Definition/General
Introduction:
Endometrial lymphoma is a rare hematologic malignancy involving the uterus
It represents 1-2% of all extranodal lymphomas
Primary uterine lymphoma is extremely rare
Most cases are secondary involvement from systemic lymphoma.
Origin:
May arise from lymphoid tissue in endometrium
MALT lymphoma from mucosa-associated lymphoid tissue
Can develop from chronic inflammation
Most commonly B-cell origin
Secondary involvement more common than primary.
Classification:
Classified according to WHO classification of lymphomas
B-cell lymphomas (90%)
T-cell lymphomas (10%)
Primary vs secondary distinction important
MALT lymphoma most common primary type.
Epidemiology:
Peak incidence in 6th-7th decades
Postmenopausal women predominantly affected
Immunocompromised patients at higher risk
Associated with chronic inflammation
EBV association in some cases.
Clinical Features
Presentation:
Abnormal uterine bleeding (most common)
Postmenopausal bleeding
Enlarged uterus
Pelvic mass
B symptoms (fever, night sweats, weight loss)
Lymphadenopathy.
Symptoms:
Heavy menstrual bleeding
Pelvic pain
Abdominal distension
Constitutional symptoms
Fatigue and weakness
Systemic symptoms if disseminated.
Risk Factors:
Immunosuppression (HIV, transplant)
Autoimmune diseases
Previous chemotherapy
EBV infection
Chronic inflammation
Advanced age.
Screening:
No specific screening recommendations
High suspicion in immunocompromised patients
Staging workup essential
Bone marrow biopsy
Imaging studies.
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Gross Description
Appearance:
Tan-gray, fleshy mass
Soft consistency
May be polypoid or diffusely infiltrative
Fish-flesh appearance
Areas of necrosis variable.
Characteristics:
Size ranges from 2-15 cm
Homogeneous cut surface
Tan-white color
May show cystic areas
Soft, brain-like consistency.
Size Location:
Variable size presentation
Involves endometrial cavity
May extend to myometrium
Diffuse involvement possible
Multifocal disease common.
Multifocality:
Often multifocal at presentation
Lymph node involvement common
Systemic disease frequent
Bone marrow involvement possible.
Microscopic Description
Histological Features:
Diffuse sheets of atypical lymphoid cells
Monotonous population
High nuclear-to-cytoplasmic ratio
Mitotic activity variable
Crush artifacts common
May show reactive lymphoid follicles.
Cellular Characteristics:
B-cell: Large cells with vesicular nuclei
Prominent nucleoli
Abundant cytoplasm
T-cell: Smaller cells with irregular nuclei
Scant cytoplasm
Lymphoglandular bodies.
Architectural Patterns:
Diffuse infiltration
Nodular pattern (follicular lymphoma)
Marginal zone pattern (MALT)
Mantle zone pattern
Angioinvasion common.
Grading Criteria:
Low-grade: Small cells, low mitotic rate
Intermediate-grade: Mixed cellularity
High-grade: Large cells, high mitotic rate, extensive necrosis.
Immunohistochemistry
Positive Markers:
B-cell: CD20
CD79a
PAX5
T-cell: CD3
CD43
CD45 (LCA)
BCL-2 (follicular)
BCL-6 (germinal center)
MUM-1 (plasma cell).
Negative Markers:
Cytokeratins (negative)
Vimentin (may be positive)
S-100 (negative)
Desmin (negative)
CD117 (negative).
Diagnostic Utility:
CD20 positivity confirms B-cell origin
CD3 positivity confirms T-cell origin
CD45 positivity confirms hematopoietic origin
Flow cytometry helpful for typing
Clonality studies important.
Molecular Subtypes:
t(14;18) BCL2-IGH (follicular)
t(11;14) CCND1-IGH (mantle cell)
t(8;14) MYC-IGH (Burkitt)
API2-MALT1 (MALT lymphoma).
Molecular/Genetic
Genetic Mutations:
TP53 mutations (aggressive lymphomas)
MYC rearrangements (high-grade)
BCL2 rearrangements (follicular)
BCL6 rearrangements
MALT1 rearrangements.
Molecular Markers:
Clonal immunoglobulin gene rearrangements
T-cell receptor rearrangements
High Ki-67 (aggressive types)
p53 overexpression
MYC expression.
Prognostic Significance:
Histological grade most important
Stage at presentation
IPI score (International Prognostic Index)
MYC/BCL2 double hit indicates poor prognosis
TP53 mutations poor prognostic factor.
Therapeutic Targets:
CD20-targeted therapy (rituximab)
BTK inhibitors (ibrutinib)
PI3K inhibitors
BCL-2 inhibitors (venetoclax)
Immunotherapy (CAR-T cells)
Combination chemotherapy.
Differential Diagnosis
Similar Entities:
Undifferentiated carcinoma
Small round cell sarcoma
Endometrial stromal sarcoma
Reactive lymphoid hyperplasia
Metastatic lymphoma.
Distinguishing Features:
Carcinoma: Cytokeratin positive
Sarcoma: Specific markers positive
Lymphoma: CD45 positive
Lymphoma: Lymphoid markers positive
Reactive: Polyclonal population.
Diagnostic Challenges:
Distinguishing primary from secondary lymphoma
Recognizing lymphoma vs reactive infiltrate
Subtyping requires immunophenotyping
Flow cytometry helpful
Clonality studies important.
Rare Variants:
MALT lymphoma
Diffuse large B-cell lymphoma
Follicular lymphoma
Mantle cell lymphoma
T-cell lymphomas (rare).
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, soft/fleshy consistency
Diagnosis
Lymphoma involving the endometrium
WHO Classification
[Specific lymphoma subtype per WHO classification]
Histological Features
Diffuse infiltrate of [small/large] lymphoid cells, mitoses: [count]/10 HPF
Immunophenotype
[B-cell/T-cell/NK-cell] phenotype
Immunohistochemistry
Lineage: CD20 [+/-], CD3 [+/-], CD45 [+/-]
Specific markers: [list relevant markers and results]
Ki-67: [percentage]%
Clonality Studies
Clonal rearrangement: [detected/not detected/not performed]
Staging
Primary vs secondary: [assessment], stage: [if known]
Final Diagnosis
[Primary/Secondary] [lymphoma subtype] involving endometrium