Avraham Hirshberg

Glandular odontogenic cyst: a challenge in diagnosis and treatment

The present review analyzes the accumulated data from all cases of glandular odontogenic cyst (GOC) reported in the English language literature. In the 20 years since it was first described, 111 cases have been reported, an incidence of 0.2% of odontogenic cysts. The age range is 14-75, mean 45.7, with a M/F ratio of 1.3:1. GOC has a predilection for the mandible (70%), affecting both anterior and posterior areas. It is typically radiolucent, well defined, either unilocular (53.8%) or multilocular (46.2%). Frequent perforation (61%) and of thinning of cortical plates (24.4%) indicate aggressiveness. Sufficient follow-up indicates that 30% of cases can recur. Treatment by enucleation or curettage carries the highest risk for recurrence, especially in large and multilocular lesions. Peripheral osteoectomy or marginal resection can eliminate the risk. Defined criteria for microscopic diagnosis are described, which in addition to Ki67 and p53 can help in differentiating GOC from lesions with histological similarities (cysts with mucous metaplasia, botryoid and surgical ciliated cysts, low-grade mucoepidermoid carcinoma). Definite diagnosis may not be possible in small incisional biopsies due to the focal presentation of characteristic features required for diagnosis. There is now evidence to support an odontogenic rather than a sialogenic origin.

Calcifying Odontogenic Cyst Associated With Odontoma: A Possible Separate Entity (Odontocalcifying Odontogenic Cyst)

The calcifying odontogenic cyst (COC) has been reported to be associated with odontoma in about 24% of cases. Separation of the cases of COC associated with odontoma (COCaO) may lead to a better understanding of the pathogenesis of this lesion. A screen of the literature revealed 52 cases of COCaO. The male to female ratio was 1:1.9, with a mean age of 16 years. The most common location was the maxilla (61.5%). The radiographic appearance of most cases (80.5%) was of a well-defined, mixed radiolucent-radiopaque lesion. Histologically, the lesions usually consisted of a single large cyst (which is similar to simple COC) with tooth-like structures that appear to be an integral part of the lesion, giving the impression of a single lesion. In addition to the unique histologic features, differences in gender and in distribution were found between the cases of COCaO and those of simple COC. COCaO may be regarded as a separate entity and classified as a benign, mixed odontogenic tumor. The term odontocalcifying odontogenic cyst is suggested.

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.

Diffusion Reflection A Novel Method for Detection of Oral Cancer

Intraoperative detection of residual disease in oral cancer may reduce the high rate of recurrences. The aim of the present study was to evaluate the detection sensitivity of diffusion reflection (DR) measurements of bioconjugated gold nanorods (GNRs) to cancerous sites in a rat model of oral squamous cell carcinoma. We used hyperspectral spectroscopy and DR measurements of GNRs bioconjugated to slide specimens of rat tongues where squamous carcinoma was induced by 4NQO (4-nitroquinoline-N-oxide). Wistar-derived male rats were used: 6 were sacrificed at wk 32 to 37 following 4NQO administration (experimental rats), as were 2 control rats at wk 32 and 36. The detection results were compared with histopathology: 19 sites of cancerous changes were identified microscopically (11 invasive cancer and 8 carcinoma in situ [CIS]). The GNRs attached selectively to areas of carcinomatous changes with an intensity exceeding 17 intensity units at 780 nm (overall specificity, 97%; overall sensitivity, 87%) when the hyperspectral spectroscopy system was used. The resulting DR slopes of the reflected intensity showed an increase of >80% in areas of invasive cancer and an increase of >30% in the CIS sites. The resulting intensity units of the hyperspectral spectroscopy system in the invasive cancer significantly exceed those of the CIS (t test, p = .0002; Mann-Whitney, p = .0024). The results demonstrate a great potential of the direct DR scanning as a new and simple tool for detecting residual disease intraoperatively.

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.

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.

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.

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.