Squamous Epithelial Tumors

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Squamous Papilloma and Papillomatosis

Squamous papillomas of the trachea are rare benign tumors composed of stratified squamous epithelium with acanthosis and papillomatosis, supported by a fibrovascular core. They are either multiple and recurrent (papillomatosis) or solitary exophytic growths into the tracheal lumen.

Biology. Squamous papillomatosis occurs as multiple and recurrent squamous cell papillomas of the trachea, often associated with upper (mostly laryngeal) and/or lower (bronchial) involvement. Children and adolescents are most commonly affected, hence the term "juvenile papillomatosis"; occasional adults with disease have been reported.1

The patient may present with stridor, wheezing, dyspnea, chest pain, or hemoptysis. The lung parenchyma is affected in about 1% of cases, most of them complicated by necrosis, cavitation, or pneumonia.

The disease sometimes regresses in adulthood, but the course is usually protracted in extensive papil-lomatosis with complications of obstruction in the trachea, larynx, or bronchi, with atelectasis, bronchi-ectasis, and pneumonia. Surgical resection, laser fulguration, and interferon therapy are usually attempted to secure patent airways in these patients.

Human papilloma virus (HPV) is a known cause of these tumors, and different types are detected. HPV types 6 and 11 are commonly found in benign lesions, whereas types 16 and 18 are mostly associated with malignant transformation.2 Other types including 31, 33, and 35 are also occasionally found in malignantly transformed cases.2

Solitary papillomas often occur in adults, but children may also have solitary tumors. Squamous cell carcinomas may develop in about one-third of solitary squamous papillomas without other risk factors.3 In contrast, malignant transformation is less common in multiple papillomas (papillomatosis), occurs on average about 15 years after initial diagnosis, and is often associated with risk factors such as radiation, cytotoxic drug therapy, and smoking.4

Pathology. Grossly, the papillomas appear as cauliflower-like excrescences, protruding into the tracheal lumen (Figures 3-1, 3-2 [Color Plate 1]).

Microscopically, papillomas are composed of loose fibrovascular cores covered by hyperplastic stratified squamous epithelium with papillomatosis. Keratinization may be present sometimes with small parakeratotic foci. Koilocytosis (perinuclear halo and nuclear wrinkling) is seen in all papillomatosis cases and in solitary papillomas associated with HPV. The epithelium is usually cytologically bland; mitoses, atypicality, or dysplastic cells are infrequent, but are occasionally seen in solitary papillomas (Figure 3-3 [Color Plate 1]).

A case of a cytologically benign papilloma was reported in a 27-year-old man, where the tumor invaded the tracheal wall and adjacent soft tissues, without nodal or distant metastasis in 4 years of follow-up. The term "invasive tracheal papillomatosis" was suggested in this case.5

Papillomas must be differentiated grossly and microscopically from papillary squamous cell carcinomas, which they resemble because of papillary configuration and layers of neoplastic squamous cells, but lack similar atypical cellular and architectural features. Squamous cell carcinomas may also arise in papil-lomas, showing focal cellular pleomorphism, loss of maturation, dyskeratosis, and increased hyperkerato-sis. It then extends through the epithelium and ultimately invades the underlying connective tissue. It may go through the tracheal wall into adjacent soft tissues and lymphatics. These can be well or moderately differentiated, with or without keratinization. Small endoscopic biopsies can result in improper interpretation, since malignant transformation can be well differentiated or focal. Conversely, some focal atypia have been observed in benign papillomas.6 Extension of squamous epithelium to bronchial glands should not be interpreted as invasion.

Squamous Cell Carcinoma

In many published series, squamous cell carcinoma is the most common primary tracheal tumor, whereas in others, it equals in frequency or comes after adenoid cystic carcinoma as the second-most common neoplasm in adults.7-9

Biology. Although one of the two most common tracheal malignancies, squamous cell carcinoma is far less common than its laryngeal or bronchogenic counterparts, which are about 75 and 180 times more frequent, respectively.10 Age distribution is between 20 and 80 years with peak incidence in the sixth and seventh decades, similar to bronchogenic squamous cell carcinoma. An infant with tracheal squamous cell carcinoma has been reported.8 Men are significantly more affected than women, with a ratio of 2:1 to 4:1 in large series.8,9 Smoking history is present in most patients, accounting for almost all cases in some series, suggesting a strong association as in bronchogenic squamous cell carcinoma.7

The lower incidence of tracheal squamous cell carcinomas compared with those of the bronchus is attributed by some to laminar airflow in the trachea (because of large diameter) and effective mucociliary clearance (because of evenness and absence of bifurcation). These may prevent accumulation of carcinogens in the mucosa which can promote a malignant transformation sequence.11 Six patients have been reported with tracheal squamous cell carcinoma arisen from tracheostomy scars, probably the result of carcinogenesis in active repair, similar to scar carcinoma elsewhere.12 One case was reported in a plumber exposed to asbestos.13

Most cases of primary squamous cell carcinoma occur as solitary lesions, but synchronous and metachronous tumors, mostly with bronchogenic, laryngeal, or esophageal squamous cell carcinomas, have been reported.14,15

Pathology. Grossly, squamous cell carcinomas usually arise from the posterior tracheal wall as polypoid growths, most commonly in the lower third, followed by the upper third (Figures 3-4,3-5 [Color Plate 1]).8 Surface ulceration is often present.

Microscopically, the tumor is composed of nests and sheets of squamous cells with various degrees of differentiation (Figures 3-6, 3-7, 3-8 [Color Plate 1]). Squamous differentiation, as in the lung, includes intercellullar bridges and keratin pearl formation. Two cases of basaloid variants have been reported, wherein like the cutaneous basal cell carcinoma, the cells are smaller, with scant cytoplasms and high nuclear to cytoplasmic ratios.16 Combined squamous cell and small cell carcinomas have also been reported.17

The differential diagnosis includes papilloma, squamous cell carcinoma arising in papilloma, mucoepidermoid carcinoma, and necrotizing sialometaplasia. It must also be distinguished from squa-mous cell carcinomas invading from adjacent structures such as the esophagus, lung, thymus, and even thyroid gland. These primaries must always be considered when squamous cell carcinoma is diagnosed by endoscopic biopsy.

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