The Turkish Journal of Gastroenterology
2007, Volume 18, No 3, Page(s) 200-205
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|Paraneoplastic porphyria cutanea tarda associated
with cholangiocarcinoma: Case report
|Mehmet SÖKMEN1, Hüseyin DEMİRSOY1, Özdal ERSOY1, Gonca GÖKDEMİR2, Nihat AKBAYIR1,
Çetin KARACA1, Kamil ÖZDİL1, Beşir KESİCİ1, Can CALIŞKAN3, Banu YILMAZ4
|Departments of 1Gastroenterology, 2Dermatology, 3Radiology and 4Pathology, Şişli Etfal Education and Research Hospital, İstanbul
|Keywords: Paraneoplastic syndromes, porphyria,
The porphyrias are a group of disorders of the heme biosynthesis
pathway that present with acute neurovisceral symptoms,
skin lesions or both. Porphyria cutanea tarda, presenting as a
non-acute form, is the most common type of porphyria that encompasses
a group of related disorders, all of which arise from
deficient activity of the heme synthetic enzyme, uroporphyrinogen
decarboxylase, in the liver. In the literature, concomitant
presentation of porphyria with hepatocellular carcinoma is
common; however, no case of porphyria cutanea tarda associated
with cholangiocarcinoma has been seen. Here, we present
a case of porphyria cutanea tarda seen in the course of cholangiocarcinoma,
which can be attributed to a paraneoplastic
syndrome. Our case is of interest because of its rarity. We also
give a brief review of the literature regarding porphyria and
The porphyrias are a group of disorders of the heme
biosynthesis pathway that present with acute
neurovisceral symptoms, skin lesions or both.
They occur as a result of the accumulation of
porphyrins and their precursors in the tissues,
which are produced in excess amounts due to lack
or deficiency of enzymes that are essential for heme
biosynthesis. They are simply classified as
acute and non-acute forms. Porphyria cutanea tarda
(PCT), presenting as a non-acute form, is the
most common type of porphyria that encompasses
a group of related disorders, all of which arise
from deficient activity of the heme synthetic enzyme,
uroporphyrinogen decarboxylase (URO-D), in
the liver. The most common photocutaneous manifestations
of PCT are due to increased mechanical
fragility of the skin after sunlight exposure;
erosions and blistering cause painful indolent sores
that eventuate in milia, dyspigmentation, and
scarring. Excretion of porphyrins in both urine
and stool is also characteristically increased.
The disease generally starts during the middle
ages. The mechanism of the enzyme deficiency has
not yet been completely understood; however, the
disease is thought to be most probably acquired.
There is also a possibility of genetic tendency, but
in most of the patients (80%), there is no mutation
in the gene related with URO-D. PCT may accompany
various malignancies; the most commonly
associated malignancies are known to be primary
liver cancers (1-5). In the literature, concomitant
presentation of porphyria with hepatocellular carcinoma
(HCC) is common; however, no case of PCT associated with cholangiocarcinoma was seen previously.
Herein, we present a case of PCT seen in
the course of cholangiocarcinoma, which can be reported
as a rare occurrence.
A 75-year-old male patient admitted to the hospital
with jaundice, discoloration of the stool, darkening
of urine, fatigue, and wound-type skin lesions
on his face, arms and legs. His past medical history
was nonsignificant apart from subtotal gastrectomy
operation performed 30 years ago.
On physical examination, jaundice was prominent
on the skin and the scleras. He had bullous, purplish-
colored skin erosions of 1-1.5 cm in diameter
on the dorsal aspects of the hands, forearms, feet
and face; some of these lesions showed spontaneous
drainage, while other erosions and blisters were
necrotic and crusted (Figure 1a-c). Abdominal
examination revealed a median operation incision
scar, and a non-tender liver with smooth margins
was palpable 4 cm below the costal margin. Examinations
of the other systems were found to be
Initial laboratory values were as follows: Hb:
11 g/dl, MCV: 62 fL, MCH: 22 pg, ESR 16 mm/1
hour, AST: 157 U/L, ALT: 218 U/L, GGT: 1212
U/L, ALP: 1006 U/L, LDH: 223 U/L, total bilirubin:
14.69 mg/dl, direct bilirubin: 10.93 mg/dl, total
protein: 6.6 g/dl, and albumin: 4.3 g/dl; other
biochemistry values were within normal limits.
HbsAg was negative, anti-HCV was negative,
AFP: 4.8 U/ml, CEA: 14.52 U/ml, CA 19-9: > 1000
U/ml, and CA 12-5: 58 U/ml. Uroporphyrin I was
59.1 μg/d in 24-h urine and coproporphyrin I and
III were 301.7 μg/d and 547.0 μg/d, respectively
(normal range for all: 25 μg/day).
Abdominal ultrasonographic (USG) examination
revealed dilatation of intrahepatic bile ducts and a
solid mass with a diameter of 4 cm near the hilus
in the left lobe of the liver and adjacent to the common
bile duct (Figure 2). Similar findings were determined
in magnetic resonance cholangiopancreatography
(MRCP) examination, but the pancreas
was found to be normal. In percutaneous transhepatic cholangiogram (PTC), right and left intrahepatic
bile ducts and the proximal part of the main
hepatic bile duct were seen as markedly dilated;
therefore, the common bile duct could not be demonstrated
and a sudden interruption at the hilar
region was seen (Figure 3). A malignant biliary
obstruction was considered. USG-guided core biopsy
of this lesion was performed, and cholangiocarcinoma
was diagnosed histopathologically (Figure
4a-b). During PTC, in order to establish the
diagnosis of cholangiocarcinoma, a 6 cm long 8 F
self-extendable Nitinol (6X8) stent was also inserted
into the common bile duct percutaneously during
the same session to remove the obstruction at
the hilar region (Figure 6a-b). Following stent placement,
total bilirubin levels rapidly decreased
from 16 mg/dl to 3 mg/dl and cholestatic enzymes
also markedly decreased. Diagnosis of PCT was
established with the characteristic skin lesions
and the increased amount of porphyrin derivatives
(uroporphyrin I, coproporphyrin I and III) in
24-h urine. The skin biopsy was also consistent
with the diagnosis of porphyria (Figure 5).
Symptomatic and palliative treatment was applied
to the patient. One month after the placement
of the common bile duct stent and the specific chemotherapy
regimen was started by the oncology
department, the patient showed improvement and
jaundice and skin lesions had disappeared.
To our knowledge, we report the first case in the
literature of porphyria cutaneous tarda occurring
in a patient with cholangiocarcinoma, which may
be a rarely seen entity.
Cholangiocarcinoma, which is the second most
common primary liver tumor, accounts for 7-25%
of primary liver tumors. Extrahepatic type tumors
(87-92%) may be classified as proximal and distal
tumors. Proximal tumors are also referred to as
hilar cholangiocarcinoma, Klatskin tumor or perihilar
tumor, whereas intrahepatic type tumors (8-
13%) are peripheral tumors and may also be referred
to as small duct or intraparenchymal tumors.
Intrahepatic types may be subclassified as mass
producing, periductal infiltrative and intraductal
growth types (6-8).
In the non-cirrhotic liver, peripheral tumors are
usually seen, whereas in the liver with chronic biliary
disease, proximal and distal tumors are more
common. However, our case represents an
example of a perihilar type tumor of a proximal
extrahepatic cholangiocarcinoma, although the
patient had a non-cirrhotic liver.
Paraneoplastic syndromes related with cancer are
common. They may be seen in approximately 1/7
cancer patients. Paraneoplastic syndromes may
affect various organs. Even though the exact pathogenesis
of the paraneoplastic syndrome is still
not known, it is most likely due to auto-immune
mechanisms. Paraneoplastic syndromes can be seen
in HCC (10, 11). To our knowledge, there is no
case of cholangiocarcinoma in the literature presenting
a paraneoplastic syndrome during its course.
Paraneoplastic syndromes may be the first symptoms
of malignancy or may occur in later stages
during the course of disease. In our case initially,
the signs of the paraneoplastic syndrome (diagnosed
as PCT) that appeared clinically were bullous
skin lesions on face, hands and feet. Jaundice, the
symptom of the underlying primary disease (diagnosed
as cholangiocarcinoma), was added to the
clinical picture afterwards.
While many paraneoplastic syndromes have an independent
course apart from the associated tumor,
in some cases, successful treatment of the underlying
disease may treat the paraneoplastic
syndrome as well (12). After removal of the causal
factors of PCT, symptoms of this paraneoplastic
syndrome may be managed (1, 2). Similarly, in our
case, after insertion of the stent into the bile duct
and application of the specific chemotherapy regimen,
the skin lesions of PCT also disappeared.
After observing the skin lesions over the organs
exposed to daylight, such as hands, feet and face,
which are the characteristic features of PCT, uroporphyrin
derivatives in 24-h urine were measured
to establish the diagnosis. Apparently high levels
of uroporphyrin I and III in the urine as well
as the increased levels of coproporphyrin I and III
supported the diagnosis of PCT.
In appropriate cases, total resection of the tumor
can be done safely and long-term survival is achieved
(6, 15, 16). Age, general condition of the patient
and concomitant diseases are the main factors
that may impede surgical therapy. Advanced age
and presence of peripheral and central type lesions in our patient precluded our performing
any surgical therapy, and therefore palliative therapy
was preferred. After the insertion of an intrahepatic
stent, chemotherapy (gemcitabine 1 g/m2
once a week, for 7 weeks) was started by the oncology
clinic. One month after stent insertion and
chemotherapy had been administered, the patient
showed improvement, and skin lesions and jaundice
had disappeared. The patient was followed
thereafter by the oncology department and was
free of skin symptoms, but he was unresponsive to
treatment and died due to sepsis six months after
Different types of paraneoplastic symptoms may
be seen in cholangiocarcinomas. However, according
to our knowledge, a clinical picture of PCT
has not previously been reported in the literature
for cholangiocarcinoma. We thus report the first
case in the literature of porphyria cutaneous tarda
occurring in a patient with cholangiocarcinoma,
which may be a rarely seen entity.
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