Multiple oral squamous epithelial lesions: are they genetically related?

The development of second primary tumors (SPTs) in patients with head and neck squamous cell carcinoma (HNSCC) has become an increasingly important factor in clinical treatment decisions. Currently, clinical and histologic parameters are used to determine whether or not SPT is present. Recent studies suggest that many SPTs in the upper aerodigestive tract have a common clonal origin, challenging the longstanding multiclonal origin concept. To determine genetic relationships among multiple oral cancerous and precancerous lesions (MOCP), we analysed 100 lesions from 26 Japanese patients. Lesion development was synchronous and metachronous. We looked for patterns of microsatellite alterations (MA) using seven markers at chromosomes 3p14, 9p21, and 17p13, where MA occurs early in oral carcinogenesis. Loss of heterozygosity (LOH) was found in 52.6% (41/78), 62.5% (60/96), and 59.3% (32/54) of informative MOCP at 3p14, 9p21, and 17p13, respectively. Microsatellite instability (MI) was observed in 11, 26 and 13% of the samples at 3p14, 9p21, and 17p13 markers, respectively. Patterns of MA were concordant in only nine (14%) of 63 lesions from four (18%) of 22 patients who initially presented with noninvasive lesions. However, two of four patients with invasive cancer as indexed lesion showed 16 (43%) clonally related MOCP among 37 lesions (P=0.003). The results suggest that the majority of MOCP arise from clonally independent cells affected by field cancerization. However, the probability of mucosal spread of clonal malignant or premalignant cells may increase along with malignant progression.     

Increased serum soluble Fas ligand associated with recurrent B-cell non-Hodgkin's lymphoma after autologous peripheral blood stem cell transplantation.

Fas-ligand (FasL) is a member of the tumor necrosis factor family and transmits apoptotic cell death signal by binding to its receptor, Fas. FasL is expressed on the cell surface of activated T-cell and natural killer (NK) cell. It has been shown that the FasL can be released from the cell surface by metalloproteinase. The serum soluble FasL (sFasL) is increased in some patients with NK cell lymphoma/large granular lymphocytic leukemia. We have recently seen a patient with recurrent B-cell lymphoma accompanied with an increased serum sFasL level after autologous peripheral blood stem cell transplantation. The sFasL was markedly decreased with the tumor regression induced by the chemotherapy. We present here the first case of an elevated serum sFasL level associated with B-cell lineage malignancy and discuss the possible clinical value of sFasL.     

Expression of cell cycle regulating proteins in an unusual transformation of mantle cell lymphoma

We describe here two patients with mantle cell lymphoma (MCL) who after a few years, developed to the diffuse large cell lymphoma (DLCL) (anaplastic centrocytic lymphoma) growing in a diffuse sheets without the classical MCL component. In both the initial and second biopsy specimens, in each case, tumor cells were positive for cyclin D1, sIgM, sIgD, and CD5, but were negative for CD10 and CD23. In a study of immunoglobulin heavy chain (IgH) gene rearrangement, using the polymerase chain reaction (PCR) method, the products obtained from each paired biopsy tissue sample were the same size, and in one case had an identical sequence to the non-mutated VH gene. Immunohistochemistry was used to examine the expression of p53, p27Kip1 and cyclin E. Interestingly, there was clear overexpression of p53 protein in case 1 but not in case 2, compared with other typical MCL cases. The expression of p27Kip1 in the second biopsies of each case was decreased compared with those in the initial biopsies. In case 2, however, p27Kip1 was clearly expressed in the first and second biopsies, in contrast to other typical MCL cases. Thus these 2 cases demonstrate not only that the variant form of MCL may arise de novo, but also that MCL may transform to DLCL at the time of relapse. Although the mechanism of tumor progression/transformation is still poorly understood, the overexpression of p53 or p27Kip1 may be linked to a cellular mechanism involved in the development of the variant form of MCL.     

Long-term third chronic phase of chronic myelogenous leukemia maintained by interferon-alpha and methotrexate

The prognosis of blast crisis (BC) of chronic myelogenous leukemia (CML) is extremely poor despite many efforts to induce remission with chemotherapy. We have recently treated a long-surviving CML patient who developed three separate episodes of BC. The administration of interferon-alpha (IFN-alpha) alone as maintenance therapy was incapable of preventing BC, which occurred twice in the first 2 years after the diagnosis of CML. Intensive chemotherapy using enocitabine, mitoxantrone, and etoposide was effective to induce hematological remission. Thereafter once per week oral administration of methotrexate (10-15 mg/week) was combined with IFN-alpha after the second BC. This treatment succeeded in obtaining a major cytogenetic response and keeping him in third chronic phase for 5 years until the last most recent third BC. We present here the rare clinical course of the patient, review the past literature, and discuss the efficacy of the combination of IFN-alpha and methotrexate in this disease.     

Results of tracheobronchoplasty for bronchogenic carcinoma

Tracheobronchial reconstruction is a safe and effective procedure for patients with the neoplasms of low grade malignancy and bronchogenic carcinoma. We present herein a series of 18 cases that had tracheobronchial reconstruction, and discuss a postoperative complication and prognosis. From 1981 to 1997, 18 patients (2.8%) of 647 cases had tracheobronchial reconstruction with mediastinal lymph node dissection. The average age of the 13 males and 5 females, was 61 (range 51-72) years. We analyzed clinical features, postoperative complication and prognosis. Seventeen patients underwent sleeve lobectomy and one lobectomy with carinal reconstruction (Barkley's montage type). There were 13 squamous cell carcinomas, and one each of adenocarcinoma, typical carcinoid, adenoid cystic carcinoma, mucoepidermoid carcinoma and undifferentiated carcinoma. Stage was IA in 3, stage IB in 6, stage IIB in 3, stage IIIA in 5, and stage IIIB in 1 patient. Curative resection was achieved in 11 patients and non-curative resection in 7 patient who had radiotherapy. Six patients (33.3%) had postoperative complications. Five-year survival and mean survival time were 92.3% and 126 months, respectively. Tracheoplasty group had significantly better prognosis than pneumonectomy group or lobectomy group (p<0.01). This study suggests that tracheobronchoplasty is a more useful procedure than pneumonectomy for lung cancer.     

Metabolic and Morphologic Characteristics of Adipose Tissue Associated with the Growth of Malignant Tumors

Changes in total body fat and the metabolic and morphologic characteristics of adipose tissue were sequentially investigated in individual rabbits implanted with VX2 tumors to elucidate the pathology of the fat reduction in animals with malignant tumors as compared with that of diet-restricted rabbits. Lipogenesis in normal, VX2–implanted, and diet-restricted rabbit groups on day 40 after the start of the experiments was 19.1±2.9, 13.3±3.5, and 41.7±6.0×l0⁵ cpm/g/h, respectively, and glycerol liberation by their adipose tissue was 199±21, 528±94, and 301±45 nmol/g/h, respectively. In addition, apoptotic cells were noted in the adipose tissue of VX2–implanted rabbits on days 20–30 after implantation, but not in diet-restricted rabbits. The results showed clear differences between the total body fat reduction profiles of VX2–implanted rabbits and diet-restricted rabbits, suggesting a characteristic lipid metabolism with enhanced lipolysis and diminished lipogenesis in VX2–implanted rabbits. The results strongly suggest that adipocyte apoptosis might be involved in these phenomena.