What are the clinical features and diagnostic differences between B-cell and T-cell primary laryngeal lymphoma in an adult patient?

Clinical Features and Diagnostic Differences Between B-Cell and T-Cell Primary Laryngeal Lymphoma

Primary laryngeal lymphoma is exceedingly rare (<1% of laryngeal malignancies), with B-cell subtypes (particularly DLBCL) being far more common than T/NK-cell variants, and the two types differ fundamentally in their immunophenotypic profiles, clinical aggressiveness, and prognosis. 1, 2, 3

Epidemiology and Frequency

• B-cell laryngeal lymphomas represent the vast majority of cases, with diffuse large B-cell lymphoma (DLBCL) being the most common histologic subtype, followed by MALT-type marginal zone B-cell lymphomas and lymphoplasmacytoid lymphomas 1, 4, 3
• T/NK-cell laryngeal lymphomas are extremely rare, with only isolated case reports in the literature, making them exceptional even among the already uncommon primary laryngeal lymphomas 2, 3

Clinical Presentation Differences

B-Cell Laryngeal Lymphoma

• Patients typically present with dysphagia and hoarseness as primary symptoms, often with a relatively brief clinical history 4
• Supraglottic involvement is common, though any laryngeal subsite can be affected 4
• Clinical stage at presentation is often localized (Stage IE) in many cases 3
• The clinical course tends to be less aggressive compared to T/NK-cell variants, with better response to standard therapies 3

T/NK-Cell Laryngeal Lymphoma

• Presents with involvement of the epiglottis and aryepiglottic folds, often with associated cervical lymphadenopathy at diagnosis 2
• Clinical behavior is extremely aggressive, with rapid local progression even after initial treatment response 2
• Prognosis is poor, with median survival measured in months rather than years, even when diagnosed in localized stages 2
• Extranasal T/NK-cell lymphomas (including laryngeal) have worse outcomes than their nasal cavity counterparts 2

Diagnostic Immunophenotypic Markers

B-Cell Laryngeal Lymphoma

• CD19 positivity is the hallmark marker, along with CD22 and cytoplasmic CD79a, establishing B-cell lineage 5, 6
• CD20 positivity confirms B-cell lineage and has therapeutic implications for rituximab-based treatment 6, 4
• TdT is typically positive in precursor B-cell lymphomas but negative in mature B-cell lymphomas (Burkitt type) 7, 5
• Surface immunoglobulin expression distinguishes mature B-cell lymphoma from precursor forms 5
• Comprehensive immunophenotyping must be performed on adequate tissue samples to establish definitive diagnosis 6, 4

T/NK-Cell Laryngeal Lymphoma

• CD2 positivity with surface CD3 negativity is characteristic of NK/T-cell lymphomas 6, 2
• Cytoplasmic CD3ε positivity distinguishes these from true NK-cell neoplasms 6
• CD56 positivity is typical of NK/T-cell lymphomas, nasal type 6, 2
• EBV-EBER positivity is characteristic, as these lymphomas are predominantly EBV-associated 6, 2
• Immunophenotyping panel must include CD2, CD3 (both surface and cytoplasmic), CD4, CD5, CD7, CD8, CD56, and EBV-EBER for accurate diagnosis 6

Diagnostic Challenges and Pitfalls

• Diagnosis is frequently delayed or missed because laryngeal lymphomas lack distinctive clinical or gross pathologic features that differentiate them from squamous cell carcinoma 2, 4
• Multiple biopsies may be required to obtain sufficient tissue for diagnosis, as superficial biopsies often yield inadequate material 1
• Deep biopsies including the edges of lesions increase diagnostic yield and should be performed under general anesthesia when initial attempts fail 6, 1
• Fine needle aspiration alone is not acceptable for initial diagnosis of lymphoma, as the revised WHO classification requires both morphology and comprehensive immunophenotyping 7
• Core biopsy combined with FNA and ancillary techniques (flow cytometry, immunohistochemistry, FISH, PCR for gene rearrangements) may be sufficient in selected circumstances when lymph nodes are not easily accessible 7
• In one reported case, the diagnosis was only established from a cervical lymph node biopsy that appeared two months after multiple failed laryngeal biopsies 1

Molecular and Cytogenetic Characterization

• Chromosomal aberrations using banded karyotyping should be performed when possible to guide treatment strategy 4
• Flow cytometry provides essential immunophenotypic profiles that distinguish B-cell from T-cell lineage and identify therapeutic targets 4
• Gene expression profiling and copy number alteration analysis can identify specific molecular subgroups, though these are not part of standard workup 7
• PCR for immunoglobulin heavy chain (IGHV) and T-cell receptor (TCR) gene rearrangements can establish clonality when morphology and immunophenotyping are equivocal 7

Staging and Extent of Disease Evaluation

• Complete systemic staging is mandatory for all laryngeal lymphomas, as they are part of systemic disease processes 6
• PET-CT imaging is essential for whole-body disease assessment and to distinguish localized from disseminated disease 6, 4
• Bone marrow biopsy is required as part of comprehensive staging workup 6
• Laboratory evaluation must include complete blood count, LDH, and comprehensive metabolic panel 7
• Careful periodic evaluation is imperative even after complete remission, as dissemination to other extranodal sites may occur, particularly in low-grade B-cell lymphomas 3

Treatment Implications Based on Lineage

B-Cell Laryngeal Lymphoma

• R-CHOP chemotherapy for 6-8 cycles is the primary treatment for DLBCL, the most common laryngeal lymphoma subtype 6, 1
• Rituximab-based regimens are standard due to CD20 positivity in B-cell lymphomas 6, 1
• Involved-field radiation therapy may be combined with chemotherapy, particularly after 3 courses of R-CHOP 1
• Complete remission rates are high with appropriate systemic therapy 3

T/NK-Cell Laryngeal Lymphoma

• Treatment must follow protocols for extranodal NK/T-cell lymphoma rather than standard DLBCL regimens 6
• Standard R-CHOP is inappropriate for T/NK-cell lymphomas, as they lack CD20 expression 6
• Prognosis remains poor even with aggressive multimodal therapy, with rapid progression common 2

Critical Distinction from Squamous Cell Carcinoma

• Laryngeal lymphoma must be distinguished from squamous cell carcinoma, as they require fundamentally different treatment approaches 6, 4
• Squamous cell carcinoma is treated with surgery, radiation, or chemoradiation, while laryngeal lymphoma requires systemic chemotherapy-based protocols 6
• The dictum to obtain reliable tissue diagnosis before initiating definitive therapy cannot be overemphasized, as misdiagnosis leads to inappropriate and potentially harmful treatment 4