Histopathological findings in a COVID-19 patient affected by ischemic gangrenous cholecystitis

Abstract

Background: Since its first documentation, a novel coronavirus (SARS-CoV-2) infection has emerged worldwide, with the consequent declaration of a pandemic disease (COVID-19). Severe forms of acute respiratory failure can develop. In addition, SARS-CoV-2 may affect organs other than the lung, such as the liver, with frequent onset of late cholestasis. We here report the histological findings of a COVID-19 patient, affected by a tardive complication of acute ischemic and gangrenous cholecystitis with a perforated and relaxed gallbladder needing urgent surgery.

Case presentation: A 59-year-old Caucasian male, affected by acute respiratory failure secondary to SARS-CoV-2 infection was admitted to our intensive care unit (ICU). Due to the severity of the disease, invasive mechanical ventilation was instituted and SARS-CoV-2 treatment (azithromycin 250 mg once-daily and hydroxychloroquine 200 mg trice-daily) started. Enoxaparin 8000 IU twice-daily was also administered subcutaneously. At day 8 of ICU admission, the clinical condition improved and patient was extubated. At day 32, patient revealed abdominal pain without signs of peritonism at examination, with increased inflammatory and cholestasis indexes at blood tests. At a first abdominal CT scan, perihepatic effusion and a relaxed gallbladder with dense content were detected. The surgeon decided to wait and see the evolution of clinical conditions. The day after, conditions further worsened and a laparotomic cholecystectomy was performed. A relaxed and perforated ischemic gangrenous gallbladder, with a local tissue inflammation and perihepatic fluid, was intraoperatively met. The gallbladder and a sample of omentum, adherent to the gallbladder, were also sent for histological examination. Hematoxylin-eosin-stained slides display inflammatory infiltration and endoluminal obliteration of vessels, with wall breakthrough, hemorrhagic infarction, and nerve hypertrophy of the gallbladder. The mucosa of the gallbladder appears also atrophic. Omentum vessels also appear largely thrombosed. Immunohistochemistry demonstrates an endothelial overexpression of medium-size vessels (anti-CD31), while not in micro-vessels, with a remarkable activity of macrophages (anti-CD68) and T helper lymphocytes (anti-CD4) against gallbladder vessels. All these findings define a histological diagnosis of vasculitis of the gallbladder.

Conclusions: Ischemic gangrenous cholecystitis can be a tardive complication of COVID-19, and it is characterized by a dysregulated host inflammatory response and thrombosis of medium-size vessels.

Keywords: COVID-19; Cholecystitis; Coronavirus; Gallbladder; Histopathology; Immunohistochemistry; SARS-CoV-2.

Conflict of interest statement

Dr. Navalesi’s research laboratory has received equipment and grants from Maquet Critical Care, Draeger, and Intersurgical S.p.A. He also received honoraria/speaking fees from Maquet Critical Care, Orionpharma, Philips, Resmed, MSD, and Novartis. Dr. Navalesi contributed to the development of the helmet Next, whose license for patent belongs to Intersurgical S.P.A., and receives royalties for that invention. Dr. Longhini and Dr. Navalesi contributed to the development of a new device, whose patent is in progress (European Patent application number EP20170199831). The remaining authors have no conflict of interest to disclose.

Figures

Fig. 1

The abdomen CT scan of day 32 (a) and day 33 (b) show relaxed gallbladder with dense content (asterisks) and perihepatic effusion (arrows), which increased in the second CT scan (b)

Fig. 2

Hematoxylin-eosin-stained sections of the gallbladder. Inflammatory infiltrates diffusely involve medium-size arteries, with obliteration of their lumen. These features indicate vasculitis with thrombosis. a Lumen obliterated by inflammatory cells with wall breakthrough is indicated by a red arrow, while normal lumen by a black arrow (magnification × 2/0.08 NA); a further magnification of the tissue is represented in c (magnification × 40/0.40 NA). b The black arrow indicates an ischemic obliteration, while the red arrow highlights the presence of nerve hypertrophy (magnification × 2/0.08 NA). d The gallbladder mucosa appears to be atrophic (red arrow); two glands are indicated by black arrows (magnification × 2/0.08 NA)

Fig. 3

Normal adipose tissue is represented in the omentum (black arrow), while vessels are thrombosed (red arrows) (magnification × 2/0.08 NA)

Fig. 4

Immunohistochemical images relative to (1) over endothelial cells expression with anti-CD31 antibody (dark brown) in a (magnification × 2/0.08 NA) and in b (magnification × 10/0.40 NA); (2) tissue macrophages with anti-CD68 antibody (brown) in c (magnification × 2/0.08 NA) and in d (magnification × 10/0.40 NA); and (3) tissue lymphocytes CD4+ (helper) with anti-CD4 antibody (brown) in e (magnification × 2/0.08 NA) and in f (magnification × 10/0.40 NA)