Signet ring cell mesothelioma; A diagnostic challenge

Abstract

Signet ring cell mesothelioma is a rare variant of epithelioid mesothelioma with limited cases published. It has a male predilection and most commonly occurs on pleura; it can also arise in the peritoneal cavity. The signet ring cell morphology can pose a challenge leading to a potential diagnostic error. A variety of benign and malignant diseases, including reactive histiocytic hyperplasia, adenocarcinoma, melanoma, and lymphoma with signet ring cell morphology should be considered in the differential diagnosis. In signet ring cell mesothelioma work up, mucin stains are of limited value. Even though immunohistochemistry is routinely used in mesothelioma diagnosis, there is no sole specific mesothelial marker. Hence, a panel of mesothelial and epithelial markers are used; these should be interpreted with caution especially in this variant. Electron microscopy and genetic testing can be very helpful in distinguishing signet ring cell mesothelioma from its mimickers.

Introduction

Malignant mesothelioma (MM) is a neoplasm occurring on serosal surfaces, such as pleura, peritoneum, pericardium, ovary, and tunica vaginalis of testes. According to the 2015 World Health Organization classification [1], MM can be subtyped into four categories: epithelioid, sarcomatoid, desmoplastic, and mixed type (biphasic), the most common which is epithelioid. A few vacuolated cells with signet ring like morphology are not uncommon in epithelioid mesothelioma; however, excessive signet ring like cells in epithelioid mesotheliomas are extremely rare and have been sub-classified as signet ring cell mesothelioma [2]. In 2003, Cook et al. published the first case report on signet ring cell mesothelioma. Thus far due to rarity, signet ring cell variant mesothelioma has had limited cases reported [[3], [4], [5], [6], [7]].

There are well established cytomorphological features to differentiate mesothelial cells, including reactive and malignant types from carcinoma cells and macrophages [8]. However, mesothelioma with signet ring cell features can be a diagnostic challenge since it morphologically mimics many benign and malignant diseases, predominantly signet ring cell adenocarcinoma from lung, stomach, breast, colon, and urinary bladder. Herein, we provide an overview of malignant signet ring cell mesothelioma, its differential diagnosis, and ancillary studies with emphasis on diagnostic pitfalls.