Desmoplastic small round cell tumor presenting as a neck mass: a case report

An unusual case study of a desmoplastic small round cell tumor presenting as a 3.5-cm, firm, supraclavicular neck mass and diagnosed by fine-needle aspirate biopsy in a 16-yr-old male is reported. Clinical, cytologic, and immunocytochemical findings are described. Histologic, immunohistochemical, and genetic features are discussed. Desmoplastic small round cell tumor should be considered in the differential diagnosis of small round cell tumors of any site; the importance of ancillary studies in arriving at the correct diagnosis is emphasized.     

Brief Communication: Role of Nuclear Background and in vivo Environment in Variable Segregation Behavior of the Aging-Dependent T414G Mutation at Critical Control Site for Human Fibroblast mtDNA Replication

Previous work had shown a large accumulation (up to 50% of mtDNA) of a noninherited T414G transversion at a critical control site for mtDNA replication in skin fibroblasts from the majority of human subjects above 65 years old, and its absence in younger individuals. In the present studies, long-term in vitro culture of several fibroblasts populations carrying the heteroplasmic T414G mutation revealed an outgrowth of the mutant cells by wild-type cells. This observation supported the previous conclusion that the mutation accumulation is an in vivo phenomenon, while, at the same time, indicating intrinsic physiological differences between mutant and wild-type cells. Furthermore, subcloning experiments revealed a striking mosaic distribution of the mutation in the original fibroblasts populations, as shown by its presence, in heteroplasmic or homoplasmic form, in a fraction (18–32%) of the fibroblasts, and its absence in the others. In other investigations, transfer of mitochondria from mutation-carrying fibroblasts into mtDNA-less 143B.TK^–0 206 cells revealed the persistence of the mosaic distribution of the mutation, however, with a near-complete shift to homoplasmy. The generality of the latter phenomenon would exclude a founder effect by one or few mitochondria in the transformation experiments, and would rather point to the important role of the nuclear background in the in vitro behavior of the T414G mutation. The stability of the homoplasmic mutation in ⁰ cell transformants provides a powerful tool for analyzing its biochemical effects.     

Serum levels of soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin-2 receptor in patients with vernal keratoconjunctivitis and allergic conjunctivitis

BACKGROUND: Vernal keratoconjunctivitis (VKC) is characterized by severe ocular allergic inflammation that may have a poor visual prognosis. Due to the high frequency of the presence of atopic dermatitis (AD) in VKC, most systemic parameters are dependent on the clinical severity of AD. METHODS: Serum levels of sICAM-1, sVCAM-1, and sIL-2R were measured by enzyme-linked immunoassay using samples from 30 VKC patients, 30 allergic conjunctivitis (AC) patients, and 20 normal subjects, to determine whether the concentrations of these molecules are elevated. RESULTS: Circulating sICAM-1 and sIL-2R levels were increased in patients with VKC with AD compared with those in VKC without AD, AC, and normal controls. Serum levels of sVCAM-1 in VKC patients with and without AD were significantly higher than those in controls. No significant difference was found in the levels of sVCAM-1 between patients with VKC with and without AD. In VKC patients with AD, the sIL-2R level correlated significantly with severity of AD, whereas no such correlation was found for sICAM-1 and sVCAM-1. CONCLUSIONS: These results suggest that serum sVCAM-1 can be used as a marker to differentiate VKC from nonproliferative ocular allergic diseases, and specific immunologic features of VKC may underlie the upregulation of serum sVCAM-1.     

Flash labelling of S-phase cells in short-term organ culture of normal and pathological human endometrium using bromodeoxyuridine and tritiated thymidine

Normal hyperplastic and malignant endometrial specimens were labelled in vitro with bromodeoxyuridine (BrdU). S-phase cells were stained after DNA denaturation, using a monoclonal antibody to BrdU and an indirect immunoperoxidase method. Various conditions for BrdU uptake, DNA denaturation, and staining were tested. BrdU labelling was compared with autoradiography using tritiated thymidine, with good correlation. Glandular labelling indices of proliferative endometrium were significantly higher than both secretory and hyperplastic endometrium but were similar to carcinoma. Stromal labelling showed the same trend but the differences were not statistically significant.     

Argyrophilic nucleolar organizer regions in colorectal malignancy: application of typing by their density

Colorectal neoplasms obtained at colonoscopy were examined by argyrophilic nucleolar organizer region (AgNOR) staining to evaluate the usefulness of AgNOR as a discriminant for malignancy. AgNOR dots were divided into two kinds: 'structures' (larger and less-densely stained) corresponding to the nucleolus, and 'units' (smaller and densely stained) presumed to be true AgNOR within the structure. The number of structures per nucleus did not differ between the adenoma and carcinoma groups, whereas the number of units per nucleus showed a significant difference. However there were several cases showing an overlap between the adenoma and carcinoma groups, leading to a difficulty in deciding whether any given case was benign or malignant. Three types of AgNOR patterns were categorized based on the ratio of units to structure. Type I was defined as the unit being indistinguishable from the structure, Type II as each structure having one to five units, and Type III as at least one structure having six or more units, irrespective of total number of units per nucleus. The colorectal lesions in which more than half of the neoplastic cells showed Type III coincided well with carcinomas histologically diagnosed, with the exception of adenomas with severe atypia. Labeling index of proliferating cell nuclear antigen (PCNA LI) differed between the adenoma and carcinoma groups with a considerable extent of overlap, and correlated to some extent with the AgNOR values. These results showed that the AgNOR staining was useful for determining malignancy and its usefulness appeared superior to PCNA LI.     

Vaccination of the Leishmania major susceptible BALB/c mouse. I. The precise selection of peptide determinant influences CD4+ T cell subset expression

BALB/c mice are susceptible to cutaneous lelshmanlasls uponinfection with Leishmania major while C57BL/6 are not. Thereis a major promastigote surface protease (PSP or gp63) whichis available in both native and recomblnant forms, and for whichthe primary amlno acid sequence is known. Immunization withPSP has been shown to offer some protection against challengewith the live organism. Therefore, we attempted to develop apeptide vaccine with PSP peptldes. In the first experiments,recall prollferatlve responses to PSP were measured using aset of 15mer peptldes spanning the entire PSP molecule whichallowed designation of major determinant regions in BALB/c,C57BL/6, and CBA mice. Several of these determinants were promiscuousand shared almost the identical core amlno acid residues inthe different strains. Immunization with major determinant peptldeswas recalled vigorously with L. major soluble antigen as wellas with PSP. The response to peptide was almost entirely T_h1as measured by a localized ELISA assay for single-cell productionof IFN-. A similar assay for IL-5, which overcomes problemsof sensitivity and inhibition by lymphoklnes produced by T_h1cells, Indicates very little production of T_h1 cells even byBALB/c. It was found that if a major responsive peak was examinedby recall with overlapping peptldes, the highest, central peptidegave a mainly Th1 response while the boundary, less efficientpeptldes gave more of a T_h2 response. Possible reasons for thiswere discussed. These results point to the importance of selectingthe exactly appropriate peptide in considering a vacclnogenthat might protect susceptible individuals. Even the choiceof a somewhat immunogenlc peptide within the determinant envelopemight actually exacerbate infection by steering the responsein a T_h2 direction.     

DAF与CD3协同刺激人外周血T细胞活化的实验研究

目的：探讨人促衰变加速因子（decay-accelerating factor,DAF)作为共刺激分子参与T细胞活化的作用机制。方法：观察3株针对DAF不同SCR的单抗单独使用或者与抗人CD3单抗联合使用时，对人外周血T细胞增殖、IL－2分泌以及胞浆Ca^2 水平的影响。结果：所用3株抗人DAF单抗不能活化T细胞，而抗人DAF单抗与抗人CD3单抗可以协同刺激T细胞增殖，促进IL－2分泌以及提高胞浆Ca^2 水平。结论：抗人DAF单抗与抗人CD3单抗可协同刺激人外周血T细胞活化。     

Thymic sarcomatoid carcinoma with skeletal muscle differentiation: report of two cases, one with cytogenetic analysis

AIMS: Malignant thymic tumour histologically resembling a soft tissue sarcoma is extremely rare and defined as sarcomatoid carcinoma in the recent World Health Organization (WHO) classification. We report two such cases in which the tumour cells showed a prominent rhabdomyoblastic differentiation and analyse whether these tumours retain an epithelial nature at least in part. METHODS AND RESULTS: One tumour occurred in a 51-year-old man (Case 1) and the other in a 40-year-old woman (Case 2). Microscopically, both tumours consisted essentially of two types of tumour cells: spindle and large round cells, with no apparent epithelial components. Osteosarcomatous small foci were also found in Case 2. Immunohistochemically, desmin and muscle-specific actin were positive in the majority of both types of tumour cells, whereas myogenin was predominant in the spindle cells and myoglobin in the large round cells. Some of both types of cells expressed cytokeratin with co-expression of myoglobin in the large round cells, but with no myogenin in the spindle cells. Some cytokeratin-positive spindle cells were also negative for desmin. Ultrastructural examination of a recurrent tumour in Case 2 revealed some epithelial features among the spindle cells. Cytogenetic study of the same tumour showed a complex abnormality including der(16)t(1;16)(q12;q12.1), an identical pattern previously reported in a case of thymic squamous cell carcinoma. CONCLUSIONS: The findings support the definition in the WHO classification of sarcomatoid carcinoma that includes purely sarcomatous tumour as in the present cases. Occurrence of this type of tumour may indicate a relationship between thymic epithelial cells and myoid cells and/or a potential for divergent differentiation in thymic epithelial tumours.     

Shared amino acid sequences in the NDβN and Nα regions of the T cell receptors of tumor-infiltrating lymphocytes within malignant glioma

The purpose of this study was to assess the V-(D)-J junctional region of the T cell receptor (TCR), the CDR3 region, which is responsible for glioma-specific antigen contact in αβ TCR-mediated recognition. We sequenced the TCR α and β chians of Vα7, and Vβ13.1 cDNA derived from tumor-infiltrating lymphocytes (TIL) of 12 glioma patients and also the corresponding clones from the patients' peripheral blood lymphocytes (PBL). A shared Vβ13.1 DJ sequence of the CDR3 region, NDβN, was demonstrated in 49 of 66 Vβ13.1⁺ clones (74.2 %) from the glioma TIL, whereas only 4 of 33 clones (12.1 %) were observed in the Vβ13.1⁺ clones from the PBL (p < 0.001). A common VDJ sequence, FCASS (Vβ13.1)-YRLPWGTSDS (NDβN)-GELFF(Jβ2.2), was observed not only in the gliomas from each patient, but also among all the patients with a preference for Vβ13.1. In contrast, the amino acid sequences of the Vβ13.1⁺ PBL clones were diverse and random. Next, we sequenced subclones from other Vβ subfamilies randomly selected to compare their VDJ region rearrangements (Vβ3 and Vβ5.1). In contrast to Vβ13.1, the amino acid sequences of these junctional regions were completely different in these subclones. The V-J junctional region of the α chain is dominated by a few clones in some patients, and no shared amino acid sequences were detected in the TCR Vα junctional region. However, in the Nα region of the Vα7-bearing TIL clones, arginine was used in 27 of 44 clones (61.4%) compared to only 3 of 12 clones from the PBL (p < 0.05). These results are consistent with the hypothesis that a clonal expansion/accumulation of glioma lineage-specific T cells occurred in vivo at the tumor site and that these T cells may be recognizing glioma-specific antigens.     

免疫耐受机制研究进展

免疫耐受是机体免疫系统在接触某种抗原后所产生的对该抗原特异性免疫无应答状态,是免疫应答的一种特殊形式,免疫应答的复杂性决定了免疫耐受诱导的复杂性和困难性.随着免疫学的发展,人们对免疫耐受产生机制有了较多的认识.本文对免疫耐受与细胞凋亡、调节性T细胞及树突状细胞的研究进展进行综述.