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Pancreatic-type acinar cell carcinoma of the stomach beneath a focus of pancreatic metaplasia of the gastric mucosa
Human Pathology (2009) 40, 746–749
www.elsevier.com/locate/humpath
Case study
Pancreatic-type acinar cell carcinoma of the stomach beneath a focus of pancreatic metaplasia of the gastric mucosa Andrea Ambrosini-Spaltro MD a,⁎, Oscar Potì MD b , Michele De Palma MD b , Marcello Filotico MD c a
Section of Anatomic Pathology, Department of Oncology and Hematology, University of Bologna, Bellaria Hospital, 40139 Bologna, Italy b Division of Surgery, Hospital of Copertino, Lecce, Italy c Centro Diagnostico Salentino, Lecce, Italy Received 17 November 2007; revised 5 October 2008; accepted 7 October 2008
Keywords: Acinar cell carcinoma; Pancreatic metaplasia; Stomach
Summary Acinar cell carcinoma is an uncommon type of carcinoma of the pancreas that can exceptionally arise in ectopic pancreatic tissue. Herein, we report a case of a 52-year-old man with pancreatic-type acinar cell carcinoma of the stomach and concomitant pancreatic metaplasia of the adjacent nonneoplastic gastric mucosa. There was neither clinical nor radiographic evidence of a tumor in the pancreas itself. A subtotal gastrectomy was performed. Macroscopically, an ulcerated tumor, measuring 4 × 1.7 cm, was found in the distal antrum. Microscopically, the biopsy and the surgical specimen revealed a neoplasm with a predominantly trabecular architecture composed of moderately atypical cells with finely dispersed chromatin and indistinct nucleoli. The neoplastic cells and those of the adjacent metaplastic mucosa were both strongly immunoreactive for alpha-1-antitrypsin, consistent with pancreatic acinar cell differentiation. Ectopic pancreatic-type acinar cell carcinoma is an extremely rare condition, having been previously reported only in 5 occasions, none of them in association with pancreatic acinar cell metaplasia of the gastric mucosa. © 2009 Elsevier Inc. All rights reserved.
1. Introduction Pancreatic carcinomas of both exocrine and endocrine type can rarely arise in ectopic sites, where they can be misinterpreted as metastatic tumors. There are more than 30
⁎ Corresponding author. Section of Anatomic Pathology, Department of Oncology and Hematology, University of Bologna, Bellaria Hospital, via Altura 3, 40139 Bologna, Italy. E-mail address: [email protected] (A. Ambrosini-Spaltro). 0046-8177/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2008.10.006
cases of ectopic pancreatic carcinomas reported in the literature, most of them diagnosed as ductal adenocarcinomas [1,2]. Most were located in the stomach and were contiguous to ectopic pancreatic nonneoplastic tissue. Acinar cell carcinoma is a rare neoplasm of the exocrine pancreas [3]. Five cases of pancreatic carcinomas with acinar cell differentiation have been described in ectopic sites, in only one of them accompanied by nonneoplastic pancreatic heterotopic tissue [4-8]. Herein, we report a case of pancreatic-type acinar cell carcinoma associated with adjacent pancreatic metaplasia of the gastric mucosa.
Pancreatic-type acinar cell carcinoma of the stomach
747
2. Materials and methods The biopsy and surgical specimen materials were fixed in neutral buffered formalin and processed according to standard methods. Hematoxylin and eosin stains were performed on 3- to 4-μm-thick sections of formalin-fixed, paraffin-embedded material. Other formalin-fixed, paraffinembedded sections were immunostained with the panel of antibodies listed in Table 1. A commercially available detection kit (Dako EnVision Plus-HRP, Dako, Glostrup, Denmark) was used according to the manufacturers' instructions in an automatic immunostainer (Dako) with 3,3'-diaminobenzidine (Sigma Chemical Co., St. Louis, MO, USA) as a chromogen substrate to obtain a brown end product. Slides were then lightly counterstained with 1% Harris' hematoxylin.
3. Clinical features A 52-year-old man presented for recently exacerbated dyspeptic symptoms. He had a history of duodenal ulcer and reflux esophagitis with sliding hiatal hernia. Gastroscopy showed a 7 mm ulcerated lesion in the gastric antrum. Multiple mucosal biopsies were obtained. Histologic examination revealed a poorly differentiated adenocarcinoma and chronic gastritis. Abdominal computed tomography scan, abdominal ultrasound, and thoracic radiography were all negative. The patient underwent a subtotal gastrectomy with Roux-en-Y reconstruction, combined with omentectomy, D2 lymphadenectomy, and cholecystectomy.
Fig. 1 Low-power view of the gastric wall showing a wellcircumscribed nodule in the submucosa and the overlying gastric mucosa (original magnification ×50).
The subsequent surgical specimen consisted of a subtotal gastrectomy measuring 15 cm along the greater curvature and 7 cm along the lesser curvature. An ulcerated tumor, measuring 4 × 1.7 cm, was present 2 cm away from the distal surgical margin. Microscopically, the tumor was composed of a well-circumscribed nodule, entirely limited to the submucosa (Fig. 1), exhibiting a trabecular architecture and focal acinar formations (Fig. 2). At high magnification, the cells were moderately atypical, with granular cytoplasm, enlarged monomorphic nuclei, finely dispersed chromatin, and indistinct nucleoli (Fig. 2, upper inset). Mitotic index was low, and tumor necrosis was not detected. The tumor was superficially ulcerated. The overlying gastric mucosa showed
4. Pathological features The preoperative biopsy material revealed a neoplastic proliferation composed of epithelial cells predominantly arranged in trabecular structures with focal acinar and glandular formations. The cells were atypical, with enlarged overlapping nuclei and slightly dispersed chromatin. Some of the adjacent nonneoplastic glands exhibited a granular, slightly eosinophilic cytoplasm, which was intensely positive for PAS (periodic acid Schiff). The tumor was initially interpreted as a poorly differentiated adenocarcinoma.
Table 1
List of antibodies
Antibody
Clone
Synaptophysin Chromogranin A
SY38 LK2H10
Source
Dako Signet Laboratories, Dedham, MA Gastrin Polyclonal Dako Alpha-1-antitrypsin Polyclonal Dako
Dilution 1:20 1:40 1:500 1:200
Fig. 2 Neoplastic nodule. The neoplastic nodule is well circumscribed, with trabecular architecture and focal acinar formations (original magnification ×100). At high magnification, the tumor cells are moderately atypical, with granular cytoplasm, enlarged monomorphic nuclei, finely dispersed chromatin and indistinct nucleoli (upper inset, original magnification ×400). There is diffuse immunoreactivity for alpha-1-antitrypsin (lower inset, original magnification ×400).
748
A. Ambrosini-Spaltro et al. examined were negative. The neoplastic population was PAS negative; immunohistochemically, it was entirely unreactive to synaptophysin, chromogranin A, and gastrin but intensely positive for alpha-1-antitrypsin (Fig. 1, lower inset). A similar immunohistochemical profile was present in the adjacent nonneoplastic ectopic pancreatic tissues (Fig. 3C).
5. Discussion
Fig. 3 Pancreatic metaplasia of the overlying mucosa. Highpower view of the overlying gastric mucosa showing numerous nonneoplastic glands with granular and slightly eosinophilic cytoplasm (A, original magnification ×400), PAS positive (B, original magnification ×400), and strongly immunoreactive for alpha-1-antitrypsin (C, original magnification ×200), consistent with pancreatic gastric metaplasia.
numerous nonneoplastic glands with granular and slightly eosinophilic cytoplasm (Fig. 3A), which was intensely reactive with the PAS stain (Fig. 3B). There was no vascular or perineurial invasion by the tumor, and all the lymph nodes
The case herein described represents a pancreatic-type acinar cell carcinoma associated with—and presumably derived from—pancreatic metaplasia of the gastric mucosa. Some of the morphological features of the tumor as seen in the hematoxylin and eosin sections, such as the predominantly trabecular pattern of growth and the finely dispersed chromatin, raised the alternative possibility of a gastric or pancreatic neuroendocrine neoplasm [9]. However, the complete negativity for neuroendocrine markers (chromogranin, synaptophysin, gastrin) ruled out this possibility. The neoplastic cells and the adjacent pancreatic metaplastic cells were strongly immunoreactive for alpha1-antitrypsin. Among gastric neoplasms, a study conducted on 5 gastric tumors exhibiting the histological features of carcinoid tumor demonstrated in 3 of them a strong reactivity for alpha-1-antitrypsin with the indirect immunofluorescent technique [10]. Among pancreatic neoplasms, alpha-1-antitrypsin has been reported to be positive in acinar cell carcinomas, in mixed acinar-endocrine cell carcinomas, and in pancreatic endocrine tumors [11]. All these findings raised the possibility that the lesion is a gastric carcinoid or an ectopic endocrine pancreatic tumor. However, the complete negativity for neuroendocrine markers excluded such alternatives. Instead, the strong cytoplasmic immunoreactivity for alpha-1-antitrypsin along with the negativity for neuroendocrine markers indicated a differentiation toward a pancreatic acinar phenotype. The neoplastic cells were PAS negative, and the adjacent pancreatic metaplastic cells were PAS positive. In the pancreatic metaplastic mucosa, PAS positivity together with alpha-1-antitrypsin immunoreactivity supported acinar cell differentiation. In the neoplastic counterpart, PAS negativity and histochemical stains have been considered relatively insensitive for demonstrating acinar differentiation due to the scarcity of zymogen granules in many pancreatic acinar cell carcinomas [12]. In the literature, more than 30 cases of pancreatic-type carcinomas arising in various extrapancreatic types in the absence of a clinically and radiologically mass in the orthotopic pancreas have been reported [1,2]. Histologically, these tumors have been classified predominantly as ductal adenocarcinomas and have been mostly located in the stomach. Acinar cell carcinoma is an uncommon malignant neoplasm of the exocrine pancreas, characterized by a generally aggressive clinical behavior [3]. Five cases of ectopic pancreatic tumors showing morphological and
Pancreatic-type acinar cell carcinoma of the stomach Table 2
749
List of carcinomas with pancreatic acinar cell differentiation reported in the literature
Author, year
Age (y)
Sex
Site
Largest tumor dimension
Associated neoplastic component
Distant metastasis
Outcome
Sun and Wasserman, 2004 [4] Mizuno et al, 2007 [5] Hervieu et al, 2008 [6] Fukunaga, 2002 [7] Makhlouf et al, 1999 [8] Bookman, 1932 [13] Cingolani et al, 2000 [14]
86 73 35 77 71 28 20
F M F F M F F
Gastric antrum Gastric pylorus Liver, left lobe Gastric fundus Proximal jejunum Duodenum Anterosuperior mediastinum
5 7.6 4 1.2 3.5 NM 9
None None None Pancreatic endocrine Focal pancreatic ductal None Mature teratoma
None Liver None None Liver None None
NM AWD 11 mo NED 6 y NED 7 mo AWD 1 y NM NED 3 mo
Abbreviations: NM, not mentioned; AWD, alive with disease; NED, no evidence of disease; M, male; F, female.
immunohistochemical evidence of acinar cell differentiation have been reported; relevant data are summarized in Table 2. Three were pure forms of pancreatic-type acinar cell tumor in the gastric antrum [4], in the gastric pylorus [5], in the liver [6], and another was a pancreatic-type mixed acinarendocrine carcinoma in the gastric fundus [7]; in none of these 4 cases was the presence of an adjacent nonneoplastic pancreatic tissue mentioned. The fifth case was an acinar cell carcinoma with focal ductal differentiation located in the jejunum, associated with nonneoplastic pancreatic tissue interpreted as submucosal pancreatic heterotopia [8]. The further case interpreted as pancreatic-type acinar cell carcinoma of the duodenum was reported in 1932, obviously without immunohistochemical confirmation [13]. Finally, a pancreatic-type tumor with acinar cell differentiation was observed as the predominant component of a mediastinal mature teratoma located in the thymic region [14]. In the stomach, pancreatic nonneoplastic tissue can be found in 2 different situations. The first is pancreatic heterotopia, which usually presents as a well circumscribed submucosal nodule with a central depression in the antropyloric region and which often includes an endocrine (islet cell) component [15]. The second is pancreatic gastric metaplasia, represented by nests, lobules, or isolated pancreatic cells in the gastric mucosa [16]. Pancreatic gastric metaplasia has been found to be significantly associated with autoimmune gastritis, but there was no evidence of such in our case [17].
Acknowledgments The authors wish to thank Dr Juan Rosai for reviewing the case and revising the manuscript.
References [1] Emerson L, Layfeld LJ, Rohr LR, Dayton MT. Adenocarcinoma arising in association with heterotopic pancreas: a case report and review of the literature. J Surg Oncol 2004;87:53-7.
[2] Brotman SJ, Pan W, Pozner J, Weiss M, Bleiweiss IJ. Ductal adenocarcinoma arising in duodeno-pyloric heterotopic pancreas. Int J Surg Pathol 1994;2:37-41. [3] Klimstra DS, Heffess CS, Oertel JE, Rosai J. Acinar cell carcinoma of the pancreas. A clinicopathologic study of 28 cases. Am J Surg Pathol 1992;16:815-37. [4] Sun Y, Wasserman PG. Acinar cell carcinoma in the stomach: a case report with literature review. HUM PATHOL 2004;35:263-5. [5] Mizuno Y, Sumi Y, Nachi S, Ito Y, Marui T, Saji S, Matsutomo H. Acinar cell carcinoma arising from ectopic pancreas. Surg Today 2007;37:704-7. [6] Hervieu V, Lombard-Bohas C, Dumortier J, Boillot O, Scoazec JY. Primary acinar cell carcinoma of the liver. Virchows Arch 2008;452: 337-41. [7] Fukunaga M. Gastric carcinoma resembling pancreatic mixed acinarendocrine carcinoma. HUM PATHOL 2002;33:569-73. [8] Makhlouf HR, Almeida JL, Sobin LH. Carcinoma in jejunal pancreatic heterotopia. Arch Pathol Lab Med 1999;123:707-11. [9] Thomas RM, Baybick JH, Elsayed AM, Sobin LH. Gastric carcinoids. An immunohistochemical and clinicopathologic study of 104 patients. Cancer 1994;73:2053-8. [10] Ray MB, Geboes K, Callea F, Desmet VJ. Alpha-I-antitrypsin immunoreactivity in gastric carcinoid. Histopathology 1982;6: 289-97. [11] Skacel M, Orsmby AH, Petras RE, McMahon JT, Henricks WH. Immunohistochemistry in the differential diagnosis of acinar and endocrine pancreatic neoplasms. Appl Immunohistochem Mol Morphol 2000;8:203-9. [12] Klimstra DS, Longnecker D. Acinar cell carcinoma. In: Hamilton SR, Aaltonen LA, editors. World health organization classification of tumours. Pathology and genetics of tumours of the digestive system. Lyon (France): IARC Press; 2000. p. 241-3. [13] Bookman MR. Carcinoma in the duodenum originating from aberrant pancreatic cells. Ann Surg 1932;45:464-7. [14] Cingolani N, Shaco-Levy R, Farruggio A, Klimstra DS, Rosai J. Alpha-fetoprotein production by pancreatic tumors exhibiting acinar cell differentiation: study of five cases, one arising in a mediastinal teratoma. HUM PATHOL 2000;31:938-44. [15] Fenoglio-Preiser CM, Lantz PE, Listrom MB, Davis M, Rilke FO. Gastrointestinal pathology. An atlas and text. Philadelphia: Lippincott Williams & Wilkins; 1997. [16] Doglioni C, Laurino L, Dei Tos AP, De Boni M, Franzin G, Braidotti P, Viale G. Pancreatic (acinar) metaplasia of the gastric mucosa. Histology, ultrastructure, immunocytochemistry, and clinicopathologic correlations of 101 cases. Am J Surg Pathol 1993;17:1134-43. [17] Jhala NC, Montemor M, Jhala D, Lu L, Talley L, Haber MM, Lechago J. Pancreatic acinar cell metaplasia in autoimmune gastritis. Arch Pathol Lab Med 2003;127:854-7.
www.elsevier.com/locate/humpath
Case study
Pancreatic-type acinar cell carcinoma of the stomach beneath a focus of pancreatic metaplasia of the gastric mucosa Andrea Ambrosini-Spaltro MD a,⁎, Oscar Potì MD b , Michele De Palma MD b , Marcello Filotico MD c a
Section of Anatomic Pathology, Department of Oncology and Hematology, University of Bologna, Bellaria Hospital, 40139 Bologna, Italy b Division of Surgery, Hospital of Copertino, Lecce, Italy c Centro Diagnostico Salentino, Lecce, Italy Received 17 November 2007; revised 5 October 2008; accepted 7 October 2008
Keywords: Acinar cell carcinoma; Pancreatic metaplasia; Stomach
Summary Acinar cell carcinoma is an uncommon type of carcinoma of the pancreas that can exceptionally arise in ectopic pancreatic tissue. Herein, we report a case of a 52-year-old man with pancreatic-type acinar cell carcinoma of the stomach and concomitant pancreatic metaplasia of the adjacent nonneoplastic gastric mucosa. There was neither clinical nor radiographic evidence of a tumor in the pancreas itself. A subtotal gastrectomy was performed. Macroscopically, an ulcerated tumor, measuring 4 × 1.7 cm, was found in the distal antrum. Microscopically, the biopsy and the surgical specimen revealed a neoplasm with a predominantly trabecular architecture composed of moderately atypical cells with finely dispersed chromatin and indistinct nucleoli. The neoplastic cells and those of the adjacent metaplastic mucosa were both strongly immunoreactive for alpha-1-antitrypsin, consistent with pancreatic acinar cell differentiation. Ectopic pancreatic-type acinar cell carcinoma is an extremely rare condition, having been previously reported only in 5 occasions, none of them in association with pancreatic acinar cell metaplasia of the gastric mucosa. © 2009 Elsevier Inc. All rights reserved.
1. Introduction Pancreatic carcinomas of both exocrine and endocrine type can rarely arise in ectopic sites, where they can be misinterpreted as metastatic tumors. There are more than 30
⁎ Corresponding author. Section of Anatomic Pathology, Department of Oncology and Hematology, University of Bologna, Bellaria Hospital, via Altura 3, 40139 Bologna, Italy. E-mail address: [email protected] (A. Ambrosini-Spaltro). 0046-8177/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2008.10.006
cases of ectopic pancreatic carcinomas reported in the literature, most of them diagnosed as ductal adenocarcinomas [1,2]. Most were located in the stomach and were contiguous to ectopic pancreatic nonneoplastic tissue. Acinar cell carcinoma is a rare neoplasm of the exocrine pancreas [3]. Five cases of pancreatic carcinomas with acinar cell differentiation have been described in ectopic sites, in only one of them accompanied by nonneoplastic pancreatic heterotopic tissue [4-8]. Herein, we report a case of pancreatic-type acinar cell carcinoma associated with adjacent pancreatic metaplasia of the gastric mucosa.
Pancreatic-type acinar cell carcinoma of the stomach
747
2. Materials and methods The biopsy and surgical specimen materials were fixed in neutral buffered formalin and processed according to standard methods. Hematoxylin and eosin stains were performed on 3- to 4-μm-thick sections of formalin-fixed, paraffin-embedded material. Other formalin-fixed, paraffinembedded sections were immunostained with the panel of antibodies listed in Table 1. A commercially available detection kit (Dako EnVision Plus-HRP, Dako, Glostrup, Denmark) was used according to the manufacturers' instructions in an automatic immunostainer (Dako) with 3,3'-diaminobenzidine (Sigma Chemical Co., St. Louis, MO, USA) as a chromogen substrate to obtain a brown end product. Slides were then lightly counterstained with 1% Harris' hematoxylin.
3. Clinical features A 52-year-old man presented for recently exacerbated dyspeptic symptoms. He had a history of duodenal ulcer and reflux esophagitis with sliding hiatal hernia. Gastroscopy showed a 7 mm ulcerated lesion in the gastric antrum. Multiple mucosal biopsies were obtained. Histologic examination revealed a poorly differentiated adenocarcinoma and chronic gastritis. Abdominal computed tomography scan, abdominal ultrasound, and thoracic radiography were all negative. The patient underwent a subtotal gastrectomy with Roux-en-Y reconstruction, combined with omentectomy, D2 lymphadenectomy, and cholecystectomy.
Fig. 1 Low-power view of the gastric wall showing a wellcircumscribed nodule in the submucosa and the overlying gastric mucosa (original magnification ×50).
The subsequent surgical specimen consisted of a subtotal gastrectomy measuring 15 cm along the greater curvature and 7 cm along the lesser curvature. An ulcerated tumor, measuring 4 × 1.7 cm, was present 2 cm away from the distal surgical margin. Microscopically, the tumor was composed of a well-circumscribed nodule, entirely limited to the submucosa (Fig. 1), exhibiting a trabecular architecture and focal acinar formations (Fig. 2). At high magnification, the cells were moderately atypical, with granular cytoplasm, enlarged monomorphic nuclei, finely dispersed chromatin, and indistinct nucleoli (Fig. 2, upper inset). Mitotic index was low, and tumor necrosis was not detected. The tumor was superficially ulcerated. The overlying gastric mucosa showed
4. Pathological features The preoperative biopsy material revealed a neoplastic proliferation composed of epithelial cells predominantly arranged in trabecular structures with focal acinar and glandular formations. The cells were atypical, with enlarged overlapping nuclei and slightly dispersed chromatin. Some of the adjacent nonneoplastic glands exhibited a granular, slightly eosinophilic cytoplasm, which was intensely positive for PAS (periodic acid Schiff). The tumor was initially interpreted as a poorly differentiated adenocarcinoma.
Table 1
List of antibodies
Antibody
Clone
Synaptophysin Chromogranin A
SY38 LK2H10
Source
Dako Signet Laboratories, Dedham, MA Gastrin Polyclonal Dako Alpha-1-antitrypsin Polyclonal Dako
Dilution 1:20 1:40 1:500 1:200
Fig. 2 Neoplastic nodule. The neoplastic nodule is well circumscribed, with trabecular architecture and focal acinar formations (original magnification ×100). At high magnification, the tumor cells are moderately atypical, with granular cytoplasm, enlarged monomorphic nuclei, finely dispersed chromatin and indistinct nucleoli (upper inset, original magnification ×400). There is diffuse immunoreactivity for alpha-1-antitrypsin (lower inset, original magnification ×400).
748
A. Ambrosini-Spaltro et al. examined were negative. The neoplastic population was PAS negative; immunohistochemically, it was entirely unreactive to synaptophysin, chromogranin A, and gastrin but intensely positive for alpha-1-antitrypsin (Fig. 1, lower inset). A similar immunohistochemical profile was present in the adjacent nonneoplastic ectopic pancreatic tissues (Fig. 3C).
5. Discussion
Fig. 3 Pancreatic metaplasia of the overlying mucosa. Highpower view of the overlying gastric mucosa showing numerous nonneoplastic glands with granular and slightly eosinophilic cytoplasm (A, original magnification ×400), PAS positive (B, original magnification ×400), and strongly immunoreactive for alpha-1-antitrypsin (C, original magnification ×200), consistent with pancreatic gastric metaplasia.
numerous nonneoplastic glands with granular and slightly eosinophilic cytoplasm (Fig. 3A), which was intensely reactive with the PAS stain (Fig. 3B). There was no vascular or perineurial invasion by the tumor, and all the lymph nodes
The case herein described represents a pancreatic-type acinar cell carcinoma associated with—and presumably derived from—pancreatic metaplasia of the gastric mucosa. Some of the morphological features of the tumor as seen in the hematoxylin and eosin sections, such as the predominantly trabecular pattern of growth and the finely dispersed chromatin, raised the alternative possibility of a gastric or pancreatic neuroendocrine neoplasm [9]. However, the complete negativity for neuroendocrine markers (chromogranin, synaptophysin, gastrin) ruled out this possibility. The neoplastic cells and the adjacent pancreatic metaplastic cells were strongly immunoreactive for alpha1-antitrypsin. Among gastric neoplasms, a study conducted on 5 gastric tumors exhibiting the histological features of carcinoid tumor demonstrated in 3 of them a strong reactivity for alpha-1-antitrypsin with the indirect immunofluorescent technique [10]. Among pancreatic neoplasms, alpha-1-antitrypsin has been reported to be positive in acinar cell carcinomas, in mixed acinar-endocrine cell carcinomas, and in pancreatic endocrine tumors [11]. All these findings raised the possibility that the lesion is a gastric carcinoid or an ectopic endocrine pancreatic tumor. However, the complete negativity for neuroendocrine markers excluded such alternatives. Instead, the strong cytoplasmic immunoreactivity for alpha-1-antitrypsin along with the negativity for neuroendocrine markers indicated a differentiation toward a pancreatic acinar phenotype. The neoplastic cells were PAS negative, and the adjacent pancreatic metaplastic cells were PAS positive. In the pancreatic metaplastic mucosa, PAS positivity together with alpha-1-antitrypsin immunoreactivity supported acinar cell differentiation. In the neoplastic counterpart, PAS negativity and histochemical stains have been considered relatively insensitive for demonstrating acinar differentiation due to the scarcity of zymogen granules in many pancreatic acinar cell carcinomas [12]. In the literature, more than 30 cases of pancreatic-type carcinomas arising in various extrapancreatic types in the absence of a clinically and radiologically mass in the orthotopic pancreas have been reported [1,2]. Histologically, these tumors have been classified predominantly as ductal adenocarcinomas and have been mostly located in the stomach. Acinar cell carcinoma is an uncommon malignant neoplasm of the exocrine pancreas, characterized by a generally aggressive clinical behavior [3]. Five cases of ectopic pancreatic tumors showing morphological and
Pancreatic-type acinar cell carcinoma of the stomach Table 2
749
List of carcinomas with pancreatic acinar cell differentiation reported in the literature
Author, year
Age (y)
Sex
Site
Largest tumor dimension
Associated neoplastic component
Distant metastasis
Outcome
Sun and Wasserman, 2004 [4] Mizuno et al, 2007 [5] Hervieu et al, 2008 [6] Fukunaga, 2002 [7] Makhlouf et al, 1999 [8] Bookman, 1932 [13] Cingolani et al, 2000 [14]
86 73 35 77 71 28 20
F M F F M F F
Gastric antrum Gastric pylorus Liver, left lobe Gastric fundus Proximal jejunum Duodenum Anterosuperior mediastinum
5 7.6 4 1.2 3.5 NM 9
None None None Pancreatic endocrine Focal pancreatic ductal None Mature teratoma
None Liver None None Liver None None
NM AWD 11 mo NED 6 y NED 7 mo AWD 1 y NM NED 3 mo
Abbreviations: NM, not mentioned; AWD, alive with disease; NED, no evidence of disease; M, male; F, female.
immunohistochemical evidence of acinar cell differentiation have been reported; relevant data are summarized in Table 2. Three were pure forms of pancreatic-type acinar cell tumor in the gastric antrum [4], in the gastric pylorus [5], in the liver [6], and another was a pancreatic-type mixed acinarendocrine carcinoma in the gastric fundus [7]; in none of these 4 cases was the presence of an adjacent nonneoplastic pancreatic tissue mentioned. The fifth case was an acinar cell carcinoma with focal ductal differentiation located in the jejunum, associated with nonneoplastic pancreatic tissue interpreted as submucosal pancreatic heterotopia [8]. The further case interpreted as pancreatic-type acinar cell carcinoma of the duodenum was reported in 1932, obviously without immunohistochemical confirmation [13]. Finally, a pancreatic-type tumor with acinar cell differentiation was observed as the predominant component of a mediastinal mature teratoma located in the thymic region [14]. In the stomach, pancreatic nonneoplastic tissue can be found in 2 different situations. The first is pancreatic heterotopia, which usually presents as a well circumscribed submucosal nodule with a central depression in the antropyloric region and which often includes an endocrine (islet cell) component [15]. The second is pancreatic gastric metaplasia, represented by nests, lobules, or isolated pancreatic cells in the gastric mucosa [16]. Pancreatic gastric metaplasia has been found to be significantly associated with autoimmune gastritis, but there was no evidence of such in our case [17].
Acknowledgments The authors wish to thank Dr Juan Rosai for reviewing the case and revising the manuscript.
References [1] Emerson L, Layfeld LJ, Rohr LR, Dayton MT. Adenocarcinoma arising in association with heterotopic pancreas: a case report and review of the literature. J Surg Oncol 2004;87:53-7.
[2] Brotman SJ, Pan W, Pozner J, Weiss M, Bleiweiss IJ. Ductal adenocarcinoma arising in duodeno-pyloric heterotopic pancreas. Int J Surg Pathol 1994;2:37-41. [3] Klimstra DS, Heffess CS, Oertel JE, Rosai J. Acinar cell carcinoma of the pancreas. A clinicopathologic study of 28 cases. Am J Surg Pathol 1992;16:815-37. [4] Sun Y, Wasserman PG. Acinar cell carcinoma in the stomach: a case report with literature review. HUM PATHOL 2004;35:263-5. [5] Mizuno Y, Sumi Y, Nachi S, Ito Y, Marui T, Saji S, Matsutomo H. Acinar cell carcinoma arising from ectopic pancreas. Surg Today 2007;37:704-7. [6] Hervieu V, Lombard-Bohas C, Dumortier J, Boillot O, Scoazec JY. Primary acinar cell carcinoma of the liver. Virchows Arch 2008;452: 337-41. [7] Fukunaga M. Gastric carcinoma resembling pancreatic mixed acinarendocrine carcinoma. HUM PATHOL 2002;33:569-73. [8] Makhlouf HR, Almeida JL, Sobin LH. Carcinoma in jejunal pancreatic heterotopia. Arch Pathol Lab Med 1999;123:707-11. [9] Thomas RM, Baybick JH, Elsayed AM, Sobin LH. Gastric carcinoids. An immunohistochemical and clinicopathologic study of 104 patients. Cancer 1994;73:2053-8. [10] Ray MB, Geboes K, Callea F, Desmet VJ. Alpha-I-antitrypsin immunoreactivity in gastric carcinoid. Histopathology 1982;6: 289-97. [11] Skacel M, Orsmby AH, Petras RE, McMahon JT, Henricks WH. Immunohistochemistry in the differential diagnosis of acinar and endocrine pancreatic neoplasms. Appl Immunohistochem Mol Morphol 2000;8:203-9. [12] Klimstra DS, Longnecker D. Acinar cell carcinoma. In: Hamilton SR, Aaltonen LA, editors. World health organization classification of tumours. Pathology and genetics of tumours of the digestive system. Lyon (France): IARC Press; 2000. p. 241-3. [13] Bookman MR. Carcinoma in the duodenum originating from aberrant pancreatic cells. Ann Surg 1932;45:464-7. [14] Cingolani N, Shaco-Levy R, Farruggio A, Klimstra DS, Rosai J. Alpha-fetoprotein production by pancreatic tumors exhibiting acinar cell differentiation: study of five cases, one arising in a mediastinal teratoma. HUM PATHOL 2000;31:938-44. [15] Fenoglio-Preiser CM, Lantz PE, Listrom MB, Davis M, Rilke FO. Gastrointestinal pathology. An atlas and text. Philadelphia: Lippincott Williams & Wilkins; 1997. [16] Doglioni C, Laurino L, Dei Tos AP, De Boni M, Franzin G, Braidotti P, Viale G. Pancreatic (acinar) metaplasia of the gastric mucosa. Histology, ultrastructure, immunocytochemistry, and clinicopathologic correlations of 101 cases. Am J Surg Pathol 1993;17:1134-43. [17] Jhala NC, Montemor M, Jhala D, Lu L, Talley L, Haber MM, Lechago J. Pancreatic acinar cell metaplasia in autoimmune gastritis. Arch Pathol Lab Med 2003;127:854-7.