Mesothelioma

Chapter 8 Mesothelioma

R Nagarjun Rao

TABLE OF CONTENTS

INTRODUCTION 107

CYTOLOGIC FEATURES OF MESOTHELIOMA 107

RARE VARIANTS 110

Clear cell pattern 110

Deciduoid pattern 110

Lymphohistiocytoid pattern 110

Signet-ring cell pattern 111

Small cell pattern 111

DIAGNOSTIC PROBLEMS 111

SPECIAL STAINS IN MESOTHELIOMA 111

IMMUNOCYTOCHEMISTRY 111

OTHER ANCILLARY METHODS 113

INTRODUCTION

Malignant mesothelioma is a tumor that arises from the surface serosal cells lining the pleural, peritoneal, and pericardial cavities. Pleural mesotheliomas are the commonest (∼90%), followed by peritoneal and pericardial mesotheliomas (6–10%).¹ Other locations are vanishingly rare, to be almost non-existent. A strong link exists between mesothelioma and asbestos exposure, first reported in 1960.² Ninety percent of patients with pleural mesothelioma present with pleuritic pain associated with recurrent, unilateral, bloody pleural effusions which usually contain malignant mesothelial cells.³ Therefore, effusion cytology assumes great clinical importance in the diagnosis of mesotheliomas. Nevertheless, cytologic diagnosis of effusions of unknown etiology is difficult. Diagnostic accuracy of effusion cytology is variable, with a particular problem being relatively high false-negative rates, owing to sampling and screening errors.⁴ In addition, there is the well-known cytologic problem of distinguishing between reactive inflammatory/hyperplastic and neoplastic mesothelial cells, and in distinguishing between mesothelioma and adenocarcinoma cells.⁴ The use of adjuvant methods is therefore highly recommended and performed as a routine in most centers.⁴

CYTOLOGIC FEATURES OF MESOTHELIOMA

Cytologic diagnosis of mesothelioma is a difficult proposition, as mentioned, mainly because of the significant overlap that exists between benign and malignant mesothelial cells, and between mesothelioma and adenocarcinoma cells. The basic diagnostic feature of mesothelioma is the resemblance to ‘normal’ or reactive mesothelial cells. On the other hand, this resemblance is at the root of a major diagnostic conundrum; i.e. is this reactive or a neoplastic mesothelial cell population? Diagnostic cytologic criteria have been outlined by various authors.⁵^–¹⁰ Relatively constant cytologic features seen in retrospective studies, which are useful for a diagnosis of mesothelioma (expanded below), include the presence of a single malignant mesothelial cell population, multinucleation, articulation between mesothelial cells (intercellular windows), cell-in-cell arrangements, cytoplasmic vacuoles, peripheral blebs, cluster formation with knobby outlines (scalloped borders), variable nuclear enlargement, prominent nucleoli, and cytoplasmic metachromasia. Based on morphologic cell types, mesotheliomas have been divided into epithelial, sarcomatous, and biphasic varieties. Effusion specimens from epithelial mesotheliomas are generally hypercellular, whereas the spindle cell components in biphasic and sarcomatoid mesotheliomas do not usually exfoliate into effusion fluids, and are not very well seen.⁵

A laboratory can decide on the optimal preparation methods for handling an effusion fluid specimen for cytologic examination. Regardless of the preparation method used, the Papanicolaou (PAP) and a Romanowsky stain are almost always used. Splitting the sample facilitates evaluation of both nuclear (PAP) and cytoplasmic (Romanowsky) characteristics and is optimal for identifying the various discriminatory features of mesothelial cells and adenocarcinoma cells (Chapter 3). In our laboratory a Cytospin preparation stained with Diff-Quik (DQ) (Romanowsky), and a liquid-based cytology preparation stained using the PAP stain are used. A cell block (Figure 8.7) is also mandatorily performed whenever a diagnosis of malignancy is clinically entertained and/or cytologically suspected (Chapter 14). Apart from providing an additional perspective to the cytologic assessment, the cell block facilitates performance of immunocytochemistry (see below and Chapter 5).

Figure 8.7 Cell block from a case of mesothelioma showing hypercellular atypical mesothelial cell groups. Extracellular mucinous material is present in the background (arrow). [Hematoxylin and eosin (HE), 40×.]

Epithelial mesotheliomas exfoliate richly into effusion fluids, producing hypercellular specimens with monolayered sheets as well as three-dimensional cell groups (Figure 8.1). These groups can take various forms, but characteristic of mesothelioma are clusters of cells with irregular, knobby outlines (Figure 8.3). Sometimes they take on a papillary architecture, reproducing a common pattern seen histologically (see Figure 8.3). Acinar formation (a feature of adenocarcinoma) is not seen in mesotheliomas, although intercellular windows between mesothelial cells may appear like acini on occasion (Figure 8.5). Cell engulfment is a common feature. Benign effusions are relatively less cellular, with smaller cell groups that are largely two-dimensional (Figure 8.2). This is an important feature, because even though the individual cells may show considerable atypia, the two-dimensional nature of the cell groups is retained. In adenocarcinoma, although the cell groups are three-dimensional and complex, they generally retain a smooth contour (the so-called ‘community border’) (Figure 8.10) as opposed to the knobby outlines of mesothelioma cell groups (Figures 8.3, 8.5).