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Non-Hodgkin's lymphoma

  1. Incidence. Non-Hodgkin's lymphomas (especially CNS lymphomas) are more common in patients with acquired immunodeficiency states and in patients receiving immunosuppressive drugs, such as renal and heart transplant patients.
  2. Etiology
    1. Cytogenetic abnormalities, such as chromosome translocations, are commonly observed in lymphoma cells.
    2. Viral infection
      1. The Epstein-Barr virus (LQ 2012) has been linked to Burkitt's lymphoma.
      2. An aggressive T-cell leukemia or lymphoma is associated with human T Lymphotropic virus type I (HTLV-I) infection.
  3. Pathology. histologic classification literature
    Classification of the Morphological Subgroups of Non-Hodgkin's Lymphomas
    1. Low-grade malignant lymphoma
      1. Small lymphocytic ≅ CLL
      2. Follicular-predominantly small-cleaved cell
      3. Follicular-mixed (small cleaved and large cell)
    2. Intermediate-grade malignant lymphoma
      1. Follicular-predominantly large cell
      2. Diffuse-small-cleaved cell
      3. Diffuse-mixed (small and large cell)
      4. Diffuse-large cell
    3. High-grade malignant lymphoma
Large cell
  1. Convoluted lymphoblastic ≅ ALL
  2. Small noncleaved cell (Burkitt's)

Extra Edge: Important translocation to be remembered


Translocation Associated Malignancy
t (8 – 14)
i. Burkitt’s lymphoma
ii. ALL (FAB type L3)
iii. Immunoblastic B cell lymphoma
t (4 – 11) ALL
t (14-18) B cell lymphomas
t (15 –17) Promyelocytic leukemia (M3 – AML)
t (11 – 14) i. CLL
ii. Mantle cell lymphoma
T (8 – 14) Burkitt

Table - Infectious Agents Associated with the Development of Lymphoid Malignancies (Ref. Hari. 18th ed., Pg-921, table 110.4)
Infectious Agent Lymphoid Malignancy
Epstein-Barr virus
  1. Burkitt's lymphoma
  2. Post–organ transplant lymphoma
  3. Primary CNS diffuse large B cell lymphoma
  4. Hodgkin's disease
  5. Extranodal NK/T cell lymphoma, nasal type
  1. Adult T cell leukemia/lymphoma
  1. Diffuse large B cell lymphoma
  2. Burkitt's lymphoma
Hepatitis C virus Lymphoplasmacytic lymphoma
Helicobacter pylori Gastric MALT lymphoma
Human herpesvirus 8 Primary effusion lymphoma
Multicentric Castleman's disease



Note: CNS, central nervous system; HTLV, human T cell lymphotropic virus; MALT, mucosa-associated lymphoid tissue; NK, natural killer.

  1. Clinical features
    1. Most patients are asymptomatic. Or may have fever, night sweats, or weight loss.
    2. Patients with indolent lymphomas may have waxing and waning adenopathy for several months before diagnosis, although persistent nodal enlargement is more common.
    3. Extranodal disease most often involve the stomach, lung, and bone, resulting in symptoms characteristic of the affected organ. Involvement of Oropharyngeal lymphoid tissue (Waldeyer Ring) causes sore throat and obstructive breathing.
    4. If bone marrow is involve that lead to pancytopenia.
    5. Skin is involve in T cell lymphoma.
  2. Staging and diagnosis
    1. The Ann Arbor staging system used to classify Hodgkin's disease is also used to stage non-Hodgkin's lymphomas.
Table - International Prognostic Index for NHL (Ref. Hari. 18th ed., Pg- 925, table 110.9)

Five clinical risk factors:
  1. Age ≥60 years
  2. Serum LDH levels elevated
  3. Performance status ≥2 (ECOG) or ≤70 (Karnofsky)
  4. Ann Arbor stage III or IV
  5. >1 site of extranodal involvement
  6. Therapy
  1. Radiation therapy. Non-Hodgkin's lymphomas are very radiosensitive. It is use for localized stage 1 disease but that is rare.
  2. Chemotherapy is the main treatment.
    1. Low-grade indolent lymphomas = chlorambucil or cyclophosphamide,
    2. High grade NHL = Chemotherapy (Most Common regimen is CHOP (cyclophosphamide, doxorubicin, vin¬cristine, and prednisone)
    3. Rituximab is also used

Recent Advance New Drug


Ibritumomab: It is useful in the treatment of relapsed or refractory low-grade, follicular or transformed B-cell NHL (Non-Hodgkin’s lymphoma)


Clinical differences between Hodgkin and non Hodgkin lymphomas (Ref. Robbins (Basic Pathology 8th ed.) Pg - 459)
Hodgkin lymphoma Non-Hodgkin lymphoma
More often localized to a single axial group of nodes (cervical, mediastinal, para-aortic) More frequent involvement of multiple peripheral nodes
Orderly spread by contiguity Noncontiguous spread
Mesenteric nodes and Waldeyer ring rarely involved Mesenteric nodes and Waldeyer ring commonly involved
Extranodal involvement uncommon Extranodal involvement common
Burkitt lymphoma is a cancer of the lymphatic system (in particular, B lymphocytes).
Burkitt's lymphoma is associated with c-myc gene translocation. This gene is found at 8q24.
The most common variant is t(8;14)(q24;q32).
Types of Burkitt’s Lymphoma
TYPE AGE SEX SITE (most common to least common)
a. Endemic 8-15 M>>>F Face, abdomen, CNS, LN, BM
b. Sporadic 8-15 M>>>F abdomen > face
c. AIDS associated Young Adults M=F LN, BM
PBF - Starry sky appearance
Highly proliferative lymphoma- Doubling time – 60 hours (most rapid)
Malignant B cell characteristics
  1. Normal B cells possess rearranged immunoglobulin heavy and light chain genes and each isolated B-cell possesses a unique IgH gene rearrangement.
  2. Since Burkitt lymphoma and other B-cell lymphomas are a clonal proliferative process, all tumor cells from one patient are supposed to possess identical IgH genes.
  3. When the DNA of tumor cells is analyzed using electrophoresis, a clonal band can be demonstrated since identical IgH genes will move to the same position.
  1. Cyclophosphamide
  2. Doxorubicin
  3. Vincristine
  4. Methotrexate
  5. Cytarabine
  6. Ifosfamide
  7. Etoposide
  8. Rituximab
Other treatments are immunotherapy, bone marrow transplants, surgery to remove the tumor, and radiotherapy.

Mycosis Fungoides

Mycosis fungoides is synonymous with Cutaneous T cell lymphoma. It is the most common form of cutaneous lymphoma.
Clinical presentation and course:
  1. Mycosis fungoides has an indolent course. 
  2. Most affected individuals have disease that remains localized to the skin for many years. 
  3. It begins on the skin and may involve only the skin for years or decades
  4. Presentation is with localized or generalized erythematous / eczematous skin lesions. 
  5. Skin lesion progress from 'patch' stage to 'plaque stage' to cutaneous 'tumors' stage. 
  6. Metastasis occurs in advanced stages to: 
1. To lymph nodes 2. Peripheral circulation
Sézary syndrome (Erythroderma and Circulating tumor cells)
Seeding of the blood by melanoma tumor cells is accompanied by diffuse erythema and scaling of the entire body surface (erythroderma).
Sezary - Lutzner cells Pautrier Microabscesses
  • Histological hall mark of Mycosis fungoides
  • These are T helper cell (CD4 positive)
Sézary - Lutzner cells characteristically form band like aggregates within the superficial dermis and invade the epidermis as single cells or small clusters called Pautrier's Microabscesses.
Treatment (Mycosis fungoides is not easily amenable to treatment) 
  1. The treatment of Mycosis fungoides is complex. Even early and aggressive treatment has not been proved to cure or prevent progression of the disease. 
  2. Cure has been possible with radiotherapy only in rare patients with early stage mycosis fungoides. 
  3. Most of the treatment for mycosis fungoides are palliative.
  4. Other T/T options are – steroid, topical nitrogen mustard & PUVA.
Note: Mycosis fungoides has an indolent course but it is not easily amenable to treatment.

Summary of the more common Lymphoid Neoplasms (Ref. Robbins, Basic Pathology 8th ed., Pg - 448)

Entity Salient Morphology Immunophenotype
Precursor B-cell lymphoblastic leukemia/lymphoma Lymphoblasts with irregular nuclear contours, condensed chromatin, small nucleoli, and scant agranular cytoplasm. TdT + immature B cells (CD19+, variable expression of other B cell markers)
Precursor T-cell leukemia/ lymphoma Identical to precursor B-cell lymphoblastic leukemia/lymphoma TdT+ immature T cells (CD2+, CD7+, variable expression of other T-cell markers)
Small lymphocytic lymphoma/ chronic lymphocytic leukemia Small resting lymphocytes mixed with variable numbers of larger activated cells; lymph nodes diffusely effaced CD5+ B cell expressing surface Ig
Follicular lymphoma Frequent small "cleaved" cells mixed with large cells; growth pattern is usually nodular (follicular). CD10+ BCL2+ mature B cells that express surface Ig
Mantle cell lymphoma Small to intermediate-sized irregular lymphocytes growing in a diffuse pattern CD5 – CD10 – mature B cells with surface Ig
Extranodal marginal zone lymphoma Variable cell size and differentiation; 40% show plasmacytic differentiation; B cells home to epithelium, creating "lymphoepithelial lesions" Mature B cells with variable expression of CD10 and surface Ig
Diffuse large B cell lymphoma Variable; most resemble large germinal center B cells; diffuse growth pattern Mature B cells with variable expression of CD10 and surface Ig
Burkitt lymphoma Intermediate-sized round lymphoid cells with several nucleoli; diffuse tissue involvement associated with apoptosis produces a "starry-sky" appearance Mature CD10+ B cells expressing surface Ig
Plasmacytoma/plasma cell myeloma Plasma cells in sheets, sometimes with prominent nucleoli or inclusions containing Ig Terminally differentiated plasma cells containing cytoplasmic Ig
Mycosis fungoides In most cases, small lymphoid cells with markedly convoluted nuclei; cells often infiltrate the epidermis (Pautrier microabscesses) CD4+ mature T cells
Peripheral T-cell lymphoma, not otherwise specified (NOS) Variable; usually a spectrum of small to large lymphoid cells with irregular nuclear contours Mature T-cell phenotype (CD3+)
Hodgkin lymphoma, nodular sclerosis type Lacunar Reed-Sternberg cell variants in a mixed inflammatory background; broad sclerotic bands of collagen usually also present CD15+, CD30+ Reed-Sternberg cells
Hodgkin lymphoma, mixed cellularity type Frequent classic Reed-Sternberg cells in a mixed inflammatory background CD15+, CD30+ Reed-Sternberg cells

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