key: cord-0871770-urqed43m
authors: Katal, Sanaz; Aghaghazvini, Leila; Gholamrezanezhad, Ali
title: Chest-CT findings of COVID-19 in patients with pre-existing malignancies; a pictorial review
date: 2020-06-09
journal: Clin Imaging
DOI: 10.1016/j.clinimag.2020.06.004
sha: 0ea06197c0e9ca3a26993f743c7839cbbfde0421
doc_id: 871770
cord_uid: urqed43m

As of April 17th, 2020, more than 2,190,010 COVID-19 cases with 147,010 deaths have been recorded worldwide. It has been suggested that a high mortality rate occurs in patients with severe disease and is associated with advanced age and underlying comorbidities, such as malignancies. To the best of our knowledge, no study has been conducted to evaluate chest CT features in patients with malignancy and concomitant COVID-19 infection. In fact, the imaging findings can be challenging and have not yet been fully understood in this setting. In this manuscript, we go over imaging findings in chest CT of patients with COVID-19 and known cancer. With the ongoing COVID-19 pandemic and exponentially increasing incidence throughout the world, in at-risk and vulnerable populations such as patients with known malignancies, infection with SARS-CoV-2 should be included in the differential considerations even with atypical image pictures. Detection of superimposed infection in patients with cancers who present with pulmonary infiltrations warrant correlation with clinical picture, contact history, and RT-PCR confirmatory testing.

In late December 2019, an outbreak of novel coronavirus disease (known as was first reported in the city of Wuhan (China). With new cases emerging rapidly across the other regions of China and worldwide, COVID-19 has been stated as a global pandemic by the World Health Organization (WHO). As of April 17th, 2020, more than 2,190,010 COVID-19 cases with 147,010 deaths have been recorded worldwide [1] .

Although most patients with COVID-19 initially present with fever and mild to moderate respiratory symptoms [2] , various degrees of pulmonary manifestations develop later on chest computed tomography (CT) studies. It has been suggested that a high mortality rate occurs in patients with severe disease and is associated with advanced age and underlying comorbidities, such as malignancies [3] [4] [5] . The study by Liang W et al. [6] on 1,590 patients with COVID- 19 in China has asserted that pre-existing conditions (including malignant neoplastic disease) correlate positively with poorer clinical outcomes, similar to previous findings in other severe acute respiratory diseases, such as SARS and MERS [7] . Eighteen patients with a history of cancer were found among 1590 patients with confirmed coronavirus disease 2019 (COVID-19), which was higher than the general population, probably indicating a higher risk of viral infection in this population. On the other hand, patients with concomitant COVID-19 and cancer were noted to have a higher risk of severe events.

Despite some uncertainties due to lack of sufficient data in this field [8, 9] , patients with cancer should be considered susceptible to infection due to their immunocompromised status caused by the malignancy and chemoradiotherapy. Therefore, during the present widespread community transmission of COVID-19 pneumonia, some practical steps regarding diagnosis and management of the infection in patients with pre-existing malignancies should be taken.

Due to the limited availability of viral testing kits and growing concern for test sensitivity from earlier reports [10] , chest CT has been considered to be a J o u r n a l P r e -p r o o f fundamental element of the evaluation of patients with suspected or known COVID-19 infection. Indeed, CT has been found to be useful as a fast and sensitive diagnostic tool for COVID-19 infection to improve patients' management. The spectrum of radiological findings seen in COVID-19 have been widely discussed in literature [11] [12] [13] [14] ; Multifocal bilateral ground-glass opacities (GGOs) with a peripheral distribution and later superimposition of consolidation and possible vascular ectasia have been reported as the main imaging features.

However, most of these publications have been merely focused on acute respiratory COVID-19 infection occurring in general population, mainly previoushealthy patients without underlying diseases. Only a few studies have described CT patterns of COVID-19 pneumonia in individuals with the pre-existing pulmonary disease [15, 16] . To the best of our knowledge, no study has been conducted to evaluate chest CT features in patients with malignancy and concomitant COVID-19 infection and the specific imaging findings have not yet been fully understood in this setting. In this manuscript, we go over imaging findings in chest CT of patients with COVID-19 and known cancer.

The spread of COVID-19 pneumonia has affected the routine diagnosis and management of most chronic diseases, including malignancies [17] [18] [19] [20] [21] . As mentioned before, patients with pre-existing cancer are not only more susceptible to the disease, but also pose a poorer clinical prognosis [6] .

Specifically, patients with lung cancer require particular attention due to the higher mortality rate [18] . However, accurate diagnosis and optimal treatment of COVID-19 in patients with lung cancer can present a real challenge to clinicians.

Many symptoms of pneumonia may resemble the symptoms or complications of lung malignancies. Even the radiologic findings of lung cancer, such as parenchymal consolidation, spiculation, and microlobulations are not specific, and infections can present similar features [22] . To carefully identify COVID-19 J o u r n a l P r e -p r o o f infection in patients with lung cancer who develop respiratory symptoms, epidemiologic data, and detailed clinical history combined with chest CT seem to be of great value.

Imaging findings of COVID-19 infection in patients with lung cancer consist of multiple patchy GGOs and consolidations [18] , which can be hardly separable from the primary lung tumor (Fig. 1) . However, although peripheral GGOs and consolidations are usually highly suggestive of superimposed COVID-19 pneumonia, these findings can be hardly distinguishable from an underlying lung malignancy or other opportunistic infections in patients with known lung cancer and warrant clinical, epidemic and laboratory correlation with PCR testing.

As per the early published reports from China, patients with cancer infected with SARS-CoV-2 are at a higher risk of complications, ICU admission, mechanical ventilation, and death (6) . Active hematologic cancers such as non-Hodgkin lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, acute lymphoblastic leukemia, and multiple myeloma [23, 24] are believed to have a significant risk for developing COVID-19 infection, due to their profound immune deficits. Patients on chemotherapy or with a history of marrow transplant constitute the most vulnerable population [25] [26] [27] [28] [29] .

J o u r n a l P r e -p r o o f Due to this high vulnerability, all patients with neutropenic fever might be considered undergoing CT-scan to determine to exclude parenchymal abnormalities. Generally, CT findings of COVID-19 pneumonia in patients with underlying hematologic malignancies include interstitial or alveolar infiltrations, resulting in reticulations or ground-glass opacities (Fig. 2, 3, and 4) . However, in leukemic patients, non-infectious diseases (such as hemorrhage and adult acute respiratory distress syndrome [ARDS] may also present with similar features [29] .

Hence, a definitive diagnosis cannot always be made based on imaging features alone.

On the other hand, it cannot be overemphasized that COVID-19 in AML patients may present with atypical or subtle findings, which presents an important challenge in their diagnosis and timely treatment. In this setting, CTscan may demonstrate only minimal small ground-glass lesions in the lungs, disproportionate to the patient's symptomatology (Fig. 2) . This suggests that during the pandemic, in patients with hematologic malignancies, COVID-19 should be considered among the differential considerations even with mild or atypical clinical presentations and subtle and atypical radiologic findings. In this specific patient population, the threshold for RT-PCR testing should be significantly lower, particularly for those who live in the endemic regions. Also, atypical radiologic presentations cannot necessarily exclude COVID-19 infection in the presence of an underlying hematologic disease.

Similar to leukemia, pulmonary infiltrative lesions in CT-scan of patients with lymphoma can be representative of various pathologies [30] . Acute respiratory SARS-CoV-2 infection may sometimes complicate the underlying pulmonary lymphomatous infiltration (Fig. 5) . In this setting, GGOs and patchy consolidation patterns could be suggestive of superimposed COVID-19, which needs confirmation by RT-PCR. However, differentiation between the various causes of J o u r n a l P r e -p r o o f radiologic pulmonary lesions in these patients is not always straightforward and may lead to diagnostic difficulties.

Like other malignancies, breast cancer patients are in lower immune status and prone to adverse reactions, such as leukopenia and other treatment-related complications during the course of chemotherapy. Therefore, they are considered to be at high risk for pneumonias and at a higher risk of developing severe events [31] . COVID-19 in patients with breast cancer demonstrate multifocal pulmonary GGOs (Fig. 6) , which can be hard to be differentiated from the underlying pulmonary metastases (Fig. 7) .

It has not yet been fully explored as to whether patients with gastrointestinal cancers are more prone to SARS-CoV-2 infection compared to the rest of the population [32] . In a recent analysis from China [6] , eighteen of 1590 COVID-19 cases (1%) had a history of cancer, among which, three patients had a history of colorectal cancer. It was found that patients with COVID-19 and cancer have a higher risk of severe complications. During the COVID-19 epidemic, patients with gastrointestinal tumors who develop respiratory symptoms should be closely monitored with clinical and epidemiologic data, chest CT-scan and, RT-PCR panel.

Pulmonary infiltrative lesions, including GGOs, even in atypical distribution, should be considered highly suspicious for COVID-19 in this setting and warrant further evaluation by RT-PCR (Fig. 8, 9, and 10 ). It should also be pointed out that a thorough investigation of chest CT-scan is mandatory in all cancer patients with suspect or known COVID-19 infection, in order to avoid missing significant accompanying pathologies, such as newly-appeared metastases ( Fig.9 and 10 ). Pulmonary infiltration in patients with malignancies can be caused by many infectious and non-infectious etiologies [33] . However, the ongoing COVID-19 pandemic and exponentially increasing incidence throughout the world, in at-risk and vulnerable populations such as patients with known malignancies, infection with SARS-CoV-2 should be included in the differential considerations.

Furthermore, given lower immune function, a substantial number of these patients may represent atypical clinical symptoms or imaging features, such as few or single pulmonary consolidations or GGOs, which makes the early diagnosis more challenging. Radiologists must be aware that atypical, rare, or subtle CT patterns may be among the presenting radiological features of COVID-19 infection in patients with pre-existing cancer, especially those with hematologic malignancies, history of multiple chemotherapies, and leukopenia. Therefore, raised clinical index of suspicion and low threshold for diagnostic testing, such as RT-PCR and chest CT is needed to allow earlier detection and treatment of this potentially life-threatening disease. Constant vigilance can help early diagnosis, not only for timely diagnosis, but also to ensure appropriate post-exposure precautions are implemented.

A fifty-year-old patient with history of lung cancer presented with new-onset fever. Axial images of chest CT reveal lobulated right para-hilar mass (a; black arrows), resulting in post-obstructive collapse and consolidation, consistent with the patient's known lung cancer. Associated ground-glass opacity involving the right upper lung (a, b; white arrows) is also noted, concerning for superimposed atypical infection, such as COVID-19, a diagnosis which was subsequently confirmed with RT-PCR. The narrowing of right main bronchus (c; curved arrow) is also observed. Furthermore, soft tissue window images of the chest reveal prominent right para-tracheal and internal mammary lymphadenopathy (d;☆), which can be metastatic in etiology or reactive to concomitant infectious/inflammatory

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