Chronic and recurrent benign lymphadenopathy without constitutional symptoms associated with human herpesvirus-6B reactivation.

Chronic/recurrent behaviour may be encountered in some distinct atypical or malignant lymphoproliferations, while recurrences are not generally observed in reactive/benign lymphadenopathies. We retrospectively analysed a consecutive series of 486 human immunodeficiency virus-negative adults, who underwent lymphadenectomy. Neoplastic and benign/reactive histopathological pictures were documented in 299 (61·5%) and 187 (38·5%) cases, respectively. Of note, seven of the 111 (6·3%) patients with benign lymphadenopathy without well-defined aetiology, showed chronic/recurrent behaviour, without constitutional symptoms. Enlarged lymph nodes were round in shape and hypoechoic, mimicking lymphoma. Reactive follicular hyperplasia and paracortical expansion were observed. Human herpesvirus (HHV)-6B positive staining in follicular dendritic cells (FDCs) was documented in all seven patients. Serological, molecular and immunological examinations suggested HHV-6B reactivation. Among the remaining 104 cases with reactive lymphoid hyperplasia in the absence of well-known aetiology and without recurrences, positivity for HHV-6B on FDCs was found in three cases, whereas in seven further patients, a scanty positivity was documented in rare, scattered cells in inter-follicular regions. Immunohistochemistry for HHV-6A and HHV-6B was invariably negative on 134 lymph nodes, with either benign pictures with known aetiology or malignant lymphoproliferative disorders, tested as further controls. Future studies are warranted to investigate a potential association between HHV-6B reactivation and chronic/recurrent benign lymphadenopathy.

Sonographic appearance of cervical lymphadenopathy due to infectious mononucleosis in children and young adults.

AIM: To depict the grey-scale and Doppler features of cervical lymphadenopathy due to infectious mononucleosis (IM) and to compare the findings with other benign conditions and lymphoma. MATERIALS AND METHODS: One hundred and four patients <30 years old with 138 enlarged lymph nodes (LNs) were enrolled for sonographic analysis. These LNs were grouped as: IM LNs (59 LNs in 30 patients), lymphoma (30 LNs in 30 patients), bacterial lymphadenitis (24 LNs in 20 patients), tuberculosis (TB; 14 LNs in 13 patients), and reactive hyperplasia (11 LNs in 11 patients). Sonographic assessments included shape, echotexture, hilum, border, matting, cystic necrosis, calcification, and vascular pattern. For each sonographic feature, Fisher's exact test was performed to determine whether the difference between IM LNs and any another aetiology were statistically significant. RESULTS: IM LNs tended to be round in shape (69%), heterogeneous in echotexture (61%), absent of echogenic hilum (66%), indistinct margins (80%), bilateral distribution (91%), and matting (83%) [even bilateral matting (66%)], and central hilar vascularity (89.8%). On analysis, bilateral matting had the highest specificity to IM LNs; however, its sensitivity was relatively low. In contrast to IM LNs, TB LNs were more likely to have unilateral matting, cystic necrosis, and calcification. Indistinct margins and decreased echogenicity of the hilum were more frequently seen in IM LNs than in bacterial LNs. Furthermore, central hilar vascularity was a common feature of IM LNs and other benignity, which can distinguish these from lymphoma and TB LNs. CONCLUSION: Although an individual sonographic feature had considerable overlaps between IM LNs and other aetiologies, the combination of several features may be helpful in the diagnosis of IM.

Evidence for reactivation of human herpesvirus 6 in generalized lymphadenopathy in a patient with drug-induced hypersensitivity syndrome.

The present case provides direct evidence of human herpesvirus 6 reactivation in resected lymph node tissue in a patient with drug-induced hypersensitivity syndrome. This case clearly demonstrates that appropriate pathological evaluation of lymphadenopathy for drug-induced hypersensitivity syndrome, which mimics malignant lymphoma in clinical, radiological, and pathological findings, is required.

[Lymphadenopathy: demarcation to malignant lymphomas]. / Lymphadenopathie: Grenzziehung zu malignen Lymphomen.

Recognition of the differential diagnosis between lymphadenitis and malignant lymphoma requires good knowledge of the basic forms of the disease as well in depth knowledge of the structure of the individual compartments. There are defined forms of lymphadenitis where the differential diagnosis to certain lymphoma entities is known. Other reactive structural alterations show indistinct limits so that a decision is only possible after using additional techniques, such as immunohistochemistry and molecular analyses. Finally, there are marginal areas which can only be clarified by including clinical data.

An unusual case of anaemia and lymphadenopathy in a soldier on deployment.

We describe the case of a British soldier, originally from southeast Africa, who presented to the British military hospital in Helmand Province, southern Afghanistan, with a history of constitutional upset, profound anaemia and diffuse lymphadenopathy with hepatosplenomegaly. Following evacuation to the UK investigations revealed a rare (and a not so rare) diagnosis. This case raises a number of questions regarding the population at risk, the prevalence of endemic diseases in this population and laboratory capabilities in the deployed setting.

Penicilliosis in children without HIV infection--are they immunodeficient?

BACKGROUND: Penicillium marneffei infection is indigenous to Southeast Asia. Majority of penicilliosis occurs in patients with AIDS, and less commonly with secondary immunodeficiencies. Penicilliosis is rare in otherwise healthy persons, but information on their immunological status is often lacking. METHODS: From 1996 to 2009, we diagnosed penicilliosis in 5 children. Their clinical features, immunological findings, and genetic studies were analyzed. A systematic review of the English and Chinese literature was performed. Case reports/series on patients <18 years with penicilliosis were included, and patients stated to be human immunodeficiency virus (HIV)-positive excluded. RESULTS: All of our 5 patients were HIV negative. Presentations included fungemia (n = 2), multifocal lymphadenopathy (n = 2), and necrotizing pneumonia (n = 1). Four patients had recurrent mucocutaneous candidiasis. Hyperimmunoglobin E syndrome was diagnosed in 1 patient, while another had functional defect in interleukin-12/interferon-γ axis. Three patients were lymphopenic with low natural killer cell counts, but a specific immune defect was not identified. Systematic review of 509 reports on human penicilliosis identified 32 patients aged 3 months to 16 years with no known HIV infection. Twenty-four patients (75%) had disseminated disease, and 55% died of penicilliosis. Eight patients had primary immunodeficiencies or blood disorders, while 4 others had abnormal immune functions. Immune evaluations of the remaining patients were unstated. CONCLUSION: Penicilliosis is a severe disease causing high mortality in children. As an AIDS-defining illness, penicilliosis should be regarded as an indicator for underlying immunodeficiency in HIV-negative individuals. Immunological investigations should be performed, especially in those with recurrent infections. Multicentered collaborative studies are needed to collect information on long-term prognosis and define immune defects underlying penicilliosis.

What a differential a virus makes: a practical approach to thoracic imaging findings in the context of HIV infection--part 2, extrapulmonary findings, chronic lung disease, and immune reconstitution syndrome.

OBJECTIVE: The Centers for Disease Control and Prevention reported more than one million people with HIV infection in the United States in 2006, an increase of 11% over 3 years. Worldwide, nearly 34 million people are infected with HIV. Pulmonary disease accounts for 30-40% of acute hospitalizations of HIV-seropositive patients, underscoring the importance of understanding the range of cardiothoracic imaging findings associated with HIV infection. This article will cover extrapulmonary thoracic diseases, chronic lung diseases, and immune reconstitution inflammatory syndrome in HIV-infected patients. Our approach is focused on the radiologist's perspective by recognizing and categorizing key imaging findings to generate a differential diagnosis. The differential diagnosis can be further refined by incorporating clinical data, such as patient demographics, CD4 count, and presenting symptoms. In addition, with prolonged survival of HIV-infected patients in the era of highly active antiretroviral therapy, radiologists can also benefit from awareness of imaging features of a myriad of chronic cardiopulmonary diseases in this patient population. Finally, the change of imaging findings and clinical status in response to treatment provides important diagnostic information, such as in immune reconstitution syndrome. CONCLUSION: Developing a practical approach to key cardiothoracic imaging findings in HIV-infected patients will aid the radiologist in generating a clinically relevant differential diagnosis and interpretation, thereby improving patient care.

Experimental infection of a newly emerging Korean type I porcine reproductive and respiratory syndrome virus isolate in colostrum-deprived pigs.

BACKGROUND: Recently, new emergence of type I PRRSV has been reported in Korea by several research groups. Although specific subgroups of type I PRRSVs in Korea were observed in the previous phylogenetic analysis, there is a lack of information about the virulence of type I PRRSV recently isolated in Korea. METHODS: One type I PRRSV isolate (G2446, 3 times passaged in primarily cultured pulmonary macrophages) in Korea was experimentally infected in colostrum-deprived pigs. The pathological and serological evaluations were performed and compared to type II PRRSV strain (CP07-401-9, 5 times passaged in MARC-145 cell lines)-infected pigs, for 21 days post challenge (dpc). RESULTS: The pneumonia found in gross examination was more severe in type I PRRSV-infected pigs than type II PRRSV-infected pigs. Both groups showed bronchointerstitial pneumonia, mild multifocal perivascular lymphohistiocytic myocarditis and lymphadenopathy at 14 dpc. However, the unique histopathologic lesions were not found in the pigs experimentally infected with a Korean type I PRRSV isolate, when compared to previous data about classical pathology of PRRSV. The PRRS-specific antibodies were detected in the first week after challenge and viremia continued at least until 21 dpc in both groups. CONCLUSION: The gross and histopathologic lesion in this study indicated that Korean type I PRRSV strain (G2446) caused classical PRRSV-specific lesions. Although this study evaluated one representative strain of Korean type I PRRSV, the results may provide information regarding the pathogenicity of type I PRRSV recently emerged in Korea.

Clinical significance of perihepatic lymphadenopathy in patients with chronic hepatitis C infection.

BACKGROUND: Patients with chronic hepatitis C (HCV) infection commonly have perihepatic lymph node enlargement (PLNE). We investigated the prognostic value of PLNE in the development of complicated cirrhosis and death, as well as the clinical and laboratory factors associated with the presence of PLNE in a cohort of HCV-infected veterans. METHODS: Using a retrospective cohort design, we compared the rate of development of decompensated cirrhosis and/or death in a group of HCV-infected patients who did not have evidence of decompensated cirrhosis stratified by the presence or absence of PLNE. We used Kaplan-Meier survival curves. We then evaluated which factors were predictive of detection of PLNE using logistic regression. RESULTS: A total of 131 patients were included in the study. Fifty-nine patients had PLNE and 72 patients did not. After a mean follow-up of 42 months, survival in the absence of progression to decompensated cirrhosis and/or death was not significantly different between the two groups (log-rank test, p = 0.27). The only factor predictive of progression to decompensated cirrhosis and/or death was the presence of cirrhosis at baseline (HR 13.13, 95% CI 2.21-79.41). In addition, cirrhosis was the only factor predictive of the detection of PLNE on CT scan (OR 3.09: CI 2.1-25.9). CONCLUSIONS: Presence of PLNE in patients with chronic HCV infection is strongly associated with subclinical cirrhosis. However, PLNE does not independently predict the progression of liver disease to decompensated cirrhosis and/or death in HCV-infected patients.

Hepatitis C virus-induced cryoglobulinemia.

In this review we discuss the clinical manifestations, pathogenesis, and treatment of hepatitis C virus (HCV)-related cryoglobulinemia. HCV is a major cause of liver-related morbidity and is increasingly recognized as an instigator of B-cell lymphoproliferative disorders such as mixed cryoglobulinemia and non-Hodgkin lymphoma. Cryoglobulinemia is characterized by the clonal expansion of rheumatoid factor-expressing B cells in the liver, lymph nodes, and peripheral blood, resulting in the presence of cryoglobulins in the circulation. Cryoglobulins are cold-insoluble immune complexes containing rheumatoid factor, polyclonal IgG, and HCV RNA that precipitate and deposit on vascular endothelium, causing vasculitis in organs such as the skin, kidneys, and peripheral nerves. A subset of patients develops a low-grade lymphoma composed of B cells that are immunophenotypically similar to the expanded B cells seen in cryoglobulinemia. HCV-related B-cell lymphoproliferative disorders likely comprise a spectrum of disease, ranging from asymptomatic clonal B-cell expansions to pathogenic cryoglobulinemia and lymphoma. It is unclear how B cells become dysregulated during the course of chronic HCV infection, and continued patient-centered research is necessary to elucidate the pathogenesis of HCV-related B-cell dysregulation.

Granulomatous hepatitis, perihepatic lymphadenopathies, and autoantibody positivity: an unusual association in a child with hepatitis C.

A 10-year-old boy with hepatitis C had granulomatous hepatitis (GH) at initial liver biopsy. He also had enlarged perihepatic lymph nodes and smooth muscle antibody (SMA) positivity. GH is a rare finding in hepatitis C virus (HCV) infection. Our patient is special since GH secondary to HCV infection was associated with both autoantibodies and multiple intraabdominal lymphadenopathies. After interferon (IFN) and ribavirin therapy, HCV RNA became negative, along with the resolution of hepatic granulomas (HG), lymphadenopathies, and SMA positivity. Although early virologic response was not achieved under IFN treatment, the therapy period was extended, contrary to routine practice, and resulted in a delayed response. We conclude that the usage of IFN for longer periods in GH-associated HCV infection might be promising.

Atypical infectious mononucleosis in a patient receiving tumor necrosis factor alpha inhibitory treatment.

The objective is to report a case of atypical acute infectious mononucleosis in a juvenile ankylosing spondylitis patient who was treated with infliximab. A 20-year-old man was hospitalized for the evaluation of lymphadenopathy and systemic symptoms. His symptoms developed at the eighth week of the infliximab treatment and he required hospitalization. Lymph node biopsy was performed and he was diagnosed as atypical infectious mononucleosis (absence of fever, pharyngitis, lymphocytosis and negative atypical lymphocytosis on blood smear). Infections have become major concerns in patients treated with TNF-blocking agents. In theoretical base, it is not surprising as TNF-alpha has a crucial role in the body's defense against both bacterial and viral invasion. Blocking the action of TNF may also change the course of the disease and could lead to a delay in the diagnosis. TNF-alpha-blocking treatment may mask the typical symptoms of infectious mononucleosis and atypical cases should be included in the differential diagnosis of lymphadenopathy in patients receiving anti-TNF-alpha agents.

A relapsing inflammatory syndrome and active human herpesvirus 8 infection.

We describe an immunocompetent 61-year-old woman who was negative for human immunodeficiency virus and who had recurrent human herpesvirus 8 (HHV-8) infection associated with a relapsing systemic inflammatory syndrome characterized by fever, lymphadenopathy, splenomegaly, edema, arthrosynovitis, and rash. Kaposi's sarcoma developed 10 months after the initial clinical presentation. A correlation was documented between the recurrent clinical manifestations and the HHV-8 load in plasma and peripheral-blood mononuclear cells. Histologic examination of an enlarged lymph node heavily infected with HHV-8 revealed an atypical lymphoproliferative disorder characterized by paracortical hyperplasia and collapsed primary and secondary follicles.

The utility of fine needle aspiration in HIV positive children.

OBJECTIVE: To determine the spectrum of disease, diagnostic accuracy and adequacy of fine needle aspirates (FNA) in human immunodeficiency virus (HIV) positive children who present with mass lesions. METHODS: Between January 1997 and December 2002, 95 FNAs were performed in 91 children aged 15 years and younger who were known to be infected with the human immunodeficiency virus (HIV). RESULTS: Head and neck masses including salivary gland swellings were the most common presentation (58.9%) followed by axillary masses (25.3%). Groin masses were aspirated in six children, flank and abdominal masses in four children, buttock masses in three children, a chest wall mass in one child and a sonar guided FNA of a lung mass in one child. Eight FNAs (8.4%) proved inadequate. Reactive lymphadenopathy was diagnosed in 42 cases, mycobacterial infection in 22, four children were diagnosed with abscess, one child had a fungal infection and five were found to have non-Hodgkin's lymphoma. There were four cases each of lymphoepithelial lesion and Kaposi sarcoma. There was one case each of nephroblastoma, rhabdomyosarcoma, myeloma, melanotic progonoma and spindle cells, not otherwise specified. CONCLUSION: Fine needle aspiration in HIV positive children is a worthwhile procedure and in most instances allows a rapid diagnosis obviating the need for surgery and enabling swift treatment to be undertaken where necessary. Ancillary studies form an important diagnostic component. Universal safety precautions must be strictly adhered to.

[Diagnostic spectrum of reactive lymph node changes]. / Das diagnostische Spektrum reaktiver Lymphknotenveränderungen.

Diagnostic lymph node pathology is primarily focused on identification, definition and classification of lymphoid neoplasms. Less attention is paid to reactive lymph node changes as their causes often cannot be elucidated. We outline several particular types of lymph node reactions that allow a delineation of potential causative agents. A thorough understanding of the morphology of reactive lymph node changes can also aid in the differential diagnosis between reactive and neoplastic lymph node changes.

HCV-related immunocytoma and type II mixed cryoglobulinemia-associated autoantigens.

Hepatitis C virus (HCV) is a hepatotropic virus causing hepatocellular damage and chronic liver inflammation that progressively can lead to cirrhosis and hepatocellular carcinoma (HCC). HCV is also lymphotropic, as demonstrated by its capacity to replicate in lymphocytes, by the recurrent detection of organ- and non-organ-specific autoantibodies in HCV-infected patients, and by the strong association found between HCV infection and type II mixed cryoglobulinemic syndrome (MC-II). Moreover, accumulating data ascribe an etiopathogenetic role in the development of B cell non-Hodgkin's lymphomas (NHL) to HCV. All these findings account for the profound effect of HCV infection in the host's immune system. The unique virus-host interactions that culminate in the generation and sustained production of autoantibodies and cryoglobulins have not been delineated. It appears that chronic antigenic stimulation could cause the emergence of specific B cell clones that produce cryoglobulins; moreover, B cell activation and/or deregulation could originate as a result of HCV binding to CD81 tetraspanin or as a consequence of its ability to replicate in B cells. In a previous study we demonstrated that, in MC-II HCV-positive patients, cryoprecipitated monoclonal IgMs, and B cell receptors (BCR) of overexpanded B cell clones share the same combinatory region. Moreover, these IgMs were reactive against both the Fc region of human IgG and the HCV-NS3 antigen. NS3 and Fc epitopes have been idengified by epitope excision approach. One of the idengified NS3 epitopes has been used to immunize a mouse and the monoclonal antibody obtained showed the same cross-reactivity as patients' IgMs. The characterization of antigenic specificity of this antibody may be useful to idengify antigens that can stimulate B cell proliferation in HCV-infected individuals.

Histological diversity of reactive and atypical proliferative lymph node lesions in systemic lupus erythematosus patients.

Localized or generalized lymphadenopathy, which may be associated with systemic symptoms such as fever, is frequently found in patients with systemic lupus erythematosus (SLE). Histologically, the lymph node lesion is characterized by varying degrees of coagulative necrosis with hematoxylin bodies or reactive follicular hyperplasia. The former histology is unique to SLE, but is rarely seen in biopsied specimens. In this review, we describe a histologic variation of SLE lymphadenopathy based on the findings of our own cases, and discuss several problems related to the differential diagnosis of various benign and malignant lymphoproliferative disorders (LPDs). Among 33 cases we encountered, 17 (51%) cases exhibited atypical LPDs: (i) reactive follicular hyperplasia with giant follicles (RFHGFs), 3 cases; (ii) histologic findings of Castleman's disease (CD), 5 cases ; (iii) atypical paracortical hyperplasia with lymphoid follicles (APHLFs), 7 cases; and (iv) atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP), 2 cases. This finding indicates that atypical LPDs frequently appear in SLE. Moreover, the majority of patients with atypical LPDs exhibited follicular hyperplasia (RFHGF, 3 cases; histologic findings of CD, 5 cases; and APHLF, 7 cases). Previously, follicular hyperplasia was usually considered a non-specific change and therefore has received little attention in the literature. However, the present review indicates that reactive follicular hyperplasia in lymph nodes from SLE occasionally poses serious problems in the differential diagnosis of various benign and malignant LPDs. The presence of numerous copies of Epstein-Barr virus was determined by in situ hybridization studies in only two (8%) of the 26 cases examined. As previously suggested, the absence of EBV, as determined by ISH studies, in the majority of LPDs associated with SLE indicates that EBV is not related to the lymphoproliferative process, and suggests that the underlying cause of the patient's lymphadenopathy may reside in the immune deficit of SLE in the majority of reactive and atypical LPDs associated with SLE.