Haem/LN/spleen/thymus Flashcards
What are the 5 subtypes of Hodgkin’s Lymphoma
- Nodular sclerosing
- Mixed cellularity
- Lymphocyte rich
- Lymphocyte depleted
- Nodular lymphocyte predominan
Pathophysiology of Hodgkin’s Lymphoma
HL arises in a single node or chain of nodes and spreads first to anatomically contiguous lymphoid tissues. Morpholgically distinctive feature of the HL is presence of neoplastic giant cells called Reed-Sternberg cells.
* o RS cells release factors that induce the accumulation of reactive lymphocytes, macrophages, granulocytes which typically make up greater than 90% of the tumour cellularity
* o RS cells derived from germinal centre or post-germinal centre B cells. Despite B cell origin they don’t express classic B cell specific genes like Ig genes.
Activation of transcription factor NF-kB is a common event in classic HL and turns on genes that are believed to promote growth and survival of RS cells.
Apparently NF-kB rescues faulty B cells from apoptosis setting the stage for further mutations.
PD-L1 and PD-L2 induced by RS cells which antagonize cytotoxic T cell responses.
* o RS cells are large cells (45m) with multiple nuclei or a single nucleus with multiple nuclear lobes each with a large inclusion like nucleolus about the size of a small lymphocyte (5-7m in diameter).
* RS cells are infected with EBV in over 90% of cases.
* Lymphocyte predominance type expresses B cell markers and is not associated with EBV.
* o Spread of disease is stereotypic:
* Nodal splenic hepatic marrow and other tissues
* o HL is highly sensitive to immune checkpoint inhibitors which antagonise the activity of PD-L1 and PD-L2 expressed on the surface of RS cells.
* Bloods can show an eosinophilia
Good prognosis 95% cure rate
LN mostly above the diaphragm, rarely disease below diaphragm or extranodal dx
Summary of HL
5 subtypes of Hodgkins lymphoma:
* Nodular sclerosing
* Mixed cellularity
* Lymphocyte rich
* Lymphocyte depleted
* Nodular lymphocyte predominant
Histo:
Reed-Sternberg cells (giant cells)
Markers
NF-kB transcription activation, PD-L1 and PD-L2 induced by Reese-Sternberg bodies
Gene:
Imaging appearance:
Usually confined to LN disease above the diaphragm. Disease spread is stereotypic, nodal → splenic → hepatic → marrow and other tissues
Prognosis/ Tx:
good, 95% cure, PDL1 and PDL2 inhibitors
What conditions are associated with Non-Hodgkin’s Lymphoma?
Associations:
* Hashimotos thyroditis small risk of B cell NHL
* Coeliac disease → EATL (enteric associated T cell lymphoma - small bowel lymphoma; EATing gluten) (not MALT)
* BRCA 2 → B cell lymphoma
* Adult intusseseception most likely caused by lymphoma or melanoma
* EBV → Burkitt lymphoma (Bad)
* H Pylori → MALT (stomach mucosa, MALT)
Burkitt Lymphoma
Burkitt = BAD
* Originating from germinal centre B cells
* All forms are associated with translocations of the MYC gene on Ch 8 leading to increased MYC protein levels. Usually t(8;14) but may also see t(2;8) and t(8;22).
* Seen in adolescents, young adults with extranodal masses. Uncommonly presenting as a leukaemia.
* Aggressive. Poor prognosis in adults (good prognosis if dx early in kids)
* Lesions progress quickly
* Associated with EBV, or other viral infection (HIV)
* Essentially all Burkitt lymphomas are latently infected with EBV, also present in 25% of HIV associated tumours and 15-20% of sporadic cases
MALT/Gastric Lymphoma
- MALT/Gastric lymphoma
- MALT (mucosa-associated lymphoid tissue (MALT), frequently of the stomach, but virtually any mucosal site can be affected e.g. salivary glands.) – gastric mucosa does not intrinsically have lymph tissue
- Dense lymphocytic infiltrate of the lamina propria. Infiltration fo gastric glands to create diagnostic lymphoepithelial lesions.
- Express B cell markers CD19, CD20. No CD5 or CD10. Positive for CD43 in 25%
- MALToma and h pylroi gastritis commonly co-exist with overlapping clinical symptoms leading to treatment with Abx in the first instance. In some cases can completely cure MALT with abx.
- Gastric lymphoma arises from MALT (low grade) in patients with H pylori containing cytotoxin-associated antigen (CagA).
- MALT can transform to extranodal marginal zone B-cell lymphoma
Marginal zone B cell lymphoma
Also known as extranodal marginal zone lymphoma
* Arises from memory B cells
* Translocations t(11;18), t(1;14), t(14;18) creating MAT1-IAP2, BCL10-IGH and MALT-IGH fusion genes
* Arising in extranodal sites in adults with chronic inflammatory diseases. Can remain localised and indolent
From Robbins:
● “Extranodal marginal zone B-cell lymphomas usually arise at sites of chronic inflammation. They can originate in the GI tract at sites of preexisting MALT such as the Peyer patches of the small intestine, but more commonly arise within tissues that are normally devoid of organized lymphoid tissue. MALT is not present in the normal stomach but can be induced, typically as a result of chronic gastritis. H. pylori infection is the most common inducer of gastric MALT and therefore is found in association with most gastric MALTomas”
● As with other low-grade lymphomas, MALTomas can transform into more aggressive tumours that are histologically identical to diffuse large B-cell lymphomas.
Follicular Lymphoma
Strongly associated with chromosomal translocations involving BCL2. Hallmark is a (14;18) translocation that juxtaposes the IGH locus on Ch 14 and the BCL2 locus on Ch18.
* T(14;18) seen in 90% of follicular lymphomas.
* Follicular lymphoma typically devoid of apoptotic cells.
* Histological transformation occurs in 30-50% of follicular lymphomas, most commonly to DLBCL
* Gereminal centre B cell origin
* Seen in older adults with generalised lymphadenopathy and marrow involvement.
* o Indolent disease.
DLBCL
- Primary NHL more common than secondary involvement.
- DLBCL NHL associated with BCL6 in 30% of cases.
- Another 10-20% of cases associated with t(14;18), similar to follicular lymphoma. Leads to overexpression of BCL2.
- 5% of DLBCL associated with translocations involving MYC
Anaplastic large cell lymphoma:
- Cytotoxic T cell origin
- See rearrangements in ALK (anaplastic large cell lymphoma kinase) in a subset, not all.
- Seen in children, young adults. Usually soft tissue and lymph node disease. Aggressive lymphoma.
Hairy cell leukaemia:
- Originates from naïve B cells
- Translocation t(11;14) creating cyclin D1-IGH fusion gene
- Seen in older men with disseminated disease.
- Moderately aggressive.
Mycosis Fungoides:Cutaneous T cell lymphoma
Lymphoma of skin-homing CD4+ T helper cells.
* · Can occur at any age but mainly in those over 40.
* · Invade the epidermis as single cells and small clusters.
* · Nodules of T cell grow deeply into the dermis to eventually spread systemically.
CNS Lymphoma:
- o Commonly seen in immunocompromised – particularly AIDS and post-transplant immunosuppression.
- o Most common CNS malignancy in immunosuppressed individuals.
- o EBV often detectable. Not clearly linked as a cause, it’s just present.
Testicular Lymphoma
- o Primary testicular lymphoma is rare
- o Most common form of testicular neoplasm in men older than 60 yrs.
- o Aggressive and usually disseminated at time of detection.
- o DLBCL, Burkitt, EBV +ve extranodal NK/T cell lymphoma.
- O treatment requires orchidectomy - due to testis blood barrier, chemo does not penetrate testis well
Breast lymphoma
- More commonly secondary involvement of NHL than primary.
- When primary usually B cell lymphoma.
- Rarer types of T-cell lymphoma associated with breast implants.
- Burkitt lymphoma can be seen in younger breastfeeding women. Massive involvement of both breasts
- Mets to the breast are rare, usually melanomas or ovarian cancers.
