Malassezia furfur—Disseminated Infection
in Premature Infants
YO HO SHEK, M.D., MELISSA C. TUCKER, M.D., ANA L. VICIANA, M.D.,
HERBERT J. MANZ, M.D., AND DANIEL H. CONNOR, M.D.
Three infants, born prematurely, died after clinical illnesses of
67, 65, and 60 days from infection by Malassezia furfur. Each
infant had been nourished with lipid emulsions delivered through
deep-line catheters. The infections, all discovered at autopsy,
were characterized by massive involvement of lungs. Two of the
three had endocardial vegetations containing M. furfur; all three
had lesions in liver, kidney, and spleen, and two had lesions in
adrenal, pancreas, and colon. In addition, one of the infants had
acute meningoencephalitis caused by M. furfur. In some of the
distant organs, yeast cells of M. furfur were growing in the lumina
of small vessels, filling the lumina, but causing no vasculitis or
infarction. In addition to these benign collections of yeasts within
vessels, there were acute inflammatory lesions as well. These
were consolidation, vasculitis, granulomatous inflammation,
septic thrombosis, and septic infarction of lung and foci of necrosis and inflammation in kidney and liver. Two previously reported autopsies described neonates with lesions in lung and
heart. The authors' three cases for which autopsies were performed had lesions in lung and heart too but, in addition, had
dissemination with acute lesions in kidney and liver. Finally, one
patient had a severe meningoencephalitis caused by M. furfur.
(Key words: Malassezia furfur; Parenteral nutrition; Lipid
emulsions; Mycotic pneumonia; Mycotic endocardial vegetations;
Mycotic meningoencephalitis) Am J Clin Pathol 1989;92:
595-603
MALASSEZIA FURFUR, lacking the ability to synthesize long-chain fatty acids, grows naturally in the keratin
layer of the skin, where fatty acids essential for its growth
are elaborated by the sebaceous glands. Growth in vitro
requires addition, to the culture media, of oil containing
the fatty acids essential for the growth of M. furfur.4-9-10
In the keratin layer of skin, M. furfur is biphasic, forming
hyphae—2.5-4 jtm across—as well as round and oval
yeasts 3-8 ^m across. The yeasts reproduce by unipolar
budding, the daughter cells being extruded repeatedly from
the parent through a distinctive collarette.3 Excessive proliferation of M. furfur in skin causes a benign mycosis—
pityriasis versicolor—characterized by flat or slightly
raised macules. The macules are oval, usually scaling and
most common on upper trunk, shoulders, arms, and neck.
Pigmentation of the macules may be altered too—darkening light skin and lightening dark skin. Pityriasis ver-
Department of Pathology, Georgetown University
School of Medicine, Washington, D.C.
sicolor tends to be chronic, with the macules enlarging
and coalescing, then regressing and recurring for many
years. Pityriasis versicolor is worldwide but apart from
cosmetic change is innocuous. In addition to pityriasis
versicolor, M. furfur has been blamed for dacryoliths,18
maxillary sinusitis," mastitis,2 and peritonitis in a patient
having peritoneal dialysis.17 In none of these reports,
however, was M. furfur demonstrated to invade or inflame
viable tissue, so its role as a pathogen in these sites remains
undefined. In 1981, however, Redline and Dahms 15 described a more aggressive infection by M. furfur. The patient was a premature infant who had received deep intravenous lipid from day 10 until death. At six weeks the
infant's respiratory status suddenly worsened, and on chest
x-ray there were bilateral infiltrates that progressed to diffuse opacification. An open-lung biopsy revealed vasculitis
and bronchopneumonia caused by M. furfur. An autopsy
confirmed this and revealed lipid droplets in the walls of
pulmonary vessels. The authors described no evidence of
infection beyond the lungs. Since then a total of 40 patients
with deep infections have been reported. These are 34
neonates (3 described herein), 1 infant (18 months old),
2 children (3.5 and 9.75 years), and 3 adults (see Table
1, Powell and associates,12 Long and associates,8 Redline
and associates,16 Dankner and associates,5 Alpert and associates,1 and Marcon and associates10). Each of these 40
patients had received lipid emulsions by deeply placed
intravenous catheters. Histopathologic studies were done
on six of these (Table 2), only one of which showed infection by M. furfur. We describe herein postmortem examinations, including histopathologic studies, on three
premature infants infected with M. furfur. All had disseminated lesions, a phenomenon not previously described.
Report of Three Cases
Received December 12, 1988; received revised manuscript and accepted for publication January 23, 1989.
Address reprint requests to Dr. Shek: Department of Pathology,
Georgetown University School of Medicine, 3900 Reservoir Road, NW,
Washington, D.C. 20007.
595
Case 1
A premature, 800-g black male infant was born at 25 weeks gestation
to a 16-year-old mother whose membranes ruptured 34 hours before
NEC, recovered
580-g birth weight, "lung"
Bilateral pulmonary streaky infiltrates
Fever
52 d
63 d
32 d
270 d
33 wk
27 wk
31 wk
28 wk
40 wk
32 wk
26 wk
t
t
t
t
t
M
F
F
M
F
M
F
F
F
F
M§
Powell and colleagues,
1984
Powell and colleagues,
1984
Powell and colleagues,
1984
Powell and colleagues,
1984
Powell and colleagues,
1984
Dankner and Spector,
1985
Dankner and Spector,
1985
Redline and colleagues,
1985
Redline and colleagues,
1985
Redline and colleagues,
1985
Redline and colleagues,
1985
Redline and colleagues,
1985
3
5
6
30 d
t
34 wk
36 wk
27 wk
30 wk
M§
F
M
F
M
Redline and colleagues,
1985
Long and colleagues,
1985
Long and colleagues,
1985
Long and colleagues,
1985
Long and colleagues,
1985
16
20
19
18
17
240 d
t
M§
Redline and colleagues,
1985
15
14
13
12
11
10
9
8
7
4
n
BPD, CHF, HLD,
hypothyroidism, died
BPD, CHF, HLD,
hypothyroidism, died
Trisomy 21, Hirschsprung's
disease, recovered
Small bowel resection,
corticosteroid therapy,
recovered
Bone marrow transplant,
GVHD, corticosteroids,
azathioprine, recovered
Cutaneous fistulae, recovered
NEC, multiple cardiac
malformations, recovered
Volvulus, small intestine,
recovered
Recovered
950-g birth weight, pneumonia, left lower lobe
27 d
t
M*
Hassall and colleagues,
1983
2
56 d
t
t
t
t
t
Apnea, lethargy, bradycardia, dusky color
Fever
Fever, tachypnea
Hemorrhagic pancreatitis
Aplastic anemia
Crohn's disease
740-g birth weight pneumonia
t
Hyperbilirubinemia, PDA,
NEC, recovered
BPD, CHF, HLD, died
740-g birth weight, apnea, bradycardia,
RDS, BPD, died
cardiomegaly, edema, cholestasis,
bronchopneumonia, pulmonary vasculitis
2/week, beginning
Volvulus and atresia, ileumFever, leukocytosis, intracardiac thrombus
at 4 weeks
postsurgical short-bowel
on catheter, consolidation left lung, embolus left
syndrome, recovered
pulmonary artery
26 d
NEC—apnea of premature,
1,644-g birth weight, lethargy, apnea, seizures,
recovered
bradycardia, hepatosplenomegaly
30 d
BPD; seizures, recovered
980-g birth weight, lethargy, apnea, fever
bradycardia, interstitial pneumonia,
37 d
BPD; apnea of prematurity,
leukocytosis, thrombocytopenia
recovered
860-g birth weight, apnea, fever, bradycardia,
interstitial
pneumonia,
leukopenia,
Possible NEC; PDA,
11 d
thrombocytosis
recovered
900-g birth weight, apnea, bradycardia, fever,
Achalasia, aspiration
15 d
interstitial pneumonia, thrombocytopenia
pneumonia, recovered
Fever,
leukocytosis,
thrombocytopenia
t
t
28 wk
1
F
Associated Diseases/Fate
Redline and Dahms,
1981
Clinical Features
Gestational
Age
Author/Reference
Case
Gender
Duration of IV
Lipids
Table 1. Infections by Malassezia Furfur
Blood culture, culture of
catheter tip
Blood culture, culture of
catheter tip
Blood culture, culture of
catheter tip
Blood culture
Blood culture
Blood culture
Blood culture
Blood culture
Blood culture (tip of
catheter), autopsy, lung
Autopsy, lung
Biopsy, lung
Blood culture
Blood culture
Blood culture (Broviac)
Blood culture (Broviac)
Blood culture (Broviac)
Blood culture (Broviac)
Blood culture (Broviac)
pneumonectomy left side
Culture of catheter,
Biopsy of lung; autopsy
Method of Diagnosis
3
E
X
m
VI
ON
Alpert a n d colleagues,
1987
Alpert a n d colleagues,
1987
Alpert a n d colleagues,
1987
Alpert a n d colleagues,
1987
Alpert and colleagues,
1987
Alpert a n d colleagues,
1987
Marcon a n d Powell,
1987
Marcon a n d Powell,
1987
22
23
24
25
26
27
Marcon a n d Powell,
1987
Marcon a n d Powell,
1987
Marcon a n d Powell,
1987
Marcon a n d Powell,
1987
Marcon a n d Powell,
1987
Marcon a n d Powell,
1987
Marcon a n d Powell,
1987
Marcon a n d Powell,
1987
Present article—Shek
and colleagues, 1988
Present article—Shek
a n d colleagues, 1988
Present article—Shek
a n d colleagues, 1988
31
32
33
34
35
36
36a**
37
38
40
25 wk
34 wk
34 wk
F
M
M
25 wk
t
F*
M
36 wk
F
26 wk
26 wk
F
F
28 wk
M
25 wk
28 wk
M
M
39 wk
M
27 wk
27 wk
F
F
28 wk
40 wk
31 wk
27 wk
37 wk
27 wk
25 wk
t
t
t
t
t
t
t
49
60
64
15
140
56
67
4
180
24
18
86
125
17
2511
2511
2511
2511
2511
2511
2511
Necrotizing enterocolitis,
pneumatosis intestinalis,
patent d u c t u s arteriosus,
died
Patent ductus arteriosus,
necrotizing enterocolitis,
died
Prematurity, p a t e n t d u c t u s
arteriosus, died
R D S , recovered
recovered
Gastroschisis, short gut,
Gastroschisis, short gut,
recovered
R D S , recovered
G l i o m a , brain stem,
recovered
Gastroschisis, short gut,
recovered
Prematurity, recovered
B P D , hydrocephalus,
recovered
B P D , seizures, recovered
recovered
B P D , hydrocephalus,
B P D , recovered
N E C , recovered
N E C , recovered
N E C , recovered
N E C , died
disease, died
Cyanotic congenital heart
B P D , recovered
B P D , P D A , recovered
Autopsy
Autopsy
culture of catheter tip
Blood culture (Broviac),
culture of catheter tip
Blood culture (Broviac),
culture of catheter hub
and tip
Blood culture, culture of
catheter tip
Blood culture (Broviac),
culture of catheter
Blood culture (Broviac),
culture of catheter tip
Blood culture (Broviac),
culture of catheter tip
Blood culture (Broviac and
peripheral), culture of
catheter tip and hub
Autopsy
Blood culture (Broviac),
Blood culture (Broviac)
Blood culture (Broviac)
Blood culture (Broviac)
Blood culture (catheter)
Blood culture (catheter)
Blood culture (catheter)
Blood culture (catheter)
Blood culture (catheter)
Blood culture (catheter)
Blood culture (catheter)
t Infant.
§ Adult.
V Average duration for patients 21 through 27 is recorded as 25 weeks with a range of 9-56 weeks.
** Same patient—second course of treatment.
765-g birth weight; respiratory distress; feeding
problems; bradycardia, intubation, a n d severe
B P D ; hemorrhage into ventricles of brain
710-g birth weight, fever
800-g birth weight, bilateral p n e u m o n i a , severe
BPD
793-g birth weight, bradycardia, interstitial
pneumonia
Fever, splenomegaly
680-g birth weight, apnea, bradycardia, interstitial
pneumonia
Fever, splenomegaly
Fever, cyanosis
800-g birth weight, apnea, bradycardia, interstitial
pneumonia
Fever
Fever, cyanosis, splenomegaly, interstitial
pneumonia
Fever, splenomegaly, hypercapnia, interstitial
pneumonia
pneumonia
750-g birth weight, bradycardia, interstitial
1,120-g birth weight, respiratory distress,
bradycardia
3,400-g birth weight, a s y m p t o m a t i c
1,250-g birth weight, tachypnea, bradycardia,
apnea, unstable temperature
760-g birth weight, lethargy
2,910-g birth weight, fever, respiratory distress
900-g birth weight, n o s y m p t o m s ,
thrombocytopenia
670-g birth weight, apnea, bradycardia
BPD = bronchopulmonary dysplasia; CHF = congestive heart failure; GVHD = graft versus host disease; HLD = hyperalimentation liver disease; NEC = necrotizing enterocolitis; PDA = patent ductus arteriosus; RDS = respiratory distress
syndrome.
* Child.
t Not stated in report.
39
Marcon a n d Powell,
1987
30
29
28
Alpert a n d colleagues,
1987
21
598
SHEK ET AL.
A.J.C.P. • November 1989
Table 2. Cases of Malassezia Furfur with Histopathologic Confirmation
Case
Reference
Gender
Biopsy Findings
Autopsy Findings
Lung, vasculitis of small arteries—including neutrophils*
bronchopneumonia, mild bronchopulmonary
dysplasia, yeasts of M. furfur in walls of vessels and
alveoli, no granulomas
Lung, vasculitis of small arteries*, lipid
droplets in walls of vessels, severe
bronchopulmonary dysplasia
Other organs, no vasculitis or lipid
infiltration beyond lung
M
Thrombus in right atrium on catheter tip, containing
yeasts of M. furfur. Gram + cocci, and dystrophic
calcification
Left lung (pneumonectomy specimen), multiple septic
infarcts with yeasts of M. furfur in infarcts and in and
around vessels, and recanalization at margin of infarct
None (recovered)
Redline and associates,
1985
F
None
Lung, severe organized BPD, no evidence
of M. furfur infection at autopsy
Redline and associates,
1985
F
None
Lung, M. furfur vasculitis
Redline and associates,
1985
F
Lung, Pneumocystis and residual A
thromboemboli
None (died)
Redline and associates,
1985
M
Lung, biopsy—M. furfur identified
None (recovered)
Shek and associates,
1988
M
None
Lung, M. furfur in thromboemboli, vessel
walls, alveoli, capillaries, bronchi, and
bronchioles
Other organs, M. furfur in heart, kidney,
liver, spleen and pancreas
CMV infection of lung, liver, kidney,
and spleen; absent thymus; minimal
lymphoid tissue throughout body
None
M. furfur in embolus at bifurcation of
pulmonary artery, M. furfur in
thrombi associated with lipid droplets
Other organs—M. furfur in heart, kidney,
pancreas, colon, kidney, adrenal, and
pancreas
Brain, meningoencephalitis caused by M.
furfur
None
Lung, multiple thrombi containing M.
furfur associated with multiple infarcts
Brain, focal encephalitis caused by
Candida species
1
Redline and Dahms,
1981
2
Hassall and associates,
1983
Shek and associates,
1988
Shek and associates,
1988
M
BPD = bronchopulmonary dysplasia; CMV = cytomegalovirus.
delivery. The Apgar scores were 5 at 1 minute and 6 at 5 minutes. The
infant was intubated immediately and required continuous ventilatory
support. There was a patent ductus arteriosus that did not close with
Indocin®, so it was ligated on day 10.
A variety of antibiotics were used throughout the course for suspected
sepsis. On day 3, parenteral nutrition, including intravenous lipids, was
begun and continued until the infant died. Afirstcatheter, placed in the
umbilical artery, became occluded and was replaced by a Broviac catheter
on day 23. Cultures of peripheral blood and blood drawn from the Broviac
catheter grew no pathogenic microorganisms. Media for fungi were not
inoculated. The cerebrospinal fluid was normal. A chest x-ray revealed
bilateral pneumonia superimposed on severe (grades 3-4) bronchopulmonary dysplasia. Circulating white blood cells were 37 X 109/L (37
X 103/ML). Band cells were 0.25 (25%) and neutrophils 0.67 (67%).
Platelets were 120 X 109/L (120 X 103/ML)- He died on day 67.
At autopsy the baby weighed 1,160 g. The tip of the Broviac catheter
was in the right atrium and free of thrombi. There were, however, en-
' Additional data on case 1 reported by Redline and associates, 1985.
docardial vegetations on the tricuspid valve and the posterior leaflet of
the mitral valve. Yeasts characteristic of M. furfur were in pulmonary
arteries, pulmonary capillaries, lumina of bronchi and bronchioles, and
alveoli. In some pulmonary arteries there were pure collections of M.
furfur not mixed with leukocytes or fibrin. These yeasts were actively
budding and not associated with vasculitis. In other pulmonary arteries
there were septic thrombi containing yeasts, fibrin, and degenerating
leukocytes. These were fixed to the intima and associated with acute
vasculitis and sometimes presented a layered or "target" appearance.
Some emboli were organizing and partially recanalized. Large histiocytes
containing yeasts were in some of these thrombi. Yeasts were also in the
walls of vessels and surrounding alveoli, which were consolidated. In
several arteries, yeasts were clustered in the cytoplasm of smooth muscle
cells. In myocardium, what appeared to be pure collections of yeasts
occluded the lumina of small vessels, but these were not in thrombi and
not associated with vasculitis or myocarditis. Major coronary vessels
were free of yeasts, thrombi, and other lesions. Discrete and clumped
Vol. 92 • No. 5
MALASSEZIA FURFUR. DISSEMINATED INFECTION
yeasts were in glomeruli of the kidney, small vessels and capillaries of
the renal cortex, and endothelial cells of the capillaries. Small collections
of yeasts were in vessels of liver, spleen, and pancreas. These had provoked
neither inflammation nor thrombosis. We found no yeasts in sections
of stomach, jejunum, ileum, colon, or adrenal. Permission to examine
the brain was denied.
There was cytomegalovirus infection of lung, liver, kidney, and spleen
with associated inflammation in lung but not in liver, kidney, or spleen.
Dissection of the anterior mediastinum revealed no thymus, and there
was only minimal lymphoid tissue throughout the body.
Case 2
A 710-g black baby girl was born at 26 weeks gestation. The mother
was 24 years old, and the pregnancy was complicated by premature
rupture of the membranes the day before delivery. Apgar scores were 5
at 1 minute and 8 at 5 minutes. The infant was intubated at birth. Shortly
after birth the white blood cell count was 22 X 109/L (22 X 103/ML) and
the hematocrit was 0.45 (45%). A patent ductus arteriosus closed after
two trials of Indocin. Several episodes of fever were treated with a variety
of antibiotics, but repeated cultures grew no pathogens. Necrotizing enterocolitis developed on day 45, and a segment of terminal ileum was
resected. At the same operation a Broviac catheter was inserted. She did
well until day 64, when she suddenly became hypoxic and hypotensive.
An echocardiogram revealed a right atrial thrombus at the tip of the
Broviac catheter. She failed to maintain adequate oxygenation and died
on day 65.
Total parenteral nutrition (TPN), beginning on day 1, included Intralipid® and was given for 60 days of the 65-day course. At first this
was administered through an umbilical venous catheter and later through
peripheral catheters. Beginning with day 45, TPN and Intralipid were
given through the Broviac catheter.
Postmortem examination revealed a thromboembolus occluding the
bifurcation of the pulmonary artery. The tip of the Broviac catheter was
in the right atrium, surrounded by thrombus and fixed to the endocardium. Microscopically, the thrombus and the thromboembolus contained
discrete and clustered yeasts characteristic of M. furfur. All lobes of both
lungs contained dark and light patches measuring up to 1 cm (Fig. 1).
The yeasts were in mycotic thrombi, and some of the thrombi contained
lipid droplets mixed with yeasts (Fig. 2). Some of the thrombi were composed of concentric layers of yeasts and fibrin, giving the cross-sections
of thrombi a "target and bull's eye" pattern (Fig. 3). Foci of infarction
surrounded some of the emboli. Yeasts were in small vessels of heart,
liver, pancreas, and large intestine. Yeasts were also in capillaries of
glomeruli, lining cells of renal tubules, abscesses of renal cortex, and
adrenal cortex. The brain weighed 220 g, was premature, and had slight
clouding of the basal leptomeninges. Coronal sections disclosed no gross
abnormalities. Microscopically, the leptomeninges of the brain stem and
cerebral convexities contained an exudate of neutrophils and macrophages. Several vessels in the subarachnoid space were occluded by septic
thrombi, and their walls were infiltrated by acute inflammatory cells and
yeasts characteristic of M. furfur. The periventricular white matter, cerebral cortex, basal ganglia, and brain stem contained many microglial
nodules and foci of necrotizing encephalitis. The latter contained yeasts
characteristic of M. furfur. The foci of necrosis consisted of zones of
parenchymal disintegration and accumulation of lymphocytes, macrophages, giant cells, and proliferation of astrocytes and microglial rod
cells (Fig. 4).
Case 3
A 765-g black baby boy was born at 25 weeks gestation to a 29-yearold woman. The pregnancy was complicated by a low-lying placenta.
599
The Apgar scores were 7 at 1 minute and 8 at 5 minutes. The infant was
intubated at three hours for respiratory distress. The baby had feeding
problems from birth, with an episode of necrotizing enterocolitis and
pneumatosis intestinalis at day 8. This was treated with antibiotics and
it was resolved in 22 days. He received TPN, including intravenous lipids
through an umbilical catheter beginning on day 1 and continuing for
one month, at which time oral feedings were restarted. Further episodes
of necrotizing enterocolitis disrupted oral feedings, and a Broviac catheter
was placed at day 24 for parenteral nutrition.
He had a patent ductus arteriosus that closed after two doses of Indocin,
only to reopen by day 14. It was closed surgically at three weeks. There
were several episodes of bradycardia that necessitated reintubation, and
this led to severe bronchopulmonary dysplasia. His condition was relatively stable until day 58, when there were signs of a systemic infection,
including circulating white blood cells of 20 X 109/L (20 X 103/nL).
Then he became bradycardic and, despite antibiotics and resuscitative
efforts, died on day 60. Intravenous lipid was given for 49 of his 60 days
of life.
At autopsy, the body weighed 1,300 g. The tip of the Broviac catheter
was at the entrance to the right atrium. There were no thrombi around
the tip or elsewhere in the heart. Many medium-sized pulmonary arteries
were occluded with thrombi that contained M. furfur. Some of the
thrombi were organized and some were recanalized. Microscopically,
two organizing thrombi contained giant cells of the foreign body type,
and these contained many yeasts of M. furfur (Fig. 5). The pulmonary
parenchyma surrounding the thrombosed vessels was mottled, with numerous hemorrhagic infarcts. In some areas the infarcts were confluent.
Clusters o(M. furfur occluded the lumina of small vessels of liver, spleen,
and kidney; some of them presented the appearance of "target thrombi."
Scattered yeasts characteristic of M. furfur were present in the myocardium. The leptomeninges werefibrotic.Sections of brain contained foci
of necrosis caused by infection with Candida species. Cultures taken just
before death grew Candida species.
Discussion
Of 37 previously reported deep infections by M. furfur
(Table 1), all patients had received lipid emulsions intravenously and 31 (84%) were neonates with an average
gestational age of 30.6 weeks. Tissue specimens—biopsy
or autopsy—were available in only 6 of the 37 patients.
Two of the autopsies had evidence of residual or resolved
infection only and thus contributed essentially nothing to
our understanding of pathogenesis (Table 2). Despite this
paucity of tissue specimens, a consistent pattern of lesions
has emerged. These are mycotic thrombi around the tips
of deeply placed catheters, vegetations of endocardium,
and inflammatory lesions of lung, including mycotic
thromboemboli, infarcts, inflamed vessels containing M.
furfur, and droplets of lipid and consolidated alveoli. Our
cases had similar lesions of heart and lung but in addition
had distant lesions, and in two of the three there was a
granulomatous component to the reaction, a feature of
M. furfur infection not previously reported.
M. furfur appears in sections of deep organs as yeasts
that are round to oval, up to 5 fim across, and with many
budding forms—the daughters sprouting from one pole
of the parent through a collarette (Fig. 6). The appearance
on electron microscopic examination is also characteris-
600
SHEK ET AL.
A.J.C.P. • November 1989
FIG. 1 (upper, left). The white areas are consolidated lung and have formed around thrombosed pulmonary arteries.
The dark areas are hyperemic. Case 1, gross lung (X4).
FIG. 2 (lower, left). A "target thrombus" in a pulmonary artery. The central area ("bull's eye") is composed of organisms and lipid and is surrounded
by layers of leukocytes and fibrin. Many yeasts are in the lumen, the wall of the vessel, and the surrounding alveoli. The wall of the vessel is inflamed.
Case 2, lung. Hematoxylin and eosin (X100).
FIG. 3 (upper, right). Another septic "target thrombus" occludes a branch of the pulmonary artery. A central "bull's eye" of organisms is surrounded
by a layer offibrinthat, in turn, is surrounded by a perimeter of more organisms. The latter are against the intima of the vessel. Case 2, lung. Gomori
methenamine silver stain (GMS) (X100).
FIG. 4 (lower, right). Brain showing perivascular collections of lymphocytes, histiocytes, and a single giant cell. Case 2, brain. Giemsa (X400).
Vol. 92 • No. 5
MALASSEZIA FURFUR, DISSEMINATED INFECTION
601
FIG. 5 (upper, left). An organized and partially recanalized mycotic thrombus in a branch of the pulmonary artery. The reaction includes a
granulomatous component, as evidenced by the giant cells that contain many yeasts of M. furfur. Case 3, lung. Periodic acid-Schiff(X400).
FIG. 6 (lower, left). Clusters of budding M. furfur yeasts in a vessel. The unipolar buds and collarette can be seen
in most of the cells. Case 1, lung. Brown and Hopps tissue Gram's stain (XI,000).
FIG. 7 (upper, right). Electron micrograph of M. furfur. The daughter cell (upper) is growing out of the parent cell (lower). The thick cross-wall
separating the two, phialitic ring, thick capsule, and internal corrugations of the capsule are all apparent and characteristic of M. furfur. This cluster
of M. furfur appears to be a pure culture—free of leukocytes and fibrin. Case 1, lung. Electron micrograph (X27,000).
FIG. 8 (lower, right). Colony of yeasts (M. furfur) in a cardiac vegetation. The GMS stain reveals more organisms and with more
contrast than the other stains we used. Case 2, endocardium. Gomori methenamine silver stain (GMS) (X400).
602
SHEK ET AL.
tic—a thick wall with corrugations on the inner surface
and a polar, circumferential thickening of the wall of the
yeast forming the distinct collarette (Fig. 7). With routine
hematoxylin and eosin staining, M. furfur yeasts are lightly
hematoxylinophilic, but morphologic features are not
distinct. M. furfur, however, is well stained with periodic
acid-Schiff (PAS), Gomori methenamine silver stain
(GMS), the Gridley fungus stain, and tissue Gram's stains.
The Brown-Hopps tissue Gram's stain shows the morphologic features especially well, but GMS appears to stain
more organisms and in greater contrast than do the other
stains we used (Fig. 8). These features enable the pathologist to distinguish M. furfur from the other pathogenic
yeasts. Histoplasma capsulatum, although approximately
the same size as M. furfur, has a narrow isthmus and lacks
the collarette that characterizes M. furfur. Candida species
are usually polymorphous in tissue sections, with hyphae,
pseudohyphae, and yeasts all present. Candida species,
furthermore, do not have the collarette of M. furfur. Cryptococcus neoformans has a wider range in size than M.
furfur—frequently from 2 to 10 /*m across—and budding
forms have a narrow isthmus. Confusion with less commonly encountered pathogenic yeasts is unlikely, but several points are worth noting. Penicillium marneffei, which
causes a disseminated and frequently fatal mycosis in
South China and Southeast Asia,6 resembles M. furfur in
size and shape but reproduces by elongated "sausage
forms" with cross-walls—quite different from the budding
forms and collarettes of M. furfur. Although anatomic
location and tissue reaction cannot be used to identify a
specific fungus, the location of yeasts in septic thrombi
should alert the pathologist to the possibility of M. furfur.
In case 2, a mycotic embolus from the tip of the catheter
in the right ventricle lodged at the bifurcation of the pulmonary artery and killed the infant. Hassall and
associates7 described nonfatal pulmonary embolization
in a child receiving long-term parenteral nutrition to
whom urokinase was given to dissolve an intracardiac
thrombus. With or without urokinase, however, pulmonary embolization—including saddle embolization and
sudden death—is a constant hazard in deep-seated M.
furfur infections.
The primary focus of infection and the emboli as well
is the tip of the deep-lying catheter. How the catheter tips
become colonized by M. furfur is not clear, but Marcon
and Powell10 listed five possible routes of infection: (1)
contamination at the time of placement, (2) infusion of
contaminated lipids, (3) hematogenous spread from a distant source, (4) migration of M. furfur from skin along
the outer wall of the catheter, and (5) migration of M.
furfur from the catheter bulb through the lumen. Recently
Powell and colleagues14 demonstrated that yeasts of M.
furfur attach to and colonize the luminal surface of Broviac
A.J.C.P. • November 1989
catheters. In another study,13 colonization of neonatal skin
by M. furfur correlated with young gestational age, low
birth weight, increased time in intensive care, increased
time in an incubator, and increased handling of infants
by multiple adults. Although our study sheds no direct
evidence on route or mechanism of infection, it seems
likely from the studies cited that the catheter tip is colonized after placement and from the skin—along the catheter's internal surfaces—rather than from a distant source
by the blood stream.
From the catheter tip, clusters of yeasts free or within
mycotic thrombi probably seed the lungs, causing vasculitis, septic thrombosis, infarction, and consolidation
of perivascular alveoli. The pattern of consolidation tends
to be symmetric and is centered around inflamed and
thrombosed arteries and arterioles. Of special interest are
the "target thrombi" (Figs. 2 and 3). How they form is
not clear. Lipid may be deposited first in walls of pulmonary vessels, predisposing the patient to growth of M.
furfur on the intima, followed by layers of fibrin and proliferating organisms. Also possible is that an embolus
containing M. furfur impacts in an artery or arteriole and
acts as a nidus for growth by accretion—either forward
with the stream or backward against the steam with deposits of successive layers of fibrin and organisms. The
destructive lesions in the lungs of our patients indicate
that M. furfur gains the systemic circulation by invading
the pulmonary veins.
In conclusion, our cases reveal that, in addition to pulmonary and cardiac lesions, there are distant lesions, including acute meningitis, necrotizing encephalitis, and
interstitial nephritis. Ourfindingsalso reveal that disseminated infection by M. furfur may be fatal in premature
infants. Finally, the "target thrombi" appear to be characteristic of infection by M. furfur.
Acknowledgments. Drs. Libera Ajello and Francis Chandler of the
Centers for Disease Control, Atlanta, Georgia, identified the fungus in
case 1 as M. furfur. From the Department of Pathology, Georgetown
University, Don Hay prepared the photomicrographs and Eileen Rusnock
and Brett Connolly prepared the electron micrograph. Dr. K. T. KwonChung of the mycology laboratory at the National Institutes of Health
reviewed the manuscript and made helpful suggestions.
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