Paracortical Areas Research Articles

Treatment of Histiocytic Necrotizing Lymphadenitis (Kikuchi's Disease) with Prolonged Fever by a Single Course of Methylprednisolone Pulse Therapy without Maintenance Therapy: Experience with 13 Cases

A 26-year-old man was hospitalized with a 1-month history of fever. Cervical lymph node biopsy showed necrosis in the paracortical area with abundant nuclear debris and proliferation of histiocytes. A diagnosis of histiocytic necrotizing lymphadenitis (HNL) (Kikuchi's disease) was made. He received methylprednisolone pulse therapy (MPT) (0.5 g/day for 3 days) without maintenance therapy and experienced dramatic improvement. We also used MPT for another 12 cases of HNL. All patients became afebrile within 1 day without adverse events. Four patients relapsed after the initial MPT, but only 1 patient relapsed during the following year. Our results suggest that MPT is warranted in HNL patients with prolonged fever.

The Clinical and Histological Characterization of Malignant Lymphoma, Kikuchi-Fujimoto Disease and L-Forms Acid-Fast Bacillus Infection

Objective: Malignant lymphoma (ML), Kikuchi-Fuljimoto disease (KFD) and L-forms Acid-fast bacillus infection (L-forms TB) usually affect the cervical lymph nodes. KFD and L-form TB are often confused with ML and take misdiagnosis and inappropriate treatment. The diagnosed of these diseases is on basis of an excision biopsy of affected lymph nodes.Methods: We analyzed 63 patients (including case diagnosed in our hospital) by clinical characteristic, laboratory, pathological morphology, histochemistry and immunohistochemistry.Results: Of 63 cases, 43 were ML, 17 were KFD and 3 were L-forms TB. In ML disease, 46% were male and 54% were female, mean age was 54 (11–82). 9% cases have persistent fever and associated with hepatosplenomegaly. In KFD, 47% were male and 53% were female, mean age was 26 (17–45). 59% cases with cervical hymphadenopath and no fever, 41% had painful, accompanied by fever. hepathosplenomegaly, occasionally leucopenia and lypadenopathy especially involving cervical region not responsive to antibiotic treatment. 29% lymph tissues were morphologically, and characterized by a necrosis in the cortical or paracortical areas of enlarged lymph node around the necrotic area. T lymphocytes were found and absence of granulocytes. 30% cases were mistaken to ML. L-forms TB disease, there were fever, clinical and histological were similar KFD and ML. 3 cases were misdiagnosis to ML or KFD. Laboratory analyses: PAM and PAS were positive, and anti acid test to found L-forms bacterium in tissues.Conclusions: Kikuchi-Fujimoto disease and L-forms Acid-Fast bacillus infection are easily confused histological and clinically with malignant lymphoma. Clinicians and pathologists must be aware of this condition. Although Malignant lymphoma, Kikuchi-Fujimoto disease and L-forms Acid-fast bacillus infection can be found any age, but should be considered for malignant lymphoma in older patients. Kikuchi-Fujimoto disease is predominantly a self-limiting disease of the young and most cases with fever, nodal biopsy showing fragmentation necrosis and karyorrhexis, not responsive to antibiotic treatment. In the L-forms Acid-fast bacillus infection, the PAM and PAS are positive, and have an effective antibiotic treatment.

Análise histopatológica de órgãos linfóides de bovinos e camundongos intoxicados experimentalmente por Baccharis coridifolia: Caracterização imunoistoquímica de linfócitos B e T

Baccharis coridifolia é uma das mais importantes plantas tóxicas para bovinos no Sul do Brasil. A intoxicação pela planta produz lesões necróticas nos tecidos linfóides e no trato gastrointestinal de bovinos. A administração experimental para camundongos produziu a maioria das lesões que ocorrem nos tecidos linfóides de bovinos. Este estudo foi conduzido para detectar as possíveis diferenças na susceptibilidade das populações de linfócitos T e B. Foram utilizados linfonodos, baço, timo e acúmulos linfóides associados ao intestino de bovinos e camundongos experimentalmente intoxicados pela planta. Os resultados foram avaliados com base na população de células lesadas ou por aquela que permaneceram nos tecidos. Em ambas as espécies, na marcação imunoistoquímica para linfócitos B (anti-BLA-36) predominou a região do centro germinativo dos linfonodos, baço e acúmulos linfóides associados ao intestino. A marcação para linfócitos T (anti-CD3) predominou na região paracortical dos linfonodos, acúmulos linfóides associados ao intestino e região periarteriolar do baço e timo de ambas as espécies. Bovinos e camundongos experimentalmente intoxicados demonstraram acentuada necrose do centro germinativo dos folículos secundários dos linfonodos, baço e intestino, onde as células necrosadas foram marcadas pela imunoistoquímica para linfócitos B e em menor freqüência para linfócitos T. Necrose celular na região paracortical do linfonodo foi discreta e sem marcação imunoistoquímica. Células necróticas no timo foram observadas somente em camundongos, com imunoistoquímica positiva para linfócitos T. A distribuição das lesões nos tecidos linfóides associadas à marcação imunoistoquímica das células necrosadas sugerem que o princípio ativo da planta é citotóxico para células T e B.

Preparation of anti-T idiotype monoclonal antibody reacting with human T leukaemic cell lines and with a small percentage of peripheral T lymphocytes

Monoclonal antibody (MoAb) KT38 raised against a human T leukaemic cell line TALL-1, reacted with another T leukaemic cell line Jurkat, but not with any other cell lines tested. The co-modulation of CD3 and KT38 antigen was observed with stimulations of either MoAb T3 or KT38 on both TALL-1 and Jurkat. Upon radioimmunoprecipitation and SDS-PAGE analysis, MoAb KT38 precipitated the heterodimer of 40-60 kD from Jurkat and TALL-1 under reducing conditions. Thus, MoAb KT38 is considered to be an anti-T idiotype (Ti) antibody to TALL-1 and Jurkat cells. MoAb KT38 was also shown to react with a minor population of peripheral blood lymphocytes (PBL) and with very few cells (0.5-2.0%) in the paracortical area of the lymph node. When PBL were stimulated in a KT38-coated culture flask for 5 days, the percentage of KT38-positive PBL was markedly increased. The CD3 antigen on these cultured PBL in the flask was modulated by the stimulation with MoAb KT38. Thus, it is suggested that a common idiotope exists on the T cell receptor of Jurkat, TALL-1 and a small percentage (1.9-6.1%) of PBL.

Helicobacter pylori invades the gastric mucosa and translocates to the gastric lymph nodes

Helicobacter pylori has been considered to be non-invasive and to rarely infiltrate the gastric mucosa, even though there is an active Th1 immune response in the lamina propria of the H. pylori-infected stomach. To elucidate whether H. pylori invades the lamina propria and translocates to the gastric lymph nodes, we examined H. pylori in formalin-fixed and paraffin-embedded tissue sections of stomach and gastric lymph nodes obtained from 51 cancer patients using real-time PCR and immunohistochemistry (IHC) with a novel anti-H. pylori monoclonal antibody that recognizes lipopolysaccharides. Fresh gastric lymph nodes were used to culture for H. pylori. In 46 patients with H. pylori in the stomach, the bacterium was found in the lymph nodes from 21 patients by culture, 37 patients by PCR, and 29 patients by IHC. H. pylori captured by macrophages was found in the lamina propria of 39 patients. In the lymph nodes, the bacterium was found in many macrophages and a few interdigitating dendritic cells at the paracortical areas. H. pylori was also found in the intracellular canaliculi of parietal cells in 21 patients, but intracytoplasmic invasion into gastric epithelial cells was not identified. When compared to the commercially available anti-H. pylori antibodies, the novel antibody showed the highest sensitivity to detect H. pylori-positive macrophages, whereas no difference was found for H. pylori in the mucous layer. The H. pylori-positive macrophages in the lamina propria correlated with chronic gastritis as well as translocation of such cells to the lymph nodes. These results suggest that H. pylori-induced gastric epithelial damage allows the bacteria to invade the lamina propria and translocate to the gastric lymph nodes, which may chronically stimulate the immune system. The bacteria captured by macrophages, whether remaining alive or not, may contribute to the induction and development of H. pylori-induced chronic gastritis.

Lymphadénite histiocytaire nécrosante ou maladie de Kikuchi-Fujimoto

Kikuchi-Fujimoto disease (KFD), first described independently by Kikuchi and Fujimoto in 1972, is a subacute necrotizing lymphadenitis of unknown cause. Although most frequent in young Asian women, KFD has a worldwide distribution. Clinically, KFD is characterized by lymphadenitis of one or more lymph nodes, predominantly in the posterior cervical region, fever, and leukopenia in up to 50% of cases. Extranodal manifestations can occur, especially skin lesions and aseptic meningitides. Diagnosis is usually confirmed by analysis of samples from an excisional biopsy of the affected nodes. Histologically, the lesions affect the cortical and paracortical areas of the node. Characteristic features include focal necrosis predominantly in the paracortical region with abundant karyorrhectic debris and atypical mononuclear cells around the necrotic zone (crescent-shaped histiocytes, plasmacytoid monocytes, and small lymphocytes and immunoblasts, mostly CD3(+)/CD8(+)), most often with an intact lymph node capsule, an absence of neutrophils, and a paucity of plasma cells. KFD has been classified into three histological subtypes and is thought to progress from the proliferative type (> 50%) to the necrotizing type (30%) and finally resolve into the xanthomatous type (< 20%). Differential diagnoses should include malignant lymphoma, infectious diseases such as toxoplasmatic lymphadenitis, tuberculous lymphadenitis and cat scratch disease, and systemic lupus erythematosus (SLE). The cause of KFD is unknown: a viral infection has been suggested, but not demonstrated, possibly involving human herpes virus 8 or Epstein-Barr virus. Apoptotic cell death plays a role: proliferating CD8(+) T-lymphocytes act as both killers and victims in the apoptotic process via Fas and perforin pathways. The course is usually benign with resolution in a few months with the use of antiinflammatory drugs. Regular follow-up is required because SLE may develop several years after the onset of Kikuchi-Fujimoto disease.

CCR7 mediates the migration of Foxp3+ regulatory T cells to the paracortical areas of peripheral lymph nodes through high endothelial venules

Thymus-derived forkhead box p3(+) naturally occurring regulatory T cells (nTreg) are thought to circulate throughout the body to maintain peripheral immunological self-tolerance through interactions with dendritic cells (DCs), resulting in regulation of conventional T cells. However, the chemokine receptors, which are putatively involved in the in vivo migration of nTreg, have not been fully established. Here, we demonstrated that lymph node nTreg preferentially migrated to the paracortical area of lymph nodes after adoptive transfer, where they were observed to make contact frequently with CD8alpha(+) DCs and CD8alpha(-) CD11b(-) DCs. This migration of nTreg to the paracortical areas was impaired severely when cells were prepared from CCR7-deficient mice. However, to some extent, CCR7-independent migration of nTreg in such CCR7-deficient mice was also observed, but this occurred mainly in the medullary high endothelial venules. Taken together, these data provide the evidence that CCR7 mediates nTreg migration to the paracortical areas of lymph nodes under steady-state conditions; however, CCR7-independent migration also takes place in the medulla.

Immune Responses to HIV Gp120 that Facilitate Viral Escape

The gp160 complex of the envelope of the HIV virus and its component gp120 are essential for viral entry into the host cell. Gp120 binding to its receptor CD4 and co-receptor, CXCR4 or CCR5 is required for fusion of viral and cellular membranes. The presence of gp120 facilitates immune escape of the virus through its profound effect on the immune cells. It is a polyclonal activator of B cells, causing them to differentiate into immunoglobulin producing cells while activating the complement cascade. This results in the formation of immune complexes that are unable to kill the virus but instead shield it from the attack of other immune cells. Such HIV-1 virus that is trapped within immune complexes and is bound to the B cells via CD21 is more infectious than the free virion. In addition, HIV virions are trapped on the membrane of follicular dendritic cells (FDC) processes in immune complexes or through complement receptors. Thus, FDC can serve as a 'Trojan horse' and transmit the trapped virus to CD4+ T lymphocytes as they migrate through the germinal centre to the follicular mantle and paracortical areas. It was demonstrated that CXCR4-binding HIV-1 X4 gp120 causes the movement of T cells, including HIV-specific CTL, away from high concentrations of the viral protein and its expression by target cells reduces CTL efficacy in vitro. Therefore, apart from the essential role in viral attachment and infection of cells, gp120 possesses several properties that affect the behavior of immune cells and skew the immune response to the virus facilitating viral escape.

Lymph node reactivity and microvessel density in neck metastases of unknown primary squamous cell carcinoma

SummaryBackgroundneoangiogenesis and the immune response are important mechanisms in metastasis development.Aimto evaluate lymph node reactivity and microvessel density in neck metastasis of occult primary squamous cell carcinoma considering their histological and clinical variables.Study designretrospesctive case-series.Method19 patients with neck metastasis of occult primary squamous cell carcinoma who underwent neck dissection between 1983 and 2000 were selected. The lymph nodes were reevaluated on the type of reactivity in both the cortical and paracortical areas, and the metastasis were assessed as to grade, desmoplasia, necrosis and microvessel density (CD34). The relationship between histological and clinical variables was evaluated.Resultsthe median microvessel density was 91 vessels/mm2, varying from 28 to 145. Paracortical hyperplasia was more common in patients below 55 years of age (90% x 44%, p=0.05), but there was no relationship between reactivity patterns and microvessel density with prognosis. The disease-free survival was 52% in 3 years, being similar in both groups, with higher or lower microvessel densities.Conclusionmicrovessel density in neck metastasis of occult primary squamous cell carcinoma had a great individual variability. It wasn't possible to establish the relationship between microvessel density and the clinical or histological variables studied.

Is Kikuchi–Fujimoto disease a manifestation of systemic lupus erythematosus?

A 32-year-old woman presented with fever and swelling in the axillae of 2 months' duration, and erythema of the face, fluid-filled lesions on the trunk, oral ulcers, crusting of the lips, and redness and watering of the eyes for 3 days. The patient was initially diagnosed with tuberculous lymphadenitis and was given antituberculous treatment. One month later, she developed the present complaints (see below). The patient was photosensitive. There was no joint pain or Raynaud's phenomenon. She had experienced three intrauterine deaths in the past with no live births. On examination, the patient was pale. Bilateral axillary lymphadenopathy was present. The lymph nodes were mobile, non-tender, and not matted. Mucocutaneous examination revealed a malar eruption, flaccid bullae on the back (Fig. 1), crusting of the lips (Fig. 2), oral ulcers, and redness and discharge from the eyes. On investigation, immunoglobulin G (IgG), IgM, and IgA for tuberculosis were negative. There was anemia and leukopenia, the erythrocyte sedimentation rate (ESR) was raised, albumin in urine was positive, enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) was negative, and venereal disease research laboratory (VDRL) test was nonreactive. Antinuclear antibody (ANA), dsDNA, and antiphospholipid antibody were positive. Fine needle aspiration cytology (FNAC) of the axillary lymph node showed loss of nodal architecture. The extensive infiltrate consisted of lymphocytes, histiocytes, immunoblasts, and necrosis of cortical and paracortical areas. There was histiocytic necrotizing lymphadenitis without granulocytic infiltration. These features were suggestive of Kikuchi-Fujimoto's disease (Fig. 3). Skin biopsy showed epidermal atrophy, basal cell vacuolation, focal hyperkeratosis, pilosebaceous atrophy, and follicular plugging. The dermis showed edema and a lymphocytic infiltrate in the upper dermis and around the blood vessels. These features were suggestive of systemic lupus erythematosus (SLE). Direct immunofluorescence of lesional skin showed a strong continuous basement membrane zone (BMZ) band of C3 and fibrinogen and a strong discontinuous granular BMZ band of IgG. IgA was negative. Covered skin showed moderate and strong positivity for IgM and IgG, respectively. C3, IgA, and fibrinogen were negative. These findings were suggestive of SLE (Fig. 4). Based on the clinical findings and investigations, a diagnosis of Kikuchi-Fujimoto's disease with SLE was made.

Histologic Evidence of Peripheral Lymphatic Organ Reconstitution Following Vascularized Bone Marrow Transplant (VBMT)

Purpose We hypothesized that VBMT can repopulate the peripheral lymphatic centers of an irradiated (XRT) semiallogenic recipient. Methods Control groups were LBNs: non-transplanted, non-irradiated (CT1) and non-transplanted, XRT (CT2). Experimental female LBN rats received 900cGy and a VBMT. Donor femurs were from male LEW rats. Results CT2 Lymph nodes: no lymphatic germinal centers; evidence of profound fibroplasia and focal areas of tissue necrosis; significant numbers of hemosiderin laden macrophages (HLM) and multinucleated giant cells. Bone marrow: areas of hypoplasia and necrosis; decreased ratio of cellular to fatty elements secondary to cellular depletion; foci of lymphocytic infiltrates; prominent HLM. Spleen: white pulp atrophy; increased HLM in red pulp; scarce small, hypochromatic lymphocytes; fibrohistiocytes present with fibroplasia. VBMT Lymph nodes: absence of tissue necrosis and multinucleated giant cells; less HLM; germinal centers present; cortical areas display more cellular depletion than paracortical areas; increased lymphocytes compared to CT2; increased fibrohistiocytes compared to CT1. Bone marrow: Host bone has normal appearing marrow with an average ratio of hematopoietic to fatty elements; hyperchromatic nuclei present. Donor bone marrow appears to be entirely normal. Spleen appears normal. Conclusions This model is capable of hematopoeitically reconstituting the peripheral lymphatic centers of XRT recipients without the development of GVHD. We speculate that the VBMT syngeneic microenvironment can serve as an extra-thymic site for immune development and tolerance induction.

Cell reservoirs in lymph nodes infected with HIV-1 subtype E differ from subtype B: identification by combined in situ polymerase chain reaction and immunohistochemistry

In Thailand, the predominant HIV subtype is E, rather than subtype B as in North America and Europe. Subtype E has the ability to replicate in vitro in Langerhans cells. We hypothesized that this cell type might constitute a reservoir for the HIV virus in infected lymph nodes. We examined lymph nodes from 25 HIV-1 subtype E-infected patients to determine the immunophenotype of HIV-1-infected cells, their numbers and their distribution. The presence of HIV was detected either by in situ reverse transcriptase-polymerase chain reaction or immunoperoxidase. Cell identity was determined by double labelling using alkaline phosphatase-based immunohistochemistry. The majority of HIV-infected cells in the lymph nodes were Langerhans cells (CD1a+S100+) and Langerhans-related dendritic cells (p55+S100+). These cells were located in the paracortical areas of lymph nodes, with a few cells scattered at the edges of germinal centers, but were absent from germinal centers themselves, in contrast to the reported distribution of subtype B virus. In addition, multinucleated giant cells were significantly more common in HIV-infected nodes (64%) compared to controls (4%) (P=0.00002). In conclusion, Langerhans histiocytes and related cells are reservoirs for HIV subtype E in lymph nodes. Disrupting the pathway of infection of Langerhans cells and related cells may be a viable strategy to interfere with transmission of HIV subtype E.

Atypical lymphoplasmacytic and immunoblastic proliferation from rheumatoid arthritis: A case report

A case of atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) in the lymph nodes associated with well-documented rheumatoid arthritis (RA) is presented. A 68-year-old Japanese female with a 6-year history of RA presented with right neck lymphadenopathy of 3 months duration. A biopsy specimen showed paracortical hyperplasia and numerous lymphoid follicles. On high-power field, the paracortical area was diffusely infiltrated by a polymorphous population consisting of numerous mature plasma cells, plasmacytoid cells, immunoblasts, including Hodgkin-like cells, small- to medium-sized lymphocytes, and histiocytes. Immunohistochemical study demonstrated that immunoblasts usually were CD20+, and a portion of them was CD30+. The histomorphological findings of the present case are similar to those of methotrexate (MTX)-induced atypical lymphoproliferative disorders (LPDs) in some aspects. However, Epstein–Barr virus-encoded small RNA-positive cells were not identified by in situ hybridization. The polytypic nature of B lymphocytes also was demonstrated by immunohistochemistry and polymerase chain reaction. Moreover, there was no history of MTX therapy in the present case, indicating that MTX-induced, LPD-like ALPIB may occur even in the RA patients not treated with MTX therapy.

Matched Skin and Sentinel Lymph Node Samples of Melanoma Patients Reveal Exclusive Migration of Mature Dendritic Cells

Mature and immature myeloid dendritic cells (DCs) are thought to differentially modulate T-cell responses in secondary lymphoid tissues. Although mature DCs are believed to induce T-cell activation under proinflammatory conditions, immature DCs are believed to maintain a state of T-cell tolerance under steady state conditions. However, little is known about the actual activation state of human DCs under these different conditions. Here, we compare the frequency and activation state of human DCs between matched skin and sentinel lymph node (SLN) samples, after intradermal administration of either granulocyte/macrophage colony-stimulating factor (GM-CSF) or saline, at the excision site of stage I primary melanoma. Although DCs remained immature (CD1a+CD83-) and mostly situated in the epidermis of the saline-injected skin (fully consistent with a quiescent steady state), mature (CD1a+CD83+) DC frequencies significantly increased in the GM-CSF-injected skin and correlated with the number of mature DCs in the SLN, indicative of increased DC migration. Interestingly, irrespective of GM-CSF or saline administration, all CD1a+ myeloid DCs in the SLN were phenotypically mature (ie, CD83+). These data are indicative of migration of small numbers of phenotypically mature DCs to lymph nodes under steady state conditions.

Atypical lymphoplasmacytic and immunoblastic proliferation from systemic lupus erythematosus. A case report

A case of atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) in the lymph nodes associated with well-documented systemic lupus erythematosus (SLE) is presented. A 30-year-old Japanese female with an 18-year history of SLE presented with right neck lymphadenopathy of 3 months duration. A biopsy specimen showed a diffuse effaced lymph node architecture without follicles and minimal sinuses. At high power field, a polymorphous population of small- to medium-sized lymphocytes, plasma cells, plasmacytoid cells, as well as large, basophilic transformed lymphocytes and immunoblasts diffusely infiltrated the paracortical area. Interestingly, the immunohistochemical study demonstrated large, irregularly shaped accumulations of follicular dendritic cells (FDCs) surrounding the small vessels, which is an immunohistochemical finding characteristic of angioimmunoblastic T-cell lymphoma (AILT). However, the present lesion showed the following differences to AILT: (a) absence of CD3+, CD4+ and CD10+ clear cells, which are tumor cells of AILT; (b) absence of pronounced arborizing vascular proliferation; (c) on molecular analysis, the present case demonstrated a polyclonal pattern converse to the monoclonal T-cell receptor γ chain gene rearrangement in most AILTs (d) absence of EBV infected lymphoid cells, which are frequently detected AILT. As previously suggested, the present case indicates that a clinical correlation as well as immunohistologic and genotypic studies may be necessary to discriminate between ALPIBPs and AILT.

Morphological changes of regional lymph node in squamous cell carcinoma of the oral cavity

Regional immune responses with various types of cancer have been studied histopathologically, however, the prognostic value remains conflicting. The aim of this study was to evaluate morphological changes related to lymph node metastasis and the prognostic value for oral cavity squamous cell carcinoma. With histopathologic whole architecture of 430 lymph nodes, gross area, germinal center (GC) area, paracortical area (PA), and tumor area were measured. Metastatic node had significantly lower distribution ratio of PA to lymphoarea than that of tumor-free node. GC area was not constantly associated with lymph node metastasis. In Cox multivariate analysis, the mean ratio of PA to gross area/lymphoarea was an independent prognostic factor. The proportion of PA to gross/lymph area was associated with lymph node metastasis and long-term survival and may be useful in stratification of those patients for a requirement of adjuvant treatments.

Local Administration of Granulocyte/Macrophage Colony-stimulating Factor Increases the Number and Activation State of Dendritic Cells in the Sentinel Lymph Node of Early-Stage Melanoma

The initial tumor-draining lymph node, the sentinel lymph node, not only constitutes the first expected site of micrometastasis but also the first point of contact between tumor-associated antigens and the adaptive immune system. A tumor-induced decrease in the frequency and activation state of sentinel lymph node dendritic cells will impair the generation of effective antitumor T-cell responses and increase the likelihood of metastatic spread. Here, we demonstrate that intradermal administration of granulocyte macrophage-colony stimulating factor around the excision site of stage I primary melanoma tumors increases the number and activation state of dendritic cells in the paracortical areas of the sentinel lymph node and enhances their binding to T cells. We conclude that local treatment of melanoma patients with granulocyte macrophage-colony stimulating factor, before surgery, conditions the sentinel lymph node microenvironment to enhance mature dendritic cell recruitment and hypothesize that this may be more conducive to the generation of T-cell-mediated antitumor immunity.

Human herpesvirus-6-associated acute lymphadenitis in immunocompetent adults

In contrast to other causes of herpetic lymphadenitis, the histological features associated with human herpesvirus-6 (HHV-6) infection have remained elusive since its discovery in 1986. We describe the histologic and phenotypic changes associated with acute HHV-6 lymphadenitis in two immunocompetent adults who presented with fever, fatigue, generalized lymphadenopathy, and elevated liver enzymes. Serologic tests for human immunodeficiency virus, acute Epstein–Barr virus, and cytomegalovirus infection were negative. Lymph node biopsies were consistent with viral lymphadenitis. Intranuclear and cytoplasmic inclusions were identified in CD4-positive T lymphocytes in expanded paracortical areas. Immunohistochemical staining with monoclonal antibody to the HHV-6 gp60/110 kDa envelope glycoprotein showed that the inclusions were positive for viral antigen. Electron microscopy demonstrated numerous viral particles in the cytoplasm and nucleus, characteristic of Herpesviridae family. Clustering of viral particles was observed, which has previously been reported only in infected tissue culture cells. PCR followed by sequencing of DNA extracted from the lymph nodes identified the virus as HHV-6, type B. This is the first report that documents distinctive histologic features of HHV-6 lymphadenitis and demonstrates that the cells harboring the virus in vivo are CD4-positive T lymphocytes.

Enigmatic Kikuchi-Fujimoto Disease

To determine the clinicopathologic significance of Kikuchi-Fujimoto disease (KFD) and review the literature on this condition, we conducted a MEDLINE search of English-language articles published between 1972 and December 2003. KFD has a worldwide distribution, and Asiatic people have a higher prevalence. Its pathogenesis remains controversial. Patients are young and seek care because of acute tender, cervical lymphadenopathy and low-grade fever. Histologic findings include paracortical areas of coagulative necrosis with abundant karyorrhectic debris. Karyorrhectic foci consist of various types of histiocytes, plasmacytoid monocytes, immunoblasts, and small and large lymphocytes. There is an abundance of T cells with predominance of CD8+ over CD4+ T cells. Differential diagnosis includes lymphoma, lymphadenitis associated with systemic lupus erythematosus, and even adenocarcinoma. KFD is an uncommon, self-limited, and perhaps underdiagnosed process with an excellent prognosis. Accurate clinicopathologic recognition is crucial, particularly because KFD can be mistaken for malignant lymphoma.

Enigmatic Kikuchi-Fujimoto disease: a comprehensive review.

To determine the clinicopathologic significance of Kikuchi-Fujimoto disease (KFD) and review the literature on this condition, we conducted a MEDLINE search of English-language articles published between 1972 and December 2003. KFD has a worldwide distribution, and Asiatic people have a higher prevalence. Its pathogenesis remains controversial. Patients are young and seek care because of acute tender, cervical lymphadenopathy and low-grade fever. Histologic findings include paracortical areas of coagulative necrosis with abundant karyorrhectic debris. Karyorrhectic foci consist of various types of histiocytes, plasmacytoid monocytes, immunoblasts, and small and large lymphocytes. There is an abundance of T cells with predominance of CD8+ over CD4+ T cells. Differential diagnosis includes lymphoma, lymphadenitis associated with systemic lupus erythematosus, and even adenocarcinoma. KFD is an uncommon, self-limited, and perhaps underdiagnosed process with an excellent prognosis. Accurate clinicopathologic recognition is crucial, particularly because KFD can be mistaken for malignant lymphoma.