Lymphoma (HL & NHL) – Pathology

What is lymphoma?

Group of diseases caused by malignant lymphocytes that accumulate in lymph nodes and cause characteristic clinical features of lymphadenopathy

What may lymphoma cells do besides involving lymph nodes?

May spill over into blood (“leukaemic phase”) or infiltrate organs outside the lymphoid tissue

What percentage of lymphoid neoplasms are of B-cell origin?

85–90%

What are lymphoid neoplasms often associated with?

Immune abnormalities

Why do lymphoid neoplasms show characteristic patterns of involvement?

Like normal lymphocytes, neoplastic B and T cells home to certain tissue sites

Classify lymphoid neoplasms according to WHO classification.

Precursor B-cell neoplasms; Precursor T-cell neoplasms; Peripheral B-cell neoplasms; Peripheral T-cell lymphomas; Hodgkin lymphoma

What entities are included under peripheral B-cell neoplasms in the WHO classification shown?

CLL/SLL, Marginal zone lymphomas, Extranodal lymphomas, Mantle cell lymphoma, Follicular lymphoma, Hairy cell leukemia, Diffuse large B-cell lymphoma, Burkitt lymphoma

What is Hodgkin disease?

A lymphoma in which Reed-Sternberg (RS) cells are found

What is the lineage of the Reed-Sternberg cell?

B-lymphoid lineage

What is the origin of Reed-Sternberg cells?

Derived from pre-apoptotic germinal center B cells

What happens to B-cell identity in Reed-Sternberg cells?

They lose their B-cell identity

What signaling abnormality is present in Reed-Sternberg cells?

Aberrant activation of multiple signalling pathways

What is the association between Hodgkin lymphoma and EBV?

EBV detected in 50% of cases; underlying pathogenesis is unknown

Describe the microscopic background of Hodgkin lymphoma.

Scattered large mononuclear Hodgkin cells and multinucleated RS cells intermixed with non-neoplastic inflammatory cells

What inflammatory cells are commonly present in the background of Hodgkin lymphoma?

Neutrophils, eosinophils, plasma cells, with variable degree of fibrosis

How does WHO classify Hodgkin lymphoma?

Classical Hodgkin lymphoma and Nodular lymphocyte predominant Hodgkin lymphoma

What are the four subtypes of Classical Hodgkin lymphoma?

Nodular sclerosing, Mixed cellularity, Lymphocyte depleted, Lymphocyte rich

What is the most common subtype of Hodgkin lymphoma?

Nodular sclerosing Hodgkin lymphoma

What percentage of Hodgkin lymphoma is nodular sclerosing subtype?

60–80%

What is the age distribution of nodular sclerosing Hodgkin lymphoma?

Bimodal peaks at 15–35 years and 50–70 years

What is the characteristic architecture of nodular sclerosing Hodgkin lymphoma?

Nodularity, dense collagen bands, thickened capsule

What Reed-Sternberg variant is characteristic of nodular sclerosing Hodgkin lymphoma?

Lacunar RS cells

What background accompanies lacunar RS cells in nodular sclerosing Hodgkin lymphoma?

Band-forming sclerosis

What effect does nodular sclerosing Hodgkin lymphoma have on lymph node architecture?

Total or partial effacement of nodal architecture

What is the prognosis of nodular sclerosing Hodgkin lymphoma?

Good prognosis

What is the male-to-female ratio in nodular sclerosing Hodgkin lymphoma?

1:1

What is the second most common subtype of classical Hodgkin lymphoma?

Mixed cellularity classical Hodgkin lymphoma

What percentage of classical Hodgkin lymphoma cases are mixed cellularity type?

20–25%

In which patient group is mixed cellularity classical Hodgkin lymphoma frequently diagnosed?

HIV-positive patients

What percentage of mixed cellularity classical Hodgkin lymphoma cases have previous EBV infection?

About 75%

What age group is commonly affected by mixed cellularity classical Hodgkin lymphoma?

Older age group

Which lymph nodes are usually affected in mixed cellularity classical Hodgkin lymphoma?

Lymph nodes of the upper extremities

What is the prognosis of mixed cellularity classical Hodgkin lymphoma?

Good prognosis

What percentage of Hodgkin lymphoma cases are lymphocyte-rich classical Hodgkin lymphoma?

About 5%

What is the typical age group affected by lymphocyte-rich classical Hodgkin lymphoma?

Adults aged 30–50 years

What is the sex predominance in lymphocyte-rich classical Hodgkin lymphoma?

Male predominance (70%)

Describe the microscopic appearance of lymphocyte-rich classical Hodgkin lymphoma.

Scattered HRS cells in a diffuse background of small lymphocytes

Which inflammatory cells are absent in lymphocyte-rich classical Hodgkin lymphoma?

Neutrophils and eosinophils

What is the prognosis of lymphocyte-rich classical Hodgkin lymphoma?

Good prognosis with treatment

What is the least common subtype of classical Hodgkin lymphoma?

Lymphocyte-depleted classical Hodgkin lymphoma (LDCHL)

What percentage of Hodgkin lymphoma cases are lymphocyte-depleted classical Hodgkin lymphoma?

Less than 1% of all HL cases

Describe the Reed-Sternberg cells in lymphocyte-depleted classical Hodgkin lymphoma.

Pleomorphic RS cells are abundant

What stromal feature is characteristic of lymphocyte-depleted classical Hodgkin lymphoma?

Extensive fibrosis

What type of reactive lymphocytes are found in lymphocyte-depleted classical Hodgkin lymphoma?

Few reactive lymphocytes known as reticular lymphocytes

At what stage is lymphocyte-depleted classical Hodgkin lymphoma usually diagnosed?

Advanced stage

Which organs are commonly involved in lymphocyte-depleted classical Hodgkin lymphoma?

Abdomen lymph nodes, liver, spleen, and bone marrow

What is the prognosis of lymphocyte-depleted classical Hodgkin lymphoma?

Poor prognosis

What percentage of Hodgkin lymphoma cases are nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)?

5%

What growth pattern is seen in NLPHL?

Nodular growth pattern

What characteristic cells are seen in NLPHL?

“Popcorn-like” lymphocytes and histiocytes

Describe the background of NLPHL.

Fibrosis-free background

Can NLPHL occur at any age?

Yes, NLPHL can occur at any age

Which age group is more commonly affected by NLPHL?

Older age

What is the sex predominance in NLPHL?

Men account for about 75% of diagnoses

Describe the morphology of a classic Reed-Sternberg cell.

Large binucleate or multinucleate cell with prominent nucleoli

What is the mononuclear Reed-Sternberg variant called?

Hodgkin cell

What is a lacunar Reed-Sternberg cell?

Large cell with a single hyperlobulated nucleus, multiple small nucleoli and eosinophilic cytoplasm retracted around the nucleus creating a lacuna

In which Hodgkin lymphoma subtype are lacunar cells classically found?

Nodular sclerosing Hodgkin lymphoma

Describe the pleomorphic Reed-Sternberg cell variant.

Multiple irregular nuclei with pleomorphic appearance

What is the “popcorn” Reed-Sternberg cell variant?

Lymphohistiocytic variant with a very lobulated nucleus and small nucleoli

Which Hodgkin lymphoma subtype is associated with popcorn cells?

Nodular lymphocyte predominant Hodgkin lymphoma

What is the peak age incidence of Hodgkin lymphoma overall?

Young adults

Is Hodgkin lymphoma common in children?

No, it is rare in children

What is the male-to-female ratio in Hodgkin lymphoma overall?

2:1

Describe the lymphadenopathy of Hodgkin lymphoma.

Painless, non-tender, asymmetrical, firm, discrete, and rubbery enlargement of superficial lymph nodes

What is the most common site of lymph node involvement in Hodgkin lymphoma?

Cervical lymph nodes (60–70%)

What percentage of Hodgkin lymphoma cases involve axillary lymph nodes?

10–15%

What percentage of Hodgkin lymphoma cases involve inguinal lymph nodes?

6–12%

How common is splenomegaly in Hodgkin lymphoma?

Present in 50% of patients

What constitutional symptoms may occur in Hodgkin lymphoma?

Fever, pruritus, weight loss, profuse sweating

Which Hodgkin lymphoma patients typically present with lymphadenopathy without systemic symptoms?

Younger patients with lymphocyte-rich, lymphocyte-predominant, or nodular sclerosing HL; Stage I or II

Which Hodgkin lymphoma patients typically present with systemic symptoms?

Disseminated disease, Stage III or IV, mixed cellularity or lymphocyte-depleted HL

Arrange Hodgkin lymphoma subtypes from best to worst prognosis.

Lymphocyte predominant > Lymphocyte rich > Nodular sclerosing > Mixed cellularity > Lymphocyte depleted

What is Stage I Hodgkin lymphoma?

One lymph node or tissue outside the lymphatic system is affected

What is Stage II Hodgkin lymphoma?

Two or more lymph nodes on the same side of the diaphragm are affected, or localized involvement outside the lymphatic system

What is Stage III Hodgkin lymphoma?

Two or more lymph nodes or organs on either side of the diaphragm are affected

What is Stage IV Hodgkin lymphoma?

Spread to at least one organ outside the lymphatic system; lymphoid tissues may or may not be affected

What does category A mean in Hodgkin lymphoma staging?

Symptoms are not reported

What does category B mean in Hodgkin lymphoma staging?

Fever, over 10% body weight loss in the past six months without dieting, and/or night sweats are present

What does category E mean in Hodgkin lymphoma staging?

Hodgkin lymphoma has metastasized to organs or tissues outside the lymphatic system

What does category S mean in Hodgkin lymphoma staging?

HL cells detected in the spleen

What percentage of Non-Hodgkin lymphomas are B-cell lymphomas?

80%

What is the normal function of B cells?

Make antibodies that attach to and help destroy antigens

How are many B-cell lymphomas thought to arise?

Mutation arising during the B-cell life cycle

What percentage of Non-Hodgkin lymphomas are T-cell lymphomas?

15%

Where do T cells mature?

Thymus

What is the main role of T cells?

Help the immune system work in a coordinated fashion

Which T-cell lymphoma mentioned is caused by a chromosome 5 gene translocation?

Anaplastic large cell lymphoma

What is the exact cause of NHL?

Exact causes are still unknown

Which chemical exposures increase risk of NHL?

Pesticides and solvents

Which viral infection is a risk factor for NHL?

Epstein-Barr virus infection

What family history factor is associated with NHL risk?

Family history of NHL, although no hereditary pattern has been established

Which immunodeficiency-associated infection increases NHL risk?

HIV infection

What are the symptoms of NHL?

Painful swelling of lymph nodes in the neck, underarm and groin; unexplained fever; night sweats; constant fatigue; unexplained weight loss; itchy skin

What is the 1-year survival rate for NHL according to the slides?

77%

What is the 5-year survival rate for NHL according to the slides?

56%

What is the 10-year survival rate for NHL according to the slides?

42%

What is the most common Non-Hodgkin lymphoma in adults?

Diffuse large B-cell lymphoma (DLBCL)

What grade of lymphoma is DLBCL?

High-grade lymphoma

What is the typical age for DLBCL?

Median age 60 years