Contents
Introduction
Non-hodgkin lymphoma is a type of lymphoma characterized by the absence of Reed-Sternberg cells.
Lymphomas are a heterogeneous group of malignant tumours of the haematopoietic system and are characterized by the aberrant proliferation of mature lymphoid cells or their precursors.
- Lymphomas can be divided into 2 major entities:
- Hodgkin’s lymphoma (HL) (10%)
- Non-Hodgkin’s lymphoma (NHL) (90%)
Classification
Non-hodgkin lymphoma (NHL) subtypes:
Characterized by the absence of Reed-Sternberg cells.
- Follicular lymphoma (F-NHL) (22.0%)
- Marginal zone lymphoma (MZL) (9.0%)
- Mantle cell lymphoma (MCL) (6.0%)
- Diffuse large B-cell lymphoma (DLBCL) (M/C worldwide & India, 35.0%)
- Burkitt Lymphoma (1.0%)
- T-cell lymphoma (7.0%)
International Working Group classification (old):
On the basis of morphology and clinical behaviour:
- Low grade: CLL/SLL, follicular lymphoma
- Intermediate grade: Mantle cell and marginal cell lymphoma
- High grade: Diffuse large B-cell lymphoma (DLBCL), Burkitt’s lymphoma
- M/aggressive NHL: DLBCL
- M/rapidly progressive human tumour: Burkitt’s lymphoma
- Pediatric NHLs are high grade and aggressive
Epidemiology
- All NHLs are more common in males (except MALT lymphomas)
Aetiology
Genetic mutation:
| Lymphoid neoplasm | Most characteristic translocation |
| Mantle-cell lymphoma | t (11;14) |
| Follicular lymphoma | t (14;18) |
| Diffuse large B-cell lymphoma | t (14;18) |
| Burkitt lymphoma | t (8:14), t (2;8), t (8;22) |
| MALT lymphoma | t (11;18) |
Pathophysiology
All Non-Hodgkin’s lymphomas involve white pulp of spleen except:
- Hairy cell leukemia
- Hepatosplenic lymphoma
Origin of mature B cell lymphomas:
Clinical features
Painless lymphadenopathy (enlarging over months):
- M/C sites: Mediastinal/neck nodes (60%) >> splenic > axillary > abdominal > hilar/inguinofemoral
- Bulky disease: Transverse diameter of tumor mass > 10 cm and confers a poorer prognosis in early-stage patients.
B-symptoms:
- Fevers, chills, night sweats or unexplained weight loss >10% of body weight
- Frequent in patients with advanced-stage or bulky disease
Extranodal involvement
GIT > skin > CNS
- Gastrointestinal lymphoma (M/C extranodal NHL, 5–20% cases)
- Primary cutaneous lymphomas (PCL) (#2 M/C extranodal NHL)
- Priamry CNS lymphoma
Gastrointestinal lymphoma: Stomach > Small intestine > Colon > Esophagus
- M/C extranodal site in immunocompromised (except HIV cases):
- MALTomas: Stomach
- Follicular lymphoma: Duodenum
- Burkitt’s lymphoma: Terminal ileum
- Mantle cell lymphoma: Terminal ileum, Jejunum, Colon
- Enteropathy-associated T cell lymphoma (EATL): Jejunum
Primary cutaneous lymphomas (PCL)
- M/C type: Mycosis fungoides (MF) > Sezary syndrome
Central Nervous system:
- M/C extranodal site in HIV
- M/C histological subtype in HIV: Diffuse large B cell lymphoma (DLBCL)
- Primary CNS lymphoma (histologically, DLBCL) is one of the AIDS-defining malignancies
Complications
Tumour lysis syndrome (TLS) (in aggressive tumours):
Potential complication of therapy due to rapid growth rates of tumour cells caused by release of cellular products overwhelming the kidneys’ excretory capacity.
- Kidney damage → Electrolyte imbalances (hyperkalemia, hyperphosphatemia, hyperuricemia) → Kidney failure
- ℞: IV hydration, hypouricemic agents (allopurinol, rasburicase) & dialysis (if indicated)
Diagnosis
Core-needle/excisional biopsy (no FNAC):
Immunophenotype:
| B cell precursors | Derived lymphomas/leukaemia | Immunophenotype |
| Pro-B cell | Pro-B cell ALL | CD34, CD19, CD79a |
| Pre-B cell | Pre-B cell ALL | CD19, CD79a, CD10, Tdt, Cytoplasmic Ig |
| Mature B cell | CLL/SLL | CD19, CD79a,CD 20, CD21, CD22, surface IgM, CD 23, CD5 |
| Mantle zone | Mantle zone lymphoma | CD19, CD79a,CD 20, CD21, CD22, surface IgM, CD5 |
| Germinal center/Follicular center | Follicular lymphoma
Diffuse large B-cell lymphoma Burkitt lymphoma |
CD 79a, CD 79b, CD 19, CD 20, CD,21,CD22, CD10, CD 23, Bcl-2
CD10, Cd23, Bcl-6 CD19, CD20, CD22, CD79a, CD10, Bcl-6 |
| Memory B cells | Extranodal marginal zone lymphoma | CD19, CD79a,CD 20, surface Ig |
Ann Arbor staging system with Cotswolds modification:
Staging system for lymphomas, both in Hodgkin’s lymphoma (formerly designated Hodgkin’s disease) and non-Hodgkin lymphoma (abbreviated NHL)
- Principal stages (determined by location):
- Stage I: Single site (nodal/extranodal)
- Stage II: ≥ 2 LN on same side of diaphragm (number of anatomic sites should be indicated in a suffix: e.g. II2)
- Stage III: LN/structures on both sides of diaphragm:
- III1: With/without splenic, hilar, celiac or portal nodes
- III2: With paraaortic, iliac or mesenteric nodes
- Stage IV: Diffuse, disseminated, several extranodal ± nodal involvement
- Modifiers (can be appended to some stages):
- A: No B symptoms
- B: B symptoms present
- S (spleen)
- E “extranodal”
- X (largest deposit is >10 cm large (“bulky disease”), or whether the mediastinum is wider than ⅓ of the chest on a chest X-ray)
St.Jude’s/Murphy classification: Pediatric NHL
- I: Single tumour site/node extending to GI/mediastinum
- II: Multiple LN involvement (on one side of diaphragm), single GI lesion
- III: Extensive GI involvement (non-resectable) with mediastinal involvement, paraspinal/epidural tumour
- IV: Stage III + CNS/bone marrow involvement
Management
Chemotherapy:
- Indolent cancer: ABVD regimen
- Adriamycin (adv. effect: cardiomyopathy)
- Bleomycin (adv. effect: pulmonary fibrosis)
- Vincristine (adv. effect: peripheral neuropathy)
- Dacarbazine (adv. effect: myelosuppression)
- Aggressive cancer: R-CHOP regimen
- Rituximab
- Cyclophosphamide (adv effect: hemorrhagic cystitis)
- Doxorubicin
- Vincristine (adv. effect: peripheral neuropathy)
- Prednisone
NHL in pregnancy:
- 1st trimester: Termination
- 2nd trimester: CHOP chemotherapy
Prognosis
International prognostic index (IPI):
- Age > 60 years
- ↑ Serum lactate dehydrogenase (LDH)
- Performance status ≥ 2 (ECOG) or ≤70 (Karnofsky)
- Ann Arbor Stage III/IV
- ≥ 2 sites of extranodal involvement