Stage-dependent Increase in Expression of miR-155 and Ki-67 and Number of Tumour-associated Inflammatory Cells in Folliculotropic Mycosis Fungoides.

Recent studies suggest that folliculotropic mycosis fungoides (FMF), the most common variant of mycosis fungoides (MF), presents with 2 distinct clinicopathological stages: early indolent stage and more aggressive advanced/tumour stage. To further characterize these stages, miR-155 expression was studied with qRT-PCR and found to be significantly higher in biopsies of tumour-stage FMF compared with early-stage FMF and inflammatory dermatoses. There was no statistically significant difference in miR-155 expression between early-stage FMF and early-stage MF, nor between tumour-stage FMF and tumour-stage MF. Immunohistochemical analysis revealed a significantly increased number of dermal Ki-67+ proliferating lymphocytes in tumour-stage FMF, together with an increased number of CD20+ B cells and CD68+ macrophages compared with early-stage FMF. Thus, similar to classic MF, miR-155, Ki-67 tumour cell immunoreactivity, and certain tumour-infiltrating inflammatory cells are differentially expressed in early- vs tumour-stage FMF. The results of this study corroborate the notion that FMF presents with 2 distinct stages.

Metastatic tumors in oral mucosa and jawbones: Unusual primary origins and unusual oral locations.

AIM: To perform clinico-pathological characterization of a large series of oral metastases, collected from 3 main medical centers in Israel and compare findings to data on frequency of primary cancer types in the population. MATERIALS: Pathology archives were searched for cases of metastatic tumors to the oral soft tissues and jawbones, 1990 - 2016. Metastases to the skin of face or to major salivary glands have been excluded. Demographic data and histopathological features were analyzed. RESULTS: Study population included 60 patients, 35 females and 25 males (ratio of 1.4:1). The age range was 17-87 years, mean 67.7 + 14.36 years. Only 3 (5%) patients were under 40 years, the remaining clustered predominantly in the 60-80 year age group. The mean age of females (59 + 13.84) was significantly lower than that of males (67.44 + 14) (p = 0.03). There was an almost equal distribution between the oral soft tissue and the jawbones (48.3% and 51.7%, respectively). The five most common organs from which metastases were distributed to the oral cavity and jawbones combined were kidney (20%), breast (15%), cutaneous (predominately melanoma, 13%), lung (11.7%) and soft tissue-sarcomas (8.3%). For comparison, Israel National Cancer Registry 2013 reported that the most frequent malignancies were breast (25.8%), colorectal cancer (16.3%), lung (12%) and prostate (10%). Malignant melanoma was 6th (5.4%), kidney malignancy was only 9th in frequency (4.2%). Although the gingiva and jawbones were the most frequent locations, some cases presented in unusual locations, (mandibular vestibule, lower lip, posterior dorsal tongue), without any specific clinical feature to suggest metastasis. CONCLUSIONS: The most frequent primary origins for oral metastasis do not correspond to the relative frequency of the primary tumors in the population, indicating that metastatic spread is not a random process. Although the majority of metastasis involves the gingiva and jawbones, any other oral mucosal location might be involved. Thus, in adult/older patients, metastasis from a distant site should be included in the differential diagnosis of oral masses at any oral location, whether the existence of a primary tumor is reported or not.

Fluorescence Lifetime Imaging Microscopy, a Novel Diagnostic Tool for Metastatic Cell Detection in the Cerebrospinal Fluid of Children with Medulloblastoma.

In pediatric brain tumours, dissemination of malignant cells within the central nervous system confers poor prognosis and determines treatment intensity, but is often undetectable by imaging or cytology. This study describes the use of fluorescence lifetime (FLT) imaging microscopy (FLIM), a novel diagnostic tool, for detection of metastatic spread. The study group included 15 children with medulloblastoma and 2 with atypical teratoid/rhabdoid tumour. Cells extracted from the tumour and the cerebrospinal fluid (CSF) 2 weeks postoperatively and repeatedly during chemo/radiotherapy were subjected to nuclear staining followed by FLT measurement and cytological study. Control CSF samples were collected from patients with infectious/inflammatory disease attending the same hospital. Median FLT was prolonged in tumour cells (4.27 ± 0.28 ns; P < 2.2*10-16) and CSF metastatic cells obtained before chemo/radiotherapy (6.28 ± 0.22 ns; P < 2.2*10-16); normal in inflammatory control cells (2.6 ± 0.04 ns) and cells from children without metastasis before chemo/radiotherapy (2.62 ± 0.23 ns; P = 0.858) and following treatment (2.62 ± 0.21 ns; P = 0.053); and short in CSF metastatic cells obtained after chemo/radiotherapy (2.40 ± 0.2 ns; P < 2.2*10-16). FLIM is a simple test that can potentially identify CSF spread of brain tumours. FLT changes in accordance with treatment, with significant prolonged median values in tumours and metastases. More accurate detection of metastatic cells may guide personalised treatment and improve the therapeutic outcome.

Lymphangiomatosis with dental involvement.

BACKGROUND: Lymphangiomatosis characterized by lymphangiomatous proliferation is a rare disease of unknown etiology, which seems to be more aggressive than Gorham-Stout Syndrome, also known as "the vanished bone disease." METHODS AND RESULTS: A woman presented with a lytic lesion in the tibia and multiple lytic lesions in teeth dentin. Upon autopsy, a single lytic bone lesion and fulminant lymphangiomatous proliferation were found in the pleura, pericardium, and peritoneum. The histological findings from a tooth lytic lesion included fibroblastic proliferation interspersed with vascular spaces embedded with fragments of lamellar bone and dentin containing osteoclast like multinucleated giant-cell lined resorption bays. CONCLUSIONS: The histological findings support the notion that hard tissue resorption is conducted by lymphangiomatosis and osteoclastic activity.

The importance of histopathological diagnosis in the management of lesions presenting as peri-implantitis.

PURPOSE: This study is a histopathological analysis of lesions clinically diagnosed as peri-implantitis (PI). MATERIALS AND METHODS: This retrospective study included microscopic findings in 117 peri-implant biopsies from lesions presenting clinical and radiographic features of peri-implantitis. RESULTS: The study group included 117 biopsies, mean age 55.2 years; 60.9% of biopsies were from failing implants during explantation, the remaining from surviving implants. All cases showed microscopic evidence for inflammation; however, although 41% exhibited only nonspecific inflammation, 29.9% exhibited actinomyces-related inflammation, 18.8% pyogenic granuloma (PG), and 10.3% giant cell granuloma (GCG). Differences in implant failure rates between pathological diagnostic groups were not statistically significant. Lesions with simple inflammation could not be distinguished clinically or radiographically from the potentially destructive lesions. CONCLUSIONS: There were no clinical features which could distinguish PI with simple inflammation from potentially destructive lesions mimicking PI, such as GCG, PG, and actinomycosis. However, to control GCG and PG surgical procedures would be recommended, actinomycosis would indicate specific antibiotics, whereas in nonspecific inflammation, these measures may not be indicated. The results of the present study provide evidence for the importance of early microscopic examination of lesions presenting clinically as peri-implantitis, a step toward more accurate diagnosis and improved treatment of PI and lesions mimicking PI.

Metastasis to the jaws as a first manifestation of hepatocellular carcinoma: report of a case and analysis of 41 cases.

INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Local metastasis is common but metastasis to the jaw is rare with 40 reported cases in the English language literature. REPORT OF CASE: We describe a case of a 54-year-old man who, for the past two months, had noticed a rapidly growing facial mass in the posterior mandibular area. The patient was known to be a hepatitis C virus carrier and suffered from liver cirrhosis but the presence of HCC was unknown. METHODS AND RESULTS: The English language literature was searched for documented cases of HCC metastasis to the jaw, applicable data was evaluated. The literature analysis revealed 41 reported cases (including the present case). In most cases (81%) the jaw lesion was the only known metastasis at the time of HCC diagnosis. Clinical presentation occurred up to 2 years before discovery of the jaw metastasis. Patients with HCC jaw metastasis have a poor survival rate with an average of 6.1 months between diagnosis and death. CONCLUSIONS: This study shows that an isolated jaw mass may be the initial presentation of HCC and therefore must be considered in the differential diagnosis, especially in the presence of known liver cirrhosis or chronic viral hepatitis.

Oral neurovascular hamartoma: a lesion searching for a name.

BACKGROUND: Neurovascular hamartoma (NVH), in particular in the oral cavity, is rarely described in the literature. The low number of cases may reflect a genuine rarity of the lesion, or it may be due to its being unrecognized and/or under-reported. OBJECTIVES: To investigate clinical and microscopic features of oral NVH and to define microscopic diagnostic criteria with emphasis on the differential diagnosis. METHODS: Archival cases diagnosed as oral NVH between 1999 and 2011 were retrieved; clinical and demographic data were collected, and a paired morphometric analysis was conducted, with each case of NVH a case of fibrous hyperplasia (FH) from the same oral location. The nerve bundle and blood vessel density were quantified in five microscopic fields at ×100 magnification. RESULTS: The study group included 25 oral NVH, 11 men and 14 women, aged 6-76 years, (mean 44). The majority occurred in the tongue (54%), followed by the buccal mucosa and lower lip (17% each), clinically presenting as asymptomatic 0.25-2.5 cm exophytic masses. Microscopic characteristics included poorly circumscribed masses of closely packed nerve bundles and blood vessels in a loose matrix, containing minimal or no inflammation. The mean nerve bundle density was significantly higher in NVH (4.28 ± 1.26) in comparison with FH (0.27 ± 0.27), (P < 0.00001), and mean vessel density was significantly lower (5.98 ± 1.4 vs. 7.8 ± 1.9, respectively), (P < 0.0003). CONCLUSION: Oral NVH may not be as rare as previously considered. Morphometric analysis demonstrated that NVH presents a separate distinct entity.

The clinical spectrum of Actinomyces-associated lesions of the oral mucosa and jawbones: correlations with histomorphometric analysis.

OBJECTIVES: To characterize the clinical manifestations of Actinomyces-associated lesions of the oral mucosa and jawbones, and to correlate the clinical course and treatment requirements with the findings of histomorphometric analysis. STUDY DESIGN: The study was a 10-year retrospective analysis of archived cases with microscopic identification of Actinomyces infection. Actinomyces colonies were identified, using hematoxylin-eosin, Gram, and periodic acid-Schiff stains, exhibiting filamentous morphology with color variation between center and periphery. Only colonies with adjacent tissue reaction (inflammation, fibrosis) were analyzed. Actinomyces density (AD) was calculated by dividing total number of colonies by tissue surface, Actinomyces relative surface (ARS) was calculated by dividing total bacterial surface by tissue surface. RESULTS: The study included 106 cases (48 male, 58 female; aged 13-84 years, mean 50.5 years). Cases presented a wide clinical spectrum, involving jawbone and/or oral soft tissues. Cases included osteomyelitis associated with bisphosphonates, osteoradionecrosis, osteomyelitis unrelated to radiation or bisphosphonates, periapical lesions, odontogenic cysts, periimplantitis, and lesion mimicking periodontal disease. The AD correlated with median length of antibiotic treatment (R = 0.284; P = .028). CONCLUSIONS: Because we were able to identify 106 such cases, the results indicate that Actinomyces-associated lesions may not be as rare as would be expected from the relatively low number of cases in the literature. Actinomyces-associated lesions presented in a wide spectrum of clinical settings and a variety of contributing factors. Quantitative analysis of the number of bacterial colonies (representing bacterial load) could help in evaluating the aggressive potential of the lesion and help in treatment planning.

Effect of local antimicrobial agents on excisional palatal wound healing: a clinical and histomorphometric study in rats.

AIM: To assess the effect of topically applied antimicrobial agents on palatal excisional wound in rats. MATERIALS AND METHODS: Excisional wounds, 5 mm in diameter, were made in the centre of the palate of 125 Wistar male rats. In four experimental groups, chlorhexidine digluconate (CHX) 0.12% solution, 1% CHX gel, phenolic compounds solution (Listerine), amine/stannous fluoride solution (Meridol) and saline solution as a control group were applied daily for 1 min. The wound area was measured photographically and the epithelialization rate was determined histologically at 3, 7, 14 and 21 days post-surgery. RESULTS: The mean wound area and mean distance between the epithelial margins decreased significantly with time (p<0.001) in experimental and control groups, with the greatest wound area reduction and rate of epithelialization on day 14. A significantly superior rate of wound epithelialization (p=0.03) was presented following use of 1% CHX gel and Listerine and a comparatively inferior one when the Meridol solution was applied. CONCLUSIONS: Each tested antimicrobial agent when applied on an excisional wound with epithelial and connective tissue deficiency did not have a negative effect on the rate of wound closure. The best results were achieved with 1%CHX gel and Listerine.

Solitary and multifocal oral melanoacanthoma.

BACKGROUND: Oral melanoacanthoma is a rare pigmented lesion characterized by sudden appearance and rapid radial growth, mimicking malignant melanoma. Oral melanoacanthoma may present as a solitary or multifocal lesion; however, the characteristics of these two clinical variants have never been addressed. In this study, we present an unusual case of multifocal oral melanoacanthoma and analyze cases of oral melanoacanthoma reported in the literature, with special emphasis on multifocal lesions. METHODS: A thorough MEDLINE search of the literature for cases of oral melanoacanthoma was performed. The demographic and clinical data, histologic features, and immunohistochemical findings were extracted from the full-text articles. RESULTS: The literature search yielded 52 patients with 67 lesions. The addition of our case increased this number to 53 patients with 72 lesions, 43 of whom had solitary lesions and 10 of whom had multifocal lesions. There was a female predominance amongst the patients with solitary oral melanoacanthoma (3 : 1), whereas multifocal oral melanoacanthoma showed an equal gender distribution (1 : 1). Multifocal lesions tended to occur more frequently on the palate, and solitary lesions on the buccal mucosa. CONCLUSIONS: Multifocal oral melanoacanthoma appears to demonstrate some demographic and clinical variations from the solitary type of lesion.

Marginal bone loss pattern around hydroxyapatite-coated versus commercially pure titanium implants after up to 12 years of follow-up.

PURPOSE: The purpose of this study was to compare the marginal bone loss (MBL), complications, and 12-year survival rates of commercially pure titanium (cpTi) and hydroxyapatite (HA)-coated implants placed in the maxilla. MATERIALS AND METHODS: The study group consisted of 120 patients (77 women, 43 men) treated from 1988 to 1997. A total of 388 implants (156 cpTi and 232 HA-coated) were placed in the maxilla. There were 126 immediate (32.5%) and 262 (67.5%) nonimmediate implants. Patients were evaluated annually. Mean follow-up was 60 +/- 32.3 months. MBL was measured on radiographs using the implant threads as the dimensional reference. MBL, complications, and 12-year survival and success rates were correlated with implant coating, time of implantation, implant dimensions, and position in arch. RESULTS: Total mean MBL was 1.07 +/- 2.16 mm. MBL was significantly lower with cpTi implants (0.55 +/- 1.04 mm) compared to HA-coated implants (1.51 +/- 2.71 mm) (P < .001). No statistical difference in regard to MBL was found between immediate and nonimmediate implants (0.86 +/- 1.8 mm vs 1.16 +/- 2.3 mm). The total 12-year survival rate was 91.4%. HA-coated implants had a significantly higher 12-year survival rate than cpTi implants (93.2% vs 89%; P < .03). Nonimmediate implants had a significantly higher failure rate (8.2%) than the immediate implants (1.3%) (P < .009). No correlation was found between type of implant coating and late implant failure. DISCUSSION: Immediate implants can serve as a predictable option, providing higher survival and success rates. HA-coated implants tended to fail less during the surgical phase, but had higher mean MBL compared to cpTi implants. CONCLUSIONS: HA-coated implants had greater MBL than cpTi implants but a higher 12-year survival rate. Immediate implants had a lower failure rate than the nonimmediate implants in this study population.