Activated cytotoxic T-lymphocyte immunotherapy is effective for advanced oral and maxillofacial cancers.

Conventional cancer treatments are surgery, radiotherapy, and chemotherapy, but treatment efficiency is insufficient and cancer recurrence is common. Immunotherapy has been added as an important cancer treatment component, but no reports on its efficacy in oral and maxillofacial cancers exist. We evaluated the clinical efficacy of adoptive immunotherapy using ex vivo-activated cytotoxic T lymphocytes (CTL) in the treatment of 7 patients with advanced oral and maxillofacial cancers with stage IV disease at diagnosis. The mean follow-up period was 26.2 months. Phenotype of the lymphocyte assay revealed that the percentage of CD4(+) T cells decreased and that of CD8(+) T cells increased among infused lymphocytes compared to that in unstimulated peripheral blood mononuclear cells (PBMCs), and infused lymphocytes produced a significantly higher level of IFN-γ than PBMCs or tumor cells alone. In a representative patient who refused surgery tumor regression was confirmed after CTL infusion. Computed tomography clearly indicated a significant reduction in tumor size followed by the complete disappearance of the tumor. Histological examination showed that the cancers in patients receiving CTL therapy were heavily infiltrated with lymphocytes. The other 2 patients who received CTL therapy as adjuvant therapy showed neither recurrent disease nor new disease lesions. The 1-year survival rates showing response and those with progressive disease were 100 and 25%, respectively. Moreover, no significant adverse reactions were reported during the study period. CTL therapy remains in the early stages of treatment options, but it has potential as a valuable treatment and improvement of quality of life for patients with otherwise incurable cancers.

Polymorphous low-grade adenocarcinoma of maxillary alveolus metastasising to the abdomen: the role of immunomarkers in diagnosis.

Polymorphous low-grade adenocarcinoma (PLGA) originating mostly in the minor salivary glands of the posterior hard and soft palate is characterised by its indolent growth and a slower rate of metastasis. Seldom does the PLGA present an aggressive behaviour and demonstrate distant metastasis, as in the present case where a 73-year-old female patient with a swelling in the maxillary alveolus was diagnosed as PLGA exhibiting high-grade transformation, subsequently metastasizing to the abdomen and lungs. The importance of immunomarkers, c-kit and ki-67 in deciphering the clinical behaviour of this PLGA is highlighted. Distant metastasis to the abdomen has not yet been reported; hence, this case of PLGA emphasises the importance of immunohistochemistry in assessing its aggressiveness and understanding a novel aspect of its pathogenesis.

[Oral Burkitt lymphoma in an immunocompetent patient]. / Lymphome de Burkitt buccal chez une enfant immunocompétente.

We report a case of Burkitt lymphoma of the jaws in an immunocompetent adolescent, revealed by intraoral swelling. An orthopantomogram showed multiple osteolytic lesions. Biopsy revealed Burkitt lymphoma. The disease was treated with chemotherapy. Complete remission was attained 15 months after the end of treatment. Burkitt lymphomas accounts for 30-40% of all non-Hodgkin lymphomas in children, with diagnosis confirmed by histology. Immunophenotyping completes the diagnosis by identifying the presence of B markers. Chemotherapy is currently the main treatment of BL, because of the high chemosensitivity of the tumor and its low radiosensitivity. Overall survival in localized stages is close to 100%.

Migration of tumor antigen-pulsed dendritic cells after mucosal administration in the human upper respiratory tract.

Tumor-specific peptide-pulsed dendritic cells (DC) were administered via different routes to a group of patients with head and neck cancers. The migration and homing patterns of such antigen-stimulated cells was carefully studied employing single photon emission computed tomography (SPECT). The DC administered directly into the nasal submucosa quickly migrated very rapidly to the regional neck lymph nodes in the neck. However, after inoculation of the cells into the palatine tonsils, the DCs remained close to the site of administration and did not migrate to the regional lymph nodes or to other mucosal regions. After nasal submucosal administration of the DC, tumor-antigen-specific cytotoxic T cells were detected in the ipsilaterals but not in the contra lateral lymph nodes. These results suggest that after antigen processing, the regional lymph nodes serve as inductive sites for development of mucosal immune responses and for induction of memory cells during the local immunological responses in the nasopharyngeal-associated lymphoid tissue in man.

CD34 expressing ameloblastic fibrosarcoma arising in the maxilla: a new finding.

Ameloblastic fibrosarcoma (AFS) is a rare malignant tumor of the jaw. The malignant mesenchymal component of AFS has been described as 'fibroblast-like', although little is known about the immunophenotype, except for vimentin expression. Here, we present a case of AFS in a 62-year-old woman. The mesenchymal component displayed the features of either dermatofibrosarcoma protuberans or fibrosarcoma, and was positive for CD34. This is the first reported case of CD34 expressing AFS in the maxilla.

[Expression of nucleolar organizer regions associated proteins of T lymphocytes in the patients with oral and maxillofacial tumors].

OBJECTIVE: To study the Ag-NORs expressive character of T lymphocyte in patients with oral and maxillofacial tumor and evaluate its diagnostic value for the patients. METHODS: Nucleolar organizer regions(NORs) of T lymphocyte from 86 normal adults, 102 patients with oral and maxillofacial benign tumors and 87 patients with oral and maxillofacial malignant tumors were analyzed through KL imaging system. RESULTS: There was significant difference among normal adults, benign and malignant patients (P < 0.01). Their average I.S% values were 7.87 +/- 0.12, 5.72 +/- 0.14, 4.19 +/- 0.13, respectively. CONCLUSION: The expression of Ag-NORs of T lymphocyte has definite relation with oral and maxillofacial tumors; detection of Ag-NORs might play valuable in diagnosis of oral and maxillofacial tumors.

Association of tapasin and HLA class I antigen down-regulation in primary maxillary sinus squamous cell carcinoma lesions with reduced survival of patients.

PURPOSE: The purpose of this research was to assess the frequency and clinical significance of antigen processing machinery component and HLA class I antigen down-regulation in primary maxillary sinus squamous cell carcinoma (SCC) lesions. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tumor biopsy specimens at pretreatment status from 70 Japanese patients with maxillary sinus SCC were examined for HLA class I antigen and endoplasmic reticulum chaperone molecule expression using an immunohistochemical method. Furthermore, the results of immunohistochemical staining of the lesions were correlated with their histopathological characteristics and with the clinical course of the disease. RESULTS: Calnexin, ERp57, calreticulin, tapasin, and HLA class I antigens were down-regulated in 13, 13, 24, 69, and 78% of the 70 lesions tested, respectively. Both tapasin and HLA class I antigen expression were significantly correlated with the number of infiltrating CD3(+) T cells into tumor lesions (P < 0.01); furthermore, tapasin expression was significantly correlated with tumor differentiation (P = 0.024). Tapasin expression was correlated with that of HLA class I antigens (P < 0.01). Furthermore, tapasin and HLA class I antigen down-regulation in SCC lesions was significantly associated with reduced survival of patients (P = 0.01 and P = 0.002, respectively). Multivariate Cox proportional hazards model analysis identified HLA class I antigen down-regulation as an independent prognostic marker. CONCLUSIONS: Tapasin expression appears to be associated with HLA class I antigen expression in primary maxillary sinus SCC lesions. Furthermore, defects in tapasin and HLA class I antigen expression in primary maxillary sinus SCC lesions may play a role in the clinical course of the disease, because these defects were associated with poor prognosis.

Basaloid squamous cell carcinoma of the maxilla: a case report and immunohistochemical analysis.

Basaloid squamous cell carcinoma (BSCC) is a recently recognized high-grade tumor with a propensity for nodal as well as systemic metastasis and can arise from different anatomic locations. The differential diagnosis includes adenoid cystic carcinoma, small cell neuroendocrine carcinoma and squamous cell carcinoma. Monoclonal antibodies reactive with cytokeratin (34betaE12, AE3, pancytokeratin), as well as other cellular antigens (vimentin [VIM]; synaptophysin [SYNF]; chromogranin A [ChA]; neuron-specific enolase [NSE]; S-100, desmin, smooth-muscle actin [SMA]), were used in an immunoperoxidase method with paraffin-embedded tissue to phenotypically characterize a case with features of BSCC arising in the maxillary sinus. Neoplastic cells reacted with the high-molecular-weight cytokeratin antibody 34betaE12, as well as with other antikeratin antibodies, but failed to react with the antibodies VIM, desmin and SMA and showed variable immunoreactivity for NSE, SYNF and S-100. The staining pattern for NSE was diffuse and intense and reactivity for ChA was inconsistent.

Oral plasmablastic lymphoma in previously undiagnosed HIV disease.

Non-Hodgkin's lymphoma is the second most common HIV-associated malignancy. This report details a case of the recently described entity plasmablastic lymphoma of the mouth in a patient who was later found to have severe HIV disease. The tumor manifested as a large ulcerated mass of the left maxillary alveolus, causing bony destruction and tooth mobility. Histologic examination of lesional tissue revealed a lymphoid tumor with a high proliferation rate containing lymphoplasmacytoid cells that were reactive to the plasma cell marker VS38c but not to CD20 or CD79a; these are features of the recently reported non-Hodgkin's lymphoma termed plasmablastic lymphoma. This is only the second report of an unusual tumor that has a predilection for the orofacial tissues.

[Burkitt lymphoma in Cameroon children: descriptive and clinico-anatomical aspects]. / Lymphome de Burkitt chez l'enfant au Cameroun: aspects descriptifs et anatomocliniques.

This retrospective study is armed to indicate the descriptive and pathological aspects of children Burkitt lymphoma in Cameroon. It was performed on a 4 year period between July 1988 and July 1992. Children from 0 to 15-year-old who were hospitalized and who had histologically provern Burkitt lymphoma were included. There were 39 patients, that is 27% of all malignant tumors in children during this period. Twenty-four were boys and 15 were girls; the median age was 90 months (+/-46) (range from 3 to 180 months). All children had Plasmodium falciparum infection. EBV serology was positive in 18 patients out of 25 (72%), 14 (36%) had a good nutritional status, the 25 other patients suffered malnutrition. Tumor localizations were: maxillary in 29 (74%) patients, abdominal in 7 (18%), other in 3 patients. Clinical stages according to Murphy classification were: stage I in 6 (15%) patients, II in 3 (8%), III in 20 (51%) and IV in 10 (26%). It is concluded from this series that clinical aspects and histological pattern in children Burkitt lymphoma in Cameroon are not different from what is observed in other endemic areas.

Prevalence of EBV RNA in sinonasal and Waldeyer's ring lymphomas.

A high incidence of a T cell phenotype of sinonasal lymphomas in other Asian countries has been associated with a high incidence of Epstein Barr virus (EBV) infection. We analyzed 13 sinonasal and 18 Waldeyer's ring lymphomas for the prevalence of EBV encoded RNA (EBER) using a sensitive and specific in situ hybridization. In addition, we examined the relationship of histologic findings and immunophenotype as well as the location of the lymphomas to the presence of EBV. The EBER was detected in each of 12 sinonasal lymphomas with a T cell immunophenotype. One B cell sinonasal lymphoma was EBER negative. Four of 18 Waldeyer's ring lymphomas were positive for EBER, including two T cell lymphomas. Two of 16 B cell Waldeyer's ring lymphomas were EBER positive. Morphologically, 11 of 20 diffuse large cell lymphomas, 2 diffuse mixed small and large cell lymphomas, 2 of 4 immunoblastic lymphomas and 1 lymphoplasmacytic lymphoma were EBER positive. Four follicular large cell lymphomas were EBER negative. A characteristic angiocentric or angiodestructive pattern was found in most T cell lymphomas and EBER positive cases. These findings indicate that EBV infection is more strongly associated with the T cell immunophenotype, angiocentric pattern and sinonasal location of the lymphoma.

Establishment of a human cell line from maxillary squamous cell carcinoma and its biological features as a stimulator for induction of cytotoxic T lymphocytes.

A cancer cell line named FS-1 was established from maxillary cancer of which histological diagnosis was well differentiated squamous cell carcinoma (SCC). The HLA class I typing showed that FS-1 expressed the same HLA class I antigens as those of the host lymphocytes. The chromosome analysis and nuclear DNA contents suggested that FS-1 was not a normal human cell. FS-1 is characteristic of SCC in that it grows adhesively on the surface of a culture flask. The structure of tumor tissue obtained from FS-1-transplanted nude mice is very much like the original tissue of SCC. The SCC-antigen was determined in the culture supernatant of FS-1. Autologous tumor killing activity was induced from peripheral blood lymphocytes of some patients suffering from head and neck SCC after mixed lymphocyte tumor culture with FS-1. Thus, FS-1 can serve as a useful allogeneic stimulator of SCC for induction of autologous tumor killing activity.

Superoxide anion generation from peripheral blood neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine in oromaxillary cancer patients.

Superoxide anion (O2-) generation levels in peripheral blood neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine were evaluated in patients with oromaxillary cancer. The levels in patients with benign tumors were nearly equal to those of normal controls. Patients with squamous cell carcinoma in stage I and II had levels that were widely distributed. On the other hand, O2- generation levels in the advanced stages (III and IV) of squamous cell carcinoma showed lower levels than those of controls (P < .01). All cases of oromaxillary carcinoma showed low levels of O2- generation within 1 month before death compared with controls (P < .01). The generation levels of O2- in the posttreatment period were lower than those before combination cancer treatments. Among cancer treatments such as chemotherapy, surgery, and irradiation, the latter had the strongest effects on O2- generation. These results suggest that low levels of O2- generation by peripheral blood neutrophils may reflect a worsening status of oromaxillary cancer patients.

Identification of colony-stimulating factor activity in patients with malignant tumors associated with excessive leukocytosis.

We have tried to demonstrate and identify colony-stimulating factor (CSF) activity in the plasma, pleural fluid, ascites or culture supernatant of tumor cells in 11 patients with malignant tumors associated with unexplained persistent leukocytosis. The specimens were treated with anti-granulocyte (G)-CSF or anti-granulocyte/macrophage (GM)-CSF monoclonal antibodies, then added to GM-progenitor (CFU-GM) cultures without exogenous CSFs. In all patients, untreated specimens generated CFU-GM-derived colonies, and colony formation was clearly inhibited by only one of the two antibodies, indicating the presence of either G-CSF or GM-CSF in the specimens. Furthermore, we measured the concentrations of G-CSF or GM-CSF in the specimens using an enzyme-linked immunosorbent assay, and confirmed the results by CFU-GM assay. Two patients were shown to have GM-CSF-producing tumors, while the other patients were G-CSF-producing. These assays are useful in identifying CSF activity in patients with CSF-producing tumors.

[Second solid tumors in childhood. Review based on three cases]. / Segundos tumores sólidos en la infancia. Revisión a propósito de tres casos.

As children with cancer survive longer, the incidence of second malignant neoplasms has increased considerably. We describe here three cases of second solid tumors after 12, 8 and 2 years of initial diagnosis of cancer: one osteosarcoma of left maxilla in a previously treated child with bilateral retinoblastoma, a temporal astrocytoma associated with acute lymphoblastic leukemia and a glioblastoma multiforme in a girl with neurofibromatosis de Von Recklinghausen, after Non Hodgkin lymphoma, respectively. We review the literature about the influence of genetic, immunologic and therapeutic factors involved in the appearance of these second tumors.

Head, neck, and maxillofacial childhood Burkitt's lymphoma: a retrospective analysis of 31 patients.

Thirty-one children with Burkitt's lymphoma of the head, neck, and maxillofacial region diagnosed between 1976 and 1988 were reviewed. The age range was 2 to 17 years (median, 7.2 years), and 77.4% were males. The most common presenting symptoms were detectable masses, floating and/or painful teeth, enlarged cervical lymph nodes, sore throat, and neurologic signs. The predominant primary tumor sites were the jaws and tonsils. All patients were staged by a clinical staging system, 17 of them having stage I-II, and 14 stage III-IV. Levels of lactate dehydrogenase and ferritin were the only significant laboratory parameters correlating with initial staging and disease-free survival. Radiologic features in the jaws were poorly circumscribed destructive lytic lesions with migration and crypt destruction of unerupted teeth buds. Complete disappearance of these findings was noted after successful chemotherapy and clinical regression of the tumor. Eighteen (58.1%) patients attained complete remission with a follow-up of 5 to 100 months. Stage was the most significant variable affecting outcome, with 90.2% disease-free survival of stage I patients, 72.4% of stage II, and 18.2% of stage III-IV. Based on these results, it is concluded that localized (stage I and II) Burkitt's lymphoma is responsive to chemotherapy and thus has a favorable prognosis.

The investigation of serum and salivary, immunoglobulin levels in patients with head and neck region cancer.

Tumor immunology has been studied in animal experiments. The studies of Prehn and Main in the year 1957, have been pioneer studies. The early diagnosis of cancer, the prognosis, proflaksia and treatment has been studied in several immunological experiments and is still being studied. In the investigations being made before the Second World War mostly the Conditions after the immunological answer has been studied from the beginning where the antigen enters the body and which organs and tissues the antigen enters, which cells do recognise and how the immunological answers is formed. By solving the secrets of the immunological system, oto-immunological, allergic diseases and cancer would be able to be treated easier it is possible that much more better results will be able to be reached with organ transformation.

Multiple myeloma presenting as localized expansile jaw tumour.

Myelomatous involvement of the maxilla is an exceptionally rare occurrence, and the presentation of the lesion as an expansile jaw bone tumour has not been reported. 2 cases, one with a maxillary lesion, the other with a mandibular lesion are presented, both of which illustrate gross bone expansions. Additionally, 1 case presented with a rare biclonal IgG kappa and IgG lambda light chain secreting myeloma. Relevant clinical, immunological, histological, biochemical and histochemical features are presented and discussed, and suggestions pertaining to surgical management made.