Lymphomas Flashcards
Lymphoid neoplasms can be due to what 3 classes of cancer?
- Hodgkin’s and non-Hodgkin’s Lymphoma (masses on lymph nodes)
- Leukemia (bone marrow and peripheral blood)
- Plasma cell dyscrasisia (arise within bones and cause systemic symptoms while producing complete or partially incomplete monoclonal immunoglobin)
Myeloid neoplasms can be due to which cancerous diseases? (3)
- Leukemias
- Myelodysplastic syndromes
- Myeloproliferative neoplasms
______ ______ ______ manifest as histiocytic neoplasms.
Langerhans cell histocytosis
All neoplasms have the capacity to ______ to ______ ______ and other tissues such as ______, spleen, and ______ ______.
Spread; lymph nodes; liver; bone marrow
Non-Hodgkins Lymphoma precursor B and T neoplasms are due to ______ ______ ______ (______) and lymphoma composed of ______ B+T cells.
Acute lymphoblastic leukemia (ALL); immature
Non-Hodgkins Lymphoma peripheral B-cell neoplasms can be due to ______ ______ _____ (______) or ______ ______ ______ (______).
Chronic lymphocytic leukemia (CLL); Small lymphocytic lymphoma (SLL).
CLL is composed of cells mostly found in ______ ______.
Peripheral blood
SLL is composed of cells found in ______ ______.
Lymphatic tissue
What is FCCL?
Follicular Lymphoma
FCCL is the ______ ______ ______ of non-Hodgkin’s lymphoma in the US. Accounting for ______% of cases.
Most common form; 40
Translocation of FCCL?
T (14;18) which causes fusion of the BCL2 gene on chromosome 18 to the IgH locus on chromosome 14
What does translocation T(14;18) do?
Causes overexpression of BCL2 protein, inhibiting apoptosis.
Characteristics of FCCL morphology? (3)
- Increased nodular proliferation
- Larger centrocytes with cleaved nuclei, indentation, and condensed chromatin
- Centroblasts can be seen as large cells with vesicular chromatin and multiple, indistinct nucleoli
B cell markers of FCCL?
CD20, CD10, and BCL6.
BCL2 is expressed in more than 85% of cases.
Bone marrow is involved in 80% of cases.
Clinical features of FCCL? (7)
- Adults older than 50
- Affects males and females equally
- Usually painless
- No cure
- Median survival rate: 10 yrs after diagnosis
- Symptomatic and bulky diseases are treated with cytotoxic drugs and rituximab (anti-CD20)
- In 30-40% of cases, FCCL progresses to diffuse large B cell lymphoma; survival rate decreases to 1 yr.
What is MCL?
Mantle cell lymphoma
MCL consists of cells that resemble ______ ______ ______ found in the mantle zones of lymphoid follicles.
Naive B cells
MCL translocation?
T (11;14) which causes the fusion of the cyclin D1 gene to the IgH locus
What does the translocation T(11;14) do?
Causes the overexpression of cyclin D1 and leads to growth by promoting progression of cells from the G1 stage to the S stage.
Characteristics of MCL morphology? (5)
- Lymph nodes are in a diffuse or vaguely nodular pattern
- Tumor cells are larger with an irregular nucleus and scant cytoplasm
- Bone marrow is involved in most cases
- Peripheral blood is involved in 20% of cases
- Can arise in the GI tract as lymphomatous polyposis
B cell markers of MCL?
CD20 and CD5
Clinical features of MCL? (5)
- Most common in men younger than 50 yrs
- Contributes to 6% of total non-Hodgkin’s cases
- Presents with lymphadenopathy and fatigue
- Aggressive and incurable
- Survival rate is 4-6 years after diagnosis
What is EMZL?
Extranodal Marginal Zone Lymphoma
EMZL is an ______ B cell tumor that arises in _______ _______. It is sustained by _______ ______.
Indolent; epithelial tissues; chronic inflammation
Triggers of chronic inflammation in EMZL include autoimmune disorders, _______ syndrome, Hashimoto’s thyroiditis, and ______ infection.
Sjogren’s; H. pylori
In EMZL, H. pylori is associated with the _______ marginal zone. Eradication of H. pylori with antibiotics can lead to ______ of tumor cells. Without H. pylori, tumor cells ______ ______ have inflammatory ______ to ______.
Gastric; regression; will not; cytokines; survive
In EMZL, chronic gastritis caused by H. pylori causes ______ of Ag-B cells.
Proliferation
B cell clones depend on antigen __-______ _____ for growth and survival in EMZL.
T-helper cells
Greater tumor cell autonomy and growth result from continued _______ _______ in EMZL.
Clonal evolution
Characteristics of EMZL morphology?
Lymphoepithelial lesions.
B cell markers in EMZL?
CD20 and IgM
Clinical features of EMZL? (3)
- Swollen salivary glands, thyroid, and orbit
- Often discovered incidentally due to H. pylori gastritis or imaging
- Cured by simple excision followed by radiotherapy
What is DLBCL?
Diffuse Large B cell Lymphoma
DLBCL is the ______ _______ lymphoma in adults. ______% of total non-Hodgkin’s cases.
Most common; 35
What are the 2 types of DLBCL and what are their associated genetic pathogeneses?
- Rearrangement in the BCL6 gene on 3q27 and an activating point mutation in the BCL6 promoter region, leading to increased production of the BCL6 protein
- T(14;18) involving BCL2 leading to the overexpression of the BCL2 protein
* These changes in BCL6 and BCL2 do not occur together, hence, two types of DLBCL.
Characteristics of DLBCL morphology?
Diffuse large B cell lymphoma with diffuse growth pattern.
Cell appearances can vary.
B cell markers of DLBCL?
All types express CD20, IgM, and IgG.
CD10 and BCL6 are variably expressed.
What are the 3 subtypes of DLBCL?
- EBV: occurs in the setting of AIDS, immunosuppression, transplant recipients, or the elderly
- Kaposi Sarcoma Herpesvirus: (HHV-8) associated with rare effusion in the pleural cavity, pericardium, and peritoneum
- Mediastinal Large B Cells: predominantly occurs in young women. Can spread to abdominal viscera and the CNS.
Clinical features of DLBCL?
- Predominately affects individuals over age 60
- Results in rapidly enlarging symptomatic masses at one or several sites
- Extranodal presentations are common, especially in the GI tract
- Without treatment, the cancer is aggressive and fatal
- When treated with anti-CD20 (rituximab), 60-80% of individuals achieved remission and 50% of those remained cancer-free
Where is Burkitt Lymphoma seen?
Endemic in Africa, but also presents in the US.
There are clinical and virological differences between them.
Pathogenesis of Burkitt Lymphoma? (6)
- Translocation of MYC gene on chromosome 8 leads to overexpression of the MYC transcription factor, causing changes in Warburg metabolism (aerobic glycolysis)
- T(8;14): fuses with the IgH gene on chromosome 14
- There are also translocations involving kappa and gamma light chains
- Fastest growing human tumor
- In most endemic cases and 20% of sporadic cases, cells also become infected with EBV
- In endemic areas, other diseases like malaria impair immune competence allowing for B cell proliferation; T cells eliminate most infected B cells, but those that survive become lymphoma cells
Characteristics of Burkitt Lymphoma morphology? (2)
- Tumor cells are intermediate in size, round, with 2-5 nucleoli
- Presence of tissue macrophages containing ingested debris leads to a “starry-sky” pattern
B cell markers of Burkitt Lymphoma?
CD20, IgM, CD10, and BCL6
Clinical features of Burkitt Lymphoma?
- Mainly affects children and young adults
- Arises at extranodal sites: maxillary and mandibular masses seen in endemic areas; abdominal tumors more common in the US
- Highly aggressive
- Very intensive chemotherapy can cure the disease
Generalized characteristics of Hodgkin’s Lymphoma? (2)
- Reed-Sternberg Cells (RS cells): giant tumor cells with a muti-lobate nucleus and eosinophilic cytoplasm. Usually with two mirror-image acidophilic nuclear lobes manifesting in an “owl-eye” appearance.
- Arises in a single lymph node or chain, spreads anatomically.
Characteristics of Hodgkin’s Lymphoma morphology? (3)
- Neoplasm arises from germinal B center
- EBV is present in 70% of cases (mostly in classical [mixed-cellularity subtype]). EBV contributes to tumor development.
- Non-neoplastic inflammatory cell infiltrate is generated by a number of cytokines
B cell markers for Hodgkin’s Lymphoma?
Classic (first 4 types): CD15, CD30, but NOT CD45 (LCA) or B+T cell antigen
Lymphocyte Predominant Type (Non-classic): CD20, but NOT CD15 or CD30
Clinical features of Hodgkin’s Lymphoma? (6)
- Painless lymphadenopathy
- Younger patients with earlier stages (I and II) are free of B symptoms
- Older adults typically have advanced stages (III and IV) and exhibit B symptoms (fever, weight loss, night sweats) + pruritus and anemia
- Very good prognosis
- Patients treated with radiotherapy have an increased risk of malignancy in the lung, breast, and CVD.
- Good response to Anti-PD1 in patients with relapsed disease
What are the 5 types of Hodgkin’s Lymphoma?
- Nodular sclerosis HL
- Mixed cellularity HL
- Lymphocyte rich HL
- Lymphocyte depletion HL
- Lymphocyte predominant HL
Characteristics of Nodular Sclerosis HL morphology? (2)
- Lacunar cells: multiple, small, multi-lobed cells with pale cytoplasm. Cytoplasm is torn away, leaving “empty-looking” cells.
- Collagen bands: Divide lymphoid tissue into nodules. The fibrosis can be scant or abundant. Cellular infiltrate contains lymphocytes, eosinophils, histiocytes, and lacunar cells.
Clinical features of Nodular Sclerosis HL? (4)
- Most common form of HL
- Affects men and women equally
- Predominantly affects adolescents and young adults
- Involves the lower cervical, supraclavicular, and mediastinal lymph nodes.
Characteristics of Mixed-cellularity HL morphology?
Many RS cells with a mix of small lymphocytes, eosinophils, plasma cells, and macrophages
Clinical features of Mixed-cellularity HL? (4)
- Most common in older patients
- Affects men more than women
- 25% of total HL cases overall
- Associated with systemic manifestations (B symptoms)
Characteristics of Lymphocyte Rich HL morphology? (2)
- Reactive lymphocytes make up majority of cellular infiltrate
- Presence of RS cells with classic profile
Clinical features of Lymphocyte Rich HL?
Uncommon form
Characteristics of Lymphocyte Depletion HL morphology? (2)
- Scarcity of lymphocytes
2. Large amount of RS cells
Clinical features of Lymphocyte Depletion HL?
Least common. Less than 5% of cases.
Characteristics of Lymphocyte Predominant HL morphology?
Variant of RS cells with presence of lymphohistiocytic (L&H) RS cells: multi-lobed puffy nucleus resembling “popcorn”. Usually found within large nodules containing small B cells and macrophages.
Clinical features of Lymphocyte Predominant HL?
- 5% of cases. Non-classic.
- Cervical or axillary lymphadenopathy
- Excellent prognosis
