# Case Report: Rare pulmonary infection and cytomegalovirus retinitis revealed a case of lymphoma

## TL;DR

A rare case of lymphoma was discovered through recurring eye infections and unusual lung infections, highlighting the importance of advanced diagnostic tools.

## Contribution

This case report is the first to describe pulmonary co-infection with Tropheryma whipplei and Penicillium digitatum as a presenting feature of EBV+ DLBCL-NOS.

## Key findings

- Recurrent CMVR and rare pulmonary infections can indicate an underlying hematologic malignancy.
- mNGS and PET-CT are essential for diagnosing complex immunodeficiency cases.
- Histopathological confirmation is crucial for definitive diagnosis of EBV+ DLBCL-NOS.

## Abstract

Recurrent cytomegalovirus retinitis (CMVR) and rare opportunistic pulmonary infections may be the initial manifestations of underlying immunodeficiency caused by occult hematologic malignancy. Epstein–Barr virus-positive diffuse large B-cell lymphoma, not otherwise specified (EBV+DLBCL-NOS) is an aggressive lymphoma associated with immune dysfunction, predisposing patients to severe opportunistic infections, including CMVR. However, pulmonary co-infection with Tropheryma whipplei and Penicillium digitatum has not been previously described as a presenting feature of EBV+ DLBCL-NOS.

A 66-year-old male presented with blurred vision and was diagnosed with CMVR, with profoundly low CD4+ T-cell counts (102 cells/μL) and high cytomegalovirus (CMV) DNA levels in blood and aqueous humor. He initially responded to ganciclovir, but CMVR recurred five months later, accompanied by new pulmonary nodules. Despite negative conventional microbiological tests, metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid identified co-infection with Tropheryma whipplei and P. digitatum. Broad-spectrum antimicrobial therapy led to partial clinical improvement, but pulmonary lesions persisted. PET-CT revealed hypermetabolic lung and lymph node lesions, and subsequent lung biopsy confirmed EBV+ DLBCL-NOS. The patient’s progressive immunodeficiency, recurrent CMVR, and refractory pulmonary infection were ultimately attributed to underlying lymphoma.

This case highlights that severe, unexplained immunodeficiency with recurrent CMVR and rare opportunistic pulmonary infections should prompt a high index of suspicion for underlying hematologic malignancy. mNGS and PET-CT are critical tools in the diagnostic workup, but definitive diagnosis relies on histopathological confirmation. Early recognition of such presentations can prevent delays in diagnosing aggressive lymphomas.