Keywords
multicentric solid pseudopapillary neoplasm - Frantz tumor - urogenital abnormalities
- pediatric - pancreas
Importance for a Pediatric Surgeon
This is one of the first reports of multicentric solid pseudopapillary neoplasm in
a pediatric patient. Middle-preserving pancreatectomy is a viable surgical approach
to patients with multiple pancreatic lesions including multicentric solid pseudopapillary
neoplasm.
Introduction
Solid pseudopapillary neoplasm (SPN) is a low-grade malignant tumor of the pancreas
with excellent clinical course. It was first described by Frantz in 1959 and was originally
called a “Frantz tumor.” Although the histogenesis is still uncertain, there are some
hypotheses regarding the tumor cell origin.[1]
[2] SPN represents 0.9 to 2.7% of pancreatic neoplasms and 5% of cystic pancreatic neoplasms.
It typically occurs in young females, with a female-to-male ratio of 9.8:1 and a mean
age of 28.5 years at presentation in the general population.[1] In pediatric patients, SPNs are the most commonly encountered pancreatic tumor,
usually found incidentally[1]
[3] at a mean age of 13.6 years.[4]
SPN is typically a solitary lesion located in the body/tail (54%) or head of the pancreas
(46%).[4] Multicentricity is rare, with fewer than 15 cases described in the literature and
only a single previously reported multicentric case in a pediatric patient. Unlike
pancreatic duct adenocarcinoma, patients rarely present with symptoms of biliary or
pancreatic obstruction.[4] Common symptoms include abdominal pain, dyspepsia, and early satiety.[3] Laboratory workup typically shows normal tumor markers.
Management is through surgical resection, and patients typically have excellent prognoses
with long-term survival.[3]
[4]
[5]
[6] Few factors predict recurrence or metastasis, including the presence of a pancreatic
head tumor, which has been linked to worse outcomes.[7] Of the 15 previously reported cases of multicentric SPN, the single pediatric patient
was treated with enucleation in the head and tail.[8] Middle-preserving pancreatectomy (MPP) has been described as a viable surgical option
for patients with pancreatic head and tail tumors.[9] There are at least two case reports of MPP in the literature for SPN, both in adults.[9] Herein, we present a unique case of multicentric SPN in a pediatric patient treated
with MPP consisting of distal pancreatectomy, splenectomy, and classic pancreaticoduodenectomy.
Case Report
A 10-year-old female with a past medical history significant for multicystic dysplastic
left kidney, persistent urogenital sinus, recurrent urinary tract infections, and
hip dysplasia presented to the emergency department with left upper quadrant, left
chest, and left shoulder pain for approximately the previous month. This patient had
a height and weight of 154 cm and 37 kg at presentation, respectively. Abdominal ultrasound
demonstrated a heterogenous mass at the pancreatic tail with several lesions adjacent
to the spleen, raising initial concern for lymphoma or other neoplastic process. Subsequent
magnetic resonance imaging (MRI) was notable for a 4.7 × 4.0 × 3.4 cm bilobed mass
in the pancreatic tail and a 1.2 × 1.0 × 1.3 cm lesion in the pancreatic head. All
tumor markers, including beta human chorionic gonadotropin (β-HCG), serum alpha fetoprotein
(AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA 19-9), were
within normal limits. Biopsies were performed to ensure that both lesions were of
the same origin. The pancreatic tail lesion was biopsied via a percutaneous core needle
and the pancreatic head mass was biopsied via endoscopic ultrasound (EUS) with a fine
needle aspiration (FNA). Histology demonstrated monotonous tumor cells admixed with
capillary-sized blood vessels. Immunostains showed tumor cells positive for β-catenin,
supporting the diagnosis of SPN ([Fig. 1A, B]).
Fig. 1 Cytology and histology of this rare multicentric solid pseudopapillary neoplasm (SPN).
(A) Fine needle aspiration of the pancreatic head mass showing cellular smears with
delicate papillary fronds. (B) Biopsy of the pancreatic tail contains a monotonous population of cells with abundant
eosinophilic cytoplasm arranged in a pseudoalveolar and papillary pattern with intervening
vasculature. (C) Immunohistochemistry demonstrating positive nuclear β-catenin expression in all
tumor cells. (D) Macroscopic examination of the Whipple resection specimen showing a well-circumscribed
tan-gray homogeneous nodule in the pancreatic head and (E) section of the distal pancreatectomy revealing a mass in the pancreatic tail extending
into the splenic hilum. The mass has a tan-pink, homogeneous soft cut surface. A few
matted tan-white lymph nodes (arrow) firmly adherent to the mass. (F) Histology of the pancreatic head mass featuring low-grade bland tumor cells detached
from blood vessels forming fibrovascular stalks, similar to the biopsy specimen as
in (B), which is diagnostic of SPN.
The patient subsequently underwent distal pancreatectomy with splenectomy and pancreaticoduodenectomy,
otherwise known as MPP. The procedure began with a midline incision. We mobilized
the stomach, spleen, and pancreatic tail to identify the large palpable pancreatic
tail tumor. The splenic artery and vein were ligated 1 cm proximal to the tumor margin
and the pancreas was transected with an Endo GIA stapler (Endo GIA Ultra Universal
Stapler, Medtronic, Minneapolis, MN) with bovine pericardium buttressing (Peri-Strips
Dry, Baxter, Deerfield, IL). The spleen was unsalvageable due to extension of tumor
into the splenic hilum. A standard pancreaticoduodenectomy was performed in the usual
fashion without complication. During the dissection, one enlarged vena cava lymph
node was excised and sent for a frozen section and found to be negative for tumor.
The remaining 6 cm of the middle pancreas appeared viable and well perfused. The operation
lasted 6 hours and 46 minutes and was without intraoperative complication.
On macroscopic examination, the tail mass measured 4.8 × 4.0 × 3.4 cm abutting the
spleen with grossly positive lymph nodes ([Fig. 1C]) and the head mass measured 1.3 × 1.2 × 1.2 cm with negative margins. Histologically
both masses shared similar morphology characteristic of solid pseudopapillary neoplasia
([Fig. 1D, E]). Five out of 34 lymph nodes were positive. Pathologic staging was mpT3N2.
The patient recovered well from surgery with a low-volume amylase-rich fluid in the
surgically placed drain in the immediate post-op period, which did not require any
intervention (Clavien–Dindo class I). She was discharged from the hospital on postoperative
day 13 tolerating a regular diet. She continued to recover well with no evidence of
endocrine or exocrine pancreatic insufficiency or recurrence for 12 months post-op.
Follow-up has included clinic visits with medical oncology and a computed tomography
(CT) of the chest and MRI of the abdomen/pelvis every 3 months for surveillance imaging.
There has been no evidence of disease recurrence or progression to date.
Discussion
Multicentric SPNs are very rare. To our knowledge, this is one of the first reported
cases of multicentric SPN in a pediatric patient. At our institution, there have been
three cases of SPN treated surgically with good results over the past 5 years ([Table 1]). Two patients with unifocal SPN lesions were treated with pancreaticoduodenectomy,
of which one patient subsequently developed both exocrine and endocrine pancreatic
insufficiency. All patients have been recurrence free on follow-up.
Table 1
Single center experience with pediatric solid pseudopapillary neoplasm
|
Age (y)
|
Sex[a]
|
Tumor location in pancreas
|
Tumor size
|
Pathology
|
Surgery
|
Stage
|
Days to discharge
|
Complications
|
Endocrine function preserved?
|
Exocrine function preserved?
|
Disease-free months
|
|
14
|
F
|
Head, neck, and body
|
8 × 7.5 × 4.5 cm
|
SPN, R0 resection, 0/7 nodes positive
|
Pylorus-preserving pancreaticoduodenectomy
|
pT3N0
|
7
|
CDII: exocrine pancreatic insufficiency, type 1 diabetes
|
No
|
No
|
12
|
|
13
|
F
|
Head and neck
|
12.5 × 9.2 × 8.9 cm
|
SPN, R0, 0/21 nodes positive
|
Pancreaticoduodenectomy
|
pT3N0
|
8
|
none
|
Yes
|
Yes
|
48
|
|
10
|
F
|
Head and tail
|
Head: 1.3 × 1.2 × 1.2 cm
Tail: 4.8 × 4 × 3.4 cm
|
SPN, tumor <1 mm from the margin. 5/34 nodes positive
|
Distal pancreatectomy and splenectomy, pancreaticoduodenectomy
|
pT3N2
|
13
|
CDI: low-volume pancreatic leak
|
Yes
|
Yes
|
12
|
Abbreviation: SPN, solid pseudopapillary neoplasm.
a Sex assigned at birth.
The decision to proceed with MPP was conducted with a multidisciplinary team, including
general pediatric surgery, adult surgical oncology, and both pediatric and adult medical
oncology. The only other previously reported case of multicentric SPN in a pediatric
patient was treated with enucleation, which, by definition, does not provide an R0
resection or complete analysis of regional lymph nodes.[8] However, the evidence of a need for R0 resection is currently limited. One study
showed that age less than 13.5 years and positive surgical margins predicted recurrence.[10] Other studies have suggested that R1/limited resection has similar clinical outcomes
to R0 resection in these patients.[11]
[12] MPP provided the advantages of R0 resection, removal of involved regional lymph
nodes, and preservation of pancreatic exocrine and endocrine function. Gupta et al
showed in their review and case presentation that MPP had a 32.1% morbidity, 25% chance
of endocrine insufficiency, and 17.8% chance of exocrine insufficiency.[13] Previously, total pancreatectomy was the surgical standard for multicentric pancreatic
lesions. Total pancreatectomy offers a shorter surgical time with fewer complications
than MPP, but causes insulin-dependent diabetes and pancreatic exocrine insufficiency
for a lifetime. Insulin-dependent diabetes, in particular, has a significant morbidity
and mortality that must be balanced with the longer, more complicated surgery of an
MPP, particularly with the extended life expectancy of a child.[9]
In our patient, 5 of 34 resected lymph nodes were positive on final pathology, which
may support the decision for surgical resection. Due to a paucity of cases, there
is no definitive predictor of metastasis or recurrent disease. One study estimates
that 43.1% of pediatric patients have metastatic disease, with predictors of recurrence
or metastasis including high Ki-67 proliferative index, large tumor size, and lymphovascular
invasion.[11] In a 2018 review, multiple studies found lymph node positivity as a negative prognostic
factor. However, other studies found no significant difference in prognosis for patients
with node-positive disease.[11]
[13]
[14]
[15] Rare cases of extremely aggressive SPN have been reported with high-grade histologic
features, including pleomorphic nuclei, extensive tumor necrosis, very high mitotic
rate, a diffuse growth pattern, and one case in which the tumor contained a component
of sarcomatoid carcinoma.[16] None of these features were present in the current case. Ultimately, our patient's
prognosis is excellent with a greater than 95% cure rate after surgical resection
and expected 97% disease-specific survival at 5 years.[1]
[7]
Of interest, our patient has multiple congenital abnormalities, including a multicystic
dysplastic left kidney and persistent urogenital sinus, which raise concern for a
genetic syndrome underlying her rare presentation with multicentric SPN. Genetic testing
was conducted on our patient and no known genetic syndromes or germline mutations
of significance were identified. There are reported cases of SPN in patients with
familial adenomatous polyposis (FAP). However, no genetic syndromes or risk factors
have been specifically associated with SPN.[1] Interestingly, there are three case reports of SPN in patients with urogenital abnormalities:
Bhattarai et al[18] reported a case of SPN in a child with left renal agenesis and bicornuate uterus,
Guan et al[19] similarly reported SPN in a young female with solitary kidney and uterus didelphys,
and Sharma et al[20] reported SPN in a child with left duplex kidney and vaginal septum. Wnt signaling is hypothesized to be the connection between SPN and urogenital abnormalities
because the loss of Wnt signaling is related to CTNNB1 mutations found in SPN and Wnt5a mutations have been linked to urogenital abnormalities.[17] However, given the rarity of these cases and the uncertain origins of SPN, it is
difficult to draw a definitive conclusion about the connection between our patient's
urogenital abnormalities and SPN.
Conclusion
SPN is a rare low-grade malignant tumor of the pancreas, with infrequent occurrence
of multicentricity. It can be found in the pediatric population, and there is increasing
frequency in teenage females. We present a case of multicentric SPN treated with middle-sparing
pancreatectomy in a pediatric patient. We achieved R0 resection of the primary tumors
and identified positive nodal involvement. This approach should be considered when
encountering future patients with multifocal pancreatic SPN disease.
