Reactive Lymphadenopathies

Question 1

To understand the microscopic appearance of lymph nodes, you must understand the development of the B and T cells that traffic through them. Where does B-cell development begin?

Answer 1

B-cell development begins in the bone marrow, where an essential step in adaptive immunity – VDJ rearrangement of immunoglobulin genes – occurs. This generates a large number of genetically and functionally distinct naïve B-cells, which migrate to the interfollicuar (or “paracortical”) regions of lymphatic tissues throughout the body. If they encounter antigens to which their surface immunoglobulins (IgM) can bind, they can generate a relatively weak immune response. But their main training course has yet to begin.

Question 2

What happens to B cells in germinal centers?

Answer 2

Interaction with antigen-presenting cells (follicular dendritic cells) and helper T-cells

Somatic hypermutation

Class switching to IgG, E, or A
(Only the strong survive- Over 99% of them die in the process – specifically, they commit suicide (apoptosis) unless instructed to express an anti-apoptotic signaling protein called Bcl-2.)

Question 3

B cells that survive the germinal center do what next?

Answer 3

They move out into the periphery – the bloodstream and other locations – to either produce immunoglobulins or be held in passive reserve (memory B-cells), able to react in the event of re-exposure to the antigens they were trained to recognize. A peripheral supply of naïve B-cells is kept, usually in fairly small numbers, just outside the “mantle” zone in the “marginal zone”.

Question 4

How do B cells appear?

Answer 4

Plasma cells have a characteristic appearance: their nuclei are round and dark with chunky chromatin, and their cytoplasm has been expanded by big pale areas.. Those areas are in fact the golgi apparati, which makes sense because the antibodies being mass produced by these cells have to be heavily glycosylated.

Question 5

T or F. Key point 2: B cells are rarely seen in peripheral blood.

Answer 5

T. Plasma cells can’t swim. Their favorite environment is the bone marrow, sometimes lymph nodes and the GI tract.

Question 6

All T-cell receptor gene rearrangements, and dispatching of self-reactive clones, occur where?

Answer 6

in the thymus.

Question 7

There is no somatic hypermutation in T-cell development, but in the periphery antigens nonetheless stimulate maturation and differentiation into different functional states. Where does this occur?

Answer 7

predominantly in the paracortex of lymph nodes and other lymphatic tissues.

Question 8

What happens to B cells If they react with the host, or fail to react with the pathogen?

Answer 8

They are induced to die – and their corpses take on the form of macrophages containing remnants of their nuclei. The remnants tend to pick up hematoxyin – they are “tingible bodies.”

Question 9

What is reactive follicular hyperplasia?

Answer 9

a lymph node hyperplasia associated with bacterial infection

Question 10

Typical clinical presentation of follicular hyperplasia?

Answer 10

enlarged axillary inguinal nodes in an individual with an abscess in a lower extremity.

Typically they do NOT need to be biopsied, but if that individual also had clinical features suspicious for a malignancy (weight loss, anemia, or other enlarged lymph nodes) a biopsy might be indicated.

Note: this finding is sensitive but not specific for bacterial infections; bacterial infections will almost always show this, but some viral infections can show a similar appearance.

Question 11

What is one key morphologic feature of the reactive lymph nodes in RFH?

Answer 11

the germinal centers are of quite variable size and shape. That’s typical of this condition.

Question 12

What is one key clinical feature of the reactive lymph nodes in RFH?

Answer 12

they are usually tender and mobile on palpation.

Nodes involved by a malignancy are in most cases non-tender, and can also have a “matted” or immobile texture on exam.

Question 13

What is a common symptom of infectious mononucleosis?

Answer 13

• paracortical expansion (T-cells, APCs)

- huge reactive “nonnuclear cells” in peripheral blood

Question 14

How do lymph nodes look histologically in an infectious mononucleosis?

Answer 14

At LOW POWER the normal architecture appears to have been wiped out, or “effaced”, by something but the POLYMORPHIC CELL POPULATION in the paracortex is a reassuring feature of response to a viral syndrome – and it would be fairly typical of any of the dozen or so viral syndromes a typical kid will get before age 18.

Biopsy of a lymph node immediately after an individual was infected with HIV might look very similar.

Question 15

What do the huge reactive mononuclear cells look like in infectious mononucleosis?

Answer 15

look like monocytes BUT the nuclei are too round, the chromatin is not ropy enough, and some of them have a really large nucleus.

The proliferation of these hard-to-classify cells in the bloodstream is what gave this condition it’s name. They are in fact activated T-cells. A very, very helpful feature to look for in order to rule out some kind of malignancy in this case (such as an acute leukemia – we’ll get to them next week): in reactive/viarl conditions these cells will NOT look like they’ve been stamped out with same cookie cutter.

Question 16

What is granulomatous lymphadenitis?

Answer 16

basically TB- caveating granulomas common

Question 17

Systemic lupus erythematosis (SLE) can have a disturbingly multifaceted clinical presentation (which goes beyond the scope of this module), and occasionally a lymph node biopsy might be the first strong evidence of this diagnosis. The pale area in the center of this (enlarged, hence biosied) lymph node from an SLE patient consists predominantly of dead cells, and most textbooks refer to these as zones of necrosis. That’s an unfortunately confusing use of the term, because a close look at a case like this will show fragments of dark-blue staining nuclear material (the technical term is hematoxylin bodies). Cell death involving breakup of the nucleus is characteristic of apoptosis, not necrosis, and that’s what is thought to be going on in lupus lymphadenitis.

Key point: Hematoxylin bodies can help if one is not sure whether an area like the one on the left might be a granuloma or not. They are not seen in granulomas.

Answer 17

Systemic lupus erythematosis (SLE) can have a disturbingly multifaceted clinical presentation (which goes beyond the scope of this module), and occasionally a lymph node biopsy might be the first strong evidence of this diagnosis. The pale area in the center of this (enlarged, hence biosied) lymph node from an SLE patient consists predominantly of dead cells, and most textbooks refer to these as zones of necrosis. That’s an unfortunately confusing use of the term, because a close look at a case like this will show fragments of dark-blue staining nuclear material (the technical term is hematoxylin bodies). Cell death involving breakup of the nucleus is characteristic of apoptosis, not necrosis, and that’s what is thought to be going on in lupus lymphadenitis.

Key point: Hematoxylin bodies can help if one is not sure whether an area like the one on the left might be a granuloma or not. They are not seen in granulomas.

Question 18

Patients with chronic skin diseases such as eczema, psoriasis, or pemphigus, may develop enlarged lymph nodes proximal to their skin lesions (typically in the inguinal or axillary regions), and in some clinical circumstances a biopsy might be indicated

Answer 18

In this case you can see a handful of normal small germinal centers with prominent mantle zones, AND a group of large pale areas that look like something else. A close look at those (upper right) shows them to consist of cells with a lot of pale cytoplasm (at this power, dot-like nuclei surrounded by a lot of space). These are histiocytes (tissue-based macrophages) and a close look at some of them shows they contain a lot of dark pigment (bottom right). The pigment turns out to be melanin. Pathogenesis: the lymph node has received a great deal of lymphatic drainage from the patient’s skin lesions, that drainage has included a lot of dead skin cell debris, and that has accumulated in histiocytes.

Key point: These big lesions are NOT caseating granulomata; they do NOT show areas of necrosis.

Question 19

Normal germinal center function requires CD4+ follicular helper cells. In their absence (late in the course of HIV infection), you might see residual mantle zones , but where you’d expect to see a cell-rich germinal center you instead see what look like histiocytes.

Answer 19

Normal germinal center function requires CD4+ follicular helper cells. In their absence (late in the course of HIV infection), you might see residual mantle zones , but where you’d expect to see a cell-rich germinal center you instead see what look like histiocytes.