*From the Institute of Pulmonology (Drs. Glazer, Nusair, Breuer, Lafair, and Berkman) and the Department of Pathology (Dr. Sherman), Hadassah University Hospital, Jerusalem, Israel.
Correspondence to: Neville Berkman, MBBCh, Institute of Pulmonology, Hadassah University Hospital, PO Box 12000, Jerusalem, Israel, 91120.
patients with pulmonary mucormycosis diagnosed during life are
described. All had underlying predisposing conditions: either
posttransplant or hematologic malignancies. In all cases, the diagnosis
was made using fiberoptic bronchoscopy. In three patients, BAL was
diagnostic. In two of these patients, the diagnosis was made by
identifying the typical hyphae of mucormycosis in the BAL fluid alone.
Transbronchial biopsy was diagnostic in three patients. Treatment was
based on IV antifungal chemotherapy together with surgical removal of
involved lung tissue whenever feasible. The clinical outcome of these
patients was dismal and was determined primarily by the underlying
Mucor, a fungus from the class of Zygomycetes, is a
ubiquitous saprophyte that resides in soil and decaying organic matter.
Humans may be infected with Mucor after inhalation of airborne fungal
spores. However, normal macrophage and neutrophil function provides
immune protection against Mucor. Therefore, patients with neutrophil
dysfunction, such as occurs in diabetes, renal failure, or prolonged
steroid therapy, are particularly vulnerable to infections with Mucor.
Additionally, neutropenic patients may also develop invasive
The most frequently observed manifestation of mucormycosis is the
characteristic rhinocerebral infection, which may initially mimic
bacterial sinusitis, and later extend to involve and destroy the hard
palate and the orbit, and further invade the carotid artery. The GI
tract and the brain may be involved in disseminated mucormycosis. The
lung is more rarely involved by infection with this fungus. Such
pulmonary involvement may progress and include invasion of blood
In reported series of invasive pulmonary mucormycosis, the diagnosis is
often made at postmortem or premortem examination by using
transbronchial biopsy (TBB) or open lung biopsy. However, many patients
at risk for this infection are thrombocytopenic, which precludes the
performance of invasive diagnostic procedures. BAL has not been
evaluated for the diagnosis of this infection.
We present five patients with pulmonary mucormycosis that was diagnosed
during life in our institution; three of the five patients had a
We searched the medical records of patients hospitalized in our
institution between the years 1992 and 1997 and identified five
patients in whom the diagnosis of pulmonary mucormycosis was made
during life. Details regarding the underlying condition, clinical and
radiologic presentation, methods of diagnosis, treatment, and clinical
outcome were documented in each case.
The definitive diagnosis was made in all patients by fiberoptic
bronchoscopy. BAL was performed in all patients, and TBB was performed
whenever there was no coagulopathy and the thrombocyte count was>
Material from TBB is embedded in paraffin blocks, and sections of 5μ
m are stained with hematoxylin-eosin. BAL fluid is routinely
cytocentrifuged and stained with Papanicolaou stain, Gomori methenamine
silver stain. BAL fluid is also sent for bacterial, fungal,
viral, and mycobacterial cultures.
A diagnosis of pulmonary mucormycosis was considered definite in the
presence of histologic evidence of invasive fungal infection. For BAL,
the finding of typical morphologic features of Mucor on direct staining
or culture in the presence of compatible clinical presentation as well
as favorable response to antifungal therapy was also considered
The clinical details of the patients are summarized in Table 1
. All patients were males, with a mean ± SD age at diagnosis of
40 ± 8.3 years. Four patients had an underlying hematopoietic
malignancy; two of the four patients had undergone bone marrow
transplantation (BMT). The fifth patient was a kidney transplant
patient. Diabetes mellitus (DM) secondary to corticosteroid (CSE)
therapy, a well-known risk factor for rhinocerebral mucormycosis, was
present in two cases. Four patients were receiving CSEs, and one
patient (patient 1) was receiving cyclosporine A at the time of
infection. Patient 5 had undergone autologous BMT, followed by
administration of allogeneic stem cell transfusion. Two patients were
neutropenic during the onset of infection with mucormycosis.
The radiologic and bronchoscopic findings in our patients are outlined
in Table 2
. Four of the patients had unilateral lung involvement, and only one
patient had bilateral lung disease. Three patients had cavitary lesions
on chest plain radiography and CT. Other radiographic findings included
a single mass in the right upper lobe and an additional nodule in the
left lower lobe in one patient, and a right lower lobe (RLL) infiltrate
in another patient.
In our five patients with pulmonary mucormycosis, TBB was performed in
three patients and was diagnostic in all. Of the five patients in whom
BAL was performed, three patients had positive findings on direct
microscopy. Only one of five patients had a positive finding on BAL
culture (Table 2). In two cases, TBB findings were positive while BAL
findings were negative for mucormycosis. In the two patients in whom
TBB was not performed, BAL alone was diagnostic. Thus overall, BAL was
diagnostic in three of the five patients (60%; Fig 1
). Culture yielded mucormycosis in only one of five cases, and this
patient had positive findings on both BAL and TBB. In one patient only
(patient 1), an initial transthoracic needle aspiration of a lung
cavity was performed, but was not diagnostic.
All patients were treated with high-dose amphotericin B (AMB);
total dose was 1.5 g. In two patients, surgical resection of the
involved lung was also performed.
The mean survival was 3.6 weeks. None of our patients survived
beyond 3 months; however, the two patients who underwent lung resection
did not have evidence of recurrence of mucormycosis up until their
death. Patient 2 died of ventilator-associated pneumonia in the
remaining lung, and patient 1 died 2 months after surgery because of
progressive hepatic failure secondary to severe chronic graft-vs-host
disease. Patient 3 survived at least 1 month past surgery but later
died due to acute myeloblastic leukemia relapse in his home country.
Mucor belongs to a unique group of fungi within the class
Zygomycetes and is generally a noninvasive saprophyte in the normal
host. Mucor infection invariably occurs in the presence of underlying
disease, most commonly seen as an infectious complication of DM, and
typically manifests as a rhinocerebral infection. In contrast,
pulmonary mucormycosis is seen infrequently in diabetic
Besides DM, other well-recognized risk factors for invasive
mucormycosis include neutropenia,2hematopoietic
malignancies, and CSE therapy.3Among solid-organ
transplants, patients undergoing renal transplantation (renal-Tx) for
end-stage diabetic nephropathy, who are more likely to develop
metabolic acidosis, may be more susceptible to
mucormycosis.4 Two of our patients had CSE-induced DM, of
which one had undergone renal-Tx. Neither patient had metabolic
acidosis as a primary event during presentation with pulmonary
The most common radiographic manifestation in our patients was the
presence of cavitary lesions. In a recent review of imaging findings in
32 cases of mucormycosis, two thirds of the patients had consolidation
as a main finding.5Forty-one percent of the patients had
cavitation within pulmonary consolidation or masses. Other radiographic
manifestations include multifocal consolidation, on “air crescent
sign” whenever a pulmonary infarct results from vascular invasion,
and rarely pleural effusion.6
The antemortem diagnosis of pulmonary mucormycosis is often missed
because the diagnosis is not suspected or pursued thoroughly enough.
Because postmortem examinations are rarely performed in our
country, this series includes only diseases diagnosed
antemortem. It is thus possible that the number of cases of pulmonary
mucormycosis in our institution is much higher than that reported
According to published studies, the diagnosis of pulmonary mucormycosis
requires the demonstration of the typical nonseptated right angle
branching-shaped hyphae within the lung tissue.3 A
positive finding from BAL culture is suggestive but not considered
definitive.6 However, since hematologic patients are
frequently thrombocytopenic, obtaining TBB is frequently not feasible.
In such cases, BAL may be the only diagnostic modality
Of our five cases, the BAL finding was positive in three (60%).
Of these, two patients were unable to undergo TBB; in these cases, the
diagnosis was made by BAL alone. In all three cases with a positive
finding on BAL, mucormycosis proved to indeed be a true pathogen and
not merely a coincidental finding; in one case, this was confirmed by
surgery (thoracotomy), and in the second by a positive finding on TBB.
In the third patient, the clinical response after the initiation of
antifungal therapy, together with failure to respond to broad-spectrum
antibacterial therapy or to identify another pathogen despite extensive
evaluation, led us to believe that mucormycosis was a true pathogen in
this patient (patient 3).
There is little available literature that describes the diagnosis
of mucormycosis by using BAL.7–8 A recent report described
a diabetic patient in whom a diagnosis of pulmonary mucormycosis was
made by BAL.9 Conventional recommendations in the
literature require demonstration of Mucor hyphae within the pulmonary
parenchyma in order to make the diagnosis of pulmonary
mucormycosis.6 Our findings suggest otherwise. We believe
that whenever mucormycosis is found in BAL cultures from a neutropenic
or immunocompromised patient, the diagnosis of invasive mucormycosis is
extremely likely and should be assumed until proven otherwise.
The diagnostic yield of fungal culture was poor (20%; one of five
cases). The culture finding was negative even in cases in which
findings from direct microscopy of BAL or lung tissue were positive.
Similar results of culture have been reported by others.5
This yield may be dependent on the specific laboratory performing these
cultures, but in our hands, culture adds little to the histopathologic
tests. Our data suggest that BAL could be a useful diagnostic procedure
for pulmonary mucormycosis, with an acceptable risk for
thrombocytopenic and critically ill patients in whom TBB is
From our data, it is not possible to comment on the negative predictive
value of BAL for excluding the diagnosis of pulmonary mucormycosis.
Conclusions regarding this issue would require the performance of open
lung biopsy or postmortem examination in all patients in whom BAL is
The recommended treatment for pulmonary mucormycosis includes treatment
of the underlying condition, surgical removal of the devitalized
tissue, and IV administration of AMB. According to recent reports,
early surgical treatment may substantially reduce mortality (45% with
surgery vs 70 to 80% with medical management only).5,7
Although surgical resection of pulmonary parenchyma involved with
mucormycosis seems to have eradicated mucormycosis in our patients, the
underlying condition was the main factor that determined their outcome
and survival. Consequently, overall survival in our group was dismal
regardless of surgical intervention.
In conclusion, pulmonary mucormycosis should be suspected in patients
with a high risk for invasive fungal pulmonary infections, particularly
when they present with single or multifocal pulmonary infiltrates with
cavitation. The diagnosis of fungal pneumonia requires the
demonstration of fungi within the pulmonary parenchyma on lung biopsy;
however, BAL, a relatively safe diagnostic tool, may allow the
diagnosis of mucormycosis in cases where lung biopsy is
contraindicated. Our findings strongly imply that the presence of
mucormycosis within the BAL fluid is diagnostic of pulmonary
mucormycosis in patients who are prone to such an infection. Although
surgical resection of pulmonary parenchyma involved with mucormycosis
may have eradicated the infection, the underlying condition was the
main factor that determined outcome and mortality.
Abbreviations: AMB = amphotericin B; BMT = bone marrow
transplantation; CSE = corticosteroid; DM = diabetes mellitis;
renal-Tx = renal transplantation; RLL = right lower lobe;
TBB = transbronchial biopsy
M = male; F = female; ALL = acute lymphoblastic
leukemia; AML = acute myeloblastic leukemia; CML = chronic myeloid
leukemia; CSA = cyclosporine A; CTX = cytotoxic therapy;
NHL = non-Hodgkin’s lymphoma; TCD-BM = T-cell depleted bone
LUL = left upper lobe; RUL = right upper lobe;
LLL = left lower lobe; NA = not available.
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