J.E. van der Wal

A review of the recent literature regarding malignant transformation of oral lichen planus

On the basis of a literature review of the period 1950-1976, Krutchkoff et al questioned the possible premalignant nature of oral lichen planus. Their criticism was largely based on insufficiencies of data in support of the initial diagnoses of the condition. In this article, a review of the literature from the period 1977-1999 has been described; the criteria used were those of Krutchkoff et al. Thirty-three (34%) of 98 reported cases were accepted as having sufficiently documented evidence of malignant transformation of oral lichen planus. Although this percentage is somewhat higher than the percentage reported by Krutchkoff et al, there apparently remains a need for uniformly accepted criteria to establish a firm diagnosis of oral lichen planus. Only when such criteria are available will it be possible to conduct long-term prospective studies on the suggested possible premalignant nature of oral lichen planus.

Clinical and Histologic Evidence of Salivary Gland Restoration Supports the Efficacy of Rituximab Treatment in Sjogren's Syndrome

OBJECTIVE To assess the effect of rituximab (anti-CD20 antibody) therapy on the (immuno)histopathology of parotid tissue in patients with primary Sjögrens syndrome (SS) and the correlation of histologic findings with the flow rate and composition of parotid saliva. METHODS In a phase II study, an incisional parotid biopsy specimen was obtained from 5 patients with primary SS before and 12 weeks after rituximab treatment (4 infusions of 375 mg/m(2)). The relative amount of parotid parenchyma, lymphocytic infiltrate, and fat, and the presence/quantity of germinal centers and lymphoepithelial duct lesions were evaluated. Immunohistochemical characterization was performed to analyze the B:T cell ratio of the lymphocytic infiltrate (CD20, CD79a, CD3) and cellular proliferation in the acinar parenchyma (by double immunohistologic labeling for cytokeratin 14 and Ki-67). Histologic data were assessed for correlations with the parotid flow rate and saliva composition. RESULTS Four patients showed an increased salivary flow rate and normalization of the initially increased salivary sodium concentration. Following rituximab treatment, the lymphocytic infiltrate was reduced, with a decreased B:T cell ratio and (partial) disappearance of germinal centers. The amount and extent of lymphoepithelial lesions decreased in 3 patients and was completely absent in 2 patients. The initially increased proliferation of acinar parenchyma in response to inflammation was reduced in all patients. CONCLUSION Sequential parotid biopsy specimens obtained from patients with primary SS before and after rituximab treatment demonstrated histopathologic evidence of reduced glandular inflammation and redifferentiation of lymphoepithelial duct lesions to regular striated ducts as a putative morphologic correlate of increased parotid flow and normalization of the salivary sodium content. These histopathologic findings in a few patients underline the efficacy of B cell depletion and indicate the potential for glandular restoration in SS.

Overexpression of Intrinsic Hypoxia Markers HIF1{alpha} and CA-IX Predict for Local Recurrence in Stage T1-T2 Glottic Laryngeal Carcinoma Treated With Radiotherapy

PURPOSE To examine the prognostic value of three endogenous hypoxia markers (hypoxia inducible factor 1 alpha subunit [HIF1 alpha], carbonic anhydrase IX [CA-IX], and glucose transporter type 1 [GLUT-1]) on the clinical outcome in patients with early-stage glottic carcinoma primarily treated with radiotherapy (RT) and to determine the predictive hypoxic profile to choose the optimal treatment of early-stage laryngeal carcinoma. METHODS AND MATERIALS Immunohistochemistry for HIF1 alpha, CA-IX, and GLUT-1 was performed on formalin-fixed, paraffin-embedded, pretreatment tissue samples of 91 glottic squamous cell carcinoma specimens. The patient group consisted only of those with early-stage (T1-T2) glottic carcinoma, and all patients were treated with RT only. Relative tumor staining was scored on the tissue samples. Receiver operating curve analysis was performed to determine the optimal cutoff value for each tumor marker. Cox regression analyses for the variables HIF1 alpha, CA-IX, GLUT-1, gender, age, hemoglobin level, T category, N category, tobacco use, and alcohol use were performed with local control and overall survival as endpoints. RESULTS HIF1 alpha overexpression in early-stage glottic carcinoma correlated significantly with worse local control (hazard ratio [HR], 3.05; p = 0.021) and overall survival (HR, 2.92; p = 0.016). CA-IX overexpression correlated significantly with worse local control (HR, 2.93; p = 0.020). GLUT-1 overexpression did not show any correlation with the clinical outcome parameters. Tumors with a nonhypoxic profile (defined as low HIF1 alpha and low CA-IX expression) had significantly better local control (HR, 6.32; p = 0.013). CONCLUSION The results of our study have shown that early-stage glottic laryngeal carcinomas with low HIF1 alpha and CA-IX expression are highly curable with RT. For this group, RT is a good treatment option. For tumors with HIF1 alpha or CA-IX overexpression, hypoxic modification before RT or primary surgical treatment should be considered.

Cortactin expression predicts poor survival in laryngeal carcinoma

Amplification of the 11q13 region is one of the most frequent aberrations in squamous cell carcinomas of the head and neck region (HNSCC). Amplification of 11q13 has been shown to correlate with the presence of lymph node metastases and decreased survival. The 11q13.3 amplicon carries numerous genes including cyclin D1 and cortactin. Recently, we reported that FADD becomes overexpressed upon amplification and that FADD protein expression predicts for lymph node positivity and disease-specific mortality. However, the gene within the 11q13.3 amplicon responsible for this correlation is yet to be identified. In this paper, we compared, using immunohistochemical analysis for cyclin D1, FADD and cortactin in a series of 106 laryngeal carcinomas which gene correlates best with lymph node metastases and increased disease-specific mortality. Univariate Cox regression analysis revealed that high expression of cyclin D1 (P=0.016), FADD (P=0.003) and cortactin (P=0.0006) predict for increased risk to disease-specific mortality. Multivariate Cox analysis revealed that only high cortactin expression correlates with disease-specific mortality independent of cyclin D1 and/or FADD. Of genes located in the 11q13 amplicon, cortactin expression is the best predictor for shorter disease-specific survival in late stage laryngeal carcinomas.

Immunohistochemical Detection of Salivary Agglutinin/gp-340 in Human Parotid, Submandibular, and Labial Salivary Glands

Salivary agglutinin is a Streptococcus mutans binding protein and a member of the scavenger receptor cysteine-rich superfamily. It is identical to lung gp-340 and brain DMBT1, which possibly play a role in innate immunity and tumor suppression, respectively. The goal of this study was to localize salivary agglutinin in human salivary glands. Two monoclonal antibodies, directed against gp-340, were characterized. mAb 213-1 reacted with sialic acid epitopes and cross-reacted with MUC7. The reaction with mAb 213-6 disappeared after reduction, suggesting that a protein epitope was recognized. In the parotid gland, immunohistochemical labeling with mAb 213-6 was found in the duct cells. In the submandibular gland and labial gland, both serous acini and demilune cells were labeled. In the labial gland, labeling was found at the luminal side of the duct cells. Salivary agglutinin was distinctly localized in salivary glands, but in distinct glandular secretions, no differences in electrophoretic behavior were observed.

Tumour infiltration depth >= 4 mm is an indication for an elective neck dissection in pT1cN0 oral squamous cell carcinoma

Patients with pT1cN0 oral squamous cell carcinomas (OSCC) are generally not treated with a neck dissection (ND). However, in 25% of cN0 patients, nodal metastases become apparent during follow-up. Infiltration depth of the primary tumour has been consistently associated with the presence of nodal metastasis, but proposed cut-off depths for performing a ND vary considerably. The aim of this study was to explore the infiltration depth as predictor for the nodal status and to recommend a cut-off depth for performing a ND. From our database of 351 primary oral carcinomas, we selected all pT1-2 tumours (n=246). Infiltration depth was measured in 212 cases. Neck status was determined by histopathological examination of the dissection specimen, or by at least two years of follow-up. Mean infiltration depth was 5.49 mm (95% CI: 4.86-6.12) in the N0 and 8.40 mm (95% CI: 7.38-9.43) in the N+ group (p<0.001). cN status, lymphovascular invasion and infiltration depth were the only independent predictors for nodal status in multiple logistic regression. ROC-analysis on pT1cN0 tumours resulted in an optimal cut-off for the prediction of the nodal status at a depth of 4.59 mm. This cut-off identified a subgroup of patients at increased risk for nodal metastasis (OR=8.3) and with significantly shorter survival. Tumour infiltration depth is an independent predictor for nodal status in pT1-2 OSCC. In pT1cN0 tumours, a cut-off at 4.59 mm results in the best predictive value. We recommend an infiltration depth of ≥4 mm as an indication to perform a neck dissection in pT1cN0 OSCC.

Comparative genomic hybridisation divides retinoblastomas into a high and a low level chromosomal instability group.

Background: Retinoblastoma is the most common intraocular malignancy in childhood and is responsible for approximately 1% of all deaths caused by childhood cancer. Aims/methods: Comparative genomic hybridisation was performed on 13 consecutive, histologically confirmed retinoblastomas to analyse patterns of chromosomal changes and correlate these to clinicopathological variables. Six cases were hereditary and seven cases were sporadic. Results: In 11 of the 13 tumours chromosomal abnormalities were detected, most frequently gains. Frequent chromosomal gains concerned 6p (46%), 1q (38%), 2p, 9q (30%), 5p, 7q, 10q, 17q, and 20q (23%). Frequent losses occurred at Xq (46%), 13q14, 16q, and 4q (23%). High level copy number gains were found at 5p15 and 6p11–12. A loss at 13q14 occurred in three cases only. Relatively few events occurred in the hereditary cases (27) compared with the non-hereditary cases (70 events). The number of chromosomal aberrations in these 13 retinoblastomas showed a bimodal distribution. Seven tumours showed less than four chromosomal aberrations, falling into a low level chromosomal instability (CIN) group, and six tumours showed at least eight aberrations, falling into a high level CIN group. In the low level CIN group the mean age was half that seen in the high level CIN group, there were less male patients, and there were more hereditary and bilateral cases. Microsatellite instability was not detected in either of the two groups. Conclusion: Despite the complex pattern of genetic changes in retinoblastomas, certain chromosomal regions appear to be affected preferentially. On the basis of the number of genetic events, retinoblastomas can be divided in low and a high level chromosomal instability groups, which have striking differences in clinical presentation.

The surgical management of recurrent or residual pleomorphic adenomas of the parotid gland. Analysis and results in 40 patients

From 1974 to 1995, 40 patients were treated surgically at the University Hospital Vrije, Universiteit Amsterdam for recurrent or residual pleomorphic adenomas of the parotid gland after previous surgery. The median interval between the initial procedure and surgery for the recurrence was 122 months. Eleven patients had one or more attempts to resect tumor recurrences prior to referral. During reoperation at this institution it was decided to refrain from tumor resection in three patients. Tumor control in two of these patients was achieved using radiotherapy. In the third patient a “wait-and-see” policy was adopted. The other 37 patients underwent en bloc surgical excisions of their tumor and/or previously incised tissues. Among the 36 patients operated for histopathologically benign disease, 16 received postoperative radiotherapy (to 6500 cGy). None developed a further recurrence, the median follow-up being 106 months. Only one of these patients experienced permanent segmental facial nerve paralysis. Malignant transformation of tumor occurred in two patients. One of these patients died of locoregional disease after surgery and radiotherapy. Radical tumor resection was deferred in the other patient, with tumor control achieved using radiotherapy (7000 cGy). However, since recurrent disease tends to be multifocal in origin, prolonged routine follow-up is required.

Radical surgical treatment in craniofacial osteosarcoma gives excellent survival. A retrospective cohort study of 14 patients

14 patients with an osteosarcoma of the craniofacial bones were evaluated retrospectively. 10 patients were males and 4 were females, ages varied from 10 to 74 years with a mean of 37 years. Ten tumours were located in the maxilla and four in the mandible. All patients underwent surgical resection of the tumour. One patient was irradiated postoperatively with 67.5 Gy and another patient received adjuvant chemotherapy with melphelan. Follow-up ranged from 6 months to 10 years with a mean of 4 years 2 months. Of 14 patients, 5 have died of local disease of whom 1 also had distant metastasis. Disease-free survival was 82.5% after 2 years and 68.8% after 5 years. Overall survival was 79.1% after 5 years. Univariate statistical analysis was carried out, revealing age < 35 years (P = 0.033) and radical surgery (P = 0.007) as statistically significant factors in disease-free survival. It is concluded that radical surgery in young patients with a craniofacial osteosarcoma gives long-term disease-free survival.

Histological reclassification of 101 intraoral salivary gland tumours (new WHO classification).

The epithelial salivary gland tumours have for many years been categorised according to the 1972 World Health Organisation (WHO) classification. In 1990 a proposed revision of this classification was elaborated. In this study 101 intraoral salivary gland tumours were reclassified accordingly. In 29 of the cases the original histological diagnosis was changed, which in most cases, occurred in the benign or malignant tumour groups. In seven cases the diagnosis was changed from benign to malignant or vice versa. The results of this study show that the histological classification of intraoral salivary gland tumours remains difficult, even when applying the new WHO classification.