The paraneoplastic syndromes are diverse and are associated with many different tumors (
Table 6.6 ). The most common paraneoplastic syndromes are hypercalcemia, Cushing syndrome, and nonbacterial thrombotic endocarditis, and the neoplasms most often associated with these and other syndromes are lung and breast cancers and hematologic malignancies. Hypercalcemia in cancer patients is multifactorial, but the most important mechanism is the synthesis of a parathyroid hormone–related protein (PTHrP) by tumor cells. Also implicated are other tumor-derived factors, such as TGF-α and the active form of vitamin D. Another possible mechanism for hypercalcemia is widespread osteolytic metastatic disease of bone; of note, however, hypercalcemia resulting from skeletal metastases is not a paraneoplastic syndrome. Cushing syndrome arising as a paraneoplastic phenomenon usually is related to ectopic production of ACTH or ACTH-like polypeptides by cancer cells, as occurs in small cell carcinoma of the lung.
Paraneoplastic syndromes also may manifest as hypercoagulability, leading to venous thrombosis and nonbacterial thrombotic endocarditis (Chapter 11). Other manifestations are clubbing of the fingers and hypertrophic osteoarthropathy in patients with lung carcinomas (Chapter 13). Still others are discussed in the consideration of cancers of the various organs of the body.
Methods to quantify the probable clinical aggressiveness of a given neoplasm and its apparent extent and spread in the individual patient are necessary for arriving at an accurate prognosis and for comparing end results of various treatment protocols. For instance, the results of treating well-differentiated thyroid adenocarcinomas localized to the thyroid gland will on average be very different from those obtained from treating highly anaplastic thyroid cancers that have invaded the neck organs. Systems have been developed to express, at least in semiquantitative terms, the level of differentiation, or grade, and extent of spread of a cancer within the patient, or stage, as parameters of the clinical gravity of the disease. Of note, when compared with grading, staging has proved to be of greater clinical value.
Grading. Grading of a cancer is based on the degree of differentiation of the tumor cells and, in some cancers, the number of mitoses and the presence of certain architectural features. Grading schemes have evolved for each type of malignancy, and generally range from two categories (low grade and high grade) to four categories. Criteria for the individual grades vary in different types of tumors and so are not detailed here, but all attempt, in essence, to judge the extent to which the tumor cells resemble or fail to resemble their normal counterparts. Although histologic grading is useful, the correlation between histologic appearance and biologic behavior is less than perfect. In recognition of this problem and to avoid spurious quantification, it is common practice to characterize a particular neoplasm in descriptive terms, for example, well-differentiated, mucin-secreting adenocarcinoma of the stomach, or poorly differentiated pancreatic adenocarcinoma.
Staging. The staging of solid cancers is based on the size of the primary lesion, its extent of spread to regional lymph nodes, and the presence or absence of blood-borne metastases. The major staging system currently in use is the American Joint Committee on Cancer Staging. This system uses a classification called the TNM system—T for primary tumor, N for regional lymph node involvement, and M for metastases. TNM staging varies for specific forms of cancer, but there are general principles. The primary lesion is characterized as T1 to T4 based on increasing size. T0 is used to indicate an in situ http://ebooksmedicine.net
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