key: cord-0682094-dfcb9kzv
authors: Rossi, Giulio; Caruso, Dora; Stella, Franco; Davoli, Fabio
title: Histologic Confounding Findings in Coronavirus disease 2019 (COVID-19) Pathology
date: 2020-11-25
journal: J Thorac Oncol
DOI: 10.1016/j.jtho.2020.06.017
sha: 0275110c2ec4cc408544456f374e5fa7de6f7608
doc_id: 682094
cord_uid: dfcb9kzv

nan

To the Editor:

We read with interest the study by Cai et al. 1 on the appearance of coronavirus disease 2019 (COVID-19) in the perioperative period among seven patients undergoing lung surgical resections for oncologic purposes. The study gives some important messages concerning the findings of ground-glass opacities and lymphopenia in the early days after pulmonary surgical resection as key signs for suspecting COVID-19. However, we would like to raise concerns about the histologic features attributed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the peritumoral lung tissue of patient number 1.

This patient had a centrally located squamous cell carcinoma and the histologic features reported in Figure 2A describes a diffuse lung interstitial inflammation and a thickened alveolar septum and fibrous connective tissue proliferation with plasma cell and macrophage in Figure 2B . Macrophages and foam cells filling the alveolar cavities are quite different from the classic pulmonary alterations so far described in SARS-CoV-2. In fact, interstitial organizing fibrosis with inflammatory infiltrates comprising plasma cells and macrophages are rather related to obstructive pneumonia secondary to neoplastic bronchial occlusion.

Inflammatory changes are quite common in squamous cell carcinoma obstructing the airways, frequently leading to interstitial inflammatory cells, alveolar accumulation of foamy macrophages, and organizing fibrosis. 2 It is possible that these tumor-related fibroinflammatory modifications may have obscured some histologic changes caused by SARS-CoV-2, but the described features in the lung parenchyma of patient number 1 should be considered with caution as they may not be completely related to COVID-19.

Of note, these pulmonary histologic changes incorrectly assigned to SARS-CoV-2 may represent confounding data that may deter correct comprehension of the COVID-19 pathogenesis. Similarly, Goldsmith et al. 3 evidenced the possible misinterpretation of viral particles as cross-sections of the rough endoplasmic reticulum with surrounding ribosomes at the electron microscope in endothelial cells. 4 As highlighted by Martines et al. 5 in a series of eight autoptic cases of patients with COVID-19, the tissue obtained from autopsies may reveal confounding features secondary to invasive ventilation, drugs, superimposed infections, important comorbidities (hypertension, obesity, cardiovascular diseases, diabetes mellitus), and even autolytic artifacts, partly or entirely, precluding a correct understanding of COVID-19.

The comprehensible urgency to have more details about this dramatic and poorly-known disease should not undermine a meticulous and deep exploration of pulmonary histopathologic lesions related to COVID-19 that may likely be obscured by coexisting pathologies.

To the Editor: We appreciate the comments and concerns raised by Rossi et al. 1 regarding our report on histologic findings in a patient with coronavirus disease 2019 (COVID-19). 2 As noted by Rossi et al., 1 it is possible that the coexisting tumor-related obstructive pneumonitis and comorbidities might have interfered with the interpretation of the histologic findings of patient 1; we would like to address this accordingly.

Obstructive pneumonitis is always observed in the lung parenchyma distal to the bronchial obstruction by a neoplasm. Patient 1 had squamous cell carcinoma, which was located at the posterior basal segment of the right lower lobe. As described in our report, an extensive interstitial inflammation of the lung was consistently observed on multiple sections, which were multisampled far from the tumor at other segments; obviously, these findings should not be considered as the result of the obstruction by the tumor.

Moreover, interpretation of the findings, given the background of the patient's comorbidity, needs extra caution. Patient 1 had interstitial lung disease and presented the usual radiographic pattern of interstitial pneumonia. The most characteristic histologic feature of interstitial pneumonia is patchy interstitial fibrosis admixed with normal parenchyma, whereas infiltration by lymphocytes and plasma cells is generally sparse. 3 However, the pathologic examination of patient 1 revealed interstitial inflammation with numerous plasma cell infiltrations and a large number of macrophages and foam cells in the alveoli. The histologic features were distinctively different from those of interstitial pneumonia. In a recent study, a predominantly large number of activated plasma cells with scattered alveolar macrophages were found in the bronchoalveolar lavage specimen from a patient with COVID-19. 4 The findings of this study suggest that the peculiar abundance of CD138-positive plasma cells in COVID-19 may be a relevant feature.

It is definitely true that preexisting or coexisting disease might hamper the correct understanding of the morphologic changes in COVID-19, particularly in the absence of diffuse alveolar damage that has been found to be the salient feature of COVID-19 pneumonitis on microscopy. 5 Nevertheless, it should be noted that, in our report, the lung specimen was taken when the patient had no symptoms, and the pathology is always consistent with the disease severity. Although there is currently lack of solid data to make an assertion, we still have reasons to speculate that the extensive interstitial inflammation with plasma cell and macrophage infiltration, and also the numerous macrophages in the alveoli might be a pathologic change related to COVID-19.

Coronavirus disease 2019 in the perioperative period of lung resection: a brief report from a single thoracic surgery department in Wuhan

Atlas of Tumor Pathology: Tumors of the Lower Respiratory Tract. Washington DC: Armed Forces Institute of Pathology

Electron microscopy of SARS-CoV-2: a challenging task

Endothelial cell infection and endotheliitis in COVID-19

Pathology and pathogenesis of SARS-CoV-2 associated with fatal coronavirus disease, United States. Emerg Infect Dis

Histologic confounding findings in coronavirus disease 2019 (COVID-19) pathology