendocrine cells in the breast or from the neuroendocrine differentiation of a ductal carcinoma.
Classification:
It is classified as a subtype of poorly differentiated neuroendocrine carcinoma of the breast.
Epidemiology:
Extremely rare, representing less than 0.1% of all breast cancers
It typically affects older women.
Clinical Features
Presentation:
Presents as a large, rapidly growing, palpable breast mass
Axillary lymph node metastasis is common at presentation.
Symptoms:
A painless breast lump is the most common symptom
Paraneoplastic syndromes can occur but are rare.
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 and hemorrhage are common.
Characteristics:
The tumor is typically large and soft.
Size Location:
Can occur anywhere in the breast.
Multifocality:
Rare.
Microscopic Description
Histological Features:
The tumor is composed of sheets of small, round, blue cells with scant cytoplasm, finely granular "salt-and-pepper" chromatin, and inconspicuous nucleoli
There is a high mitotic rate, extensive necrosis, and nuclear molding.
Cellular Characteristics:
The cells are small, with a high N/C ratio
The nuclear chromatin is finely granular
Nuclear molding is a key feature.
Architectural Patterns:
The growth pattern is diffuse and infiltrative
Azzopardi effect (basophilic staining of blood vessel walls due to DNA from necrotic tumor cells) can be seen.
Grading Criteria:
This is a high-grade carcinoma by definition.
Immunohistochemistry
Positive Markers:
The tumor cells are positive for neuroendocrine markers such as synaptophysin, chromogranin A, and CD56
They are also positive for TTF-1 in about 50% of cases
They are positive for cytokeratins (CAM5.2, AE1/AE3).
Negative Markers:
Typically triple-negative (ER, PR, and HER2 negative).
Diagnostic Utility:
IHC is essential for diagnosis and to differentiate from other small round blue cell tumors
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 often involve TP53 and RB1 mutations, similar to small cell lung cancer.
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
The behavior is similar to that of small cell lung cancer.
Therapeutic Targets:
Treatment is primarily with platinum-based chemotherapy, similar to small cell lung cancer
The role of surgery and radiation is less clear.
Differential Diagnosis
Similar Entities:
Metastatic small cell carcinoma from the lung
Lymphoma
Lobular carcinoma.
Distinguishing Features:
Excluding a lung primary is crucial and requires clinical and radiological correlation
Lymphoma is negative for cytokeratins and positive for lymphoid markers (e.g., CD45)
Lobular carcinoma is ER-positive and negative for neuroendocrine markers.
Diagnostic Challenges:
The main challenge is confirming a primary breast origin
The presence of an in situ component (DCIS) with transition to small cell carcinoma is the best evidence but is rarely found.
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]