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Spontaneously complete regression of pseudolymphoma of the remnant pancreas after pancreaticoduodenectomy
Pancreatology 12 (2012) 215e218
Contents lists available at SciVerse ScienceDirect
Pancreatology journal homepage: www.elsevier.com/locate/pan
Case report
Spontaneously complete regression of pseudolymphoma of the remnant pancreas after pancreaticoduodenectomy B. Nakata a, *, R. Amano a, J. Matsuoka a, S. Sugimori b, M. Ohsawa c, K. Wakasa c, Y. Egashira d, K. Kimura a, N. Yamada a, K. Hirakawa a a
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan Department of Diagnostic Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan d The First Department of Pathology, Osaka Medical College, Osaka, Japan b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 10 December 2011 Received in revised form 19 January 2012 Accepted 17 February 2012
Background: Pancreatic pseudolymphoma is extremely rare. Method: We present multiple pseudolymphomas in the head and body of the pancreas. The hypoechoic lesions observed by endoscopic ultrasound were enhanced in late-phase angio-computed tomography and homogeneously hypointensive in T1-weighted magnetic resonance imaging (MRI). 18F-fluorodeoxyglucose positron emission tomography showed strong accumulation in the lesions. The lesions were suspected to be non-functioning islet cell carcinoma. The intraoperative pathological diagnosis for the specimen obtained by a pylorus-preserving pancreaticoduodenectomy was non-neoplastic lymphoid cells. The remnant lesion in the pancreatic body was preserved. Results: Macroscopically, the mass was well-circumscribed gray-white colored lesion. The pathological diagnosis was pancreatic pseudolymphoma. The lesion in the remnant pancreas spontaneously disappeared within one year after the operation. Conclusion: The differential diagnosis of pancreatic pseudolymphoma from malignant tumor is very difficult, however, the image findings demonstrated here may be informative. The spontaneous disappearance of pancreatic pseudolymphoma was firstly observed in the present case. Copyright Ó 2012, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.
Keywords: Angio-computed tomography Immunohistochemistry Magnetic resonance imaging Natural history Positron emission tomography
1. Introduction
2. Case report
Pseudolymphoma, one entity of which is benign lymphoid hyperplasia, has also been named nodular lymphoid hyperplasia, reactive lymphoid hyperplasia, localized lymphoid hyperplasia and lymphoreticular hyperplasia. Pseudolymphoma of the pancreas is a very rare, with only two cases published so far in the English language case reports [1,2]. It remains difficult to distinguish pseudolymphoma from malignant disease, even with recent improved diagnostic modalities. Reported herein is a case with multiple pancreatic pseudolymphomas which were pathologically diagnosed using tissue taken by pancreaticoduodenectomy. The remnant lesion in the pancreatic body was observed to completely regress without any treatment.
A 51-year-old woman with renal stones but no other complaints was undergoing an abdominal ultrasound when a hypoechoic mass 15 mm in diameter was observed in the pancreatic head. Further examination using endoscopic ultrasound (EUS) demonstrated two well-defined homogeneous hypoechoic lesions 17 and 10 mm in diameter in the pancreatic head and one lesion 23 mm in diameter in the pancreatic body (Fig. 1a). Preoperative pathological diagnosis using an EUS fine-needle aspiration (FNA) biopsy specimen could not be accomplished due to the occurrence of minor esophageal perforation with mediastinal emphysema during the examination. This iatrogenic complication was treated conservatively and healed within 10 days. Dynamic abdominal computed tomography (CT) did not demonstrate any masses in the pancreas. Enhanced masses in late-phase angio-computed tomography (Figs. 1b and 2a) and hypointense homogeneous lesions in T1-weighted magnetic resonance imaging (MRI) (Fig. 2b) were observed to be concordant with the hypoechoic lesions seen in EUS. T2-weighted MRI revealed the
* Corresponding author. Tel.: þ81 6 6645 3838; fax: þ81 6646 6450. E-mail address: [email protected] (B. Nakata).
1424-3903/$ e see front matter Copyright Ó 2012, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. doi:10.1016/j.pan.2012.02.011
216
B. Nakata et al. / Pancreatology 12 (2012) 215e218
Fig. 1. a: A homogeneous hypoechoic tumor in the pancreatic head on endoscopic ultrasound. b: A hyperperfused tumor in the pancreatic head on late-phase angio-computed tomography (CT). c: Increased accumulation of 18F-fluorodeoxy glucose in the pancreatic head tumor on positron emission tomography. d: The reactive germinal center (GC) and well-preserved mantle zone (MZ) in the resected pancreas head. Fibrosis in the interfollicular region is observed. Pathological diagnosis was pseudolymphoma of the pancreas (Hematoxylin and eosin staining; Original magnification 100).
mass to be isointense with surrounding pancreatic tissue. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) demonstrated hypermetabolic focuses in the regions of interest (standardized uptake value: 3.74 in the pancreatic head and 3.67 in the pancreatic body) (Fig. 1c). Tumor markers (CA 19-9, SPan-1, DUPAN-2, and CEA), hormones (insulin, glucagon, and gastrin), and lactate dehydrogenase (LDH) examined in her serum were all within normal limits. Peripheral blood counts and serum amylase were also within normal limits. She had no histories of antiepileptic use or any recent vaccination. The preoperative diagnosis was multiple non-functioning islet cell tumors of the pancreas. The patient hoped to undergo subtotal pancreatectomy under informed consent. There was no preoperative pathological diagnosis; therefore, a pylorus-preserving pancreaticoduodenectomy was performed in order to acquire intraoperative pathological diagnosis for the pancreatic head lesions. Unexpectedly, pathological findings using frozen sections revealed that the mass was composed predominantly of non-neoplastic lymphoid cells with proliferative interstitial tissue that had grown to compress the normal pancreatic tissue. Consequently, the remnant pancreas was preserved with a mass in the pancreatic body. Macroscopically, both masses in the pancreatic head were wellcircumscribed gray-white colored lesions without capsules, and measured the same as the preoperative imaging studies. The final pathological diagnosis using a formalin-fixed paraffin-embedded specimen was pseudolymphoma of the pancreas because of the following microscopic findings: a well-demarcated mass that was comprised of numerous enlarged lymph follicles with germinal centers intermingled with centrocytes, centroblasts and tingiblebody macrophages. Many mitotic figures were also seen in
germinal centers. Mantle zones were preserved but were not expanded. There was no area showing expansion of marginal zone lymphocytes. Infiltration of mature plasma cells and small lymphocytes was seen in interfollicular areas with a small amount of fibrosis (Fig. 1d). There was no finding of pancreatitis in pancreatic tissue surrounding the lesion. Immunohistochemical staining was performed. The centroblasts and centrocytes in germinal centers and the cells in the mantle zone showed positive staining with L-26 pan-B-cell marker. Bcl-2 was negative in the proliferating cells in the germinal centers in contrast to Bcl-2positive cells in the mantle zone. UCHL1 pan-T-cell marker was positive in the small lymphocytes distributed in germinal centers and the interfollicular area. Immunoglobulin light chain reactivity for plasma cells was polyclonal with a kappa to lambda ratio of approximately 2 to 1. These findings were consistent with a reactive process. The marginal zone cells were negative for CD5 and Cyclin D1, suggesting exclusion of mantle cell lymphoma. Epithelial markers such as AE1þAE3 and CAM 5.2 were negative in the lymphoid lesion. The postoperative course was uneventful. The lesion in the remnant pancreas spontaneously disappeared as visualized by a MRI examination 1 year after the operation (Fig. 2c and d). No disease relapse has been observed during yearly MRI follow-up for 5 years following the operation. 3. Discussion Pseudolymphoma is a benign inflammatory tumor that demonstrates a mixed cellular infiltration of reactive lymph follicles with mature lymphocytes predominating and the presence of
B. Nakata et al. / Pancreatology 12 (2012) 215e218
217
Fig. 2. a: A hyperperfused lesion in the pancreatic body on late-phase preoperative angio-CT. b: Low-intensity lesion in pancreatic body on preoperative T1-weighted (T1-W) magnetic resonance imaging (MRI). c: The size of the low-intensity lesion in the pancreatic body decreased on T1-W MRI at 6 months after the operation. d: No tumor was observed in the pancreatic body, and a slight dilation of the main pancreatic duct was seen on T1-W MRI at 12 months after the operation.
a true germinal center. Although pseudolymphoma can occur in any tissue, the favorite sites of this infrequent disorder are the skin, orbit, lung, intestine, liver and breast. Many cases of so-called pseudolymphoma of the stomach were reported until the concept of extranodal marginal zone B-cell lymphoma of mucosaassociated lymphoid tissue (MALT lymphoma) was advocated by Isaacson and Wright in 1983. However, most of the reported gastric “pseudolymphomas” are presently thought to be MALT lymphoma or other kinds of malignant lymphomas [3]. Anecdotal case reports concerning pseudolymphoma of the kidney, testis, prostate, thyroid, larynx, tongue, esophagus, gallbladder and spleen have been published. Although pseudolymphoma occurs frequently in a background of chronic inflammation, the exact etiology of pseudolymphoma is unknown. Both of the cases of pancreatic pseudolymphoma that were previously reported underwent pancreatectomy. The first case, reported by Nakashiro et al. in 1991, was a 57-year-old woman with malaise and obstructive jaundice who underwent pancreaticoduodenectomy under the clinical diagnosis of pancreatic cancer [1]. The mass was detected with abdominal ultrasonography as a hypoechoic lesion approximately 2 cm in diameter. The pancreatic parenchyma was demonstrated to be adjacent to the pseudolymphoma and generally intact, and no particular findings relevant to lesion formation such as ulceration or lithiasis were observed. The second case, reported by Hatzitheoklitos et al. in 1994, was a 68-year old woman who complained of malaise and a 5 kg weight loss [2]. She was found with abdominal ultrasonography to have a 5 2.5 cm hypoechoic mass of the pancreatic body. An increased concentration of contrast medium in the region of the suspected tumor was observed by celiacomesenteric angiography. Under the diagnosis of pancreatic cancer, distal pancreatectomy
was performed. The ultrasonographic hypoechoic mass and hyperperfusion pattern on angiography of previous cases were concordant with findings of the present case. A low signal intensity mass on T1-weighted MRI and accumulation of 18F-FDG PET were firstly demonstrated in the current case of pancreatic pseudolymphoma. In hepatic and pulmonary pseudolymphoma, similar MRI [4] and PET [5,6] findings have been reported. The administrations of anticonvulsant or vaccine have been suggested as etiologies in some cases of pseudolymphoma [7,8], however, the present case and the previous two cases of pancreatic pseudolymphoma [1,2] did not have such histories. Both of the previously reported cases of pseudolymphoma of the pancreas were solitary while the present case was multiple. Multiple pseudolymphoma has been observed in the lung in 36% of cases and in the liver in 19% of cases [9,10]. Multiple lesions of pancreatic islet cell tumors occur at a rate of approximately 5% and are mostly associated with multiple endocrine neoplasm I (MEN I) [11]. The patient in the present study had no parathyroid, pituitary, or cutaneous tumors suggestive of MEN I. In this context, the possibility of multiple islet cell tumors might have been low in the present case. However, the findings of a homogeneous hypoechoic mass, hypervascularity and low signal intensity on T1-weighted MRI in the present case were concordant with an islet cell tumor of the pancreas [11,12]. Moreover, the hot spots in 18F-FDG PET strongly suggested malignancy. Based on these imaging findings, surgical resection was performed. Recently, EUS-FNA has made it possible to achieve a pathological diagnosis for a pancreatic mass before operation. Unfortunately, an iatrogenic complication precluded pathological diagnosis using tissue obtained by EUS-FNA in the present case. Therefore, pancreatoduodenectomy was scheduled, with the plan that the pancreatic body would be
218
B. Nakata et al. / Pancreatology 12 (2012) 215e218
resected if necessary and pancreatic tail would be left intact. Distal pancreatectomy at first may have been another option for the present case. However, if the intraoperative pathologic diagnosis would have been islet cell tumor as was highly anticipated, total pancreatectomy would have been performed. A majority of pseudolymphomas are resected due to the difficulty of differential diagnosis from malignant tumors, therefore, the natural history of this disease has been infrequently observed. The present case is the first report of spontaneous complete regression of a pancreatic pseudolymphoma. There have been a few case reports that have delineated spontaneous diminution in size or disappearance of pseudolymphoma [10,13], and in some cases malignant transformation of pseudolymphoma into lymphoma has been suggested [14,15]. Although primary pancreatic lymphoma (PPL) is rare tumor, more than 100 cases have been reported in the English medical literature. PPL should be mainly treated with chemotherapy. Most of PPL are intermediate or high-grade non-Hodgkin’s lymphoma and the predominant histotype is diffuse large B-cell lymphoma. The most common symptoms of PPL are abdominal pain (83%), abdominal mass (58%), and weight loss (50%) [16]. Weight losses were observed in both of the patients with pancreatic pseudolymphoma previously reported [1,2]. LDH is thought as essential serum marker for PPL. The present case and the previously reported cases of pancreatic pseudolymphoma did not show the elevated levels of LDH in sera. The majority of PPL locates in pancreatic head and forms rather large tumor with the mean dimension of 8 cm. The EUS findings of PPL are strongly hypoechoic mass, pancreatic hypertrophy, and multiple isoechoic peripancreatic lymph nodes. There are two morphologic types of PPL in CT and MRI; a localized and well-circumscribed tumoral form; a diffuse enlargement infiltration or replacing most of the pancreatic gland. Most of PPLs are homogeneous and less dense than muscle in plain CT, and are poorly enhanced by contrast medium. PPL appears a low intensity and homogeneous mass in T1-weight MRI, and a heterogeneous mass with a low to intermediate intensity in T2-weight MRI [16]. PET has been thought useful for lymphoma staging, however, there have been only two reports regarding 18F-FDG accumulations in PPL [17]. Some of the image findings described above may be informative for the differential diagnosis between PPL and pancreatic pseudolymphoma, however, a cytohistological examination using CT- or EUS-FNA biopsy specimen is mandatory [16]. Considering these unsolved problems of natural history and the diagnostic difficulty regarding pseudolymphoma, careful
observation is required when the mass is not resected. Although pancreatic pseudolymphoma is extremely rare, pancreatic surgeons should include it in the differential diagnosis of a pancreatic mass. References [1] Nakashiro H, Tokinaga O, Watanabe T, Ishibashi K, Kuwaki T. Localized lymphoid hyperplasia (pseudolymphoma) of the pancreas presenting with obstructive jaundice. Hum Pathol 1991;22:724e6. [2] Hatzitheoklitos E, Büchler MW, Friess H, DiSebastiano P, Poch B, Beger HG, et al. Pseudolymphoma of the pancreas mimicking cancer. Pancreas 1994;9: 668e70. [3] Abbondanzo SL, Sobin LH. Gastric “pseudolymphoma. Cancer 1997;79: 1656e63. [4] Hayashi M, Yonetani N, Hirokawa F, Asakuma M, Miyaji K, Takeshita A, et al. An operative case of hepatic pseudolymphoma difficult to differentiate from primary hepatic marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. World J Surg Oncol 2011;9:3. [5] Lin E. Reactive lymphoid hyperplasia of the liver identified by FDG PET. Clin Nucl Med 2008;33:419e20. [6] Suga K, Kawakami Y, Hiyama A, Hori K, Tanaka N, Ueda K. F-18 FDG PET/CT findings in a case of multifocal nodular lymphoid hyperplasia of the lung. Clin Nucl Med 2009;34:374e6. [7] Choi TS, Doh KS, Kim SH, Jang MS, Suh KS, Kim ST. Clinicopathological and genotypic aspects of anticonvulsant-induced pseudolymphoma syndrome. Br J Dermatol 2003;148:730e6. [8] Pham-Ledard A, Vergier B, Doutre MS, Beylot-Barry M. Disseminated cutaneous lymphoid hyperplasia of 12 years’ duration triggered by vaccination. Dermatology 2010;220:176e9. [9] Abbondanzo SL, Rush W, Bijwaard KE, Koss MN. Nodular lymphoid hyperplasia of the lung. A clinicopathological study of 14 cases. Am J Surg Pathol 2000;24:587e97. [10] Zen Y, Fujii T, Nakamura Y. Hepatic pseudolymphoma: a clinicopathological study of five cases and review of the literature. Mod Pathol 2010;23: 244e50. [11] Lee DS, Jeffrey RB, Kamaya A. Islet-cell tumors of the pancreas: spectrum of MDCT findings. A pictorial essay. Appl Radiol 2009;36:10e32. [12] Herwick S, Miller FH, Keppke AL. MRI of islet cell tumors of the pancreas. Am J Roentogenol 2006;187:W472e80. [13] Miyoshi S, Hamada H, Katayama H, Hamaguchi N, Irifune K, Ito R, et al. A case of pulmonary nodular lymphoid hyperplasia with a resected cavity, followed by spontaneous regression of the remaining lesions. Int Med 2010;49: 1617e21. [14] Kulow BF, Cualing H, Steele P, VanHorn J, Breneman JC, Mutasim DF, et al. Progression of cutaneous B-cell pseudolymphoma to cutaneous B-cell lymphoma. J Cutan Med Surg 2002;6:519e28. [15] Koss MN, Hochholzer L, Nichols PW, Wehunt WD, Lazarus AA. Primary nonHodgkin’s lymphoma and pseudolymphoma of lung: a study of 161 patients. Hum Pathol 1983;14:1024e38. [16] Saif MW. Primary pancreatic lymphomas. J Pancreas 2006;7:262e73. [17] Abe Y, Tamura K, Sakata I, Ishida J, Mukai M, Ohtaki M, et al. Unique intense uptake demonstrated by 18F-FDG positron emission tomography/computed tomography in primary pancreatic lymphoma: a case report. Oncol Lett. 2010; 1:605e7.
Contents lists available at SciVerse ScienceDirect
Pancreatology journal homepage: www.elsevier.com/locate/pan
Case report
Spontaneously complete regression of pseudolymphoma of the remnant pancreas after pancreaticoduodenectomy B. Nakata a, *, R. Amano a, J. Matsuoka a, S. Sugimori b, M. Ohsawa c, K. Wakasa c, Y. Egashira d, K. Kimura a, N. Yamada a, K. Hirakawa a a
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan Department of Diagnostic Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan d The First Department of Pathology, Osaka Medical College, Osaka, Japan b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 10 December 2011 Received in revised form 19 January 2012 Accepted 17 February 2012
Background: Pancreatic pseudolymphoma is extremely rare. Method: We present multiple pseudolymphomas in the head and body of the pancreas. The hypoechoic lesions observed by endoscopic ultrasound were enhanced in late-phase angio-computed tomography and homogeneously hypointensive in T1-weighted magnetic resonance imaging (MRI). 18F-fluorodeoxyglucose positron emission tomography showed strong accumulation in the lesions. The lesions were suspected to be non-functioning islet cell carcinoma. The intraoperative pathological diagnosis for the specimen obtained by a pylorus-preserving pancreaticoduodenectomy was non-neoplastic lymphoid cells. The remnant lesion in the pancreatic body was preserved. Results: Macroscopically, the mass was well-circumscribed gray-white colored lesion. The pathological diagnosis was pancreatic pseudolymphoma. The lesion in the remnant pancreas spontaneously disappeared within one year after the operation. Conclusion: The differential diagnosis of pancreatic pseudolymphoma from malignant tumor is very difficult, however, the image findings demonstrated here may be informative. The spontaneous disappearance of pancreatic pseudolymphoma was firstly observed in the present case. Copyright Ó 2012, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.
Keywords: Angio-computed tomography Immunohistochemistry Magnetic resonance imaging Natural history Positron emission tomography
1. Introduction
2. Case report
Pseudolymphoma, one entity of which is benign lymphoid hyperplasia, has also been named nodular lymphoid hyperplasia, reactive lymphoid hyperplasia, localized lymphoid hyperplasia and lymphoreticular hyperplasia. Pseudolymphoma of the pancreas is a very rare, with only two cases published so far in the English language case reports [1,2]. It remains difficult to distinguish pseudolymphoma from malignant disease, even with recent improved diagnostic modalities. Reported herein is a case with multiple pancreatic pseudolymphomas which were pathologically diagnosed using tissue taken by pancreaticoduodenectomy. The remnant lesion in the pancreatic body was observed to completely regress without any treatment.
A 51-year-old woman with renal stones but no other complaints was undergoing an abdominal ultrasound when a hypoechoic mass 15 mm in diameter was observed in the pancreatic head. Further examination using endoscopic ultrasound (EUS) demonstrated two well-defined homogeneous hypoechoic lesions 17 and 10 mm in diameter in the pancreatic head and one lesion 23 mm in diameter in the pancreatic body (Fig. 1a). Preoperative pathological diagnosis using an EUS fine-needle aspiration (FNA) biopsy specimen could not be accomplished due to the occurrence of minor esophageal perforation with mediastinal emphysema during the examination. This iatrogenic complication was treated conservatively and healed within 10 days. Dynamic abdominal computed tomography (CT) did not demonstrate any masses in the pancreas. Enhanced masses in late-phase angio-computed tomography (Figs. 1b and 2a) and hypointense homogeneous lesions in T1-weighted magnetic resonance imaging (MRI) (Fig. 2b) were observed to be concordant with the hypoechoic lesions seen in EUS. T2-weighted MRI revealed the
* Corresponding author. Tel.: þ81 6 6645 3838; fax: þ81 6646 6450. E-mail address: [email protected] (B. Nakata).
1424-3903/$ e see front matter Copyright Ó 2012, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. doi:10.1016/j.pan.2012.02.011
216
B. Nakata et al. / Pancreatology 12 (2012) 215e218
Fig. 1. a: A homogeneous hypoechoic tumor in the pancreatic head on endoscopic ultrasound. b: A hyperperfused tumor in the pancreatic head on late-phase angio-computed tomography (CT). c: Increased accumulation of 18F-fluorodeoxy glucose in the pancreatic head tumor on positron emission tomography. d: The reactive germinal center (GC) and well-preserved mantle zone (MZ) in the resected pancreas head. Fibrosis in the interfollicular region is observed. Pathological diagnosis was pseudolymphoma of the pancreas (Hematoxylin and eosin staining; Original magnification 100).
mass to be isointense with surrounding pancreatic tissue. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) demonstrated hypermetabolic focuses in the regions of interest (standardized uptake value: 3.74 in the pancreatic head and 3.67 in the pancreatic body) (Fig. 1c). Tumor markers (CA 19-9, SPan-1, DUPAN-2, and CEA), hormones (insulin, glucagon, and gastrin), and lactate dehydrogenase (LDH) examined in her serum were all within normal limits. Peripheral blood counts and serum amylase were also within normal limits. She had no histories of antiepileptic use or any recent vaccination. The preoperative diagnosis was multiple non-functioning islet cell tumors of the pancreas. The patient hoped to undergo subtotal pancreatectomy under informed consent. There was no preoperative pathological diagnosis; therefore, a pylorus-preserving pancreaticoduodenectomy was performed in order to acquire intraoperative pathological diagnosis for the pancreatic head lesions. Unexpectedly, pathological findings using frozen sections revealed that the mass was composed predominantly of non-neoplastic lymphoid cells with proliferative interstitial tissue that had grown to compress the normal pancreatic tissue. Consequently, the remnant pancreas was preserved with a mass in the pancreatic body. Macroscopically, both masses in the pancreatic head were wellcircumscribed gray-white colored lesions without capsules, and measured the same as the preoperative imaging studies. The final pathological diagnosis using a formalin-fixed paraffin-embedded specimen was pseudolymphoma of the pancreas because of the following microscopic findings: a well-demarcated mass that was comprised of numerous enlarged lymph follicles with germinal centers intermingled with centrocytes, centroblasts and tingiblebody macrophages. Many mitotic figures were also seen in
germinal centers. Mantle zones were preserved but were not expanded. There was no area showing expansion of marginal zone lymphocytes. Infiltration of mature plasma cells and small lymphocytes was seen in interfollicular areas with a small amount of fibrosis (Fig. 1d). There was no finding of pancreatitis in pancreatic tissue surrounding the lesion. Immunohistochemical staining was performed. The centroblasts and centrocytes in germinal centers and the cells in the mantle zone showed positive staining with L-26 pan-B-cell marker. Bcl-2 was negative in the proliferating cells in the germinal centers in contrast to Bcl-2positive cells in the mantle zone. UCHL1 pan-T-cell marker was positive in the small lymphocytes distributed in germinal centers and the interfollicular area. Immunoglobulin light chain reactivity for plasma cells was polyclonal with a kappa to lambda ratio of approximately 2 to 1. These findings were consistent with a reactive process. The marginal zone cells were negative for CD5 and Cyclin D1, suggesting exclusion of mantle cell lymphoma. Epithelial markers such as AE1þAE3 and CAM 5.2 were negative in the lymphoid lesion. The postoperative course was uneventful. The lesion in the remnant pancreas spontaneously disappeared as visualized by a MRI examination 1 year after the operation (Fig. 2c and d). No disease relapse has been observed during yearly MRI follow-up for 5 years following the operation. 3. Discussion Pseudolymphoma is a benign inflammatory tumor that demonstrates a mixed cellular infiltration of reactive lymph follicles with mature lymphocytes predominating and the presence of
B. Nakata et al. / Pancreatology 12 (2012) 215e218
217
Fig. 2. a: A hyperperfused lesion in the pancreatic body on late-phase preoperative angio-CT. b: Low-intensity lesion in pancreatic body on preoperative T1-weighted (T1-W) magnetic resonance imaging (MRI). c: The size of the low-intensity lesion in the pancreatic body decreased on T1-W MRI at 6 months after the operation. d: No tumor was observed in the pancreatic body, and a slight dilation of the main pancreatic duct was seen on T1-W MRI at 12 months after the operation.
a true germinal center. Although pseudolymphoma can occur in any tissue, the favorite sites of this infrequent disorder are the skin, orbit, lung, intestine, liver and breast. Many cases of so-called pseudolymphoma of the stomach were reported until the concept of extranodal marginal zone B-cell lymphoma of mucosaassociated lymphoid tissue (MALT lymphoma) was advocated by Isaacson and Wright in 1983. However, most of the reported gastric “pseudolymphomas” are presently thought to be MALT lymphoma or other kinds of malignant lymphomas [3]. Anecdotal case reports concerning pseudolymphoma of the kidney, testis, prostate, thyroid, larynx, tongue, esophagus, gallbladder and spleen have been published. Although pseudolymphoma occurs frequently in a background of chronic inflammation, the exact etiology of pseudolymphoma is unknown. Both of the cases of pancreatic pseudolymphoma that were previously reported underwent pancreatectomy. The first case, reported by Nakashiro et al. in 1991, was a 57-year-old woman with malaise and obstructive jaundice who underwent pancreaticoduodenectomy under the clinical diagnosis of pancreatic cancer [1]. The mass was detected with abdominal ultrasonography as a hypoechoic lesion approximately 2 cm in diameter. The pancreatic parenchyma was demonstrated to be adjacent to the pseudolymphoma and generally intact, and no particular findings relevant to lesion formation such as ulceration or lithiasis were observed. The second case, reported by Hatzitheoklitos et al. in 1994, was a 68-year old woman who complained of malaise and a 5 kg weight loss [2]. She was found with abdominal ultrasonography to have a 5 2.5 cm hypoechoic mass of the pancreatic body. An increased concentration of contrast medium in the region of the suspected tumor was observed by celiacomesenteric angiography. Under the diagnosis of pancreatic cancer, distal pancreatectomy
was performed. The ultrasonographic hypoechoic mass and hyperperfusion pattern on angiography of previous cases were concordant with findings of the present case. A low signal intensity mass on T1-weighted MRI and accumulation of 18F-FDG PET were firstly demonstrated in the current case of pancreatic pseudolymphoma. In hepatic and pulmonary pseudolymphoma, similar MRI [4] and PET [5,6] findings have been reported. The administrations of anticonvulsant or vaccine have been suggested as etiologies in some cases of pseudolymphoma [7,8], however, the present case and the previous two cases of pancreatic pseudolymphoma [1,2] did not have such histories. Both of the previously reported cases of pseudolymphoma of the pancreas were solitary while the present case was multiple. Multiple pseudolymphoma has been observed in the lung in 36% of cases and in the liver in 19% of cases [9,10]. Multiple lesions of pancreatic islet cell tumors occur at a rate of approximately 5% and are mostly associated with multiple endocrine neoplasm I (MEN I) [11]. The patient in the present study had no parathyroid, pituitary, or cutaneous tumors suggestive of MEN I. In this context, the possibility of multiple islet cell tumors might have been low in the present case. However, the findings of a homogeneous hypoechoic mass, hypervascularity and low signal intensity on T1-weighted MRI in the present case were concordant with an islet cell tumor of the pancreas [11,12]. Moreover, the hot spots in 18F-FDG PET strongly suggested malignancy. Based on these imaging findings, surgical resection was performed. Recently, EUS-FNA has made it possible to achieve a pathological diagnosis for a pancreatic mass before operation. Unfortunately, an iatrogenic complication precluded pathological diagnosis using tissue obtained by EUS-FNA in the present case. Therefore, pancreatoduodenectomy was scheduled, with the plan that the pancreatic body would be
218
B. Nakata et al. / Pancreatology 12 (2012) 215e218
resected if necessary and pancreatic tail would be left intact. Distal pancreatectomy at first may have been another option for the present case. However, if the intraoperative pathologic diagnosis would have been islet cell tumor as was highly anticipated, total pancreatectomy would have been performed. A majority of pseudolymphomas are resected due to the difficulty of differential diagnosis from malignant tumors, therefore, the natural history of this disease has been infrequently observed. The present case is the first report of spontaneous complete regression of a pancreatic pseudolymphoma. There have been a few case reports that have delineated spontaneous diminution in size or disappearance of pseudolymphoma [10,13], and in some cases malignant transformation of pseudolymphoma into lymphoma has been suggested [14,15]. Although primary pancreatic lymphoma (PPL) is rare tumor, more than 100 cases have been reported in the English medical literature. PPL should be mainly treated with chemotherapy. Most of PPL are intermediate or high-grade non-Hodgkin’s lymphoma and the predominant histotype is diffuse large B-cell lymphoma. The most common symptoms of PPL are abdominal pain (83%), abdominal mass (58%), and weight loss (50%) [16]. Weight losses were observed in both of the patients with pancreatic pseudolymphoma previously reported [1,2]. LDH is thought as essential serum marker for PPL. The present case and the previously reported cases of pancreatic pseudolymphoma did not show the elevated levels of LDH in sera. The majority of PPL locates in pancreatic head and forms rather large tumor with the mean dimension of 8 cm. The EUS findings of PPL are strongly hypoechoic mass, pancreatic hypertrophy, and multiple isoechoic peripancreatic lymph nodes. There are two morphologic types of PPL in CT and MRI; a localized and well-circumscribed tumoral form; a diffuse enlargement infiltration or replacing most of the pancreatic gland. Most of PPLs are homogeneous and less dense than muscle in plain CT, and are poorly enhanced by contrast medium. PPL appears a low intensity and homogeneous mass in T1-weight MRI, and a heterogeneous mass with a low to intermediate intensity in T2-weight MRI [16]. PET has been thought useful for lymphoma staging, however, there have been only two reports regarding 18F-FDG accumulations in PPL [17]. Some of the image findings described above may be informative for the differential diagnosis between PPL and pancreatic pseudolymphoma, however, a cytohistological examination using CT- or EUS-FNA biopsy specimen is mandatory [16]. Considering these unsolved problems of natural history and the diagnostic difficulty regarding pseudolymphoma, careful
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