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Steinbrück K,
et al.
,
2019; 18 (1): 258-262
258
Biliary Paracoccidioidomycosis:
An Unusual Infection Simulating
Malignant Neoplasm
Klaus Steinbrück, Reinaldo Fernandes
Hepatobiliary Surgery, Bonsucesso Federal Hospital, Health Ministry, Rio de Janeiro, Brazil.
January-February, Vol. 18 No. 1, 2019: 258-262
CASE REPORT
The Official Journal of the Mexican Association of Hepatology,
the Latin-American Association for Study of the Liver and
the Canadian Association for the Study of the Liver
Manuscript received:Manuscript received:
Manuscript received:Manuscript received:
Manuscript received: October 12, 2017. Manuscript accepted:Manuscript accepted:
Manuscript accepted:Manuscript accepted:
Manuscript accepted: January 30, 2018.
DOI:10.5604/01.3001.0012.7935
ABSTRACTABSTRACT
ABSTRACTABSTRACT
ABSTRACT
Paracoccidioidomycosis is a systemic granulomatous disease caused by the dimorphic fungus
Paracoccidioides brasiliensis
and is
restricted to Latin America. It normally affects lungs, skin and lymph nodes. Abdominal organs are usually not involved. In rare cas-
es paracoccidioidomycosis may simulate neoplasm. Herein we describe our experience with four cases of paracoccidioidomycosis
mimicking cholangiocarcinoma. To the best of our knowledge, this is the largest case series on this subject produced in English.
Paracoccidioidomycosis must be considered as a differential diagnosis of cholangiocarcinoma, especially in individuals who come
from endemic areas.
Key words.Key words.
Key words.Key words.
Key words. Paracoccidioidomycosis. Cholangiocarcinoma. Biliary tract. Liver.
INTRODUCTION
Paracoccidioidomycosis (PCM) is one of the most im-
portant deep mycoses in Latin America1 and was originally
described by Adolfo Lutz in 1908.2 The etiologic agent is
the dimorphic fungus Paracoccidioides brasiliensis.1 It presents
itself in two major forms: subacute (3-5% of cases), affect-
ing mostly children and young adults, frequently compro-
mising the reticuloendothelial system,1,3 and chronic (90%
of cases), involving predominantly adult males, normally af-
fecting lungs, lymph nodes and skin.1,3 Identification of the
fungus in the affected tissue (paracoccidioidal granuloma)
or culture of exudate establishes diagnosis.1 Herein we de-
scribe four cases of PCM simulating cholangiocarcinoma.
CASE REPORT
Patient 1
A 53-year-old man, from the rural area of Rio de Janei-
ro, Brazil, was admitted with a three-month history of
jaundice, pruritus, acholic stools, choluria and weight loss
of 10 kg. He denied fever. Physical examination revealed a
painful and palpable left liver lobe in the epigastrium. No
peripheral lymphadenopathy was detected. Anemia and el-
evated liver enzymes and bilirubin were present (Table 1).
Tumor markers (CEA and CA19-9) were normal. Thorax
X-ray was normal. Abdominal ultrasonography showed
hepatomegaly, intrahepatic left bile duct dilatation with-
out perihilar linphadenomegaly and an empty gallbladder.
MRI confirmed left bile duct dilatation without extrinsic
compression (Figure 1A).
Two years earlier, he had been diagnosed with ganglio-
nar PCM located in the cervical region and has been being
treated since with itraconazole 200 mg/day. No history of
other diseases or previous surgery was known.
An early stage intrahepatic cholangiocarcinoma was sus-
pected and the patient was referred to surgery. Left hepa-
tectomy with common bile duct resection and Roux-en-Y
biliary-enteroanastomosis reconstruction was performed.
He was discharged without complications after seven days.
Histopathological evaluation revealed areas of cavitation
and biliary abscesses in the liver, in which fungal elements
compatible with P. brasiliensis were present (Figure 2A).
After diagnosis of biliary PCM, treatment with itracona-
zole was resumed. One year after surgery, he developed a
new episode of ganglionar PCM in the inguinal region.
He is doing well, six years after hepatectomy.
© 2019, Fundación Clínica Médica Sur, A.C. Published by Elsevier España S.L.U. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
259
Biliary Paracoccidioidomycosis.
,
2019; 18 (1): 258-262
Table 1. Admission patients’ blood tests results.
Blood test Patient 1 Patient 2 Patient 3 Patient 4
Alkaline phosphatase (mg/dL) 3,848 561 268 2,503
GGT (mg/dL) 4,402 463 481 3,892
AST (U/L) 264 106 80 207
ALT (U/L) 125 174 46 180
Total bilirubin (mg/dL) 13.8 9.01 8.4 16.5
Direct bilirubin (mg/dL) 8.2 7.52 7.1 13.3
Figure 1. A.Figure 1. A.
Figure 1. A.Figure 1. A.
Figure 1. A. Patient 1: MR T2-weighted showing an important biliary tree dilatation, mostly in left duct. B.B.
B.B.
B. Patient 2: MRI image showing an infiltrative
mass inside the hepatocholedocus (arrow heads). C.C.
C.C.
C. Patient 3: Percutaneous cholangiography during biliary drain placement. Main duct blockage is evidenced
(arrow heads). D.D.
D.D.
D. Patient 4: MR T2-weighted showing obstruction of common bile duct with upstream dilatation.
AA
AA
ABB
BB
B
CC
CC
CDD
DD
D
Patient 2
A 22-year-old man, from Rio de Janeiro was trans-
ferred from a primary hospital with one-month history
of jaundice associated with diarrhea and a substantial
weight loss of 20 kg. He denied fever or abdominal pain.
No peripheral lymphadenopathy was found. No morbid-
ities were known. No history of rural work or previous
fungal disease was reported. Laboratory exams confirmed
anemia and elevation of serum bilirubin as well as liver
Steinbrück K,
et al.
,
2019; 18 (1): 258-262
260
enzymes (Table 1). Serology for hepatitis and HIV were
negative. MRI showed an infiltrative mass inside the
hepatocholedocus, with restricted diffusion, obstructing
primary and secondary biliary ducts, especially in the
right side (Figure 1B), suggestive of extra-hepatic cholan-
giocarcinoma.
The patient was submitted to laparotomy. The liver
had some whitish lesions suggestive of secondary im-
plants. A large quantity of lymph nodes was observed in
the hepatic hilum, hepatic artery and para-aortic. A fro-
zen section biopsy of the liver and para-aortic lymph
node did not show malign neoplasia. Transcystic
cholangiography showed obstruction of the passage of
contrast through the distal bile duct. The illness was
considered to be at an advanced stage, and surgical team
decided to perform cholecystectomy, internal/external
drainage of the biliary tract, lymph node excision, and
biopsies. After surgery, he developed biliary fistula and
pancreatitis and responded well to clinical therapy. Mi-
croscopic analysis revealed granulomatous chronic in-
flammatory process affecting the gallbladder, liver and
lymph nodes, associated to numerous giant multinucle-
ated cells and fungal structures compatible with P. bra-
siliensis (Figure 2B). After 30 days of intravenous
amphotericin B, the patient left the hospital in a gener-
ally good state, taking itraconazole orally. The biliary
drain was removed after one year and, five years after
surgery, the patient is doing well.
Figure 2Figure 2
Figure 2Figure 2
Figure 2. A.A.
A.A.
A. Patient 1: area of granuloma containing fungal spherical elements (arrow) compatible with
P. brasiliensis
, H&E stain x400. B.B.
B.B.
B. Patient 2: fungal
structures with budding affecting lymph node, Grocott‘s methenamine silver stain x400. CC
CC
C and DD
DD
D. Patient 3 and 4: fungal structure with characteristic “Mickey
Mouse” and “steering wheel” budding, respectively, Grocott‘s methenamine silver stain x400.
AA
AA
ABB
BB
B
CC
CC
CDD
DD
D
261
Biliary Paracoccidioidomycosis.
,
2019; 18 (1): 258-262
Patient 3
A 53-year-old woman was transferred from a primary
hospital from the rural area of Rio de Janeiro with a three-
month history of jaundice, pruritus, acholia, choluria and
weight loss of 13 kg. At the primary hospital, she was sub-
mitted to percutaneous transhepatic cholangiography,
which showed intrahepatic biliary dilatation and main bile
duct blockage. An internal-external biliary drain was
placed at the same time (Figure 1C). Admission blood
tests showed anemia and elevated serum bilirubin and ca-
nalicular enzymes (Table 1). CT scan confirmed biliary
dilatation above hepatic confluence and identified gall-
bladder with thick and infiltrated wall, compatible with
cholecystitis, as well as para-aortic and celiac trunk lym-
phadenomegaly. The patient was considered to have ad-
vanced illness and treatment was limited to antibiotic
therapy for cholecystitis, once biliary tract was already
drained. After 9 days, she presented abdominal sepsis and
underwent emergency laparotomy. During surgery,
choledocoduodenal fistula, cholecystitis and inflammatory
pseudotumoral involvement of duodenum were identi-
fied. The emergency team opted to perform cholecystec-
tomy, Billroth II distal gastrectomy, and mesenteric lymph
node biopsy. After surgery, the patient experienced
cholangitis, but responded well to antibiotics. His-
topathological evaluation revealed granulomatous chronic
inflammatory process with round fungal structures, com-
patible with P. brasiliensis affecting the gallbladder, gall-
stones, mesenteric lymph node, and stomach wall (Figure
2C). The patient received amphotericin B for 30 days and
was discharged 47 days after surgery taking itraconazole
orally. The biliary drain was detached one year after sur-
gery and patient is well and asymptomatic, 38 months after
surgery.
Patient 4
A 48-year-old woman from Rio de Janeiro was admit-
ted with a two-month history of abdominal pain, choles-
tatic jaundice and weight loss of 12 kg. She had arterial
hypertension, which was under control, and had under-
gone a hysterectomy 10 years before, due to myomatosis.
No peripheral lymphadenopathy was found. Laboratory
tests confirm cholestasis (Table 1). MRI showed obstruc-
tion of main bile duct next to the confluence (Figure 1D).
The patient was submitted to percutaneous biliary drain-
age and posteriorly referred to surgery.
Bilateral subcostal laparotomy was performed. Hepatic
pedicle had a thick tissue evocative of malignant infiltra-
tion. Lymphadenomegaly was present in the hepatic
hilum, as well as celiac trunk and retropancreatic. An anal-
ysis of these lymph nodes revealed caseous material with
frozen section negative for neoplasia. An inflammatory or
infectious pathology was suspected. As the biliary tract was
already drained, no other procedure was performed.
Anatomopathological examination revealed granulomatous
chronic inflammatory process with round fungal struc-
tures with budding, compatible with P. brasiliensis (Fig-
ure 2D). The postoperative period was uneventful. She
received amphotericin B intravenously for 30 days and
completed treatment with oral itraconazole. Biliary drain
was removed after 10 months. The patient is in good shape,
with mild canalicular enzymes elevation 32 months after
surgery.
DISCUSSION
PCM constitutes a serious public health problem be-
cause it is potentially quite disabling, affecting people dur-
ing the economically productive years, predominantly
male individuals (1 female : 10-15 male).1 It is considered
to be the third leading cause of death from chronic infec-
tious disease, in Brazil.1 About 80% of the cases reported
occurred in Brazil and most of the remaining ones oc-
curred in Venezuela, Colombia and Argentina.1 In Mexi-
co, the endemic area is located in the South between the
Gulf of Mexico and the Pacific Coast.4
The pathogen agent is the dimorphic fungus Paracoccidi-
oides brasiliensis, which is present in nature in filaments con-
taining infective propagules called conidia. Once inhaled,
the propagules give rise to fungi yeast forms that will con-
stitute their parasitic form in host tissues.1
The major risk factor for infection are professions or
activities related to management of soil contaminated with
the fungus, such as agricultural activities, earthmoving,
soil preparation, gardening, and transport of plant goods.
Contamination is primarily acquired in the first two-dec-
ade of life, but the presentation of clinical manifestations
occurre more frequently in adults between 30 and 50 years,
after reactivation of latent endogenous focus.1
Abdominal involvement in PCM is normally seen in
the sub-acute form, with a wide variety of clinical mani-
festations, ranging from nausea, vomiting, ascites, jaundice,
variable abdominal pain, hepatosplenomegaly, malabsorp-
tion syndrome, tumor mass, intestinal obstruction, perito-
nitis, and mesenteritis, to even acute perforative
abdomen.3,5 Jaundice usually appears at a late stage, and it is
associated with more severe disease.6 It is normally caused
by extrinsecal compression of the common bile duct by
lymph nodes.6 Other causes described are intraluminar
granulomatous lesion of the common bile duct (intrinsic
lesion), hepatic lesion caused by blastomycotic hepatitis
and pancreatic PCM.6-8
Steinbrück K,
et al.
,
2019; 18 (1): 258-262
262
In the cases reported here, the presence of jaundice
associated with other symptoms, as well as imaging ex-
ams compatible with cholangiocarcinoma, led us to
this misdiagnosis. Patient 1 had a segmental intrahe-
patic biliary obstruction, which was probably caused
by portal granulomas, as described by Brito, et al.9 Pa-
tient 2 displayed a mass causing obstruction of
choledocus, compatible with intraluminar granuloma-
tous lesion of the common bile duct. Patients 3 and 4
were misdiagnosed with Bismuth type 1 and 2 Klatskin
tumor respectively. In both cases, extrinsecal com-
pression of the common bile duct by lymph nodes and
hepatic hilum inflammatory infiltration caused by
PCM infection were posteriorly considered the rea-
sons for biliary obstruction.
Once the diagnostic hypothesis was cholangiocarcino-
ma, patients 1, 2 and 4 were submitted to intention-to-treat
surgery. Patient 3 was considered to have advanced neo-
plasia, but underwent emergency surgery due to abdomi-
nal sepsis. Choledocoduodenal fistula was identified,
which is a complication of PCM infection not yet de-
scribed. In all cases, diagnosis of PCM was confirmed af-
ter anatomopathological examination of specimen. In
patient 3, even the gallbladder and stomach were involved
with P. brasiliensis.
After PCM was diagnosed, patients were investigated
for fungal involvement of other organs, like lungs, skin,
nasopharynx or lymph nodes and specific treatment was
proposed. The usual therapy involves antifungal drugs,
such as sulfanilamide derivatives, azole compounds and
amphotericin B, which has been used in advanced cas-
es.1 Patient 1 was already using itraconazole, due to a
past history of ganglionar PCM, and treatment was re-
sumed. Patients 2, 3 and 4 manifested the disease in a
more advanced state and were initially treated with am-
photericin B, which was changed to itraconazole after
hospital discharge. Recommended dosage of itracona-
zole is 200 mg per day. Treatment can last up to 24
months and should not be interrupted.1 A cure for PCM
patients may never be achieved because there is always a
chance of later recurrence, as could be observed with
patient 1.
CONCLUSION
The cases reported here are good examples of infec-
tious disease mimicking a neoplasm. In the presence of
obstructive jaundice and suspicion of cholangiocarcinoma,
in Brazil and other endemic areas in Latin America, we
should regard PCM as a differential diagnosis, particularly
if the patient has a previous history of infection by Paracoc-
cidioides brasiliensis.
ABBREVIATIONS
• PCM: paracoccidioidomycosis.
CONFLICTS OF INTEREST
The authors declares that there is no conflict of interest
regarding the publication of this article.
SUPPORTIVE FOUNDATIONS
There was no funding source.
DISCLOSURE
Patient 1 has been published previously as a case
report.
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Correspondence and reprint request:
Klaus Steinbrück, M.D.
Surgeon, Cirurgia Hepato-Biliar, Hospital Federal de Bonsucesso,
Ministério da Saúde, Av. Londres, 616, prédio 3/2º andar, Rio de
Janeiro, RJ, CEP: 21041-030, Brazil.
Tel. and Fax: +55-21-39779811
E-mail: steinbruck@gmail.com
