What is the management approach for an adult patient with primary laryngeal lymphoma, specifically comparing B cell (B-cell) and T cell (T-cell) types?

Management of Primary Laryngeal Lymphoma: B-Cell vs T-Cell Types

For primary laryngeal lymphoma, B-cell types (predominantly diffuse large B-cell lymphoma) should be treated with systemic R-CHOP chemotherapy for 6-8 cycles with or without involved-field radiation therapy, achieving excellent outcomes, whereas T-cell and NK/T-cell laryngeal lymphomas carry significantly worse prognosis and require more aggressive multiagent chemotherapy, though optimal regimens remain poorly defined. 1, 2, 3

Critical Diagnostic Distinction

Laryngeal lymphoma must be distinguished from squamous cell carcinoma of the larynx, as they require fundamentally different treatment approaches. 1 Squamous cell carcinoma is managed with surgery, radiation, or chemoradiation, whereas lymphoma requires systemic chemotherapy-based protocols. 1, 4

Diagnostic Challenges

• Multiple biopsies may be required to establish the diagnosis, as initial samples are often inadequate or show extensive necrosis. 2, 3
• Deep biopsies including the edges of lesions increase diagnostic yield. 4, 2
• Comprehensive immunophenotyping is mandatory to distinguish B-cell from T-cell lineage. 4
• For B-cell lymphomas: CD20 positivity confirms B-cell lineage. 4, 5
• For T/NK-cell lymphomas: typical immunophenotype includes CD2+, surface CD3-, cytoplasmic CD3ε+, CD56+, with EBV-EBER positivity. 4

B-Cell Laryngeal Lymphoma (Predominantly DLBCL)

Standard Treatment Approach

R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) for 6-8 cycles is the primary treatment. 1, 2, 5

Treatment options include:

• 6-8 cycles of R-CHOP alone (preferred for most patients) 1, 2
• 3 cycles of R-CHOP followed by involved-field radiation therapy (alternative approach) 2
• For elderly patients with cardiac dysfunction: R-COP (omitting doxorubicin) at reduced doses may be considered. 2

Staging Requirements

Complete systemic staging is mandatory before treatment: 1

• PET-CT scan for whole-body disease assessment 1
• Bone marrow biopsy 1
• Complete laboratory evaluation per lymphoma staging protocols 1

Expected Outcomes

B-cell laryngeal lymphomas have favorable prognosis with appropriate chemotherapy-based treatment. 2, 5 Stage IE disease can achieve complete resolution with standard R-CHOP therapy. 5

Relapsed/Refractory B-Cell Disease

For patients with primary refractory or early relapsed DLBCL after initial therapy:

• CAR T-cell therapy (axicabtagene ciloleucel or lisocabtagene maraleucel) is now recommended as second-line therapy for fit patients. 4, 6
• Autologous stem cell transplant (ASCT) is appropriate only for chemosensitive disease in fit patients. 6
• For transplant-ineligible patients: lisocabtagene maraleucel is a reasonable option. 6
• Alternative salvage regimens include gemcitabine-based regimens with rituximab, bendamustine with rituximab, or lenalidomide with rituximab (particularly for non-germinal center B-cell subtype). 4

T-Cell and NK/T-Cell Laryngeal Lymphoma

Critical Prognostic Information

T-cell and NK/T-cell laryngeal lymphomas carry significantly worse prognosis compared to B-cell types, with most patients dying within 32 months despite treatment. 3

Treatment Approach

More aggressive multiagent chemotherapy should be considered, though optimal regimens remain controversial due to rarity. 3

• Conventional chemotherapy or radiotherapy alone has not been effective. 3
• NK/T-cell lymphomas are predominantly extranodal and often EBV-associated. 4
• Treatment should follow protocols for extranodal NK/T-cell lymphoma rather than standard DLBCL regimens. 4

Diagnostic Considerations for T/NK-Cell Types

• Diagnosis is particularly challenging and often delayed. 3
• Necrosis is very common in biopsies; multiple biopsies from lesion edges are essential. 4, 3
• Immunophenotyping must include: CD2, CD3 (surface and cytoplasmic), CD4, CD5, CD7, CD8, CD56, and EBV-EBER. 4
• Cytotoxic granule proteins (TIA1, perforin, granzyme B) are usually expressed. 4

Multidisciplinary Management Requirements

The treatment team must include: 1

• Medical oncology/hematology (primary management) 1
• Radiation oncology 1
• Pathology (for accurate diagnosis and immunophenotyping) 1
• Otolaryngology 1

Common Pitfalls to Avoid

• Do not treat laryngeal lymphoma with larynx-preservation surgery or chemoradiation protocols designed for squamous cell carcinoma. 1, 4 This represents a fundamental treatment error.
• Do not accept inadequate biopsy specimens—repeat biopsies are often necessary for diagnosis. 2, 3
• Do not delay systemic staging—laryngeal lymphoma requires complete staging workup before treatment initiation. 1
• Do not assume all laryngeal lymphomas have similar prognosis—T-cell and NK/T-cell types have dramatically worse outcomes than B-cell types. 3

Rare Composite Presentations

Primary laryngeal composite lymphoma (containing both B-cell and T-cell components) has been reported but is exceptionally rare. 7 Such cases require treatment addressing the most aggressive component, typically following protocols for the T-cell component given its worse prognosis. 7