Vinko Kambič

Acid posterior laryngitis. Aetiology, histology, diagnosis and treatment.

The authors have treated 44 patients with posterior chronic acid laryngitis. Biopsy was performed in all patients. Characteristic changes typical of the hyper-regenerative or atrophic phase of reflux oesophagitis were identified in all specimens. Gastric hypersecretion was proven in all but two patients. The aetiologic factors of acid posterior laryngitis are gastro-oesophageal reflux, with friction of both vocal processes during phonation and vocal abuse. The preferred therapy is removal of circumscribed lesions with a suitable medical regimen.

Vocal cord polyps: Incidence, histology and pathogenesis

On the basis of clinical and histologic examination, history and epidemiologic survey of 591 patients with vocal cord polyps, the authors evaluate the morphology of the pathologic substrate, indicate possible pathogenesis and analyse the most frequent factors in the formation of polyps such as vocal abuse and unfavourable microclimate at work. Sex does not play any role in the incidence, and the histologic structure is not related to the time factor.

Expression of Ki-67 antigen and proliferative cell nuclear antigen in benign and malignant epithelial lesions of the larynx

In an attempt to analyse the proliferative activity in benign and malignant laryngeal epithelial lesions, and to determine the relationship to their histologic grade, we studied the expression of proliferative cell nuclear antigen (PCNA) and Ki-67 antigen on 20 squamous carcinomas, and on 30 biopsies of epithelial hyperplasia categorized according to the Kambic-Lenart classification into simple, abnormal, and atypical hyperplasias. In simple hyperplasia, both antibodies stained the nuclei of the occasional cells in the basal layer. In abnormal hyperplasia (mild dyplasia), positive cells occupied up to a third, and in atypical hyperplasia (moderate and severe dysplasia) they occupied from two-thirds to the entire epithelial thickness. In squamous carcinoma, we have found a statistically significant correlation between its grade and the percentage of Ki-67-(p < 0.01) and PCNA-(p < 0.00001) positive cells. Our results suggest that the proliferative fraction progressively increases with the degree of epithelial hyperplasia and the grade of carcinoma. We conclude that the patterns of immunoreactivity to PCNA and Ki-67 antigen correspond to the histologic grade of both benign and malignant epithelial lesions of the larynx. This method should be regarded as a useful adjunct to traditional histological techniques allowing more objective grading of benign and malignant epithelial lesions.

Proliferation of Myofibroblasts in the Stroma of Epithelial Hyperplastic Lesions and Squamous Carcinoma of the Larynx

Objectives: The immunohistochemical phenotype, distribution and significance of proliferation of myofibroblasts in laryngeal epithelial hyperplastic lesions (EHL) and squamous carcinoma (SC) were analyzed. Methods: Samples of 42 resected larynxes and 40 laryngeal biopsies of EHL and SC were included. Immunohistochemistry was performed using antibodies against vimentin, α-smooth muscle actin (SMA), desmin and leukocyte common antigen. Results: Myofibroblasts were vimentin- and SMA-positive, and were found exclusively in SC, indicating that invasion beyond the basement membrane is necessary to evoke a myofibroblastic stromal reaction. We observed two patterns of stromal reaction in SC: one was characterized by a marked proliferation of myofibroblasts and desmoplasia, with scarce lymphocytic infiltration; this pattern tended to be associated with well- or moderately differentiated SC. The other was characterized by few myofibroblasts, weak desmoplasia, and dense lymphocytic infiltration; the latter pattern tended to be associated with moderately or poorly differentiated SC. The degree of myofibroblast proliferation was inversely related to the density of lymphocytic infiltration. Antibodies against SMA also stained stromal blood vessels, demonstrating a gradual increase of vessel density as the grade of EHL increased. Conclusions: Immunohistochemical analysis of myofibroblasts provides useful information on the phenotypic characteristics of the stroma in laryngeal EHL and SC, and can serve as an additional marker of invasion.

Epithelial hyperplastic lesions--a challenging topic in laryngology.

Adequate diagnosis, treatment and prognosis of particular pathologic entities of the laryngeal mucosa depend entirely on the histological changes of the epithelium. The basis for the classification of epithelial hyperplastic lesions of the larynx (EHLL) is the progression of the histologic features of these lesions to cancer. Considering various criteria thought to be typical for the transformation of benign EHLL to carcinoma, they are most frequently classified into three different groups. However, difficulties begin with the lack of uniformity and inconsistency of terminology, and the fact that the histomorphological features and biological behavior are not always in accordance. It is emphasized that the surface keratosis in laryngeal pathology has no prognostic significance per se and that the term risky epithelium should replace the expression precancerosis. This term does not predict the evolution of the lesion in any way, and it does not exclude any possible future development; but it warns the laryngologist to exercise extreme caution and to follow the patient closely. Present knowledge of laryngeal cancer, its therapeutic options and consequences, force us to pay increasing attention to early detection and adequate treatment of EHLL.

Difficulties in management of vocal cord precancerous lesions

Hyperplastic aberrations are differently classified and the term of precancerosis diversely interpreted; therefore, it is extremely difficult to evaluate the effectiveness of particular therapeutic methods. A standardized classication would enable an objective assessment of the treatment for precanceroses. Our own conception of the histologic patterns in precanceroses is presented. In the period 1960-1975, a total of 2,700 biopsies were performed in patients with hyperplastic aberrations in the vocal cord mucosa. In 133 patients, histology revealed precancerosis. In the patients who had received medical therapy, no improvement was obtained; on the contrary, in 16 patients the process became malignant. Among the patients who had undergone de-epithelialization (61), 44 were cured. After the de-epithelialization, no precancerous case turned malignant. De-epithelialization has been shown to be the procedure of choice for the treatment of precanceroses of the vocal cord.

Epithelialized microvascular iliac crest flap for reconstruction of subglottic and upper tracheal stenosis: A preliminary report

A new method for the management of laryngotracheal stenosis using an epithelialized microvascular iliac crest flap is described. This flap offers firm support to the frontal wall, an inner epithelial lining, and is well vascularized. The operation must be carried out in two sessions: skin grafting the flap and transfer with interposition of the flap. In the reconstruction procedure, the otolaryngologist and an experienced microvascular surgeon should cooperate. The method is suitable particularly for solving severe stenosis of the cricoid region and of the upper part of the trachea.

Chromosomes 7,17 polysomies and overexpression of epidermal growth factor receptor and p53 protein in epithelial hyperplastic laryngeal lesions

Purpose: To visualize directly a sequence of genetic changes underlying the entire spectrum of epithelial hyperplastic laryngeal lesions (EHLL) and laryngeal cancer by the use of non-isotopic in situ hybridization (ISH) for chromosomes 7 and 17 in correlation with overexpression of p53 protein and epidermal growth factor receptor (EGFR). The specific aim was to compare the results and prognostic significance between the two types of EHLL: isolated, mainly atypical hyperplasia or risky epithelium, and EHLL associated with squamous cell carcinoma (SCC). Patients and Methods: 59 tissue specimens of EHLL obtained from 34 patients, graded according to the Ljubljana classification into simple (SH), abnormal (AbH) and atypical hyperplasia (AtH), and carcinoma in situ (CIS) were included in the study. Non-fluorescent ISH for chromosomes 7 and 17 was performed by biotinylated α-satellite DNA probes. Immunohistochemical staining for EGFR and p53 protein was analyzed on the same tissue samples. Results: Polysomy for both chromosomes increased in correlation with progressive grades of EHLL. The most important finding was the statistically significant difference in chromosome copy numbers between the isolated AtH and AtH associated with SCC. Overexpression of EGFR and p53 protein was found in 61 (36/59) and 52% (31/59) of cases, respectively. The immunoreactivity for both markers increased with the grade of lesions, but the staining pattern was not so uniform in isolated EHLL. On the other hand, the immunoreactivity was expressed more constantly in EHLL adjacent to SCC. Conclusions: Numerical changes in chromosomes 7 and 17 might be associated with an upregulation of EGFR and p53 genes, and could contribute to critical events in laryngeal carcinogenesis. For daily practice, the cytogenetic and immunohistochemical analyses could be of assistance in distinguishing between low- and high-risk groups of AtH. However, the isolated forms of atypical hyperplasia need considerable further study by evaluating genetic changes with the described methods regarding their ultimate transformation to carcinoma.

Laryngeal chondrosarcoma: is conservative surgery adequate treatment?

A case of laryngeal chondrosarcoma in a 63-year-old woman is presented. The report illustrates most of the features of this rare neoplasm, the difficulties in the histopathological evaluation and supports the previous ones that recommend an initial conservative attitude towards low grade laryngeal chondrosarcomas.

The role of testosterone in laryngeal carcinogenesis

Testosterone levels in the plasma of 25 women and 25 men with carcinoma of the larynx and of 15 women and 15 men with hyperplastic aberrations in the laryngeal mucosa were determined to evaluate the etiologic relation between hyperplastic aberrations in the laryngeal mucosa (including cancer) and the male sex hormones. Patients with laryngeal cancer showed statistically significant increases in plasma testosterone levels compared with the control group. No statistically significant differences were found in plasma testosterone levels or in the testosterone/estradiol index between patients with hyperplastic aberrations of the laryngeal mucosa (including precancerous conditions) and the control subjects. The authors believe that greater attention should be paid to endogenous factors, particularly the male sex hormones, in further studies of the etiology of laryngeal carcinoma.