Identification of occult micrometastases and isolated tumour cells within regional lymph nodes of previously diagnosed non‐metastatic (stage 0) canine carcinomas

Abstract

Metastatic dissemination of carcinomas to lymph nodes impacts prognosis and treatment recommendations in human and veterinary medicine. Routine histopathologic evaluation of regional lymph nodes involves haematoxylin and eosin (H&E) staining to identify intra-nodal neoplastic cells; however, identification of small volume metastases (micrometastases and individual tumour cells) may be missed without the aid of immunohistochemistry or additional step-sections. The aim of this study was to identify occult carcinoma metastases in previously diagnosed non-metastatic lymph nodes using step-sections and pancytokeratin (panCK) immunohistochemistry. Samples from 20 regional lymph nodes diagnosed as non-metastatic were serially sectioned and evaluated with panCK. Of these, 25% (n = 5) contained micrometastases (n = 1) or isolated tumour cells (n = 4). This study demonstrates the increased efficacy of serial step-sections combined with panCK immunohistochemistry to identify small volume metastases in regional lymph nodes. The prognostic significance of micrometastases and isolated tumour cells in regional lymph nodes warrants further investigation in veterinary medicine.

Diagnostic accuracy of contrast‐enhanced computed tomography for assessment of mandibular and medial retropharyngeal lymph node metastasis in dogs with oral and nasal cancer

“…It is possible that these techniques may have revealed metastatic cells, previously unidentified microscopically. Step sections and immunohistochemistry are standard practice in assessment of human lymph nodes and have recently been evaluated in veterinary patients . It is likely that the use of immunohistochemistry would have increased the number of lymph nodes in our population identified as containing isolated tumour cells; however, no change would be expected in the number of lymph nodes with macrometastasis .…”

“…Step sections and immunohistochemistry are standard practice in assessment of human lymph nodes and have recently been evaluated in veterinary patients . It is likely that the use of immunohistochemistry would have increased the number of lymph nodes in our population identified as containing isolated tumour cells; however, no change would be expected in the number of lymph nodes with macrometastasis . Ultimately, the use of step sections and immunohistochemistry would not be expected to alter the conclusions of this study and may have led to a further decrease in overall sensitivity of CT for lymph node metastasis.…”

“…41,[55][56][57] It is likely that the use of immunohistochemistry would have increased the number of lymph nodes in our population identified as containing isolated tumour cells; however, no change would be expected in the number of lymph nodes with macrometastasis. 57 Ultimately, the use of step sections and immunohistochemistry would not be expected to alter the conclusions of this study and may have led to a further decrease in overall sensitivity of CT for lymph node metastasis. This study is also limited by shrinkage artefact associated with fixation and tissue processing, damage to tissue during handling and underestimation of metastatic volume due to measurement of only the apparently largest of several metastases.…”

Surgical margins in the veterinary cancer patient

“…Immunohistochemistry for keratin proteins on sentinel lymph nodes from women with breast cancer finds metastatic disease in 18% of axillary lymph nodes that are negative on routine histopathology . Recent literature suggests this same concept is also applicable to identification of canine metastatic carcinomas …”

“…One publication estimated that for melanoma in situ , breadloafing at 1, 2, 4 and 10 mm intervals would have a 58, 37, 19 and 7% chance of detecting positive margins respectively . As illustrated in the sentinel lymph node literature, detection sensitivity might be improved by serial sections and special techniques . Immunohistochemistry for keratin proteins on sentinel lymph nodes from women with breast cancer finds metastatic disease in 18% of axillary lymph nodes that are negative on routine histopathology .…”