W4-LP-LYMPHOID NEOPLASM Flashcards
List 3 functions of the lymph node
- lymphopoiesis
- Filtration of lymph
- Processing of antigens
What are the 2 main disoders of lymphoid cells?
- Proliferations:
-Reactive
-Neoplastic - Deficiencies
Name the CD surface membrane receptors on the surface of B cells, T cells, and Macrophages
B cells-CD 19 & CD 20
T cells- CD 3
Macrophages- CD 68
Name the visible immunological markers that mark these CD receptors by light microscopy.
- immunoperoxidase
- immunohistochemical stains
CLINICAL ASSESSMENT OF A PATIENT WITH SUSPECTED LYMPHOMA
- History:
Presence of non-painful lymphodenopathy, accompained by: fever, sweating, weight loss, malaise, weakness and
pruritis. These symptoms usually suggest advanced, widespread disease - Physical examination
- Diagnostic tests
a). Formal lymph node biopsy:
Perform biopsy on the largest lymph node as it is most likely
to show specific abnormalities.
-The entire lymph node should be resected; partial
resection or needle biopsies are not acceptable in the initial workup of the patient
as they may miss the involved areas of the node.
-If infection is
suspected, lymph node tissue should also be submitted for microbiology culture
b) bone marrow examination – aspirate and trephine biopsy
c) less commonly, mediastinal biopsy and liver biopsy may be
performed
- Blood tests: full blood count, erythrocyte sedimentation rate, liver and renal function tests
- Radiological investigations: chest X-ray, CT scan, ultrasound in some cases. PET
scans are starting to be used to detect disease as wel
Malignant neoplasms that arise from B-cells, T-cells.
Lymphomas
What are the 2 main groups of lymphomas?
- The non-Hodgkin lymphomas (NHL)
- Hodgkin Lymphoma (HL)
T/F
Both Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphoma (NHL) are types of malignant lymphomas.
TRUE
What differentiates the Hodkin’s lymphoma (HL) from the non-Hodkin’s lymphoma (NHL)?
Presence of large neoplastic Reed-Sternberg cells in the HL
What is the common location of NHL in the body?
nodal in location and may involve any one or more of the lymph node groups in the body.
May involve other lymphoreticular organs or tissues such as spleen, bone marrow, liver, tonsils or extranodal lymphoid tissue in many organs. It may even involve tissue such as the skin, thyroid and brain in which lymphoid tissue is not normally seen
NHL
2-5 times more frequent than Hodgkin’s lymphoma
NHL
List 4 histological types of B cell NHL and outline how they distribute among different age groups
- Lymphoblastic lymphoma most commonly affects children and young adults.
- Small lymphocytic lymphoma affects men more than women. It is a disease of the elderly.
- Endemic Burkitt’s lymphoma is a tumour of childhood. The sporadic form also
affects children and young adults. - Large cell anaplastic lymphoma has a bimodal age distribution, affecting
children and the elderly.
Group of neoplasms composed of immature precursor B or T lymphocytes,
referred to as blasts
Precursor neoplasms:
Acute lymphoblastic lymphoma/leukaemia (ALL)
Name all PERIPHERAL B CELL NHLs
- B cell small lymphocytic lymphoma/Chronic lymphocytic leukaemia
- Mantle cell lymphoma
- Follicular lymphoma
- Diffuse large B cell lymphoma
- Immune deficiency associated large B cell lymphoma
- Body cavity large B cell lymphoma
- Burkitt’s lymphoma (BL)
- Primary extranodal lymphomas
B cell small lymphocytic lymphoma/Chronic lymphocytic leukaemia.
Neoplasms composed of small lymphocytes that may present as either lymphomas or leukaemias.
*incidence increases after the age of 50 years.
Discuss the histology of Small Lymphocytic Lymphoma or leukemia
- Small lymphocytic neoplasms show a monotonous infiltration (uniform appearance of the cells infiltrating the affected tissues) of small cells, which
- express B cell markers, and surface markers CD5 and CD23.
- Smudge cells are a tell-tale sign
A very small percentage of patients with SLL will
transform to a more aggressive lymphoid neoplasm, such as a diffuse large B cell lymphoma. What is the transition called?
This is known as Richter’s transformation
Outline the features of Mantle cell lymphoma
- Usually presents with lymphadenopathy, but may be found at extranodal sites, notably the gastrointestinal tract
- Affect mostly males
- median age of patients is 60 years
- Median survival of the neoplasm<5 yrs
- neoplastic cells tend to
“home” to the mantle zones of lymphoid follicles - Mantle cell lymphoma is associated with a characteristic
(11;14) reciprocal chromosomal translocation. This results in overexpression of the gene
which codes for cyclin-D1. This protein can be demonstrated with immunohistochemistry.
The hallmark of_____lymphoma is the (14; 18) chromosomal translocation, which juxtaposes the BCL-2 gene to the IgH or heavy chain gene, with overexpression of BCL-2. This is an anti-apoptotic protein which results in cells accumulating due to decreased
apoptosis.
Follicular lymphoma
*This disease is slowly progressive, but difficult to cure.
Outline the features of Diffuse large B cell lymphoma
- One of the commonest categories of NHL, constituting about 20% of all NHL’s,
and about 60% of aggressive lymphomas. - incidence is markedly increased in HIV positive people
- There is a male preponderance
- Common morphologic features of these tumours are monomorphic, relatively large cells, and a diffuse growth pattern
- These mature B cell tumours express CD 20, and are negative for TdT.
- As a group, these tumours are aggressive and rapidly fatal if untreated
Name the 3 special subtypes of B cell NHL
- Immune deficiency associated large B cell lymphoma:
Arise in setting of severe T cell immune deficiency. The neoplastic cells are often latently infected with Epstein-Barr virus (EBV) - Body cavity large B cell lymphoma:
-Arise as malignant pleural effusions or ascites.
-Most cases are seen in patients with advanced HIV infection, but a few have been observed in HIV negative elderly patients.
-In all cases, the tumour cells are infected with human herpes virus 8 (HHV8), which
may play a causal role in the development of these tumours - Burkitt Lymphoma:
Three categories are recognized:
a). African (endemic) BL.
b). Sporadic (non-endemic) BL
c). Subset of aggressive lymphomas (BL-like) occurring in patients infected with
HIV
Outline the features of African type Burkitt lymphoma
- Endemic in Central Africa, in areas where malaria is endemic
- Classically presents in children 4-9 years of age as a jaw tumour
- There is also often involvement of the orbit and growth into the mouth.
- The tumour is characterized by t(8;14) chromosomal translocation, with c-myc
overexpression. - In most endemic cases, EBV DNA is found in the malignant cells.
Outline the features of Sporadic BL (non-endemic)
- Usually occur in older children and young adults.
- The tumour presents in retroperitoneal soft tissues, thyroid gland, kidneys, ovaries and central nervous system.
- They too are associated with (c-myc) translocations.
- Morphologically, BL shows malignant medium sized B cells with basophilic cytoplasm.
- There is a high mitotic rate.
- Interspersed between the tumour cells are macrophages
containing cellular debris, giving the characteristic “starry sky” appearance
Outline the features of Primary extranodal lymphomas
- Briefly, this is a distinct group of tumours, predominantly of B cell phenotype.
- Common sites of extranodal lymphoma, in descending order of frequency are the GIT, skin,
Waldeyer’s ring, salivary glands, thymus gland, ocular adnexa, thyroid gland, lung
and testis
Name all the T cell and NK cell neoplasms (NHL)
- Adult T cell lymphoma/leukaemia
- Peripheral T cell lymphoma, unspecified
- Anaplastic large cell lymphoma
- Mycosis fungoides/Sezary syndrome
Outline the features of Adult T cell lymphoma/leukaemia
- Confined to patients infected with the HTLV-1 retrovirus
- Caribbean.
- This is a disease of adults
- The lymph node involved is diffusely replaced by neoplastic T cells, which vary in cell
size and regularity. Neoplastic cells may also be seen in peripheral blood. - Patients often have aggressive disease, associated with lytic bone lesions and
hypercalcaemia.
Features of Peripheral T cell lymphoma, unspecified
-This is also a disease of adults.
- It has an aggressive course, but is potentially curable.
- These neoplasms typically contain a mixture of small and large neoplastic T cells,
often with irregular nuclei.
- There may be marked infiltration of non-neoplastic cells in the background, including macrophages and eosinophil
Features of Anaplastic large cell lymphoma
- The majority of cases are children or young adults
- The clinical pattern is variable, some showing widespread involvement of lymph nodes
and other sites, and others being confined to skin. - The neoplastic cells tend to be
larger than in any other type of lymphoma, with bizarre large cells, some multinucleated. - In most cases, cell lineage markers indicate a T cell phenotype.
- A t(2;5) chromosomal translocation, causing fusion of ALK and NMP genes, may be
demonstrated, detectable by immunostaining for ALK protein. - The tumours with this translocation tend to have a better prognosis.
Features of Mycosis fungoides/Sezary syndrome
- Mycosis fungoides is a T cell lymphoma seen most commonly in the skin, but which is referred to as Sezary syndrome when the characteristic cells are also found in the peripheral circulation.
- The neoplastic cells accumulate in the epidermis, where they may form localized pockets
referred to as “Pautrier’s micro-abscesses”, and have typical convoluted cerebriform
nuclear morphology.
As the disease progresses it can spread to lymph nodes, where the interfollicular zones are infiltrated.
- The cells express T cell markers and are almost always of CD4 helper subtype.
Discuss the epidemiology of HL
- The age of presentation varies in different socioeconomic groups and countries.
- The USA and Britain, see a bimodal age curve, with
the first peak occurring between 15-35 years of age and the second peak beyond 50
years of age. - In underdeveloped countries, the disease is much more frequent under the age of 10 years.
- Overall, males and females are equally affected. Nodular sclerosing HL affects women
more frequently
Large, abnormal lymphocytes that are the hallmark of Hodgkin Lymphoma.
Typically, they have a distinctive appearance with two nuclei that look like “owl’s eyes
Reed- Steenburg ccells
Unique to_______ lymphoma is that these cells occur amidst a background of other cells, all of which are apparently benign and reactive. These include lymphocytes, histiocytes, eosinophils, plasma cells and fibroblasts
Hodkin’s lymphoma
*The neoplastic cells usually make up a small fraction of the total cellular component.
Clinical presentation of Hodkin’s lymphoma
- HL starts as unifocal or unicentric disease.
- In the vast majority of patients, HL is initially confined or localized to the superficial lymph nodes (particularly cervical lymph nodes).
- There are well -defined, orderly and predictable patterns of spread in most patients. HL usually spreads to contiguous sites (areas or tissues that are next to or touching each other)
Name the 4 subtypes of classic Hodkin’s lymphoma
- Nodular sclerosis Hodgkin lymphoma
- Lymphocyte-rich classic Hodgkin lymphoma
- Mixed cellularity Hodgkin lymphoma
- Lymphocyte depletion Hodgkin lymphoma
∗ Nodular lymphocyte predominance Hodgkin lymphoma
Discuss the features of Nodular Sclerosis Hodkin’s Lymphoma
- most common type occurring in females
- The neoplasm involves the
mediastinum more commonly than all other types combined. - A very high incidence of contiguous spread is noted; i.e. occurring in more than
90% of cases.
There are characteristic hallmarks of NS subtype:
- The lymph node capsule shows fibrous thickening, from which broad bands extend
into the parenchyma of the node, subdividing it into nodules. - A distinctive variant of the Reed-Sternberg cell, termed the “lacunar” cell occurs.
- The cell cytoplasm shrinks and the nucleus appears to lie in a clear space
Features of mixed cellularity Hodkin’s lymphoma
- The lymph node contains a mixed infiltrate of abnormal and reactive cells.
- Diagnostic Reed-Sternberg cells are fairly easily found, as are mononuclear variants with prominent nucleoli.
- Patients with this subtype often present with lymphadenopathy in two or more sites and
systemic symptoms. This is considered a poor prognostic group.
Outline the features of lymphocyte depleted HL
- This subtype shows depletion of lymphocytes and numerous, often bizarre Reed- Sternberg cells.
- Patients frequently have systemic “B” symptoms of fever and weight loss, as well as pancytopenia
Outline the features of lymphocyte rich HL
- The reverse pattern of lymphocyte depletion, with abundant lymphocytes and scarce Reed-Sternberg cells, is seen.
Outline the features of lymphocyte predominant HL
- Scattered neoplastic cells are seen against a background of an abnormal cellular infiltrate.
- Most of the neoplastic cells, however, known as “L & H” (lymphocytic and histiocytic) or “popcorn” cells, lie within large nodular areas made up of small lymphoid cells.
- Molecular studies have shown that the neoplastic cells in this subtype are of B cell phenotype, different from that of classic Reed-Sternberg cells.
- This subtype of HL shows a striking male predominance and its pattern of spread differs
from that of the other HL subtypes. - It tends to be an indolent, slowly progressive disease, although occasional cases transform after a period into large cell lymphoma,
usually of B cell type.
PROGNOSTIC FACTORS IN HL
- Stage of disease (assessed clinically and pathologically).
- The presence or absence of B symptoms (indicative of advanced disease)
- Histologic subtype – lymphocyte predominant most favourable and lymphocyte
depleted disease, the worst subtype - Age – prognosis worsens with increasing age, especially over 60 years
TREATMENT FOR HL
- Irradiation (usually for localized disease).
- Multi-agent chemotherapy, given in disseminated disease.
