Melanotic Neuroectodermal Tumor of Infancy Occurring in the Left Thigh of a 6-Month-Old Female Infant

We report an exceptional case of melanotic neuro-ectodermal tumor of infancy (MNTI) occurring in the soft tissue of the left thigh of a 6-month-old female infant. The tumor consisted mainly of small round cells (neuroblasts) arranged in cords and nests that were separated by broad fibrovascular areas. In addition, there were a few medium-sized tumor cells containing melanin pigment (melano-cytic cells) that in electron microscopy contained melanosomes as well as tonofilaments. Both tumor cell types immunostained for neuron-specific enolase (NSE) and vimentin, and the melanocytic cells reacted additionally with the antikeratin antibody KL1. Within the tumor stroma, neurofilament- and S-100-protein-positive neural cells and vimentin- and desmin-positive myofibroblasts were seen. Although densecore granules were demonstrated ultrastructurally in some neuroblasts, no immunostaining for chromogranin A, Leu-7, serotonin, or regulatory peptides was found. MNTI located in an extremity can be confused with malignant small round and blue cell tumors of childhood. The distinction between MNTI and these tumors is of clinical significance because MNTI, in most cases, is a benign tumor that, in contrast to the latter, can be cured by complete excision. The presence of a biphasic cell population with neuroblasts and melanocytic cells must be considered the main diagnostic feature of MNTI.     

Cardiovascular patterns associated with threat and challenge appraisals: a within-subjects analysis

Previous studies demonstrated distinct cardiovascular patterns associated with threat and challenge appraisals for groups of participants. We extend these results by assessing whether appraisals continue to be associated with these cardiovascular response patterns within an individual as appraisals change. Participants completed four verbal mental arithmetic tasks for which they made appraisals before and after each task. Cardiac reactivity and total peripheral resistance (TPR) were calculated for the first and last minutes of each task, and the number of responses and percent correct were measured for each task. In line with our prediction, pretask appraisals were related to some task-related cardiac responses across the four tasks. In addition, task-related cardiovascular reactivity and behaviors both influenced appraisals following the task. Our findings suggest that an idiographic analysis of appraisals, cardiovascular physiology, and task-related behaviors provides a richer understanding of the appraisal process and reveals sex differences deserving further assessment.     

Induction of immunoglobulin-producing human peripheral blood lymphocytes in serum-free medium

Induction of immunoglobulin-secreting cells from human peripheral blood lymphocytes in a serum-free culture medium was studied. Albumin, transferrin, insulin and fibronectin can replace serum entirely for support of pokeweed mitogen (PWM)-stimulated B lymphocytes, measured by a reverse hemolytic plaque assay using protein A-coated red cells. In this serum-free system, growth and maturation to IgM and IgG secretion occur at the same or higher efficiency as in conventional serum-containing medium, with maximum numbers of plaque-forming cells on day 6 at optimal dose of PWM, 0.5 ～ 5 μg/ml. This system can be used to avoid the interference from undefined serum components.     

Fine-needle aspiration cytology of malignant peripheral nerve sheath tumors

The histopathologic features of malignant peripheral nerve sheath tumors (MPNSTs) have been well described. There have been limited studies on the cytologic features of MPNST. In this present study, we have retrospectively reviewed eight histopathology confirmed cases of MPNST over a 5-year period. Detailed cytomorphological analysis of these cases was carried out individually by two observers. On cytology, these cases were diagnosed as benign spindle-cell tumor (two), spindle-cell tumor possibly benign (one), spindle-cell tumor possibly malignant (one), malignant spindle-cell tumor (two), spindle-cell tumor, and neural origin (two). The cardinal cytomorphologic features were loosely cohesive clusters and fascicular arrangement of spindle cells with rounded ends. The kinking of nuclei was not a conspicuous finding. Fibrillary background was noted in two of the cases. Nuclear pleomorphism was ranged from mild to moderate degree. One case exhibited extensive intranuclear pseudoinclusions. Mitotic figures (including atypical forms) were present in almost all the cases. Possibly a constellation of cytologic features such as clusters of short and long fascicles of cells admixed with dissociated spindle cells of round-ended nuclei and prominent nucleoli on myxoid or fibrillary background and frequent mitosis may be helpful in diagnosis of MPNSTs. The cytomorphologic features along with clinical correlation are necessary to increase the diagnostic accuracy of MPNST on aspiration cytology.     

2-Mercapto-ethanol enhancement of agglutination reaction--a possible in vitro serological correlate for assessment of functional immunity in simian malaria

Conventional indirect haemagglutination test was performed in rhesus monkey sera (collected from Plasmodium knowlesi infected animals) with and without prior treatment of sera with 2-mercapto-ethanol (2-ME). Surprisingly, many sera samples showed significant enhancement of final titre with 2-ME. The 2-ME enhancement effect was more pronounced in the sera of hyperimmune monkeys on further injection of antigen or parasites. It was also noticeable in the sera during primary drug-suppressed P. knowlesi infection and appeared to have a bearing on the immune status of the animals to rechallenge. The use of a soluble antigen prepared from P. knowlesi infected erythrocytes was found to be essential in IHA test to demonstrate the 2-ME enhancement effect. Antigen prepared from freed parasites (commonly used) failed to show a similar effect in IHA. The possible role of certain T-lymphocyte products - antigen binding, non-agglutinating, 2-ME sensitive molecules - in malarial immunology has been proposed.     

Regionally defective colonization of the terminal bowel by the precursors of enteric neurons in lethal spotted mutant mice

In order to gain insight into the process of colonization of the bowel by the neural crest-derived precursors of enteric neurons, the development of the enteric nervous system was examined in lethal spotted mutant mice, a strain in which a segment of bowel is congenitally aganglionic. In addition, nerve fibers within the ganglionic and aganglionic zones of the gut of adult mutant mice were investigated with respect to their content of acetylcholinesterase, immunoreactive substance P, vasoactive intestinal polypeptide and serotonin, and their ability to take up [³Hserotonin. In both the fetal gut of developing mutant mice and in the mature bowel of adult animals abnormalities were limited to the terminal 2 mm of colon. The enteric nervous system in the proximal alimentary tract was indistinguishable from that of control animals for all of the parameters examined. In the terminal bowel, the normal plexiform pattern of the innervation and ganglion cell bodies were replaced by a coarse reticulum of nerve fibers that stained for acetylcholineserase and were continuous with extrinsic nerves running between the colon and the pelvic plexus. These coarse nerve bundles contained greatly reduced numbers of fibers that displayed substance P- and vasoactive intestinal polypeptide-like immunoreactivity, but a serotonergic innervation was totally missing from the aganglionic bowel. During development, acetylcholineserase and uptake of [³Hserotonin appeared in neural elements in the foregut of mutant mice on the 12th day of embryonic life (E12), about the same time these markers appeared in the forgut in normal mice. By day E14, neurons expressing one or the other marker were recognizable as far distally as about 2 mm from the anus. The appearance of neurons in segments of gut grown for 2 weeks as expiants in culture was used as an assay for the presence of neuronal progenitor cells in the segments of fetal bowel at the time of explantation. Both acetyl- cholinesterase activity and uptake of [³Hserotonin developed in neuronsin vitro in expiants of proximal bowel between days E10 and E17. At all times, however, the terminal 2mm of mutant but not normal fetal gut gave rise to aneuronal cultures. In some mutant mice rare, small, ectopically-situated pelvic ganglia were found just outside aganglionic segments of fetal colon. Uptake of [³Hserotonin, normally a marker for intrinsic enteric neurites, was found in these ganglia.The experiments suppport the hypothesis that the terminal 2 mm of the gut in lethal spotted mutant mice is intrinsically abnormal and thus cannot be colonized by the precursors of enteric neurons. The defect seems to be specific in that both cells and processes of intrinsic enteric neurons, including all serotonergic and most peptidergic neurites, seem to be excluded from the abnormal region while extrinsic nerve fibers, including sympathetic and sensory axons, are able to enter the aganglionic zones. Since examination of neural progenitor cells has failed to reveal a significant proximo-distal displacement of these cells through the enteric tube during development of the murine bowel, a defect in the migration of precursor cells down the alimentary tract to the terminal gut seems unlikely to be substantially involved in the pathogenesis of aganglionosis. This conclusion is supported by the normal enteric nervous system in proximal regions of the mutant gut and the presence of enteric type neurons outside of, but at the same level as the aganglionic region.     

Variation in the histological pattern of nodal involvement by gamma/delta T-cell lymphoma

AIMS: Gamma-delta (gammadelta) T-cell non-Hodgkin's lymphomas (NHLs) usually present with liver, spleen and marrow infiltration. Lymph node involvement by gammadelta T-cell NHL has been rarely documented so far; its histological pattern needs to be further defined. METHODS AND RESULTS: Two cases of nodal gammadelta T-cell NHL are reported: case 1, a 44-year-old man, presented with cytomegalovirus retinitis and superficial lymphadenopathies. Histological analysis of an inguinal lymph node showed complete destruction by a diffuse pleomorphic lymphoid proliferation, which was positive for CD2, CD3, CD43, CD45, TIA-1 and granzyme B, and displayed a gammadelta phenotype (deltaTCR1+, Vdelta1+, Vdelta2-, Vdelta3-, betaF1-). Bone marrow was normal. Case 2, a male 24-year-old patient with a history of renal transplantation, presented with hepatosplenomegaly and supraclavicular lymph node enlargement. Lymph node architecture was globally preserved. Peripheral sinuses contained scattered nests of medium-sized irregular lymphoid cells. Bone-marrow was infiltrated. Phenotype showed positivity for CD2, CD3, CD45 and TIA1 and expression of gammadelta TCR (deltaTCR1+, deltaV1+, deltaV2-, deltaV3-, betaF1-). Both patients died a short time after diagnosis. CONCLUSIONS: These observations suggest that at least two forms of nodal gammadelta T-cell NHL may be encountered: one mimicking classical alphabeta T-cell NHL, with diffuse pleomorphic cell proliferation, and one displaying sinusoidal neoplastic infiltration suggesting a close relationship with hepatosplenic gammadelta T-cell NHL.     

Malignant peripheral nerve sheath tumor of small round cell type with pleomorphic spindle cell sarcomatous areas

An unusual case of malignant peripheral nerve sheath tumor (MPNST) arising in the posterior mediastinum of a 59-year-old man is reported. Histopathologically, the tumor showed an admixture of a dense proliferation of small round cells resembling a primitive neuroectodermal tumor (PNET) and a pleomorphic spindle cell sarcomatous area. Abortive rosettes, primitive neural tube-like structures, and a few glandular structures were found in the small round cell area. Small round cells were immunoreactive for neural cell adhesion molecule and synaptophysin, but were not immunoreactive for MIC2 and neuron-specific enolase. Pleomorphic spindle cells were occasionally arranged in a storiform pattern and were diffusely immunoreactive for S-100 protein. The MPNST of small round cell type is distinguishable from PNET by its negative immunoreactivity for MIC2, and the present tumor is assumed to be derived from primitive neuroectodermal cells in the peripheral nerve capable of bidirectional (neuron and Schwann cell) differentiation.     

Recombination pattern of the TCR γ locus in human peripheral T-cell lymphomas

The recombination events of the γ and β T-cell receptor (TCR) loci were analysed in a series of 39 peripheral T-cell lymphomas (PTCLs) in association with the expression of TCR chains. In TCR αβ PTCLs, 22/23 cases showed a γ-gene rearrangement while only 18/23 showed a concomitant β-gene rearrangement. The germline configuration of the β locus was found in angioimmunoblastic lymphadenopathy and lymphoepithelioid lymphomas. Three γδ PTCLs rearranged both γ and β genes. TCR silent PTCLs showed three different patterns of γ- and β-gene rearrangements. Three cases were in germline configuration for both loci; five cases had a rearranged γ and a germline β locus; and five cases had the two loci rearranged. Regarding the variable genes in the γ-rearranged alleles, members of the VγI subgroup were the most frequently presented (39/50), followed by VγII, VγIII, and VγIV (9/50, 1/50, and 1/50, respectively). Joining segment usage was as follows: J1 or J2 (32/50), JP1 or JP2 (17/50), and JP (1/50). Taken together, these data demonstrate that the γ locus is more frequently rearranged whatever the TCR expression. The γ-locus analysis provides a better diagnostic yield than the β locus in the study of PTCL clonality.