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Childhood pancreatic tumors: a single institution experience
Journal of Pediatric Surgery (2009) 44, 2267–2272
www.elsevier.com/locate/jpedsurg
Childhood pancreatic tumors: a single institution experience☆,☆☆ David C. Yua,b , Harry P. Kozakewichc , Antonio R. Perez-Ataydec , Robert C. Shamberger a , Christopher B. Weldona,⁎ a
Department of Pediatric Surgery, Children's Hospital Boston, Harvard Medical School, Boston, MA, 02115, USA Department of Surgery, Tulane University School of Medicine, New Orleans LA, 70112, USA c Department of Pathology, Children's Hospital Boston, Harvard Medical School, Boston, MA, 02115, USA b
Received 17 July 2009; accepted 31 July 2009
Key words: Pancreas; Neoplasm; Cancer; Tumor; Pediatric
Abstract Purpose: The rarity and histopathologic diversity of primary pancreatic neoplasms in children have made it difficult to predict prognosis and to develop optimal management protocols. Methods: A 90-year (1918-2007), single institution, retrospective review of all patients with neoplastic pancreatic masses was performed. Results: Eighteen patients were identified with 7 distinct histopathologic subtypes. The most common were gastroenteropancreatic neuroendocrine, solid pseudopapillary, and acinar tumors. There were 6 benign and 12 malignant tumors. Six patients had disease outside the pancreas at their initial operation. There were 7 deaths (41%), 2 related to the initial operation, 3 from disease progression, 1 from a small bowel obstruction, and 1 from necrotizing pancreatitis. Five deaths were in patients with extrapancreatic disease found at initial operation. The median duration of follow-up for the 10 survivors was 41 months. Conclusion: In adults, pancreatic ductal adenocarcinoma is by far the most common histopathologic subtype, with other subtypes more common in children. Stage is an important prognostic factor. Long-term disease-free survival in childhood pancreatic malignancies is achievable with complete surgical resection, prognosis, and adjuvant treatment, depending on the histopathologic type. © 2009 Elsevier Inc. All rights reserved.
Presented at the 42nd Annual Meeting of the Pacific Association of Pediatric Surgeons, Hong Kong, China, May 10-14, 2009. ☆ Sponsor information: Kevin P. Lally, Children's Cancer Hospital, University of Texas Health Science Center at Houston. E-mail: Kevin.p. [email protected]. Tel.: +1 713 500 7301; fax: +1 713 500 7295. ☆☆ None of the authors have financial disclosures to make. ⁎ Corresponding author. Tel.: +1 617 355 4503; fax: +1 617 730 0477. E-mail address: [email protected] (C.B. Weldon). 0022-3468/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2009.07.078
1. Background Neoplasms of the pancreas in children are rare. The limited number of cases and the diversity of histopathologic subtypes have made it difficult to predict prognosis and develop optimal treatment protocols. The incidence of malignant lesions, frequency of lymph node involvement and synchronous metastatic disease, and mortality rates vary
2268
D.C. Yu et al.
Table 1
The tumors were classified according to the current WHO classification scheme.
Distribution of pancreatic tumors
Histopathologic tumor type
n
GEP-NET Solid pseudopapillary carcinoma Acinar cell carcinoma Ductal adenocarcinoma Sarcoma Mucinous cyst adenoma Intraductal papillary-mucinous adenoma Total
5 4 3 3 1 1 1 18
among recently published series [1-3]. Surgical therapy has been, and remains, the mainstay of treatment. The role of adjuvant treatment is anecdotal. Another challenge in analyzing the literature on pediatric pancreatic tumors is that in the past half century, the pathologic nomenclature has evolved significantly with the reclassification of known entities and the description of new ones. The World Health Organization (WHO) classification separates pancreatic lesions into exocrine and gastroenteropancreatic neuroendocrine tumors (GEP-NETs) [4,5]. The aforementioned pancreatic tumor series in children [1-3] were published before the current WHO classification was published, and hence, a slightly different nomenclature is used.
2. Methods Following institutional review board approval, a search of the pathology database was undertaken for primary pancreatic tumors from 1918 to 2008. Twenty-five tumors were identified, but 2 were eliminated because multiple organs were involved and their precise anatomic origin could not be determined. Five specimens were submitted for pathologic consultation only. Eighteen were patients cared for at our institution, including 3 previously published [6]. Medical records and pathologic material were reviewed in all patients.
Table 2
3. Results Eighteen patients presented at our institution between 1952 and 2007 with 7 in the last 7 years and only 4 before 1980. There were 11 males and 7 females, with a mean age of 14 years (range, 5-27 years). Three patients presented with jaundice and 2 with tumor rupture. Five tumors were GEP-NETs and 13 were exocrine tumors (Tables 1-3). The GEP-NET tumors were all in the head of the pancreas and were smaller than the exocrine lesions. Tumors of exocrine origin occurred in all parts of the pancreas. Twelve tumors were malignant, and 6 were benign. There were several unusual tumor types, including a synovial sarcoma, a mucinous cystadenoma, and an intraductal papillary-mucinous adenoma. Half of the patients (6/12) with malignant tumors had disease outside the pancreas at the initial operation, and all but 1 have died. Three patients with disseminated disease received chemotherapy, and all died of their disease (Tables 4 and 5). There were significant treatment complications including 2 operative deaths. A third patient died from aspiration with a concomitant adhesive small bowel obstruction 19 months after tumor resection. There were 5 additional surgical complications, none of which required reoperation. A total of 7 patients died, including the 3 mentioned above. Two patients (#3 and #12) had disseminated disease at presentation, and their tumors were never resected. One patient (#13) died of necrotic pancreatitis unrelated to his tumor, and 1 patient (#11) died of metastatic disease after resection. Seventeen of the 18 patients have documented follow-up, 10 are alive at their last visit. The median follow-up for the 10 survivors is 41 months (range, 3-353 months). Two patients presented with tumor rupture. A 9-yearold boy (#9) had small peritoneal deposits, too numerous to resect at the time of initial resection of his solid
Presentation and treatment of patients with pancreatic GEP-NETs
Case
Age (y)
Sex
Presenting symptom
Tumor location
Tumor size, largest dimension
Pancreas resection
Tumor type
1
14
Male
Head
3.5 cm
Enucleation
2
18
Female
Mental status changes, hypoglycemia Fainting, hypoglycemia
Head
1.0 cm
Enucleation
3
14
Male
Hypoglycemia
Head and duodenum
1.3 cm (4 tumors)
PDD
4
17
Male
Head
3 cm
PDD
5
13
Male
Puritis, jaundice, 20 kg weight loss Confusion, diaphoresis, hypoglycemia (MEN1)
Head
1.8 cm
Enucleation
Well-differentiated endocrine tumor Well-differentiated endocrine tumor Well-differentiated endocrine tumor Well-differentiated endocrine tumor Well Differentiated Endocrine Tumor
PDD indicates pancreaticoduodenectomy; MEN, multiple endocrine neoplasia.
Childhood pancreatic tumors
2269
Table 3
Presentation and treatment of patients with pancreatic exocrine tumors
Case Age
a
Sex
Presenting symptom
Tumor Size b location
Pancreas resection PDD
1
9
Female Abdominal mass
Head
8
2
7
Tail
19
3
18
Head
9
4
10 12
Tail/ Body Head
25
5 6
5
Female Abdominal mass, vomiting Male Jaundice, history of metastatic Wilms tumor, chemotherapy, and radiation Male Suprapubic pain, abdominal mass Female Right upper quadrant pain, vomiting Male Abdominal mass
7
9
8
18
9
9
10 11
15 16
12
14
13
28
Female Abdominal pain, constipation Female Left lower quadrant pain Male Epigastric pain, vomiting (tumor rupture) Female GERD Male Abdominal trauma (tumor rupture) Male Abdominal pain, weight loss, diarrhea Male Jaundice, from hemorrhagic pancreatitis. History of NHL with chemotherapy and bone marrow transplant with subsequent graft-vs-host disease. Mass was found incidentally in debridement specimen.
Tumor type
Ductal adenocarcinoma, undifferentiated type Enucleation, Acinar cell carcinoma None Ductal adenocarcinoma
DP
Unknown PDD
Adjuvant treatment
Tumor outside of pancreas
None
None
None
None
None
Lymph nodes and liver
Acinar cell carcinoma SPPC
None
Peritoneum
None
None
Acinar cell carcinoma SPPC
Chemotherapy, Lymph nodes 131I seeds None None None
None
None
Peritoneum
None None Chemotherapy Liver
Body/ tail Tail
12
PDD
3.4
DP
Tail
16
DP
Body/ tail
10
DP
Mucinous cyst adenoma SPPC
Head Tail
8.8 21
PD DP
SPPC Synovial sarcoma
Tail
Unknown None
Tail
Unknown DP
Ductal Chemotherapy Peritoneum adenocarcinoma Intraductal None None papillary-mucinous adenoma
PDD indicates pancreaticoduodenectomy; DP, distal pancreatectomy; SPPC, solid pseudopapillary carcinoma; GERD, gastroesophageal reflux disease; NHL, non–Hodgkin lymphoma. a Age reported in years at time of surgery. b Tumor size reported in centimeters for the largest dimension.
pseudopapillary tumors (SPTs). He has since undergone 2 additional laparotomies with 21 and 3 foci of SPT resected, respectively. He is alive more than 2 years after his initial operation. He received no adjuvant therapy and is currently being followed with several small, stable pelvic masses on imaging. The other patient presenting with tumor rupture (#11) is a 16-year-old boy who had resection of a 21-cm synovial sarcoma on initial exploration followed by doxorubicin and ifosfamide chemotherapy. After completion
of chemotherapy, he underwent resection of 5 hepatic nodules, an involved segment of ileum, and the gallbladder. Multiple small peritoneal implants, too numerous to resect, were also noted. Thirteen months later, he died in hospice care with progressive disease. Finally, there was a 9-year-old girl (#7) who had an SPT resected with no evidence of residual tumor. Eight years later, she developed epigastric pain, and an ultrasound examination showed an omental mass that was resected
2270
D.C. Yu et al.
Table 4
Outcomes of patients with pancreatic GEP-NETs
Case Complication 1 2 3 4 5
Additional Outcome surgery
Pancreatic fistula None None None None Unknown None None None None
Alive NED Alive NED Unknown Alive NED Alive NED
Follow-up (mo) 24 82 Unknown 3 43
NED indicates no evidence of disease.
and found to be SPT. A year later, she is disease-free and well.
4. Discussion Pediatric pancreatic primary neoplasms are rare. Only 18 cases were found during a 90-year period at our institution. When comparing our cohort to those found in the 3 recent pediatric series [1-3], tumor incidence is highly variable. This review found SPT and endocrine tumors to be the most common, and no cases of pancreatoblastoma were encountered. Solid pseudopapillary tumor is a slowly growing, lowgrade malignancy that occurs predominantly in girls. Limited data show SPT to have the best prognosis of the pediatric pancreatic malignancies, and several recent multi-institutional, non-English, studies from Asia have shown excellent survival and high cure rates with complete surgical resection [7-9]. The role of adjuvant therapy in SPT is anecdotal, but radiation, hormonal, and chemotherapy have all been of
Table 5
benefit in isolated cases [3,10,11]. Two patients (#7, #9) in our study illustrate the importance of primary tumor resection despite local regional spread and of continued long-term surveillance after extirpation. Only 17% of the tumors in our series were acinar cell carcinomas. This tumor is more prevalent in children than adults [3]. Four of 8 pediatric exocrine tumors described by Lack et al [6] from our institution were of acinar cell origin. However, only 1 patient had been treated at our institution, and 3 were histopathologic consultations resulting in a skewed incidence of this tumor. We encountered several unusual tumors. The first was a mucinous cystadenoma. To our knowledge, less than 10 cases of this tumor have been reported in children [12]. Given the reported association of this tumor with cytomegalovirus infection [13], the occasional transformation into rhabdomyosarcoma [2], and the absence of a pediatric malignant counterpart (cystadenocarcinoma), some authors have questioned whether this lesion is a cystic malformation rather than a neoplasm [3]. However, a recent report of a cystadenocarcinoma in an adolescent with cystic fibrosis would not support this contention [14]. Furthermore, we describe the first reported pediatric pancreatic synovial sarcoma. Synovial sarcoma is found most often in the extremities, is more common in adolescents, and can arise at almost any site [15]. Our series had 7 deaths (7/17; 1 patient had no follow-up), the highest mortality rate (41%) in any recent series [1-3]. Our series also had the highest incidence of lymph node or metastatic disease at presentation. Examining the entire malignant tumor cohort of 40 patients from these 4 series, the mortality rate for patients presenting without disease spread was 12% (3/26). The mortality rate for patients that had
Outcomes of patients with pancreatic exocrine tumors
Patient Complication
Additional surgery
Outcome
Follow-up a
1 2 3 4 5 6 7 8 9
Subphrenic abscess Adhesion, SBO None ACS, hemorrhage None Abscess, aortoenteric fistula None None Post–splenectomy sepsis Pancreatitis Pancreatic leak
NED Died after aspiration. NED Died of disease Died NED Died of aortic rupture NED NED Alive with suspicious pelvic lesion on recent CT/PET NED Died of disease
353 19 0 0 52 2 104 39 29
10 11 12 13
None None
None None None Exploratory laparotomy None Drainage of abscess Resection of omental recurrence None Resection of recurrent/residual disease in the abdomen and pelvis None Resection of residual disease in the liver, ileum and gallbladder None None
Died of disease Died from multisystem organ failure as a result of presenting pancreatitis
6 15 8 0
SBO indicates small bowel obstruction; NED, no evidence of disease; ACS, abdominal compartment syndrome; CT, computed tomography; PET, positron emission tomography. a Follow-up in months after surgery.
Childhood pancreatic tumors
Fig. 1
2271
Algorithm for evaluation of suspected pancreatic tumors in children.
tumor spread at presentation was 64% (9/14). Finally, of the 5 patients that presented with extrapancreatic disease who survived, 3 had the diagnosis of SPT. This fact demonstrates the importance of both disease stage and histopathologic tumor type in the prognosis of patients with pancreatic tumors. As demonstrated by this series, pancreatic tumors in children are a heterogenous group of neoplastic lesions. In adults, where ductal adenocarcinoma is the dominant subtype, the outcomes are generally poor. Luttges et al [16], in a review of the literature, demonstrated that when looking at ductal adenocarcinoma exclusively, there was a similar prognosis for children and adults. Initial workup for children with suspected pancreatic tumors must include primary imaging and a metastatic evaluation. In addition, secondary tests may be indicated for diagnostic dilemmas or operative planning. When possible, patients with no distant metastasis should have the primary tumor resected. Patients with either inoperable primary tumors or distant metastases can undergo neoadjuvant treatment or palliative procedures (Fig. 1).
5. Conclusions The rarity of pancreatic neoplasms in children results in a limited experience at individual institutions and has hindered the development of multimodality treatment protocols. Our series reinforces the concept that long-term, disease-free survival in childhood pancreatic malignancies is achievable
with complete surgical resection. Furthermore, prognosis and adjuvant treatment will depend on the histopathologic type and stage.
References [1] Jaksic T, Yaman M, Thorner P, et al. A 20-year review of pediatric pancreatic tumors. J Pediatr Surg 1992;27:1315-7. [2] Grosfeld JL, Vane DW, Rescoria FJ, et al. Pancreatic tumors in childhood: analysis of 13 cases. J Pediatr Surg 1990;25:1057-62. [3] Shorter NA, Glick RD, Klimstra DS, et al. Malignant pancreatic tumors in childhood and adolescence: the memorial Sloan-Kettering experience. 1967-present. J Pediatr Surg 2002;37:887-92. [4] Hamilton SR, Aaltonen LA. World Health Organization Classification of Tumors: Pathology and genetics of tumors of the digestive system. Lyon, France: IARC Press; 2000. [5] DeLellis RA, Llyod RV, Heitz PU, et al. World Health Organization Classification of Tumors. Pathology and tumours of endocrine organs. Lyon, France: IARC Press; 2004. [6] Lack EE, Levey R, Cassady JR, et al. Tumors of the exocrine pancreas in children and adolescents: a clinical and pathologic study of eight cases. Am J Surg Path 1983;7:319-27. [7] 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. [8] Zhu X, He L, Zeng J. Solid and cystic tumor of pancreas. Analysis of 14 Pediatric Cases Zhonghua Yi Xue Za Zhi 2002;82:1180-2. [9] Zhang KR, Jia HM, Shu H, et al. Solid cystic papillary tumor of pancreas in children: a repot of eight cases with literature review. Ai Zheng 2006;25:220-3. [10] Rebhandl W, Felberbaur FX, Puig S, et al. Solid-pseudopapillary tumor of the pancreas (Frantz tumor) in children: report of four cases and review of the literature. J Surg Oncol 2001;76:289-96.
2272 [11] Fried P, Cooper J, Balthazar E, et al. A role for radiotherapy in the treatment of solid and papillary neoplasms of the pancreas. Cancer 1985;56:2783-5. [12] Monterro M, Vazquez JL, Rihuete AM, et al. Serous cystadenoma of the pancreas in a child. J Pediatr Surg 2003;38:E36. [13] Chang CH, Perrin FV, Hertzler J, et al. Cystadenoma of the pancreas with cytomegalovirus infection in a female infant. Arch Pathol Lab Med 1980;104:7-8.
D.C. Yu et al. [14] Oermann CM, Al-Salmi Q, Seilheimer DK, et al. Mucinous cystadenocarcinoma of the pancreas in an adolescent with cystic fibrosis. Pediatr Dev Pathol 2005;8:391-6. [15] Eilber FC, Dry SM. Diagnosis and management of synovial sarcoma. J Surg Oncol 2008;97:314-20. [16] Luttges J, Stigge C, Pacena M, et al. Rare ductal adenocarcinoma of the pancreas in patients younger than age 40 years: an analysis of its features and a literature review. Cancer 2004;100:173-82.
www.elsevier.com/locate/jpedsurg
Childhood pancreatic tumors: a single institution experience☆,☆☆ David C. Yua,b , Harry P. Kozakewichc , Antonio R. Perez-Ataydec , Robert C. Shamberger a , Christopher B. Weldona,⁎ a
Department of Pediatric Surgery, Children's Hospital Boston, Harvard Medical School, Boston, MA, 02115, USA Department of Surgery, Tulane University School of Medicine, New Orleans LA, 70112, USA c Department of Pathology, Children's Hospital Boston, Harvard Medical School, Boston, MA, 02115, USA b
Received 17 July 2009; accepted 31 July 2009
Key words: Pancreas; Neoplasm; Cancer; Tumor; Pediatric
Abstract Purpose: The rarity and histopathologic diversity of primary pancreatic neoplasms in children have made it difficult to predict prognosis and to develop optimal management protocols. Methods: A 90-year (1918-2007), single institution, retrospective review of all patients with neoplastic pancreatic masses was performed. Results: Eighteen patients were identified with 7 distinct histopathologic subtypes. The most common were gastroenteropancreatic neuroendocrine, solid pseudopapillary, and acinar tumors. There were 6 benign and 12 malignant tumors. Six patients had disease outside the pancreas at their initial operation. There were 7 deaths (41%), 2 related to the initial operation, 3 from disease progression, 1 from a small bowel obstruction, and 1 from necrotizing pancreatitis. Five deaths were in patients with extrapancreatic disease found at initial operation. The median duration of follow-up for the 10 survivors was 41 months. Conclusion: In adults, pancreatic ductal adenocarcinoma is by far the most common histopathologic subtype, with other subtypes more common in children. Stage is an important prognostic factor. Long-term disease-free survival in childhood pancreatic malignancies is achievable with complete surgical resection, prognosis, and adjuvant treatment, depending on the histopathologic type. © 2009 Elsevier Inc. All rights reserved.
Presented at the 42nd Annual Meeting of the Pacific Association of Pediatric Surgeons, Hong Kong, China, May 10-14, 2009. ☆ Sponsor information: Kevin P. Lally, Children's Cancer Hospital, University of Texas Health Science Center at Houston. E-mail: Kevin.p. [email protected]. Tel.: +1 713 500 7301; fax: +1 713 500 7295. ☆☆ None of the authors have financial disclosures to make. ⁎ Corresponding author. Tel.: +1 617 355 4503; fax: +1 617 730 0477. E-mail address: [email protected] (C.B. Weldon). 0022-3468/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2009.07.078
1. Background Neoplasms of the pancreas in children are rare. The limited number of cases and the diversity of histopathologic subtypes have made it difficult to predict prognosis and develop optimal treatment protocols. The incidence of malignant lesions, frequency of lymph node involvement and synchronous metastatic disease, and mortality rates vary
2268
D.C. Yu et al.
Table 1
The tumors were classified according to the current WHO classification scheme.
Distribution of pancreatic tumors
Histopathologic tumor type
n
GEP-NET Solid pseudopapillary carcinoma Acinar cell carcinoma Ductal adenocarcinoma Sarcoma Mucinous cyst adenoma Intraductal papillary-mucinous adenoma Total
5 4 3 3 1 1 1 18
among recently published series [1-3]. Surgical therapy has been, and remains, the mainstay of treatment. The role of adjuvant treatment is anecdotal. Another challenge in analyzing the literature on pediatric pancreatic tumors is that in the past half century, the pathologic nomenclature has evolved significantly with the reclassification of known entities and the description of new ones. The World Health Organization (WHO) classification separates pancreatic lesions into exocrine and gastroenteropancreatic neuroendocrine tumors (GEP-NETs) [4,5]. The aforementioned pancreatic tumor series in children [1-3] were published before the current WHO classification was published, and hence, a slightly different nomenclature is used.
2. Methods Following institutional review board approval, a search of the pathology database was undertaken for primary pancreatic tumors from 1918 to 2008. Twenty-five tumors were identified, but 2 were eliminated because multiple organs were involved and their precise anatomic origin could not be determined. Five specimens were submitted for pathologic consultation only. Eighteen were patients cared for at our institution, including 3 previously published [6]. Medical records and pathologic material were reviewed in all patients.
Table 2
3. Results Eighteen patients presented at our institution between 1952 and 2007 with 7 in the last 7 years and only 4 before 1980. There were 11 males and 7 females, with a mean age of 14 years (range, 5-27 years). Three patients presented with jaundice and 2 with tumor rupture. Five tumors were GEP-NETs and 13 were exocrine tumors (Tables 1-3). The GEP-NET tumors were all in the head of the pancreas and were smaller than the exocrine lesions. Tumors of exocrine origin occurred in all parts of the pancreas. Twelve tumors were malignant, and 6 were benign. There were several unusual tumor types, including a synovial sarcoma, a mucinous cystadenoma, and an intraductal papillary-mucinous adenoma. Half of the patients (6/12) with malignant tumors had disease outside the pancreas at the initial operation, and all but 1 have died. Three patients with disseminated disease received chemotherapy, and all died of their disease (Tables 4 and 5). There were significant treatment complications including 2 operative deaths. A third patient died from aspiration with a concomitant adhesive small bowel obstruction 19 months after tumor resection. There were 5 additional surgical complications, none of which required reoperation. A total of 7 patients died, including the 3 mentioned above. Two patients (#3 and #12) had disseminated disease at presentation, and their tumors were never resected. One patient (#13) died of necrotic pancreatitis unrelated to his tumor, and 1 patient (#11) died of metastatic disease after resection. Seventeen of the 18 patients have documented follow-up, 10 are alive at their last visit. The median follow-up for the 10 survivors is 41 months (range, 3-353 months). Two patients presented with tumor rupture. A 9-yearold boy (#9) had small peritoneal deposits, too numerous to resect at the time of initial resection of his solid
Presentation and treatment of patients with pancreatic GEP-NETs
Case
Age (y)
Sex
Presenting symptom
Tumor location
Tumor size, largest dimension
Pancreas resection
Tumor type
1
14
Male
Head
3.5 cm
Enucleation
2
18
Female
Mental status changes, hypoglycemia Fainting, hypoglycemia
Head
1.0 cm
Enucleation
3
14
Male
Hypoglycemia
Head and duodenum
1.3 cm (4 tumors)
PDD
4
17
Male
Head
3 cm
PDD
5
13
Male
Puritis, jaundice, 20 kg weight loss Confusion, diaphoresis, hypoglycemia (MEN1)
Head
1.8 cm
Enucleation
Well-differentiated endocrine tumor Well-differentiated endocrine tumor Well-differentiated endocrine tumor Well-differentiated endocrine tumor Well Differentiated Endocrine Tumor
PDD indicates pancreaticoduodenectomy; MEN, multiple endocrine neoplasia.
Childhood pancreatic tumors
2269
Table 3
Presentation and treatment of patients with pancreatic exocrine tumors
Case Age
a
Sex
Presenting symptom
Tumor Size b location
Pancreas resection PDD
1
9
Female Abdominal mass
Head
8
2
7
Tail
19
3
18
Head
9
4
10 12
Tail/ Body Head
25
5 6
5
Female Abdominal mass, vomiting Male Jaundice, history of metastatic Wilms tumor, chemotherapy, and radiation Male Suprapubic pain, abdominal mass Female Right upper quadrant pain, vomiting Male Abdominal mass
7
9
8
18
9
9
10 11
15 16
12
14
13
28
Female Abdominal pain, constipation Female Left lower quadrant pain Male Epigastric pain, vomiting (tumor rupture) Female GERD Male Abdominal trauma (tumor rupture) Male Abdominal pain, weight loss, diarrhea Male Jaundice, from hemorrhagic pancreatitis. History of NHL with chemotherapy and bone marrow transplant with subsequent graft-vs-host disease. Mass was found incidentally in debridement specimen.
Tumor type
Ductal adenocarcinoma, undifferentiated type Enucleation, Acinar cell carcinoma None Ductal adenocarcinoma
DP
Unknown PDD
Adjuvant treatment
Tumor outside of pancreas
None
None
None
None
None
Lymph nodes and liver
Acinar cell carcinoma SPPC
None
Peritoneum
None
None
Acinar cell carcinoma SPPC
Chemotherapy, Lymph nodes 131I seeds None None None
None
None
Peritoneum
None None Chemotherapy Liver
Body/ tail Tail
12
PDD
3.4
DP
Tail
16
DP
Body/ tail
10
DP
Mucinous cyst adenoma SPPC
Head Tail
8.8 21
PD DP
SPPC Synovial sarcoma
Tail
Unknown None
Tail
Unknown DP
Ductal Chemotherapy Peritoneum adenocarcinoma Intraductal None None papillary-mucinous adenoma
PDD indicates pancreaticoduodenectomy; DP, distal pancreatectomy; SPPC, solid pseudopapillary carcinoma; GERD, gastroesophageal reflux disease; NHL, non–Hodgkin lymphoma. a Age reported in years at time of surgery. b Tumor size reported in centimeters for the largest dimension.
pseudopapillary tumors (SPTs). He has since undergone 2 additional laparotomies with 21 and 3 foci of SPT resected, respectively. He is alive more than 2 years after his initial operation. He received no adjuvant therapy and is currently being followed with several small, stable pelvic masses on imaging. The other patient presenting with tumor rupture (#11) is a 16-year-old boy who had resection of a 21-cm synovial sarcoma on initial exploration followed by doxorubicin and ifosfamide chemotherapy. After completion
of chemotherapy, he underwent resection of 5 hepatic nodules, an involved segment of ileum, and the gallbladder. Multiple small peritoneal implants, too numerous to resect, were also noted. Thirteen months later, he died in hospice care with progressive disease. Finally, there was a 9-year-old girl (#7) who had an SPT resected with no evidence of residual tumor. Eight years later, she developed epigastric pain, and an ultrasound examination showed an omental mass that was resected
2270
D.C. Yu et al.
Table 4
Outcomes of patients with pancreatic GEP-NETs
Case Complication 1 2 3 4 5
Additional Outcome surgery
Pancreatic fistula None None None None Unknown None None None None
Alive NED Alive NED Unknown Alive NED Alive NED
Follow-up (mo) 24 82 Unknown 3 43
NED indicates no evidence of disease.
and found to be SPT. A year later, she is disease-free and well.
4. Discussion Pediatric pancreatic primary neoplasms are rare. Only 18 cases were found during a 90-year period at our institution. When comparing our cohort to those found in the 3 recent pediatric series [1-3], tumor incidence is highly variable. This review found SPT and endocrine tumors to be the most common, and no cases of pancreatoblastoma were encountered. Solid pseudopapillary tumor is a slowly growing, lowgrade malignancy that occurs predominantly in girls. Limited data show SPT to have the best prognosis of the pediatric pancreatic malignancies, and several recent multi-institutional, non-English, studies from Asia have shown excellent survival and high cure rates with complete surgical resection [7-9]. The role of adjuvant therapy in SPT is anecdotal, but radiation, hormonal, and chemotherapy have all been of
Table 5
benefit in isolated cases [3,10,11]. Two patients (#7, #9) in our study illustrate the importance of primary tumor resection despite local regional spread and of continued long-term surveillance after extirpation. Only 17% of the tumors in our series were acinar cell carcinomas. This tumor is more prevalent in children than adults [3]. Four of 8 pediatric exocrine tumors described by Lack et al [6] from our institution were of acinar cell origin. However, only 1 patient had been treated at our institution, and 3 were histopathologic consultations resulting in a skewed incidence of this tumor. We encountered several unusual tumors. The first was a mucinous cystadenoma. To our knowledge, less than 10 cases of this tumor have been reported in children [12]. Given the reported association of this tumor with cytomegalovirus infection [13], the occasional transformation into rhabdomyosarcoma [2], and the absence of a pediatric malignant counterpart (cystadenocarcinoma), some authors have questioned whether this lesion is a cystic malformation rather than a neoplasm [3]. However, a recent report of a cystadenocarcinoma in an adolescent with cystic fibrosis would not support this contention [14]. Furthermore, we describe the first reported pediatric pancreatic synovial sarcoma. Synovial sarcoma is found most often in the extremities, is more common in adolescents, and can arise at almost any site [15]. Our series had 7 deaths (7/17; 1 patient had no follow-up), the highest mortality rate (41%) in any recent series [1-3]. Our series also had the highest incidence of lymph node or metastatic disease at presentation. Examining the entire malignant tumor cohort of 40 patients from these 4 series, the mortality rate for patients presenting without disease spread was 12% (3/26). The mortality rate for patients that had
Outcomes of patients with pancreatic exocrine tumors
Patient Complication
Additional surgery
Outcome
Follow-up a
1 2 3 4 5 6 7 8 9
Subphrenic abscess Adhesion, SBO None ACS, hemorrhage None Abscess, aortoenteric fistula None None Post–splenectomy sepsis Pancreatitis Pancreatic leak
NED Died after aspiration. NED Died of disease Died NED Died of aortic rupture NED NED Alive with suspicious pelvic lesion on recent CT/PET NED Died of disease
353 19 0 0 52 2 104 39 29
10 11 12 13
None None
None None None Exploratory laparotomy None Drainage of abscess Resection of omental recurrence None Resection of recurrent/residual disease in the abdomen and pelvis None Resection of residual disease in the liver, ileum and gallbladder None None
Died of disease Died from multisystem organ failure as a result of presenting pancreatitis
6 15 8 0
SBO indicates small bowel obstruction; NED, no evidence of disease; ACS, abdominal compartment syndrome; CT, computed tomography; PET, positron emission tomography. a Follow-up in months after surgery.
Childhood pancreatic tumors
Fig. 1
2271
Algorithm for evaluation of suspected pancreatic tumors in children.
tumor spread at presentation was 64% (9/14). Finally, of the 5 patients that presented with extrapancreatic disease who survived, 3 had the diagnosis of SPT. This fact demonstrates the importance of both disease stage and histopathologic tumor type in the prognosis of patients with pancreatic tumors. As demonstrated by this series, pancreatic tumors in children are a heterogenous group of neoplastic lesions. In adults, where ductal adenocarcinoma is the dominant subtype, the outcomes are generally poor. Luttges et al [16], in a review of the literature, demonstrated that when looking at ductal adenocarcinoma exclusively, there was a similar prognosis for children and adults. Initial workup for children with suspected pancreatic tumors must include primary imaging and a metastatic evaluation. In addition, secondary tests may be indicated for diagnostic dilemmas or operative planning. When possible, patients with no distant metastasis should have the primary tumor resected. Patients with either inoperable primary tumors or distant metastases can undergo neoadjuvant treatment or palliative procedures (Fig. 1).
5. Conclusions The rarity of pancreatic neoplasms in children results in a limited experience at individual institutions and has hindered the development of multimodality treatment protocols. Our series reinforces the concept that long-term, disease-free survival in childhood pancreatic malignancies is achievable
with complete surgical resection. Furthermore, prognosis and adjuvant treatment will depend on the histopathologic type and stage.
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