Medical Archive

Introduction

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.

WHO classification of lymphoid malignancies

Mature (peripheral) B-cell neoplasms

Mature (peripheral) T-cell neoplasms

Lymphoplasmacytic lymphoma (Waldenstrom’s macroglobulinemia) Hairy cell leukemia  Splenic marginal zone B-cell lymphoma Extranodal marginal zone B-cell lymphoma of MALT type Nodal marginal zone B-cell lymphoma  Follicular lymphoma Mantle cell lymphoma Diffuse large B-cell lymphoma (including subtypes)  High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements  High grade B-cell lymphoma NOS  Burkitt’s lymphoma/Burkitt’s cell leukemia  Primary mediastinal large B-cell lymphoma  Plasmablastic lymphoma  Primary ewusion lymphoma  HHV8+ DLBCL NOS  Intravascular large B-cell lymphoma  ALK+ large B-cell lymphoma

T-cell granular lymphocytic leukemia Adult T-cell leukemia/lymphoma (HTLV-1+)  Extranodal NK/T-cell lymphoma, nasal type  Enteropathy-associated T-cell lymphoma  Hepatosplenic T-cell lymphoma  Subcutaneous panniculitis-like T-cell lymphoma  Mycosis fungoides  Sezary syndrome  Peripheral T-cell lymphoma, NOS  Angioimmunoblastic T-cell lymphoma  Anaplastic large cell lymphoma, ALK+  Anaplastic large cell lymphoma, ALK-

Epidemiology and etiology

<??>
NHL:HD = 8:1
m/c: DLBL
2nd: MALToma
? ???? T cell/NK cell type? ?? (esp. Extranodal, Peripheral)

Immunology

Approach to the patient

Diagnosis

??: P/E, ??/??/?? CT, ?? ??
??: SPECT or PET: large cell lymphoma / EGD: Waldeyer ring

Ann-Arbor Staging for both lymphoma

I	Single LN or lymphoid structure
II	2~ LN – diaphragm ??
III	Diaphragm ??
IV	Disseminated (extralymphatic, ‘E’??? ?.)
A	No B Sx
B	?? ? 1? ??: Wt loss, fever>38?, night sweat (HD? ?? ??? ????? ?? ? ??? ??)
E	??, ?? involve of extra-lymphatic tissue (?, ?? ??)

Clinical features, treatment, and prognosis of specific NHL

Clinical features

• Indolent – ?? ??? ???? ?? ???
  • Follicular lymphoma
• Aggressive – curable
  • DLBL (m/c)
• Highly aggressive – ?? leukemia? ??
  • Burkitt’s, lymphoblastic lymphoma

Treatment

Indolent

Limited: IFRT (involved field RTx)

Advanced, Sx (-): close f/u

Advanced, Sx (+): CTx (chlorambucil or CVP), local Sx? ?? local RTx

Aggressive

Limited: R-CHOP + IFRT

Advanced: R-CHOP

MALToma: gastric origin. H.pylori ????? 80% ?? ??.

Hairy cell lymphoma? cladribine or pentostatin.

Prognosis 

IPI(International progsnostic index) for NHL. 

• “60 APLES”
  • Age>60
  • Performance >2 or <70
  • LDH ?
  • Stage III, IV
  • Extranodal involve
• 0,1 low
• 2 low-intermediate
• 3 high-intermediate
• 4,5 high

Follicular lymphoma

Neoplastic proliferation of small B cells (CD20+) that form follicle-like nodules 

• Genetics
  • t(14;18) — heavy-chain Ig(14) with BCL-2(18)
  • Results in over-expression of Bcl2, which inhibits apoptosis
• Presentation
  • In late adulthood with painless “waxing and waning” general lymphadenopathy
• Treatment
  • Reserved for patients who are symptomatic and involves low-dose chemotherapy or rituximab (anti-CD20 antibody).
• Complication
  • Progression to diffuse large B-cell lymphoma; presents as an enlarging lymph node

• Distinguished from reactive follicular hyperplasia by… 
  • Disruption of normal lymph node architecture
  • Lack of tingible body macrophages in germinal centers
  • Bcl2 expression in follicles
  • Monoclonality 
  • Centrocytes and fewer numbers of centroblasts

Mantle cell lymphoma

Neoplastic proliferation of small B cells (CD20+) that expands the mantle zone

• Genetics
  • t(11;14) — cyclin D1 (11) and heavy-chain Ig (14), CD 5+
• Presentation
  • In late adulthood with painless lymphadenopathy

Driven by t(11;14)
Overexpression of cyclin D1 promotes G1/S transition in the cell cycle, facilitating neoplastic proliferation.

Marginal zone lymphoma

Neoplastic proliferation of small B cells (CD20+) that expands the marginal zone
The marginal zone is formed by post-germinal center B cells.
MALToma is marginal zone lymphoma in mucosal sites.
Gastric MALToma may regress with treatment of H.Pylori.

• Genetics
  • t(11;18)
• Presentation
  • Associated with chronic inflammatory states such as Hashimoto thyroiditis, Sjögren syndrome, and H.pylori gastritis

Burkitt lymphoma

Neoplastic proliferation of intermediate-sized B cells (CD20+); associated with EBV

• Genetics
  • T(8;14) — c-myc(8) with heavy-chain Ig(14)
  • Overexpression of c-myc oncogene promotes cell growth.
• Microscopy
  • Uniform, round, medium-sized tumor cells with basophilic cytoplasm containing prominent lipid vaculoes
  • High mitotic index and ‘starry-sky’ appearance d/t the presence of macrophages and apoptotic bodies in a sea of medium-sized lymphocytes. 
• Presentation
  • Classically presents as an extra-nodal mass in a child or young adult
  • African form usually involves the jaw.
  • Sporadic form usually involves pelvis or abdomen.

Diffuse large B-cell lymphoma

Neoplastic proliferation of large B cells (CD20+) that grow diffusely in sheets.
M/c form of NHL, clinically aggressive (high-grade)
Arises sporadically or from transformation of a low-grade lymphoma (e.g., follicular lymphoma)

• Genetics
  • Alterations in Bcl-2, Bcl-6
• Presentation
  • In late adulthood as an enlarging lymph node or an extranodal mass

Hairy cell leukemia

• Neoplastic proliferation of mature B cells characterized by hairy cytoplasmic processes
• 2% of adult leukemia cases, m/c in middle age men.
• Clinical manifestations
  • Pancytopenia d/t BM fibrosis
  • Splenomegaly (due to accumulation of hairy cells in red pulp)
  • Hepatomegaly/lymphadenopathy rare
• Diagnosis
  • PBS – “hairy” leukocyte cells
  • “Dry tap” on bone marrow aspiration (due to marrow fibrosis). 
  • Cells are positive for tartrate-resistant acid phosphatase (TRAP) – largely replaced with flow cytometry.
• Treatment
  • Indication
    • Cytopenia, splenomegaly.
  • Excellent response to 2-CDA (dadribine), an ADA inhibitor; adenosine accumulates to toxic levels in neoplastic B cells.
  • If refractory, replace with pentostatin or rituximab
  • Life expectancy is often near-normal. Median survival without treatment is 5 years.

Adult T-cell leukemia/lymphoma (ATLL)

Associated with HTLV-1; most commonly seen in Japan and the Caribbean

• Presentation
  • Rash (skin infiltration)
  • Generalized lymphadenopathy with hepatosplenomegaly
  • Lytic (punched-out) bone lesions with hypercalcemia.

Mycosis fungoides

Neoplastic proliferation of mature CD4+ T cells.

• Presentation
  • Infiltrate the skin, producing localized skin rash, plaques, and nodules. 
  • Pautrier microabscesses — aggregates of neoplastic cells in the epidermis
  • Cells can spread to involve the blood, producing Sézary syndrome 
    • Lymphocytes with cerebriform nuclei (Sézary cells) are seen on blood smear