Hodgkin Lymphoma (HL) - Hyperexcision

Hodgkin lymphoma is characterised by Reed-Sternberg (RS) cells. It presents as a painless lymphadenopathy and has a contiguous pattern of spread.

Hodgkin lymphoma has a bimodal peak at 30 years and 70 years. Nodular sclerosing type commonly affects young adults, while the mixed-cellularity type affects elderly adults.

Classical Hodgkin Lymphomas

Classical Hodgkin Lymphoma	Description
Lymphocyte rich	Composed of reactive lymphocytes mostly, Mononuclear type RS cells predominate
Mixed cellularity	Composed of many different cell types, Classical Owl’s eye RS cells predominate
Nodular sclerosis	Bands of fibrosis, Lacunar RS cells present
Lymphocyte depleted	Composed of many RS cells and their variants

Non-classical Hodgkin Lymphomas

Non-classical Hodgkin lymphoma	Description
Nodular lymphocyte-predominant	Composed mostly of B-cells with few RS cells and variants, predominantly popcorn cells or Lymphohistiocytic variant (behaves like low-grade B-cell NHL with CD20+, can advance to DLBCL – Richter’s syndrome)
Hodgkin Lymphoma unclassifiable with DLBCL features	Characterized by a syncytium of Reed-Sternberg cells (mononuclear variant) that are CD20+

Staging of Hodgkin lymphoma

Stage	Sites involved	5-year survival
I	One Lymph node site	90%
II	Two or more lymph node sites on one side of the diaphragm	90%
III	Two or more lymph node sites on both sides of the diaphragm	80%
IV	Extranodal sites (lungs, liver, bone marrow, etc.) with or without lymph node involvement	70%

Reed Sternberg Cell Variants

Variant	Description
Classical Reed-Sterberg cell	Predominant in mixed cellularity and lymphocyte rich hodgkin lymphma. Has the classical Owl’s eye appearance of bilobed nuclei and mirrored nucleoli.
Mononuclear variant	Predominant in mixed and lymphocyte-rich HL
Lacunar cell	Predominant in nodular sclerosis subtype. Has folded multilobed nucleus within an open space (lacuna), which is an artefact of processing
Lymphohistiocytic variants or Popcorn cells	Predominant in the nodular lymphocyte-predominant subtype. CD20+, CD79a+ and CD45+, and BCL-6 positive. These have an infolded nuclear membrane, small nucleoli, fine chromatin, and abundant pale cytoplasm
Anaplastic (pleomorphic) cells	Seen in lymphocyte-depleted subtype
Mummified cells	Non-specific

Risk Factors for Hodgkin Lymphoma
- History of EBV infection
- Immunodeficiency
  - Transplantation
  - HIV
  - Immunosuppressants
  - Chemotherapy
- Autoimmune disease
  - Rheumatoid Arthritis
  - Sarcoidosis
Signs and symptoms
- Lymphadenopathy
- Chest pain, dry cough, and breathlessness due to mediastinal lymphadenopathy
- Hepatosplenomegaly
- B-symptoms: night sweats, unintentional weight loss >10%, and Fever > 38 C
- Pel-Ebstein fevers are specific for Hodgkin lymphoma. These are cyclical fevers that rise and fall every 1 or 2 weeks
- Alcohol-induced pain or lymphadenitis- highly specific for Hodgkin lymphoma
- Generalized or localized pruritus
Investigations
- Complete Blood Count
  - Elevated or decreased WBC count
  - Anemia
  - Eosinophilia
- Serum chemistries
  - Increased LDH
  - Hypercalcemia due to paraneoplastic production of calcitriol
- Raised ESR
- Excisional Biopsy and Histology
  - Reed-stenberg cells
  - Polynuclear fused Hodgkin cells
  - Hodgkin cells (mononuclear malignant B-cell)
  - Inflammatory background (lymphocytes, neutrophils, eosinophils, and macrophages)
  - Granuloma formation
- Immunohistochemistry
  - CD15+
  - CD30+
  - CD20+, CD45+, and CD79a+ in Nodular lymphocyte predominant HL
- HIV antigen-antibody test
- Chest X-ray for mediastinal mass
- Whole body PET scan and Bone Marrow biopsy for staging
Treatment
- Psychological support
- Radiation therapy +/- Low-dose chemotherapy (ABVD) for Stage I and II
- Chemotherapy (ABVD) for stage III and IV or B-symptoms present
  - Adriamycin → causes dilated cardiomyopathy
  - Bleomycin → causes pulmonary fibrosis
  - Vincristine → causes peripheral neuropathy
  - Dacarbazine → causes myelosuppression
Factors for poor prognosis
- Advanced age
- High-stage lymphoma
- Elevated ESR
- B-symptoms present

Reference Intervals ›

Biochemistry

ACTH	P: <80 ng/L
ALT	P: 5–35 U/L
Albumin	P: 35–50 g/L
Aldosterone	P: 100–500 pmol/L
Alk. phosphatase	P: 30–130 U/L
α-Amylase	P: 0–180 IU/dL
α-Fetoprotein	S: <10 kU/L
Angiotensin II	P: 5–35 pmol/L
ADH	P: 0.9–4.6 pmol/L
AST	P: 5–35 U/L
Bicarbonate	P: 24–30 mmol/L
Bilirubin	P: 3–17 μmol/L
BNP	P: <50 ng/L
CRP	P: <10 mg/L
Calcitonin	P: <0.1 mcg/L
Calcium (ionized)	P: 1.0–1.25 mmol/L
Calcium (total)	P: 2.12–2.60 mmol/L
Chloride	P: 95–105 mmol/L
Cholesterol	P: <5.0 mmol/L
VLDL	P: 0.128–0.645 mmol/L
LDL	P: <2.0 mmol/L
HDL	P: 0.9–1.93 mmol/L
Cortisol AM	P: 450–700 nmol/L
Cortisol Midnight	P: 80–280 nmol/L
CK ♂	P: 25–195 U/L
CK ♀	P: 25–170 U/L
Creatinine	P: 70–100 μmol/L
Ferritin	P: 12–200 mcg/L
Folate	S: 2.1 mcg/L
FSH	P: 2–8 U/L ♂; >25 menopause
GGT ♂	P: 11–51 U/L
GGT ♀	P: 7–33 U/L
Glucose (fasting)	P: 3.5–5.5 mmol/L
Growth hormone	P: <20 mu/L
HbA1C (DCCT)	B: 4–6%
HbA1C (IFCC)	B: 20–42 mmol/mol
Iron ♂	S: 14–31 μmol/L
Iron ♀	S: 11–30 μmol/L
Lactate (venous)	P: 0.6–2.4 mmol/L
Lactate (arterial)	P: 0.6–1.8 mmol/L
LDH	P: 70–250 U/L
LH	P: 3–16 U/L
Magnesium	P: 0.75–1.05 mmol/L
Osmolality	P: 278–305 mosmol/kg
PTH	P: 0.8–8.5 pmol/L
Potassium	P: 3.5–5.3 mmol/L
Prolactin ♂	P: <450 U/L
Prolactin ♀	P: <600 U/L
PSA	P: 0–4 mcg/mL
Protein (total)	P: 60–80 g/L
Red cell folate	B: 0.36–1.44 μmol/L
Renin (erect)	P: 2.8–4.5 pmol/mL/h
Renin (recumbent)	P: 1.1–2.7 pmol/mL/h
Sodium	P: 135–145 mmol/L
TBG	P: 7–17 mg/L
TSH	P: 0.5–4.2 mU/L
T4	P: 70–140 nmol/L
Free T4	P: 9–22 pmol/L
TIBC	S: 54–75 μmol/L
Triglycerides	P: 0.50–2.3 mmol/L
T3	P: 1.2–3.0 nmol/L
Troponin T	P: <0.1 mcg/L
Urate ♂	P: 210–480 μmol/L
Urate ♀	P: 150–390 μmol/L
Urea	P: 2.5–6.7 mmol/L
Vitamin B12	S: 0.13–0.68 nmol/L
Vitamin D	S: 50 nmol/L

Arterial Blood Gases

pH	7.35–7.45
PaCO₂	4.7–6.0 kPa
PaO₂	>10.6 kPa
Base excess	±2 mmol/L

Urine

Cortisol (free)	<280 nmol/24h
Hydroxyindole acetic acid	16–73 μmol/24h
Hydroxymethylmandelic acid	16–48 μmol/24h
Metanephrines	0.03–0.69 μmol/mmol cr.
Osmolality	350–1000 mosmol/kg
17-Oxogenic steroids ♂	28–30 μmol/24h
17-Oxogenic steroids ♀	21–66 μmol/24h
17-Oxosteroids ♂	17–76 μmol/24h
17-Oxosteroids ♀	14–59 μmol/24h
Phosphate (inorganic)	15–50 mmol/24h
Potassium	14–120 mmol/24h
Protein	<150 mg/24h
Protein/creatinine ratio	<3 mg/mmol
Sodium	100–250 mmol/24h

Haematology

WCC	4.0–11.0 ×10⁹/L
RBC ♂	4.5–6.5 ×10¹²/L
RBC ♀	3.9–5.6 ×10¹²/L
Hb ♂	130–180 g/L
Hb ♀	115–160 g/L
PCV ♂	0.4–0.54 L/L
PCV ♀	0.37–0.47 L/L
MCV	76–96 fL
MCH	27–32 pg
MCHC	300–360 g/L
RDW	11.6–14.6%
Neutrophils	2.0–7.5 ×10⁹/L (40–75%)
Lymphocytes	1.0–4.5 ×10⁹/L (20–45%)
Eosinophils	0.04–0.44 ×10⁹/L (1–6%)
Basophils	0–0.10 ×10⁹/L (0–1%)
Monocytes	0.2–0.8 ×10⁹/L (2–10%)
Platelets	150–400 ×10⁹/L
Reticulocytes	0.8–2.0% / 25–100 ×10⁹/L
Prothrombin time	10–14 s
APTT	35–45 s

Paediatric

Pulse Rate (bpm)
Neonate	140–160
Infant <1yr	120–140
1–5 years	110–130
5–12 years	80–120
>12 years	70–100
Respiratory Rate (tachypnoea)
0–2 months	≥60/min
2–12 months	≥50/min
1–5 years	≥40/min
>5 years	≥30/min
Blood Pressure (mmHg)
Term	65/45
1 year	75/50
4 years	85/60
8 years	95/65
10 years	100/70
Weight Formulas
3–12 months	(a + 9)/2 kg
1–6 years	2a + 8 kg
>6 years	(7a − 5)/2 kg
Haemoglobin (g/dL)
Term newborn	13–20
1 month	11–18
2 months	10–15
1–2 years	10–13
>2 years	11–14
MUAC (6 months–5 years)
Obese	>17.5 cm
Normal	13.5–17.4 cm
At risk	12.5–13.4 cm
Moderate malnutrition	11.5–12.4 cm
Severe malnutrition	<11.5 cm
Developmental Milestones
Social smile	1.5 months
Head control	4 months
Sits unsupported	7 months
Crawls	10 months
Stands unsupported	10–12 months
Walks	12–13 months
Talks	18 months
CSF WBC (/mm³)
Term newborn	0–25
>2 weeks	0–5

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