Please enable JavaScript.
Coggle requires JavaScript to display documents.
HEMATOPATHOLOGY 2 (LYMPH NODES) - Coggle Diagram
HEMATOPATHOLOGY 2
(LYMPH NODES)
LYMPHADENITIS
architectural patterns
ACUTE NON-SPECIFIC
LYMPHADENITIS
acute inflammation in LNs draining from an infected site
almost exclusively bacterial
from focal infiltration by neutrophils to necrosis and suppuration with abscess formation
THERE ARE GRANULOCYTES !
--> typical of acute reactions or Hodgkin lymphoma
areas involved:
cervical region: due to drainage of microbes or microbial products from infections of teeth or tonsils
axillary or inguinal regions: caused by infections in the extremities
mesenteric LNs: in the setting of acute appendicitis and other inflammatory conditions involving the gut
systemic viral infections and bacteremia often produce acute generalized lymphadenopathy
morphology
nodes are swollen, gray-red and engorged
micro: prominence of large reactive germinal centres containing numerous mitotic figures
macrophages often contain particulate debris (dead bacteria, necrotic cells)
when pyogenic organisms are the cause, neutrophils are prominent and the centres of the follicles may undergo necrosis
sometimes the entire node is converted to pus with many granulocytes and the presence of suppurative necrosis
FOLLICULAR
HYPERPLASIA
more common pattern
caused by stimuli that activate the humoral immune response
defined by the presence of large oblong germinal centres, surrounded by a collar of small resting naive B cells
germinal centres are polarized
a light zone with proliferating blast-like B cells (centroblasts)
a dark zone composed of B cells with irregular or cleaved nuclear contours (centrocytes)
interspersed among the GC B cells is an inconspicuous network of antigen-presenting follicular dendritic cells and macrophages
(TINGIBLE-BODY MACROPHAGES)
these macrophages appear as large cells with dot bodies in the cytoplasm, present alongside with an higher mitotic figure count
causes
RA
toxoplasmosis
early HIV infection
differential diagnosis with
FOLLICULAR LYMPHOMA
features of non-neoplastic hyperplasia:
preservation of the LN architecture, including the interfollicular T cell zones and the sinusoids
marked variation in the shape and size of some follicles
presence of frequent mitotic figures, phagocytic macrophages and recognizable light and dark zones
in a normal GC there is higher proliferative activity than in follicular lymphoma, tested with ICH Ki-67:
lymphoma: 10-20%
reactive situations: 99%.
THIS IS THE OPPOSITE OF WHAT HAPPENS IN SOLID TUMORS
PARACORTICAL
HYPERPLASIA
caused by stimuli that trigger T-cell–mediated immune responses, such as acute viral infections
T cell regions typically contain immunoblasts
activated T cells features:
3-4x the size of resting T cells
round nuclei
open chromatin
several prominent nucleoli
moderate amounts of pale cytoplasm
morphoogically similar to centroblasts, but located in the paracortical area and not in the germinal centre
SINUS
HISTIOCYTOSIS
aka "reticular hyperplasia"
characterized by an increase in the number and size of the endothelial cells lining the sinusoids and by an increased number of intrasinusoidal macrophages --> expansion and distorsion of sinusoids
particularly prominent in LNs draining cancers duch as carcinoma of lungs or breast
the vascular transformation of LN sinuses shows a sinus pattern
differential diagnosis with
KAPOSI SARCOMA
it can be distinguished from SH by the proliferation of spindle-shaped KS clls forming cleft-like vascular spaces that contain RBCs
GRANULOMATOUS
LYMPHADENOPATHY
formation of epithelioid granulomas in lNs
the LN architecture is substituted by the presence of newly formed granulomatous structres
granulomas are nodular structures, but they replace LNs
types
caseating granulomas
epithelioid granulomas that form central necrosis and caseation; they are typically seen in M. tuberculosis lymphadenitis
the forming cells are histiocytes, which are expanding and they look like epithelial cells
roundish large cells with aboundant cytoplasm and big nuclei
a special staning (Ziehl-Neelsen) is used to detect the bacilli as bright red, slender, beaded microorganisms (the background is blue)
necrotising, non-caseating granulomas
found in cat-scratch disease, caused by Bartonella henselae (black with Warthin-Starry stain), in which suppurative granulomas with stellate microabscesses surrounded by palisading histiocytes predominate
necrotizing granulomas
containing karyorrhectic debris
no neutrophils
Kikuchi-Fujumoto lymphadenopathy
common in young Asian women
non-necrotising, non-caseating granulomas
characteristic of sarcoidosis lymphadenopathy
granulomas are found in mediastinal LNs and in LNs in lung parenchyma
composed primarily of epithelioid histiocytes with scattered multinucleated giant cells, lymphocytes and plasma cells
sarcoidosis granulomas are coalescent and forming aggregation of granulomas
fibrosing granulomas can form on the long term
this type of granuloma is also found in draining LNs of Crohn's disease
chronic lymphadenitis
lymph nodes are non-tender, as enlargement occurs slowly over time
tissue damage typical of acute inflammation is absent
particularly common in inguinal and axillary nodes
they can promote the appearance of organized collections of immune cells in non-lymphoid tissues
these collections are sometimes called "tertiary lymphoid structures" (TLS)
classic examples
chronic gastritis caused by H. pylori
aggrgates of mucosal lymphocytes are seen, that stimulate the appearance of Peyer patches
Lymphotoxin involvement?
rheumatoid arthritis
B cell follicles often appear in the inflamed synovium
LYMPHOID NEOPLASMS
old classification
LYMPHOMAS
proliferations of white cells (typically lymphocytes), usually presenting as discrete tissue masses
LEUKEMIAS
widespread involvement of the bone marrow and sometimes peripheral blood
PLASMA CELL
NEOPLASIAS
most often arising in the bone marrow and rarely involving lymph nodes or peripheral blood
WHO classification
precursor B cell neoplasms (immature B cells)
peripheral B cell neoplasms (mature B cells)
precursor T cell neoplasms (immature T cells)
peripheral T cell and NK cell neoplasms (mature T and NK cells)
Hodgkin lymphomas (neoplasms of Reed-Stenberg cells and variants)
etiologic and pathogenetic factors in lymphoid cell neoplasias
CHROMOSOMAL TRANSLOCATIONS
and other acquired mutations
mutations commonly seen in lymphomas and myeloid neoplasms
proto-oncogenes (MYC, BCL6) are often activated in lymphoid cells by errors that occur during attempted antigen receptor gene diversification
among lymphoid cells, potentially oncogenic mutations occur most frequently in GC B cells
B lymphoid neoplasms classification
according to the differentiating stage of the cell from which they originate
precursor B cell neoplasms: ALL
pre-GC cell neoplasms: mantle cell
lymphoma and a subset of CLL/SLL
neoplasms that originate from GC cells:
follicular lymphoma, Burkitt lymphoma,
Hodgkin lymphoma, a subset of DLBCL
neoplasms originsting from post-GC cells:
marginal or MALT lymphoma, lymphoplasmacytic
lymphoma, a soubgroup of CLL/SLL, a subgroup
of DLBCL and plasma cell myeloma
clinical presentation
determined by the anatomic distribution
2/3 of NHLs and all HLs present as enlarged non-tender LNs (often >2 cm)
the remaining NHLs present with symptoms related to the involvement of extranodal sites (e.g. skin, stomach, brain)
lymphocytic leukemias have symptoms related to the suppression of normal hematopoiesis by tumor cells in the bone marrow
the most common plasma cell leoplasm (multiple myeloma) causes bony destruction of the skeleton and often presents with pain due to pathologic fractures
other symptoms are frequently caused by protein secretion from tumor cells or immune cells responding to the tumor
plasma cell tumors
secretion of whole Abs
or Ig fragments
Hodgkin lymphoma
fever related to the release of cytokines
peripheral T-cell lymphomas
release pro-inflammatory cytokines and chemokines
general principles of lymphoid neoplasms
antigen receptor gene rearrangement generally precedes the transformation of lymphoid cells
all cells derived from the malignant progenitor share the same antigen receptor gene configuration and synthesize identical (monoclonal) antigen receptor proteins
normal immune responses are composed of polyclonal populations of lymphocytes
most lymphoid neoplasms resemble some recognizable normal stage of B- or T-cell differentiation
90% of lymphoid neoplasms are of B cell origin
lymphoid neoplasms are often associated with immune abnormalities
susceptibility to infections
breakdown of tolerance
(autoimmunity)
individuals with inherited or acquired immunodeficiency are at high risk of developing certain lymphoid neoplasms
e.g. EBV
neoplastic B and T cells tend to recapitulate the behavior of their normal counterparts
like normal lymphocytes, neoplastic B and T cells express adhesion molecules and chemokine receptors that govern their homing to certain tissues
hodgkin lymphoma spreads in an orderly stepwise fashion
whereas most forms of NHL disseminate widely and unpredictably early in the course
markers
lymphoid neoplasia can be suspected based on clinical features, but histologic examination of LNs or other involved tissues is required for diagnosis
aka "clusters of differentiation" (CD)
specifically and characteristically expressed on the surface of specific lymphoid cells during the different phases of their maturation
according to the presence or the absence of specific CDs, it is possible to make the diagnosis
specific examples
CD45
leukocyte common antigen,
found in all leukocytes
very useful in the differentiation
between a SCLC or lymphoma