Diagnostic Challenges in Epithelioid Pleural Mesothelioma: Case Series with Support from Electron Microscopy

Abstract

The histological diagnosis of pleural epithelioid mesothelioma can be difficult in the case of rare variants or in the definition of neoplasm origin in patients with previous or concomitant tumours. Currently, several immunohistochemical reactions are available in the surgical pathologist's armamentarium that allow us to obtain a more sensitive and specific diagnosis of malignant pleural mesothelioma. However, in some cases, the final interpretation remains inconclusive. Historically, ultrastructural examination has represented a useful tool for the definition of the mesothelial nature of neoplastic cells due to their peculiar morphological characteristics. The recent international guidelines for pathological diagnosis of pleural mesothelioma suggest the use of electron microscopy when the immunohistochemical reactions are equivocal or when further support of a diagnosis of mesothelioma is needed. This paper presents three cases of pleural epithelioid mesothelioma whose diagnoses were finally supported by ultrastructural examination.

Keywords: histology; immunohistochemistry; mesothelioma; transmission electron microscopy.

Figure 1

Panoramic view of the pleural tumour showing a prevalent solid pattern with papillary fronds (a, haematoxylin and eosin stain, original magnification ×50), and several foci of squamous differentiation were evident at higher magnification (b, haematoxylin and eosin stain, original magnification ×100). Immunohistochemistry showing the positivity of Calretinin (c, immunoperoxidase staining, original magnification ×200), D2-40 (d, immunoperoxidase staining, original magnification ×400), positivity of p40 in the squamous cells (e, immunoperoxidase staining, original magnification ×200), and loss of nuclear expression of BAP1 in both the neoplastic components (f, immunoperoxidase staining, original magnification ×200). TEM showing the presence of microvilli and tight junctions (yellow arrows) (g,h, original magnification ×20,000).

Figure 2

CT scan showing an intrathoracic mass with peripheric cystic changes (a), as visible at the cut surface of the gross specimen (b). At histology, the tumour comprised epithelioid cells with eosinophilic cytoplasm and brisk lymphocytic infiltrate (c, haematoxylin and eosin stain, original magnification ×200) that were immunoreactive for Calretinin (d, immunoperoxidase staining, original magnification ×200) and D2-40 (e, immunoperoxidase staining, original magnification ×200). TEM showing the presence of numerous microvilli in direct contact with collagen bundles (yellow arrows). Although some morphological details are affected by a non-optimal conservation, the structures useful for the diagnostic definition of mesothelioma appear to be well preserved (f,g, original magnification ×12,000, ×10,000).

Figure 3

Panoramic view of the pleural biopsy showing a papillary proliferation (a, haematoxylin and eosin stain, original magnification ×25). Immunohistochemistry showing weak positivity for Calretin (b, immunoperoxidase staining, original magnification ×100), D2-40 (c, immunoperoxidase staining, original magnification ×200), loss of nuclear expression of BAP1 (d, immunoperoxidase staining, original magnification ×200), and rare cells positive for estrogen receptor (e, immunoperoxidase staining, original magnification ×400). TEM showing tight junctions (yellow arrows) and branched and elongated microvilli (f–h, original magnification ×3500, ×7000, ×30,000).