What is the black arrow pointing at and what is this disease and its characteristics?
The black arrow points out where the lymphocytes have gone past the limits of the capsule, which is suspiciously malignant behavior. Often, they form follicle-like structures within fat outside the lymph node, which are called "pseudo-follicles," because they are formed from proliferating malignant B lymphocytes, not normal primary or secondary follicles that would contain polyclonal B cells, T cells, and dendritic cells. Follicular lymphoma.
What is this an image of?
Normal lymph node
In the disease follicular lymphoma what is the object circled in red referred to as?
What is this within the lymph node?
In a benign, reactive lymph node, germinal centers show polarization.
Besides its abbreviation for hockey fans, what is NHL?
Follicular lymphoma is a type of "Non-Hodgkin lymphoma"
What is the most likely cellular origin of follicular lymphoma?
Follicular lymphoma is a lymphoma of follicle center B- cells
Is there a strongly associated chromosomal translocation with follicular lymphoma?
Yes, a translocation of chromosome 14 & 18 results in over expression of the BCL-2 gene. BCL-2 is strongly anti-apoptotic & a proto-oncogene. Its overexpression promotes follicular precursor & memory B cells to be long lived--allowing for the development of 'second hits' to occur & establish follicular lymphoma.
How does follicular lymphoma differ from a reactive lymph node?
The reactive lymph node has numerous follicles & the medullary sinus is very evident. The reactive lymph node's germinal centers have "polarity." This, seen earlier, is visible at higher power and shows a visible distinction between lighter and darker cells.
Conversely, in the follicular lymphoma lymph node, the "pseudo follicles" encroach on the meduallary area of the lymph node. The pseudo follicles are throughout this lymph node and there is little normal tissue visible. You can visualize the follicular lymphoma extending beyond the capsule: this is a neoplastic process.
What is this and what are the defining characteristics?
Celiac In the abnormal specimen, note the increased magnification, and the black arrow which identifies the muscularis propria. Going any deeper with the biopsy would risk perforation of the bowel. Note the marked absence of villi, giving the mucosal surface a ‘blunted’ appearance. Crypts are still present, when compared to normal, but there is a prominent lymphoid infiltrate (which is responsible for the pathology!).
What is one of the defining lymphocyte characteristics associated with celiac disease?
However, in the abnormal slide, there are abnormally high numbers of lymphocytes in the lamina propria. This is evident under high power. If these sections were stained by immunoperoxidase, one would find a high proportion of activated CD4+ T cells, antigen presenting cells, CD8+ killer T cells and plasma cells.
Celiac disease is multi-symptomatic. What are the causative associations between celiac disease and the blistering skin disease Dermatitis herpetiformis?
Circulating IgA antibodies in the blood mistakenly bind to the transglutaminase in the dermal papillae of the epidermis. When the IgA binds, neutrophils are recruited and they start an inflammatory reaction. This creates a rash on the skin.
What is the clinical significance of villous atrophy in celiac disease?
Villi are responsible for absorption in the small intestine. Thus, villous atrophy disrupts the process of absorption. Malabsorption may lead to a number of symptoms, including diarrhea (failure to absorb water), steatorrhea (failure to absorb fat), and anemia (failure to absorb iron and vitamin B12). Patients may also experience weight loss. The treatment for celiac disease is a gluten-free diet. Most symptoms are resolved with this diet. However, some patients may still experience chronic inflammation and immune activation. Over time, this may lead to small bowel cancer and T cell lymphoma.
Celiac disease is often considered an autoimmune disease. Why? What antigen is the primary cause of the pathogenic immune response?
Celiac disease is often considered an autoimmune disease because gluten triggers the immune system to attack the small intestine. The antigen responsible for the pathogenic immune response is gliadin, a 33 amino acid peptide component of gluten.
What is this an image of?
Lymph node andencarcinoma
What is the rationale behind sentinel lymph node biopsy?
Because lymph nodes don't have a basement membrane, it's easier for tumor cells to invade them as opposed to blood vessels. This makes a lymph node the first place where you'll find metastases, so much so that cancer cells in a lymph node aren't always considered metastatic.
The sentinal nodes are the closest to the primary tumor so they are the most likely to house tumor cells. And if they have tumor cells, then further metastasis is highly likely.
What other tests could be performed to confirm the diagnosis of invasive ductal carcinoma?
Some sort of image guided biopsy.
Fine needle aspiration is generally preferred because it is minimally invasive and can be done quickly but it does not distinguish between in situ and invasive cancers.
Core needle biopsy can usually diagnose between invasive and in situ ductal carcinoma. Preferred imaging guidance is stereotactic (prone patient, specific machine) but tomosynthesis can also be used (basically 3-D mammography).
Lymph nodes are the site of initiation of immune reactions, and a primary function of the immune system is tumor surveillance. Would there be an immune response to cancer cells that lodge in a lymph node? Why or why not?
There might be an immune response. Cancer cells replicate very quickly and tend to accrue DNA damage, if that damage results in decreased expression of MHC I or any other deactivating receptors/ligands that regulate NK activity, then the NK cells will react to and kill the tumor cell via perforin. Eliminating MHC I is kind of preferential for tumor cell survival because it prevents T cells from identifying them and mounting an immune response.
What is this an image of? How would you describe it?
The thymus is the site at which T cell progenitors from the bone marrow become “educated”, learning to distinguish self from non-self. It is located in the upper mediastinum anterior to the heart. It is encapsulated and bi-lobed; each lobe is further sub-divided into lobules by connective tissue septa. The thymus is prominent in childhood and, at puberty, involutes.
Why are there no germinal centers in the thymus?
The thymus is the site of T-cell maturation/education, while germinal centers are where the germinal reaction between B and T-cells occurs in order to activate B-cells place. This occurs in peripheral lymphoid organs not the thymus, as such the thymus lacks germinal centers.
What is this an image of?
What is this an image of and structures are delineated by the yellow arrows and encircled in yellow?
Hassall's Corpuscle and adipose tissue
What are T reg cells? What is their function?
T reg cells (regulatory T cells) develop in the thymus or peripheral tissues after recognizing self antigens and suppress the activation of potentially harmful lymphocytes specific for these self antigens . Most T reg cells are CD4 +, have high levels of CD25 (alpha chain of IL-2 receptor), and express transcription factor FoxP3.
What constitutes the blood-thymus-barrier?
The blood thymus barrier consists of capillary endothelium, epithelia reticular cells, and macrophages within the perivascular connective tissue.
Which cells present antigen in the thymus during development?
Thymic epithelial cells (TECs): present self-Ags on MHC to thymocytes; this helps promote self-tolerance
Within the lymph node what is the black and blue arrows pointing to?
Immediately below the sub-capsular sinus (black arrow) is the cortex, which stains more darkly than the deeper and more central medulla. The trabecular sinus branches off the sub-capsular sinus (blue arrow).
What is this an image of?
This benign, hyperplastic lymphnode stained with CD20 (a pan-B cell marker) and CD3 for T cells. On the H&E-stained section, you can appreciate that the number and size of follicles has expanded, to include the medullary area, when compared with the normal Lymph Node. Germinal centers are distinguished by several distinct zones: the mantle zone is a ring of immature B cells (See also Fig. 13-3 and Fig. 13-12, Robbins and Cotran, 9th Edition) the germinal center itself contains actively proliferating and differentiating B cells, which are easily demonstrated here by the pan-B cell CD20 immunostain. Dendritic and T cells are also present within the follicle center, although they are less abundant than the B cells (see below). Once these B cells have fully differentiated, they are then called plasma cells, and begin to secrete copious quantities of antibodies, and assume a position in the paracortex or medulla of the lymph node.
What is circled in this picture?
The limits of this follicle are outlined by a blue line. Notice that CD3+ cells (a pan-T cell marker) stain occasional cells within the follicle center, as mentioned above, but the majority of positively-stained T cells are located in the paracortical (deep cortex) area, surrounding the approximate limits of the follicle.
What are selectins and addressins? What is their role in lymphocyte homing?
Selectins and addressins are adhesion proteins. Addressins are displayed on the endothelial wall of blood vessels and will interact with the selectin . They are important in leukocyte adherence to sites of infection
What are the interactions that allow lymphocytes to exit the bloodstream?
autotaxin- allows lymphocytes to enter secondary lymph nodes from HEV
What are the most common organisms that cause reactive (inflammatory) lymphadenitis?
Group A Streptococcus, EBV, cytomegalovirus (can be viral, bacterial, or fungal)