Hodgkin Lymphoma

Epidemiology:

• 32y average age
• Nodular sclerosis type (75% of cases)
• mixed cellularity type:
• M > F
• Biphasic (young adults and 55)
• Lymphocyte rich:
• M > F
• Older adults
• Lymphocyte depletion:
• Older males
• HIV-infection
• Developing countries
• Lymphocyte predominance:
• Young males

Common sites:

• nodular sclerosis:
• frequent mediastinal
• lymphocyte predominance:
• cervical or axillary lymphadenopathy
• mediastinal

Gross features:

Histologic features:

• Reed-Sternberg cells and variants:
• Large (15-45 microns)
• Either multiple nuclei or a single nucleus with multiple lobes
• Large nucleoli the size of lymphocytes
• Abundant cytoplasm
• Mononuclear variant:
• Single round or oblong nucleus
• Large inclusion-like nucleolus
• Lacunar variant:
• Delicate folded or multilobate nuclei
• Abundant pale cytoplasm
• Lymphohistiocytic variant (L&H cells)
• Polypoid nuclei resembling popcorn
• Inconspicuous nucleoli
• Mummified cells – half apoptotic, densely eosinophilic cells
• Granulomatous inflammation maybe
• Castleman-like changes associated maybe
• Hyaline vascular follicles
• Increased paracortical vascularity
• Numerous paracortical plasma cells
• nodular sclerosis type:
• frequent lacunar Reed-Sternberg cells
• folded or multilobated nucleus
• surrounded by a clear space
• occasional diagnostic Reed-Sternberg cell
• background infiltrate:
• T cells
• Eosinophils
• Macrophages
• Plasma cells
• Fibrous bands dividing cellular areas into nodules
• EBV in 40%
• Grading (only for NSHD):
• Grade I (NSI)
• < 25% of nodules show lymphocyte depletion, OR
• < 25% of nodules show numerous anaplastic Hodgkin cells without depletion of lymphocytes
• Grade II (NSII)
• 25% or more of nodules show lymphocyte depletion, OR
• 25% or more of nodules show numerous anaplastic Hodgkin cells without depletion of lymphocytes
• Mixed cellularity type:
• Frequent mononuclear and diagnostic R-S cells
• Background infiltrate:
• T cells
• Eosinophils
• Macrophages
• Plasma cells
• 70% EBV pos
• lymphocyte-rich
• frequent mononuclear and diagnostic R-S cells
• background infiltrate rich in T-cells
• 40% EBV pos
• lymphocyte depletion
• reticular variant:
• frequent diagnostic R-S cells
• paucity of background reactive cells
• diffuse fibrosis variant:
• hypocellular fibrillar background
• scattered diagnostic R-S cells
• few reactive cells
• most EBV pos
• nodular lymphocyte predominance:
• Frequent L&H (popcorn cell) variants
• Background infiltrate
• Follicular dendritic cells
• Reactive B cells
• EBV neg
• Nodular variant (nodular lymphocyte-predominant Hodgkin lymphoma)
• Progressive transformation of germinal centres may be seen at edges

Immunophenotype & Special Stains:

Marker:	Sensitivity:	Specificity:
CLASSIC HD:
CD15 (R-S cells) Stains golgi and/or membrane	Not as good as CD30	Neutrophils are positive
CD30 (R-S cells) Golgi and/or membrane pattern	98% of classic HD	Immunoblasts / large transformed lymphocytes are positive
EBV	~70%
CD20 (neg) Pan B (neg)	Some are positive (inverse relationship with CD15)
Pan T (R-S cells neg)
CD3 (lymphocytes immediately surrounding R-S cells)
CD45 (neg)	May be + on frozen section
EMA (neg)
EBER	+/-
NLPHD:
CD45
Pan B (CD19, 20, 22, 79a)
OCT-2
CD75
EMA	+/-
CD15 (neg)
CD30 (neg)	Some +
J-chain	+/-
Ig	+/-
CD57 (small T lymphocytes surrounding L&H cells)
EBER (neg)

Molecular features:

• Immunoglobulin and TCR genes usually germline (both classic and NLPHD)
• IgH gene rearrangement occasionally
• Bcl-2 gene rearrangement occasionally

Other features:

• Prognostic indicators:
• Age > 40-50 is worse prognosis
• Systemic (B) symptoms associated with worse prognosis:
• Fever > 38.5
• Weight loss > 10%
• Night sweats
• Tumour burden (bulk and number of sites)
• Ex. large mediastinal mass (> 1/3 of widest thoracic diameter)
• Amount of tumour in the spleen (4 or more nodules)
• Combination of total extent and volume of tumour
• Tumour stage (Ann Arbor):
• Prognosis stage I and II is very good
• Grade (for NSHD only):
• Controversial
• May be irrelevant with current therapy
• Histologic type is not prognostically significant
• Most are thought to arise from germinal centre or post-germinal centre B cells
• Cureable in most cases
• Nodular sclerosis type:
• Most stage 1 or 2
• Mixed cellularity type:
• Most stage 3 or 4
• Lymphocyte depletion type:
• More likely advanced

References: