Review
Clinical significance of micrometastasis in lung and esophageal cancer: a new paradigm in thoracic oncology

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Abstract

In the past decade, detection of micrometastatic disease in different clinical samples including pleural lavage, lymph node, bone marrow, and blood has become a rapidly growing area of interest in research of non-small cell lung cancer and esophageal cancer. The results of these studies support the concept that, just as in many other solid malignancies, systemic spread may happen at an early stage in non-small cell lung cancer and esophageal cancer. Such systemic spread is often occult (micrometastases) at the time of primary diagnosis, which may have adverse effects on survival. Improved staging can be expected with information on micrometastases, and a subgroup of patients who will benefit most from adjuvant therapy might be identified. Although reliable and standard methods need to be developed before detection of micrometastasis is incorporated in the routine clinical practice, we suggest that it be considered an important correlate in clinical trials in non-small cell lung cancer and esophageal cancer.

Section snippets

Definition of micrometastasis

In this review, we have defined “micrometastasis” as a metastasis from a nonhematopoietic malignancy that is not detected with conventional clinicopathologic methods of staging. This has different meanings based on the location involved (pleural cavity, lymph node, blood, and bone marrow) [2]. “Occult pleural dissemination” of tumor cells is defined as tumor cells found by pleural lavage cytology (PLC) during surgical intervention in patients with EC or NSCLC who have no clinical or radiologic

Cytology

Cytology is an old but useful tool in the diagnosis of cancer. Peritoneal lavage cytology has been found to be a useful staging procedure during operations for gastric cancer and malignant ovarian neoplasms. In recent years, PLC has been used to identify occult disseminated tumor cells in the chest for NSCLC and EC during surgical intervention.

Immunocytochemistry and immunohistochemistry

Detection of occult epithelial tumor cells in lymph node, bone marrow, and blood relies on methods that distinguish cells with different origins (eg,

Pleural cavity

Like the peritoneal cavity, the pleural cavity is a good place for tumor cell transplant of intrathoracic malignancies. Pleural lavage cytology has been applied to detect occult pleural dissemination in the past. In addition to cytology, the reverse transcriptase PCR technique has been used for detection of peritoneal dissemination of gastric and ovarian cancers, and the technique was proved to be more sensitive [8]. However, there are few reports on the application of such new molecular

Pleural lavage cytology in NSCLC and EC

In recent years, several reports have been published on the prognostic value of PLC in NSCLC patients without a pleural effusion who are undergoing surgical resection 14, 15, 16, 17, 18, 19, 20, 21. The positive rate of PLC for NSCLC varied widely, from 3.7% to 38.6%, a difference that might be attributable to different stages of patients enrolled and different techniques or diagnostic standards used (Table 1). Although the results of the relationship between positive PLC and clinicopathologic

General considerations and future directions

The presence of metastases at the time of diagnosis of a primary tumor is a well-established poor prognostic indicator. The impact of micrometastases on outcome is less clear in most solid tumors. Nevertheless, there is increasing evidence to suggest that, in NSCLC and EC, the presence of LNM and BMM on presentation indicates a more biologically aggressive tumor, as evidenced by the verification of viability of micrometastasis tumor cells and, most important, by increased locoregional and

Acknowledgements

The authors thank Dr Stephen J. Meltzer for reviewing the manuscript.

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    Copyright © 2002 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.