Definition/General
Introduction:
Primary melanoma of the breast is an extremely rare malignancy
Most cases of melanoma in the breast are metastases from a cutaneous primary
The diagnosis of primary breast melanoma requires the exclusion of a primary melanoma elsewhere.
Origin:
It is thought to arise from melanocytes present in the breast ducts or skin of the breast
The presence of an in situ component is required to confirm a primary origin.
Classification:
Classified according to the histological subtypes of melanoma, such as superficial spreading, nodular, and lentigo maligna melanoma, although these are less well-defined in a non-cutaneous primary.
Epidemiology:
Extremely rare, with only a few hundred cases reported in the literature
It can affect a wide age range of women.
Clinical Features
Presentation:
Presents as a palpable breast mass
The mass may be pigmented
Nipple discharge can occur
It can mimic other breast malignancies clinically and radiologically.
Symptoms:
A breast lump is the most common symptom
It may be associated with pain or skin changes.
Risk Factors:
The risk factors are not well understood due to its rarity
General risk factors for melanoma (e.g., UV exposure) are not relevant for a primary breast melanoma.
Screening:
There is no specific screening
It is usually diagnosed after investigation of a palpable mass
Mammography and ultrasound findings are non-specific.
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Gross Description
Appearance:
The tumor is often a well-circumscribed, firm mass
It may be pigmented (brown or black), but can also be amelanotic (flesh-colored).
Characteristics:
Size is variable
Areas of necrosis and hemorrhage may be present.
Size Location:
Can occur anywhere in the breast.
Multifocality:
Multifocality is rare.
Microscopic Description
Histological Features:
The histology is that of malignant melanoma, with sheets of large, pleomorphic cells with irregular nuclei, prominent eosinophilic nucleoli, and often, melanin pigment
An in situ component in the breast ducts or epidermis is necessary for a diagnosis of primary breast melanoma.
Cellular Characteristics:
The tumor cells are typically large and epithelioid or spindled
The cytoplasm can be eosinophilic, clear, or contain brown melanin pigment
Intranuclear pseudoinclusions are common.
Architectural Patterns:
The growth pattern is typically diffuse or nested.
Grading Criteria:
Grading is not typically applied to melanoma in the same way as carcinomas
Prognostic features include tumor thickness (Breslow depth), ulceration, and mitotic rate.
Immunohistochemistry
Positive Markers:
The tumor cells are positive for melanoma markers such as S100, HMB-45, Melan-A, and SOX10.
Negative Markers:
Negative for cytokeratins, which distinguishes it from carcinoma
Also negative for hormone receptors (ER, PR) and HER2.
Diagnostic Utility:
IHC is essential for diagnosis and to differentiate melanoma from poorly differentiated carcinoma or sarcoma.
Molecular Subtypes:
Molecular subtyping based on gene expression profiling (e.g., luminal, basal-like) is not used for melanoma.
Molecular/Genetic
Genetic Mutations:
Mutations in BRAF (V600E), NRAS, and c-KIT can be found, similar to cutaneous melanoma
Testing for these mutations is important for targeted therapy.
Molecular Markers:
Detection of specific mutations can guide therapy.
Prognostic Significance:
The prognosis is generally poor, similar to or worse than cutaneous melanoma of similar thickness
The presence of metastases is the most important prognostic factor.
Therapeutic Targets:
Treatment involves wide surgical excision
Targeted therapy (BRAF/MEK inhibitors) and immunotherapy (checkpoint inhibitors) are used for metastatic disease, based on the molecular profile.
Differential Diagnosis
Similar Entities:
Metastatic melanoma
Poorly differentiated carcinoma
Sarcoma
Pigmented Paget disease.
Distinguishing Features:
Distinguishing primary from metastatic melanoma requires a thorough clinical examination to exclude a primary cutaneous or ocular melanoma
Carcinomas are positive for cytokeratins
Sarcomas have a different IHC profile
Paget cells are cytokeratin positive.
Diagnostic Challenges:
The main challenge is excluding a metastatic origin
The presence of a clear in situ component is the most reliable feature of a primary breast melanoma.
Rare Variants:
Amelanotic melanoma is a rare variant that lacks pigment and can be particularly challenging to diagnose.
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]