Hematopathology Diagnoses Too Easy to Miss!
Specific Benign Entities that Can be Easily Misdiagnosed as a Lymphoma (continued)
Marsha Kinney, James Cook and Steven Swerdlow
Kikuchi-Fujimoto Disease (KFD) (Synonym:Histiocytic Necrotizing Lymphadenitis)
17 year-old Caucasian male with right cervical
lymphadenopathy and no evidence of autoimmune disease.
Lymph node sections reveal reactive follicles and pale areas
of paracortical alteration of nodal architecture by a variable mixture of histiocytes, large and small
lymphocytes, and apoptotic debris. At low magnification, the paracortical areas have a "mottled"
appearance due to numerous histiocytes. Focal areas of frank coagulative necrosis with considerable
apoptotic debris are present. Neutrophils are notably absent. Numerous large lymphocytes and
histiocytes are present in the paracortex, particularly surrounding the areas of necrosis. Phagocytic
and non-phagocytic histiocytes with crescentic (or "C"-shaped nuclei) are admixed with immunoblasts and
large transformed lymphocytes. Some of the large lymphocytes have atypical, folded nuclei with very
prominent nucleoli. Some histiocytes have a plasmacytoid appearance with eccentric nuclei and abundant
eosinophilic cytoplasm. Scattered plasma cells are present, and there are focal areas of monocytoid
B-cell proliferation next to sinuses and near follicles. Other areas of the node (not on the digitized
slide) reveal large foci of cortical/paracortical necrosis surrounded by foamy histiocytes and some
involvement of the capsule. A few small vessels near the necrotic areas contain fibrin.
The follicles and only a few lymphocytes in the
interfollicular areas are CD20+ B-cells. The paracortical T-cells show a marked predominance of the CD8+
subset. Many of the T-cells express the cytotoxic granule protein TIA-1. CD68+/ myeloperoxidase (MPO)+
histiocytes are present. Staining for CD123 highlights histiocytes with plasmacytoid morphology seen in
the paracortex and around the necrotic areas. There is a minor population of scattered CD30+ large
The patient is a healthy college student who plays basketball
and describes rare "episodes" similar to those when he was diagnosed with KFD.
This case is presented to illustrate the difficulty in diagnosing lymphoproliferative disorders when
the clinical setting is unusual (male, 17 years old) or the cytology is disturbing (numerous large
atypical cells with large areas of necrosis).
This case was contributed by Lt. Col. Dale M. Selby, M.D.,
Wilford Hall Medical Center, San Antonio, TX.
Background and Clinical Features:
Histiocytic necrotizing lymphadenitis
was first described in 1972 independently by Dr. Kikuchi and Dr. Fujimoto in Japan
has been reported in a wide geographic distribution.
The first report outside of Japan
was by Pileri et al. in 1982 and included predominantly patients from West Germany but also Italy, Iran,
South Korea and Spain.  KFD is typically a self-limited cause of tender lymphadenopathy with
low-grade fever in young adult Asian females under the age of 30 years. Patients may have an upper
respiratory prodrome (30%-50%). The female to male predominance (4:1) varies and approaches 1:1 in
recent studies from Eastern countries or in the pediatric population.
The median age is
21-30 years (range 19 months-75 years).
ervical lymphadenopathy is present in 56%-98%
of cases most commonly in the posterior cervical triangle (88.5%) and is unilateral in 88.5%. Axillary
adenopathy is the next most common site and generalized adenopathy is present in 1%-22%. 
Lymph node size ranges from 0.5 to 4 cm with occasional lymph nodes being greater than 6 cm.
Mediastinal, peritoneal and retroperitoneal involvement is rare.
Laboratory abnormalities include high ESR, mild leukopenia (neutropenia), lymphocytosis with atypical
lymphocytes (25%-31%), or anemia.
 Lactate dehydrogenase and aminotransferase may be
increased in some patients. CT and MRI examinations can mimic lymphoma and other nodal diseases with
necrosis including infection and metastatic tumor. KFD symptoms typically disappear within 1-5 months,
but recurrence has been reported in approximately10% of patients and in pregnancy.
KFD rarely occurs in pediatric patients
with a median age 9.5-16 years and often
with a male predominance.
The distribution of disease (unilateral posterior cervical
adenopathy in 83% with a size range of 0.5-3 cm, in 52.2% and 3-6 cm in 39.1%) is similar to adult
patients. Other clinical features include; leukopenia (22%-82%),
 fever (30.4%), and less
commonly skin rash, hepatomegaly, weight loss, and mild liver dysfunction. Most pediatric patients have
resolution of their symptoms within 6 months. However, up to 38% of pediatric patients can develop new
symptoms compatible with an autoimmune process during follow-up with neurological symptoms being the most
common. SLE has been reported in one patient five years after KFD.  These findings suggest
long-term follow-up is necessary to monitor for the development of rheumatologic disease. A high ANA
titer may be associated with a more protracted course. 
Association with autoimmune disease:
Similarities between KFD and SLE
(young females, similar histologic features on lymph node biopsy, and tubuloreticular structures on
electron microscopy) have led to speculation that KFD is an SLE-like autoimmune disease. The
co-existence of SLE and KFD has been described in a small number of cases (reviewed in references 3 and
The diagnosis of KFD can precede (20%-30%), coincide (50%-60%), or occur after the
diagnosis of SLE (10%-20%). Lymph node enlargement occurs in approximately two-thirds of SLE patients
(approximately 40%-50% of cases are in the cervical region). As there are good serologic tests to
diagnose SLE, a lymph node biopsy is not performed in most cases; therefore, it is difficult to determine
how often KFD type changes are seen in SLE. When KFD-like lesions occur in patients with SLE, it is
likely a manifestation of lupus rather than the simultaneous occurrence of two diseases; also, antecedent
KFD may actually be an early manifestation of SLE.  Because it may be very difficult to
distinguish KFD from lesions seen in SLE, serologic testing for SLE should be recommended in all cases.
Other autoimmune or abnormal immune manifestations reported in patients with KFD include: polymyositis,
polyarthritis, systemic juvenile rheumatoid arthritis, bilateral uveitis,  cutaneous
necrotizing vasculitis and pulmonary hemorrhage,  asthma, chronic eczema, and hay
The histologic appearance of KFD is variable. The
characteristic findings include discrete or confluent pale paracortical areas of necrosis with abundant
karyorrhectic or apoptotic debris, large numbers of histiocytes, and proliferation of immunoblasts or
large lymphocytes. The lymphocytes in KFD are a mixture of small and large lymphocytes with the latter
often predominating. The large lymphocytes are immunoblasts or large non-cleaved (or transformed) cells
and often have an atypical cytologic appearance. Reed-Sternberg-like cells are not typically seen.
Numerous histiocytes of various types are present including tingible body macrophages, nonphagocytic
crescentic histiocytes (with C-shaped nuclei), and foamy (or xanthomatous) histiocytes. Plasmacytoid
dendritic cells (also previously known as plasmacytoid T-cells or plasmacytoid monocytes) are also
present. Histiocytes can be misinterpreted as abnormal large lymphocytes. Histiocytes with signet
ring-like morphology are seen in approximately 10% of cases.  Necrosis can be patchy or
confluent and vary from karyorrhexis and eosinophilic debris to frank coagulative necrosis. The capsule
and surrounding soft tissue are involved in about 20% of cases. Thrombosed vessels are not a prominent
feature but can be seen around the areas of necrosis. Neutrophils are absent and plasma cells are absent
or scarce. Reactive lymphoid follicles are present in 50%-60% of cases with follicular hyperplasia in
approximately 10%.  Sinus distension by focal clusters of monocytoid (parafollicular) B-cells
may be present.
Three histologic types or possible stages in evolution of the lesion have been described. 
The proliferative type (~30%) has plasmacytoid dendritic cells,
immunoblasts, and histiocytes with little or no necrosis. The second, necrotic
type (~55%) has large areas of necrosis with extensive karyorrhexis and karyolysis. The
third or xanthomatous type is characterized by resorption and return to
normal histology. The earliest lesion consists of paracortical clusters of plasmacytoid monocytes with
interspersed karyorrhexis and crescentic histiocytes. It is not known if the three different histologies
represent different stages of the disease or reflect differences in the etiology or host response.
The large lymphocytes are predominantly T-cells with few
B-cells. Most T-cells are CD8+ TIA-1+ (cytotoxic granule protein) cytotoxic T-cells.
histiocytes variably express CD68, lysozyme, myeloperoxidase (MPO), and CD4.
 The expression
of MPO in histiocytes is useful in the differential diagnosis as other benign causes of lymphadenopathy
(except SLE) and lymphomas lack MPO+ histiocytes.
 Plasmacytoid dendritic cells express
CD123 (IL-3 receptor alpha chain). CD30 is usually expressed in 10% or less of the T-cells but may be
seen in 25%-50% of the T-cells in 20% of cases.  Studies to detect EBV are negative.
Other sites of disease:
Extranodal disease is relatively rare in KFD.
Bone marrow involvement and liver dysfunction have been reported. Nonspecific cutaneous findings have
been reported in up to 40% of cases. The gross appearance of skin lesions is non-specific and includes
rashes, nodules, erythematous-crusted papules, indurated erythematous lesions, erythema multiforme, and
erythematous maculopapular eruptions mainly affecting the face and upper body.
Histologic examination reveals vacuolar interface change with necrotic keratinocytes, superficial and
deep perivascular and interstitial lymphohistiocytic infiltrate (similar to that of the lymph node) with
varying amounts of papillary dermal edema and abundant karyorrhectic debris and absent
neutrophils.  These features resemble SLE, but papillary dermal edema is an exception in
lupus dermatitis. Patients with Sjogren syndrome may have painful indurated skin lesions mimicking
KFD  and rare coexistent KFD and Sjogren syndrome have been described.
Biology and Pathogenesis:
The etiology of KFD remains speculative. The
clinical symptoms suggest a viral infection (upper respiratory prodrome, atypical lymphocytosis, lack of
response to antibiotics, etc.). Proposed agents include parasites (e.g. Toxoplasma), bacteria (e.g.,
Brucella, Yersinia enterocolitica), and viruses (e.g., EBV, CMV, parvovirus B19, HHV-6 and HHV-8,
rubella, parainfluenza, and varicella-zoster) (reviewed in reference 3). Bartonella henselae gene
sequence has also recently been detected in lymph nodes of children.  Giardia lamblia
intestinalis infection has been reported two months prior to the onset of KFD.  Others have
suggested KFD represents a common pattern of response to variety of agents rather than a specific
clinicopathologic entity.  Another consideration is an exuberant T-cell response
(hyperimmune reaction) in genetically susceptible people to a variety of non-specific stimuli. HLA class
II alleles DPA1*01 and DPB1*0202 (genes more commonly expressed in Korean, Japanese, French and Italian
individuals) are higher in patients with KFD than in control patients. By ultrastructural analysis,
tubular reticular structures (seen in viral infection and autoimmune diseases) have been identified in
lymphocytes and histiocytes, suggesting KFD could represent a self-limited SLE-like autoimmune condition,
but standard rheumatologic tests have been negative except for in the small number of patients with SLE
and KFD (discussed on previous page). Other triggers of KFD include pacemaker implantation and silicone
from a leaking breast implant. 
The predominant lymphocyte in KFD is a cytotoxic CD8+ TIA-1+ T-cell that might act as killer and
victim (reviewed in reference 3).
KFD is likely a cell-mediated process sustained by
activated CD8+ T-cells. Activation of the FAS-FASL and perforin pathways and endonuclease DNase gamma
support the apoptotic nature of cell death in the cellular debris seen in KD.
presence of CD123+ plasmacytoid dendritic cells that are capable of producing large amounts of type I
interferon may promote a Th1 T-cell reaction and a cytotoxic immune response, suggesting that CD8+ T-cell
mediated death is histiocyte dependent. Additional chemokines and cytokines such as interleukin-18,
monokine induced by gamma interferon, and Cys-X-Cys chemokine IFN-g -inducible protein-10 are increased.
A curious feature of KFD is the striking absence of granulocytes despite the prominent necrotizing
features. The MPO+/CD68+ histiocytes likely correspond to a similar population of peripheral blood
monocytes that can substitute for neutrophilic MPO for the production of advanced glycation products at
sites of inflammation. Plasmacytoid dendritic cells are frequently seen in KFD often in the uninvolved
parenchyma rather than as a prominent component of the lesion. They lack MPO and express
CD68.  Dendritic cells are hematopoietic cell derived migratory antigen presenting cells
that can be divided into myeloid (CD11c+, mDC) and lymphoid (CD11c-, plasmacytoid, pDC) types. DCs
capture foreign antigens in peripheral tissue through pattern recognition receptors such as the Toll-like
receptors (TLRs 1-10) of the innate immune system. The ligands of some TLRs are known. TLR-9 recognizes
unmethylated CpG rich DNA of bacterial or viral origin. Stimulated by foreign antigens, immature DCs
migrate toward lymph nodes, mature and present antigen to T-cells to initiate a primary immune
response.  In a recent study by Lin CW et al., 2005, TLR7 was found in every KFD case,
confirming the universal presence of pDCs. 
Transcripts of TLR9 (another receptor on pDCs for
microbial unmethylated CpG-rich DNA) were correlated with the presence of oligoclonal T-cells implying
T-cell expansion in response to a microbe.  PCR of bacterial 16S rDNA has been negative
indicating a bacterial origin is unlikely, but a virus would be a candidate. PDC lack the maturation
marker CD83 suggesting ineffective stimulation of T-cells.
The differential diagnosis of KFD includes benign
and neoplastic disorders causing necrotizing lymphadenopathy. See table on page 25.
In early studies up to 40% of KFD were initially
diagnosed as lymphoma
but even more recent reports emphasize KFD can still be confused
with lymphoma. 
The clinical circumstances and pathologic features in KFD that suggest lymphoma include:
Features in KFD that are compatible with a benign process and useful in distinguishing it from
lymphoma include: 
- Unilateral cervical adenopathy with little fever, systemic symptoms
- Clinical symptoms are unresponsive to antibiotics and can persist for up to 5
- CT scan may show homogeneous
enhancing lesions without necrosis, suggesting lymphoma 
- Necrosis and large atypical cells
- Organism stains/molecular studies are negative
- Predominance of CD8+, TIA-1+ T-cells
- T-cells can be oligoclonal
- No definitive laboratory tests are available to confirm the diagnosis
- Rare cytogenetic abnormalities have been
- Most lymph nodes involved by lymphoma are not tender
- Patent sinuses in non-pathologic areas
- Partial preservation of architecture
- Prominent mottling by histiocytes or transformed lymphocytes in the intervening paracortical areas between the necrotic foci
- Although histiocytes have atypical crescentic nuclei, their chromatin is bland similar to other histiocyte nuclei
- Lack of a "starry sky" appearance; karyorrhectic debris outside of histiocytes (in lymphoma the macrophage cytoplasm contains the debris)
- Plasmacytoid dendritic (histiocytes) cells at the periphery or immediately outside the pathologic foci
As the pattern of infiltration in KFD is paracortical, and the predominant large cell is a CD8+ cell,
the differential would include a peripheral T-cell lymphoma. Most node-based lymphomas arise from CD4+
T-cell populations. CD8+, TIA+ lymphomas typically occur at extranodal sites; many of these lymphomas
spread to other extranodal sites and only rarely involve lymph nodes. Anaplastic large cell lymphoma
(ALCL) can arise, in a small number of cases, from CD8+ cytotoxic T-cells. ALCL is excluded based on the
lack of sinus involvement; CD30 is expressed only in a subset of large cells, and lack of EMA, ALK-1, and
clusterin expression. (ALCL will be discussed further in Case 8). Other extranodal CD8+ TIA-1+
lymphomas tend to have a mixture of small, medium, and large cells and can express CD56, have a
γδ phenotype (hepatosplenic lymphoma, cutaneous γδ T-cell lymphoma),  and
be associated with EBV (nasal/nasal type NK/T-cell lymphoma).
Viral driven lymphoproliferations, particularly
infectious mononucleosis (IM), are in the differential of KFD and can be confused with lymphoma. The
presence of atypical clinical features (older age; lack of fever, pharyngitis, and splenomegaly;
asymmetrical tonsillar enlargement; and negative serology) lead to biopsy and risk for misdiagnosis as
lymphoma. The histologic appearance of IM varies with the stage of disease. Initially the follicles are
large with prominent germinal centers with many transformed lymphocytes, mitoses, and tingible body
macrophages. With disease progression, the follicles are disrupted by expansion of the paracortical
region by immunoblasts, Reed-Sternberg (RS) like cells, plasma cells, and histiocytes. The immunoblastic
proliferation can become extensive and obscure the germinal centers and sinuses. The sinuses are
expanded by a similar population of cells but are preserved (as best seen on a PAS stain). Capsular
invasion, large numbers of immunoblasts, RS-like cells, and vascular proliferation are features shared
with lymphoma. Necrosis is often present and can be focal, patchy or extensive.  RS-like
cells are not typically seen in KFD and immunophenotypically the large lymphocytes/immunoblasts in IM are
predominantly B-cells rather than the T-cells seen in KFD.  The large cells are often CD30+
and express EBV-LMP or are EBER+ (EBV encoded RNA).
 Plasma cells and granulocytes are
usually seen with the necrosis of IM. Atypical mononucleosis-like infections due to CMV can have similar
features and the RS-like cells can be CD15+!  CMV inclusions may be present. See Table 1
for comparison of IM with lymphoma.
A rare case of parvovirus B19 associated hemophagocytic syndrome with lymphadenopathy resembling KFD
has been described.  Herpes simplex and Herpes zoster infection are also in the differential
and may be distinguished by the presence of viral inclusions. Herpes simplex in particular may have
associated necrosis with cellular debris resembling KFD, but neutrophils are often present.
Another potential pitfall is the presence of large cell
proliferations associated with viral infection in patients with small B-cell lymphoma or chronic
lymphocytic leukemia may be misinterpreted as large cell transformation of the neoplasm. 
Table 1. Comparison of Immunophenotypic and Molecular Features of Infectious Mononucleosis and Malignant Lymphoma
|Antigen ||IM ||Classical Hodgkin Lymphoma ||B-NHL ||ALCL|
| CD45 RB (LCA) ||+/- ||- ||+/- ||+/-|
| CD20 ||+/- ||-/+ ||+ ||-|
| T-cell antigens ||-/+ ||rare ||- ||+/-|
| CD15 ||-* ||+ ||- ||-/+|
| CD30 ||+ ||+ ||-/+ ||+|
| LMP/EBER ||+ ||+/- ||-/+ ||-|
| EMA ||- ||-** ||-*** ||+/-|
| BCL-2 ||variable ||variable ||variable ||variable|
| IgH rearrangement ||polyclonal ||polyclonal^ ||monoclonal ||-|
* CMV "atypical IM" may be CD15+ **Lymphocyte predominant HL is EMA+ in a
*** Rare NHL, ALK+ B-NHL is EMA+; small subset of other B-NHL may express EMA ^ HL is
monoclonal by microdissection and sensitive PCR
+ > 75% +/- = 25%-75% -/+ = 5%-24% - = < 5%
The most difficult, if not impossible, entity to
distinguish from KFD histologically is SLE. Focal or large areas of necrosis that may be acellular or
contain karyorrhectic debris with or without neutrophils are present in SLE. Plasma cells are more
prominent in SLE than in KFD. The presence of hematoxylin bodies (PAS+ amorphous, 5-12 um round
structures representing karyorrhectic lymphocyte nuclei) and necrosis and thrombosis of small arterioles
are findings that are more specific of SLE. The deposition of basophilic material around blood vessels,
similar to that seen in oat cell carcinoma ("Azzopardi effect"), has been described. The KFD-like
lesions in SLE predominantly show necrosis and do not have the proliferative or xanthomatous type lesions
of KFD. [19 ]In addition, the increase in cytotoxic lymphocytes present in KFD is not seen. All
this aside, the "bottom line" is that SLE must be ruled out (with serologic testing) before a final
diagnosis of KFD is made.
Bacterial infection often causes microabscess
formation. Cat scratch disease (Bartonella henselae) typically has stellate microabscess with numerous
neutrophils surrounded by palisading histiocytes. These lesions are in the lymph node cortex and can be
associated with capsular thickening and plasmacytosis. Monocytoid B-cell proliferation can be present in
the sinuses. Small coccobacilli in endothelial cells, macrophages, or adjacent to the abscesses or
germinal centers may be identified on Warthin-Starry or Steiner stains (note: use formalin-fixed
Yersinia enterocolitica adenitis (typically mesenteric in location) shows microabscesses with
granulocytes frequently in follicle germinal centers and aggregates of epithelioid histiocytes. 
Rare patients with KFD-like lesions have been described with Yersinia enterocolitica serogroups 3
and 9. 
Rare cases of toxoplasma lymphadenitis show
necrosis raising the differential with KFD. The presence of follicular hyperplasia, clusters of
epithelioid histiocytes abutting the germinal centers, and prominent proliferation of monocytoid B-cells
around the sinuses is characteristic of toxoplasma. Toxoplasma trophozoites or cysts are only rarely
Kawasaki disease (mucocutaneous lymph node syndrome),
predominantly a disease of young children, is a rare cause of lymphadenopathy in adults and is in the
differential of KFD. In Kawasaki disease there is patchy lymph node necrosis with neutrophils, necrosis
of follicles, and thrombosed small vessels.  The diagnosis of Kawasaki disease is made based
on clinical features: children < 5 years of age with fever, polymorphous exanthem, bilateral
non-exudative conjunctivitis, inflammation of the lips and oral mucosa (red lips, strawberry tongue,
diffuse injection of the oral and pharyngeal mucosa, palmar and plantar erythema and/or edema, with later
desquamation, and cervical adenopathy (usually >1.5 cm, unilateral). In adults, the median age is
27.6 +/- 10.3 years (range 18-68); 74% are < 30 years.
 Adenopathy is present in 93% of
adult patients (as compared to 75% of children) and is painful, symmetrical, and sometimes unilateral and
most frequent in the cervical region. Axillary, subclavicular, and inguinal adenopathy can also occur.
Articular involvement is more common and meningitis less frequent in adults than in children. Fewer
coronary aneurysms are seen in adults (5% of cases) than children (20% of cases). Treatment of Kawasaki
disease in the first seven to ten days with high dose intravenous immunoglobulin has been show to reduce
the incidence of coronary abnormalities seen in this disease.
It should be mentioned that other large cell neoplasms
(metastatic carcinoma, melanoma, acute leukemia, malignant histiocytosis) can involve the
paracortical/sinus areas of the lymph node and may be associated with necrosis. These diseases would be
distinguished by the appropriate immunostaining with antibodies to keratin, melanocytic markers (S-100,
HMB-45, Mart1), and histiocytic antigens (S-100, CD1a, CD68, CD21).
Malignant lymphoma, acute leukemia, and metastatic carcinoma can
cause massive infarction due to vascular thrombosis, tumor compression/invasion of vessels, or production
of inflammatory cytokines. There is coagulative necrosis with cell ghosts and variable degrees of
inflammation. Previous surgical trauma (or FNA) may also be responsible for the infarction.
Differential Diagnosis of Kikuchi-Fujimoto Disease
|Diagnosis ||Clinical Distribution ||Morphology ||Immunophenotype ||Other Differential Features|
|Kikuchi-Fujimoto Disease ||Predominantly cervical LN ||Proliferative; necrotic; xanthomatous ||Increased cytotoxic CD8+, TIA-1+ T-cells ||CD68+ MPO+ histiocytes; crescentic histiocytes; plasmacytoid dendritic cells|
|T-Cell Lymphoma (TCL) ||Nodal or extranodal ||Large areas of necrosis with extracellular apoptotic debris are unusual; ||Most nodal T-cell lymphomas are CD4+; CD8+ TCL are primarily extranodal; use CD56 and EBER in situ hybridization to rule out nasal type NK/TCL; CD30, EMA, ALK-1, clusterin to rule out ALCL ||Clonal TCR gene rearrangement; admixed histiocytes are CD68+, MPO-|
|Infectious Mononucleosis ||Adenopathy, splenomegaly ||Necrosis, immunoblasts, RS-like cells ||Large cells are predominantly B-cells; EBV+ ||EBV serology+|
|Systemic Lupus Erythematosus ||Lymphadenopathy in 60%-70%; 40%-50% in cervical region ||Necrosis with apoptotic debris; hematoxylin bodies; necrosis/ thrombosis of small arteries; plasma cells ||Note: may also have MPO+/CD68+ histiocytes ||+ ANA; + dsDNA|
|Yersinia Enterocolitica ||Mesenteric LN ||Microabscess formation with numerous neutrophils often in germinal centers; aggregates of epithelioid histiocytes || |
|Cat Scratch Disease (CSD) ||Axillary, cervical; epitrochlear, inguinal LN ||Microabscess formation with numerous neutrophils || ||Warthin-Starry or Steiner stain for CSD: small coccobacilli|
|Kawasaki Disease (Mucocutaneous lymph node syndrome) ||Children usually < 5 yrs. Acute febrile illness with inflamed lips and oral mucosa; desquamation of palms and soles ||Necrosis with adjacent intracapillary fibrin thrombi || |
|Herpes Simplex ||Lymphadenopathy is uncommon with involvement of various sites; if localized usually inguinal ||Histiocytic and atypical large lymphocyte infiltrate with necrotic nuclear and eosinophilic debris; viral inclusions; multinucleated cells with ground glass nuclei; neutrophils often present ||Large lymphocytes are T-cells; viral immunostains against HSV may be positive ||Mucocutaneous lesions|
|Herpes Zoster ||Cervical, supraclavicular, axillary LN; tender ||Atypical large lymphocytes; tingible body macrophages; plasma cells; intranuclear viral inclusions ||Large lymphocytes are T-cells ||Cutaneous lesions|
|Other Large Cell Proliferations (Metastatic Adenocarcinoma, Acute Leukemia, Malignant Histiocytosis) ||Various sites || ||Use antibodies against keratins, myeloid (CD15, CD68, CD117, myeloperoxidase), immature cell antigens(CD34, TdT), and histiocyte antigens (S-100, CD1a, CD68) to rule out |
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