I.   Classify the Non-Hodgkin lymphoma

Non-Hodgkin’s lymphoma is a tumor that gives rise from the lymphatic system, which is a network of lymphatic vessels throughout the body that contain a fluid called lymph to the heart, this system is important for immunity of the body.
In Non-Hodgkin’s lymphoma cancer cells get developed from lymphocytes (which are a segment of white blood cells), this type of lymphoma is more common than other types of lymphoma (example : Hodgkin lymphoma). There are many subtypes of this lymphoma , for insistence , follicular and Diffuse large b-cell lymphoma are the most common types of this lymphoma.
Non-Hodgkin’s lymphomas (NHL) are cancers of mature B, T, and NK cells. They were distinguished from Hodgkin lymphoma (HL) upon recognition of the Reed-Sternberg (RS) cell, and differ from HL with respect to their biologic and clinical characteristics. Whereas ~80–85% of patients with HL will be cured of their lymphoma by chemotherapy with or without radiotherapy, the prognosis and natural history of NHL tends to be more variable. NHL can be classified as either a mature B-NHL, or a mature T/NK-NHL depending on whether the cancerous lymphocyte is a B, T, or NK-cell, respectively. Within each category are lymphomas that grow quickly and behave aggressively, as well as lymphomas that are more indolent, or slow growing in nature. For a list of the World Health Organization (WHO) classification of lymphoid neoplasms
It has 5 common types :-
• Chronic lymphocytic leukemia
• Cutaneous B-cell lymphoma
• Cutaneous T-cell lymphoma
• Follicular lymphoma
• Waldenstrom macroglobulinemia

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1- Burkitt lymphoma:-

Burkitt lymphoma occurs in adolescents or young adults, its mutation is T(8;14)- Translocation and c-myc(8) and heavy-chain Ig(14), it has a “starry sky” appearance, sheets of lymphocytes with interspersed “tangible body” macrophages, associated with EBV.
Jaw lesion in endemic form in Africa;pelvia or abdomen in sporadic form.
Burkitt’s lymphoma. The neoplastic cells are homogeneous, medium-sized B cells with frequent mitotic figures, a morphologic correlate of high growth fraction. Reactive macrophages are scattered through the tumor, and their pale cytoplasm in a background of blue-staining tumor cells gives the tumor a so-called starry sky appearance.

Diffuse large B-cell lymphoma:-

Occurs in usually in older adults, but 20% in children, genetic mutations include alterations in BCl-2,BCl-6, it is the commonest tyoe of non-hodgkin lymphoma in adults.
Diffuse large B-cell lymphoma. The neoplastic cells are heterogeneous but predominantly large cells with vesicular chromatin and prominent nucleoli.
3- follicular lymphoma :-

It occurs in adults, it occurs in mutations t(14-18)-translocation of heavy-chain Ig(14) and BCL-2 (18). Indolent course ;Bel-2 inhibits apoptosis and clinical features include presents with painless “waxing and waning” lympthadenopathy.

Follicular lymphoma. The normal nodal architecture is effaced by nodular expansions of tumor cells. Nodules vary in size and contain predominantly small lymphocytes with cleaved nuclei along with variable numbers of larger cells with vesicular chromatin and prominent nucleoli.
4- Multiple myeloma :-
Monoclonal plasma cells (“fried egg” appearance) cancer that arises in the marrow and produces large amounts of IgG (55%) or IgA(25%). Bone marrow >10% monoclonal plasma cells. Most common 1 degree tumor arising within bone in people less then 40-50 years old.
Assoicated with rouleaux formation, high susceptibility to infection, Ig light chains In urine, M spoike on serum protein electrophoresis, punched-out lytic bone lesions on X ray and primary amyloidosis(AL).
5- Small lymphocytic lymphoma:-
Age effected is greater then 60, it is the most common type of adult leukemia. CD20+,CD23+,CD%+ B-cell neoplasm. Often asymptomatic, progresses slowly; smudge cell in peripheral blood smear; autoimmune hemolytic anemia. CLL is crushed little lymphocytes (smudge cells).
Richter transformation – CLL/SLL transformation into aggressive lymphoma, most common diffuse large B-cell lymphoma (DLBCL).
6- Anaplastic Large Cell Lymphoma
ALCL is the next most common T-cell lymphoma after AITL but is more common in children, accounting for up to 10% of pediatric lymphomas. Approximately 40–60% of cases with harbor t(2;5) which fuses a portion of the nucleolar protein nucleophosmin-1 (NPMI) gene to a part of the anaplastic lymphoma kinase (ALK) gene, the product of which has constitutive tyrosine kinase activity. These patients have a much more favorable prognosis compared to ALK-negative ALCL, akin to that of DLBCL. There is an additional, more indolent and favorable subtype that occurs in the breast tissue of patients with breast implants, and there is a cutaneous variant. In general, this is a disease that is more common in men. ALK-positive disease is a disease of younger patients with a median age at diagnosis of 34 years, whereas the median age at diagnosis of ALK negative patients is 58. With the exception of the cutaneous variant and the variant associated with breast implants, most patients present with rapidly growing lymphadenopathy with or without extranodal involvement; B symptoms are common.

Most cases of ALCL involve large atypical lymphocytes with a horseshoe-shaped nuclei with prominent nucleoli (“hallmark” cells). Tumor cells tend to be localized within the lymph node sinuses, and almost all are positive for CD30 but negative for CD15. A majority will also express CD3, CD25, CD43, and CD4. ALK rearranged ALCL can be diagnosed by FISH cytogenetics for t(2;5) or by immunohistochemical staining for ALK.

ALCL is generally treated with CHOP, although like PTCL NOS, CHOEP may benefit younger patients, particularly with ALK+ disease. Overall, ALCL has a better prognosis than PTCL, and this is particularly true for ALK-positive disease, which has an 8-year OS of 82 versus 49% for ALK-negative disease. Relapsed ALK-positive ALCL is treated similarly to relapsed DLBCL, with salvage combination chemotherapy to identify chemotherapy sensitivity followed by autologous stem cell transplant. For patients with chemoinsensitive diseaese or for ALK- negative disease, the conjugated anti-CD30 antibody to monomethyl aurostatin E (MMAE) brentuximab is highly active with a response rate of 86% and a complete response rate of 57%. It is currently being investigated in combination with cyclophosphamide, adriamycin, and prednisone for the primary treatment of disease. The ALK inhibitors, including crizotinib, are active in refractory ALK-positive ALCL with excellent outcomes.

Chapter 104: Non-Hodgkin’s Lymphoma Caron A. Jacobson; Dan L. Longo fir
First aid for usmle step 1, 2018, page 394-413


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