Gross & microscopic appearance	Pathologic basis of disease	Clinical correlation	
Gross:
•	Enlarged, flesh gray tan lymph node.
•	Absence of well-defined nodules or fibrosis.

Microscopic:
•	Reed-Sternberg cell: large & binucleate with two mirror image containing large pink-staining nucleoli.
•	Lacunar cell: delicate folded or multilobate nuclei surrounded by abundant pale cytoplasm; shrinkage towards cell wall leaves clear space.
•	Mononuclear variant: single round or oblong nucleus with a large inclusion-like nucleolus.
•	Lymphocytic & histiocytic variants: polypoid nuclei resembling popcorn kernels.

Histological subgroups:
•	Lymphocyte-predominant (slowly progressive): lymphocytes form extensive sheets within which are scattered few Reed-Sternberg cells.
•	Mixed cellularity (intermediate progression): even distribution of lymphocytes & histiocyte-like cells.
•	Lymphocyte-depleted (aggressive disease): affected nodes are replaced by sheet of large pleomorphic cells & Reed-Sternberg cells.
•	Nodular sclerosis (slowly progressive): deposition of broad irregular bands of fibrous tissues which separate tumor mass into islands.	Etiology:
•	A malignant neoplasm of the lymphoreticular system.
•	Implicates Epstein-Barr virus infection.

Incidence:
•	Commonest type of lymphoma.
•	May occur at any age.
•	Two peaks of incidence: around adolescence & in late middle & older age.

Natural course:
•	Majority of cases evolve slowly – several years
•	A minority progress rapidly – months

Presentation & spread:
•	First becomes manifest by lymph node enlargement but later by splenomegaly, hepatomegaly and bone marrow.
•	Disease begins in lymph node.
•	Spread to other lymphoid tissue: nodes in central spleen & spleen.
•	Spread to other organs: marrow, liver, GI tract.

Prognosis:
•	5-year survival for stages I & IIa: 90% with many appeared cured.
•	Advanced disease: 60-70% 5-year survival.	•	Painless enlargement of lymph nodes
•	Variable fatigue
•	Weight loss
•	Intermittent fever
•	Night sweats
•	Pruritus
•	Hematological: anemia, neutrophil leucocytosis
•	Depression of T cell function

Complications of therapy:
•	Increased risk of developing second hematologic cancers: myelodysplastic syndromes, acute myelogenous leukemia or solid cancers of the lung, breast, stomach, skin or soft tissues.
•	Pulmonary fibrosis
•	Accelerated atherosclerosis

Staging:
•	I: disease involving single node or group of nodes.
•	II: disease in more than one site – all lesions either above or below the diaphragm.
•	III: disease on both sides of diaphragm.
•	IV: widespread involvement of extralymphoid sides.