Q3 LONG ANSWER 10M ★ High-yield

Classify lymphomas. Describe Hodgkin lymphoma and differentiate it from non-Hodgkin lymphoma.

Pathology · 2nd Professional — Para-Clinical

Definition and Classification

Lymphomas are malignant neoplasms of lymphoid tissue, arising in lymph nodes or extranodal lymphoid tissue, and divided into hodgkin and non-hodgkin lymphoma.

Hodgkin Lymphoma

Bimodal age distribution — a peak in young adults (15–35) and another after 50
Arises in a single node or chain and spreads contiguously to adjacent groups — which is what makes it curable by radiotherapy
The neoplastic cell is the REED–sternberg cell, which forms only a small minority of the tumour mass; the bulk is a reactive infiltrate of lymphocytes, eosinophils, plasma cells and histiocytes

The Reed–Sternberg cell

Large cell with a bilobed or bi-nucleate nucleus, each with a prominent eosinophilic nucleolus surrounded by a clear halo — the "owl-eye" appearance
Immunophenotype — CD15 and CD30 positive; CD45 and CD20 negative
Derived from a germinal centre B cell that has lost its B cell programme
Variants — lacunar cell (nodular sclerosis), popcorn or lymphohistiocytic cell (nodular lymphocyte predominant, which is CD20 positive and CD15/CD30 negative), and mummified cells

Subtype	Frequency	Features	Prognosis
Nodular sclerosis	The commonest, 65–70%	Young women; mediastinal mass; broad collagen bands dividing the node into nodules; lacunar cells	Good
Mixed cellularity	20–25%	Older men; abundant classical Reed–Sternberg cells in a mixed inflammatory background; associated with EBV and HIV	Intermediate
Lymphocyte rich	5%	Few Reed–Sternberg cells	Very good
Lymphocyte depleted	Under 5%	Elderly, HIV; abundant Reed–Sternberg cells with few lymphocytes	Worst
Nodular lymphocyte predominant	5%	Popcorn cells; CD20 positive; behaves like a B cell lymphoma	Good, but late relapses

CLINICAL PEARL

The prognosis follows the lymphocyte count, not the Reed–Sternberg count. The more lymphocytes and the fewer neoplastic cells, the better the outcome — lymphocyte-rich does best and lymphocyte-depleted worst. The reactive infiltrate represents the host response, and its vigour predicts survival.

Non-hodgkin Lymphoma

Far more heterogeneous — over 60 entities in the WHO classification; about 85% are of B cell origin
Spreads non-contiguously and is often disseminated at presentation, with frequent marrow and extranodal involvement
Extranodal sites — stomach (malt), skin, brain, testis, thyroid, Waldeyer ring

Type	Genetics	Features
Diffuse large B cell lymphoma	Bcl-6, bcl-2, MYC rearrangements	The commonest NHL; aggressive but curable with R-chop
Follicular lymphoma	T(14;18) — bcl-2 overexpression	Indolent but incurable; cells accumulate because they do not die
Burkitt lymphoma	T(8;14) — MYC	"starry sky" appearance from tingible-body macrophages among sheets of blasts; the fastest growing human tumour; endemic African form affects the jaw and is EBV-associated; sporadic form affects the abdomen
Malt lymphoma	T(11;18)	Gastric; caused by helicobacter pylori and may regress on eradicating it
Mantle cell lymphoma	T(11;14) — cyclin D1	Aggressive, poor prognosis
Adult T cell leukaemia/lymphoma	HTLV-1	Skin lesions, hypercalcaemia, lytic bone lesions

Hodgkin Compared with Non-hodgkin

Feature	Hodgkin	Non-hodgkin
Spread	Contiguous and orderly	Non-contiguous, unpredictable
Stage at presentation	Often localised	Usually disseminated
Extranodal involvement	Uncommon	Common
Mesenteric nodes and Waldeyer ring	Rarely	Commonly
Marrow involvement	Uncommon	Common
B symptoms	Frequent	Less common
Diagnostic cell	Reed–Sternberg cell in a reactive background	Sheets of neoplastic lymphoid cells
Prognosis	Generally better — over 80% cure	Very variable

Staging and B Symptoms

Ann Arbor stage	Extent
I	One lymph node region
II	Two or more regions on the same side of the diaphragm
III	Regions on both sides of the diaphragm
IV	Diffuse extranodal involvement — marrow, liver, lung

Suffix A — no systemic symptoms; suffix B — B symptoms present: unexplained fever above 38°C, drenching night sweats, and weight loss of more than 10% in six months
Suffix E — localised extranodal extension; S — splenic involvement
PEL–ebstein fever — a cyclical fever over one to two weeks alternating with afebrile periods; characteristic of Hodgkin lymphoma though uncommon
Alcohol-induced pain in involved nodes is rare but almost specific

Applied Aspects

Diagnosis requires an excision biopsy of a whole node — fine needle aspiration and core biopsy are inadequate, because the architecture is essential to classification
In India, tuberculous lymphadenitis is the chief differential of persistent lymphadenopathy, and must be excluded by staining and culture
Late effects of cure are now a major concern — second malignancies (breast cancer after mantle radiotherapy, AML after alkylating agents), cardiac disease, hypothyroidism and infertility
Fertility preservation must be discussed before treatment, since these are young patients with a high chance of cure
Pet-CT is used for staging and for assessing response, and an early interim pet now guides how much treatment is given
Rituximab (anti-CD20) transformed B cell NHL, and is the reason diffuse large B cell lymphoma is now curable in the majority

All questions in Haematology II: Leukaemias, Lymphomas & Haemostasis

Every Pathology chapter →