Chinese Medical Journal 2010;123(22):3364-3366
Relapse of acute lymphoblastic leukemia in the pancreas after allogeneic bone marrow transplantation

ZHAO Xiao-mu,  ZHANG Zhong-tao,  LI Jian-she,  HAN Wei

ZHAO Xiao-mu (Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China)

ZHANG Zhong-tao (Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China)

LI Jian-she (Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China)

HAN Wei (Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China)

Correspondence to:ZHANG Zhong-tao,Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China (Tel: 86-10-63138475. Fax:86-10-63023261. E-mail:zhangzht@medmail.com.cn)
Keywords
pancreas; acute leukemia; relapse; allogeneic bone marrow transplantation
Abstract
The occurrence of metastatic lesions in the pancreas of patients with cancer, including hematological cancers, is uncommon (1.6%–37.5%) and of these, the majority of patients will have widespread disease.1-7 Isolated potentially resectable pancreatic metastases are rarely seen. Resection of metastatic tumors of the pancreas has been reported, but its role in improving survival rates or quality of life is not clear.7,8 However, recent studies have shown that surgical resection can be performed in selected patients with isolated pancreatic metastases, resulting in long-term survival and good palliation.1,9 We report a case of pancreatic relapse of acute lymphoblastic leukemia (ALL) following allo-bone marrow transplantation (BMT) which was treated by surgical resection, and review the literature in this area.
 
CASE REPORT
 
A 37-year-old man was referred to our hospital with progressive debility. Bone marrow aspiration and biopsy led to a diagnosis of ALL of B-cell lineage. Immunophenotype showed CD19 (+), CD20 (+), CD10 (+), human leukocyte antigen (HLA)-DR (+), CD58 (+), CD9 (+), CD45 (+), TdT (+), PAX-5 (+) and CD117 (−), CD7 (−), CD33 (−), CD34 (−), CD11b (−), CD56 (−), clgM (−), CD13 (−), CD7 (−), MPO (−). Cytogenetics finding is t(9;22) and BCR-ABL transcripts was detected. After four cycles of chemotherapy, he underwent HLA-matched related-donor ABO-compatible stem cell transplantation on January 2, 2007, resulting in complete remission (CR). On day 658 post allo-BMT, he underwent a radiological assessment and was found to have a pancreatic lesion. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) confirmed a 4.0 cm × 3.0 cm × 3.0 cm mass in the body and tail of the pancreas (Figure 1). Complete blood count showed white blood cell 4.88×109/L, lymphocytes 41.8%, granulocyte 55.4%, hemoglobin 96 g/L and platelet 149×109/L. These findings supported a pre-operative diagnosis of a primary pancreatic carcinoma.
 
On October 29, 2008, resection of the body and tail of the pancreas and a splenectomy were performed. The excised tissues are shown in Figure 2. The relapse of ALL to the pancreas was diagnosed histologically (Figure 3). Immunophenotype showed CK(L) (−), CK(H) (−), CD20 (−), CD79a (−), CD3 (−), CD7 (−), CD34 (−), CD30 (−), MPO (−), EBER (−) and PAX-5 (+), TdT (+). Regretfully, the cytogenetics and BCR-ABL transcripts were not checked. On post-operative day 2, leukemia cells were found in the patients’ bone marrow and two cycles of chemotherapy were given. The patient died on January 5, 2009. The cause of death was thought to be the result of an invasion of the central nervous system by ALL. Post-relapse survival was 11 weeks.
 

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Figure 1. Images of the pancreatic mass. Magnetic resonance imaging (MRI, A) and enhanced computed tomography (CT, B) show a mass (white arrow) in the body and tail of the pancrease.
Figure 2. Specimens of the body and tail of the pancreas and spleen post-operation. A: The overall sample of the mass in the body and tail of the pancreas (white arrow). B: Vertical incision of the mass, a poorly-defined lesion (white arrow) can be seen.
 

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Figure 3. PAX-5 immunohistochemistry staining shows pre-B leukemia cell infiltrated in the pancreas (Original magnification ×100).
 
CLINICAL OVERVIEW
 
Extramedullary relapses after allogeneic BMT occur in 20% of patients who undergo BMT for AML and 6%–30% of patients with ALL.10,11 The frequency of secondary pancreatic neoplasms varies markedly among studies (1.6%–37.5%), mainly reflecting the differences in the methods by which the diagnosis is established (biopsy vs. autopsy) and referral bias.3-9 Interestingly, this figure increases to 42% among patients with previously diagnosed primary cancers and a solitary mass in the pancreas.9 The majority of metastatic tumors are of epithelial origin and the most common sites of the primary lesions are the lung, kidney and gastrointestinal tract. The routes of spread can be divided into five categories: (1) lymphatic spread, (2) vascular spread, (3) lymphatic and vascular spread, (4) direct invasion, and (5) dissemination. Imaging studies such as dynamic contrast enhanced CT scans and MRI may support this, especially if multiple tumors are noted.
 
Relapse to the extramedullary region of the pancreas secondary to ALL is uncommon. To the best of our knowledge, only two cases of pancreatic relapse in acute leukemia patients after allo-BMT have been reported in the English language literature12,13 and there are no reported characteristics regarding these secondary tumors. Because approximately one-third of secondary tumors of the pancreas are clinically mistaken as primary tumors,2 accurate diagnosis presents several challenges to the clinician. The symptoms of a solitary metastatic tumor and a primary pancreatic carcinoma are similar: pain, weight loss, obstructive jaundice, upper gastrointestinal tract bleeding and acute pancreatitis. The patient in our study did not have any of these symptoms.
 
STRATEGIES
 
The differential diagnosis between a solitary metastatic tumor and a primary pancreatic carcinoma may be very difficult and radiological imaging is unable to differentiate primary from secondary pancreatic lesions.14 Highly vascular tumors, as indicated by contrast enhanced CT, MRI, or angiography are more likely to be metastatic than primary pancreatic cancers, but these primary neuroendocrine tumors are also hypervascular. Metastasis may also be more likely when there is a large tumor of the pancreatic head without a dilated bile duct or when the retro-pancreatic fat is not removed in a patient with a large pancreatic mass.15 Fluorine 18-FDG-PET has proven to be useful for the accurate staging of tumors.16 Percutaneous fine-needle aspiration (FNA) is helpful in establishing the correct pre-operative diagnosis, especially in patients who are not amenable to surgery, and in assisting in decisions related to the possibility and type of chemotherapy.17
 
Indications for pancreatic resection have not been defined, though some surgeons will consider pancreatectomy as long as the results of pre-operative radiological studies demonstrate no evidence of metastases to organs other than the pancreas.7 In patients with jaundice, relief of the extra-hepatic bile duct obstruction using surgical bypass or a biliary stent may result in 1-year-plus survival rates.16 Pancreatic resection may be possible in exceptional cases and result in even better survival rates.18 Five-year survival rates of 31% have been predicted for patients undergoing pancreatic resection due to renal cell carcinoma.19
 
There is no established treatment strategy for extramedullary relapse post-allo-BMT. It is clear that surgical excision has the potential to improve prognosis if the primary site and other metastases are well-controlled. Although the prognosis is still unfavorable, prolonged survival is often possible in some of these patients, sometimes with relatively simple treatment such as local surgery or radiotherapy.20,21
 
CLINICAL DIFFICULTIES
 
Since few cases have been reported, there were no clinical features and the diagnosis of relapse of ALL in the pancreas after allogeneic bone marrow transplantation is difficult. First, the diagnosis mainly depended on the preoperative or postoperative pathological and immunohistochemistry examination. But the obtainment of the relapsed specimens preoperative was difficult, the diagnosis was still a problems plagued clinicians. In addition, except this case, there has not been reported that the operation performed in patients with this condition. Though the risk of the pancreatectomy was lower than before and surgical technique has matured, the prognosis is not clear and the chemotherapy can not be ignored.
 
PERSONAL OPINIONS
 
By reporting this rare case, we would like to draw our attention that the presentation of a pancreatic mass in a patient with a remote history of malignancy may suggest a pancreatic relapse. Under the condition permitted, lesions fine-needle aspiration is recommended. This would help to diagnose and guide the further treatment. Furthermore, although there is no defined treatment strategy in acute lymphoblastic leukemia patients with pancreatic relapse after allogeneic bone marrow transplantation, local combined with systemic treatment may be an option to improve the survival.
 
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