Diagnosis and Treatment of Lymphoma
Diagnostic Approach
Lymphoma diagnosis requires an excisional lymph node biopsy providing adequate tissue for histopathological examination and immunohistochemistry studies according to WHO classification 1, 2.
Tissue Acquisition
- Surgical excisional lymph node biopsy is mandatory, providing both fresh frozen and formalin-fixed samples for comprehensive analysis 1, 2
- Fine needle aspiration or core biopsies are inadequate for proper diagnosis and should only be used in rare emergency situations requiring immediate treatment 1, 2
- Immediate processing by an experienced pathology institute must be guaranteed to ensure diagnostic quality 1
Staging Workup
Once tissue diagnosis is confirmed, complete staging includes 1, 2:
- CT scan of thorax, abdomen, and pelvis
- Bone marrow aspirate and biopsy
- Complete blood count, LDH, uric acid levels
- HIV and hepatitis B/C screening
- Ann Arbor staging system classification with notation of bulky disease 1, 2
Prognostic Assessment
- For follicular lymphoma: use Follicular Lymphoma International Prognostic Index (FLIPI) 1, 2
- For large cell lymphomas: use International Prognostic Index (IPI) 2
Treatment by Stage and Histology
Limited Stage (I-II) Follicular Lymphoma
Radiotherapy is the treatment of choice with curative potential for limited-stage disease 1, 3.
- Extended or involved field radiotherapy at 30-40 Gy (or 24 Gy per more recent recommendations) should be administered 1, 3
- For patients with large tumor burden, systemic therapy may be applied before radiation 1
Advanced Stage (III-IV) Follicular Lymphoma
Treatment should be initiated only upon occurrence of symptoms including B-symptoms, hematopoietic impairments, bulky disease, or lymphoma progression 1, 3.
First-Line Therapy for Symptomatic Disease
- Rituximab or obinutuzumab combined with chemotherapy (bendamustine or CHOP) is the standard approach 1, 3
- Rituximab maintenance every 2 months for 2 years following immunochemotherapy is recommended 3
- Alternative single-agent options (fludarabine, bendamustine, chlorambucil, or rituximab monotherapy) remain available for patients with contraindications to intensive immunochemotherapy 1
Watchful Waiting
- Asymptomatic patients with low tumor burden should be managed with observation, as spontaneous regressions occur in 15-20% of cases 1, 3
Large Cell Non-Hodgkin Lymphoma
R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) given every 21 days for 8 cycles is the standard treatment for CD20+ large-cell NHL of all stages 2, 4.
- For limited-stage disease: abbreviated chemotherapy followed by involved-field radiation therapy 2, 4
- For advanced-stage disease: full course of R-CHOP chemotherapy 2, 4
Hodgkin Lymphoma
Treatment differs from non-Hodgkin lymphoma 5, 6:
- Early-stage disease: combined-modality therapy with abbreviated chemotherapy (ABVD: doxorubicin, bleomycin, vinblastine, dacarbazine) followed by involved-field radiation 4, 5
- Advanced-stage disease: prolonged combination chemotherapy with ABVD, Stanford V, or BEACOPP regimens 4, 5
Response Evaluation and Monitoring
Radiological assessment should be performed after every 2-3 cycles of therapy and after completion of chemotherapy 1, 2.
- Patients with incomplete or inadequate response require evaluation for early salvage regimens 1, 2
- PET-CT after induction identifies patients with adverse prognosis in follicular lymphoma 3
Follow-Up Protocol
Clinical Surveillance
- History and physical examination every 3 months for 2 years, then every 6 months for 3 additional years, then annually 1, 2
- Special attention to transformation and secondary malignancies including secondary leukemia 1, 2
Laboratory Monitoring
- Blood count at 3,6,12, and 24 months, then only as needed for suspicious symptoms 1, 2
- Thyroid function evaluation at 1,2, and 5 years for patients receiving neck irradiation 1
Imaging Surveillance
Critical Management Considerations
Relapsed/Refractory Disease
- For early relapse (<12-24 months): use non-cross-resistant regimen 3
- For rituximab-refractory cases: obinutuzumab-bendamustine plus obinutuzumab maintenance is recommended 3
- High-dose chemotherapy with autologous stem cell transplant should be considered for patients with brief first remissions 3, 5
Important Safety Measures
- In patients with positive hepatitis B serology, prophylactic antiviral medication up to 2 years beyond last rituximab exposure is mandatory 3
- At suspected relapse or progression, obtain confirmatory biopsy 3
- Adequate hydration during chemotherapy to reduce urinary tract toxicity 7
Treatment-Related Toxicities
Common long-term complications include 4: