Inflammatory pseudotumor in head and neck

Background

Inflammatory pseudotumor (IPT) is a tumefactive lesion characterized by fibroblastic proliferations and a prominent inflammatory component. It behaves as a locally benign or aggressive lesion, clinically and radiologically mimicking a neoplastic process. Numerous entities can be diagnosed as IPT, from reactive lesions to true neoplasms. The diagnosis of IPT requires further elaboration, and IPT should be distinguished from other similar entities such as inflammatory myofibroblastic tumor and IgG4-related sclerosing disease.

Case summary

We report two cases of IPT arising from the head and neck region. One occurred at the orbit and the other at the parapharyngeal space. Histologically, they showed aggregates of myofibroblasts and inflammatory cells. Immunohistochemically, the number of IgG4-positive cells was less than 40% of the number of IgG positive cells, and the myofibroblastic cells were negative for anaplastic lymphoma kinase. The diagnosis was IPT/not otherwise specified. One patient was treated by systemic administration of corticosteroid and had good response. The other, who was treated by local administration of corticosteroid, partially responded and is currently stable with limited disease.

Discussion

IPT has been reported to occur in various anatomical sites, most commonly in the lungs. The incidence in the head and neck area is extremely rare. Treatment of IPT is controversial and may involve corticosteroids or surgical resection, or both. Other chemotherapeutic agents and radiotherapy may be considered in steroid-resistant patients. The pathological subtype, safety of resection, and safety of corticosteroid use must be included in the decision-making process for treatment.     

Significance of nucleic acid extraction for the performance of COBAS AMPLICOR Mycobacterium-PCR assay]

On an AMPLICOR-PCR assay for the diagnosis of mycobacterial infections, it has been found that approximately 10% of the routinely performed assays appear as indefinable cases with internal control (IC)-negative, which is caused by contaminant PCR-inhibitory substances in the extracted nucleic sample. To decrease the number of indefinable cases, we studied the IC performance of four nucleic acid extraction methods in one manual method(A) and three commercial kits(B, C and D). Thirty samples from 10 kinds of specimens without mycobacterial infections were subjected to the four nucleic extraction methods and the nucleic extracts were compared on PCR-inhibitory. The frequency of IC-negative samples was different among the four methods and the rates were 33.3%(n = 10) in A, 30.0%(n = 9) in B, 16.7%(n = 5) in C and 6.7%(n = 2) in D. In the PCR-inhibitory experiments using serially diluted IC-negative samples, the recovery of IC positivity was also different according to the method used. Although the IC-negative nucleic samples by D method easily became IC-positive at the 1/5 range of dilution, some of the IC-negative nucleic samples by A, B or C method were still IC-negative in the 1/10 range. These results indicate that the occurrence rate of indefinable cases with IC-negative is markedly different in the nucleic extraction method, suggesting that utilizing a suitable nucleic acid extraction method is important when using the diagnostic AMPLICOR-PCR assay.     

Two relatively distinct patterns of ameloblastoma: an anti-apoptotic proliferating site in the outer layer (periphery) and a pro-apoptotic differentiating site in the inner layer (centre)

AIMS: This study was performed to determine the apoptotic behaviour of ameloblastomas by analysing the role of bcl-2 family proteins in ameloblastomas and the location of terminally apoptotic cells in the ameloblastoma epithelial tissues. METHODS AND RESULTS: For immunohistochemistry, tissue sections of 32 patients were treated with an antigen-retrieval METHOD: Primary antibodies against the apoptosis-related proteins, bcl-2, bcl-X, bax, and bak were applied. Besides immunohistochemistry, Western blotting and TUNEL were also performed. Most of the outer layer cells were predominantly stained by the bcl-2 antibody, while most of the inner layer cells were stained by antibodies against the apoptosis-modulating proteins, bax and bak. Among the bcl-2 family, bcl-2 was the most ubiquitously expressed protein in ameloblastomas, while bcl-X was expressed in the greatest concentrations. The major bcl-X protein was bcl-XL. Some of the inner layer cells entered the terminal apoptotic stage, which were revealed by TUNEL. The acanthomatous areas over-expressed the apoptosis-modulating proteins, especially bak. CONCLUSIONS: Ameloblastoma has much more apoptosis-inhibiting protein than the apoptosis-modulating protein. Ameloblastoma has two relatively distinct patterns, an anti-apoptotic proliferating site in the outer layer (periphery) and a pro-apoptotic differentiating site in the inner layer (centre). The acanthomatous area, which was stained strongly by bak antibody and contained numerous terminally apoptotic cells, was considered as the differentiated area.     

The role of dihydropyrimidine dehydrogenase expression in resistance to 5-fluorouracil in head and neck squamous cell carcinoma cells

5-Fluorouracil (5-FU) is one of the most widely used chemotherapeutic drugs to treat cancer patients. However, the presence of drug resistant tumor cells may cause a poor response to 5-FU based chemotherapy. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the degradation of pyrimidine bases and is also responsible for the degradation of 5-FU. In this study, we examined whether DPD expression affects the cytotoxic activity of 5-FU against head and neck squamous cell carcinoma (HNSCC) and the role of DPD in the biological regulation of HNSCC. We constitutively expressed the DPD cDNA in a HNSCC cell line. The effect of DPD expression on in vitro cell growth, cell cycle and 5-FU cytotoxicity was examined. In addition, we also evaluated the association between DPD expression and the proliferation of tumor cells in surgical specimens, and prognosis of the patients with HNSCC. DPD overexpression decreases the cytotoxicity of 5-FU. CDHP, a strong DPD inhibitor, enhances the cytotoxic effect of 5-FU in HNSCC cells in vitro. DPD expression level does not effect cell proliferation and does not seem to have prognostic value in HNSCC. The present results strongly indicate that DPD expression plays an important role in the sensitivity of HNSCC to 5-FU chemotherapy, suggesting the possibility of personalized chemotherapy including the prediction of response and adverse effects.     

Intractable otitis media with eosinophils: Importance of diagnosis and validity of treatment for hearing preservation

This study investigated hearing levels in cases of intractable otitis media with eosinophils and validated the treatment strategy. Medical charts were reviewed retrospectively. The diagnosis was made when the proportion of eosinophils in middle ear secretions exceeded 10%. Twelve patients were identified and treated with an antihistaminergic agent, leukotriene receptor antagonist and topical steroid. The air-bone conductance gap decreased significantly with the relief of subjective symptoms. Bone conduction hearing levels at 4 and 8 kHz were higher than at lower frequencies. There was a significant correlation between subjective symptom duration and bone conduction hearing level at 8 kHz, which diminished with treatment. Compared with suppurative otitis, active otitis with eosinophilia damages high-tone sensory hearing in a time-dependent manner, and antiallergic treatment prevents progression of the high-tone sensory hearing loss. We emphasize the importance of diagnosis and the validity of treatment for intractable otitis media with eosinophils.     

Imatinib induces demethylation of miR-203 gene: An epigenetic mechanism of anti-tumor effect of imatinib

MicroRNA (miRNA) is an important regulator of cellular proliferation, differentiation and death. Leukemia-specific signature of miRNAs suggests that epigenetic dysregulation of miRNAs is important for leukemogenesis. We focused on the role of DNA methylation of miR-203 which targets BCR-ABL1 mRNA. The microarray analysis showed that 48 miRNAs of CpG-rich 212 miRNAs were upregulated over 2-fold after imatinib treatment. Imatinib induced the demethylation of the miR-203 promoter region, resulting in low expression of targeted BCR-ABL1 gene, and loss of proliferation of leukemic cells. In conclusion, demethylation of miR-203 is one of the molecular mechanisms of imatinib-induced inhibition of BCR-ABL1-positive leukemic cells.     

Effects of N-(3-[3-(1-piperidinylmethyl)phenoxy]propyl)-acetoxyacetamide hydrochloride (TZU-0460), a histamine H2-receptor antagonist, on gastric acid secretion and ulcer formation

N-(3-[3-(1-Piperidinylmethyl)phenoxy]propyl)-acetoxyacetamide++ + hydrochloride (TZU-0460) was compared with cimetidine for the effects on gastric acid secretion in dog and rat and on ulcer formation in rat. TZU-0460 as well as cimetidine, given i.v. or p.o., produced a dose-dependent inhibition of acid secretion stimulated by histamine, pentagastrin or carbachol in Heidenhain gastric pouch dogs and gastric lumen-perfused rats. In dog, the relative potencies of TZU-0460 to cimetidine, given p.o. and i.v., were 6.2 and 5.1, respectively, in acid secretion stimulated by histamine, and those gained by i.v. route were 3.5 by pentagastrin and 4.2 by carbachol. In rat, however, relative potencies of TZU-0460 to cimetidine, given i.v., were 2.8, 2.2 and 1.6 in acid secretion stimulated by histamine, pentagastrin and carbachol, respectively. TZU-0460, given p.o., prevented the formation of gastric ulcers induced by exposure to stress, pylorus-ligation, both pylorus-ligation and acetylsalicyclic acid, indometacin or reserpine in rats. TZU-0460 was about twice as active as cimetidine on these experimental models of gastric ulcers. TZU-0460, given p.o., prevented the formation of duodenal ulcer induced by cysteamine in rats, whereas cimetidine failed to prevent it significantly.     

Increased circulating activated T-cells in lung cancer

T-cell activation (Tac) antigens, which are closely associated with the receptors for interleukin 2 (IL 2) and expressed on activated human T-lymphocytes, are found on a small percentage of normal peripheral T-cells. Elevated levels of Tac antigen-positive (Tac+) cells were observed in a high proportion of patients with untreated primary lung cancer assessed by using monoclonal anti-Tac antibody. The mean percentage of Tac+ cells in peripheral blood lymphocytes was 13.1 +/- 6.4 percent in patients with primary lung cancer (n = 67), as compared with 4.3 +/- 1.9 percent in normal controls (n = 30) (p less than 0.001). No significant differences were observed among the cell types of lung cancer examined (adenocarcinoma and squamous and small cell carcinoma). The stages of the disease also showed no significant differences in the development of Tac+ cells. Our results suggest that T-cell-mediated active immune mechanisms against malignant cancer cells are operative in patients with lung cancer, resulting in an increase in activated T-cells in the peripheral blood, although it remains to be elucidated whether these activated T-cells exert a favorable or unfavorable effect on their host.