Conventional Squamous Cell Carcinoma



Conventional Squamous Cell Carcinoma





Conventional squamous cell carcinoma (SCC) is the most common malignant diagnosis made based on biopsy specimens from the upper aerodigestive tract. In fact, it may be the most common diagnosis of any type rendered on biopsy specimens from this area. This chapter discusses the epidemiology and clinical aspects of the disease, the histologic features of conventional SCC, and some difficulties that can be faced with biopsy specimens. Specific variants of SCC that generally lead to more diagnostic difficulties are discussed in Chapter 5.


EPIDEMIOLOGY

SCC of the upper aerodigestive tract is a disease of older individuals, especially of men. A few notable exceptions occur (Epstein-Barr virus [EBV]-related nasopharyngeal carcinoma and human papillomavirus [HPV]-related oropharyngeal carcinoma); however, more than 90% of cancers of the oral cavity and pharynx and more than 95% of cancers of the larynx are diagnosed in patients older than 45 years.1,2 According to the National Cancer Institute, slightly more than 35,000 cancers of the oral cavity and pharynx and nearly 13,000 cancers of the larynx were diagnosed in the United States in 2010. In the same year, there were approximately 7,800 deaths from oral and pharyngeal cancers and approximately 3,600 deaths from laryngeal cancers. Thus, the combined incidence of these cancers is similar to that of pancreatic cancer, whereas their mortality is similar to that of renal cell carcinoma.

Stage is the most important prognostic factor for these tumors.1,2 The overall 5-year relative survival rates for laryngeal and oral/pharyngeal cancers were 61%, but were 77% and 82%, respectively, when the diseases were found to be localized. While 57% of laryngeal cancers were localized at the time of diagnosis, only 33% of oral/pharyngeal cancers were.


SCC of the upper aerodigestive tract is strongly linked to the use of alcohol and tobacco products.3,4,5,6,7 and 8 Indeed, using the two products together carries a relative risk of more than 20 for the development of these cancers.6 The risk is dose related, and heavy users are much more likely to develop these malignancies than infrequent or occasional users.8 Furthermore, the cessation of smoking is associated with a decreased risk for the development of these malignancies.

With regard to tobacco products, smoked tobacco is the major culprit.6 Chewed tobacco, however, is also considered to be a risk factor, especially for the development of oral SCCs, although its role remains somewhat unclear, and it carries a significantly lower relative risk for the development of malignancy at all sites when compared with smoking.9 Indeed, some have suggested that individuals should be encouraged to switch from smoked to chewed tobacco to reduce their risk for developing these malignancies.

In recent years, the incidence rate of tobacco product use has declined in the United States. Following this trend, there is now a wellestablished decline in the incidence rate of upper aerodigestive SCCs at sites most commonly related to the use of tobacco products (e.g., the larynx and mouth).

Other risk factors are both familial and environmental.10,11,12,13,14,15,16,17 and 18 Although the data are somewhat unclear, some elucidation has been based on young patients with SCCs who have little or no history of exposure to alcohol or tobacco products. The better understood familial cancer syndromes, including Li-Fraumeni syndrome, Lynch syndrome, and familial atypical mole-melanoma syndrome, with germ line mutations of the genes encoding for the p53 protein, mismatch repair proteins, and the p16 protein all carry increased risk for the development of SCCs of the upper aerodigestive tract.17,18 and 19 Some human leukocyte antigen types are also more prone to develop SCCs, particularly EBV-associated nasopharyngeal carcinomas.10,20,21 and 22

Aside from tobacco and alcohol use, environmental factors include both dietary and infectious factors. Although not commonly chewed in the United States, betel quid (a combination of a stimulant and an alkaloid) has been associated with the development of oral SCC through the development of the precursor lesion, submucosal fibrosis (see Chapter 3).13 Diets deficient in iron can lead to Plummer-Vinson syndrome (dysphagia, iron deficiency, and esophageal webs), which is associated with an increased risk for the development of hypopharyngeal SCC.23 Finally, people whose diets are rich in fruits and vegetables may be at decreased risk for the development of SCC of the upper aerodigestive tract.14

EBV is believed to play a role in the development of some SCCs, namely with undifferentiated SCCs.24 These tumors almost always occur in the nasopharynx; however, they can occur anywhere throughout the upper aerodigestive tract. The exact role that EBV plays in the development of these tumors is unclear. EBV-associated tumors are discussed in more detail in Chapter 5.


High-risk HPV also plays an important role in the development of SCCs of the upper aerodigestive tract, especially in younger patients with no history of alcohol or tobacco abuse.25,26,27 and 28 Our understanding of the role that HPV plays in the development of these tumors has progressed quickly over the past decade. We know that these tumors are almost always located in the oropharynx (the palatine and lingual tonsils), although the tumors rarely can occur throughout the entire tract. HPV-related SCCs are most commonly nonkeratinizing or basaloid (see Chapter 5), although they may sometimes be keratinizing or associated with other variant morphologies. In spite of their often high stage at presentation, the tumors appear to have a better overall prognosis than SCCs secondary to tobacco and alcohol use and are more radiosensitive. While the incidence rate of laryngeal and oral SCCs has declined recently, there has been a surge in the incidence rate of oropharyngeal SCCs, leading some to claim that we now have an epidemic of HPV-related upper aerodigestive tract malignancies.29


CLINICAL

Patients who develop SCCs of the upper aerodigestive tract tend to be older and the disease is much more common in men. As noted earlier, exceptions include EBV-related and HPV-related tumors. Also, tumors with chromosomal rearrangement of the nuclear protein of the testis gene (NUT midline carcinomas) occur in patients of all ages (discussed in Chapter 5).30

Patients’ symptoms depend on the location of their tumor and stage of their disease. Most present with the nonspecific findings of a mass lesion, obstruction, pain, and bleeding. Laryngeal lesions are typically associated with hoarseness. Any tumor, especially those that develop in the nasopharynx and oropharynx, can present with metastases, for example, as a neck mass, without symptoms related to the primary tumor. More advanced tumors can present with symptoms secondary to distant metastases or with systemic complaints such as weight loss.



Jun 18, 2016 | Posted by in OTOLARYNGOLOGY | Comments Off on Conventional Squamous Cell Carcinoma

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