Anneroth G, Batsakis J, Luna M: Review of the literature and a recomnnended system of malignancy grading in oral squamous cell carcinomas. Scand J Dent Res 1987; 95: 229-49.Abstract -A review of histologic classification systems for grading of malignancy in squamous eel] carcinomas of tbe head and neck region is presented. Reasons behind the varying results obtained in studies using histomorphologic grading schemes are presented and potential errors involved in this type of clinical research are discussed. Requirements for the study of correlations between malignancy grade scoring, and recurrence and survival rates are presented. These include factors as patient selection, clinical staging, and follow-up principles. Special attention must be given to treatment modalities, establishment of negative surgical margins and occurrence of regional lymph node and/or distant metastases.

13-cis-Retinoic acid has been reported to be effective in treating oral leukoplakia. We randomly assigned 44 patients with this disease to receive 13-cis-retinoic acid (24 patients) or placebo (20), 1 to 2 mg per kilogram of body weight per day for three months, and followed them for six months. There were major decreases in the size of the lesions in 67 percent (16 patients) of those given the drug and in 10 percent (2 patients) of those given placebo (P = 0.0002); dysplasia was reversed in 54 percent (13 patients) of the drug group and in 10 percent (2 patients) of the placebo group (P = 0.01). The clinical response to the drug correlated with the histologic response in 56 percent (9 of 16) of the patients evaluated. Relapse occurred in 9 of 16 patients two to three months after treatment ended. The toxic effects of the drug were acceptable in all but two patients. Cheilitis, facial erythema, and dryness and peeling of the skin were common; conjunctivitis and hypertriglyceridemia also occurred. All adverse reactions could be reversed by reducing the dose or temporarily discontinuing the drug. We conclude that 13-cis-retinoic acid, even in short-term use, appears to be an effective treatment for oral leukoplakia and has an acceptable level of toxicity.

To better understand genetic alterations in oral premalignant lesions, we examined 84 oral leukoplakia samples from 37 patients who had been enrolled in a chemoprevention trial. The samples were analyzed for two microsatellite markers located at chromosomes 9p21 and 3p14. Loss of heterozygosity (LOH) at either or both loci was identified in 19 of the 37 (51%) patients. Of these 19 patients, seven (37%) have developed head and neck squamous cell carcinoma (HNSCC) while only one of 18 (6%) of patients without LOH developed HNSCC. Our data suggest that clonal genetic alterations are common in oral premalignant lesions; that multiple genetic alterations have already occurred in oral premalignant lesions, allowing at least a focal clonal expansion; and that losses of the 9p21 and 3p14 regions may be related to early processes of tumorigenesis in HNSCC. These genetic alterations in premalignant tissues may serve as markers for cancer risk assessment.

We analyzed 55 primary salivary gland tumors including 22 mucoepidermoid carcinomas (MECs) to determine the association of MECT1/TORC1/CRTC1-MAML2 fusion transcript to tumor types, level of MEC differentiation and clinicopathologic parameters. Our primary salivary gland tumors were composed of 22 MECs, 11 Warthin's tumors, 10 adenoid cystic carcinomas, two basaloid carcinomas, five salivary duct carcinomas, and five adenocarcinomas, not otherwise specified. We also included, for the first time, three primary MECs of the thyroid gland. We used nested RT-PCR and subsequent sequencing techniques for detection and verification of the fusion transcript in fresh and archival specimens. Eighteen (81%) of the 22 primary salivary and one of the three thyroid glands with MEC were positive for the fusion transcript. The transcript was detected equally in low, intermediate and high grade as well as low and high stage MECs. Significant correlation between fusion negative tumors and distant metastasis was noted (P = 0.005). Four (36%) of the 11 Warthin's tumors were also positive for the transcript. None of the 22 primary non-MEC gland salivary carcinomas were positive for the transcript. We conclude that the CRTC1/MAML2 transcript may be detected in both low and high grade MEC, that fusion negative tumors may define a subset of biologically aggressive MEC's tumors, that the fusion is present in primary MECs of the thyroid gland and is also detectable in Warthin's tumor, and that a subset of MECs can be targeted for therapeutic intervention.

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M. D. Anderson Hospital cases diagnosed as adenocarcinoma of minor salivary glands before 1977 were reviewed. Within this heterogeneous group of neoplasms there was identified one clinicopathologic tumor entity, which we have designated “polymorphous low‐grade adenocarcinoma.” The 14 tumors in that category were characterized by cytologic uniformity and histologic diversity; growth patterns varied (both within and among cases) from solid to tubular to papillary to cribriform (pseudoadenoid cystic) to fascicular, while the cells were always small to medium‐sized, regular, and lacking in nuclear atypia. Mitotic figures were infrequent, and tumor necrosis was seen in only one instance (a recurrent neoplasm). Clear cytoplasm, oxyphilic and mucinous metaplasia, and intratubular calcification were sometimes present, and stromal mucinization and hyalinization were common. The tumors were always unencapsulated, and exhibited extension into surrounding tissues including bone. The 14 patients ranged in age from 27 to 76 years (median, 64 years). Eight were male and six were female; eight were white and six were black. The neoplasm was intraoral in all cases, involving the palate in 11, the buccal mucosa in two, and the posterior mandibular area in one. Local recurrence developed in one case, cervical lymph node metastasis in one, and both recurrence and cervical lymph node metastasis in two. The number of successive recurrences ranged up to three, and the interval to recurrence varied up to nine years (the interval to metastasis up to five years). Although radical surgical procedures were necessary for tumor control in some cases, no distant metastases occurred and all patients were clinically tumor‐free at latest follow‐up.

When preceded by high-dose induction therapy, low-dose isotretinoin therapy was significantly more active against leukoplakia than beta carotene and was easily tolerated.

The involvement by a disease process of the parapharyngeal and retropharyngeal spaces poses significant diagnostic and therapeutic problems. Neoplasms, the majority histologically benign, comprise the greatest number of parapharyngeal space lesions. Inflammatory lesions and metastases to lymph nodes are the preponderant disorders affecting the retropharyngeal space.