Received: 20 September 2019 Revised: 28 October 2019 Accepted: 29 October 2019

DOI: 10.1002/dc.24343

BRIEF REPORT

Cytologic features of vaping-induced lung injury: A case report

Fernando Alekos Ocampo-Gonzalez MD | Ji-Weon Park MD

Department of Pathology, Rush University

Medical Center, Chicago, Illinois
Correspondence
Fernando Alekos Ocampo-Gonzalez, MD,
1750 W. Harrison St. Suite 570, Chicago,
Illinois.
Email: fernando_a_ocampogonzalez@rush.edu
Abstract
Vaping-induced lung injury is a recently recognized phenomenon owing to the ris-
ing popularity of e-cigarette use. A cluster of cases of varying severity, including
six deaths, was recently reported in the United States by the Centers for Disease
Control. The objective of this report is to highlight the cytologic features sugges-
tive of vaping-induced lung injury. A 20-year-old previously healthy man presented
with a 7-day history of progressively worsening respiratory symptoms including
dyspnea on exertion, cough, and fever, with no improvement after initiating a
course of antibiotics. No relevant travel or occupational history was reported, but
patient endorsed daily use of e-cigarette with a fluid containing both tetrahydro-
cannabinol and nicotine. Radiographic studies demonstrated scattered areas of
interlobular septal thickening and diffuse ground-glass opacities in both lungs.
Laboratory tests for HIV and influenza were negative. Bronchoscopy and
bronchoalveolar lavage were performed, with cytologic study showing clusters of
benign bronchial cells and an increase in lipid-laden macrophages by Oil Red O
stain. Patient was placed on steroid and steadily improved for the next 2 days. He
was discharged on a steroid taper and follow-up with respiratory clinic. Case
reports and series have shown a variety of lung injury patterns in previously
healthy patients who are frequent users of e-cigarettes and among them features
suggestive of lipoid pneumonia with increased lipid-laden macrophages. The clini-
cal utility of this finding is still unclear.

KEYWORDS

e-cigarette, lipoid, macrophages, vaping

1 | I N T RO DU CT I O N symptoms including tachycardia, fever, and chills, with a reported his-

Vaping-induced lung injury is a recently recognized phenomenon
owing to the rising popularity of e-cigarette use, especially among the
younger population, with a growth in use of over 900% from 2011 to
1
2015 in the American high-school population. A cluster of 380 con-
firmed cases of varying severity, including 6 deaths, was recently iden-
tified in the United States by the Centers for Disease Control, as
defined by an onset of respiratory findings, including nonproductive
cough, shortness of breath, and pleuritic chest pain appearing several
days to weeks before hospitalization, with associated constitutional
tory of e-cigarette use.2 Although the exact mechanism of damage to
the respiratory system has not been fully elucidated, several reports
have identified features suggestive of lipoid pneumonia, with
increased lipid-laden macrophages on both bronchoalveolar lavage
and lung biopsy samples.3-5 Two recent case series highlighting the
pathological features of vaping-induced lung injury reported no spe-
cific histologic findings but suggested that it represents a form of
airway-centered chemical pneumonitis.6 Here, we present an addi-
tional case of a previously healthy young adult with history of vaping
and clinical and laboratory findings similar to the ones reported.

Diagnostic Cytopathology. 2019;1–3. wileyonlinelibrary.com/journal/dc © 2019 Wiley Periodicals, Inc. 1

2 OCAMPO-GONZALEZ AND PARK
F I G U R E 1 Alveolar macrophages (center) with abundant,
vacuolated foamy cytoplasm consistent with lipid accumulation.
(Papanicolaou, ×40)
2 | CASE REPORT
A previously healthy 20-year-old man presented to the emergency
department with dyspnea on exertion, fever, and cough with white
sputum for 3 days and malaise for 7 days. He was seen at an outside
clinic 3 days before, diagnosed with pneumonia, and started antibi-
otics with no improvement. On admission, patient was tachypneic,
tachycardic, hypoxic, and febrile, with coarse breath sounds. A chest
CT showed scattered areas of interlobular septal thickening and dif-
fuse ground-glass opacities in both lungs, with associated bronchial
wall thickening.
Patient reported daily vaping with a liquid containing both tetra-
hydrocannabinol (THC)/nicotine and a recent change in provider for
this product, as well as occasional marijuana use. There was no rele-
vant history of travel or occupational exposure. Tests for influenza
and HIV were negative. Patient was intubated and admitted to the
medical intensive care unit. Bronchoscopy was performed with cytol-
ogy showing normal bronchial mucosa, no endobronchial lesions, and
no secretions. Bronchoalveolar lavage was performed with microbiol-
ogy studies showing no evidence of infection.
Cytological examination of the bronchoalveolar lavage sample
showed clusters of benign appearing bronchial cells and abundant
alveolar macrophages with expanded, vacuolated cytoplasm. Back-
ground showed no significant inflammatory activity. Special stains for
organisms (Fite, gomori methenamine silver, periodic acid-schiff) were
reviewed and found to be negative. There was, however, a marked
increase in lipid-laden macrophages (Figure 1) as demonstrated with
Oil Red O stain, highlighting approximately 80% of these (Figure 2).
Intracellular lipid levels within macrophages were graded with a score
of 0 to 4, where 0 is not opacified and 4 is complete opacification.
The Lipid Laden Macrophage Index was then determined by adding
the total grades of 100 cells (allowing for a range of 0-400).7
F I G U R E 2 Oil Red O stain highlighting lipid droplets inside the
cytoplasm of alveolar macrophages. (Oil Red O, ×40)
Patient was placed on steroids, showing marked improvement
over the following 2 days. He was discharged with a steroid taper and
follow-up with the respiratory clinic.
3 | DI SCU SSION
Vaping-induced lung injury is a recently recognized phenomenon,
with case reports published from 2014 to 2018 and a recent cluster
of 53 cases identified in Illinois and Wisconsin in 2019.8 Patients
usually present with respiratory and constitutional symptoms includ-
ing dyspnea on exertion, cough, nausea, and fever, with some evolv-
ing to acute respiratory failure necessitating intensive care. Although
an exact mechanism of injury has not been identified, several mecha-
nisms have been proposed. The majority of patients presenting with
these symptoms consumed both nicotine and THC and cannabidiol
products,2 with the possibility of these mixtures generating
unknown toxic agents when used together. Additional possibilities
include contamination or toxic agents used as flavorants. Reported
cases have demonstrated a wide variety of lung injury patterns,
including acute eosinophilic pneumonia, organizing pneumonia, dif-
fuse alveolar damage, and lipoid pneumonia. This last pattern has
been reported in multiple cases as a consistent finding, usually show-
ing more than 50% of lipid-laden macrophages by Oil Red O or
Sudan Black stain.3-5 Reported histopathological findings of vaping-
associated lung injury include acute fibrinous pneumonia, diffuse
alveolar damage, and organizing pneumonia, as well as the presence
of foamy macrophages and pneumocyte vacuolization in the majority
of reported cases.6,10
Lipoid pneumonia is a pattern of lung injury most commonly asso-
ciated with the use of mineral oil laxatives or accidental ingestion of
lipid-rich materials, such as kerosene. It manifests clinically in a spec-
trum going from asymptomatic to life-threatening acute respiratory
OCAMPO-GONZALEZ AND PARK
failure. Diagnosis is usually rendered on a history of exposure to
known etiologic agents and the presence of lipid-laden macrophages
3.
on bronchoalveolar lavage analysis.9
The understanding and characterization of vaping-related lung
disease is still ongoing. The utility of lipid-laden macrophages as a 4.
marker for vaping-induced lung injury has been proposed owing to its
consistent appearance in several case reports and case series. How-
5.
ever, caution in the interpretation of this finding has been suggested,
as none of the cases in two recent case series centered on the histo-
pathology of vaping-associated lung injury showed evidence of this 6.
6,10
finding. This, taken together with the heterogeneity of lung-injury
patterns associated with vaping,8 means that the clinical significance 7.
of this finding is still unclear. More studies are needed in order to fully
characterize and understand the pathologic mechanism of vaping-
8.
related lung injury.
CONF LICT OF IN TE RE ST 9.
The authors declare no potential conflict of interest.
10.
ORCID
Fernando Alekos Ocampo-Gonzalez https://orcid.org/0000-0002-
5978-5813
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How to cite this article: Ocampo-Gonzalez FA, Park J-W.
Cytologic features of vaping-induced lung injury: A case
report. Diagnostic Cytopathology. 2019;1–3. https://doi.org/
10.1002/dc.24343