Lymphoid neoplasms Flashcards
- What’s the difference between leukaemia and lymphoma?
Both of this are malignancy of white blood cell, however, Leukaemia arises from any of the haematopoietic cells in the bone marrow and can be of lymphoid or myeloid origin. Lymphoma is malignancy arising in B or T cells and arises in the lymph nodes or other secondary lymphoid organs resulting in a solit tumour.
- Which system is used to stage CLL/SLL?
Rai classification system is used to stage CLL/SLL based on appearance of bone marrow, hepatosplenomegaly, full blood count parameters
- What is Richter’s transformation?
This is the term used when a low-grade lymphoma transforms into a high-grade lymphoma which is more aggressive and has a worse prognosis. For instance, chronic lymphocytic leukaemia is a low grade lymphoma and can transform into diffused large B-cell lymphoma.
- What are the complications of CLL/SLL
- Pancytopenia – due to infiltration of bone marrow with abnormal leucocytes which causes increased risk to bacterial and fungal infection due to decreased leucocytes, pallor, tiredness and shortness of breath due to anaemia and bleeding and purpura due to thrombocytopenia
- Immunoparesis – suppressed B-cell function leading to decreased levels of immunoglobulins (hypogammaglobulinemia).
- Secondary malignancies – solid organ and melanoma
- Richter’s transformation: CLL is a low-grade lymphoma with a good prognosis, however, this could transform into diffuse B-cell lymphoma or another type of high-grade lymphoma. This is characterised by sudden onset of lymphadenopathy, splenomegaly and night sweats.
- Distinguish between the different types of HL.
Nodular sclerosis • This is the most common form and tends to occur in the cervical and supraclavicular lymph nodes
• On histology there are collagen bands that extend from the node capsule to encircle nodules of abnormal tissues
• There is the presence of lacunar and classical reed-Sternberg cells
Lymphocyte-rich • Has a good prognosis
• Mediastinal and peripheral lymph nodes are often involved
• On histology this is characterised by a background high in lymphocytes, classic and mononuclear reed-Sternberg cells and a few eosinophils and plasma cells
Lymphocyte-depleted • Poor prognosis
• Associated with human immunodeficiency virus
• Lymph nodes often involved are retroperitoneal
• On histology there is
Mixed cellular lymphoma • Often represents with B symptoms (night sweats, unexplained fever
• The background has several types of cells including lymphocytes, eosinophils, plasma cells and histiocytes and the classic reed-Sternberg cells are abundant
Nodular lymphocyte-predominant lymphoma • Excellent prognosis
• Lacks the classic R-S cells as its not always CD30+/CD15+ but is CD20+/OCT2+/BOB1+
- A 4 year old boy is brought to A&E because of severe epistaxis. Examination reveals multiple bruises on both arms and legs, together with a LUQ (lower upper quadrant) mass. CBC shows;
WCC: 21.3 x 109 / L
Hgb: 9.3 g/dL
Plt: 13 x 109 / L
APTT / INR: WNL (within normal limits)
a) What is the most likely diagnosis and differential diagnosis.
b) What investigations are done on the patient.
Given the age of the patient and presentation the child likely has acute lymphocytic leukaemia.
differential diagnosis: AML
- Full blood count – there is usually pancytopenia due to the bone marrow being overcrowded with leukemic cells, however, there might be leucocytosis
- Peripheral blood smear – this reflects what is observed in FBC – low thrombocyte and normocytic normochromic anaemia but blasts cells are often seen in abundance with this type of malignancy
- Bone marrow aspirate and trephine biopsy: more than 20% blasts in the bone marrow is confirmation of acute leukaemia.
- Immunophenotyping and cytogenetic analysis are used to confirm diagnosis and determine prognosis
- Biochemistry – increased urate, lactate dehydrogenase and sometimes calcium ion
- Chest x-ray may show mediastinal lymphadenopathy or thymic enlargement if the leukaemia is T-ALL
- Infection screen, CRP and culture to rule out infectious mononucleosis, juvenile rheumatoid arthritis and immune thrombocytopenic purpura.
- A 43-year-old man presents with painless enlarged lymph nodes in his neck. After blood tests failed to reveal anything, a lymph node was surgically removed. The histology laboratory received a fresh lymph node measuring 4 cm in size.
a) Why was the lymph node received fresh? (4 marks)
The lymph node is received fresh, wrapped in saline because 10% Neutral buffered formalin causes methylene bridges to form between proteins. This facilitates the use of flow cytometry, cytogenetics etc as formaldehyde prevents the use of these techniques. Flow cytometry is needed for confirmatory and differential diagnosis of lymphoma while cytogenetics may be needed to look at the prognosis
i. Confirm patient identification on the container matches that on the request form and look at the patient’s clinically history on the request form or through the laboratory information system (LIS).
ii. The maximum dimensions (length, width and height) of the lymph nodes are measured
iii. If the lymph node it is sliced into two section and if it is large it is serially sliced. It is important to be held with forceps and no excessive pressure is put on it to preserve the architecture.
iv. One section is placed in a special fixative for flow cytometry and transferred to haematology.
v. The other section is placed in a histology cassette and a drop of eosin is added, then placed in formalin for fixation, the tissue is processed as usual – dehydrated, cleared, paraffinized, cut into sections, mounted on a slide and stained with stained with Haematoxylin and eosin and immunohistochemistry
c) What are the differences between Hodgkin and non-Hodgkin lymphoma and why is this distinction of essential clinical importance? (5 marks)
Hodgkin Lymphoma
• Localised to a single group of nodes
• Contiguous spread
• Extranodal involvement is not common
• Mesenteric nodes and Waldeyer ring are not usually involved
• Malignant cell is the characteristic Reed-Sternberg (R-S).
• This cell attract other non-malignant cells such as lymphocytes, plasma cells and macrophages by release of cytokines.
Non-Hodgkin Lymphoma
• Often involves more than one peripheral nodes
• Erratic spread
• Extranodal involvement especially spleen and liver
• Mesenteric nodes and Waldeyer ring are often involved
• The malignant cell arises from B or T-cells and this is proliferates and infiltrates the lymph node or extranodal sites.
• R-S is absent in all cases.
It is important to differentiate between Hodgkin and non-Hodgkin lymphoma because although they present with similar symptoms, they are treated differently and have different prognosis. For instance, anti-CD30 (brentuximab) therapy can be given to some Hodgkin lymphoma subtypes but is useless in most NHL.
d) What is the difference between high-grade and low-grade non-Hodgkin lymphomas? Mention a single example in each class. (5 marks)
Low-grade
Indolent
Slow growing,
bone marrow is often involved and may also involve liver and spleen
Doesn’t respond well to chemotherapy
extranodal involvement is unusual
Follicular lymphoma, marginal zone lymphoma, mantle cell lymphoma,
High-grade Aggressive Rapid proliferation of cells Bone marrow is often uninvolved Responds well to chemotherapy extranodal involvement is common Burkitt’s lymphoma, diffuse large B-cell lymphoma, peripheral T-cell lymphoma
g) What test can be performed to assess for light chain restriction? What is the significance of light chain restriction and is this finding in keeping with the histopathologist’s diagnosis of lymphoma?
Light-chain restriction is when on flow-cytometry there is an abundance of one type of light chain (kappa or lambda). This is indicative of malignancy as B-cell lymphomas arise from proliferation of one aberrant B-cell that produce one type of light chains, A population that is abundant in both light chains is suggestive of a reactive lymph node as they arise from different B-cells.
Therefore, light chain restriction further confirms the Histopathologists diagnosis of lymphoma.
However, it’s important to note that certain lymphomas such as Hodgkin lymphoma, do not show light chain restriction, as the Reed-Sternberg cells is not abundant and, rare co-existing conditions which result from proliferation of 2 different type of B-cell can result in a mixed popu-lation as well.
b. What further laboratory investigations are performed?
- Serum protein electrophoresis and Serum immunoglobulins (IgG, IgA and IgM) levels determined by nephelometry - detect the presence and quantify the gamma globulins and subtyping them by
- Immunofixation – to determine the subtype of immunoglobulin – heavy and light chain
- Bone marrow aspirate and trephine biopsy – atypical plasma cells infiltrate the bone marrow and is the technique used for confirmation
- Flow-cytometry: shows light chain restriction
- Cytogenetics
