Laryngeal Papillomatosis

ICD-O:8060/0

Laryngeal squamous cell papillomas (LSCPs) are the most frustrating benign lesions in the head and neck region. Because of their clinical specificities, such as multiplicity, recurrence and the propensity to spread to adjacent areas, it has been suggested that LSCPs should be renamed recurrent respiratory papillomatosis (RRP) [34, 89, 91, 187].

Recurrent respiratory papillomatosis is aetiological-ly related to HPV [4, 212, 283, 289, 352]. HPV-6 and -11 are the most frequent genotypes associated with RRP (Fig. 1.4b) [4, 126, 212, 284, 289, 330].

Characteristically, LSCPs show a bimodal age distribution: the first peak is before the age of 5 years with no gender predominance; the second peak occurs between the ages of 20 and 40 years with a male to female ratio of 3:2 [34, 87, 91, 189, 216].

Human papillomavirus transmission in children is associated with perinatal transmission from an infected mother to the child [34, 88, 217]. The mode of HPV infection in adults remains unclear. The reactivation of a latent infection acquired perinatally or a postpar-tum infection with orogenital contacts has been suggested [4, 188]. In contrast to RRP, a solitary keratinising squamous papilloma or papillary keratosis of adults appears not to be associated with viral infection, although it may recur or be occasionally associated with malignant transformation [20].

Recurrent respiratory papillomatosis almost invariably involves the larynx, especially the true and false vocal cords, subglottic areas and ventricles [4]. An extrala-ryngeal spread may occur successively to the oral cavity, trachea and bronchi. Although RRP has been traditionally divided into juvenile and adult groups [87, 189, 216, 352], the prevailing opinion has recognised the disease as a unified biological entity with differences in clinical courses, caused by HPV genotypes 6 or 11 [28, 126, 189, 218, 321]. For children, multiple and extensive growth with rapid recurrence after excision is characteristic. The small diameter of the airways in children may cause dangerous or even fatal airway obstruction. The clinical course in adults is usually not so dramat-

Fig. 1.3. Laryngeal papillomatosis. Numerous clusters of papillomas obliterate the laryngeal lumen

ic, although RRP can be aggressive with multiple recurrences [43, 284]. Most children present with dysphonia and stridor, and less commonly with a chronic cough, recurrent pneumonia, dyspnoea, and acute life-threatening events [34, 43, 88]. Affected adults present mostly with dysphonia and hoarseness [43, 181].

Grossly, papillomas are exophytic, branching, pedunculate or sessile masses, pink or reddish in colour, with a finely lobulated surface, presenting either singly or in clusters (Fig. 1.3).

Histologically, RRP is composed of finger-like projections of the squamous epithelium, covering thin fi-brovascular cores. A basal and parabasal hyperplasia of the squamous epithelium is most frequently seen, usually extending up to the mid-portion (Fig. 1.4a). Mitotic features may be prominent within this area. Irregularly scattered clusters of koilocytes are seen in the upper part of the epithelium. Epithelial changes, such as mild to moderate nuclear atypia and hyperchromatism, increased nuclear cytoplasmic ratio, increased mitotic activity with pathological features, and prominent surface keratinisation are rarely found in RRP [181].

Various lesions with a papillary structure must be considered in the differential diagnosis of RRP. In ver-rucous carcinomas, the squamous fronds are thicker and are covered by a prominent keratotic layer, bulbous rete pegs infiltrate fibrous stroma in a blunt, pushing manner and koilocytosis is usually absent. The papillary squa-mous carcinoma usually shows an architectonic similarity to RRP. In contrast to RRP, papillary structures in the papillary squamous carcinoma are covered by a clearly neoplastic epithelium showing invasive growth.

The clinical course of RRP is unpredictable, characterised by periods of active disease and remissions. HPV present in apparently normal mucosa serves as a virus reservoir responsible for repeated recurrence of papillo-

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Fig. 1.4. Laryngeal papillomatosis. a Branches of laryngeal papil- b Positive in situ hybridisation signal for HPV genotypes 6 and 11 loma are covered with hyperplastic squamous cell epithelium. Nu- in an adult laryngeal papilloma merous koilocytes are seen in the upper part of the epithelium.

mas [301, 330]. The presence of RRP in the neonatal period is a negative prognostic factor with a greater need for tracheotomy and likelihood of mortality [88]. One report on the spontaneous disappearance of the disease, especially during puberty, has not been further supported [4]. Increased histologic changes (atypia of epithelial cells) are reported to be associated with increased severity and recurrence of RRP [75, 288]. Others have suggested that the histologic changes of RRP are not a good predictor of eventual malignant transformation [133].

Malignant transformation occurs mainly in patients with a history of previous irradiation or heavy smoking [290], and rarely without any predisposing factors [143, 296]. In children, carcinomas preferentially appear in the bronchopulmonary tree, and in adults in the larynx [141]. HPV genotype 11 is assumed to be most frequently associated with malignant transformation of RRP [70, 206, 218, 290], followed by HPV-16 [92] and HPV-18 [311].

The overall mortality rate of patients with RRP ranges from 4 to 14% [20], and is mostly causally related to asphyxia, pulmonary complications and cancer development [17, 20, 338].

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