Proliferating cells in histiocytic necrotizing lymphadenitis

The phenotypes of proliferating cells in histiocytic necrotizing lymphadenitis (HNL) were examined. The affected areas consisted mainly of CD 8-positive (suppressor/cytotoxic T-cells) and CD 4-positive (helper/inducer T-cells) in association with some CD 15-positive cells (monocytes). A marker of proliferating cells (Ki-67) and monoclonal antibodies for determining the phenotypes of cells (CD 4, CD 8, CD 15) in the affected areas were applied using a double-staining method. Ki-67-positive proliferating cells were mainly CD 8-positive. A few CD 4-positive cells and rare CD 15-positive cells were also Ki-67-positive. The percentage of CD 8-positive cells increased gradually over time and the ratio of CD 8-positive to proliferating cells did not decrease throughout the observation period of 6 weeks. These results suggest that the proliferation of CD 8-positive T-cells together with the accumulation of CD 4- and CD 15-positive cells is the main phenomenon occurring in HNL.     

Kikuchi's histiocytic necrotizing lymphadenitis. Diagnosis by fine needle aspiration

Two cases of Kikuchi's histiocytic necrotizing lymphadenitis diagnosed by fine needle aspiration (FNA) of enlarged lymph nodes are reported. The FNA smears contained randomly activated lymphoid cells, necrotic debris, karyorrhectic cells and prominent histiocytes, suggesting the presence of reactive lymph nodes. The true nature of the lesions was evident from the examination of cell block sections prepared from tissue fragments in the aspirates, which preserved the architectural relationships of the different cell types. The same patterns were found in retrospectively and subsequently examined excised lymph nodes from these cases. The differential diagnosis of this entity, which may simulate a malignant lymphoma because of the presence of large numbers of activated lymphoid cells, is discussed and the value of preparing FNA cell blocks is emphasized. Though this rare benign disease may be suspected clinically in the more typical cases, such as young women with cervical lymphadenopathy, fever, neutropenia and otherwise excellent condition, the diagnosis cannot be made without a lymph node biopsy, which FNA may be able to provide in some instances.     

Histiocytic necrotizing lymphadenitis without granulocytic infiltration

About 50 cases of histiocytic necrotizing lymphadenitis without granulocytic infiltration were published till now. The authors describe the case of a 19-year-old patient with the right ear and the right ring finger bitten by squirrel about 40-50 days before the appearance of an axillary homolateral painful lymphadenomegaly and fever. Histopathologic examination of excised lymph nodes showed areas of necrosis, necrobiosis and nodular histiocytosis. Histiocytes were dystrophic or showed evidence of macrophagy. Problems referring to morphogenesis and etiology are discussed.     

Proliferating satellite cells express acidic fibroblast growth factor during in vitro myogenesis.

Recent in vitro studies have indicated that the proliferation of satellite cells, which are involved in muscular regeneration in vivo, is stimulated by exogenous addition of fibroblast growth factor (FGF). We present evidence that satellite cell cultures produce acidic, but not basic FGF. Acidic or basic FGF content was measured by enzyme immunoassay on cellular extracts after partial purification by heparin-Sepharose chromatography. During maximal cell proliferation, the level of acidic fibroblast growth factor (aFGF) was increased over fivefold from the values obtained before plating. aFGF content drastically dropped at the postmitotic stage to almost the threshold of detection, and remained weak as differentiation was completed. The immunolocalization of aFGF using highly purified anti-aFGF antibodies confirmed these results and indicated that aFGF was cytoplasma- or membrane-associated. Our work suggests that an endogenous production of aFGF by satellite cells may trigger cell proliferation by an intra- or autocrine mechanism, and therefore play an important role in muscular regeneration.     

Proliferating cells in suborbital tissue drive eye migration in flatfish

The left/right asymmetry of adult flatfishes (Pleuronectiformes) is remarkable given the external body symmetry of the larval fish. The best-known change is the migration of their eyes: one eye migrates from one side to the other. Two extinct primitive pleuronectiformes with incomplete orbital migration have again attracted public attention to the mechanism of eye migration, a subject of speculation and research for over a century. Cranial asymmetry is currently believed to be responsible for eye migration. Contrary to that hypothesis, we show here that the initial migration of the eye is caused by cell proliferation in the suborbital tissue of the blind side and that the twist of frontal bone is dependent on eye migration. The inhibition of cell proliferation in the suborbital area of the blind side by microinjected colchicine was able to prevent eye migration and, thereafter, cranial asymmetry in juvenile Solea senegalensis (right sideness, Soleidae), Cynoglossus semilaevis (left sideness, Cynoglossidae), and Paralichthys olivaceus (left sideness, Paralichthyidae) with a bottom-dwelling lifestyle. Our results correct the current misunderstanding that eye migration is driven by the cranial asymmetry and simplify the explanation for broken left/right eye-symmetry. Our findings should help to focus the search on eye migration-related genes associated with cell proliferation. Finally, a novel model is proposed in this research which provides a reasonable explanation for differences in the migrating eye between, and sometimes within, different species of flatfish and which should aid in our overall understanding of eye migration in the ontogenesis and evolution of Pleuronectiformes.     

Cryptococcal lymphadenitis in a dog.

We describe a case of canine crytococcosis, the clinical symptoms were: feverish syndrome, vomiting and diarrhoeas and bilateral lymphadenitis in superficial lymph nodes. Microbiology and histopathology study of popliteal lymph node biopsy demonstrated the presence of round yeasts of some 3 microm of diameter, which we identified as Cryptococcus neoformans. Thirty months after suspending the medication the dog returned to the surgery; the dog was very thin and it had nervous symptoms; the owners decided it upon euthanasia. After carrying out the necropsy we take samples for their microbiology and histopathology study, both techniques detect to C. neoformans in marrow, CNS tissue and lymph nodes.     

Superficial mycobacterial lymphadenitis in Saskatchewan.

A total of 43 bacteriologically verified cases of superficial mycobacterial lymphadenitis were reported in Saskatchewan between 1981 and 1986; 35 (81%) were due to Mycobacterium tuberculosis. Among the eight cases (19%) due to nontuberculous mycobacteria the agent most frequently isolated was M. avium-intracellulare. Five additional cases were smear-positive and culture-negative. Direct smears of node tissue or aspirate were positive for acid-fast bacilli in 7 (88%) of the 8 cases of nontuberculous mycobacterial lymphadenitis but in only 16 (46%) of the 35 cases due to M. tuberculosis. Superficial tuberculous lymphadenitis was most frequent in female North American Indian or Asian-born adults and most commonly involved the cervical nodes. Nontuberculous mycobacterial lymphadenitis was most frequent in female white children, and most commonly involved the submandibular nodes. The cases of both tuberculous and nontuberculous mycobacterial lymphadenitis were spread throughout the province. There was an urban concentration of cases of tuberculous lymphadenitis in those of Asian origin. It is important to distinguish between superficial mycobacterial lymphadenitis due to M. tuberculosis and that due to nontuberculous mycobacteria for treatment and management purposes.     

Deoxynucleoside overproduction in deoxyadenosine-resistant, adenosine deaminase-deficient human histiocytic lymphoma cells

Deoxyadenosine toxicity toward lymphocytes may produce immune dysfunction in patients with adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) deficiency. The relationship between endogenous deoxynucleoside synthesis in adenosine deaminase-deficient cells and sensitivity to adenosine and deoxyadenosine toxicity is unclear. The human histiocytic lymphoma cell line (DHL-9) naturally lacks adenosine deaminase, and has minimal levels of thymidine kinase. Dividing DHL-9 cells excrete deoxyadenosine and thymidine into the extracellular space. The present experiments have analyzed nucleoside synthesis and excretion in a mutagenized clone of DHL-9 cells, selected for increased resistance to deoxyadenosine toxicity. The deoxyadenosine-resistant cells excreted both deoxyadenosine and thymidine at a 6-7-fold higher rate than wild-type lymphoma cells. The deoxyadenosine overproduction was accompanied by a reduced ability to form dATP from exogenous deoxyadenosine, and a 2.5-fold increase in ribonucleotide reductase activity. The pace of adenosine excretion, the growth rate, and the levels of multiple other enzymes involved in deoxyadenosine and adenosine metabolism were equivalent in the two cell types. These results suggest that the excretion of deoxyadenosine and thymidine, but not adenosine, is exquisitely sensitive to alterations in the rate of endogenous deoxynucleotide synthesis. Apparently, small changes in deoxynucleotide synthesis can significantly influence cellular sensitivity to deoxyadenosine toxicity.     

Proliferating mesodermal cells in murine embryos exhibiting macrophage and lymphendothelial characteristics

Background  

The data on the embryonic origin of lymphatic endothelial cells (LECs) from either deep embryonic veins or mesenchymal (or circulating) lymphangioblasts presently available remain inconsistent. In various vertebrates, markers for LECs are first expressed in specific segments of embryonic veins arguing for a venous origin of lymph vessels. Very recently, studies on the mouse have strongly supported this view. However, in the chick, we have observed a dual origin of LECs from veins and from mesodermal lymphangioblasts. Additionally, in murine embryos we have detected mesenchymal cells that co-express LEC markers and the pan-leukocyte marker CD45. Here, we have characterized the mesoderm of murine embryos with LEC markers Prox1, Lyve-1 and LA102 in combination with macrophage markers CD11b and F4/80.     

Interdigitating reticulum cells in dermatopathic lymphadenitis: freeze-fracture and ultrathin-section morphology

Dermatopathic lymphadenitis is a non-neoplastic lesion found with various chronic skin lesions and associated with hyperplasia of the thymus-dependent (T) areas. These areas consist chiefly of interdigitating reticulum cells (IDC's), which are known to be accessory cells for T-cell-dependent immune reactions. The most characteristic features of IDC's are the bizarre-shaped cell nucleus, numerous cytoplasmic processes, deep cytoplasmic invaginations, and a close topographical relationship to surrounding (T) lymphocytes. The cytoplasmic processes of IDC's do not interdigitate with adjacent lymphocytes, as previously reported in the literature, but show close interdigitations with the processes of neighboring IDC's. With the freeze-fracture technique it can be seen that IDC's exhibit a characteristic distribution of intramembranous particles (IMP). While, for example, macrophages, epithelioid cells and lymphocytes display a clearly greater number of IMP on the P face than on the E face, IDC's show an equally high particle density on both the P face and the E face. The organelle content of IDC's in dermatopathic lymphadenitis varies considerably. Tubular profiles, the Golgi apparatus and vesicles may be increased in number. Birbeck granules are also found in IDC's, but only rarely. Variations in the numbers of the different cytoplasmic organelles may be a reflection of varying degrees of metabolic activity of IDC's.     

Short course chemotherapy for tuberculous lymphadenitis in children.

OBJECTIVE--To assess the efficacy of a short course chemotherapy regimen for treating tuberculosis of the lymph nodes in children. DESIGN--Open, collaborative, outpatient clinical trial. SETTING--Outpatient department of the Tuberculosis Research Centre, paediatric surgery departments of the Institute of Child Health and Hospital for Children and the Government Stanley Hospital, Madras, South India. PATIENTS--Children aged 1-12 years with extensive, multiple site, superficial tuberculous lymphadenitis confirmed by biopsy (histopathology or culture). INTERVENTIONS--Patients were treated with a fully supervised intermittent chemotherapy regimen consisting of streptomycin, rifampicin, isoniazid, and pyrazinamide three times a week for two months followed by streptomycin and isoniazid twice a week for four months on an outpatient basis. Surgery was limited to biopsy of nodes for diagnosis and assessment. MAIN OUTCOME MEASURES--Response to chemotherapy was assessed by regression of lymph nodes and healing of sinuses and abscesses during treatment and follow up. Compliance with treatment and frequency of adverse reactions were also estimated. RESULTS--197 Patients were admitted to the study and 168 into the analysis. The regimen was well tolerated and compliance was good with 101 (60%) patients receiving the prescribed chemotherapy within 15 days of the stipulated period of six months. Those whose chemotherapy extended beyond that period received the same total number of doses. Clinical response was favourable in most patients at the end of treatment. Sinuses and abscesses healed rapidly. Residual lymphadenopathy (exceeding 10 mm diameter) was present in 50 (30%) patients at the end of treatment; these nodes were biopsied. Fresh nodes, increase in size of nodes, and sinuses and abscesses occurred both during treatment and follow up. After 36 months of follow up after treatment only 5 (3%) patients required retreatment for tuberculosis. CONCLUSION--Tuberculous lymphadenitis in children can be successfully treated with a short course chemotherapy regimen of six months.