Molecular subclassification determined by human papillomavirus and epidermal growth factor receptor status is associated with the prognosis of oropharyngeal squamous cell carcinoma.

Human papillomavirus (HPV) infection is an indicator of good response to chemoradiotherapy in oropharyngeal squamous cell carcinoma (OPSCC), and epidermal growth factor receptor (EGFR) is a molecular-therapeutic target in head and neck squamous cell carcinoma. Here we investigated the prevalence and prognostic significance of HPV infection and EGFR alteration in OPSCC. We analyzed the presence of high-risk HPV using in situ hybridization, protein expressions of p16 and EGFR using immunohistochemistry, and the EGFR gene copy number gain using chromogenic in situ hybridization (CISH) in 105 cases of OPSCC. The biopsy specimens before chemoradiotherapy were used for these analyses. HPV infection and p16 protein overexpression were detected in 53.3% and 52.4% of the OPSCCs, and each factor was associated with better overall survival (P = .0026 and P = .0026) and nonkeratinizing histology (P = .0002 and P = .0004), respectively. EGFR gene copy number gain (high polysomy or amplification) was detected in 12.4% of the OPSCCs and was correlated with EGFR protein overexpression (P = .0667) and worse overall survival (P < .0001). HPV infection and EGFR gene copy number gain (EGFR CISH positive) were mutually exclusive. The HPV-negative/EGFR CISH-positive OPSCCs had significantly worse overall survival than did the HPV-positive/EGFR CISH-negative OPSCCs and HPV-negative/EGFR CISH-negative OPSCCs (P < .0001 and P < .0001, respectively). The EGFR CISH-negative OPSCCs had favorable prognosis irrespective of HPV infection. Our results suggest that EGFR gene copy number gain-positive tumors represent an HPV-negative, aggressive subgroup of OPSCCs. The molecular subclassification of OPSCCs based on HPV infection and EGFR status may serve as important information for appropriate therapeutic strategy.

Mucous and ciliated cell metaplasia in epithelial linings of odontogenic inflammatory and developmental cysts.

The incidence of mucous and ciliated cells in epithelial linings was examined among odontogenic inflammatory cysts (radicular cysts) and developmental cysts (dentigerous and primordial cysts). Mucous cells were found in 20.8% of all cysts examined, while ciliated cells were found in 11.4%; however, ciliated cells were always accompanied by mucous cells. The incidence of mucous cells in radicular cysts and dentigerous cysts and that of ciliated cells in radicular cysts was higher in the maxilla than in the mandible, while the incidence of mucous cells in primordial cysts and that of ciliated cells in dentigerous cysts and primordial cysts was higher in the mandible than in the maxilla. The present results regarding mucous cells and ciliated cells in the epithelial linings of intraosseous odontogenic cysts indicate a metaplasic origin, but the cause and biological significance of this phenomenon is not known. Mucous cells were present in the surface layer of epithelial linings, and intraepithelial gland-like structures lined with mucous cells were observed in the hyperplastic regions of epithelial linings of several radicular and dentigerous cysts. Such gland-like structures lined by mucous cells in the thickened epithelial lining, which have not been demonstrated previously, resembled the glandular structures of "glandular odontogenic cysts".

Pigmented pleomorphic adenoma, a novel melanin-pigmented benign salivary gland tumor.

This paper reports a pleomorphic adenoma with grossly visible pigmentation resulting in the macroscopic appearance of melanotic lesion in a 33-year-old Japanese male. In addition to the characteristic histopathological features of a benign pleomorphic adenoma, variously formed and -sized cells, many of which were considered to be melanocytes, containing melanin pigment in their cytoplasm, were distributed in the epithelial component. In addition, melanin pigment was deposited in tumor cells of duct structures. Furthermore, condensed secretory substances with marked pigmentation were frequently seen in the tubular lumina. Perusal of the English language literature revealed only two cases of parenchymal pigmentation of salivary gland tumors: both were mucoepidermoid carcinoma. The possible histogenesis of melanocytes in the salivary gland lesions is discussed, though no firm conclusion could be drawn.

Latent form of multiple dermoid cysts in the jaw bone.

Dermoid cysts of the jaw are exceedingly rare, and only six such cases have been documented. The present paper reports a case with multiple microcysts showing histological characteristics of dermoid cyst in the surgically resected mandibular bone. These cysts were located near the inferior border of the mandibular bone, and histologically composed of an inner thin layer of squamous epithelium with marked hyperorthokeratinization and an outer layer of fibrous tissue containing numerous mature sebaceous glands. In addition, a hair follicle-like epithelial sphere was seen in part. The present microcysts suggest that it arises de novo, and one possible cause of jaw cysts could be sequestration of the stomadeal ectoderm that may have been trapped deep in the surface and embedded in the developing mandibular bone during embryogenesis. It may not be possible that such cysts developed from the odontogenic epithelial remnant undergoing dermoid metaplasia.

Sialolith of the submandibular gland with bone formation.

An unusual case of sialolith with bone formation, occurring in the submandibular gland of a 33-year-old woman, is reported. In addition to the irregularly laminated structure of sialolith, sparsely scattered foci of bone tissue were found. Some of them were mature, lamellar bone with lacunae containing osteocytes, endosteum and a bone marrow-like element. Others were immature bone associated with or without multinucleated giant cells. Foci of bone tissue were in contact with caliculi or fibrous tissue, and no epithelial component was seen around them. These observations suggest that bone formation in the present case may be in the nature of pathological ossification, and that in the earlier stage, the bone that is deposited is woven and is replaced through successive remodeling cycles by lamellar bone. This is the first case of sialolith with bone formation, although sialolithiasis is a common disease of the salivary glands.

Expression of the endothelial receptor tyrosine kinase Tie2 in lobular capillary hemangioma of the oral mucosa: an immunohistochemical study.

BACKGROUND: Lobular capillary hemangioma (LCH) usually occurs in the skin or mucous membranes as a rapidly growing red nodule. LCH is one of the most common vascular lesions in the oral mucosa. Tie2 is a novel, human endothelial receptor tyrosine kinase which may play an important role in blood vessel formation. In this study, we investigated its immunohistochemical expression in LCH of the oral mucosa. METHODS: Double immunostaining with anti-CD34 and antialpha smooth muscle actin (SMA) antibodies was performed to characterize the cellular expression of Tie2 in 15 cases of this condition. RESULTS: We found Tie2 immunoreactivity in the ovoid cells only, which were frequently intermingled with alphaSMA-positive cells, especially in the hypercellular portion of LCH. CONCLUSIONS: These results suggest that the expression of Tie2 in ovoid cells and the interaction between ovoid cells and alphaSMA-positive cells play an important part in the development and progression of LCH.

Age-related changes in the D-aspartic acid content of the cranial bones in senescence-accelerated mice (SAM).

We measured the age-related changes in the D/L-aspartic acid ratio (D/L ratio) of cranial bones in two different sublines of senescence-accelerated mice (SAM/Iw): SAMP2/Iw (SAM, prone 2/Iwate) and SAMR1/Iw (SAM, resistant 1/Iwate). In SAM/Iw under 9 months of age, the D/L ratio in SAMP2/Iw was higher than that in SAMR1/Iw (p<0.001). However, in all 12-month old SAM/Iw, whether SAMP2/Iw or SAMR1/Iw, the D/L ratio was higher in males than in females. There were minor differences in the age-related changes in the D/L ratios between different types of cranial bone. In 1-month old SAM/Iw the rectal temperature was similar in both males and females. However from the age of 2 months, there was a divergence, with the rectal temperature measurement in SAMP2/Iw reaching a peak 2 months of age, whereas SAMR1/Iw had the highest temperature readings at 6 months of age. In both SAMP2/Iw older than 2 months, and SAMR1/Iw older than 6 months, the temperature readings tended to gradually decrease with age in both males and females. These results suggest that the differences in D/L-aspartic acid ratios were dependent on the age, gender, and strain of SAM/Iw, but were not dependant on the type of cranial bone studied. It seems likely that these differences may be related mainly to changes in body temperature.