Journal of Pediatric Surgery xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Solid-pseudopapillary neoplasm of the pancreas in children: Can we predict malignancy?☆ Jihee Hwang a, Dae Yeon Kim a,⁎, Seong Chul Kim a, Jung‐Man Namgoong a, Seung‐Mo Hong b a b
Department of Pediatric Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
a r t i c l e
i n f o
Article history: Received 20 August 2014 Accepted 5 September 2014 Available online xxxx Key words: Solid-pseudopapillary neoplasm Malignancy Children Recurrence
a b s t r a c t Purpose: We aimed to review clinical and histologic findings of solid-pseudopapillary neoplasm (SPN) in children and determine the predictive factor of the malignancy. Method: The records of 45 patients (9 males, 36 females) who underwent surgery for SPN in the Asan Medical Center from 1992 to 2012 were retrospectively analyzed. We analyzed the factors between histologic benign group (n = 36) and malignant group (n = 9). Results: The mean age of children was 14.9 ± 3.15 years (range 9–20 years). Mean size of the tumor was 6.36 ± 3.61 cm, and most common site in the pancreas was the tail (n = 23). Three patients had distant metastasis at initial diagnosis. The sites were the liver (n = 2) and the omentum (n = 1). All patients underwent complete resection, and the median follow up period was 34 months. Recurrence (n = 4) was more common in the malignant group (p b 0.05). We calculated the proportion of solid component by manual volumetry with a CT scan. The median value was 41.5% in benign group and 88.4% in malignant group. On comparative analysis, the proportion of solid component was found to have significant association with malignancy (p b 0.05). Conclusion: Histologic malignant SPN has high risk of recurrence. We should consider more radical resection when finding a predominantly solid tumor in a CT scan. © 2014 Elsevier Inc. All rights reserved.
According to the most recent World Health Organization's classification, solid-pseudopapillary neoplasm (SPN) is a low grade malignant neoplasm that occurs predominantly in young women [1]. Although SPN usually has an excellent long-term outcome after complete resection, SPN is considered as a malignant neoplasm because of its malignant potential to metastasize and relapse. However, predicting its aggressive behavior is challenging because there are no reliable prognostic factors. Therefore, we aimed to review the clinical and histologic findings of SPN in children to determine the predictive factors for malignancy.
1.2. Definition of malignant solid-pseudopapillary neoplasm Each SPN was classified as either benign or malignant. The criteria that distinguish benign from malignant SPN include the following [2,3]: perineural invasion, angioinvasion, peripancreatic soft tissue invasion, capsular invasion, lymph node (LN) involvement, adjacent organ invasion, and distant metastasis.
1.3. Computed tomography volumetry 1. Materials and methods 1.1. Patients The medical records of 45 patients (≤20 years old) who underwent surgery for SPN at the Asan Medical Center from 1992 to 2012 were retrospectively reviewed. The clinical characteristics, surgical and pathological data, and prognoses were gathered. The study protocol was approved by our institutional review board (AMC IRB SOP 2014-0071).
☆ Financial member of PAPS: DaeYeon Kim. ⁎ Corresponding author at: (138–736) Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, South Korea. Tel.: +82 2 3010 3961; fax: +82 2 474 9027. E-mail address: [email protected] (D.Y. Kim).
All patients underwent computed tomography (CT) of the abdomen and pelvis. We measured the total volume of the mass and its solid portion. During the measurements, three researchers manually traced the contour of the mass on each CT slice. The DICOM viewer with a tracing tool, which was developed at our institution, was used for tracing each slice (Petavision, version 2.0; Asan Medical Center, Seoul, Korea). The programmed software automatically measured the extent of the area that the researchers traced, and it summed up the volumes obtained by multiplying the areas of the manually traced regions in each slice by the reconstruction interval. After measuring the total volume, the volume of the solid portion was measured in the same manner. The proportion of the solid portion was calculated using the total volume and solid volume. The mean value of the measured values was used in the analysis. The reliability of the data was verified using an intra-class correlation test (value: 0.79, 95% confidence interval: 0.68–0.88).
http://dx.doi.org/10.1016/j.jpedsurg.2014.09.011 0022-3468/© 2014 Elsevier Inc. All rights reserved.
Please cite this article as: Hwang J, et al, Solid-pseudopapillary neoplasm of the pancreas in children: Can we predict malignancy? J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.09.011
2
J. Hwang et al. / Journal of Pediatric Surgery xxx (2014) xxx–xxx
Table 1 Demographic difference between benign SPN and malignant SPN. Total (n = 45) Age (years) Sex (%) M F Clinical manifestation (%) Incidental finding Abdominal pain/discomfort Indigestion Palpable mass Periods of symptom(month) Tumor location (%) Head of pancreas Body and tail of pancreas Tumor size(cm) Calcification (%) Mass volume(cc) Solid volume(cc) Solid proportion (%) Type of operation (%) PPPD or PD (%) Distal pancreatectomy (%) Median segmentectomy (%) Enucleation (%)
Benign (n = 36)
Malignant (n = 9)
P-value
15 (9–20)
15 (9–20)
15 (10–20)
NS
9 (20) 36 (80)
7 (19.4) 29 (82.6)
2 (22.2) 7 (77.8)
NS
7 (15.6) 32 (71.1) 5 (11.1) 6 (13.3) 1 (0–24)
6 (16.7) 27 (75.0) 2 (5.6) 4 (11.1) 1 (0–24)
1 (11.1) 5 (55.6) 3 (33.3) 2 (22.2) 1 (0–19)
NS
16 (35.6) 29 (64.4) 5.5 (1.8–15) 3 (6.6) 64.3 (2.1–877.8) 17.9 (0.5–650.0) 50.2 (1.3–95.2) 12 (26.6) 21 (46.6) 4 (8.8) 8 (17.7)
13 (36.1) 23 (63.9) 5 (2–15) 2 (6.1) 60.7 (2.1–495.7) 14.7 (0.5–290.5) 41.5 (1.3–95.2)
NS NS
3 (33.3) 6 (66.7) 10 (1.8–13) 1 (14.3) 198.4 (4.0–877.8) 184.9 (2.4–650.0) 88.5 (71.3–93.0)
9 (25) 17 (47.2) 4 (11.1) 6 (13.3)
0.058 NS NS 0.034 0.008 NS
3 (33.3) 4 (44.4) 0 (0) 2 (22.2)
NS, not significant; PPPD, pylorus preserving pancreaticoduodenectomy; PD, pancreaticoduodenectomy.
1.4. Statistical analysis Categorical data were analyzed using the Fisher's exact test, continuous variables were compared using the Mann–Whitney test, and p-value b .05 was defined as statistically significant. All statistical analyses were performed using SPSS version 18. 2. Result 2.1. Clinical findings We treated 45 patients (36 females, 9 males); the median age at presentation and surgery was 15 years old (range, 9–20 years old) (Table 1). The most common chief complaint was abdominal pain (32 cases), and the median period of symptoms was 1 month. Seven patients were incidentally found to have SPN. The tail of the pancreas was the most common site of SPN (n = 26) followed by the head of the pancreas (n = 16). The median maximum diameter of the tumor was 5.5 cm (range, 1.8–15 cm). CT scan showed that only 5 patients had calcification within the mass. Three patients had metastases at the initial investigation: in the liver (2 patients) and the omentum (1 patient). 2.2. Pathology According to the pathologic reports, 9 patients had malignant SPN, and the malignant features of each tumor are shown in Table 2. Three patients had peripancreatic soft tissue invasion, and of these, one
patient suffered recurrence. In this patient, the invasion of the tumor was very close to the splenic hilum. There were 2 cases of capsular invasion and 1 case of perineural invasion. However, LN involvement and invasion of adjacent organs were not observed. 2.3. Benign vs. malignant solid-pseudopapillary neoplasm Comparative analysis was performed between the benign and malignant SPNs. There were no significant differences between the groups in terms of age, sex, and clinical manifestations, including the specific symptoms and their duration. The location of the tumor on CT images did not differ between the groups. However, malignant SPNs tended to be larger in diameter than benign SPNs (median 10 cm vs. median 5 cm, respectively; p = 0.058). Additionally, the proportion of the solid portion was greater in malignant SPNs than in benign SPNs (median 41.5% vs. median 88.5%, respectively; p = 0.008). 2.4. Outcomes All patients underwent surgical resection of their tumors (Table 1). The median follow-up period was 34 months. Among the 45 patients, 4 had recurrence of the SPN (Table 2). The primary tumor was malignant in 3 patients and benign in 1 patient. Table 2 shows the malignant findings of the primary tumor. The site of recurrence was the liver (n = 2), surgical margin (n = 1), and aortocaval LN (n = 1). Three patients underwent extensive resection of the recurrent tumor, and 1 patient Table 3 Predictive factors for recurrence.
Table 2 Pathologic findings indicating malignant SPN.
No recurrence (n = 41)
Malignant SPN (n = 9) Recurrence⁎ (n = 4) Peripancreatic soft tissue invasion Capsule invasion Perineural invasion Adjacent organ invasion LN involvement Systemic metastasis Liver Omentum
⁎
3 2 1 0 0
1 0 1 0 0
2 1
1 0
The primary tumor was benign SPN in 1 patient.
Age (years) Sex (%) M F Tumor location (%) Head Body and tail Tumor size(cm) Malignancy (%) Calcification (%) Solid portion (%)
Recurrence (n = 4)
p-value
15 (9–20)
16.5 (12–19)
NS NS
9 (22.0) 32 (78.0)
0 (0) 4 (100) NS
15 (36.6) 26 (63.4) 5.3 (1.8–15.0) 6 (14.6) 3 (8.1) 50.4 (1.3–95.22)
1 (25.0) 3 (75.0) 10.6 (3.5–13.5) 3 (75.0) 0 (0) 78.6 (40.17–82.52)
0.021 NS NS
NS: not significant.
Please cite this article as: Hwang J, et al, Solid-pseudopapillary neoplasm of the pancreas in children: Can we predict malignancy? J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.09.011
J. Hwang et al. / Journal of Pediatric Surgery xxx (2014) xxx–xxx
3
Fig. 1. A 15-year-old girl was found to have a 5.3 cm SPN in the head of the pancreas. On CT scan (A), the tumor appeared as a predominantly solid mass (measured proportion 88%). She underwent PPPD for SPN (B). The pathologic examination revealed the tumor invaded into peripancreatic soft tissue. (C) shows microscopic finding with a dense collection of viable tumor cells.
underwent radio frequency ablation (RFA) for multiple liver metastases. In the comparative analysis (Table 3), the malignancy of the primary tumor had a significant association with the recurrence (13.6% vs. 75%; p = 0.021). In the case of recurrence of a benign SPN, the patient was a 19-year-old female who underwent pylorus preserving pancreaticoduodenectomy for an 8.3 cm SPN, which was pathologically confined in the pancreas parenchyma with a clear resection margin without any evidence of malignant features such as LN involvement (0/24 LNs). After 34 months, an enlarged aortocaval LN was revealed on CT scan, which contained metastatic SPN. 3. Discussion SPN is a rare epithelial solid tumor of the pancreas that often develops degeneration resulting in hemorrhage, necrosis, and cysts filled with necrotic debris. Thus, SPN presents with heterogeneously enhanced solid and cystic masses on CT scan. The radiologic solid areas correlate to the highly cellular areas that include microscopic solid and pseudopapillary areas, and these areas include the dense concentration of viable tumor cells. The radiologic cystic areas correlate with the necrotic and hemorrhagic areas with scant viable tumor cells. In our study, we found that the predominantly solid tumor on CT scan was associated with the pathologically malignant SPN (Figs. 1 and 2). Although almost all SPNs have excellent outcomes, there are a few exceptions. The tumor biology of SPNs is rarely predictive, and they behave unexpectedly. Some studies reported on patients with residual SPN who survived for long periods without tumor progression [4,5]. Conversely, other studies report on the aggressive behavior of SPNs
that are ultimately fatal [6,7]. Moreover, predicting the aggressive behavior is challenging because there are no reliable prognostic factors [1,8]. Tumor rupture and metastasis have been referenced as the most common risk factors for recurrence [9,10], but some series include recurrences without any pathologic and clinical risk factors [11,12]. This is why surgeons should assume that every SPN has a malignant potential. Perineural invasion, angioinvasion, or deep infiltration into the surrounding tissue is some indicators of a tumor with invasive potential. It is debatable whether this invasiveness can accelerate into malignant behavior [1]. Many of the adult series reported on recurrences where these invasive pathologies were shown in the primary tumor [3,13–15]. In our report, 2 patients with perineural invasion and peripancreatic tissue invasion suffered recurrences (Table 2). The mainstay of treatment for SPN is surgical resection, which should be complete. Incomplete resections are frequently associated with more local recurrences and poor prognosis. Thus, complete resection should be performed even in patients with metastases at presentation [6,16]. After complete surgical resection, 85–95% of patients are cured, and long periods without recurrences have been reported, even in patients who had local spread or metastases. Surgical resection is also the treatment of choice for recurrence [8,9,17]. Our study demonstrated the excellent outcomes after complete resection; 95% (41/45) of patients, including 2 patients with metastatic SPN, had no evidence of recurrence, and none died from SPN. However, our median followup period (34 months) was short for a low grade malignant tumor, which is a limitation of our study. The most common sites of recurrence are the liver and the peritoneum [9,10,17]. Many studies reported excellent outcomes after complete tumor resection even after multiple recurrences. In the case of liver
Fig. 2. An 11-year-old girl had a 7 cm SPN in the head of the pancreas. On CT scan (A), the tumor appeared as a cystic mass (measured solid proportion: 4.4%). She underwent enucleation of the SPN (B). The pathologic examination revealed the tumor having no malignant features and negative resection margins. (C) shows microscopic finding of extensive necrotic debris with scant tumor cells.
Please cite this article as: Hwang J, et al, Solid-pseudopapillary neoplasm of the pancreas in children: Can we predict malignancy? J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.09.011
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J. Hwang et al. / Journal of Pediatric Surgery xxx (2014) xxx–xxx
metastases, surgical resection and RFA have been performed with successful outcomes [18,19]. Even liver transplantation has been performed for unresectable multiple liver metastases [20,21]. There has been controversy regarding the optimal surgical procedure for SPN. Some authors suggest that tissue-sparing minimal resection such as enucleation would be enough to prevent postpancreatectomy diabetes mellitus [22,23]. However, considering the malignant potential of these tumors, enucleation cannot ensure oncological safety [13,16]. Determining the adequate extent of resection has been a dilemma among surgeons. In our study, which is the largest single institution series of pediatric SPN published to date, the proportion of the solid component was associated with the pathologically malignant SPN. We recommend that surgeons consider a more radical resection when a predominantly solid tumor is identified on a CT scan. References [1] Bosman FT, Carneiro F, Hruban RH, et al. WHO classification of tumours of the digestive system. 4th ed. Lyon: IARC Press; 2010. [2] Hamilton SR, Aaltonen LA. Pathology and genetics of tumours of the digestive system. Lyon: IARC Press; 2000. [3] Kim CW, Han DJ, Kim J, et al. Solid pseudopapillary tumor of the pancreas: can malignancy be predicted? Surgery 2011;149:625–34. [4] Zinner MJ, Shurbaji MS, Cameron JL. Solid and papillary epithelial neoplasms of the pancreas. Surgery 1990;108:475–80. [5] Nishihara K, Nagoshi M, Tsuneyoshi M, et al. Papillary cystic tumors of the pancreas. Assessment of their malignant potential. Cancer 1993;71:82–92. [6] van den Akker M, Angelini P, Taylor G, et al. Malignant pancreatic tumors in children: a single-institution series. J Pediatr Surg 2012;47:681–7. [7] Martin RC, Klimstra DS, Brennan MF, et al. Solid-pseudopapillary tumor of the pancreas: a surgical enigma? Ann Surg Oncol 2002;9:35–40. [8] Speer AL, Barthel ER, Patel MM, et al. Solid pseudopapillary tumor of the pancreas: a single-institution 20-year series of pediatric patients. J Pediatr Surg 2012;47:1217–22.
[9] Lee SE, Jang JY, Hwang DW, et al. Clinical features and outcome of solid pseudopapillary neoplasm: differences between adults and children. Arch Surg 2008;143:1218–21. [10] Levy P, Bougaran J, Gayet B. Diffuse peritoneal carcinosis of pseudo-papillary and solid tumor of the pancreas. Role of abdominal injury. Gastroenterol Clin Biol 1997;21:789–93. [11] Huang HL, Shih SC, Chang WH, et al. Solid-pseudopapillary tumor of the pancreas: clinical experience and literature review. World J Gastroenterol 2005;11:1403–9. [12] Yu DC, Kozakewich HP, Perez-Atayde AR, et al. Childhood pancreatic tumors: a single institution experience. J Pediatr Surg 2009;44:2267–72. [13] Tipton SG, Smyrk TC, Sarr MG, et al. Malignant potential of solid pseudopapillary neoplasm of the pancreas. Br J Surg 2006;93:733–7. [14] Nagri S, Abdu A, Anand S, et al. Liver metastasis four years after Whipple's resection for solid-pseudopapillary tumor of the pancreas. JOP 2007;8:223–7. [15] Sperti C, Berselli M, Pasquali C, et al. Aggressive behaviour of solid-pseudopapillary tumor of the pancreas in adults: a case report and review of the literature. World J Gastroenterol 2008;14:960–5. [16] Laje P, Bhatti TR, Adzick NS. Solid pseudopapillary neoplasm of the pancreas in children: a 15-year experience and the identification of a unique immunohistochemical marker. J Pediatr Surg 2013;48:2054–60. [17] Choi SH, Kim SM, Oh JT, et al. Solid pseudopapillary tumor of the pancreas: a multicenter study of 23 pediatric cases. J Pediatr Surg 2006;41:1992–5. [18] Li JX, Wu H, Huang JW, et al. Synchronous intraoperative radiofrequency ablation for multiple liver metastasis and resection of giant solid pseudopapillary tumors of the pancreas. Chin Med J (Engl) 2012;125:1661–3. [19] Foltys D, Moench C, Burck I, et al. The solid pseudopapillary tumor (SPT)—a rare neoplasm of the pancreas. Z Gastroenterol 2008;46:689–94. [20] Sumida W, Kaneko K, Tainaka T, et al. Liver transplantation for multiple liver metastases from solid pseudopapillary tumor of the pancreas. J Pediatr Surg 2007;42: e27–31. [21] Moon JI, Selvaggi G, Nishida S, et al. Intestinal transplantation for the treatment of neoplastic disease. J Surg Oncol 2005;92:284–91. [22] Kloppel G, Maurer R, Hofmann E, et al. Solid-cystic (papillary-cystic) tumours within and outside the pancreas in men: report of two patients. Virchows Arch A Pathol Anat Histopathol 1991;418:179–83. [23] Akiyama H, Ono K, Takano M, et al. Solid-pseudopapillary tumor of the pancreatic head causing marked distal atrophy: a tumor originated posterior to the main pancreatic duct. Int J Gastrointest Cancer 2002;32:47–52.
Please cite this article as: Hwang J, et al, Solid-pseudopapillary neoplasm of the pancreas in children: Can we predict malignancy? J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.09.011
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Solid-pseudopapillary neoplasm of the pancreas in children: Can we predict malignancy?☆ Jihee Hwang a, Dae Yeon Kim a,⁎, Seong Chul Kim a, Jung‐Man Namgoong a, Seung‐Mo Hong b a b
Department of Pediatric Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
a r t i c l e
i n f o
Article history: Received 20 August 2014 Accepted 5 September 2014 Available online xxxx Key words: Solid-pseudopapillary neoplasm Malignancy Children Recurrence
a b s t r a c t Purpose: We aimed to review clinical and histologic findings of solid-pseudopapillary neoplasm (SPN) in children and determine the predictive factor of the malignancy. Method: The records of 45 patients (9 males, 36 females) who underwent surgery for SPN in the Asan Medical Center from 1992 to 2012 were retrospectively analyzed. We analyzed the factors between histologic benign group (n = 36) and malignant group (n = 9). Results: The mean age of children was 14.9 ± 3.15 years (range 9–20 years). Mean size of the tumor was 6.36 ± 3.61 cm, and most common site in the pancreas was the tail (n = 23). Three patients had distant metastasis at initial diagnosis. The sites were the liver (n = 2) and the omentum (n = 1). All patients underwent complete resection, and the median follow up period was 34 months. Recurrence (n = 4) was more common in the malignant group (p b 0.05). We calculated the proportion of solid component by manual volumetry with a CT scan. The median value was 41.5% in benign group and 88.4% in malignant group. On comparative analysis, the proportion of solid component was found to have significant association with malignancy (p b 0.05). Conclusion: Histologic malignant SPN has high risk of recurrence. We should consider more radical resection when finding a predominantly solid tumor in a CT scan. © 2014 Elsevier Inc. All rights reserved.
According to the most recent World Health Organization's classification, solid-pseudopapillary neoplasm (SPN) is a low grade malignant neoplasm that occurs predominantly in young women [1]. Although SPN usually has an excellent long-term outcome after complete resection, SPN is considered as a malignant neoplasm because of its malignant potential to metastasize and relapse. However, predicting its aggressive behavior is challenging because there are no reliable prognostic factors. Therefore, we aimed to review the clinical and histologic findings of SPN in children to determine the predictive factors for malignancy.
1.2. Definition of malignant solid-pseudopapillary neoplasm Each SPN was classified as either benign or malignant. The criteria that distinguish benign from malignant SPN include the following [2,3]: perineural invasion, angioinvasion, peripancreatic soft tissue invasion, capsular invasion, lymph node (LN) involvement, adjacent organ invasion, and distant metastasis.
1.3. Computed tomography volumetry 1. Materials and methods 1.1. Patients The medical records of 45 patients (≤20 years old) who underwent surgery for SPN at the Asan Medical Center from 1992 to 2012 were retrospectively reviewed. The clinical characteristics, surgical and pathological data, and prognoses were gathered. The study protocol was approved by our institutional review board (AMC IRB SOP 2014-0071).
☆ Financial member of PAPS: DaeYeon Kim. ⁎ Corresponding author at: (138–736) Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, South Korea. Tel.: +82 2 3010 3961; fax: +82 2 474 9027. E-mail address: [email protected] (D.Y. Kim).
All patients underwent computed tomography (CT) of the abdomen and pelvis. We measured the total volume of the mass and its solid portion. During the measurements, three researchers manually traced the contour of the mass on each CT slice. The DICOM viewer with a tracing tool, which was developed at our institution, was used for tracing each slice (Petavision, version 2.0; Asan Medical Center, Seoul, Korea). The programmed software automatically measured the extent of the area that the researchers traced, and it summed up the volumes obtained by multiplying the areas of the manually traced regions in each slice by the reconstruction interval. After measuring the total volume, the volume of the solid portion was measured in the same manner. The proportion of the solid portion was calculated using the total volume and solid volume. The mean value of the measured values was used in the analysis. The reliability of the data was verified using an intra-class correlation test (value: 0.79, 95% confidence interval: 0.68–0.88).
http://dx.doi.org/10.1016/j.jpedsurg.2014.09.011 0022-3468/© 2014 Elsevier Inc. All rights reserved.
Please cite this article as: Hwang J, et al, Solid-pseudopapillary neoplasm of the pancreas in children: Can we predict malignancy? J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.09.011
2
J. Hwang et al. / Journal of Pediatric Surgery xxx (2014) xxx–xxx
Table 1 Demographic difference between benign SPN and malignant SPN. Total (n = 45) Age (years) Sex (%) M F Clinical manifestation (%) Incidental finding Abdominal pain/discomfort Indigestion Palpable mass Periods of symptom(month) Tumor location (%) Head of pancreas Body and tail of pancreas Tumor size(cm) Calcification (%) Mass volume(cc) Solid volume(cc) Solid proportion (%) Type of operation (%) PPPD or PD (%) Distal pancreatectomy (%) Median segmentectomy (%) Enucleation (%)
Benign (n = 36)
Malignant (n = 9)
P-value
15 (9–20)
15 (9–20)
15 (10–20)
NS
9 (20) 36 (80)
7 (19.4) 29 (82.6)
2 (22.2) 7 (77.8)
NS
7 (15.6) 32 (71.1) 5 (11.1) 6 (13.3) 1 (0–24)
6 (16.7) 27 (75.0) 2 (5.6) 4 (11.1) 1 (0–24)
1 (11.1) 5 (55.6) 3 (33.3) 2 (22.2) 1 (0–19)
NS
16 (35.6) 29 (64.4) 5.5 (1.8–15) 3 (6.6) 64.3 (2.1–877.8) 17.9 (0.5–650.0) 50.2 (1.3–95.2) 12 (26.6) 21 (46.6) 4 (8.8) 8 (17.7)
13 (36.1) 23 (63.9) 5 (2–15) 2 (6.1) 60.7 (2.1–495.7) 14.7 (0.5–290.5) 41.5 (1.3–95.2)
NS NS
3 (33.3) 6 (66.7) 10 (1.8–13) 1 (14.3) 198.4 (4.0–877.8) 184.9 (2.4–650.0) 88.5 (71.3–93.0)
9 (25) 17 (47.2) 4 (11.1) 6 (13.3)
0.058 NS NS 0.034 0.008 NS
3 (33.3) 4 (44.4) 0 (0) 2 (22.2)
NS, not significant; PPPD, pylorus preserving pancreaticoduodenectomy; PD, pancreaticoduodenectomy.
1.4. Statistical analysis Categorical data were analyzed using the Fisher's exact test, continuous variables were compared using the Mann–Whitney test, and p-value b .05 was defined as statistically significant. All statistical analyses were performed using SPSS version 18. 2. Result 2.1. Clinical findings We treated 45 patients (36 females, 9 males); the median age at presentation and surgery was 15 years old (range, 9–20 years old) (Table 1). The most common chief complaint was abdominal pain (32 cases), and the median period of symptoms was 1 month. Seven patients were incidentally found to have SPN. The tail of the pancreas was the most common site of SPN (n = 26) followed by the head of the pancreas (n = 16). The median maximum diameter of the tumor was 5.5 cm (range, 1.8–15 cm). CT scan showed that only 5 patients had calcification within the mass. Three patients had metastases at the initial investigation: in the liver (2 patients) and the omentum (1 patient). 2.2. Pathology According to the pathologic reports, 9 patients had malignant SPN, and the malignant features of each tumor are shown in Table 2. Three patients had peripancreatic soft tissue invasion, and of these, one
patient suffered recurrence. In this patient, the invasion of the tumor was very close to the splenic hilum. There were 2 cases of capsular invasion and 1 case of perineural invasion. However, LN involvement and invasion of adjacent organs were not observed. 2.3. Benign vs. malignant solid-pseudopapillary neoplasm Comparative analysis was performed between the benign and malignant SPNs. There were no significant differences between the groups in terms of age, sex, and clinical manifestations, including the specific symptoms and their duration. The location of the tumor on CT images did not differ between the groups. However, malignant SPNs tended to be larger in diameter than benign SPNs (median 10 cm vs. median 5 cm, respectively; p = 0.058). Additionally, the proportion of the solid portion was greater in malignant SPNs than in benign SPNs (median 41.5% vs. median 88.5%, respectively; p = 0.008). 2.4. Outcomes All patients underwent surgical resection of their tumors (Table 1). The median follow-up period was 34 months. Among the 45 patients, 4 had recurrence of the SPN (Table 2). The primary tumor was malignant in 3 patients and benign in 1 patient. Table 2 shows the malignant findings of the primary tumor. The site of recurrence was the liver (n = 2), surgical margin (n = 1), and aortocaval LN (n = 1). Three patients underwent extensive resection of the recurrent tumor, and 1 patient Table 3 Predictive factors for recurrence.
Table 2 Pathologic findings indicating malignant SPN.
No recurrence (n = 41)
Malignant SPN (n = 9) Recurrence⁎ (n = 4) Peripancreatic soft tissue invasion Capsule invasion Perineural invasion Adjacent organ invasion LN involvement Systemic metastasis Liver Omentum
⁎
3 2 1 0 0
1 0 1 0 0
2 1
1 0
The primary tumor was benign SPN in 1 patient.
Age (years) Sex (%) M F Tumor location (%) Head Body and tail Tumor size(cm) Malignancy (%) Calcification (%) Solid portion (%)
Recurrence (n = 4)
p-value
15 (9–20)
16.5 (12–19)
NS NS
9 (22.0) 32 (78.0)
0 (0) 4 (100) NS
15 (36.6) 26 (63.4) 5.3 (1.8–15.0) 6 (14.6) 3 (8.1) 50.4 (1.3–95.22)
1 (25.0) 3 (75.0) 10.6 (3.5–13.5) 3 (75.0) 0 (0) 78.6 (40.17–82.52)
0.021 NS NS
NS: not significant.
Please cite this article as: Hwang J, et al, Solid-pseudopapillary neoplasm of the pancreas in children: Can we predict malignancy? J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.09.011
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Fig. 1. A 15-year-old girl was found to have a 5.3 cm SPN in the head of the pancreas. On CT scan (A), the tumor appeared as a predominantly solid mass (measured proportion 88%). She underwent PPPD for SPN (B). The pathologic examination revealed the tumor invaded into peripancreatic soft tissue. (C) shows microscopic finding with a dense collection of viable tumor cells.
underwent radio frequency ablation (RFA) for multiple liver metastases. In the comparative analysis (Table 3), the malignancy of the primary tumor had a significant association with the recurrence (13.6% vs. 75%; p = 0.021). In the case of recurrence of a benign SPN, the patient was a 19-year-old female who underwent pylorus preserving pancreaticoduodenectomy for an 8.3 cm SPN, which was pathologically confined in the pancreas parenchyma with a clear resection margin without any evidence of malignant features such as LN involvement (0/24 LNs). After 34 months, an enlarged aortocaval LN was revealed on CT scan, which contained metastatic SPN. 3. Discussion SPN is a rare epithelial solid tumor of the pancreas that often develops degeneration resulting in hemorrhage, necrosis, and cysts filled with necrotic debris. Thus, SPN presents with heterogeneously enhanced solid and cystic masses on CT scan. The radiologic solid areas correlate to the highly cellular areas that include microscopic solid and pseudopapillary areas, and these areas include the dense concentration of viable tumor cells. The radiologic cystic areas correlate with the necrotic and hemorrhagic areas with scant viable tumor cells. In our study, we found that the predominantly solid tumor on CT scan was associated with the pathologically malignant SPN (Figs. 1 and 2). Although almost all SPNs have excellent outcomes, there are a few exceptions. The tumor biology of SPNs is rarely predictive, and they behave unexpectedly. Some studies reported on patients with residual SPN who survived for long periods without tumor progression [4,5]. Conversely, other studies report on the aggressive behavior of SPNs
that are ultimately fatal [6,7]. Moreover, predicting the aggressive behavior is challenging because there are no reliable prognostic factors [1,8]. Tumor rupture and metastasis have been referenced as the most common risk factors for recurrence [9,10], but some series include recurrences without any pathologic and clinical risk factors [11,12]. This is why surgeons should assume that every SPN has a malignant potential. Perineural invasion, angioinvasion, or deep infiltration into the surrounding tissue is some indicators of a tumor with invasive potential. It is debatable whether this invasiveness can accelerate into malignant behavior [1]. Many of the adult series reported on recurrences where these invasive pathologies were shown in the primary tumor [3,13–15]. In our report, 2 patients with perineural invasion and peripancreatic tissue invasion suffered recurrences (Table 2). The mainstay of treatment for SPN is surgical resection, which should be complete. Incomplete resections are frequently associated with more local recurrences and poor prognosis. Thus, complete resection should be performed even in patients with metastases at presentation [6,16]. After complete surgical resection, 85–95% of patients are cured, and long periods without recurrences have been reported, even in patients who had local spread or metastases. Surgical resection is also the treatment of choice for recurrence [8,9,17]. Our study demonstrated the excellent outcomes after complete resection; 95% (41/45) of patients, including 2 patients with metastatic SPN, had no evidence of recurrence, and none died from SPN. However, our median followup period (34 months) was short for a low grade malignant tumor, which is a limitation of our study. The most common sites of recurrence are the liver and the peritoneum [9,10,17]. Many studies reported excellent outcomes after complete tumor resection even after multiple recurrences. In the case of liver
Fig. 2. An 11-year-old girl had a 7 cm SPN in the head of the pancreas. On CT scan (A), the tumor appeared as a cystic mass (measured solid proportion: 4.4%). She underwent enucleation of the SPN (B). The pathologic examination revealed the tumor having no malignant features and negative resection margins. (C) shows microscopic finding of extensive necrotic debris with scant tumor cells.
Please cite this article as: Hwang J, et al, Solid-pseudopapillary neoplasm of the pancreas in children: Can we predict malignancy? J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.09.011
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metastases, surgical resection and RFA have been performed with successful outcomes [18,19]. Even liver transplantation has been performed for unresectable multiple liver metastases [20,21]. There has been controversy regarding the optimal surgical procedure for SPN. Some authors suggest that tissue-sparing minimal resection such as enucleation would be enough to prevent postpancreatectomy diabetes mellitus [22,23]. However, considering the malignant potential of these tumors, enucleation cannot ensure oncological safety [13,16]. Determining the adequate extent of resection has been a dilemma among surgeons. In our study, which is the largest single institution series of pediatric SPN published to date, the proportion of the solid component was associated with the pathologically malignant SPN. We recommend that surgeons consider a more radical resection when a predominantly solid tumor is identified on a CT scan. References [1] Bosman FT, Carneiro F, Hruban RH, et al. WHO classification of tumours of the digestive system. 4th ed. Lyon: IARC Press; 2010. [2] Hamilton SR, Aaltonen LA. Pathology and genetics of tumours of the digestive system. Lyon: IARC Press; 2000. [3] Kim CW, Han DJ, Kim J, et al. Solid pseudopapillary tumor of the pancreas: can malignancy be predicted? Surgery 2011;149:625–34. [4] Zinner MJ, Shurbaji MS, Cameron JL. Solid and papillary epithelial neoplasms of the pancreas. Surgery 1990;108:475–80. [5] Nishihara K, Nagoshi M, Tsuneyoshi M, et al. Papillary cystic tumors of the pancreas. Assessment of their malignant potential. Cancer 1993;71:82–92. [6] van den Akker M, Angelini P, Taylor G, et al. Malignant pancreatic tumors in children: a single-institution series. J Pediatr Surg 2012;47:681–7. [7] Martin RC, Klimstra DS, Brennan MF, et al. Solid-pseudopapillary tumor of the pancreas: a surgical enigma? Ann Surg Oncol 2002;9:35–40. [8] Speer AL, Barthel ER, Patel MM, et al. Solid pseudopapillary tumor of the pancreas: a single-institution 20-year series of pediatric patients. J Pediatr Surg 2012;47:1217–22.
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Please cite this article as: Hwang J, et al, Solid-pseudopapillary neoplasm of the pancreas in children: Can we predict malignancy? J Pediatr Surg (2014), http://dx.doi.org/10.1016/j.jpedsurg.2014.09.011
