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dOI 10.11603/IJMMR.2413-6077.2019.2.10456

pRIMARY LARYNGEAL ASpERGILLOSIS IN AN IMMUNOCOMpETENT 
pATIENT (case report)

K.S. Rajmohan1, *I.D. Khan1, U. Kapoor2, S.A. Hashmi1, 
R.M. Gupta3, S. Sen3, G.L. Nair1, K.K. Singh2, K. Tandel4, M.Malik4

1 – ARMY COLLEGE OF MEDICAL SCIENCES AND BASE HOSPITAL, NEW DELHI, INDIA
2 – COMMAND HOSPITAL (NC), UDHAMPUR, INDIA

3 – ARMED FORCES MEDICAL COLLEGE, PUNE, INDIA
4 – ARMY HOSPITAL RESEARCH AND REFERRAL, NEW DELHI, INDIA

Background. Aspergillus is an inherently ubiquitous, weakly pathogenic fungus causing opportunistic 
infections. It is very rarely localized in the larynx, although laryngeal Aspergillosis may develop in the 
immunocompromised patients including those with leukaemia and severe aplastic anaemia.

Objective. The aim of the research was to explore the primary laryngeal Aspergillosis in an immunocompetent 
patient thru a case report. 

Methods. A case report of primary laryngeal Aspergillosis in an immunocompetent patient is presented.
Results. A male patient of 40 years old, presenting with chronic worsening hoarseness, was found to have 

a smooth, white spheroid submucosal growth on left vocal cord with preserved bilateral cord movements on 
videostroboscopy. Histopathological examination of vocal cord growth revealed squamous epithelium containing 
septate hyphae with acute angle dichotomous branching pattern consistent with Aspergillus. Voice improved 
after a four-week course of oral itraconazole 200 mg/day. Post therapy follow up of 24 months was unremarkable.

Conclusions. Primary laryngeal Aspergillosis develops in the immunocompetent patients. Iatrogenic, vocal 
abuse, occupation and lifestyle factors may be contributory. Optimal diagnosis and management mandates a 
high index of suspicion.

KEY WORDS: primary laryngeal aspergillosis; videostroboscopy.

*Corresponding author: Dr. Inam Danish Khan, Associate 
Professor, Clinical Microbiology and Infectious Diseases, Army 
College of Medical Sciences and Base Hospital, New Delhi 
110010, India. E-mail: titan_afmc@yahoo.com

Introduction
Aspergillus is an inherently ubiquitous, 

weakly pathogenic fungus causing opportunistic 
infections [1]. It is very rarely localized in the 
larynx [2], although laryngeal Aspergillosis may 
develop in the immunocompromised patients 
including those with leukaemia and severe 
aplastic anaemia [2-4]. Current healthcare is 
witnessing a surge in emerging fungal infections 
due to multiple exposure to antimicrobials, 
which can further antimicrobial resistance [5-
11]. Invasive Aspergillosis of glottic, subglottic 
and epiglottis have been described following 
steroid and radiation therapy [12-15]. There are 
diagnostic challenges in resource-limited 
facilities due to overlapping presentation [16, 
17]. We report a case of primary laryngeal 
Aspergillosis in an immunocompetent patient.

Case Report
A 40-year-old male patient presenting to 

the otolaryngology clinic (Army College of 

Medical Sciences and Base Hospital, New Delhi 
110010, India) with complaints of chronic 
worsening hoarseness for two months. He was 
found to have a smooth, white spheroid sub-
mucosal growth on the anterior surface of left 
vocal cord with preserved bilateral cord move-
ments on videostroboscopy. No history of vocal 
abuse, laryngeal trauma, sore throat, cough, 
dyspnea, fever or prolonged antimicrobial inta-
ke was present. There was no history of gene-
ralized immune deficiency, leukaemia, malig­
nant disease, diabetes mellitus or use of immu-
nosuppressive drugs and corticosteroids. No 
history of diabetes, tuberculosis or malig nancy 
was present. Neither history of tobacco abuse 
nor history of social drinking was pre sent. 
General, systemic examination and chest X-ray 
revealed insignificant changes. Oral cavi ty, oro­
pharynx and neck were normal. HIV se ro logy 
was negative. Hemoglobin was 13.5 gm/dl, total 
leucocytes 7800/mm3 with normal differential 
count. Renal and liver function tests were in 
norm. Histopathological examination of vocal 
cord growth revealed squamous epithelium 
containing septate hyphae with acute angle 

International Journal of Medicine and Medical Research 
2019, Volume 5, Issue 2, p. 15-19
copyright © 2019, TNMU, All Rights Reserved

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dichotomous branching pattern consistent with 
Aspergillus (Fig. 1).

The findings were seconded by PAS (Periodic 
Acid-Schiff) stain, Grocott’s (Grocott methe-
namine silver (GMS)) stain and KOH (Potassium 
hydroxide) mount, wherein hyaline hyphae with 
narrow angle branching were seen. Aspergillus 
fumigatus was isolated from the vocal cord 
tissue consecutively on Sabouraud’s dextrose 
agar at 22 °C and 37 °C after incubation for 
48 hours. Lactophenol cotton blue tease mount 
from blue-green suede like surface revealed 
septate hyaline hyphae with columnar smooth 
walled uniseriate conidiophores bearing 
phialides and conidia over flask shaped vesicles. 
Thermotolerance at 55 °C was observed. This 
was confirmed by amplification of Internal 
Transcribed Spacer (ITS) of 5.8S rDNA using 
ITS1 and ITS4 primers. Blood cultures were 
negative. Voice improved after a four-week 
course of oral itraconazole 200 mg/day. The 
patient was explained about good vocal prac-
tices and oral hygiene. Post therapy follow up 
for 24 months revealed no significant changes. 

Discussion
Approximately 50 cases of primary laryngeal 

Aspergillosis have been reported, half of them 
involved immunocompetent patients [18-24]. 
Aspergillus is non-pathogenic, or very weakly 
pathogenic, and causes opportunistic infections. 
Aspergillosis occurs due to deficient host's 
defense rather than fungal pathogenicity [21]. 
Isolated laryngeal Aspergillosis may follow 
colonization of larynx, which may be furthered, 
by local factors, rather than systemic immu no-
suppression. Further, systemic immunode-
ficiency may not contribute to the development 
of isolated laryngeal Aspergillosis. Iatrogenic 
factors such as radiation therapy, inhaled ste-
roids and laser treatment may, also, be con-
tributory [12-15]. Vocal abuse and oral sex may 
impair local protective barrier provided by 
healthy mucosal covering and allow colonization 
and subsequent invasive Aspergillosis [21]. 
Laryngeal Aspergillosis can even occur in a true 
vocal-fold cyst or laryngocoele. Systemic factors 
include previous prolonged antimicrobial 
therapy, which is implicated in altering local flora 
and disturbing the ecological balance between 
bacteria and fungi, thus allowing the growth of 
Aspergillus. Occupation, avocation and lifestyle 
may be contributory to exposures in healthy 
patients. Farmers and carpenters may be at 
higher risk as Aspergillus is a soil saprophyte. 
Aspergillosis had a shift in its host range as a 

higher incidence in males since the beginning 
of the 21st century has now turned to a higher 
incidence in females aged 20-40 years old [21].

Opportunistic infections mandate clinical 
intrepidity, diagnostic efficiency, appropriate 
timely therapy and prognostication for favou-
rable results [25-31]. 

Primary Aspergillosis is often reported late 
due to prolonged low-grade infection and de-
layed onset of clinical features. Fungal growth 
in tissues may not corroborate to clinical pre-
sen tation leaving scope for further complications 
such as invasion of adjacent tissues, abscess 
development and dissemination, for which 
radical surgery and aggressive antifungal the-
rapy may be required. Fatal invasive Aspergillosis 
of larynx has also been reported [32].

Conclusions
Primary laryngeal Aspergillosis develops in 

immunocompetent patients. Iatrogenic, vocal 
abuse, occupation and lifestyle factors may be 
contributory. Optimal diagnosis and manage-
ment mandates high index of suspicion.

Funding
This research received no external funding.
Conflict of Interests
The authors declare no conflict of interest.
Author Contributions
Rajmohan K.S. – conceptualization, formal 

analysis, Khan I.D. – conceptualization, formal 
analysis, investigation, writing – original draft, 
review & editing, Kapoor U. – investigation, data 
curation, Hashmi S.A. – conceptualization, 
Gupta R.M. – writing – original draft, review & 
editing, Sen S. – writing – original draft, review 
and editing, Nair G.L. – data curation, Singh K.K. – 
data curation, Tandel K. – formal analysis, 
Malik M. – formal analysis.

Fig. 1. Photomicrograph H&E, X400. Vocal cord 
growth. Squamous epithelium containing septate 
hyphae with acute angle dichotomous branching 
pattern consistent with Aspergillus.

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перВинниЙ аспергілЬоз гортані у імунокомпетентного пацієнта 
(клінічний випадок)

K.S. Rajmohan1, I.D. Khan1, U. Kapoor2, S.A. Hashmi1, 
R.M. Gupta3, S. Sen3, G.L. Nair1, K.K. Singh2, K. Tandel4, M.Malik4

1 – ARMY COLLEGE OF MEDICAL SCIENCES AND BASE HOSPITAL, NEW DELHI, INDIA
2 – COMMAND HOSPITAL (NC), UDHAMPUR, INDIA

3 – ARMED FORCES MEDICAL COLLEGE, PUNE, INDIA
4 – ARMY HOSPITAL RESEARCH AND REFERRAL, NEW DELHI, INDIA

Вступ. Aspergillus – один з найпоширеніших видів грибів з низькою патогенністю, котрий може 
спричиняти опортуністичні інфекції. Він надзвичайно рідко локалізується у гортані, однак може 
викликати аспергильоз гортані у осіб з ослабленою імунною системою, до прикладу при лейкемії чи 
апластичній анемії. 

Мета. Дослідити особливості перебігу первинного аспергильозу гортані у імунокомпетентного 
пацієнта на прикладі клінічного випадку. 

Методи дослідження. Описано та проаналізовано клінічний випадок первинного аспергильозу 
гортані у імунокомпетентного пацієнта.

Результати. 40-річний чоловік звернувся до лікаря зі скаргами на хронічну прогресуючу захриплість. 
При огляді виявлено гладкий, білого кольору, сфероїдної форми утвір на лівій голосовій зв’язці. Рухливість 
зв’язок збережена білатерально, що підтверджено на відеостробоскопії. Гістологічне дослідження 
утвору голосової зв’язки виявило септований міцелій

грибів роду Aspergillus (плоскоклітинний епітелій з септами з гострим кутом дихотомічного 
розгалуження, що відповідає аспергильозу). Покращення голосу спостерігалося після чотирьох-
тижневого курсу ітраконазолу, перорально в дозі 200 мг/день. При обстеженні через 24 місяці після 
лікування жодних відхилень не виявлено. 

Висновки. Первинний аспергильоз гортані може розвиватися у імунокомпетентних пацієнтів. 
Ятрогенні чинники, перевантаження голосових зв'язок, професійні шкідливі впливи та певний спосіб 
та стиль життя можуть сприяти його розвитку. Необхідно бути настороженим щодо можливого 
розвитку таких опортуністичних інфекцій для їх успішного діагностування та лікування. 

КЛЮЧОВІ СЛОВА: первинний аспергильоз гортані; гістологічні зміни; відеостробоскопія.

Information about the authors 
Dr. K.S. Rajmohan, Professor Pathology, Neuropathologist and Head of Department, Army College of 

Medical Sciences and Base Hospital, New Delhi 110010, India, ORCID 0000-0003-0047-3265, e-mail 
drksrajmohan24@gmail.com 

Dr. Inam Danish Khan, Associate Professor, Clinical Microbiology and Infectious Diseases, Army College 
of Medical Sciences and Base Hospital, New Delhi 110010, India, ORCID 0000-0002-9824-8711, e-mail 
titan_afmc@yahoo.com. 

Dr. Umesh Kapoor, Professor and Head Pathology, Command Hospital (NC), Udhampur 182101, India 
ORCID 0000­0003­1432­1254, e­mail drukapoor@gmail.com 
Dr. Syed Asif Hashmi, Assistant Professor Pathology, Army College of Medical Sciences and Base 

Hospital, New Delhi 110010, India
ORCID 0000­0002­7432­9058, syedasifhashmi@gmail.com 
Dr. Alpana Gupta, Assistant Professor Pathology, Army College of Medical Sciences and Base Hospital, 

New Delhi 110010, India
ORCID 0000­0003­3335­9821, e­mail dralpanangupta@gmail.com 
Dr. Sourav Sen, Professor and Head Microbiology, Armed Forces Medical College, Pune 411040, India
ORCID 0000-0001-9117-2235
Dr. GL Nair, Assistant Professor Pathology, Army College of Medical Sciences and Base Hospital, New 

Delhi 110010, India, ORCID 0000-0002-2301-7302, e-mail lakshminairg@gmail.com 
Dr. Samresh Kumar Singh, Pathologist and Senior Resident Nephropathology, All India Institute of 

Medical Sciences, New Delhi, India
ORCID 0000­0002­8624­8052, e­mail drsksingh78@gmail.com 
Dr. Kundan Tandel, Assistant Professor Microbiology, Army Hospital Research and Referral, New Delhi 

110010, India, ORCID 0000­0001­7478­2656, e­mail tandel.kundan@yahoo.co.in
Dr. Muqtadir Malik, Resident Microbiology, Army Hospital Research and Referral, New Delhi 110010, 

India, ORCID 0000-0003-2865-5773, e-mail drmuqtadirmalik@gmail.com 

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Received 24 September 2019; revised 05 November 2019;
accepted 15 December 2019.

This is open access article distributed under the Creative Com-
mons Attribution License, which permits unrestricted use, 
distribution, and reproduction in any medium, provided the 
original work is properly cited.

K.S. Rajmohan et al.