Definition
A.Malignancies that develop from lymph nodes and lymphoid tissues are broadly classified into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).
B.NHL encompasses a diverse group of diseases with more than 50 distinct subtypes, which are further classified by histology and clinical presentation. These various subtypes are determined based on the cells from which they arise (B-cells, T-cells, natural killer cells) or by their degree of indolence versus aggressiveness.
C.Patients with indolent lymphomas typically survive for several years even without therapy. However, patients with aggressive lymphomas may only have months to live.
Incidence
A.NHL is relatively common in the United States with greater than 70,000 new cases each year (accounting for 4.3% of all cancer diagnoses), as compared to approximately 8,000 cases of HL each year.
B.The majority of NHL cases are B-cell neoplasms (85%), whereas T-cell/NK-cell neoplasms account for only 15% of NHLs.
C.The median age at diagnosis is 66, although it is seen in all age groups.
D.Between the years 2004 and 2013, rates of new cases have remained stable, though the rate of mortality has decreased an average of 2.4% each year.
Pathogenesis
A.Tumors associated with NHL originate from lymphoid tissues.
B.Most NHLs come from B-cell expansion.
Predisposing Factors
A.Immunodeficiency states.
B.Epstein–Barr virus (EBV) infection.
C.HIV infection.
D.Human T lymphotropic virus type 1 (HTLV-1) infection.
E.Autoimmune rheumatoid diseases (lupus, Sjögren’s, rheumatoid arthritis).
F.Herbicide/pesticide exposure.
Subjective Data
A.Common complaints/symptoms.
1.Rapidly enlarging lymph nodes (most commonly in neck or abdomen).
2.B Symptoms: Fever greater than 38°C, drenching night sweats, unintentional weight loss of greater than 10% body weight.
B.Common/typical scenario.
1.Other nonspecific symptoms: Malaise, fatigue, chronic pain, early satiety, cough/chest discomfort (seen with mediastinal involvement).
2.Approximately 34% of all patients present with primary extranodal lymphoma at the time of diagnosis; the gastrointestinal (GI) tract is the most common site, followed by the skin.
Physical Examination
A.Vital signs.
B.Head and neck: Facial edema/jugular venous distention (JVD) can indicate superior vena cava syndrome (most commonly seen in primary mediastinal lymphoma).
C.Lymphatics: Cervical, axillary, inguinal, Waldeyer’s ring (tonsils, base of tongue, nasopharynx).
D.Cardiopulmonary: Evaluate for signs of dyspnea/airway obstruction, evidence of malignant pleural effusion (decreased breath sounds/crackles), and signs of pericardial effusion/tamponade.
E.Abdomen: Evaluate for hepatomegaly/splenomegaly and ascites.
F.Neurological: Evaluate for signs of spinal cord compression, altered mental status, memory impairment, or cranial nerve dysfunction.
Diagnostic Tests
A.Laboratory data.
1.Complete blood count (CBC) with differential.
2.Comprehensive metabolic panel (CMP).
3.Magnesium.
4.Phosphorus.
5.Lactate dehydrogenase (LDH).
6.Uric acid.
7.Coagulation studies: Prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time (PTT).
B.Lymph node biopsy.
C.PET/CT scan.
D.Bone marrow biopsy.
E.Lumbar puncture and brain/spine MRI if at risk for central nervous system (CNS) involvement.
F.Formal ophthalmologic examination if at risk for/confirmed CNS involvement (can also rarely be seen in mantle cell lymphoma and marginal zone lymphoma).
G.Hepatitis B and C serologies (risk of reactivation due to Rituxan).
H.HIV screen.
I.+/− serum protein electrophoresis (SPEP).
J.+/− echocardiogram (for patients who will receive an anthracycline).
K.Diagnosis/staging.
1.Definitive diagnosis is confirmed with excisional or core needle biopsy (not fine needle aspiration [FNA]).
2.The Lugano classification system, based on Ann Arbor Staging, is the most widely used classification system employed in NHL.
Differential Diagnosis
A.Solid tumors.
B.Hematological malignancies.
C.Hodgkin’s lymphoma.
Evaluation and Management Plan
A.General plan/therapy.
1.The indicated treatment varies greatly depending on the type of NHL, staging, and age/performance status/comorbidities.
2.A majority of NHL is treated with chemotherapy alone, though there are variants of indolent lymphoma in which watchful waiting is appropriate.
3.For some subtypes, radiation therapy is indicated as monotherapy.
4.Infrequently, surgery is employed for excision of lymphoid tumors.
5.Stem cell transplant (autologous or allogenic) is typically reserved for aggressive/late-stage disease, or for relapsed/refractory NHLs.
B.Acute care issues in lymphomas.
1.Neutropenic fever (see sections on Leukemias).
2.Tumor lysis syndrome (TLS; see sections on Leukemias).
3.Superior vena cava (SVC) syndrome.
a.The obstruction of blood flow through the SVC caused by external lymph node compression or by thrombus within the vena cava, and is most commonly seen associated with cases of primary mediastinal B-cell lymphoma.
b.Clinical presentation most commonly reveals dyspnea, cough, facial swelling, upper extremity edema, or chest pain.
c.Treatment should be initiated after the cause of the obstruction is clarified, so as not to confound accurate diagnosis; and is focused on treating the underlying cause with chemotherapy and/or radiation. Stent placement or surgical bypass are reserved for severe cases, and are rarely utilized.
4.Spinal cord compression.
a.Involvement of the spinal cord is not an unusual finding in patients with NHLs, and spinal cord compression typically manifests as severe back pain at the level of involvement, weakness (typically involving lower extremities), or paresthesia below the level of spinal involvement, bladder/bowel dysfunction (late finding).
b.Diagnosis is confirmed with MRI.
c.High-dose steroids and radiation therapy are the mainstays of treatment.
Follow-Up
A.Based on individual needs and individual oncologists.
B.Basic schedule includes:
1.Visits every 3 to 6 months for the first 2 years, every 6 to 12 months in years 3 to 5, and annually after year 5.
2.Usual tests are physical examination, blood work, imaging as indicated, and surveillance of symptom changes.
Consultation/Referral
A.Hematology oncology to manage patients with NHL.
B.Radiation oncology and surgery for placement of ports should be initiated.
C.Infectious disease is often consulted to manage neutropenic fevers.
Special/Geriatric Considerations
A.Elderly patients with NHL show similar features and prognostic factors as younger patients, suggesting similar treatment strategies should be offered to both groups.
B.Chronological age should not be the main determinant in treatment options, even in elderly patients older than 80 years.
Bibliography
National Cancer Institute. (2016, September 12). Surveillance, epidemiology, and end results program. Retrieved from https://seer.cancer.gov/faststats/selections.php?series=cancer
Krol, A. D. G., le Cessie, S., Snijder, S., Kluin-Nelemans, J. C., Kluin, P. M., & Noordijk, E. M. (2003). Primary extranodal non-Hodgkin’s lymphoma (NHL): The impact of alternative definitions tested in the Comprehensive Cancer Centre West population-based NHL registry. Annals of Oncology, 14(1), 131–139. doi:10.1093/annonc/mdg004