1. 
   

   Small cell carcinomas arise at what anatomical sites?

   
   
2. 
   

   How do squamous cell carcinomas behave differently from small cell carcinomas?

   
   
3. 
   

   How does the behavior and treatment of hormone-sensitive adenocarcinomas differ from hormone-independent adenocarcinomas?

In the preantibiotic era of the late nineteenth century, William Osler instructed clinicians to “Know syphilis in all its manifestations and relations and all other things clinical will be added unto you.” In the current era, with Treponema pallidum infection no longer a lifelong and endemic condition, Osler would have little objection to the application of his advice to the dozens of diseases we refer to as cancer. In this chapter, some of the more common clinical presentations and manifestations of solid cancers will be reviewed. This will include, with a deferential nod to Carl Jung, four solid cancer “archetypes,” each with a distinctive character and management approaches. Molecular phenotypes may replace these histological identities in the future. To the degree that pattern recognition can expedite diagnosis and treatment, these descriptions may be of value in providing a sense of the “personality” of common cancers and their presentations and complications. That said, an open mind and high index of suspicion should always be maintained as cancer can be a fascinatingly unpredictable disease.

Solid cancers display impressive heterogeneity, even within the same anatomical tumor sites, but a few general comments can be made. First, solid cancers that are not cured typically recur within months to a few years after completing initial therapy and have an inexorably progressive course to death over a period of months to years. Exceptions occur in clear cell renal cell carcinoma, breast adenocarcinoma, and melanoma patients who may experience recurrences decades after initial diagnosis and treatment. Interestingly, melanoma and renal cell tumors have also been observed to undergo spontaneous remission. Second, solid cancers that have metastasized to distant organs are generally not curable. There are three potential exceptions to this: (1) metastatic germ cell tumors, which typically arise in the testicle in young men (but also rarely in the ovary, pineal gland, mediastinum, or of uncertain primary origin) and are usually cured with systemic chemotherapy; (2) a portion of solid cancer patients with micrometastases treated with anticancer drug therapy added to local therapy can be cured, and this is the basis for adjuvant chemotherapy in breast, colorectal, and lung cancer; and (3) uncommonly, patients with oligometastatic disease treated surgically may be cured, for example, metastatectomy of a solitary lung or liver metastasis in a patient with a soft tissue sarcoma or colorectal cancer. If the clinical situation is at all uncertain, these possibilities should be considered before labeling a solid cancer patient incurable. Thirdly, treatment of the primary tumor in patients with incurable metastatic disease has not been shown to be of clinical benefit and is generally discouraged unless necessary to treat or avert symptoms, with the exceptions of clear cell renal cell carcinoma and ovarian carcinoma, in which surgical treatment of the primary (with cytoreductive nephrectomy and tumor debulking, respectively) have been associated with improved survival.

Cancer is a clonal cellular disease involving loss of normal controls on cell proliferation and differentiation. So the term “cancer” really describes a mechanism of disease that is the basis for more than 100 different diseases we currently classify by anatomy and histology. Cancers arise in the cells of these tissues due to acquired somatic mutations in normal cells. These in turn lead to an increase in positively acting growth cells and a decrease in negatively acting growth signals, and a decrease in activity in pathways leading to programmed cell death (apoptosis). Populations of cancer cells then survive in a hostile microenvironment and metastasize to other organs by conscripting or evading other physiological processes or defenses such as neoangiogenesis and the immune system. In contrast to antimicrobial therapy, which exploits differences in cell biology based in interspecies differences, it should not be surprising that a true “magic bullet” that destroys malignant cells without affecting a patient’s normal cells has yet to be identified in any cancer. This means that current therapies using radiation and drugs attempt to exploit subtle differences between normal and malignant cells’ response to cellular damage. As a result, the therapeutic index for most cancer treatments is extremely narrow. With this and the consequences of incurable cancer firmly in mind, perhaps nowhere in the practice of medicine are patients and physicians more willing to routinely accept high treatment risks in an effort to cure or even “just” control malignant disease. So it remains common for cancer patients to become seriously ill as a result of their anticancer treatment, despite advances in supportive care. Although virtually all modern solid cancer treatment is done in the outpatient setting, patients frequently require hospitalization, and the need for this may not only result from the locoregional, metastatic, or paraneoplastic effects of the disease itself, but also from treatment complications (Table 183-1). The identification of effective cancer drugs has been and remains largely empirical and only recently in the era of molecular biology have the mechanisms of the anticancer action of these drugs started to become truly understood. In addition to numerous hormonal therapies, several dozen cytotoxic agents are in common use for cancer treatment, and a number of “molecularly-targeted” agents have entered routine practice (Table 183-2). It is hoped that current efforts to improve cancer treatment toward a less empiric and more individualized approach will ultimately succeed, allowing the use of agents targeted to treat cancers identified as vulnerable while minimizing adverse effects for the patient.