Definition/General
Introduction:
Primary breast lymphoma (PBL) is a rare malignancy, defined as lymphoma localized to the breast with or without regional lymph node involvement, but with no evidence of systemic disease at diagnosis
It accounts for less than 0.5% of all breast malignancies.
Origin:
Most PBLs are of B-cell origin, with Diffuse Large B-Cell Lymphoma (DLBCL) being the most common subtype
They are thought to arise from intramammary lymphoid tissue.
Classification:
PBL is classified according to the World Health Organization (WHO) classification of hematopoietic and lymphoid tissues
The most common subtype is DLBCL, followed by follicular lymphoma and MALT lymphoma.
Epidemiology:
PBL typically affects older women, with a median age in the 60s
It is extremely rare in men
There are no well-defined risk factors, although some association with autoimmune diseases has been suggested.
Clinical Features
Presentation:
Presents as a painless, palpable breast mass
It can be unilateral or bilateral
The mass is often rubbery and mobile
Skin changes are uncommon.
Symptoms:
A breast lump is the most common symptom
B-symptoms (fever, night sweats, weight loss) are uncommon in PBL.
Risk Factors:
No specific risk factors are well-established
Association with autoimmune conditions like Sjögren syndrome has been reported
Prior history of lymphoma elsewhere is an exclusion criterion.
Screening:
Mammographically, it often appears as a well-circumscribed or ill-defined mass without calcifications
Ultrasound typically shows a hypoechoic mass.
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Gross Description
Appearance:
The tumor is typically a well-circumscribed, fleshy, tan-white mass
Necrosis and hemorrhage are uncommon.
Characteristics:
The size is variable, ranging from small nodules to large masses involving the entire breast
The consistency is usually soft and fleshy.
Size Location:
Can occur anywhere in the breast, with no specific predilection
Size is variable.
Multifocality:
Multifocality can occur, especially in low-grade lymphomas.
Microscopic Description
Histological Features:
The histology depends on the lymphoma subtype
In DLBCL, there is a diffuse infiltrate of large, atypical lymphoid cells with vesicular nuclei and prominent nucleoli
In follicular lymphoma, a nodular pattern of neoplastic follicles is seen
MALT lymphoma shows an infiltrate of small lymphocytes with lymphoepithelial lesions.
Cellular Characteristics:
The neoplastic cells are lymphoid in origin
In DLBCL, they are large with scant cytoplasm
In follicular lymphoma, a mix of centrocytes and centroblasts is seen
MALT lymphoma has small, monocytoid B-cells.
Architectural Patterns:
The infiltrate is typically diffuse, surrounding and sometimes destroying breast ducts and lobules
Lymphoepithelial lesions are characteristic of MALT lymphoma.
Grading Criteria:
Grading is based on the specific lymphoma subtype according to the WHO classification.
Immunohistochemistry
Positive Markers:
The IHC profile depends on the subtype
For DLBCL, cells are positive for B-cell markers like CD20, CD79a, and PAX5
A subset expresses BCL2, BCL6, and MUM1
For follicular lymphoma, cells are positive for CD20, CD10, and BCL2
MALT lymphoma is positive for CD20 and CD79a but negative for CD5 and CD10.
Negative Markers:
Negative for cytokeratins, which distinguishes it from carcinoma
E-cadherin is also negative.
Diagnostic Utility:
IHC is essential for diagnosis and subtyping of the lymphoma
A panel of lymphoid markers is required
Cytokeratin stains are crucial to rule out a poorly differentiated carcinoma.
Molecular Subtypes:
For DLBCL, molecular subtyping into GCB and non-GCB (ABC) can be done using IHC algorithms (Hans algorithm).
Molecular/Genetic
Genetic Mutations:
The genetic alterations depend on the lymphoma subtype
For follicular lymphoma, the characteristic translocation is t(14;18) involving the BCL2 gene
For MALT lymphoma, t(11;18) can be seen.
Molecular Markers:
Clonal rearrangements of the immunoglobulin heavy and light chain genes can be detected by PCR.
Prognostic Significance:
The prognosis depends on the lymphoma subtype and stage
DLBCL of the breast is considered to have a relatively aggressive course with a tendency for CNS relapse
Low-grade lymphomas like MALT lymphoma have a more indolent course.
Therapeutic Targets:
Treatment is based on the lymphoma subtype and typically involves chemotherapy and immunotherapy (e.g., R-CHOP for DLBCL)
Radiation may be used for localized disease
Surgery is mainly for diagnosis.
Differential Diagnosis
Similar Entities:
Poorly differentiated carcinoma
Medullary carcinoma (which has a prominent lymphocytic infiltrate)
Chronic lymphocytic mastitis
Metastatic lymphoma.
Distinguishing Features:
Carcinomas are positive for cytokeratins
Medullary carcinoma has malignant epithelial cells mixed with lymphocytes
Chronic mastitis has a polyclonal lymphoid infiltrate without atypia
Distinguishing primary from secondary lymphoma requires clinical staging.
Diagnostic Challenges:
The main challenge is distinguishing lymphoma from a poorly differentiated carcinoma, especially on small biopsies
A broad IHC panel is essential.
Rare Variants:
Rare subtypes like Burkitt lymphoma, T-cell lymphomas, and Hodgkin lymphoma can also occur as PBL.
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]