Please enable JavaScript.
Coggle requires JavaScript to display documents.
Lymphomas (Hodgkin’s (Investigation (Diagnosis (lymph node biopsy: …
Lymphomas
Hodgkin’s
origin: germinal centre B-cell
Reed-Sternberg [cells owl’s] eyes {mixed cellularity} or variants (lacunar cell {nodular sclerosis}, popcorn {lymphocyte predominance} ) in the affected tissues
cells in affected lymph node are polyclonal reactive lymphoid cells, not neoplastic cells.
Investigation
Diagnosis
lymph node biopsy:
Nodular lymphocyte predominance
Nodular sclerosis, Mixed cellularity
Presence of inflammatory cell infiltrates distinguishes HL from NHL
Ann Arbor staging system
based on physical examination, CT scan (chest, abdomen, pelvis), and bone marrow biopsy.
Stage I: Involvement of single lymph node or single extralymphatic site
Stage II: involvement of two or more lymph nodes but on same side.
Stage III: both sides of diaphragm involved
Stage IV: dissemination of disease to extralymphatic sites
For diagnosis
history and examination, Chest X-ray for mediastinal widening,
CT scan of chest, abdo, pelvis, ± neck, PET scan
± Bone marrow (for stage III or IV or HIV positive) Blood count, differential, film
For planning therapy
UEs, LFTs and biochemistry, Serum uric acid
Virology: HIV, hepatitis B, C, Cardiac & Respiratory function, Fertility
Hasenclever score
used for prognostication (treatment planning)
Epidemiology
less frequent than non-Hodgkin
M > F
bimodal age distribution—one peak in the 20s and 60s.
etiological factors
EBV infection
immunodeficiency
higher socio-economic status
caucasian > non-caucasian
genetic predisposition
Clinical features
painless lymphadenopathy commonly in Cervical, supraclavicular, and axillary
cough (secondary to mediastinal lymph node involvement)
“B” symptoms (fever, night sweats, and weight loss)
pruritus
Treatment and Prognosis
Stage I,II
ABVD (adriamycin [doxorubicin], bleomycin, vinblastine, and dacarbazine) x 2-4 & radiation, 80-90% 5 year survival
Stage III,IV
ABVD x 6-8, 70-80% 5 year survival
prognostic factors
Serum albumin, Haemoglobin, Age, Sex, Stage, Leucocytosis, Lymphopenia
major short-term toxicity relates to myelosuppression and mucositis
Long term complications of treatment
infertility
MOPP > ABVD; males > females
sperm banking should be discussed
premature menopause
secondary malignancy
skin, AML, lung, MDS, NHL, thyroid
cardiac disease
classification
Classical Hodgkin’s lymphoma (cHL): 90–95% of cases
hallmark of which is the Reed–Sternberg cell
Nodular sclerosis HL 70%، Mixed cellularity HL 20%
Lymphocyte-rich HL 5%، Lymphocyte-depleted HL (worst prognosis) Rare
Nodular lymphocyte predominant HL (NLPHL):
characterized by the Reed–Sternberg cell variant, the ‘popcorn cell’.
Hodgkin’s lymphoma 5%
Non-Hodgkin’s
Risk factors
inherited syndromes, e.g. ataxia-telangiectasia and Wiskott–Aldrich syndrome
human T-cell leukaemia virus type 1 (HTLV-1) related to adult T-cell lymphoma/leukaemia.
immunosuppression or immunodeficiency
connective tissue disease
family history of lymphoma
infectious agents (HIV, EBV, H.pylori)
ionising radiation
International Prognostic Index (IPI)
Five clinical risk factors:
age > 60 l.
Performance status (WHO) ≥ 2
Ann Arbor stage > II
. > 1 site of extranodal involvement
serum LDH elevated
Clinical features
Local: lymphadenopathy, splenomegaly most common
Systemic: B symptoms, pruritus
Variable:
from asymptomatic to extremely ill
time: over weeks, months, or years
anemia, leukopenia, eosinophilia, high LDH, and high ESR
neoplastic transformation of both the B (80%) and T (20%) cell lymphatic cells.
twice as common as Hodgkin
can spread to extralymphatic organs and the bloodstream.
The staging system for NHL is the same as that for Hodgkin disease
Diagnosis
as in Hodgkin
Classification
Primary cutaneous lymphoma
(T or B cell)
Mycosis fungoides,
Sézary syndrome
commonest cutaneous lymphoma
later in the disease spreading to other organs.
Presents with eczematoid skin lesions
cribriform shape of lymphocytes
Cutaneous B-cell lymphoma
B-cell
Follicular lymphoma 29%
second commonest non-Hodgkin’s lymphoma.
occurs in middle to late life
patients present with painless lymphadenopathy, some with ‘B’ symptoms.
antibody therapy (rituximab), targeting the CD20 antigen might help.
Transformation to diffuse large B-cell lymphoma up to 25%
aggressive
associated with BCL-2 gene rearrangement [t(14;18)]
treatment if asymptomatic (“watch-and-wait”)
chemotherapy options if symptomatic
Diffuse large B-cell lymphoma (DLBCL) 37%
commonest lymphoma in the adult population.
second commonest in childhood.
aggressive
presentation:
painless lymphadenopathy, clinically at one or several sites.
extra-nodal involvement is common
curable in 60%
t(3; 4) BCL6
Burkitt’s lymphoma 0.8%
commonest childhood malignancy
male > female
three types:
Endemic (involves facial bone and jaw): EBV-associated, in Africa, malaria
Sporadic: 30% EBV-related
AIDS-related
translocation: t(8;14) MYC/IGH
(highly aggressive)
Mantle cell lymphoma 7%
male > female.
painless lymphadenopathy, often generalized.
hepatosplenomegaly
t(11; 14)
Lymphoplasmacytic lymphoma 1.4%
uncommon
when associated with an IgM paraprotein and bone marrow infiltration is known as Waldenström’s macroglobulinaemia.
same in men and women
t(9; 14), PAX5/IGH
Primary extranodal lymphoma
Primary CNS lymphoma:
diffuse large B-cell lymphoma,
in both the immunocompetent and the immunosuppressed
diagnosis: biopsy, MRI
Primary gastric lymphoma: 9%
MALT lymphoma,
closely related to Helicobacter infection,
t(11; 18), BIRC3/MALT1
T and natural killer (NK) cell lymphomas
Peripheral T-cell lymphoma – (aggressive) 25.9%
Angioimmunoblastic 18.5%
Extranodal natural killer/T-cell lymphoma 10.4%
Adult T-cell leukaemia/lymphoma (very aggressive) 9.6%
Anaplastic large cell lymphoma, ALK+ (aggressive)6.6%
Anaplastic large cell lymphoma, ALK− (aggressive)5.5%
treatment
Indolent
Grade I - II
“Watchful waiting”
Radiptherapy
Grade III - IV
Chemoimmunotherapy incorporating rituximab is the treat- ment of choice
‘CHOP-R’ (cyclo- phosphamide, doxorubicin, vincristine and prednisolone + rituximab) and the less intensive ‘R-CVP’ (rituximab + cyclophosphamide, vincristine and prednisolone)
“Watchful waiting”
Purin analoges (2CdA, Fludarabina)
Alkylating agent
polychemotherapy
monoclonal antibodies +/- chemotherapy
Agressive
Chemotherapy CHOP (cyclophosphamide, hydroxy-adriamycin, onco- vin [vincristine], prednisone) 8 cycles with monoclonal antibody
autoPBSCT depends on IPI
Relapses of NHL can be controlled with autologous bone marrow transplantation.
low-gradelymphomas— Cure is rare. Median survival is 5 to 7 years.
Intermediate-grade lymphomas—Fifty percent of patients can be cured with aggressive therapy. Median survival is about 2 years.
High-grade lymphomas—Up to 70% can be cured with aggressive therapy. Median survival without treatment is a few months.
Prognostic factors
Age >60 years,
Stage III or IV, i.e. advanced disease
High serum lactate dehydrogenase level
More than one extranodal site involved
complications of lymphoma
bone marrow failure (infiltration)
CNS infiltration
immune hemolysis or thrombocytopenia
compression of structures by bulky disease
pleural/pericardial effusions, ascites
• Increased risk of infection.
• Recurrence and metastasis.
• Increased risk of cardiovascular disease.
• Complications of chemotherapy.
• Neurological complications.
Tumor lysis syndrome
oncologic emergency caused by massive tumor cell lysis, with the release of large amounts of potassium, phosphate, and uric acid into the systemic circulation.
most often occurs after the initiation of cytotoxic therapy in patients with high-grade lymphoma (particularly Burkitt’s and acute lymphoblastic leukemia)
Patients should receive prophylactic oral or IV allopurinol plus adequate IV hydration to maintain high urine output (>2.5 L/day).
potentialcompli- cation of chemotherapy seen in acute leukemia and high-grade NHl.
Rapidcelldeathwith release of intracel- lular contents causes hyperkalemia, hyper- phosphatemia, and hyperuricemia.