Metastases to bones

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Abstract

Metastatic tumors involving the bones may derive from a number of visceral primary sites, and they can assume several histological appearances. In selected instances, diagnostic confusion with some primary bone tumors may eventuate, necessitating the use of adjunctive pathologic studies to reach a final interpretation. This review considers metastatic osseous neoplasms in the small-cell, large-polygonal-cell, and spindle-cell-pleomorphic microscopic categories. The use of immunohistology and molecular analysis to study such tumors is discussed.

Section snippets

Clinical considerations

Many visceral carcinomas are capable of dissemination to secondary bony sites. At autopsy, up to 50% of patients with selected malignant epithelial neoplasms have metastatic osseous involvement.6 In that context, cancers of the prostate, breast, lung, kidney, and thyroid are most commonly implicated.7 Accordingly, adenocarcinomas are more frequently observed as bony metastases than are epithelial neoplasms with other lineages. In surgical pathology practice, recent studies have reported that

Pathological diagnosis of metastatic carcinomas: A pattern-based approach

Selected special histological features of metastatic tumors may be used as potential diagnostic aids. For example, renal cell carcinomas tend to exhibit intratumoral hemorrhage into the lumina of neoplastic tubules (Fig. 4). Also, obvious intracellular mucinogenesis is a relatively common finding in adenocarcinomas of the gastrointestinal tract, pancreas, and lung.25

In addition to the specific microscopic features that have just been mentioned, a systematic approach can be used to the diagnosis

Immunohistochemistry in the determination of primary tumor site

As mentioned throughout the foregoing discussion, immunohistological analysis is the most expeditious means to address the probable origin of a metastatic carcinoma in the bone, if a primary neoplasm is inapparent clinically [metastatic carcinoma of unknown origin (MCUO)]. The underlying tenets for that avenue of study are complex, and they have been discussed in detail in other publications that are devoted especially to diagnostic immunohistology.65, 66, 67, 68, 69, 70 An algorithmic approach

Gene-set analyses of metastatic carcinomas of unknown origin

Using either fresh or formalin-fixed paraffin-embedded tumor tissues, with or without some type of tumor enrichment by microdissection, molecular techniques have been applied to supplement information that is supplied by morphologic assessment and immunohistochemistry in the study of MCUO.71 Extracted DNA or RNA from tissue samples is used with applied gene expression profiling technologies to further characterize the lesion.72 The principal techniques that are now used are represented by

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