NephroticsyndromeVariouscancersTumorantigens,immunecomplexes
ACTH, Adrenocorticotropichormone;IL-1, interleukin-1;TGF-α, transforminggrowthfactor-α;TNF, tumornecrosisfactor.
lesion. N0 would mean no nodal involvement, whereas N1 to N3 would denote involvement of an increasing number and range of nodes. M0 signifies no distant metastases, whereas M1 or sometimes M2 reflects the presence and estimated number of metastases.
In modern practice, grading and staging of tumors are being supplemented by molecular characterization, described later.
Cachexia, definedasprogressivelossofbodyfatandleanbodymass,accompaniedbyprofoundweakness,anorexia,andanemia,iscausedbyreleaseofcytokinesbythetumororhost.
Paraneoplasticsyndromes,definedassystemicsymptomsthatcannotbeexplainedbytumorspreadorbyhormones appropriatetothetissue,arecausedbytheectopicproductionandsecretionofbioactivesubstancessuchasACTH,PTHrP,orTGF-α.
Gradingoftumorsisdeterminedbycytologicappearanceandisbasedontheideathatbehavioranddifferentiationarerelated,withpoorlydifferentiatedtumorshavingmoreaggressivebehavior.
Staging(extentoftumor),determinedbysurgicalexplorationorimaging,isbasedonsize,localandregionallymphnodespread,anddistantmetastases.Stagingisofgreaterclinicalvaluethangrading.
Every year the approach to laboratory diagnosis of cancer becomes more complex, more sophisticated, and more specialized. For virtually every neoplasm mentioned in this text, the experts have characterized several subcategories; we must walk, however, before we can run. Each of the following sections attempts to present the state of the art, avoiding details of technologies.
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In most instances, the laboratory diagnosis of cancer is not difficult. The two ends of the benign–malignant spectrum pose no problems; in the middle, however, lies a “no man’s land” where the wise tread cautiously. Clinicians tend to underestimate the contributions they make to the diagnosis of a neoplasm. Clinical and radiologic data are invaluable for optimal pathologic diagnosis. Radiation-induced changes in the skin or mucosa can be similar to those of cancer. Sections taken from a healing fracture can mimic an osteosarcoma. The laboratory evaluation of a lesion can be only as good as the specimen submitted for examination. The specimen must be adequate, representative, and properly preserved.
Several sampling approaches are available, including excision or biopsy, fine-needle aspiration, and cytologic smears. When excision of a lesion is not possible, selection of an appropriate site for biopsy of a large mass requires awareness that the margins may not be representative and the center may be largely necrotic. Requesting frozen section diagnosis is sometimes desirable, as, for example, in determining the nature of a mass lesion or in evaluating the regional lymph nodes in a patient with cancer for metastasis. This method, in which a sample is quick-frozen and sectioned, permits histologic evaluation within minutes. In experienced, competent hands, frozen section diagnosis is accurate, but there are particular instances in which the superior histologic detail provided by more time-consuming routine methods is needed. In such instances, it is better to wait a few days, despite the drawbacks, than to perform inadequate or unnecessary surgery.