Updated: 4/9/2020

Non-Hodgkin Lymphoma

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https://upload.medbullets.com/topic/111025/images/lymphadenop_1.jpg
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Snapshot
  • A 9-year-old girl is brought to the free clinic by her parents. The family members are refugees from South Sudan who just settled into the United States a month ago. With the help of a translator, the pediatrician learns that the girl has experienced swelling in her left lower jaw for the past 15 days. The swelling is not painful but has caused difficulty chewing as it has rapidly increased in size in the past week. Physical examination reveals enlarged bilateral submandibular lymph nodes. An excisional lymph node biopsy is performed on her submandibular lymph nodes and is sent to pathology.  Histology of the biopsy specimen is shown in the image.
Introduction
  • Overview
    • non-Hodgkin lymphomas (NHLs) are tumors that originate from lymphoid tissues (i.e., lymph nodes)
  • Epidemiology
    • incidence
      • approximately 74,000 new cases/year in the US
      • 5 times more common than Hodgkin lymphoma
    • demographics
      • most commonly in people aged 65-74
        • median age at diagnosis is 67 years of age
  • Pathophysiology
    • progressive clonal expansion of mature B-cells or T-cells arising from activated oncogenes or inactivated tumor suppressor genes
      • 85% of NHLs are of B-cell origin
      • NHLs of B-cell origin
        • Burkitt lymphoma
        • diffuse large B-cell lymphoma
        • follicular lymphoma
        • mantle cell lymphoma
        • marginal zone lymphoma
        • primary CNS lymphoma
      • NHLs of T-cell origin
        • adult T-cell lymphoma
        • mycosis fungoides (cutaneous T-cell lymphoma)
    • may result from chromosomal translocations, infections, environmental factors, immunocompromised states, and chronic inflammation
  • Genetics
    • chromosomal translocations
    • Burkitt lymphoma
      • t(8;14)
        • translocation of c-myc and heavy-chain Ig
    • diffuse large B-cell lymphoma
      • ↑ expression of Bcl-2 and Bcl-6
        • ↑ levels of Bcl-2 inhibits apoptosis
    • follicular lymphoma
      • t(14;18)
        • translocation of heavy-chain Ig and BCL-2
    • mantle cell lymphoma
      • t(11;14)
        • translocation of cyclin D1 and heavy-chain Ig
    • marginal zone lymphoma
      • t(11;18)
        • translocation of API2 and MALT1
          • promotes the continuous activation of the transcription factor NF-κB
  • Prognosis
    • 5-year relative survival rate of patients with NHL is 71%
    • prognosis depends on several factors (i.e., tumor histology, tumor stage, and patient age)
      • primarily dependent on histopathology
      • secondarily influenced by clinical parameters, including age, presence of extranodal disease, and stage
Presentation
  • Symptoms
    • low-grade NHLs
      • painless and slowly-progressive peripheral lymphadenopathy
        • enlarged lymph nodes may spontaneously regress
      • fatigue
      • weakness
    • intermediate and high-grade NHLs
      • lymphadenopathy
      • "B-symptoms"
        • fever
        • night sweats
        • weight loss
      • > 1/3 patients present with extranodal involvement
        • most common sites
          • GI tract
          • skin
          • bone marrow
          • sinuses
          • genitourinary tract
          • thyroid
          • CNS
  • Physical exam
    • peripheral lymphadenopathy
    • splenomegaly
    • hepatomegaly
    • skin lesions in cutaneous T-cell lymphoma
    • large abdominal mass in Burkitt lymphoma
Imaging
  • CT scan of neck, chest, abdomen, and pelvis
    • indications
      • for staging
  • PET scanning
    • indications
      • for staging
  • Upper GI series
    • indications
      • for patients with symptoms suggesting GI involvement
        • endoscopy is helpful in tumor localization and staging, detection of bleeding lesions, and the obtaining of biopsy specimens
  • MRI of brain and spinal cord
    • indications
      • for patients with suspected primary CNS lymphoma
Studies
  • CBC
    • may show anemia, pancytopenia, lymphocytosis, and thrombocytosis
  • LDH levels
    • may be ↑
  • Serum β2-microglobulin
    • may be ↑
  • Excisional lymph node biopsy
    • histology
Treatment
  • Medical
    • chemotherapy
      • main treatment for most patients with NHL
        • one of the most common combinations: CHOP
          • Cyclophosphamide, doxorubicin (or Hydroxydaunorubicin), vincristine (Oncovin) and Prednisone
    • radiation therapy
      • can be used as main treatment for some types of NHL if in stage I or II
      • sometimes used along with chemotherapy for advanced and more aggressive lymphomas
      • may palliate symptoms caused by lymphoma that has metastasized to internal organs
    • bone marrow transplantation
      • potential use in patients with relapsed NHL
  • Surgical
    • tumor resection
      • rarely, may be used to treat lymphomas that start outside the lymphatic system (i.e., the spleen)
 

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Questions (3)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.ON.13.29) A 17-year-old male African immigrant visits his primary care physician with a mass on the right side of his jaw. He denies drug or alcohol use and does not take any medication. Serology for Epstein-Barr Virus (EBV) infection is positive. A biopsy of the lesion is taken and shown in Figure A. Which of the following chromosomal translocations is most likely present in this tissue? Review Topic | Tested Concept

QID: 101339
FIGURES:
1

t(9;22)

4%

(6/148)

2

t(8;14)

83%

(123/148)

3

t(11;22)

5%

(8/148)

4

t(14;18)

5%

(8/148)

5

t(15;17)

1%

(1/148)

L 1 E

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(M1.ON.13.147) A 40-year-old male presents to his primary care physician for a regularly scheduled check-up. Physical examination reveals nontender cervical lymphadenopathy. A biopsy of the lymph node reveals aggregates of follicular architecture, and cytogenic analysis shows a t(14;18) translocation. The protein most likely responsible for the patient’s condition does which of the following: Review Topic | Tested Concept

QID: 101457
1

Regulates passage through the cell cycle

11%

(10/89)

2

Activates DNA repair proteins

8%

(7/89)

3

Provides mitotic cytoskeleton

6%

(5/89)

4

Inhibits apoptosis

57%

(51/89)

5

Regulates cell growth through signal transduction

16%

(14/89)

L 1 E

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