Detection of Nodal Micrometastases in Head and Neck Cancer by Serial Sectioning and Immunostaining

Detection of Nodal Micrometastases in Head and Neck Cancer by Serial Sectioning and Immunostaining

Drs. Ambrosch and Brinck appropriately emphasize the problems and limitations encountered when using routine pathologic procedures to examine lymph nodes from head and neck cancer specimens. Extraordinary processing techniques have repeatedly yielded a larger number of small nodes and, on occasion, have demonstrated the presence of micrometastases. The majority of these observations come from examination of breast specimens and their axillary dissections. Labor-intensive clearing techniques have varied to some extent, but generally involve progressive removal of opaque fat with alcoholic solvents of increasing percentages culminating in absolute alcohol (100%). Final visualization involves submerging the defatted specimen in cedarwood oil, followed by careful examination and dissection of the backlighted specimen.

Pickren was among the first to advocate this procedure [1]. Subsequent studies failed to uniformly demonstrate the beneficial effect of this time-consuming, expensive procedure as it applies to the management of patients with breast carcinoma. As with breast carcinoma, conflicting reports have appeared concerning the efficacy and utility of these laborious pathologic examinations of specimens from the head and neck.

The authors correctly point out that the presence of micrometastases in the head and neck region leaves many unanswered questions. The present contribution does give us additional insights, and once again demonstrates that, in utilizing a routine technique, we overlook small metastatic deposits of carcinoma in the necks of selected patients.

Importance of Diligent Pathologic Examination

It is now clearly established that the size, number, and level of involved cervical nodes are important prognostic predictors and that extracapsular spread has a negative impact on the patient's final outcome. The authors' finding that approximately 8% of clinically negative necks (N0) harbored micrometastatic disease should alert pathologists and clinicians to the possibility of a negative clinical impact, particularly in patients with lesions of the mouth and oral pharynx. This finding reaffirms the need for diligent pathologic examination to search for small lymph nodes, since metastases were demonstrated in nodes less than 5 mm in diameter.

In the current era of worldwide cost containment, it seems imprudent to suggest the routine use of clearing, immunohistochemistry, or serial sections, as was performed by Ambrosch and Brinck. It is obvious that we should continue to search for micrometastases and particularly for extracapsular extension. I agree with the authors that it is exceedingly difficult to prospectively determine the depth of invasion; however, in our experience, the use of MRI and CT has greatly improved our T-staging sensitivity. Also, as the authors note, the accuracy of nodal assessment has shown approximately a 50% improvement.


I am in complete agreement with the authors' conclusion that serial microscopic sectioning of lymph nodes reveals additional micrometastases but is impractical for routine use. Selective individualized treatment of the neck in patients at risk for failure in this area seems quite rational, particularly when correlated with image analysis performed by experienced radiologists.

Cooperative studies conducted by a multidisciplinary group, including radiation oncologists, surgeons, and pathologists with expertise in this area, are needed to establish optimal treatment approaches [2]. As with all malignant disease, the goal of management for head and neck cancer remains early detection prior to metastases and, when the volume of tumor permits, ablation with minimal morbidity.


1. Pickren J: Significance of occult metastases. Cancer 121:1266-1271, 1961.

2. Janot F, Klijanienko J, Russo A, et al: Prognostic value of clinicopathological parameters in head and neck squamous cell carcinoma: A prospective analysis. Br J Cancer 73:531-538, 1996.

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