Pseudotumor presentation of CMV disease: Diagnostic dilemma and association with immunomodulating therapy

Abstract

Cytomegalovirus (CMV) infection is a significant cause of morbidity in immunocompromised patients where a predictable spectrum of illness has been well described. Atypical presentations of CMV infection, including those mimicking mass lesions, otherwise known as pseudotumors, have been occasionally reported in the literature. These lesions were first seen in the context of significant immunosuppression associated with human immunodeficiency virus (HIV) but more recently, cases have been described in the non-HIV setting. Here within, the authors present two cases in patients receiving newly developed immunomodulatory therapy in the form of pembrolizumab for the management of cancer and belatacept in a kidney transplant recipient. A review of other non-HIV cases reported in the literature was also undertaken to gain a better understanding of this unusual presentation.

A Novel Intersection - Cytomegalovirus Gastritis Following Cemiplimab and Talimogene Laherparepvec in a Patient with Advanced Cutaneous Squamous Cell Carcinoma: a Case Report

“…Tay et al [3] noted a mere 0.3% overall occurrence of CMV detection in those administered ICIs. In a vast majority of cases, invasive CMV disease in patients with solid malignancies on ICIs complicated irAEs that required high-dose corticosteroids and other immunomodulatory drugs [3,[10][11][12][13][14][15][16][17][18][19][20], which could be explained by the fact that CMV has tropism to in amed tissues. Consequently, there's a signi cant occurrence of CMV infection among patients with severe acute in ammatory bowel disease (IBD), and the frequency is even higher in those with steroid-resistant conditions.…”

“…Furthermore, there was no concurrent H. pylori infection or a history of current immunosuppression, as reported in the literature. [3,4,[10][11][12][13][14][15][16][17][18][19][20]22] However, our patient complained of dyspepsia for 6 months halfway through his cemiplimab therapy course, which may have represented an unrecognized form of irAE-gastritis before he was diagnosed with CMV.…”

Cytomegalovirus Infections in Patients Treated With Immune Checkpoint Inhibitors for Solid Malignancies

“…The remaining 5 of 16 cases (including the case presented here) developed CMV disease without a history of immunosuppressive treatment: 4 had CMV gastritis, and 1 had CMV pseudotumor of the left lower jaw. In 3 of them, CMV disease developed either concurrently with an irAE [ 12 ] or at sites of a previous inflammation (current report and [ 22 ]). Fifteen patients underwent a biopsy of the affected organ and in 14 of 15, cytopathic changes consistent with CMV disease were identified on histology.…”

“…Smibert et al proposed that localized trauma (because of tumor resection) triggered increased viral shedding. Subsequently, the addition of ICI led to the restoration of virus-specific T cells and an exaggerated inflammatory response to CMV antigens, leading to an immune reconstitution inflammatory-like syndrome [ 22 ]. The severity of pathology findings in our patient, despite the low numbers of identified CMV + cells, is consistent with the above mechanism.…”

Resistant herpes simplex virus infections – who, when, and what's new?

“…1c), a verrucous lesion(s) that appears exophytic and proliferative resembling either a wart or pseudotumor, characterized by a predominant polyclonal lymphoplasmacytic infiltration [4]. Cytomegalovirus can also cause pseudotumors [5]. Fortunately, systemic infections such as meningoencephalitis and visceral disease from ACV-R HSV are rarely reported, although clinicians should think of this diagnosis in patients not responding to ACV, especially given the significant morbidity and mortality with systemic infections.…”