Introduction
Perivascular epithelioid cell tumors (PEComas) are mesenchymal cell neoplasms that
can occur in every part of the human body [1]. PEComa of the pancreas is extremely rare, and to our knowledge within the English
literature, there are 21 described and only five where diagnosed preoperatively by
endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA).
Case report
A 49-year-old woman presented to her GP with diffuse abdominal pain localized in the
right and left upper quadrant and intermittent watery diarrhea for the last 2 months.
Apart from uterine myomatosis with occasional menorrhagia, the patient’s past medical
history was unremarkable, and there was nothing of note in her family history. She
was a smoker (30 pack-years), consumed little alcohol, and took proton pump inhibitors
(PPIs) when required due to the above-mentioned pain; however, she did not experience
any symptom relief.
Physical examination and routine laboratory results did not show any pathological
findings apart
from a mild iron deficiency anemia most likely due to the hypermenorrhea. Abdominal
ultrasound performed by the GP showed a round, defined, 25mm hypoechogenic mass in
the pancreatic body without dilation of the pancreatic duct which was confirmed on
subsequent CT and MRI ([Fig. 1]). As a pancreatic neuroendocrine tumor (NET) was suspected, Chromogranin A serum
level was measured showing only a slight elevation of 145 µg/L (reference < 102 µg/L).
Fig. 1 T1-weighted MRI of the abdomen showing a hypointense mass in the body of the pancreas.
We performed endoscopic ultrasound (EUS) (with Pentax radial scanner, Pentax EG36704URK,
Pentax Europe, Hamburg, Germany) which confirmed the homogenous appearance of the
pancreatic tissue but with a well-defined heterogeneous, predominantly hypoechoic
mass with lateral shadowing in the pancreatic body and measuring 25 × 20 mm without
dilation of the pancreatic duct ( [Fig. 2], [Video 1]). EUS elastography indicated that the lesion had a rather hard ( = blue) tissue
appearance ([Fig. 3], [Video 1]). With B-mode (power)-Doppler, the hypervascularity of the lesion could already
be suspected. Contrast Enhanced Low Mechanical Index Endosonography (CELMI-EUS) (SonoVue,
Bracco, Italy) showed a clear and long-lasting hyperperfusion with late “wash-out”
of the lesion ([Video 1]).
Fig. 2 Endoscopic ultrasound (EUS) showing a well-defined heterogeneous, predominantly hypoechoic
mass with lateral shadowing in the pancreatic body measuring 25 × 20 mm without dilation
of the pancreatic duct.
Fig. 3 Elastography indicated that the lesion had a rather hard (= blue) tissue appearance.
Video 1 PEComa in EUS. Doppler imaging, elastography, contrast-enhanced EUS, and contrast
enhanced low mechanical index endosonography (CELMI-EUS).
EUS-Guided fine-needle aspiration (EUS-FNA) with a 22-gauge needle (EchoTip Ultra,
Cook Medical, Limerick, Ireland) was performed using the fanning technique with slow-pull
of the stylet and the tissue material obtained was fixed in CytoRich Red (Fisher Scientific,
Schwerte, Germany) solution for further cell block analysis.
Hematoxylin and eosin (H&E) staining revealed cells consisting of sheets of uniform,
epithelioid-spindle shaped cells with abundant granular eosinophilic cytoplasm and
distinct prominent nucleoli ([Fig. 4b]). Additional immunohistochemical stains were also performed. The tumor cells showed
positivity for smooth muscle markers desmin and actin as well as for melanocytic markers
HMB-45 ([Fig. 4c]) and Melan-A ([Fig. 4d]), but negativity for synaptophysin, chromogranin A, cytokeratin (panCK, CK20, CK7),
CD-117, and S-100.
Fig. 4 a Resected specimen showed a well-circumscribed encapsulated tumor, surrounded by normal
lobular pancreatic parenchyma. b H&E staining revealed cells consisting of sheets of uniform epithelioid-spindle shaped
cells with abundant granular eosinophilic cytoplasm and distinct prominent nucleoli.
The tumor cells showed positivity for melanocytic markers HMB-45 (c) and Melan-A (d).
Based on these findings, the diagnosis of a perivascular epithelioid cell tumor (PEComa)
of the pancreas was made and other potential diagnoses such as NET, metastasis, or
pancreatic cancer could be excluded. Due to the malignant potential of pancreatic
PEComas, laparoscopic left-sided pancreatectomy with splenectomy was performed. The
resected specimen showed a 2.5 cm × 2.5 cm × 2.3 cm well-circumscribed encapsulated
spherical tumor with a homogeneous light brown cut surface, surrounded by normal lobular
pancreatic parenchyma with tumor-free margins. Furthermore, spleen and resected lymph
nodes were free from metastases. Histological and immunohistological analysis of the
resected specimen revealed the same features as already shown by previous EUS-FNA
([Fig. 4]).
Discussion
Perivascular epithelioid cell tumors (PEComas), first described by Bonetti et al.
in 1992 [1], are rare mesenchymal cell neoplasms that can occur in every part of the human body
including soft tissue, bone, abdominopelvic sites, and retroperitoneal sites such
as the uterus or kidney. In 1996, Zamboni et al. reported on the occurrence of PEComas
in the pancreas and introduced the term “sugar tumor” due to the clear cell cytoplasm
of the perivascular epithelioid cells, which are rich in glycogen in this tumor [2]. Histopathologically, these tumors are characterized by cells with a spindle or
epithelioid shape typically spread around blood vessels. The characteristic immunohistochemical
profile shows positivity for melanocytic markers (such as HMB-45 and Melan-A) and
smooth muscle markers (such as actin and desmin) [3].
To our knowledge, at the present time, only 21 cases of primary PEComa of the pancreas
have been reported since the first description in 1996 by Zamboni et al. [2], and most recently in the report by Zhang et al. [4]. These tumors can arise at any age, can affect either sex, but as in our case, seem
to have a predilection for middle-aged women. Patients mostly present with fluctuant
abdominal pain, swelling in the right upper quadrant, and occasionally diarrhea, though
in some cases, patients are asymptomatic. There are no specific laboratory tests to
screen for PEComas [4]. In our case, the mild anemia was probably caused by the hypermenorrhea, and the
slightly elevated Chromogranin A most likely due to occasional intake of PPIs [5].
In all image modalities (abdominal US, EUS, CT, MRI), pancreatic PEComas are usually
characterized by well-circumscribed, oval- to round-shaped masses with surrounding
normal pancreatic tissue, lack of infiltration, and signs of arterial hypervascularity
when color Doppler or contrast-enhanced modes are used [6]. As shown in our case, elastography demonstrated a hard tissue lesion with lateral
shadowing, consistent with an encapsulated tumor. All of these imaging findings mimic
pancreatic NETs but can already help to differentiate it from pancreatic adenocarcinoma,
where the appearance is that of a poorly defined hypodense mass with infiltrating
growth [6]. Furthermore, we observed a very long-lasting contrast enhancement in CELMI-EUS
which might even help to differentiate this lesion from pancreatic NETs.
Other lesions to keep on the list of differentials include pseudopapillary neoplasm,
gastrointestinal stroma tumor (GIST), acinar cell carcinoma of the pancreas, and metastasis
of clear cell renal cell carcinoma or melanoma, though pancreatic NET remains the
most important alternative diagnosis to exclude. European guidelines recommend enucleation
at surgery for suspected NET with a solid pancreatic lesion > 2 cm [7]. The present case impressively demonstrates the advantages of EUS-FNA, combining
the best imaging modality with the ability to obtain a tissue diagnosis, showing that
a suspected NET can be a PEComa on histopathology. Thus, exact tissue diagnosis before
further treatment seems to be most reasonable as it influences clinical management.
Reviewing the literature, in 14 of 22 cases including our case a preoperative EUS-FNA
was performed. In only six, the diagnosis “PEComa” was established preoperatively
following the use of immunohistochemical staining for HMB-45. The other eight cases
were either nondiagnostic or misinterpreted as carcinoma or neuroendocrine tumors
[4]
[8]. Collins et al. noticed that, in these cases, the material obtained was only used
for preparing a cytological smear. The material was very scant or nondiagnostic, in
their understanding most likely due to extreme cohesion of PEComa cells to each other
and the matrix [8]. Thus, the benefit of smear cytology in diagnosing solid pancreatic lesions such
as PEComa seems questionable. For a definitive diagnosis, microscopic examination
of a H&E stained tissue cell block with the option to perform immunohistochemistry
would be advised. Formalin fixed histology might be a good alternative but requires
core tissue material which cannot always be obtained by EUS-guided tissue sampling.
The great majority of pancreatic PEComas are considered benign and the prognosis is
relatively good with most patients remaining free from relapse and metastasis [4]. So far, to our knowledge, four primary malignant pancreatic PEComas have been reported.
In two cases, liver metastases occurred, and in two cases the tumor showed malignant
features such as infiltrating growth, necrosis, and size > 5 cm, most recently reported
by Zhang et al. In this case, adjuvant chemotherapy with a sarcoma regimen with epirubicin
and ifosfamide seems to be effective [4].
In general, PEComas might have an association with tuberous sclerosis complex (TSC).
However, the association between pancreatic PEComa and TSC remains vague, since there
is only one described case of a women with TSC and pancreatic PEComa reported by Hartley
et al. [9]. In our case, no signs of TSC were observed.
In conclusion, PEComa of the pancreas remains an extremely rare diagnosis of a solid
pancreatic tumor with malignant potential. In EUS, which generally provides a very
good image modality for diagnosing pancreatic lesions with high sensitivity and specificity,
PEComas show very similar characteristics to NET, but in CELMI-EUS, a longer lasting
contrast enhancement can be seen.
However, additional EUS-FNA with further adequate immunohistochemical processing seems
reasonable to establish the right diagnosis to guide further therapy.
