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Histogenesis of solid pseudopapillary tumor of the pancreas: the case for the centroacinar cell of origin
Experimental and Molecular Pathology 81 (2006) 101 – 107 www.elsevier.com/locate/yexmp
Case Report
Histogenesis of solid pseudopapillary tumor of the pancreas: The case for the centroacinar cell of origin Nathash Kallichanda, Steve Tsai, Bruce E. Stabile, Virgil Buslon, Doris L. Delgado, Samuel W. French ⁎ Departments of Pathology and Surgery, Harbor-UCLA Medical Center, 1000 W. Carson St., Torrance, CA 90509, USA Received 5 May 2005 Available online 17 August 2006
Abstract Solid pseudopapillary tumor (SPT) is an unusual pancreatic neoplasm of low malignant potential that most frequently occurs in young women. The tumor is indolent, with long patient survival, even in the presence of extension into adjacent organs and metastases. Histologically, it is a solid and cystic tumor with a prominent vascular network and degenerative pseudopapillae formation. Despite its distinctive morphology and cytological features, its histogenesis is unclear. Herein, we report a case of solid pseudopapillary tumor in a 41-year-old female in which the tumor cells immunohistochemically and ultrastructurally suggest a centroacinar cell origin. The tumor cells and the normal centroacinar cells stained positive for alpha-antitrypsin (α-AT), CD10, cyclin D1 and NSE. Ultrastructural examination shows similarities in nuclear shape, nucleoli location and cytoplasmic contents between neoplastic cells and normal centroacinar cells of the pancreas. Based on both immunohistochemical and ultrastructural features, we propose that the centroacinar cell is the origin of SPT. © 2006 Elsevier Inc. All rights reserved. Keywords: Solid pseudopapillary tumor of the pancreas (SPT); Histogenesis; Centroacinar cells
Introduction Solid pseudopapillary tumor (SPT) of the pancreas is an uncommon but clinicopathologically distinct neoplasm (Solcia et al., 1995; Klimstra et al., 2000). It is well known for its indolent behavior and favorable prognosis with a predilection for young women (Matsunou and Konishi, 1990; Sanchez et al., 1990). Despite diverse studies with electron microscopy and immunohistochemistry, the cell of origin remains undetermined (Kosmahi et al., 2000). Putative origins include ductal, acinar, neuroendocrine and neurocrest (Lieber et al., 1987; Von Herbay et al., 1990; Miettinen et al., 1987; Chen et al., 2004). Some investigators favor the theory that SPT originates from multipotential primordial cells capable of multidirectional differentiation (Stommer et al., 1991; Kissone, 1994). Herein, we report a case of SPT in which the tumor cells resemble normal centroacinar cells of the pancreas ⁎ Corresponding author. E-mail address: [email protected] (S.W. French). 0014-4800/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.yexmp.2006.05.005
both immunohistochemically and ultrastructurally. To the best of our knowledge, there are not many case reports that show SPT ultrastructurally and immunohistochemically resembling the centroacinal cells of the pancreas. This supports the concept that the histogenesis of SPT is the centroacinar cell. Case report A 41-year-old Hispanic female with a past surgical histology of an appendectomy at age 15 years presented to the Emergency Department in November 2004 with a fourday history of bilateral lower quadrant abdominal pain. On examination, the patient was afebrile with normal vital signs and with tenderness to palpation in both lower abdominal quadrants. A pelvic ultrasound revealed a tubular structure in the left adnexal area consistent with a left hydrosalpinx. A computed tomography (CT) scan of the abdomen and pelvis confirmed a left hydrosalpinx without acute inflammatory changes, together with an incidental finding of a 2.7 × 2.0 cm
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Fig. 1. CT scan of abdomen and pelvis reveals a 2.7 × 2.0 cm solid mass in the neck of the pancreas (between arrows).
mass in the neck of the pancreas. This hypodense mass was felt to be consistent with a cystic pancreatic lesion (Fig. 1). The patient was seen in general surgery clinic several weeks later and then was lost to follow-up for approximately 5 months. The patient continued to have vague midabdominal pain. She then returned, and an endoscopic ultrasound of the pancreas confirmed a 2.7 × 2.0 cm lesion in the neck of the
Fig. 3. Gross photograph of the well circumscribed solid mass in the neck of the pancreas. The tumor has been cut through to show the cross-section (arrows).
pancreas that was noted to be a solid, well circumscribed and heteroechoic tumor. A transgastric fine needle aspiration (FNA) of the mass was performed. Material obtained by FNA showed round to oval monomorphic cells arranged in pseudopapillary fronds. The cells had bland nuclear features and rare grooves with a moderate amount of cytoplasm. Mitotic figures were not present (Fig. 2A). These cells stained positive for CD10 (Fig. 2B), alpha1-antitrypsin (Fig. 2C), alpha1-chymotrypsin (Fig. 2D)
Fig. 2. (A) FNA of the pancreatic neck mass. H&E ×840. (B) FNA of the pancreatic neck mass. Cells positive for CD10. ×840. (C) FNA of the pancreatic neck mass. Cells positive for alpha1-antitrypsin. ×840. (D) FNA of the pancreatic neck mass. Cells positive for alpha1-antichymotrypsin. ×840.
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discrete mass at the junction of the neck and body of the pancreas. A distal pancreatectomy and splenectomy were performed. Frozen section examination of the pancreatic resection margin revealed it to be free of tumor. Postoperatively, the patient had an uneventful recovery and was discharged home. At follow-up 2 months postoperatively, the patient had no complaints of pain or other symptoms. The resected tumor grossly was a circumscribed solid mass measuring 3.4 × 2.2 × 1.0 cm (Fig. 3). The cut surface of the tumor was tan-brown. No areas of hemorrhage or necrosis were appreciated. Histologic findings Microscopically, the tumor was composed of monomorphic cells in a pseudopapillary pattern. The spaces between the pseudopapillary strictures were filled with RBCs and fibrin (Fig. 3A1). On higher magnification, the tumor cells were polygonal epithelioid cells with eosinophilic to clear vacuolated cytoplasm. The nuclei were round to oval, some with nucleoli. Rare nuclear indentations were seen. Mitoses were rare (Fig. 3A2). The tumor tissue was well demarcated from the normal pancreas. No metastases were found in the submitted 2 peripancreatic lymph nodes. Immunohistochemically, most tumor cells were positive for CD10 (Fig. 5A), cyclin D1 (Fig 5B), alpha1-antitrypsin (Fig. 5C), alpha1-antichymotrypsin (Fig. 5D), NSE (Fig. 5E), vimentin (Fig. 5F) and cytokeratin (Fig. 5G), and some tumor cells were positive for neuroendocrine markers synaptophysin and chromogranin. The tumor cells were negative for the islet cell hormones glucagon, insulin, pancreatic polypeptide and somatostatin and other antigens such as CEA, CA19-9, S100, melanin A and Fontanna. Rare cells were positive for M1B. The tumor cells formed abundant basement membrane material that stained positive for Alcian blue PAS (Fig. 5H).
Fig. 4. (A1) Low-power view of the tumor showing both solid and cystic areas. Loss of adhesions resulted in the pseudopapillary formation. H&E ×420. (A2) High-power view of the tumor reveals monomorphic cells, some with clear cytoplasm. Note the nuclear condensation next to the nuclear membrane. H&E × 840. (B) High-power view of the normal pancreatic tissue, showing centriacinar cells, with pale clear cytoplasm (arrow). H&E ×840.
and cyclin D1 and did not stain for neuroendocrine markers. The cytologic diagnosis of solid pseudopapillary tumor of the pancreas was made. A complete laboratory work-up that included liver function tests, amylase and lipase, and tumor markers including CEA, CA125, CA19-9 and chromogranin A was unrevealing. In view of the cytologic diagnosis, the patient underwent laparotomy on June 10, 2005. Inspection of the pancreas did not reveal any obvious tumor, but palpation defined a
Ultrastructural findings on formalin-fixed tissue The tumor cells had central to subcentrally located, round to slightly indented, nuclei (Fig. 7B), some with an eccentric nucleolus bound to slightly hyperchromatic nuclear rim. The cytoplasm contained rare mitochondria and few Golgi complexes. Some myelin figures and scattered secretory granules were present. Some disintegrated granules and vesicles were also present: the exact nature of these disintegrated organelles is not known. Discussion SPT of the pancreas was first described by Frantz (1959) and was seen predominantly among the Asian and African American populations. SPT is a low grade malignant neoplasm that has excellent long-term survival after resection. The male:female ratio is 1:9.5 (Mao and Guuvendi, 1995). The tumor occurs predominantly in adolescent girls and young women. It has been shown that the tumor has the same biological behavior and prognosis in men as in women (Ohashi et al., 1993). The diagnosis of SPT in the present
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Fig. 5. (A) Pancreatic neck mass cells stain positive for CD10. ×840. (B) Pancreatic neck mass cells stain positive for cyclin D1. ×840. (C) Pancreatic neck mass cells stain positive for alpha1-antitrypsin. ×840. (D) Pancreatic neck mass cells stain positive for alpha1-antichymotrypsin. ×840. (E) Pancreatic neck mass cells stain positive for NSE. NSF ×420. (F) Pancreatic neck mass. Positive for vimentin. ×420. (G) Pancreatic neck mass cells stain positive for cytokeratin AE1/AE3. ×840. (H) Pancreatic neck mass. Alcian blue PAS stained the basement membrane material blue and red. ×420.
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Fig. 6. (A) Normal pancreatic centroacinar cells stain positive for CD10. ×840. (B) Normal pancreatic centroacinar cells stain positive for cyclin D1. ×840. (C) Normal pancreatic centriacinar cells positive for alpha1-antitrypsin. ×840. (D) Normal pancreatic centriacinar cells stain positive for alpha1-antichymotrypsin. ×840. (E) Normal pancreatic centriacinar cells stain positive for NSE. ×420. (F) Normal pancreatic centriacinar cells stain positive for vimentin. ×420. (G) Normal pancreatic centriacinar cells stain positive for cytokeratin AE1/AE3. ×840.
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Fig. 7. (A) EM, normal pancreatic centriacinar cells have round to slightly indented nuclei with focal chromatin condensation at the nuclear periphery and empty cytoplasm. ×2500. (B) EM, pancreatic neck mass cells have empty cytoplasm and nuclei with chromatin condensation focally at the nuclear envelope. ×3000.
case is supported by the indolent clinical course, characteristic pathologic findings and immunophenotyping. The tumor cells were not only positive for consistently expressed markers for this type of neoplasm, such as AAT, AACT and NSE, but also some newly identified markers including CD10 and cyclin D1. The new finding in this case is that the tumor cells and the centroacinar cells in the adjacent normal pancreatic tissue had a similar light microscopical (Figs. 4A2 and B), immunohistochemical (Figs. 5A–G, 6A–G) and ultrastructural features (Figs. 7A,B). On light microscopy, both the tumor cells and normal centroacinar cells (Figs. 4A2 and B) were bland appearing with round to oval nucleus, inconspicuous eccentric nucleoli and abundant eosinophilic cytoplasm. Immunohistochemical analysis of both tumor cells and normal centroacinar cells (Table 1) was positive for CD10, cyclin D1, alpha1-antitrypsin, alpha1-antichymotrypsin, NSE, vimentin and cytokeratin AE1/AE3. Ultrastructurally, both tumor cells and centroacinal cells were similar in having round to oval nucleus, some nuclear indentation, finely dispersed chromatin and some small eccentric nucleoli bound to the nuclear membrane. The cytoplasm was abundant with some mitochondria and few Golgi complexes. Both cells lacked dense core granules, an indicator of acinar and islet cell differentiation. The histogenesis of SPT remains unsettled because of discrepancies in the immunohistochemical and electron microscopic findings. A neuroendocrine origin has been suggested by a diffusely positive reaction for NSE (Miettinen et al., 1987) and by alleged positivity for pancreatic polypeptide somatostatin (Von Herbay et al., 1990), glucagon (Miettinen et al., 1987) and insulin (Von Herbay et al., 1990) in a few cases and by the occasional presence of organelles resembling neurosecretory granules. Other studies, including
the present case, have failed to demonstrate hormone production by SPT (Schlosnagle and Campbell, 1981). Furthermore, immunoreactivity for NSE should not be taken as evidence of neuroendocrine differentiation because this marker is also expressed by a variety of non-neuroendocrine neoplasms (Vinores et al., 1987). Neuroendocrine tumors and acinar cell carcinomas both lack the distinctive pseudopapillary pattern and degenerative changes of solid pseudopapillar tumors of the pancreas. Annulate lamellae have been observed by many researchers and are considered to be indicative of immaturity or poor differentiation. In this case, the homology between tumor cells and centroacinar cells, both immunohistochemically and electron microscopically, suggests that the histogenesis of SPT of pancreas is from centroacinar cells. Table 1 Immunohistochemical analysis of solid pseudopapillary tumor (SPT) and normal centroacinal cells (CAC) of pancreas Antibody
SPT
CAC
Alpha1-antitrypsin Alpha1-antichymotrypsin CD10 Cyclin D1 AE1/AE3 Vimentin NSE EMA Glucagon Insulin Somatostatin S100 Melanin A Pancreatic polypeptide CEA Synaptophysin Chromogranin
+ + + + + + + − − − − − − − − +/− +/−
+ + + + + + + − − − − − − − −
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Acknowledgments The authors thank Adriana Flores for typing the manuscript. The study was supported by NIH/NIAAA Alcohol Center Grant P50-019991-on the Liver and Pancreas, Morphology Core. References Chen, C., Jing, W., Gulati, P., Vargas, H., French, S.W., 2004. Melanocytic differentiation in a solid pseudopapillary tumor of the pancreas. J. Gastroenterol. 39, 579–583. Frantz, U.K., 1959. Tumor of the pancreas. Atlas of Tumor Pathology. Armed Forces Institute of Pathology, Washington, pp. 32–33. Kissone, J.M., 1994. Pancreatoblastoma and solid and cystic papillary tumor: Two tumors related to pancreatic ontogeny. Semin. Diagn. Pathol. 11, 152–164. Klimstra, D.S, Wenig, B.M., Heffes, S., 2000. Solid-pseudopapillary tumor of the pancreas: a typically cystic carcinoma of low malignant potential. Semin. Diagn. Pathol. 17, 66–80. Kosmahi, M., Seada, L.S., Janig, U., Harms, D., Kloppel, G., 2000. Solidpseudopapillary tumor of the pancreas: its origin revisited. Virchows Arch. 436, 473–480. Lieber, M.R., Lack, E.E., Robers, J.R.J., 1987. Solid and papillary epithelial neoplasm of the pancreas. An ultrastructure and immunocytochemical study of six cases. Am. J. Surg. Pathol. 11, 85–93.
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Mao, C., Guuvendi, M., 1995. Papillary cystic and solid tumors of the pancreas: a pancreatic embryonic tumor? Studies of 3 cases and cumulative review of the world's literature. Surgery 118, 821–825. Matsunou, H., Konishi, F., 1990. Papillary-cystic neoplasm of the pancreas. Cancer 65, 283–291. Miettinen, M., Partanen, S., Fraki, O., Kivilaakso, E., 1987. Papillary cystic tumor of the pancreas: an analysis of cellular differentiation by electron microscopy and immunohistochemistry. Am. J. Surg. Pathol. 11, 855–865. Ohashi, K., Nakajima, Y., Hisanaga, M., Nakano, H., Tsutsumi, M., Kondoh, S., Konishi, Y., 1993. A solid and papillary tumor of the pancreas occurring in a 26-year-old man: case report. Surg. Today 23, 551–555. Sanchez, J.A., Newman, K.D., Eicherlberger, M.R., 1990. The papillary-cystic neoplasm of the pancreas. An increasingly recognized clinicopathologic entity. Arch. Surg. 125, 1502–1505. Schlosnagle, D.C., Campbell, W.G., 1981. The papillary and solid neoplasm of the pancreas: a report of 2 cases with electron microscopy. One containing neurosecretory granules. Cancer 47, 2603–2610. Solcia, E., Capella, C., Kloppel, C., 1995. Atlas of tumor pathology. Tumor of the Pancreas. Armed Forces Institute of Pathology, Washington, DC, pp. 120–127. Stommer, P., Kraus, J., Stolte, M., 1991. Solid and cystic pancreatic tumor. Clinical histochemical, and electron microscopic features in ten cases. Cancer 67, 1635–1641. Vinores, S.A., Bonnin, J.M., Rubinstein, L.J., 1987. Immunohistochemical demonstration of NSE in neoplasms of CNS and other tissues. Arch. Pathol. Lab. Med. 108, 536–540. Von Herbay, A., Sieg, B., Otto, H.F., 1990. Solid-cystic tumor of the pancreas. An endocrine neoplasm? Virchows Arch. A 416, 535–538.
Case Report
Histogenesis of solid pseudopapillary tumor of the pancreas: The case for the centroacinar cell of origin Nathash Kallichanda, Steve Tsai, Bruce E. Stabile, Virgil Buslon, Doris L. Delgado, Samuel W. French ⁎ Departments of Pathology and Surgery, Harbor-UCLA Medical Center, 1000 W. Carson St., Torrance, CA 90509, USA Received 5 May 2005 Available online 17 August 2006
Abstract Solid pseudopapillary tumor (SPT) is an unusual pancreatic neoplasm of low malignant potential that most frequently occurs in young women. The tumor is indolent, with long patient survival, even in the presence of extension into adjacent organs and metastases. Histologically, it is a solid and cystic tumor with a prominent vascular network and degenerative pseudopapillae formation. Despite its distinctive morphology and cytological features, its histogenesis is unclear. Herein, we report a case of solid pseudopapillary tumor in a 41-year-old female in which the tumor cells immunohistochemically and ultrastructurally suggest a centroacinar cell origin. The tumor cells and the normal centroacinar cells stained positive for alpha-antitrypsin (α-AT), CD10, cyclin D1 and NSE. Ultrastructural examination shows similarities in nuclear shape, nucleoli location and cytoplasmic contents between neoplastic cells and normal centroacinar cells of the pancreas. Based on both immunohistochemical and ultrastructural features, we propose that the centroacinar cell is the origin of SPT. © 2006 Elsevier Inc. All rights reserved. Keywords: Solid pseudopapillary tumor of the pancreas (SPT); Histogenesis; Centroacinar cells
Introduction Solid pseudopapillary tumor (SPT) of the pancreas is an uncommon but clinicopathologically distinct neoplasm (Solcia et al., 1995; Klimstra et al., 2000). It is well known for its indolent behavior and favorable prognosis with a predilection for young women (Matsunou and Konishi, 1990; Sanchez et al., 1990). Despite diverse studies with electron microscopy and immunohistochemistry, the cell of origin remains undetermined (Kosmahi et al., 2000). Putative origins include ductal, acinar, neuroendocrine and neurocrest (Lieber et al., 1987; Von Herbay et al., 1990; Miettinen et al., 1987; Chen et al., 2004). Some investigators favor the theory that SPT originates from multipotential primordial cells capable of multidirectional differentiation (Stommer et al., 1991; Kissone, 1994). Herein, we report a case of SPT in which the tumor cells resemble normal centroacinar cells of the pancreas ⁎ Corresponding author. E-mail address: [email protected] (S.W. French). 0014-4800/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.yexmp.2006.05.005
both immunohistochemically and ultrastructurally. To the best of our knowledge, there are not many case reports that show SPT ultrastructurally and immunohistochemically resembling the centroacinal cells of the pancreas. This supports the concept that the histogenesis of SPT is the centroacinar cell. Case report A 41-year-old Hispanic female with a past surgical histology of an appendectomy at age 15 years presented to the Emergency Department in November 2004 with a fourday history of bilateral lower quadrant abdominal pain. On examination, the patient was afebrile with normal vital signs and with tenderness to palpation in both lower abdominal quadrants. A pelvic ultrasound revealed a tubular structure in the left adnexal area consistent with a left hydrosalpinx. A computed tomography (CT) scan of the abdomen and pelvis confirmed a left hydrosalpinx without acute inflammatory changes, together with an incidental finding of a 2.7 × 2.0 cm
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Fig. 1. CT scan of abdomen and pelvis reveals a 2.7 × 2.0 cm solid mass in the neck of the pancreas (between arrows).
mass in the neck of the pancreas. This hypodense mass was felt to be consistent with a cystic pancreatic lesion (Fig. 1). The patient was seen in general surgery clinic several weeks later and then was lost to follow-up for approximately 5 months. The patient continued to have vague midabdominal pain. She then returned, and an endoscopic ultrasound of the pancreas confirmed a 2.7 × 2.0 cm lesion in the neck of the
Fig. 3. Gross photograph of the well circumscribed solid mass in the neck of the pancreas. The tumor has been cut through to show the cross-section (arrows).
pancreas that was noted to be a solid, well circumscribed and heteroechoic tumor. A transgastric fine needle aspiration (FNA) of the mass was performed. Material obtained by FNA showed round to oval monomorphic cells arranged in pseudopapillary fronds. The cells had bland nuclear features and rare grooves with a moderate amount of cytoplasm. Mitotic figures were not present (Fig. 2A). These cells stained positive for CD10 (Fig. 2B), alpha1-antitrypsin (Fig. 2C), alpha1-chymotrypsin (Fig. 2D)
Fig. 2. (A) FNA of the pancreatic neck mass. H&E ×840. (B) FNA of the pancreatic neck mass. Cells positive for CD10. ×840. (C) FNA of the pancreatic neck mass. Cells positive for alpha1-antitrypsin. ×840. (D) FNA of the pancreatic neck mass. Cells positive for alpha1-antichymotrypsin. ×840.
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discrete mass at the junction of the neck and body of the pancreas. A distal pancreatectomy and splenectomy were performed. Frozen section examination of the pancreatic resection margin revealed it to be free of tumor. Postoperatively, the patient had an uneventful recovery and was discharged home. At follow-up 2 months postoperatively, the patient had no complaints of pain or other symptoms. The resected tumor grossly was a circumscribed solid mass measuring 3.4 × 2.2 × 1.0 cm (Fig. 3). The cut surface of the tumor was tan-brown. No areas of hemorrhage or necrosis were appreciated. Histologic findings Microscopically, the tumor was composed of monomorphic cells in a pseudopapillary pattern. The spaces between the pseudopapillary strictures were filled with RBCs and fibrin (Fig. 3A1). On higher magnification, the tumor cells were polygonal epithelioid cells with eosinophilic to clear vacuolated cytoplasm. The nuclei were round to oval, some with nucleoli. Rare nuclear indentations were seen. Mitoses were rare (Fig. 3A2). The tumor tissue was well demarcated from the normal pancreas. No metastases were found in the submitted 2 peripancreatic lymph nodes. Immunohistochemically, most tumor cells were positive for CD10 (Fig. 5A), cyclin D1 (Fig 5B), alpha1-antitrypsin (Fig. 5C), alpha1-antichymotrypsin (Fig. 5D), NSE (Fig. 5E), vimentin (Fig. 5F) and cytokeratin (Fig. 5G), and some tumor cells were positive for neuroendocrine markers synaptophysin and chromogranin. The tumor cells were negative for the islet cell hormones glucagon, insulin, pancreatic polypeptide and somatostatin and other antigens such as CEA, CA19-9, S100, melanin A and Fontanna. Rare cells were positive for M1B. The tumor cells formed abundant basement membrane material that stained positive for Alcian blue PAS (Fig. 5H).
Fig. 4. (A1) Low-power view of the tumor showing both solid and cystic areas. Loss of adhesions resulted in the pseudopapillary formation. H&E ×420. (A2) High-power view of the tumor reveals monomorphic cells, some with clear cytoplasm. Note the nuclear condensation next to the nuclear membrane. H&E × 840. (B) High-power view of the normal pancreatic tissue, showing centriacinar cells, with pale clear cytoplasm (arrow). H&E ×840.
and cyclin D1 and did not stain for neuroendocrine markers. The cytologic diagnosis of solid pseudopapillary tumor of the pancreas was made. A complete laboratory work-up that included liver function tests, amylase and lipase, and tumor markers including CEA, CA125, CA19-9 and chromogranin A was unrevealing. In view of the cytologic diagnosis, the patient underwent laparotomy on June 10, 2005. Inspection of the pancreas did not reveal any obvious tumor, but palpation defined a
Ultrastructural findings on formalin-fixed tissue The tumor cells had central to subcentrally located, round to slightly indented, nuclei (Fig. 7B), some with an eccentric nucleolus bound to slightly hyperchromatic nuclear rim. The cytoplasm contained rare mitochondria and few Golgi complexes. Some myelin figures and scattered secretory granules were present. Some disintegrated granules and vesicles were also present: the exact nature of these disintegrated organelles is not known. Discussion SPT of the pancreas was first described by Frantz (1959) and was seen predominantly among the Asian and African American populations. SPT is a low grade malignant neoplasm that has excellent long-term survival after resection. The male:female ratio is 1:9.5 (Mao and Guuvendi, 1995). The tumor occurs predominantly in adolescent girls and young women. It has been shown that the tumor has the same biological behavior and prognosis in men as in women (Ohashi et al., 1993). The diagnosis of SPT in the present
104
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Fig. 5. (A) Pancreatic neck mass cells stain positive for CD10. ×840. (B) Pancreatic neck mass cells stain positive for cyclin D1. ×840. (C) Pancreatic neck mass cells stain positive for alpha1-antitrypsin. ×840. (D) Pancreatic neck mass cells stain positive for alpha1-antichymotrypsin. ×840. (E) Pancreatic neck mass cells stain positive for NSE. NSF ×420. (F) Pancreatic neck mass. Positive for vimentin. ×420. (G) Pancreatic neck mass cells stain positive for cytokeratin AE1/AE3. ×840. (H) Pancreatic neck mass. Alcian blue PAS stained the basement membrane material blue and red. ×420.
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Fig. 6. (A) Normal pancreatic centroacinar cells stain positive for CD10. ×840. (B) Normal pancreatic centroacinar cells stain positive for cyclin D1. ×840. (C) Normal pancreatic centriacinar cells positive for alpha1-antitrypsin. ×840. (D) Normal pancreatic centriacinar cells stain positive for alpha1-antichymotrypsin. ×840. (E) Normal pancreatic centriacinar cells stain positive for NSE. ×420. (F) Normal pancreatic centriacinar cells stain positive for vimentin. ×420. (G) Normal pancreatic centriacinar cells stain positive for cytokeratin AE1/AE3. ×840.
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Fig. 7. (A) EM, normal pancreatic centriacinar cells have round to slightly indented nuclei with focal chromatin condensation at the nuclear periphery and empty cytoplasm. ×2500. (B) EM, pancreatic neck mass cells have empty cytoplasm and nuclei with chromatin condensation focally at the nuclear envelope. ×3000.
case is supported by the indolent clinical course, characteristic pathologic findings and immunophenotyping. The tumor cells were not only positive for consistently expressed markers for this type of neoplasm, such as AAT, AACT and NSE, but also some newly identified markers including CD10 and cyclin D1. The new finding in this case is that the tumor cells and the centroacinar cells in the adjacent normal pancreatic tissue had a similar light microscopical (Figs. 4A2 and B), immunohistochemical (Figs. 5A–G, 6A–G) and ultrastructural features (Figs. 7A,B). On light microscopy, both the tumor cells and normal centroacinar cells (Figs. 4A2 and B) were bland appearing with round to oval nucleus, inconspicuous eccentric nucleoli and abundant eosinophilic cytoplasm. Immunohistochemical analysis of both tumor cells and normal centroacinar cells (Table 1) was positive for CD10, cyclin D1, alpha1-antitrypsin, alpha1-antichymotrypsin, NSE, vimentin and cytokeratin AE1/AE3. Ultrastructurally, both tumor cells and centroacinal cells were similar in having round to oval nucleus, some nuclear indentation, finely dispersed chromatin and some small eccentric nucleoli bound to the nuclear membrane. The cytoplasm was abundant with some mitochondria and few Golgi complexes. Both cells lacked dense core granules, an indicator of acinar and islet cell differentiation. The histogenesis of SPT remains unsettled because of discrepancies in the immunohistochemical and electron microscopic findings. A neuroendocrine origin has been suggested by a diffusely positive reaction for NSE (Miettinen et al., 1987) and by alleged positivity for pancreatic polypeptide somatostatin (Von Herbay et al., 1990), glucagon (Miettinen et al., 1987) and insulin (Von Herbay et al., 1990) in a few cases and by the occasional presence of organelles resembling neurosecretory granules. Other studies, including
the present case, have failed to demonstrate hormone production by SPT (Schlosnagle and Campbell, 1981). Furthermore, immunoreactivity for NSE should not be taken as evidence of neuroendocrine differentiation because this marker is also expressed by a variety of non-neuroendocrine neoplasms (Vinores et al., 1987). Neuroendocrine tumors and acinar cell carcinomas both lack the distinctive pseudopapillary pattern and degenerative changes of solid pseudopapillar tumors of the pancreas. Annulate lamellae have been observed by many researchers and are considered to be indicative of immaturity or poor differentiation. In this case, the homology between tumor cells and centroacinar cells, both immunohistochemically and electron microscopically, suggests that the histogenesis of SPT of pancreas is from centroacinar cells. Table 1 Immunohistochemical analysis of solid pseudopapillary tumor (SPT) and normal centroacinal cells (CAC) of pancreas Antibody
SPT
CAC
Alpha1-antitrypsin Alpha1-antichymotrypsin CD10 Cyclin D1 AE1/AE3 Vimentin NSE EMA Glucagon Insulin Somatostatin S100 Melanin A Pancreatic polypeptide CEA Synaptophysin Chromogranin
+ + + + + + + − − − − − − − − +/− +/−
+ + + + + + + − − − − − − − −
N. Kallichanda et al. / Experimental and Molecular Pathology 81 (2006) 101–107
Acknowledgments The authors thank Adriana Flores for typing the manuscript. The study was supported by NIH/NIAAA Alcohol Center Grant P50-019991-on the Liver and Pancreas, Morphology Core. References Chen, C., Jing, W., Gulati, P., Vargas, H., French, S.W., 2004. Melanocytic differentiation in a solid pseudopapillary tumor of the pancreas. J. Gastroenterol. 39, 579–583. Frantz, U.K., 1959. Tumor of the pancreas. Atlas of Tumor Pathology. Armed Forces Institute of Pathology, Washington, pp. 32–33. Kissone, J.M., 1994. Pancreatoblastoma and solid and cystic papillary tumor: Two tumors related to pancreatic ontogeny. Semin. Diagn. Pathol. 11, 152–164. Klimstra, D.S, Wenig, B.M., Heffes, S., 2000. Solid-pseudopapillary tumor of the pancreas: a typically cystic carcinoma of low malignant potential. Semin. Diagn. Pathol. 17, 66–80. Kosmahi, M., Seada, L.S., Janig, U., Harms, D., Kloppel, G., 2000. Solidpseudopapillary tumor of the pancreas: its origin revisited. Virchows Arch. 436, 473–480. Lieber, M.R., Lack, E.E., Robers, J.R.J., 1987. Solid and papillary epithelial neoplasm of the pancreas. An ultrastructure and immunocytochemical study of six cases. Am. J. Surg. Pathol. 11, 85–93.
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