Benign and Potentially Malignant Lesions of the Squamous Epithelium and Squamous Cell Carcinoma


1.1 Squamous Cell Papilloma and Related Lesions 2

1.1.1 Squamous Cell Papilloma,

Verruca Vulgaris, Condyloma Acuminatum and Focal Epithelial Hyperplasia 2

1.1.2 Laryngeal Papillomatosis 3

1.2 Squamous Intraepithelial Lesions (SILS) 4

1.2.1 General Considerations 4

1.2.2 Terminological Problems 4

1.2.3 Aetiology 5 Oral Cavity and Oropharyn 5

1.2.4 Clinical Features and Macroscopic Appearances 6 Oral and Oropharyngeal Leukoplakia, Proliferative Verrucous Leukoplakia and Erythroplakia 6 Laryngeal and Hypopharyngeal Leukoplakia and Chronic Laryngitis 7

1.2.5 Histological Classifications 8 WHO Dysplasia System 8 The Ljubljana Classification 9 Comparison Between the Ljubljana Classification and WHO 2005 Classification 11

1.2.6 Biomarkers Related to Malignant Potential of SILs Recognised by Auxiliary and Advanced Molecular Methods 12

1.2.7 Treatment and Prognosis 12 Oral Cavity and Oropharynx 12

1.3 Invasive Squamous Cell Carcinoma 13

1.3.1 Microinvasive Squamous Cell Carcinoma 13

1.3.2 Conventional Squamous Cell Carcinoma 13 Aetiology 14 Pathologic Features 14 Grading 14 Invasive Front 15 Stromal Reaction 15 Differential Diagnosis 15 Treatment and Prognosis 15

1.3.3 Spindle Cell Carcinoma 16 Aetiology 16 Pathologic Features 16 Differential Diagnosis 17 Treatment and Prognosis 17

1.3.4 Verrucous Carcinoma 17 Aetiology 17 Pathologic Features 18 Differential Diagnosis 18 Treatment 18 Prognosis 19

1.3.5 Papillary Squamous Cell Carcinoma 19 Aetiology 19 Pathologic Features 19 Differential Diagnosis 20 Treatment and Prognosis 20

1.3.6 Basaloid Squamous Cell Carcinoma 20 Aetiology 20 Pathologic Features 20 Differential Diagnosis 21 Treatment and Prognosis 21

1.3.7 Adenoid Squamous Cell Carcinoma 22 Pathologic Features 22 Differential Diagnosis 22 Treatment and Prognosis 22

1.3.8 Adenosquamous Carcinoma 23 Aetiology 23 Pathologic Features 23 Differential Diagnosis 23 Treatment and Prognosis 24

1.3.9 Lymphoepithelial Carcinoma 24 Aetiology 24 Pathologic Features 24 Differential Diagnosis 25 Treatment and Prognosis 25

1.4 Second Primary Tumours 25

1.5 Tumour Spread and Metastasising 25

1.5.1 Invasion of Lymphatic and Blood Vessels 26

1.5.2 Perineural Invasion 26

1.5.3 Regional Lymph Node Metastases 26 Extracapsular Spread in Lymph Node Metastases 26 Metastases in the Soft Tissue of the Neck 27

1.5.4 Distant Metastasis 27

1.5.5 Micrometastasis 27

1.6 Molecular Pathology of Squamous Cell Carcinoma 28

1.6.1 Detecting Tumour Cells 28

1.6.2 Clonal Analysis 28

1.6.3 Assessment of Risk for Malignant Progression . . . . 29

1.6.4 DNA/RNA Profiling in Predicting Metastatic Disease 29

References 29

Squamous Cell Papilloma and Related Lesions

Benign, exophytic, papillary or verrucous lesions of the squamous epithelium of the oral cavity, oropharynx and larynx include similar entities such as squamous cell papilloma (SCP), verruca vulgaris (VV), condyloma acuminatum (CA), and focal epithelial hyperplasia (FEH). However, not every papillary lesion in these areas can be placed into one of the listed categories. It seems that the majority of lesions are similar variants of mucosal proliferations, frequently induced by infections by human papillomaviruses (HPV). They show more or less overlapping clinical and morphological properties, but different biological behaviour, ranging from rather inconspicuous to potentially life threatening. Classification of these changes into infectious (VV, CA, FEH), and neoplastic (SCP), is thought to be rather inconsistent and not well founded. Papillary lesions, except for laryngeal papillomatosis, generally have a favourable outcome.

1.1.1 Squamous Cell Papilloma, Verruca Vulgaris, Condyloma Acuminatum and Focal Epithelial Hyperplasia not genotypes 2 and 4, which are characteristic of mucosal VV [22]. Other, non-infectious aetiological factors are not well known for oral papillary lesions (Fig. 1.1).

Histologically, SCPs are composed of narrow papillary projections of soft fibrous stroma covered by kera-totic or parakeratotic squamous epithelium (Fig. 1.2).

Koilocytosis, the only visible cytopathic effect of HPV infection, which is caused by viral replication in the upper intermediate and superficial zone of the squamous epithelium, is rarely visible in SCPs. VV shows similar histological features, but peripheral papillary projections are usually centrally bend, and koilocytosis and the granular layer are prominent. The characteristics of CAs are obvious: koilocytosis and bulbous rete ridges of the covering epithelium [100, 285]. Koilocyto-sis, apoptotic bodies and epithelial hyperplasia are significant in FEH [61, 285].

In the differential diagnosis of squamous cell oral papillary lesions, verrucous carcinoma is the most important consideration. An evident downgrowth of bulbous epithelial projections favours a diagnosis of verru-cous carcinoma. Oral SCPs in patients with acquired im-


Squamous cell papilloma, the most frequent papillary lesion of the oral cavity and oropharynx, is usually a single, pedunculated, white or pink lesion, consisting of finger-like mucosal projections (Fig. 1.1). It may occasionally be sessile with a granular or verrucous surface. The lesion, usually smaller than 1 cm, grows rapidly and has predilections for the hard and soft palate and lateral border of the tongue [2, 285]. Multiple sessile lesions in children are characteristic of VV; they are found on the lips, palate and gingiva. CAs are usually larger than SCPs, multiple dome-shaped nodular lesions that mainly appear on the lips and soft palate. FEHs are characterised by multiple sessile or elevated papules, usually distributed over the buccal, labial and tongue mucosa.

Aetiologically, it is extremely difficult to establish their accurate relationship to HPV infection due to variations in tissue samplings, the ethnic and geographic origin of patients, and the use of non-molecular vs. molecular methods for HPV detection with different levels of sensitivity [285, 374]. However, more than 20 HPV genotypes have been detected in oral papillary lesions [285]. SCPs are mainly related to HPV genotypes 6 and 11 [386], VV to HPV genotypes 2, 4, 6, 11, and 16 [142, 244], CA to HPV genotypes 6, 11, 16, and 18 [100, 201] and FEH to HPV genotypes 13 and 32 [285, 286]. Only a few cases of VV have been described in the larynx. Barnes and co-workers studied a single case and unexpectedly found it to contain HPV genotypes 6 and 11 and

Fig. 1.1. Whitish papillary lesion of the palate. Courtesy of Dr. J. Fischinger, Ljubljana, Slovenia
Fig. 1.2. Oral squamous cell papilloma. Projections of fibrovas-cular stroma are covered by parakeratotic squamous epithelium

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