A. Normal lymph node histology

Doc. MUDr. L. Boudová, Ph. D.
Lecture on lymph node pathology.
Most important: you have to understand normal lymph node histology and reactive patterns –
hyperplasia of LN compartments. You should be able to describe the patterns of hyperplasia and give
examples of etiologic agents that may cause them (very important). In the rest of this text, disease entities
are explained (sorted by etiology) - more advanced - to complete the information.
This is a practical working text giving the basic plan for learning– not a section of a textbook.
Other recommended sources: Robbin´s Pathologic Basis of Disease– 7th edition; lectures on immunology
and histology, lectures on pathology
Abbreviations: DD: differential diagnosis; LN: lymph node; LF: lymphoid follicle; Ig : immunoglobulin
FDC follicular dendritic cell; IDC interdigitating dendritic cell; LAIS: lymphadenitis; GC: germinal centre; CC:
centrocyte; CB: centroblast
A. Normal lymph node histology
B. Reactive lymphoid hyperplasia
C. Nonlymphoid tumours in lymph nodes
A. Normal lymph node histology
The lymphatic system
circulating lymphocytes
lymphatic tissues: primary and secondary.
primary lymphatic tissues or organs (central): humans, bone marrow and the thymus
peripheral lymphatic organs lymph nodes, spleen, and mucosa associated lymphoid tissue,
fibrous capsule.
cortex, paracortex, medulla, and sinuses
multiple afferent lymph vessels
single efferent lymphatic vessel in the hilus.
The cortex
B-cells, lymhoid follicle - primary and secondary, round meshworks of FDC
memory B-cells and plasma cells formed..
Secondary lymphoid follicle: response to antigenic stimulation
germinal center and a mantle zone of small lymphocytes
The paracortex T-cell dependent
small T-lymphocytes, immunoblasts, interdigitating dendritic cells, and HEV. The IDC
present antigens to T-cells.
Doc. MUDr. L. Boudová, Ph. D.
Lecture on lymph node pathology.
activation of B- and T-cells in the primary immune reaction and in some other situations.
the medulla sinuses and cords of plasma cells.
Important terms
Lymphadenopathy – disease of LN -biological dignity not specified
often used for any enlarged LN
Lymphadenomegaly –LN enlargement
Lymphadenitis – inflammation of the LN
B. Reactive lymphoid hyperplasia
Reactive changes of lymph nodes - responses to
microbiologic agents, cell debris /own necrotic tissues /, foreign materials
from: the tissues drained by the lymph node or distant sites of the body
Acute inflammation of the lymph node = acute lymphadenitis
Localised or generalised
localised - the most commonly affected areas:
Cervical /teeth and tonsils/
Axillary, inguinal: infections, wounds of the extremities, inguinal: also genital infections
Similarly: mesenteric - caused by acute appendicitis - or may be primary (Yersinia) - simulate
Remember: systemic viral inf. and bacteremia often produce generalized lymph node
enlargement (particularly in children/
Relationship of etiology/ histological pattern
categorise reactive changes in the lymph nodes by etiology or by a predominant histological
pattern in the LN. One predominant pattern – for example enlargement of the follicles - may
be caused by various agents. On the other hand, one disease may typically produce one certain
pattern in the LN. Some diseases may show a mixture of several histological changes
The main histological patterns
Follicular hyperplasia
inflam. processes that activate B-cells /see the list/
Enlarged secondary lymphoid follicles with prominent GC –different shape and size (this
variation in the size and shape is very important!!)
LN architecture preserved .
Doc. MUDr. L. Boudová, Ph. D.
Lecture on lymph node pathology.
GC : polarization, mitotic activity, macrophages phagocytosing debris /tingible body
around the follicles: plasma cells, histiocytes, granulocytes
Progressive transformation of GC: enlarged,; small lymphocytes coming from the mantle. GC
cells „diluted“ by small mantle lymphocytes
In a small proportion of cases, PTGC in association with Hodgkin´s lymphoma – type of
nodular lymphocyte predominance
Regressive transformation- GC burnt out, small. Devoid of lymphoid cells, A mantle of
concentrically arranged small lymphocytes -onion skin
Examples: Castleman´ s dis., spent phase lymphadenopathy of HIV infection
Paracortical hyperplasia
Mainly the T-zone reacts /interfollicular /
Expansion - nodular /dermatopathic Lais/ –rashes, skin tumours
Diffuse – viral lymphadenitis, drug reactions
Between the follicles:mixed cellular infiltrate „salt and pepper“
Prominent blood vessels – high endothelial venules
Sinus histiocytosis /sinus hyperplasia/
distention and prominence of lymphoid sinuses, within them: macrophages
Examples: LN draining infections or cancers, Rosai-Dorfman dis., Langerhans histiocytosis,
Whipple dis., vascular transformation of the sinuses
Granulomatous inflammation
Infections, foreign body reactions, LN draining carcinoma, patients with Hodgkin´s
In most cases combination of clinical, mortphologic, bacteriologic data is necessary to
determine the etiology
Doc. MUDr. L. Boudová, Ph. D.
Lecture on lymph node pathology.
Reactive lymphoid hyperplasia: predominant pattern by etiology
follicular hyperplasia
1. bacterial infection
2. rheumatoid arthritis
3. HIV infection /early/
4. Syphilis
5. Castleman ´s disease
paracortical h.
1. viral inf.
2. Dermatopathic lymphadenopathy
3. Postvaccination lymphadenopathy
4. Drug-induced hypersensitivity reaction – phenytoin /Dilantin/
5. Kikuchi´s dis.
6. Systemic lupus erythematosus
7. Draining region of suppurative inflammation /some cases/
8. Lymh nodes draining carcinoma /rarely/
sinusoidal expansion
1. lymphangiogram effect
2. Whipple´s dis /some cases/
3. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman)
4. Lymph nodes draining carcinoma /rarely/
granulomatous lymphadenitis bacterial inf. – e. g. cat scratch dis., tularemia,
lymphogranuloma venereum, yersinial lymphadenitis,
Whipple´s dis.
Fungal inf.
Lymh nodes draining carcinoma /rarely/
Mixed pattern
Kimura´s dis.
Doc. MUDr. L. Boudová, Ph. D.
Lecture on lymph node pathology.
Acute nonspecific lymphadenitis
sinus dilatation resulting from an increased flow of lymph , accumulation of neutrophils,
vascular dilatation, edema of the capsule
Suppurative Lais: staphylococci, mesenteric Lais, lymphogranuloma venereum, cat-scratch
Necrotizing features: bubonic plague, tularemia, anthrax, typhoid fever, melioidosis,
necrotizing Kikuchi LAis
Chronic nonspecific lymphadenitis
lymph nodes show various patterns of hyperplasia
Viral lymphadenitis
Infectious mononucleosis
EBV, young /
If more severe: hepatosplenomegaly, generalized lymphadenopathy, hepatic dysfunction,
peripheral cytopenia
most cases self-limited, but: rarely fatal
LN architecture distorted but not effaced - expanded paracortex – polymorphous
inflammatory infiltration, necrotic foci, follicles present,
Differential diagnosis: other inflammations, lymphomas
Herpes simplex Lais
Unusual: . A half of patiens: hematolymphoid malignancy
accompanies mucocutaneous lesions
Localized (most commonly inguinal) or generalized enlargement of lymph nodes
Paracortical hyperplasia, evt. necrosis, intranuclear inclusions
IM-like illness
May be otherwise asymptomatic
Bacterial infections
Cat scratch disease
common, Bartonella henselae – a gram-negative rod
Doc. MUDr. L. Boudová, Ph. D.
Lecture on lymph node pathology.
Skin papule, lymphadenopathy /typically axillary/. 50%: fever, may have other symptoms
mild, self limited
Precise identification: serology, PCR /
If well developed: granulomatous.purulent LAIs (GP LAIS)
Other GP LAIS: lymphogranuloma venereum /Ch. trachomatis/, tularemia /Francisella t./,
Hemophilus ducreyi /chancroid/, Yersinia entrocolitica, /mesenteric LAIS/, listeriosis,
glanders /Pseudomonas malleui/, Pyogenic cocci: Staphylococcus, Streptococcus – acute
suppurative lAIS similar to cat scratch disease, Mycobacteria
Mycobacterial infections
Myc. LAIS – isolated or in conjunction with pulmonary TB or disseminated dis.
LA - slowly enlarging, nontender, most commonly cervical LN
casesous necrosis + granulomatous rim (epithelioid histiocytes) + Langhans multinucleate
giant cells
Children – more commonly: atypical myc. /scrofulaceum. Kansasii, avium/
Ziehl-Neelsen stain, culture
Myc, leprae;
tuberculoid (TB) or lepromatous (LL) or intermediate – depending on the immunologic status
of the host
TB L – non cas. granulomas /mild enlargement/, localized
L L: often generalized – histiocytes form aggregates or diffuse infiltrates, in the cytoplasm:
numerous bacilli – lepra cells
DD : also storage dis
immunosuppressed patients- (HIV, malignancy /often – lymphoma/, iatrogenic IS)
Histoplasma capsulatum, Cryptococcus neoformans
Often with pulmonary or disseminated dis
Granulomatous infection -may be necrotizing , fibrosis, calcification
Toxoplasma gondii (TG)(Piringer-Kuchinka) – IMPORTANT!
The most common clin. manifestation of TG infection in an immunocompetent host Lymphadenopathy, mainly cervical, asymptomatic or with fever, sore throat
Doc. MUDr. L. Boudová, Ph. D.
Lecture on lymph node pathology.
Rarely complication
Histological picture characteristic: Florid follicular hyperplasia,bands of monocytoid B-cells,
paracortical hyperplasia, clusters ofhistiocytes - in paracortex and in the GC
Confirmation: serology ; DD: important : not to misdiagnose as Hodgkin lymphoma!
Mesenteric LAIS
Yersinia pseudotuberculosis or Y. enterocolitica /gram –negative/
Benign, self-limited. Simulates appendicitis clinically.
HIST.: sinus hyperplasia, follicular hyperplasia, paracortical hyperplasia
RA, juvenile RA, SLE, PBC, MCTD
LN are biopsied in these patients to exclude malignancy
Systemic lupus erythematodes( SLE)
Young women, broad clin. spectrum: arthritis, fever, rash, renal dis, nausea, vomiting,
neurologic problems
Two thirds of cases: lupus lymphadenitis – cervical and other LN, rarely generalized
Hist: complicated. Sometimes very characteristic hematoxylin boides
Rheumatoid arthritis
chronic systemic illness - destructive arthritis, other manifestations hematologic,
cardiovascular, neurologic, pulmonary; adults, more commonly females
75 per cent: lymphadenopathy – genneralized or localized
HIST: prominent follicular hyperplasia, Increased frequency of lymphomas
Uncommon, unknown etiology, more commonly blacks, women,
Typically affects: LN and lungs, course variable
LN: Multiple well-formed granulomas, epithelioid hist., multinucleated giant cells, often
confluent, inclusions – several types; diagnosis of exclusion, a very broad DD
Necrotizing histiocytic lymphadenitis
Kikuchi; typ.: young Asian women; persistent painless cervic. Lymphadenopathy, fever
HISTOLOGY: necrotic areas in the paracortex; practically no neutrophils in the necrosis
Doc. MUDr. L. Boudová, Ph. D.
Lecture on lymph node pathology.
Evolution : benign, self-limited. The etiology unknown, most important DD: lymphoma
Sinus histiocytosis with massive lymphadenopathy /Rosai-Dorfman/
Children, young; blacks
Massive. Painless, bilateral cervical lymphadenopathy
Fever, leukocytosis, anemia, higher ESR, higher Ig
Usually benign, enlarged lymph nodes, sinuses dilated – large pale histiocytes,
Castleman´s dis.
1. Hyaline –vascular /90 per cent/ = angiofollicular
2. Plasma cell variant /10 per cent/
1. young, localised , typ. mediastinum. Asymptomatic, regressively transformed GC; cured
by the excision
2. localized or multicentric –often sytemic symptoms – anemia, higher ESR, weight loss,
hyperglobulinemia. If multicentric – more severe, often hepatosplenomegaly, POEMS
syndrome. Clinical course varies ; rarely: sarcoma of dendritic cells may develop
Kimura´s dis
chronic inflammation in the area of the head and neck
Asian adults, lesions in the salivary glands and the skin, peripheral eosinophilia and higher
IgE levels in the serum
Niemann-Pick, Gaucher
Lymphangiogram lymphadenopathy
lipogranulomas, multinucleated giant cells
Reaction in LN close to joint prostheses – histiocytes and metal particles
lymphoid x nonlymphoid
Primary - lymphoid (lymphomas); nonlymphoid: VERY RARE: tumors of dendritic cells,
histiocytes, Langerhans cell histiocytosis; hemangioma
Secondary - MORE COMMON THAN PRIMARY!: metastases of carcinomas; melanoma