HISTOPATHOLOGY AND CYTOPATHOLOGY IN THE DIAGNOSIS AND ASSESSMENT OF AND MESOTHELIOMA

GUIDELINES

INTRODUCTION

Histopathology and/or cytopathology play a central role in and mesothelioma. For lung cancer, they are crucial also to its staging, in , and in the confirmation of .

of lung cancer usually involves examination of cells shed in sputum, washed or brushed from airways, or aspirated from a pulmonary mass. Less often, a primary diagnosis may be obtained from deposits in lymph nodes or other tissues or from fluid aspirated from the pleural space. For mesothelioma, it involves examination of cells aspirated from the pleural space.

Similarly, histological assessment for initial diagnosis of lung cancer usually involves examination of bronchial, transbronchial, or transthoracic needle biopsy specimens. Rarely, it is obtained from pulmonary tissue taken at video-assisted thoracoscopy or at thoracotomy. Sometimes, a primary diagnosis is obtained from tissue sampled by needle, incisional or excisional biopsy of lymph nodes, the pleura, or other tissues into which a tumour might have invaded or . If there is strong suspicion of malignancy but no morphological diagnosis has been achieved, an intraoperative frozen section diagnosis is often requested. For mesothelioma, diagnosis may be based on material obtained by needle biopsy or at video-assisted thoracoscopy or thoracotomy.

The principles of diagnosis are similar for both cytology and histopathology, involving morphological assessment after appropriate basic staining (classically Papanicolaou and Giemsa for cytology; haematoxylin and eosin for histology) supplemented, as necessary, by immunochemistry. Accurate morphological assessment by a in the pathology of pulmonary tumours is the cornerstone of diagnosis, supplemented by the judicious use of immunochemistry.

GUIDELINES

Specimens should be handled and reported by a pathologist experienced in the diagnosis of pulmonary neoplasia, and malignant cases (and others as decided by the local Multidisciplinary Team) should be reviewed by the local lead thoracic pathologist (or their deputy), who should attend the appropriate Multidisciplinary Team Meetings.

Material for cytology must be well-preserved to allow critical assessment of cellular morphology. It must be transported to the laboratory as quickly as possible in a suitable preservative or prepared ‘at the bedside’, in which case care must be taken to ensure the operator is able to produce preparations of appropriate quality. Routine staining with Papanicolaou or Giemsa is usually sufficient for the diagnosis of carcinoma. from pleural fluid should routinely involve preparation of a cell block and immunochemistry.

Specimens for histology should be immediately placed in formalin. Small biopsy specimens should be sectioned at multiple levels, but not to extinction of the specimen; ideally, half of the specimen should remain in the wax block. Examination after routine staining with haematoxylin and eosin is usually sufficient for the diagnosis of lung cancer. The diagnosis of mesothelioma should always include immunochemistry.

Intraoperative frozen section diagnosis should be arranged as far in advance of surgery as possible and after consultation between the surgical team and a pathologist experienced in the interpretation of frozen sections of pulmonary tumours. The fresh specimen should be transported to the laboratory by an appropriate member of medical or technical staff.

Tumours should be classified (and graded where appropriate) according to the criteria and using the terminology of the latest (1999) World Health Organisation’s Histological Typing of Lung and Pleural Tumours.

Immunochemistry should be employed as deemed appropriate. For initial diagnosis of lung cancer, this is usually for one of two indications:

(i) To determine whether an adenocarcinoma in the lung is primary or metastatic. The most useful antigens in this differential diagnosis are (TTF)-1 and cytokeratins of class 7 (expressed by primary pulmonary adenocarcinomas) and cytokeratins of class 20 (expressed by extrapulmonary adenocarcinomas, especially those of the gastrointestinal tract). Others might be employed in specific instances, especially in an individual known to have had a previous malignancy elsewhere.

(ii) To differentiate between neuroendocrine (predominantly small cell and large cell neuroendocrine carcinoma) and non-neuroendocrine (‘non-small cell’) carcinoma of the lung. The most sensitive and specific antigenic markers of neuroendocrine differentiation in this context are NCAM (CD56), synaptophysin and chromogranin, but these are not always expressed by poorly differentiated neuroendocrine tumours.

It should be noted that there no antigens currently available to distinguish between primary and metastatic squamous cell carcinoma in the lung.

For the diagnosis of mesothelioma, particularly its distinction from pleural involvement by adenocarcinoma, immunochemistry using a panel of antibodies recognising antigens indicative of both mesothelial and glandular differentiation is essential. None of those currently available is adequately sensitive or specific alone and panels vary according to the preference of the individual pathologist. Most often applied in the recognition of mesothelial differentiation are cytokeratins of classes 5/6, calretinin, N-cadherin, thrombomodulin, and the HBME-1 antigen. Most often used in the recognition of glandular differentiation are epithelial glycoprotein, carcinoembryonic antigen and the CD15 antigen. For histopathology in particular, the pattern of expression of these antigens should be interpreted in the context of the morphology.

Resected tumours should be examined to permit assessment according to the requirements of the Royal College of Pathologist’s ‘minimum dataset’, a copy of which is attached. This is essentially a ‘list’ of objective characteristics that should be seen as an adjunct to a comprehensive narrative report rather than a replacement of it.

JR Gosney
April 2005

Reviewed / accepted May 09 by Chair of Pathology CNG