• Direct extension from mediastinal/ hilar nodes (via bronchial lymphatics) or origination in bronchial mucosal lymphatic tissue


Pathology (Working formulation/ classification usually requires having adequate lymph node architecture on biopsy):
-Low-grade NHL (usually widespread in nodes/ marrow and less likely to be extranodal):
1) Small, lyphocytic (diffuse)
2) Small cleaved cell (follicular)
3) Mixed small cleaved and large cell (follicular)
-Intermediate grade NHL (more likely to be localized at time of diagnosis and to be extranodal):
1) Large cell (follicular)
2) Small cleaved cell (diffuse)
3) Mixed small cleaved cell and large cell (diffuse)
4) Large cell, cleaved and noncleaved (diffuse)
-High-grade NHL (more likely to be localized at time of diagnosis and to be extranodal):
1) Large cell, immunoblastic (diffuse)
2) Lymphoblastic
3) Small noncleaved cell (diffuse): includes Burkitt’s and Non-Burkitt’s types


FOB: BAL/ TBB/ EBB may be useful
FNA: may be useful (especially with immunohistochemical stains, markers)
OLB: may be necessary
Cytologic studies: for cell surface markers/ 14:18 translocation (for follicular types) may be useful for diagnosis of NHL

CXR/Chest CT Pattern:
-Low-grade patterns:
1) “Alveolar” pattern: alveolar parenchymal infiltrates
-May also have effusion
2) “Bronchovascular-lymphangitic” pattern: lymphangitic mets
-May also have effusion
3) “Nodular” pattern: isolated parenchymal lung nodules (round, ovoid, triangular, polyhedral with fuzzy border and no lobar predilection, no calcification/ large cell types may produce “cyst-like” lesions, mimicking cavitation)
-Most common CXR pattern

-Intermediate/ high-grade patterns:
1) Bulky mediastinal adenopathy: usually bilateral
2) Nodular pattern (see above)
3) Isolated pleural mass:
4) Isolated bone mass:

Liver Bx/ BM Bx/ Nodal Bx: may be necessary for staging

Clinical patterns (systemic symptoms, like fever, night sweats, and weight loss, may accompany below presentations):

1) Solitary lung mass: may be asymptomatic
2) Diffuse lung involvement (typically “alveolar” or “lymphangitic” patterns): cough/ dyspnea/ chest pain
3) Lung lesions near airway: cough/ hemoptysis obstructive symptoms
4) Pleural effusion:

Immunocompromised hosts:
-Post-transplant NHL: see above
-Congenital immunodefic-iency-associated NHL: usually int/ high-grade B-cell type with extranodal disease
-AIDS-associated NHL: see above

Complications: paraneo-plastic syndromes (hypercal-cemia/ autoimmune/ etc.)

Lymphoma Involving Upper Airway

  • Physiology: lymphomatous infiltration of vocal cords
  • Clinical: upper airway obstruction (see [[Obstructive Lung Disease]])

Post-Transplant Lymphoma/Lymphoproliferative Disease

  • Physiology: possibly EBV-related
  • Clinical: usually widespread with aggressive course
  • Treatment: Cessation of immunosup-pressives/ Anti-B-cell monoclonal Ab: may slow course in some cases

HIV-Associated Lymphoma

  • NHL is the 2nd most common neoplasm in AIDS (next to KS)
  • Occur more commonly in homosexual AIDS cases than in IVDA/ heterosexual AIDS cases (similar to KS)
  • Incidence: increasing
  • In AIDS, intrathoracic involvement by KS is more common than by NHL
  • Physiology: possibly EBV-related (17 reported cases associated with EBV)
  • Pathologic Pattern: usually intermediate/ high-grade B-cell type with extra nodal disease
  • Diagnosis
    • FNA/Bx of extrathoracic site: common diagnostic method
    • FOB: TBB/ TBNA may be useful
    • TTNA: may be useful
    • Pleural Bx: few cases diagnosed by this method
    • CXR/Chest CT Pattern:
      • Pleural effusion (most common, occur in 50% of cases):
      • Hilar/ mediastinal adenopathy (25% of cases): isolated intrathor-acic adenopathy without extratho-racic nodal involvement is rare
      • Diffuse reticulonodular infiltrates (25% of cases): usually bilateral, heterogeneous
      • Single, multiple lung nodules (distinct margins, as opposed to fuzzy margins of KS nodules): more common in AIDS-related NHL than in normal NHL
  • Clinical
    • Usually have disseminated extranodal disease at time of diagnosis
    • Lung involvement (0-25% at time of diagnosis, higher at autopsy):
    • Pericardial/myocardial involvement: may occur
  • Treatment
    • Poor response to and poor tolerance of therapy
    • XRT: palliative for airway lesions/compressive lesions
  • Prognosis: median survival <1 year


-Stage 1/2 (expect remissions without cure): local XRT or XRT + chemo
-Diffuse lung involvement: favor chemo
-Stage 3/4: chemo (start when symptomatic: earlier interven-tion does not prolong survival)

Intermediate/ high-grade:
-Stage 1: XRT (65-100% 5-year survival, even with extranodal disease)
-Stage 2: chemo + XRT (>80% 5-year survival)
-Stage 3/4: combination chemo with XRT to local bulky sites

Complications of treatment: NHL, Sarcoma, Lung cancer (in irradiated field), Bladder cancer, Leukemia, Osteosarcoma may occur even years later

Post-treatment recurrence: may occur in nodal / extranodal sites
-May involve new sites or sites of previous bulky disease
-Low-grade: usually recur (may recur as high-grade types)
-Intermediate/ high-grade: recur rapidly (most diffuse large cell recurrences occur in first 3 years after first remission)


  • Worse for intermediate/ high-grade NHL (but these are only types considered to be curable/ although chemo has equal responsiveness for low-grade and intermediate/ high-grade types)
  • Extranodal disease does not change prognosis