2. Content:
⢠Introduction
⢠Level of lymphnodes
⢠Histology of lymphnode
⢠Classification
1. Lymphadenopathies
2. Lymphadenopathies associated with clinical syndrome
3. Iatrogenic lymphadenopathy
4. Vascular lymphadenopathy
5. Foreign body lymphadenopathy
6. Lymph node inclusions
3. Lymphnode
⢠They are especially concentrated in the cervical, axillary, and inguinal regions close to the
body surface, and in thoracic, abdominal, and pelvic groups deep in the body cavities
⢠The medulla consists largely of a branching network of medullary cords composed of
lymphocytes, plasma cells, macrophages, reticular cells, and reticular fibers.
⢠The lymph node is a âbottleneckâ that slows down lymph flow and allows time for cleansing
it of foreign matter.
6. What is lymphadenopathy
⢠Lymphadenopathies are reactive processes of lymph nodes in response to a variety of
exogenous and endogenous stimulants.
⢠The etiology and pathogenesis of many lymphadenopathies are still unknown; thus, the
category remains heterogeneous and poorly defined.
7. Classification of cervical lymphadenopthy :
A. Lymphadenopathies:
1. Reactive Lymphoid Hyperplasia
2. Atypical Lymphoid Hyperplasia
3. Progressive Transformation of Germinal Centers
B. Lymphadenopathies associated with clinical syndrome:
1. Kimura Lymphadenopathy
2. Sinus Histiocytosis with Massive Lymphadenopathy
3. Kikuchi Lymphadenopathy
4. Sarcoidosis Lymphadenopathy
5. Systemic Lupus Lymphadenopathy
6. Rheumatoid Lymphadenopathy
7. Dermatopathic Lymphadenopathy
8. Castleman Lymphadenopathy
9. Lymphadenopathies of Salivary Glands
10. Tumor-Reactive Lymphadenopathy
C. Iatrogenic lymphadenopathy
D. Vascular lymphadenopathy
E. Foregin body lymphadenopathy
F. Lymph node inclusions Ioachim's Lymph Node Pathology 4th edition
8. Reactive Lymphoid Hyperplasia
Definition
Enlargement of lymph nodes or other lymphoid organs as a consequence of hyperplasia
of some or all of the cellular components, reflecting stimulation of the lymphoid cells by
a variety of antigens and representing a benign, reversible process.
Epidemilogy:
⢠Enlargement of lymph nodes.
⢠Majority of enlarged lymph nodes are non-neoplastic.
⢠Age of patients : in children, most lymphadenopathies are benign, whereas in adults,
the probability of malignancy (metastatic carcinoma more so than lymphoma)
increases with age.
⢠Environmental factors such as tobacco smoking, occupational exposure to silicon,
beryllium
9. Etiology
⢠The causes of reactive lymphoid hyperplasia (RLH) include a bacteria, viruses, chemicals,
environmental pollutants, drugs, altered tissue components, and numerous other
substances acting as antigens.
⢠Iatrogenic agents, including various medications such as phenytoin, atenolol, gold,
penicillins, quinidine.
⢠The hyperplastic lymph node reaction to some of these noxious agents includes
characteristic morphologic features, the recognition of which is helpful in determining
the cause.
10. HISTOPATHOLOGY/ FNAC :
1. Nonhomogeneous lymphocyte population
2. Reactive germinal center with centroblasts, centrocytes,
immunoblast ,plasma cells and tingible-body
macrophages.
IHC :
⢠The B cell zones are positive for pan B cell markers
(CD19, CD20) and T cell zones for pan T cell markers
(CD3, CD4, CD8)
⢠The immunoblasts are positive for CD20 and CD30
⢠BCL2 is negative in reactive follicular centers (in contrast
to follicular lymphoma, in which neoplastic follicles are
BCL2 positive)
11. Kimura Lymphadenopathy
The disease, first reported by Chinese authors Kimm and Szeto in 1937
described in 1948 by Kimura and coworkers they noted the vascular component and
referred to it as an âunusual granulation combined with hyperplastic changes in lymphoid
tissueâ
Definition
Kimura disease is a chronic inflammatory disorder prevalent in Asians.
It involves subcutaneous tissues and lymph nodes predominantly in the head and neck
region and is characterized by angiolymphoid proliferation and eosinophilia.
Synonym
Kimura disease; eosinophilic lymphogranuloma.
Etiology
Kimura disease is suggestive of an infectious origin, but no pathogen has been
demonstrated.
12. Clinical Features
⢠IT is located deep in the subcutaneous tissues and in almost all
cases involves the regional lymph nodes.
â˘
⢠Its a chronic inflammatory condition which presents with a
characteristic triad of signs and symptoms, namely a painless,
slowly enlarging soft tissue mass (or masses), associated
lymphadenopathy and peripheral eosinophilia.
⢠Occurs predominantly in young adults;
⢠age range is 27 to 40 years and
⢠male-to-female ratio is 3:1.
⢠May complain of local or generalized pruritus and sub acute or
chronic dermatitis
Lab diagnosis:
Peripheral blood eosinophiliaâ10% to 50%âand elevated serum
immunoglobulin E (IgE)
13. FNAC showed eosinophilia
Biopsy
Dilated blood vessels, some with bizarre and irregular shapes in the reticular dermis (Fig. 2).
Inflammatory infiltrate contained mainly lymphocytes and eosinophils (HE x 100).
Case :
15 years old male who had a swelling in the left cervical area for the past 8 months. The swelling was 5cm x 3cm and was
non tender but firm in consistency It was non adherent to mandible. The skin overlying the swelling was normal.
Patient was treated conservatively with antibiotics and analgesics for two weeks but the swelling persisted.
http://www.odermatol.com/issue-in-html/2013-3-15-kimuras/
14. Kimura's disease - An unusual presentation involving subcutaneous tissue, parotid gland and lymph node
Figure 1: Clinical image of the
patient showing bilateral
swelling in the parotid region Figure 2: Radiographic
image of contrast-
enhanced coronal
computed tomography
scan showing enlarged left
parotid gland and
well-defined irregular soft
tissue enhancing lesion in
right buccal space and
Figure 3: Radiographic image of contrast
enhanced axial CT scans showing
enlargement of following lymph nodes
(red arrows), (a) Left level IB, (b) Left
level II, (c) Left level III, (d) Left level V d
15. Figure 4: Histopathological image shows (a) Lymphoid tissue with reactive follicular hyperplasia (arrows; H&E stain,
Ă100); (b) Germinal centers with deposits of eosinophilic proteinaceous material (red arrows) and areas of
folliculolysis (black arrows; H&E stain, Ă200); (c) Intense eosinophilic infiltration (circles) with formation of
eosinophilic microabscesses (arrows; H&E stain, Ă400); (d) Numerous thin-walled vessels with flattened endothelial
lining and absence of epithelioid or vacuolated cells (arrows; H&E stain, Ă400) d c
https://www.researchgate.net/publication/260396593_Kimura%27s_disease_-
_An_unusual_presentation_involving_subcutaneous_tissue_parotid_gland_and_lymph_node
16. Histopathology
⢠Lymphoid infiltrates with formation of follicles and germinal centers accompanied by plasma cells, mast
cells, and particularly large amounts of eosinophils are present in the subcutis.
⢠Thin-walled capillaries are also present.
⢠The lymph nodes, enlarged 1 to 4 cm in diameter and frequently adherent to one another, show markedly
hyperplastic follicles with reactive germinal centers and a well-defined peripheral mantle zone
Lymphoid follicle with reactive germinal center
(right) Intense eosinophilia with formation of
eosinophilic microabscess (left)
Reactive follicle (upper right). Eosinophilia,
polykaryocytes and capillary hyperplasia
(center).
17. Diffuse eosinophilia, eosinophilic microabscesses, and infiltration of germinal centers, sometimes resulting in
folliculolysis, are part of the process
Folliculolysis with marked
apoptosis (left) intense
eosinophilia (right).
Involuted follicle with hyperplasia of
mantle zone and abundant
eosinophilia in the surrounding
cortical area.
Eosinophilic microabscess in
cervical lymph node.
18. Immunohistochemistry
⢠Deposits of IgE in the germinal centers can be demonstrated with anti-IgE antibodies in
immunofluorescence or by immunoperoxidase staining.
⢠Variable amounts of IgG, IgM, and fibrinogen may also be deposited in the germinal centers.
⢠The vascular endothelial cells stain strongly with factor VIII and with Ulex europaeus agglutinin (UEA-1).
Cytopathology
⢠Fine needle aspiration : Dissociated and clustered endothelial cells, eosinophils, lymphocytes, and
Warthin-Findkeldey giant cells.
19. Sinus Histiocytosis with Massive Lymphadenopathy
Described by Destombes in 1965.
Rosai and Dorfman subsequently recognized this disease as a clinicopathologic entity
and coined the term sinus histiocytosis with massive lymphadenopathy.
Definition
A rare benign disorder of histiocytes characterized histologically by intracellular
engulfment of lymphocytes.
Synonyms
Rosai-Dorfman disease;
Histiocytose lipidique ganglionnaire pseudotumorale de Destombes;
lymphadenitis with massive hemophagocytic sinus histiocytosis of Lennert.
Etiology
⢠The etiology remains unknown.
⢠Although the clinical manifestations and histologic appearance are suggestive of
an infectious process, no microorganism has yet been identified.
20. Clinical Features
⢠Initially, Rosai and Dorfman described this disorder as
massive, bilateral, and mostly cervical lymphadenopathy in
young black children
⢠The age of patients ranged from newborn to 74 years (mean,
20.6 years).
⢠M:F= 3:2
Immunology
⢠Some patients have one or more immune disorders, such as
polyarthralgia, asthma, or hemolytic anemia, preceding or
associated with the onset of SHML.
⢠Abnormalities in serum protein levels are detected in most
patients, who usually show moderate polyclonal
hypergammaglobulinemia.
⢠In patients tested, a reversal in the ratio of CD4-to-CD8
circulating lymphocytes was recorded
22. Histopathology
Involved lymph nodes are large and matted
and exhibit fibrosis of the capsule and
pericapsular fibrofatty tissues.
The architecture is altered by marked
dilatation of the sinuses
Sinus histiocytosis with massive
lymphadenopathy. Markedly
widened sinuses alter normal
lymph node architecture.
The sinuses are obstructed by static lymph
and contain a mixed population of cells,
including lymphocytes, plasma cells, and
histiocytes
Sinus histiocytosis with massive
lymphadenopathy. The sinuses are
expanded by histiocytes, lymphocytes,
and plasma cells.
The most characteristic cells in the sinuses are
histiocytes that have that marked phagocytic
properties (henceforth referred to as SHML
cells). The SHML cells are generally large and
irregularly shaped, with abundant,
acidophilic, sometimes vacuolated cytoplasm.
These cells usually have one nucleus and can
have a distinct, central nucleolus
Sinus histiocytosis with massive
lymphadenopathy. High power
magnification of distended sinus with
a histiocyte containing numerous
lymphocytes (emperipolesis).
23. Necrosis is usually not present,
but superimposed infarction
necrosis can rarely occur Sinus histiocytosis with massive
lymphadenopathy. On the left side
of this field, the lesion has
undergone infarction necrosis.
24. Kikuchi Lymphadenopathy
Synonyms
Kikuchi disease; Kikuchi Fujimoto lymphadenopathy; Histiocytic necrotizing lymphadenitis.
Definition
Subacute necrotizing regional lymphadenopathy associated with mild fever, more common in young Asian
people.
Epidemiology
⢠Described independently in 1972 by Kikuchi and Fujimoto et al.,
⢠commonly recognized in Asia and sporadically in Western countries.
⢠The patients are generally young adults, and a slight female prevalence has been reported.
Etiology
⢠The etiology of necrotizing lymphadenitis is unknown.
⢠A viral infection is suggested by the clinical and histologic features
⢠various viruses including Epstein-Barr (EBV) virus, cytomegalovirus, parvovirus B19, human herpesvirus 6
(HHV-6) and HHV-8 have been investigated, so far with negative results
25. Pathogenesis
⢠The extensive cell death is attributed to early apoptosis, which is characterized by excessive nuclear
fragmentation.
⢠The same authors have determined that the CD8+ T lymphocytes are the cells that predominantly
undergo apoptosis in this lymphadenopathy.
⢠Ohshima et al. have also noted that the serum concentrations of interferon-?, interleukin-6, FAS-L, and
other cytokines are increased in the acute phase of Kikuchi disease
26. Clinical Features
⢠young adults, predominantly women,
⢠the average age was 27.4 years and the male-to-female ratio 1:1.6
⢠More than 85% of the patients present with swollen cervical lymph nodes, unilateral in 88.5% of cases,
usually involving the posterior cervical triangle
⢠Less commonly axillary, inguinal lymph nodes are involved and cases of generalized lymphadenopathy
have been also reported.
⢠The lymphadenopathy is painless and unaccompanied by other symptoms or associated with moderate
fever, chills, myalgia, sore throat, and skin rashes resembling measles or drug eruptions in 20% to 30% of
cases.
â˘
⢠The course is benign with spontaneous resolution of the adenopathy in a few weeks or months and rare
recurrences.
⢠Involvement of extranodal sites, such as a moderate liver and spleen enlargement.
27. Histopathology
The lymph node architecture is
partially maintained and residual
follicles have reactive germinal
centers. Patchy areas of necrosis,
irregularly shaped and occasionally
confluent are randomly distributed
often as cortical wedge-shaped
areas.
Patches of necrosis (center),
lymph node capsule and
follicles with reactive germinal
centers (right), area of
histiocyte proliferation (left)
The necrosis consists of brightly eosinophilic fibrinoid deposits including nuclear fragments surrounded by large
accumulations of pale-staining histiocytes
Irregularly shaped area of necrosis
consisting of bright eosinophilic
fibrinoid deposits and apoptotic cells
in unaffected lymphoid tissue (lower
right)
Necrosis with fibrinoid deposits
(left) and apoptotic cells (center),
histiocytes (right).
Necrosis, fibrinoid deposits, and
extensive apoptosis of lymphoid
cells.
Center of necrotic area with
intense necrosis and apoptosis
(right).
28. Occasionally, the tissue necrosis is represented only by isolated apoptotic cells scattered throughout large
aggregates of histiocytes admixed with cellular debris and nuclear dust.
necrosis and fibrin deposits (right), apoptosis (right), and
histiocytes (center, left).
Some authors consider histiocytic proliferation rather than necrosis the characteristic feature of the Kikuchi-
Fujimoto lymphadenopathy and even include in this entity cases that lack overt necrosis and show only scattered
cells with pyknosis or karyorrhexis.
areas of histiocytic proliferations
surrounding the necrotic center.
29. ⢠The cellular debris is actively phagocytosed by numerous histiocytes, cells with abundant
cytoplasm and peripheral, compressed, crescentic nuclei resembling signet-ring cells.
⢠The areas of histiocytosis also include small lymphocytes, activated T lymphocytes, and a
moderate amount of plasma cells.
⢠Neutrophiles and eosinophiles are consistently absent, constituting a distinctive feature of
this lesion. At the periphery of necrotic areas often are thrombosed vessels as well as nests
of plasmacytoid monocytes and immunoblasts.
⢠Some of these cells have large, atypical nuclei that could be mistaken for lymphoma.
⢠There is usually a degree of perilymphadenitis with lymphocytes, often apoptotic, and
histiocytes infiltrating
30. Dermatopathic Lymphadenopathy
This lesion was originally described by Pautrier and Woringer in French in 1937 but the name
dermatopathic lymphadenitis was coined and published in English by Hurwitt in 1942.
Its associated with chronic dermatologic lesions and represents a lymph node reaction to the
drainage of melanin and various skin antigens.
Its a distinctive type of paracortical hyperplasia in which interdigitating dendritic cells are
greatly increased.
Clinical Features.
⢠Occurred twice as often in males as in females, and most patients had associated skin
disease.
⢠Typically, dermatopathic lymphadenopathy occurs in lymph nodes draining sites of chronic
cutaneous disease such as infections and cutaneous neoplasms.
⢠The benign skin diseases commonly associated with DL are often exfoliative or eczematoid:
toxic-shock syndrome, pemphigus, psoriasis, neurodermatitis, eczema
31. Pathologic Features. The paracortical regions of lymphnode are expanded by interdigitating dendritic cells,
Langerhans cells, and lymphocytes. Interdigitating dendritic cells are large with relatively abundant pale
cytoplasm, folded or twisted nuclei, thin nuclear membranes, and small nucleoli. In advanced cases, other
inflammatory cells such as plasma cells and eosinophils may be present and histiocytes contain melanin
pigment.
Treatment and Prognosis. There is no specific therapy. The lymphadenopathy resolves if antigenic stimulation
subsides.
A, At low power, the paracortical regions are pale and expanded.
B, Small lymphocytes are relatively decreased, and numerous interdigitating dendritic cells and fewer Langerhans cells with
twisted nuclei and linear grooves are present. Some histiocytes contain
melanin pigment.
C, Touch imprint highlights interdigitating dendritic cells with coffee beanâshaped nuclei.
32. At this low-power
magnification, nodular,
palely stained areas can
be identified in the
paracortical regions.
Hyperplastic lymphoid
follicles are also present.
A hyperplastic follicle is
present at the upper left.
The pale areas in Fig.
41.1 correspond to a
mixture numerous
interdigitating dendritic
cells, Langerhans cells,
and small lymphocytes.
High-power
magnification showing
the twisted nuclei and
abundant cytoplasm of
the interdigitating
dendritic and
Langerhans cells.
Numerous pigment-
containing histiocytes
were present in this
case.
33. Immunohistochemistry
A: S100 protein is expressed by numerous interdigitating
dendritic cells and Langerhans cells.
B: CD1a is expressed by Langerhans cells.
C: CD3 is expressed by numerous T cells in the
background. Immunohistochemistry with hematoxylin
counterstain.
34. Castleman Lymphadenopathy
Definition
In the original reports by Castleman et al.
Itâs a large, benign, asymptomatic mass involving mediastinal lymph nodes.
it is now recognized that Castleman was describing the hyaline vascular variant.
Subsequent recognition of the plasma cell variant of CD, both localized and multicentricâfollowed relatively
recently by the recognition human herpes virus type-8 (HHV-8) in a subset of multicentric casesâillustrates that
the term âCastleman diseaseâ is used to describe a heterogeneous group of diseases with variable clinical
presentations and prognosis.
Synonyms
Angiofollicular lymph node hyperplasia,
Giant lymph node hyperplasia,
Angiomatous lymphoid hamartoma,
Benign giant lymphoma.
Variants
Localized,
hyaline-vascular (HV) variant,
plasma cell (PC) variant,
unicentric or multicentric.
35. HISTOPATHOLOGY:
HYALINE-VASCULAR TYPE â
Abnormal follicles with atrophic or
âregressedâ hyalinized germinal centers, which contain numerous
follicular dendritic cells
The follicles are surrounded by broad
mantle zones of small lymphocytes, present in an âonion skinâ
arrangement
Two or more adjacent germinal centers
may be surrounded by a single mantle zone
The regressed germinal centers are often
radially penetrated by a hyalinized blood vessel (âlollipop
follicleâ)
36. PLASMA CELL TYPE
⢠Mixture of hyperplastic germinal centers and
regressed follicles
⢠Interfollicular region is hypervascular and contains
sheets of plasma cells
PLASMABLASTIC TYPE
⢠Atypical-appearing large cells with plasmablastic
morphology (previously called âmicrolymphomaâ)
⢠Present inside germinal centers and in interfollicular
areas
37. Special Stains and Immunohistochemistry :
⢠CD21-positive, CD23-positive follicular dendritic cell meshworks
⢠Plasma cell variant may contain monotypic plasma cells, usually of IgGΝ or IgAΝ isotype
(up to half of the cases)
⢠Plasmablastic type contains IgMÎťârestricted atypical large cells
Other Techniques for Diagnosis :
â˘Elevated serum levels of IL-6
â˘Tissue PCR for HHV-8
â˘IgH gene rearrangement shows no evidence of B-cell clonality
38. IATROGENIC LYMPHADENOPATHIES
DRUG INDUCED:
CLINICAL FEATURE :
either mephenytoin (Mesantoin) or phenytoin (Dilantin) 1 to 6 weeks before
experiencing tender bilateral cervical lymphadenopathy accompanied by fever,
eosinophilia, and a variety of skin changes, ranging from morbilliform rashes to exfoliative
dermatitis.
HISTOPATHOLOGY :
Early lesions were characterized by PARTIAL EFFACEMENT.
histiocytes , immunoblasts, plasma cells, and eosinophils with
varying degrees of vascular proliferation are seen .
SPECIAL STAINS AND IMMUNOHISTOCHEMISTRY - Immunoblasts express CD30 and are
negative for CD15 .
39. Polymorphous lymphoproliferative disorder in a patient with rheumatoid arthritis being treated with
methotrexate.
A: The lymph node architecture is subtotally effaced but occasional follicles are spared and many
sinuses are patent (bottom of field).
B: The lesion is composed of a mixture of mature and immature plasma cells, small and large
lymphocytes, immunoblasts, and histiocytes.
The plasma cells expressed polyclonal Ig light chains in this case (not shown). Hematoxylin-eosin stains.
Ioachim's Lymph Node Pathology > Part Four - Lymphadenopathies > Section III - Iatrogenic Lymphadenopathies >
40. VASCULAR LYMPHADENOPATHIES
LYMPH NODE INFARCTION
⢠Result from infection, vasculitis, or trauma
⢠Lymphomas associated with lymph node infarction are typically diffuse large-b-
cell lymphomas, but they also include follicular lymphoma, t-cell lymphomas,
and HL.
HISTOPATHOLOGY :
⢠Massive ischemic necrosis
⢠Peripheral rim of spared lymphoid tissue
⢠Ghost like necrotic lymphocytes or
lymphoma cells
⢠Preservation of reticulin network
⢠Thrombosis of intranodal vessels
41. VASCULAR TRANSFORMATION OF LYMPH NODE SINUSES
Vascular transformation of lymph node sinuses is usually found incidentally after
resection of a nearby tumor.
HISTOPATHOLOGY :
1. Vascular proliferation within lymph node sinuses
2. Association with vascular obstruction
3. Cleft-like, rounded, solid, and plexiform patterns
4. Erythrocyte extravasation
5. Fibrosis
43. 2. SILICONE LYMPHADENOPATHY :
Histiocytes with fine strands of
refractable material probably
polyurethane surrounded by
foreign-body giant cells.
44. Inclusion bodies
Epithelial Cell Inclusions in Lymph Nodes
Definition
Clusters of benign, well-differentiated epithelial cells in lymph nodes.
Pathogenesis
The presence of epithelial cells in lymph nodes is usually the result of metastasis from a
regional carcinoma. Their detection is of great clinical importance because it determines
the staging, and consequently the treatment, of malignant tumors.
45. Salivary gland inclusion in parotid
lymph node. Salivary gland duct with
hyperplastic lining epithelium lies
within the nodal lymphoid tissue.
Thyroid inclusions in cervical
lymph node; several clusters of
colloid-filled follicles in the
peripheral sinus
Nicastri AD, Foote FW Jr., Frazell EL. Benign thyroid inclusions in cervical lymph nodes. JAMA 1965;194:113â116
Nonpapillary, colloid-containing
follicles lined by flattened cuboidal
epithelium in peripheral sinus
46. Glandular inclusions in peritoneal lymph
node of 42-year-old woman with no
neoplastic disease. The glands have
bizarre shapes, are lined by low columnar
epithelium, and are surrounded by
fibrocollagen.
Glandular inclusions with ciliated
epithelial lining surrounded by
nondesmoplastic stroma in pelvic
lymph node of patient with
endometrial carcinoma.
Glandular inclusion lined by
ciliated epithelium of
endosalpingiosis type with
intraluminal secretion in pelvic
lymph node
Editor's Notes
Warthin-Findkeldey giant cells- seen in measles,hiv infected ppl
Virus mediated cell fusion
Rosai and Dorfman1 described the triad of massive cervical lymphadenopathy, expanded lymph node sinuses, and characteristic histiocytes showing emperipolesis as a novel entity among the histiocytosis. Lymphocytophagocytosis (emperipolesis) describes the presence of lymphocytes within the histiocytes.
The active phagocyte is a histiocyte that is positive for s-100 protein, CD68; and the histiocytic proliferation is polyclonal.2