Non-Hodgkin Lymphoma (NHL)

Lymphoma Definition

• Malignant neoplasm of lymphoid origin
• Typically causes solid tissue mass
• Presents as lymphadenopathy or an extra nodal mass in the brain or intestines

WHO Classification of Lymphoid Neoplasms

• Non-Hodgkin lymphoma (NHL)
  • B cell lymphoma
  • T cell/ NK cell lymphoma
• Hodgkin lymphoma

Non-Hodgkin Lymphoma (NHL) Epidemiology

• Most common hematopoietic neoplasm
• Seventh most common cancer
• Five times more common than Hodgkin lymphoma (HL)
• More prevalent in males than females
• Typically affects individuals older than 50 years
• Higher risk in white people compared to black and Asian American people

NHL Etiology

• Chromosomal translocations, especially t(14;18)
• Immunodeficiency states like AIDS and immunosuppression
• Chronic inflammation related to autoimmune conditions, for example, Sjögren syndrome and Hashimoto thyroiditis
• Infections
  • Human T-cell leukemia virus type-1 (HTLV-1)
  • Epstein-Barr virus
  • Hepatitis C virus (HCV)
  • Kaposi sarcoma-associated herpesvirus (KSHV)
  • Helicobacter pylori
• Environmental factors
  • Chemicals like pesticides, herbicides, solvents, organic chemicals, wood preservatives, and hair dye
• Chemotherapy
• Radiation exposure

Nodal and Extra-nodal Sites for NHL

• Nodal lymphoma starts in the lymph nodes
• Extra-nodal lymphoma sites include:
  • Intestine
  • Central nervous system
  • Skin
  • Brain
  • Testis
  • Spleen
  • Ovary

General clinical manifestations

• Asymptomatic lymphadenopathy (peripheral, progressive, and painless) is common
• "B symptoms" include:
  • Fever
  • Night sweats
  • Weight loss of >10% within 6 months
• Extra-nodal involvement may cause:
  • Splenomegaly
  • Hepatomegaly
  • Large abdominal mass
  • Testicular mass

General Investigations

• Complete blood cell (CBC) count
• Chest radiography
• Computed tomography (CT) scan of the neck, chest, abdomen, and pelvis
• Positron emission tomography (PET) scan
• Lymph node biopsy
• Bone marrow aspirate and biopsy
• Biopsy of extra-nodal sites

General Morphological Features

• Enlarged lymph nodes
• Soft and fleshy texture
• Grayish-white color
• Foci of hemorrhage and
• Necrosis

Microscopic Features

• Loss of normal architecture
• Diffuse infiltration by monoclonal malignant lymphoid cells
• Subtyping via immunohistochemistry
  • B cell lymphoma is CD20 positive
  • T cell lymphoma is CD3 and CD5 positive

Origin and Classification of NHL: B-cell Neoplasms

• Precursor B-cell Neoplasms
  • Lymphoblastic leukemia/lymphoma
• Peripheral B-Cell Neoplasms
  • Chronic Lymphocytic leukemia/small Lymphocytic Lymphoma
  • Diffuse large B-cell lymphoma
  • Lymphoplasmacytic lymphoma
  • Mantle cell Lymphoma
  • Follicular Lymphoma
  • Marginal Zone Lymphoma
  • Burkitt Lymphoma

B-cell lymphomas

• Account for nearly 90% of all lymphomas
• Diffuse large B-cell lymphoma (DLBL)
  • Most common type of NHL
  • Highly aggressive
• Follicular lymphoma
  • Second most common type
  • Slow-growing (indolent)

Burkitt Lymphoma (BL) Characteristics

• Type of peripheral B cell neoplasm
• Originates from germinal center cells
• Typically affects children or young adults
• Males are affected 2-3 times more often than females
• Characterized by translocations of the c-MYC gene on chromosome 8
• Highly aggressive
• Responds well to intensive chemotherapy
• High cure rate

Three types of Burkitt Lymphoma

• African (endemic) BL
• Sporadic (nonendemic) BL
• Associated with HIV

Endemic Burkitt Lymphoma

• Most common in children aged 4-7 years
• Prevalent in certain regions of Africa
• Infected with EBV
• Common sites include the mandible, kidneys, ovaries, and adrenal glands

Sporadic Burkitt Lymphoma Common Sites

• Ileocecum
• Peritoneum

Microscopic features of Burkitt Lymphoma

• Characteristic "Starry sky" pattern
• Intermediate-sized malignant lymphoid cells
• Tingible body macrophages
• Macrophages with abundant clear cytoplasm, containing phagocytosed nuclear remnants of apoptotic cells

Origin and Classification of NHL: T-cell and NK cell neoplasms

• Precursor T cell neoplasms includes T cell acute lymphoblastic leukemia/lymphoma (T-ALL)
• Peripheral T-cell and NK cell neoplasms
  • T cell prolymphocytic leukemia
  • Large granular lymphocytic leukemia
  • Mycosis fungoides and Sezary syndrome
  • Peripheral T. cell lymphoma, unspecified
  • Aggressive NK cell leukemia
  • Anaplastic large cell lymphoma (ALCL)
  • Angio-immunoblastic T-cell lymphoma
  • Adult T-cell leukemia/lymphoma (HTLV1+)
  • NK cell leukemia

T cell and natural killer (NK) cell lymphomas

• Account for 10% of all NHL cases
• More aggressive than B-cell lymphomas
• Peripheral T cell lymphomas are more common in Asia
• NK cell lymphomas are more common in the Far East
• Most common subtype is Peripheral T-cell lymphoma, unspecified

Staging of NHL

• Uses the Ann Arbor staging system
• Used for treatment decisions and prognosis

Treatment Options

• Radiation therapy
• Chemotherapy
• Monoclonal antibodies

Non-Hodgkin Lymphoma (NHL) is a malignant neoplasm of lymphoid origin and the most common hematopoietic neoplasm. It typically presents as a solid tissue mass, such as lymphadenopathy or an extra nodal mass. NHL is more prevalent in males and affects individuals older than 50 years.