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HMS Homeostasis I > Lymphomas > Flashcards

Lymphomas Flashcards

1
Q

Reed-Sternberg cells are derived from ____.

A

Reed-Sternberg cells are derived from germinal center B cells.

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2
Q

The inflammatory response to Reed-Sternberg Cells (RSC) in Hodgkin Lymphoma is the product of ___.

A

The inflammatory response to Reed-Sternberg Cells (RSC) in Hodgkin Lymphoma is the product of cytokines expressed by the RSC.

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3
Q

Most Non-Hodgkins lymphomas involve. . .

A

. . . recombination involving the IgH promoter

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4
Q

Follicular lymphoma

A
  • Arises in germinal center of lymphoid follicle
  • Recombination of IgH promoter and Bcl2
  • Oncogenesis by “failure to die”
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5
Q

Diffuse large B cell lymphoma

A
  • IgH promoter and Bcl6 recombination
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6
Q

Burkitt’s Lymphoma

A
  • Very deadly - put down your sandwich
  • IgH promoter and myc recombination
  • Large, irregular, highly euchromatic nuclei
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7
Q

SVC syndrome

A

Compression of the SVC by a retrosternal mass may result in facial redness and facial edema.

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8
Q

Secondary symptoms of lymphoma

A
  • B symptoms
  • Immunosuppression
  • Loss of tolerance
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9
Q

HHV-8 (Kaposi’s Sarcoma Virus)

A

Strongly associated with primary effusion lymphoma, a rare, aggressive, B-cell lymphoma that arises within chronic effusions, typically in the pleural or peritoneal spaces.

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10
Q

HTLV-1

A

Human T-cell Lymphotrophic Virus-1

A retrovirus directly associated with adult T-cell leukemia/lymphoma (ATLL).

Much like HIV, integrates into CD4 T cell DNA.

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11
Q

HIV and lymphomas

A

While HIV itself does not cause lymphomas directly, it degrades the immunity to existing viruses within hosts that can cause lymphoma, like EBV. It also causes a strong mononucleusos-like reaction in its acute phase, which puts stress on germinal centers and may precipitate a B cell lymphoma.

It is not at all uncommon for someone infected with HIV with poor management to develop an EBV-positive tumor from an EBV infection in their distant past that was previously under check by their immune system.

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12
Q

H. pylori and lymphoma

A

H. pylori infection causes chronic gastric inflammation that may precipitate a gastric extranodal marginal zone lymphoma, aka MALT lymphoma.

This mechanism is similar to how MALT lymphoma is produced in Sjogren syndrome and Hashimoto’s thyroiditis.

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13
Q

CLL / SLL

A

Chronic lymphocytic leukemia / small lymphocytic lymphoma

Two manifestations of the same disease. Unlike many lymphomas, does not involve translocation or the IgH promoter.

Characterized by overwhelming numbers of small, fragile lymphocytes with packed chromatin and scant cytoplasm either in peripheral blood or in bone marrow, with “proliferation centers” in the lymph nodes. Prolymphocytes are actively dividing cells in proliferation centers have especially large nuclei with very prominent nucleoli. Image of proliferation center is shown below.

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14
Q

Diagnosing CLL/SLL

A
  • CLL will present with lymphocytosis while otherwise asymptomatic
  • SLL will often present with diffuse lymphadenopathy while otherwise asymptomatic
  • Unlike most cancers, does not produce B symptoms. Thus, associated fevers should be assumed to be due to infection
  • Diagnosis established by flow cytometry
  • Tissue biopsy of marrow or lymph node usually unnecessary for CLL, but often is for SLL.
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15
Q

Flow features of CLL/SLL

A
  • pan-B cell markers: CD20, CD23
  • CD5, usually T cell marker, misexpressed in CLL/SLL
  • Exhibit kappa/lambda clonality
  • Usually low level of surface IgM
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16
Q

When to Treat CLL/SLL

A
  • As many as 60% of patients do not need treatment, but indications for those that do include:
  • Cytopenias (myelophthesis)
  • Symptomatic lymphadenopathy and organomegaly
  • Symptomatic autoantibodies
  • Appearance of B symptoms (not usually present in this disease)
  • Richter transformation (5% of patients, transformation to an aggressive lymphoma resembling diffuse large B-cell lymphoma, poor prognosis)
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17
Q

Treatment of CLL/SLL

A
  • In patients who present with indication for treatment:
  • Chemoimmunotherapy (purine mimetics or alkylating agents with rituxumab)
  • Oral kinase inhibitors targeting Bruton tyrosine kinase and PI3K
18
Q

Hairy Cell Leukemia

A

Tumor of mature B cells, A rare indolent lymphocytic leukemia. Unique clinicopathologic features and response to therapy.

Strongly associated with activating mutations in BRAF. Often presents with splenomegaly and monocytopenia, with increased susceptibility to atypical mycobacteria, and eventually with severe pancytopenia.

Has a very characteristic look on microscopy.

19
Q

Treatment of Hairy Cell Lymphoma

A

Has an excellent response to certain chemotherapy agents such as the purine analog cladribine, which produces long-lasting remissions in most affected patients. In those who fail conventional chemotherapy, BRAF inhibitors are now available that are highly active and produce remissions in most patients, even those whose tumors have become resistant to chemotherapy.

Now one of the most curable cancers.

20
Q

Follicular lymphoma

A

Most common indolent lymphoma. Most patients are asymptomatic at presentation, presenting with only painless lymphadenopathy.

Over 90% due to a translocation between IgH promoter and Bcl2, usually accompanied by a histone demethylase loss-of-function.

21
Q

Diagnosis of follicular lymphoma

A
  • Lymph node biopsy is key
    • Reveals replacement of normal architecture by neoplastic follicles. Lack of apoptosis, lack of mitoses, but very high Bcl2 expression
22
Q

The image below is stained for Bcl-2 and is taken from a lymph node. What is the likely diagnosis?

A

Follicular lymphoma

23
Q

Clinical course of follicular lymphoma

A
  • Waxing and waning lymphadenopathy
  • 20% of patients experience spontaneous remission, but these remissions only last for ~1 year
  • Asymptomatic patients are followed until symptoms begin to present
  • 2%/yr risk of transformation into a more aggressive lymphoma mimicking diffuse large B cell lymphoma
24
Q

Treating follicular lymphoma

A
  • There is no evidence that early treatment leads to better outcomes, so patients are only treated when symptoms present. Indications to begin treatment include:
    • >5cm node or evidence of compression of other structures
    • B symptoms
    • Extranodal manifestations like pleural effusion
    • Cytopenias due to marrow involvement
    • Splenomegaly
  • Early treatment with radiation is highly effective, curative in some cases
  • Advanced cases indicate chemotherapy and rituximab
  • Leads to remission, but after ~5 years resistance often develops
25
Q

Diffuse large B cell lymphoma

A

Most common lymphoma in Western countries. 2/3 present within lymph nodes, 1/3 at extranodal sites.

Most commonly involves translocations with BCL6, a TF required for germinal center B differentiation.

Heterogeneous with many subtypes.

26
Q

Diagnosing diffuse large B cell lymphoma

A
  • Patients present with rapidly growing mass or B symptoms
  • LDH elevated in 50% of patients
  • Diagnosis made by tissue biopsy, showing effacement of tissue architecture with large lymphoid cells
  • Immunophenotyping also essential for diagnosis
  • Tumors are CD20+ with high BCL6 and variable CD10, Bcl-2, and surface Ig
  • Markedly positive by PET scan due to very high metabolic rate
27
Q

Treatment of diffuse large B cell lymphoma

A
  • Treated with combination chemotherapy plus rituximab
  • 65% of patients cured on this regimen, 90% of those with no risk factors
28
Q

Burkitt’s Lymphoma

A

Highly aggressive, represents 2% of adult lymphomas. Previous EBV infection or malaria infection can be a substantial risk factor.

Translocation involving myc and IgH (chromosomes 8 and 14). Rarely produced by a translocation of myc to be under the kappa or lambda light chain promoters (chr 2 and 22).

One of the fastest growing human tumors. Often arises in extranodal sites like the intestine.

29
Q

Diagnosis of Burkitt’s Lymphoma

A
  • Biopsy reveals medium-sized lymphoid cells with many mitotic figures, some apoptosis, and consumption by reactive macrophages. This creates a “starry sky” appearance.
  • Immunophenotyping reveals CD20+, CD10+, Bcl6+, Bcl2-
  • Often Ki-67+ in every single cell
  • Cytogenetics used to detect myc rearrangement
30
Q

What pathology does the image show?

A

Burkitt’s Lymphoma

Has the pathognomonic “starry sky” appearance due to the presence of macrophages eating lymphoid cells

31
Q

Treatment of Burkitt’s lymphoma

A
  • Endemic form often localized to single extranodal site and very responsive to chemotherapy
  • Sporadic Burkitt’s lymphoma has a tendency to spread to the CNS
  • Intensive chemotherapy and rituximab produce good outcomes
  • Usually coupled with intrathecal therapy to decrease bad outcomes in the CNS
  • Care must be taken to avoid tumor lysis syndrome - allopurinol and close observation
32
Q

Major features of Hodgkin’s Lymphoma

A
  • Presence of Reed-Sternberg cells, which promote an enormous reactive leukocytosis
  • A strong tendency to arise within a single lymph node
  • A very predictable, stepwise spread, from one lymph node to the next
33
Q

Subtypes of Hodgkin’s Lymphoma

A
  • Nodular sclerosis: Presence of lacunar-type Reed-Sternberg cell and large bands of collagen deposited by fibroblasts. Not associated with EBV.
  • Mixed cellularity: Diffuse polymorphous infiltrate in lymph nodes of many lineages, high percentage of mononuclear Reed-Sternberg cells. 70% of cases associated with EBV.
  • Lymphocyte rich: Infiltrate consists predominantely of lymphocytes. 40% of cases associated with EBV.
  • Lymphocyte depleted: No lymphocytes. Rare except in HIV patients. Virtually always in an HIV+ EBV+ patient.
  • Nodular lymphocyte predominant: Characterized by popcorn-kernel Reed-Sternberg cells with rare or absent classical cells. Not assocaited with EBV.
34
Q

What does this H and E show?

A

Lacunar Reed-Sternberg cells

Seen within spaces created by tearing away of the wispy cytoplasm during tissue sectioning

35
Q

What does the H and E show?

A

Mononuclear Reed-Sternberg cell

Variant with a single, enormous, eosinophilic nucleolus is present in the middle of the field.

36
Q

What does this H and E show?

A

A classic Reed-Sternberg cell

Two nuclei, each with a large nucleolus, and abundant cytoplasm

37
Q

What does this H and E show?

A

A lymphocytic and histiocytic, aka popcorn-kernel, Reed-Sternberg cell

38
Q

Interactions between Reed-Sternberg cells and inflammatory cells

A
39
Q

Latent membrane protein-1

A

Latent protein of EBV that is essentially a constitutively active TNF receptor

Results in overdrive of NFkB expression

40
Q

Clinical presentation of Hodgkin’s lymphoma

A
  • Regardless of subtype
  • painless lymphadenopathy, most commonly in the cervical or supraclavicular region
  • nodular sclerosis often involves mediastinum, producing dyspnea and cough and rarely SVC syndrome
  • B symptoms in 1/3 of patients
  • Pruritis in the absence of rash
  • Lab studies show leukocytosis and eosinophilia, often accompanied by anemia of chronic inflammation
41
Q

Diagnosis of Hodgkin’s lymphoma

A
  • Reed-Sternberg cells on lymph node biopsy are the hallmark
  • Reed-Sternberg cells can rarely be false positives, so IHC is necessary to confirm the diagnosis
  • In classical Hodgkin’s lymphoma: CD20-, CD15+, CD30+, CD45+, and often EBV+
  • In H&L Hodgkin’s lymphoma: CD20+, CD15-, CD30-, CD45-
42
Q

Treatment of Hodgkin’s Lymphoma

A
  • Very good prognosis. 60-90% cure rate
  • Low-stage disease with minimal B symptoms: treated with chemotherapy and low-grade radiation, sometimes chemotherapy only
  • More significant disease: Combination chemotherapy and radiotherapy for masses.
  • Almost all Hodgkin’s lymphomas express PD-L1 and PD-L2, so PD-1 blockade is extraordinarily effective in Hodgkin’s lymphoma
  • More patients now die of complications of therapy than from Hodgkin lymphoma itself
    • Valvular heart disease
    • Accelerated cardiovascular disease
    • Secondary malignancies

HMS Homeostasis I (62 decks)

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