Primary Types of Laryngeal Lymphoma
Primary laryngeal lymphoma is an extremely rare extranodal malignancy accounting for less than 1% of all primary laryngeal neoplasms, with diffuse large B-cell lymphoma (DLBCL) being the most common histologic subtype, followed by extranodal NK/T-cell lymphoma (nasal-type) and MALT-type marginal zone B-cell lymphoma. 1, 2, 3
Most Common Histologic Types
Diffuse Large B-Cell Lymphoma (DLBCL)
- DLBCL represents the predominant histologic subtype of primary laryngeal lymphoma in reported cases 1, 2, 4
- The tumor cells are CD20-positive, which is present in 86-100% of cases 5, 2
- Immunophenotyping typically shows positivity for PAX5, BCL2, BCL6, and MUM1, with variable expression of CD10 4
- DLBCL can present with unusual manifestations including laryngeal stenosis, subglottic involvement, or even tracheal fistula formation 6, 4
Extranodal NK/T-Cell Lymphoma, Nasal-Type
- This represents an extremely aggressive subtype that rarely involves the larynx, with most cases occurring in the nasal cavity 3
- The typical immunophenotype includes CD20-, CD2+, cytoplasmic CD3ε+ (surface CD3-), CD56+, with EBV-EBER positivity 7, 3
- Cytotoxic granule proteins (TIA1, perforin, granzyme B) are usually expressed 7
- Primary laryngeal involvement carries a poor prognosis even when diagnosed in localized stages, with rapid progression despite initial chemotherapy response 3
MALT-Type Marginal Zone B-Cell Lymphoma
- MALT lymphoma represents one of the recognized but less common subtypes affecting the larynx 3
- This indolent B-cell lymphoma accounts for 5% of all NHL cases in general populations 8
Rare Composite Presentations
Composite Lymphoma
- The first reported case of primary laryngeal composite lymphoma consisted of both DLBCL and peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) occurring simultaneously 6
- This extremely rare presentation can manifest with atypical clinical features including fistula formation, esophageal diverticulum, and neck abscess without a discrete mass 6
Critical Diagnostic Considerations
Biopsy Requirements
- Excisional or incisional lymph node biopsy is mandatory for definitive diagnosis; fine needle aspiration is insufficient 8
- Multiple deep biopsies may be required, as superficial laryngeal biopsies can show only crush artifacts or insufficient tissue 1, 4
- In difficult cases, diagnosis may ultimately require biopsy of adjacent lymph nodes that appear weeks to months after initial presentation 1
Essential Immunophenotyping
- All cases require comprehensive immunophenotyping to distinguish B-cell from T-cell/NK-cell lineage 9, 8
- For B-cell lymphomas: CD20, CD19, PAX5, BCL2, BCL6, CD10, MUM1, cyclin D1, and kappa/lambda light chains 4
- For T-cell/NK-cell lymphomas: CD3 (surface and cytoplasmic), CD2, CD4, CD5, CD7, CD8, CD56, TCRαβ, TCRγδ 7, 3
- EBV-EBER in situ hybridization is critical for NK/T-cell lymphoma diagnosis 7, 3