Case Report

MYCOSIS OF THE
UPPER RESPIRATORY TRACT
Fajriani

Supervisor: dr. Soekimin, Sp.PA (K)

DEPARTMENT OF ANATOMIC PATHOLOGY, FK-USU

RSU HAJI MEDAN
2019
1
 INTRODUCTION

•Respiratory tract infections are globally responsible for one-third of infectious

disease–associated mortality, accounting for 4.3 million annual deaths

•Among these, fungal infections of the respiratory tract are largely unrecognized, and
the true burden is elusive

2
INTRODUCTION...
Fungi are eukaryotic
organisms
Among this group of
comprising of
organisms only
moulds, yeasts,
about 0.1% are
mushrooms and
human pathogens
other similar
organisms
The term mycosis is
used to define
diseases caused by
Of thefungi
more than
400,000 known
fungal species,
approximately 400
are human
pathogens, only 50
of which cause
systemic or central
nervous system
3
infection
INTRODUCTION...

Many of these fungi are ubiquitous in our

environment

Although many people are colonized by fungi, an

intact immune system prevents subsequent
infection

Although several fungi have been implicated to

cause sinus infection, Aspergillus, Bipolaris, and
Rhizopus are the more commonly implicated
organisms causing fungal sinusitis

4
 CASE REPORT
• Three patients were reported
– the first patient was a 9-year-old girl with a clinical
diagnosis of nasopharyngeal angiofibroma and
hypertrophic adenoids
– the second patient was a 42-year-old male
– the third patient was a 39-year-old woman with a clinical
diagnosis of nasal polyps, maxillary sinus and etmoid sinus
• The three patients came to Gunung Tua Hospital and
performed biopsy measures then the tissue was sent to the
laboratory of the anatomic pathology department of the
faculty medicine of Universitas Sumatera Utara for
histopathological examination and all three tissues are
numbered 🡪 SK/059/19, 371/PA/19, and 405/19
5
Macroscopic
• On macroscopic examination of the cavum nasi
tissue (SK/059/10), which is received 2 pieces of
grayish white tissue, irregular shape, springy
consistency, the largest tissue size is 1x0.4x0.2 cm
and the smallest tissue is a fraction of rice.
• Macroscopic from nasopharyngeal tissue
(371/PA/19), that is received tissue such as
brownish yellow mucus, irregular shape, soft
consistency, with a tissue volume of ± 2 cc.
• Macroscopic from sinonasal tissue (405/19), that
is received grayish brown tissue, irregular shape,
springy consistency, with a tissue volume of ± 5 cc
6
Figure 1. Macroscopic tissue. A. Tissue from cavum nasi. B. Tissue from
nasopharinx. C. Tissue from sinonasal.

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Microscopic
• On microscopic examination of the cavum nasi tissue
(SK/059/19), the distribution of hyphae appeared on
septa and branching forming an angle of 450 🡪 also
appears the focus of necrotic mass and lymphocyte
inflammation cell distribution.
• Microscopic examination of nasopharyngeal tissue
(371/PA/19) showed diffuse masses such as septic
hyphae and branching forming an angle of 450 🡪 also
appears the focus of necrotic mass and lymphocyte
inflammation cells.
• Microscopic examination of sinonasal tissue (405/19)
showed diffuse masses such as hyphae with septa and
branched to form a 450 angle with spread of spore
distribution and also the focus of the necrotic mass
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Microscopic...

Staining with Grocott-Gomori's Methanamine Silver (GMS) on all three tissue

preparations shows the structure of hyphae with septa and branching forming an
angle of 450.

Based on previous microscopic descriptions, these three patients can be concluded as

an Aspergillus fungal infection

9
Figure 2. A. On microscopic examination of the cavum nasi tissue, the distribution of
hyphae appeared on septa and branching forming an angle of 450. Also appears the
focus of necrotic mass and lymphocyte inflammation cell distribution. B. Microscopic
examination of nasopharyngeal tissue showed diffuse masses such as hyphae with
septa and branching forming an angle of 450 and spread of spore distribution. Also
appears the focus of necrotic mass and lymphocyte inflammation cells. C. Microscopic
examination of sinonasal tissue showed diffuse masses such as hyphae with septa and
branched to form a 450 angle and also the focus of the necrotic mass (H.E stain x400).
10
Figure 3. Microscophic tissue A,B,C. Staining with Grocott-Gomori's Methanamine
Silver (GMS) on all three tissue preparations shows the structure of hyphae with septa
and branching forming an angle of 450 (GMS stain, x400).

11
 DISCUSSION
An estimated 1.5 million fungal species inhabit earth, with the
vast majority poorly described or undiscovered

Because fungi are present throughout the environment,

human exposure is inevitable and normal respiration will
routinely deposit fungal elements within the nose and
paranasal sinuses
In most instances, the presence of fungal elements in the
nose is of no consequence and will remain unknown to the
individual unless elaborate culture techniques are used

In select instances, fungal species can cause sinonasal

disease, with clinical outcomes ranging from mild symptoms
to intracranial invasion and death

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DISCUSSION...

• Studies indicate about a dozen fungal species to be

actively involved in human infections
• Classically fungi exists in three forms:
― Yeast form
― Mould form
― Spore form
• Exposure to fungal organism occur on a daily basis
• Our immune system invariably tackles the initial fungal
infections
• In some patients fungal infections may become
invasive leading to disastrous consequences
• Hence it is very important for the treating physician to
differentiate invasive fungal infections from non
invasive ones
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DISCUSSION...

• Recent epidemiologic studies clearly outline the link

between fungal sensitization and exacerbations of allergic
asthma, leading to increased morbidity and mortality
• The major respiratory manifestations caused by fungi
include allergic bronchopulmonary mycoses (ABPM), severe
asthma with fungal sensitization (SAFS), hypersensitivity
pneumonitis, fungal sinusitis and allergic rhinitis
• In contrast to other allergens (e.g. pollen), fungi also pose a
life-threatening risk for invasive pneumonia in
immunocompromised patients; further emphasizing their
significant impact on human health
• It is now understood that the pathogenesis of diseases like
asthma and allergy is determined by the interactions
between host, genes and environment

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DISCUSSION...

•Aspergillus species is the most common fungal infection of the paranasal

sinuses
•The causative organism is a spore-forming filamentous fungus which occurs
as a saprophyte in soil and decaying vegetable matter and is spread by
airborne transmission
•Transmission between humans is unknown
•Aspergillus is recognized histologically by its septate hyphae, which branch at
a 45° angle and reproduce as asexual conidia
•The three species which are most commonly implicated in human
pathogenicity are A. fumigatus, A. flavus, and A. niger

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DISCUSSION...

Broadly fungal infections involving paranasal

sinuses can be classified under two broad
categories
•Non invasive: Saprophytic infections, fungal ball,
allergic fungal sinusitis
•Invasive: Acute fulminant invasive sinusitis,
Chronic invasive sinusitis and granulomatous
invasive fungal sinusitis

16
DISCUSSION...

Clinically 6 different types of fungal sinusitis have been

described depending on the pathophysiology and clinical
features:

•Acute fulminant invasive fungal sinusitis

•Chronic invasive fungal sinusitis
•Granulomatous invasive fungal sinusitis
•Fungal ball
•Allergic fungal rhinosinusitis (AFRS)
•Eosinophilic fungal rhinosinusitis (EFRS)

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Acute fulminant invasive fungal sinusitis

The entire duration of illness in these patients is less than a month

These patients are invariably immunocompromised

Immune compromise could be due to:

•Diabetes mellitus
•AIDS
•Patients on immunosuppresive medicines
•Patients with malignancy causing immunosuppression

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Acute fulminant invasive fungal sinusitis...

Acute fulminant invasive fungal sinusitis is caused by fungal infections due to:

•Mucoracea family 🡪 seen under microscope as broad hyphae which very rarely
septates 🡪branching out is seen at right angles 🡪 clearly seen under
methanamine/PAS staining of the tissue
•Aspergillous family 🡪 seen under the microscope as narrow and septate hyphae
🡪branching could be seen to occur at acute angles

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Figure 4. showing mucormycosis under high power.

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Figure 5. Showing aspergillosis

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Acute fulminant invasive fungal sinusitis...

Considering the amount of tissue necrosis involved

in these patients, surgical debridement followed by
intravenous antifungal medications (amphotericin B)
is the treatment of choice

This should also be

associated with good
euglycaemic control

Since granulocytes are necessary in combating

this condition, granulocyte transfusion has been
attempted with certain degree of success in
these patients following wound debridement
22
Chronic invasive fungal sinusitis
• This condition is also known as non granulomatous chronic
invasive fungal sinusitis
• This condition is commonly seen in patients with diabetes
mellitus
• Feature of this infection is low grade inflammation with
tissue necrosis
• Usually this disease lasts between 4-6 weeks
• Vascular invasion is not seen
• Granuloma formation is classically seen
• Orbital involvement (Orbital apex syndrome) is common in
these patients
• This condition affects immunocompetent patients
• Fronto ethmoidal region is commonly involved

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Chronic invasive fungal sinusitis...

• Maxillary sinus and sphenoid sinus are very rarely

affected
• More than 80% of these patients have fronto
ethmoidal sinus involvement
• Aspergillosis have been implicated as the commonest
pathogen involved
• managed by surgical debridement followed by
systemic antifungal drugs like amphotericin B infusion
• Chronic invasive fungal sinusitis is rather rare
• According to Ferguson (2005) it constitutes less than
0.003% of all forms of fungal sinusitis operated on

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Figure 6. (A). Coronal computed tomography scan of immunosuppressed patient
with amyloidosis and chronic invasive mucormycosis in chronic invasive fungal
rhinosinusitis. Right ethmoid and pterygopalatine space involvement. (B).
Nongranulomatous chronic inflammatory infiltrate with transverse section of
fungal hyphae eosinophilic Splendore-Hoeppli phenomenon on hematoxylin and
eosin stain (×200). (C). Periodic acid-Schiff stain (×400). (D). Gomori
methenamine-silver stain (×200). 25
 Granulomatous invasive fungal sinusitis
• This condition is also known as “Indolent fungal sinusitis”
• Classically these patients have intact cell mediated immune response
• These lesions are caused by Aspergillus flavous
• Clinically this condition is indistinguishable from chronic invasive
fungal sinusitis
• Granulomas could be seen surrounding the fungal elements there by
effectively preventing their invasion
• Granulomas typically non caseating and demonstrate the presence of
multinucleated giant cells and eosinophils
• This condition is effectively managed by surgical debridement
• After successful wound debridement the intact immune system takes
care of the disease
• Treatment with itraconazole/varioconazole has shown promising
results
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Figure 7. (A). Computed tomography scan of patient with chronic granulomatous fungal
rhinosinusitis involving the right nasal cavity in a chronic invasive granulomatous fungal
rhinosinusitis with bony destruction of paranasal sinuses extending into right orbit. (B).
Extensive granulomatous process in a fibrotic background on hematoxylin and eosin stain
(×100). (C). Fungal hyphae inside giant cells on periodic acid-Schiff stain (×400). (D).
Fungal hyphae inside giant cells on Gomori methenamine-silver stain (×400) 27
 Fungal ball
These are also
known as
Mycetomas
mycetomas
commonly present
as unilateral
opacification of
maxillary/sphenoid
This condition is
Fungal ball in
sinusesrare
rather is
composed
ethmoid andof frontal
tightly
packed hyphae
sinuses
mostly from
(Aspergillus,
Alternaria and
Nasal mucosais is
This disease
Pseudallescheria
absolutely normal
classically caused
boydii)
in
duethese patients of
to inhalation
spores, which
eventually gets
sequestered
Fungal growth either
into maxillary
occurs or
within the
sphenoidofsinuses
confines the
affected sinus
cavity
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Fungal ball...

• Fungal growth occurs because of the ability of the infecting

pathogen to avoid host immune response
• Signs and symptoms may mimic chronic rhinosinusitis in
advanced cases
• This condition is managed by surgical removal of the fungal
ball and creating good ventilation to the involved sinuses by
widening the sinus ostium
• Systemic antifungal agents are not indicated in these
patients
• Topical antifugal agents have been administered with
varying degrees of success.
• In majority of these patients this condition was diagnosed
as an incidental finding when routine imaging of nose and
sinuses were performed

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Figure 8. (A). Computed tomography scan showing a fungus ball in the left
maxillary sinus on coronal view with hyperdense secretions. (B). Gross photo of
a fungal ball. (C). Fungal hyphae on periodic acid-Schiff stain (×200). (D) Gomori
methenamine-silver stain (×200)
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Allergic fungal rhinosinusitis (AFRS)
• This rather poorly understood entity was first reported in 1976
• In 1983 Katzenstein et al described a condition and coined the
terminology allergic aspergillus sinusitis
• They made the diagnosis based on the presence of histological
triad of “clumps/sheets of necrotis eosinophils,
Charcot-Leyden crystals probably from degenerating
eosinophils and non invasive fungal hyphae resembling
aspergillus species
• These patients have a combination of nasal polyposis, crust
formation and positive culture for aspergillus. It was Robson in
1989 11 who introduced the term allergic fungal sinusitis to
describe the findings associated with this disease
• According to Cody aspergillus species was responsible for only
15% of allergic fungal sinusitis

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Allergic fungal rhinosinusitis (AFRS)...

Incidence of allergic fungal sinusitis among chronic sinusitis is placed around 6-7%

Bent's criteria for the diagnosis of allergic fungal sinusitis:

•Demonstrable type I hypersensitivity to fungi

•Nasal polyposis
•Radiological findings (Heterodense mass lesion)
•Presence of eosinophilic mucin mixed with non invasive fungus
•Positive fungal stain/fungal culture

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Allergic fungal rhinosinusitis (AFRS)...

Bent and Khun modified their diagnostic criteria for diagnosis of allergic
fungal sinusitis by adding major and minor diagnostic criteria

33
Allergic fungal rhinosinusitis (AFRS)...

Clinical features of allergic funcal sinusitis:

•Progressive nasal obstruction, crusting, rhinorrhoea, and

chronic rhinosinusitis, visual loss and total nasal obstruction.

Classically radiology

•Unilateraly expansile lesion of the sinuses associated with

bony erosion.
•The mass appears as heterodense due to the presence of
metallic elements in the fungal hyphae
•Unilateral asymmetric involvement of sinuses is the classic
The mechanism
feature of causation of allergic fungal sinusitis is
of this condition

•IgE mediated hypersensitivity to fungal proteins especially to

aspergillus.
•Both type I and type III hypersensitivity reactions to fungal
proteins have been implicated. 34
•Allergic fungal sinusitis still remains an under reported
Allergic fungal rhinosinusitis (AFRS)...

35
Allergic fungal rhinosinusitis (AFRS)...

Administration of systemic steroids

This condition is best managed by
surgical removal of mucinous element
and providing lasting drainage and
ventilation to the involved sinuses
helps in reducing the incidence of
recurrence in these patients as this
condition is attributed to
immunological reaction to fungal
protein

Currently immunotherapy has shown

promising results in these patients

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Figure 9. (A) Computed tomography coronal scan showing recurrence of
allergic fungal rhinosinusitis following prior surgery. Hyperdensity of mucin
within right ethmoid and maxillary sinuses. (B) Allergic fungal sinusitis with
allergic mucin (×100). (C) Fungal hyphae inside allergic mucin on periodic
acid-Schiff stain (×400). (D) Gomori methenamine-silver stain showing hyphae
within the mucin (×100). 37
Eosinophilic fungal rhinosinusitis (EFRS)
• This terminology was introduced by Ponikau et al to explain
pathophysiology of chronic sinusitis
• This disorder is usually bilateral
• Fungal hyphae has been demonstrated in almost all these
patients
• Hypersensitivity reaction has been ruled out as a cause for
this type of fungal sinusitis
• It has been postulated that this condition could be caused
by abnormal cell mediated immunity to fungal proteins
• These patients respond well to surgical removal of
polypoidal mucosa, and creation of wide antrostomy which
improves ventilation to the sinus mucosa

38
Eosinophilic fungal rhinosinusitis (EFRS)...

39
 CONCLUSSION
Three tissue preparations from three patients were sent from
Gunung Tua Hospital

On microscopic examination of the three tissue preparations

showed diffuse masses such as hyphae with septa and
branching forming an angle of 450 and a necrotic mass

One of the tissue preparation, spore distribution appears.

Staining with Grocott-Gomori's Methanamine Silver (GMS) on

all three tissue preparations shows the structure of hyphae
with septa and branching forming an angle of 450

Based on previous microscopic descriptions, these three

patients can be concluded as an Aspergillus fungal infection

40
41
42
Microscopic observations of fungal infections

43
Aspergillus flavus

44
Aspergillus fumigatus

45
Aspergillus niger

46
47