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Diagnosis of tuberculous lymphadenitis in an area of HIV infection and limited diagnostic facilities.

In order to evaluate procedures leading to the diagnosis of tuberculous lymphadenitis, a prospective clinical study was carried out of patients with lymphadenopathy admitted to the medical wards of a referral hospital in Tanzania. The yield of diagnostic procedures (direct auramine/Ziehl-Neelsen (ZN) stained smears, Löwenstein-Jensen (LJ) cultures, cytology and histological examinations of fine needle aspirations (FNA) and biopsy material of lymph nodes, respectively, was compared. We also tried to identify clinical diagnostic markers. One hundred and twenty-eight (99 HIV-seropositive) patients were included. In 89 (67 HIV-positive) patients TB lymphadenitis could be proven. Histology and LJ culture of a lymph node biopsy had the highest diagnostic yield, 85% and 88% respectively, followed by detection of acid-fast bacilli (AFB) in biopsy smear (53%) and in fine-needle aspirations (35%). The diagnostic yield of the several procedures was not affected by associated HIV infection. Macroscopic caseation was 100% predictive for TB with a sensitivity of 69%. Firm and matted lymph nodes, ESR > 100 mm/hr, a positive PPD skin test and pleural opacity on a chest x-ray proved to be independent predictors for TB. Retrospective testing of a stepwise diagnostic approach based on direct smears of FNA, macroscopic visible caseation and direct smear of biopsy tissue, suggests that in 93% of the patients a definite diagnosis of TB lymphadenitis could have been made. Our data suggest that in HIV/TB epidemic areas most of the cases of TB lymphadenitis can be diagnosed correctly by simple and cheap methods which are generally available at district hospitals. Our findings need further prospective validation, however.

Adolescent↗

Expression of apoptosis-associated protein RCAS1 in macrophages of histiocytic necrotizing lymphadenitis.

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1), which is recognized by the 22-1-1 monoclonal antibody (MoAb) against human uterine adenocarcinoma cell line SiSo, has been identified on various kinds of cancer cells. RCAS1 appears to be an apoptosis-associated protein that induces apoptosis in activated T-cells and erythroid progenitor cells. We previously demonstrated that monocytes/macrophages express RCAS1. In the present study, we investigated RCAS1 expression by 22-1-1 MoAb in histiocytic necrotizing lymphadenitis (HNL), which is characterized by necrotic lesions consisting of T-cells undergoing apoptosis and macrophages in proliferation. Expression of RCAS1 was analyzed by immunohistochemical staining in 9 cases of HNL and in 9 cases of reactive lymphadenitis used as a control. The ratio of RCAS1+ cells to CD68+ cells (monocytes/macrophages) was significantly higher in the patients with HNL than in the patients with reactive lymphadenitis (P = .0002; paired t test). Our findings suggest that RCAS1 expressed on macrophages may play an important role in the induction of activated T-cell apoptosis in cases of HNL.

Adolescent↗

The histopathology of cutaneous lesions of Kikuchi's disease (necrotizing lymphadenitis): a report of five cases.

Kikuchi's disease (KD) is an idiopathic, self-limited necrotizing lymphadenitis that can clinically and histologically mimic high-grade lymphoma, including Hodgkin's disease, or can be mistaken for the lymphadenitis of systemic lupus erythematosus (SLE). Involvement of extranodal sites is unusual but well documented, especially in Asia, where KD is more common than in North America or Europe. The successful distinction of KD from malignant lymphoma and SLE is imperative for the appropriate treatment of affected patients. We describe five patients with cutaneous involvement by KD, all of whom presented with fever, lymphadenopathy, and an eruption on the skin of the upper body, which in one case was clinically suspected to be due to SLE and in another, polymorphous light eruption. The patients ranged in age from 10 months to 42 years (median, 33 years) and included three females and two males. All five patients had negative serologic studies for collagen vascular disease. Each patient had a lymph node biopsy showing the typical necrotizing lymphadenitis of KD. Skin biopsies from all five patients shared a specific constellation of histologic features: vacuolar interface change with necrotic keratinocytes, a dense lymphohistiocytic superficial and deep perivascular and interstitial infiltrate, varying amounts of papillary dermal edema, and abundant karyorrhectic debris with a conspicuous absence of neutrophils and a paucity of plasma cells, paralleling the nodal histology in KD. CD68 immunohistochemistry on paraffin-embedded sections showed many histiocytes and plasmacytoid monocytes in all cases, whereas CD3, CD4, and CD8 showed highly variable staining among the cases. There was only rare staining with TIA-1 and CD30. We believe that the papular eruption of KD has recognizable histopathologic features and that a CD68 stain that marks many cells that initially seem to be lymphocytes can be performed to confirm the diagnosis.

Adult↗

Differentiation of BCG-induced lymphadenitis from tuberculosis in lymph node biopsy specimens by molecular analyses of pncA and oxyR.

Without culture, differentiation of bacille Calmette-Guérin-induced lymphadenitis (BCG-LA) from tuberculosis (TB) is sometimes difficult by histology, but is important because of different treatment schemes. The purpose of this study was to investigate the feasibility of differentiating BCG-LA from TB in lymph nodes (LNs) by molecular analyses of two recently identified genes, pncA and oxyR. In both genes, a single tuberculosis difference exists between Mycobacterium bovis and M. tuberculosis. M tuberculosis complex (MTC) DNA was first detected in nine of ten formalin-fixed, paraffin-embedded LNs from patients aged under 20 years with suspected mycobacterial infections, using polymerase chain reaction (PCR) for IS6110, an insertion sequence specific for MTC species. PCR, together with direct DNA sequencing and PCR-restriction fragment length polymorphism (RFLP) assay, was then performed to identify polymorphic nucleotide in pncA and oxyR, respectively. For comparison, 37 adult cases of tuberculous lymphadenitis were also analysed by PCR-single strand conformation polymorphism (SSCP) assay for pncA and by PCR-RFLP for oxyR. The results revealed that five of the nine IS6110-positive child cases had a G residue at nucleotide 169 in pncA, and also had a three-band pattern after digesting the amplified oxyR segment with AluI, suggesting BCG-LA. The remaining four child cases, as well as all adult cases with detectable IS6110, showed no motility shift in pncA PCR-SSCP and had the same one-band pattern as M. tuberculosis in oxyR PCR-RFLP, suggesting TB lymphadenitis. The data from molecular analyses showed a good correlation with the vaccination history and clinicopathological findings, except for one case. This study indicates that molecular assay of either oxyR or pncA could be a rapid and useful tool to distinguish BCG-LA from TB.

Adolescent↗

Hodgkin's disease mimicking suppurative lymphadenitis: a fine-needle aspiration report of five cases.

Spontaneous, suppurative-necrotizing changes associated with Hodgkin's disease (HD) are not infrequent. They are mostly observed in the nodular sclerosis variant of HD and can cause an erroneous histologic diagnosis of suppurative lymphadenitis. Few cytologic reports describing this presentation of HD are available. We describe 5 cases of HD that showed cytologic abscess-like smears dominated by a massive neutrophilic infiltrate and necrosis. Since therapy can induce similar changes, this study did not include patients with known HD. In 2 cases erroneously diagnosed as suppurative lymphadenitis, the presence of neoplastic cells was minimal and only detected after revision. A third case was misdiagnosed as abscessified metastasic carcinoma. Two cases were correctly identified as HD, although in one, the possibility of anaplastic large-cell lymphoma could not be ruled out. In conclusion, necrosis and massive neutrophilic infiltrates can occur spontaneously and can be prominent findings in smears from patients with HD, mainly the nodular sclerosis variant. The cytopathologist should always consider this possibility in the presence of an abscessified, suppurative, lymphadenitis-like aspirate. A detailed search for the characteristic neoplastic cells of HD is mandatory in these cases.

Adolescent↗

Cervical lymphadenitis caused by nontuberculous mycobacteria in immunocompetent children: clinical and therapeutic experience.

BACKGROUND: Cervical lymphadenitis is a frequent manifestation of nontuberculous mycobacteria (NTM) infection in immunocompetent children. Surgical excision, the treatment of choice, is often incomplete and may be difficult. A medical approach could reduce treatment morbidity. METHODS: Systemic antibiotic therapy was administered to seven children for at least 6 months as treatment for cervical lymphadenitis due to NTM: rifabutin and clarithromycin in 4 cases; rifabutin, clarithromicyn, and ethambutol in 2 cases; rifabutin, amikacin, and cycloserine in 1 case. RESULTS: All patients, six followed for a mean of 3 years and one for 6 months, were initially seen with regression of local signs of infection without relapse. Toxicity, likely due to rifabutin, was represented by neutropenia in three patients and yellow skin pigmentation in one patient. CONCLUSIONS: Systemic antibiotic therapy was safe and effective in children with lymphadenitis due to NTM. This approach could represent a sound alternative or adjunct to surgery.

Anti-Bacterial Agents↗

Histiocytic necrotizing lymphadenitis (Kikuchi's disease): cytologic diagnosis by fine-needle biopsy.

A cytologic diagnosis of histiocytic necrotizing lymphadenitis (Kikuchi's lymphadenitis) was made in a 14-yr-old female with cervical lymphadenopathy, fever, neutropenia, and hepatosplenomegaly. A predominance of reticulum cells, foamy macrophages, and karyorrhectic debris are clues to the diagnosis in the fine-needle biopsy smears. Subsequent histology confirmed the diagnosis of Kikuchi's lymphadenitis. The differential diagnoses are discussed including malignant lymphoma, which was excluded by morphology as well as flow cytometry and polymerase chain reaction (PCR) studies.

Adolescent↗

IRTA1+ monocytoid B cells in reactive lymphadenitis show a unique topographic distribution and immunophenotype and a peculiar usage and mutational pattern of IgVH genes.

The origin and function of monocytoid B cells (MBCs) are poorly understood. Taking advantage of their strong expression of IRTA1 (a receptor that is also associated with MALT marginal zone B cells), we have comprehensively analysed MBCs in 25 cases of lymphadenitis of different aetiologies, shedding new light on the topographical distribution, immunophenotype and IgV(H) gene usage and mutational profile of this B cell subset. IRTA1(+) MBCs, although predominantly located in the subcapsular and intermediary sinuses, were also observed scattered within germinal centres (GCs) in all lymphadenitis cases examined. The molecular characterization of IgV(H) genes revealed that IRTA1(+) MBCs residing in different areas of the lymph node (subcapsular sinus, intermediary sinuses and GCs) can be clonally related (with intraclonal variation), and that those located in GCs are consistently more mutated and selected for expression of a functional antigen receptor than those located in the sinuses. Moreover, by contrast, IRTA1(+) MBCs in GCs express the memory B cell marker CD27. Finally, in toxoplasmic lymphadenitis, the IRTA1(+) MBC population shows a highly preferential usage of the V(H) genes 3-7 and 3-30 (without any obvious peculiarity in their CDR3s), possibly suggesting that a superantigen expressed by Toxoplasma gondii may be involved in the early activation of this B cell subset.

B-Lymphocyte Subsets↗

Xanthogranulomatous lymphadenitis.

A case of an unusual type of granulomatous lymphadenitis, initially suspected of being a malignant lymphoma, is reported. Histologically, this lesion shows a striking xanthomatous appearance, due to collections of foamy histiocytes interspersed with chronic inflammatory cells, and resulting in a storage-like aspect. Evidence indicates that this process merely represents the reabsorption and healing phases of an acute suppurative lymphadenitis, with histopathologic features comparable to those of xanthogranulomatous pyelonephritis. The term xanthogranulomatous lymphadenitis is suggested for this previously inadequately described lesion, and the likely non-specific degenerative character of the xanthomatous response is stressed.

Adolescent↗

Therapy of regional lymphadenitis following BCG vaccination.

In this study we presented 92 cases with regional lymphadenitis (over 1 cm in diameter) which was caused by BCG vaccination generally performed a few days after birth. The patients were divided into four therapy groups. In group I, the lymphadenitis in 26 cases was excised totally by a surgical operation and they improved in a median period of four weeks (average: 4.4). No therapy was applied in 33 patients constituting group II and their periods of improvement were 28 weeks (average: 29.1). Sixteen cases in group III were given isoniazid (INH) 10 mg/kg for six months in addition to total surgical excision and their healing period was 4.5 weeks (average: 4). Seventeen cases in group IV were administered only INH for six months and the median improvement period was found to be 27 weeks (average: 28.2). The statistical differences in terms of the improvement periods between groups I and III, and groups II and IV were found to be insignificant (p greater than 0.05) but these differences were significant between groups I and II, groups I and IV, groups II and III, and groups III and IV (p less than 0.05). These results show that spontaneous healing is possible. Total excision is the best therapy for BCG lymphadenitis in suppurative forms and INH has no effect in shortening the therapy period.

BCG Vaccine↗

Mesenteric lymphadenitis due to Yersinia enterocolitica.

The histopathological diagnosis of Yersinia enterocolitica infections in mesenteric lymph nodes is described on the basis of biopsy material from 14 cases collected at the Lymph Node Registry in Kiel. In all cases, the aetiological diagnosis was verified by demonstrating significant antibody titres in serological tests and, in two cases, by isolating Yersinia enterocolitica from faeces. The mesenteric lymph nodes showed a rather specific histological picture. In all cases, the capsule was thickened by oedema and stained metachromatically. The cortical and paracortical pulp was always hyperplastic owing to an increase in the number of immunoblasts, plasmablasts, and plasma cells. The sinuses were dilated and filled with intensely basophilic cells that varied in size from small to large (plasmacytoid cells and precursors). Small, or relatively large accumulations of "immature histiocytes" (transformed lymphocytes) were seen in the sinuses in about two thirds of the cases. Occasionally, there were small foci of small histiocytes (emigrated monocytes) in the cortical pulp. An abscess similar to the abscesses found in abscess-forming reticulocytic lymphadenitis due to Yersinia pseudotuberculosis was evident in only one case. The differential diagnosis is also discussed. The diseases to be considered are mesenteric lymphadenitis due to Yersinia pseudotuberculosis or salmonella infection, and nonspecific mesenteric lymphadenitis.

Adolescent↗

Infrequent detection of Toxoplasma gondii genome in toxoplasmic lymphadenitis: a polymerase chain reaction study.

The diagnosis of toxoplasmic lymphadenitis is currently established by histologic evaluation with confirmation by serologic studies. We used a sensitive and specific polymerase chain reaction methodology for the identification of toxoplasmic genomes previously reported by others to investigate whether this technology could contribute to the diagnosis. We were able to reliably detect toxoplasmic genomes in paraffin-embedded tissues of toxoplasmic encephalitis and myocarditis, and serial dilution studies indicated a high degree of sensitivity. Nonetheless, we identified toxoplasmic genomes in frozen tissue from only one of nine cases of toxoplasmic lymphadenitis. In the one positive case, only one of three frozen samples from the lymph node biopsy was positive, indicating a focal infection within the lymph node. It is concluded that polymerase chain reaction studies, at their current level of sensitivity, are not of great use in contributing to the evaluation of cases of suspected toxoplasmic lymphadenitis, which continues to be best diagnosed by accurate histopathologic examination.

Adolescent↗

Subacute necrotizing lymphadenitis.

We report the skin manifestations and abnormalities of subacute necrotizing lymphadenitis. As far as we are aware, this is the first report of this disease in the dermatology literature. The main features of subacute necrotizing lymphadenitis are fever, a cervical lymphadenopathy, and, occasionally, a skin eruption resembling urticaria, rubella, or a drug-induced erythema. A skin biopsy specimen showed a mild lymphohistiocytic perivascular infiltrate of cells in the papillary and mid dermis and deposition of fibrinogen around the capillary vessels. Subacute necrotizing lymphadenitis responds to oral corticosteroid therapy but not to antibiotics.

Acute Disease↗

Kikuchi's disease: a rare cause of cervical lymphadenitis and fever.

Cervical lymphadenitis and fever are common in patients presenting to the Emergency Department (ED). Kikuchi's disease is a rare, self-limited cause of fever and cervical lymphadenitis often misdiagnosed as lymphoma or lupus and inappropriately treated, potentially causing numerous ED visits for unrelieved symptoms. The case described is that of a 29-year-old with persistent fever and cervical lymphadenitis who presented to the ED with a suspected allergic reaction to an antibiotic. The diagnosis of Kikuchi's disease was made in association with nasopharyngeal carcinoma and partial hydatidiform mole. The case highlights the clinical features, diagnosis, and treatment of Kikuchi's disease.

Adult↗

Mycobacterium abscessus cervical lymphadenitis: an immunocompetent child.

Nontuberculous mycobacterium (NTM) is one of the well-known causes of cervicofacial lymphadenopathy in children under 5 years of age. Children often present with a painless cervical mass that fails to respond to conventional antibiotics. They are often referred under the suspicion of a neoplasm or bacterial adenitis rather than NTM cervical lymphadenitis. The lack of systemic symptoms, modest or negative purified protein derivative test and absence of exposure to active tuberculosis are characteristics of NTM lymphadenitis. The diagnosis usually requires the isolation of pathogen or pathologic proof. Complete excision is the choice of treatment by the majority of authors in the literature. This not only enables rapid diagnosis but ensures the lowest recurrence rate. Medical management is sometimes successful when complete resection is impossible or refused. To our knowledge, the incidence of NTM cervical lymphadenitis in children is increasing throughout the world. However, such reports of children in Taiwan is lacking. Clinicians should suspect a possible nontuberculous mycobacterial infection when a cervical lump is found in a child.

Child↗

Acute viral lymphadenitis mimicking low-grade peripheral T-cell lymphoma. A clinicopathological study of nine cases.

Acute viral lymphadenitis, especially infectious mononucleosis (IM), often shows the presence of Reed-Sternberg-like cells, resulting in confusion with Hodgkin's disease. However, acute viral lymphadenitis requiring differential diagnosis from non-Hodgkin's lymphoma is not widely recognized. We describe the clinicopathological and immunohistochemical features of lymph node lesions from nine such patients which pose serious problems of differential diagnosis from low-grade peripheral T-cell lymphoma. There were three males and six females with ages ranging from 21 to 44 years (median 25 years). All patients had "B" symptoms and multicentric lymphadenopathy. The clinical course was also self-limiting. Each lymph node specimen showed an obvious expansion of an interfollicular area by pleomorphic and polymorphous infiltration with an increased number of arborizing postcapillary venules. The infiltrate was composed of variable numbers of small and medium-sized lymphocytes, immunoblasts, plasma cells in various stage of maturation and occasional granulocytes. The small lymphocytes usually had regular round nuclei, whereas the medium-sized lymphocytes occasionally showed nuclear pleomorphism. Hyperreactivity of B-lymphocytes, including hyperplastic germinal centers and/or foci of monocytoid B-cells, was seen in parts of the lesion. The majority of the interfollicular T-lymphocytes, including T-immunoblasts, expressed CD8 antigen. Various numbers of TIA-1-positive small and medium-sized T-cells were observed in the paracortical area. Despite these findings, the overall histological picture of this series posed serious difficulties when differentially diagnosing this condition from low-grade peripheral T-cell lymphomas such as angioimmunoblastic T-cell (AILD) and T-zone types, indicating that viral lymphadenitis occasionally presents with histological features of AILD and T-zone lymphomas. To avoid overdiagnosis and overtreatment, we emphasize the need to pay careful attention to the clinical and laboratory findings as well as the morphological features.

Acute Disease↗

Immunohistochemistry using a Mycobacterium tuberculosis complex specific antibody for improved diagnosis of tuberculous lymphadenitis.

The clinical and histological criteria used to diagnose lymphadenitis caused by Mycobacterium tuberculosis complex organisms have poor specificity. Acid-fast staining and culture has low sensitivity and specificity. We report a novel method for diagnosis of tuberculosis that uses immunohistochemistry to detect the secreted mycobacterial antigen MPT64 on formalin-fixed tissue biopsies. This antigen has not been detected in non-tuberculous mycobacteria. Polymerase chain reaction (PCR) for amplification of IS6110 from DNA obtained from the biopsies was used as a gold standard. Fifty-five cases of granulomatous lymphadenitis with histologically suspected tuberculosis obtained from Norway and Tanzania were evaluated. Four known tuberculosis cases were used as positive controls, and 16 biopsies (12 foreign body granulomas and four other non-granulomatous cases) as negative controls. With immunohistochemistry, 64% (35/55) and with PCR, 60% (33/55) of granulomatous lymphadenitis cases were positive. Using PCR as the gold standard, the classical tuberculosis histology had sensitivity, specificity, positive and negative predictive values of 92, 37, 60, and 81%, respectively, and immunohistochemistry had sensitivity, specificity, positive and negative predictive values of 90, 83, 86, and 88%, respectively. The observed agreement between PCR and immunohistochemistry was 87% (kappa = 0.73). Immunohistochemistry with anti-MPT64 antiserum is a rapid, sensitive, and specific method for establishing an etiological diagnosis of tuberculosis in histologic specimens. Immunohistochemistry has the advantages over PCR of being robust and cheap, and it can easily be used in a routine laboratory.

Adolescent↗

Assessment of cell proliferation by Ki-67 staining and flow cytometry in fine needle aspirates (FNAs) of reactive lymphadenitis and non-Hodgkin's lymphomas.

This study was undertaken to assess cell proliferation in FNAs from a series of 57 non-Hodgkin's lymphomas (NHL) and 11 cases of reactive lymphadenitis using Ki-67 staining and flow cytometry (FCM). The results were compared and correlated to the cytomorphological subgrouping according to Kiel classification. The mean percentages of Ki-67 positivity were 16.6% and 61.1% for low and high grade lymphomas, respectively (P < 0.001). The mean S-phase fraction (SPF) determined by FCM was 4.61% for low grade and 12.9% for high grade lymphomas (P < 0.001). The figures for Ki-67 positivity and S-phase fraction in reactive lymphadenitis were 16.8% and 40%, respectively. We observed a strong correlation in low grade lymphomas between Ki-67 and SPF. A good correlation was also found in reactive lymphadenitis. In high grade lymphomas, however, with highly scattered Ki-67 and S-phase values, this correlation was lost. In some cases this discrepancy can be explained by a rich admixture of non-neoplastic, non-proliferating cells in aspirates from diploid tumours. In addition, the existence of a minor aneuploid tumour cell population of high proliferation such as that in Ki-1 lymphomas will not be accurately analysed by FCM but is easily assessed by Ki-67 staining. However, the main reason seems to be a high variability between the fraction of cells in S-phase and the total number of cells in G1, S and G2 in individual tumours.

Adult↗