Immunophenotypic and clinical differences between the nasal and extranasal subtypes of upper aerodigestive tract natural killer/T-cell lymphoma.

PURPOSE: To investigate, in a large cohort of patients, the immunophenotypic and clinical differences of nasal and extranasal extranodal nasal-type natural killer/T-cell lymphoma of the upper aerodigestive tract (UADT-NKTCL) and examine the relevance of the immunophenotype on the clinical behavior, prognosis, and treatment. METHODS AND MATERIALS: A total of 231 patients with UADT-NKTCL were recruited. One hundred eighty-one patients had primary location in the nasal cavity (nasal UADT-NKTCL), and 50 patients had primary extranasal UADT-NKTCL. RESULTS: Patients with extranasal UADT-NKTCL had more adverse clinical features, including advanced-stage disease, regional lymph node involvement, B symptoms, and poor performance status, than patients with nasal UADT-NKTCL. In addition, CD56 and granzyme B were less frequently expressed in extranasal UADT-NKTCL. The 5-year overall survival rate was 74.1% for the entire group and 76.0% for early-stage disease. The 5-year overall survival rate for extranasal UADT-NKTCL was similar or superior to that of nasal UADT-NKTCL for all disease stages (76.9% vs 73.4%, P=.465), stage I disease (75.9% vs 79.2%, P=.786), and stage II disease (83.3% vs 50.3%, P=.018). CD56 expression and a Ki-67 proliferation rate ≥ 50% predicted poorer survival for extranasal UADT-NKTCL but not for nasal UADT-NKTCL. CONCLUSIONS: Patients with nasal and extranasal UADT-NKTCL have significantly different clinical features, immunophenotypes, and prognosis. Extranasal UADT-NKTCL should be considered as a distinct subgroup apart from the most commonly diagnosed prototype of nasal UADT-NKTCL.

Primary lymphoplasmacytoid lymphoma of the trachea with immunoglobulin G paraprotein.

A primary tracheal lymphoma with immunoglobulin G (IgG)-associated monoclonal serum paraprotein treated with surgery and chemotherapy is reported. As far as we know this is the first lymphoplasmacytoid lymphoma reported in the tracheobronchial tree and the first with a serum and tissue IgG monoclonal paraprotein. Differential diagnosis must be made essentially with extramedullary plasmacytoma and mucosa-associated lymphoid tissue lymphoma. CD-45RB strong positivity and the absence of lymphoepithelial lesions may help to differentiate lymphoplasmacytoid lymphoma from them. We expand the spectrum of lymphoid lesions with plasmacytoid features that can occur in the tracheobronchial tract.

Association of Kaposi's sarcoma associated herpesvirus (KSHV) DNA in bronchoalveolar lavage fluid of HIV infected individuals with bronchoscopically diagnosed tracheobronchial Kaposi's sarcoma.

OBJECTIVES: To determine the frequency of detection of Kaposi's sarcoma associated herpesvirus (KSHV), also known as human herpesvirus (HHV) type 8, DNA in bronchoalveolar lavage (BAL) fluid from HIV infected individuals with and without KS and to compare this with the detection rate in peripheral blood. Also to identify whether KSHV was associated with specific cell types in lavage fluid. METHODS: Nested PCR was used to detect KSHV DNA in BAL fluid from 41 consecutive individuals with Kaposi's sarcoma (KS) and in 41 controls with similar CD4 lymphocyte counts. Semiquantification of viral DNA was by end point titration. A positive cell sorting selection procedure was used to isolate specific BAL fluid cell types. RESULTS: KSHV DNA was detected in BAL fluid from 24 of 29 (83%) individuals with a bronchoscopic diagnosis of tracheobronchial KS. None was detected in 12 individuals with only cutaneous KS, or in 41 matched controls without KS. In five, KSHV DNA was detected in the cell depleted and cellular fractions of BAL fluid and in 1/5 in the CD14 (macrophage) fractions. None was detected in the CD19 (B lymphocyte) or CD4/CD8 (T lymphocyte) fractions. CONCLUSIONS: There was a clear association between the diagnosis of tracheobronchial KS and detection of KSHV DNA in BAL fluid. The cell type supporting KSHV in the respiratory tract is not CD 19 positive and has yet to be conclusively identified.

Common leukocyte antigen staining of a primitive sarcoma.

A 4-year-old boy presented with symptoms of tracheal obstruction and was found to have a polypoid tracheal mass, which was studied by biopsy. Light microscopy showed a tumor composed of small cells with round to oval dark nuclei, clumped chromatin, one to two nucleoli, and small, variable amounts of indistinct pink cytoplasm. In other areas the tumor had a loose, spindle appearance, with some cells showing more elongated nuclei, and fibrillar pink cytoplasm consistent with strap cells. Cross striations were not found. Electron microscopy showed desmosomes and 7 to 10 nm cytoplasmic filaments forming dense bodies. The findings are most consistent with a primitive sarcoma, probably rhabdomyosarcoma. Immunoperoxidase with three monoclonal antibodies for common leukocyte antigen showed diffuse membraneous staining with fresh-frozen tissue. All other lymphocyte and monocyte marker studies were negative. We believe that this case of anticommon leukocyte antigen staining, a rhabdomyosarcoma, represents the first report of a false positive reaction with monoclonal antibody to common leukocyte antigen.

Natural cytotoxicity and interferon production in patients with recurrent respiratory papillomatosis.

The observation that interferon (IFN) therapy causes regression of lesions in some patients with recurrent respiratory papillomatosis (RRP) raises the possibilities that these patients may have abnormalities in endogenous IFN production or in antitumor immune responses stimulated by IFN. We have measured IFN production and natural cytotoxicity (NK activity) in nine patients with RRP, three of whom were receiving exogenous IFN at the time of testing. Production of IFN-gamma induced by the T cell mitogen Staphylococcus enterotoxin A was normal in all patients. Production of IFN-alpha induced by two viruses (Sendai and Newcastle disease viruses) was normal in the six untreated patients, but significantly lower in the patients on IFN therapy. Natural cytotoxicity against K562 target cells, both spontaneous and IFN-stimulated, was normal in all RRP patients tested. Thus, we have shown that the NK-IFN system was intact in untreated patients with RRP. IFN-alpha production in the RRP patients on IFN therapy was low. The significance of these findings is discussed.

Monoclonal antibodies directed against rat tracheal epithelial cells transformed in vitro.

Cloned hybridoma cell lines were obtained by fusion of murine myeloma cells with spleen lymphocytes of either F344 rats or BALB/c mice immunized against the malignant F344 tracheal cell line, 2-10-1. Monoclonal antibodies were selected for their ability to bind to the immunizing cell line and not to normal tracheal epithelial cells. Results from quantitative binding assays indicated that such monoclonal antibodies recognized six epitopes. Each epitope was detected on four other malignant tracheal epithelial cell lines, and was also expressed during early preneoplastic cell passages (i.e. before the cells acquired the ability to produce carcinomas in vivo). Quantitative differences in epitope expression between non-tumorigenic and tumorigenic passages of individual cell lines could not be detected for five of the epitope groups. However, two monoclonal antibodies, recognizing the same epitope, did show quantitative binding differences between non-tumorigenic and tumorigenic cell passages on three of the five cell lines tested. Our results show that carcinogen-altered tracheal cell populations can be distinguished from non-altered cells (by our current assay methods) by use of monoclonal antibodies. The suggest that the antigen expression is an early event associated with the transformation of rat tracheal epithelial cells in culture.

Syngeneic immune response to rat tracheal epithelial cells transformed in vitro by N-methyl-N-nitro-N-nitrosoguanidine.

Two cell lines (2-10-1 and 8-10-2) derived by exposure to primary tracheal explants to MNNG in vitro were not tumorigenic in syngeneic F-344 rats or athymic BALB/c (nu/nu) mice at early passage, but became tumorigenic at late passage. These cell lines are therefore suited to study the expression of neoantigens during neoplastic development. Transplantation resistance to late-passage, tumorigenic cells was indicated in syngeneic rats using an immunization protocol of repeated cell inoculation and tumour ablation. Spleen cells from such animals were reactive in 20h microcytotoxicity assays against neoplastic cell lines, but unreactive to normal tracheal epithelial cells. Similarly, immune spleen cells co-cultivated in vitro for 6 days with irradiated neoplastic cell lines before assay for microcytotoxicity were strongly reactive, whereas co-cultivation with normal epithelial cells did not stimulate reactivity. Antibody to these neoplastic cell lines was demonstrated in sera of tumour-resistant rats by an indirect radiolabelled-antibody binding test and by indirect immunofluorescence. There was no significant binding to normal tracheal epithelial cell outgrowths.

Demonstration of cellular and humoral immunity to transplantable carcinomas derived from the respiratory tract of rats.

Previous studies with respiratory tract tumors in mice have suggested that such tumors are not immunogenic or are only weakly so. To determine whether this is a general characteristic of neoplasias found in the airways of rodents, we investigated seven transplantable carcinomas in rats, six of which originated from tracheal epithelium and one of which orginated from the distal lung. These carcinomas were all of the squamous type and were induced by three different carcinogenic polycyclic hydrocarbons. All of the tumors were shown to be immunogenic, capable of mobilizing cellular and humoral immune responses in isogenic hosts upon immunization. This was demonstrated by induction of transplantation resistance, by Winn's neutralization test, and by the detection of antibodies in the sera of tumor-immune hosts by two independent methods (antibody-dependent cytotoxicity and antibody-binding test). The degree of immunogenicity varied among the tumor lines. The most metastatic tumor was clearly the least immunogenic. The relationship between carcinogenic insult and immunogenicity, as well as the possible nature of the tumor-associated antigens involved, is discussed.