Leukemic Infiltration of the Appendix as an Unusal Site of Extramedulary Relapse: Report of Two Cases and Review of the Literature
Authors: Mahdi Shahriari, Mohammadreza Bordbar, Bita Geramizadeh, Mehran Karimi
Abstract: The appendix is an unusual site for extramedulary relapse of acute leukemia. The present case report describes two cases of late course acute lymphoblastic leukemia presented with leukemic infiltration of the appendix and complete remission of bone marrow. The signs and symptoms of the cases suggest that leukemic involvement of the appendix should be considered in the differential diagnosis of leukemia patients presenting with acute abdomen
ran J Med Sci 2010; 35(3): 248-250.
Keywords: Acute lymphoblastic leukemia, appendix , Appendicitis
Introduction: Acute leukemia is the most frequent malignancy of the child- hood. Increased survival and prolonged remission of leukemic patients, as a result of modern combined anticancer therapies, has led to more frequent extramedulary infiltration of leukemic cells.1 However, the involvement of the appendix in leukemia is extremely rare, especially when the disease is diagnosed ante-mortem or when a patient's bone marrow (BM) is in remission.
Only sporadic reports of the antemortem recognition of leukemic appendiceal involvement have appeared in the literature.2-6
The present report describes the clinicopathologic features
of two cases of acute lymphoblastic leukemia (ALL), while in complete BM remission, presented with leukemic involvement of the appendix and acute abdominal pain, which mimicked acute appendicitis requiring prompt appendectomy.
An 8.5 years old girl presented with one month history of fever, abdominal pain, and ankle and hip joints pain on Janu-
ary 2001. She had a moderate pallor, but no lymphadenopathy
or hepatosplenomegaly. Complete blood count (CBC) revealed a hemoglobin level of 8.5 gm/dL, leukocyte count of 5700/mm3 with 43% lymphocyte and 6% lymphoblast, and platelet count of 209000/mm3. Bone marrow aspiration confirmed the diag- nosis of ALL, with positive immunoreactivity of malignant cells
for CD79α, CD19, CD68, CD13, and negative immunoreactiv- ity for CD10, CD7, CD3 and IgM. Chemotherapy of the patient began according to standard-risk pre-B-cell ALL protocol.7
After two years of chemotherapy, she was in complete BM remission, and her treatment was discontinued for almost two years. In March 2004, she referred back with the right lower quadrant abdominal pain that had been around for one month. Abdominopelvic sonography showed appendicular and bilateral ovarian masses. Exploratory laparatomy revealed a large unresectable retroperitoneal mass, an appendicular mass, and a bilateral ovarian mass. Biopsies of the above-mentioned masses revealed leukemic infiltration (figure 1). Meanwhile, BM examination was normal. Systemic re-induction chemotherapy began according to the recurrent ALL protocol using vincristine, methotrexate, Ara-C and L-asparginase.
She was on maintenance chemotherapy using daily 6-mercaptopurine (6-MP), weekly methotrexate and monthly reinforcement courses of vincristine until January 2008, when she again developed abdominal pain. Abdominopelvic CT scan revealed multiple metastatic lesions in the bowel loops, mesentry, kidneys, ovaries and liver, suggestive of leukemic involvement. Biopsies of omental lymph nodes and small bowel mesentry were in favor of B-cell origin acute lymphoblastic leukemia/lymphoma. Her BM was still in remission, and she was treated according to recurrent ALL protocol,7 for the second time.
In July 2008, she presented with unilateral facial palsy. Her brain MRI was normal but cerebrospinal fluid (CSF) analysis confirmed CNS involvement. Bone marrow examination showed more than 80% lymphoblasts. Since she did not have any HLA-identical donor (related or unrelated), chemotherapy was changed to Ara-C, Mitoxantrone and Etoposide. However, she developed severe neutropenia followed by fulminant sepsis and severe coagulopathy, and finally died of disseminated Aspergillus infection.
An 18 month old boy presented with one week history of diarrhea, fever and abdominal pain on December 1998. Complete blood
count showed thrombocytopenia and lym-
phoblasts in the peripheral blood. Bone mar- row examination confirmed the diagnosis of ALL. Treatment started with vincristine, L- asparginase and prednisone. He was in con- tinuous complete remission until February
2002, when CSF analysis revealed CNS relapse. He was treated using the recurrent ALL protocol,7 followed by 12 sessions of 2400
CGY cranial irradiation.
He was in complete BM and CNS remissions until March 2005, when he presented with fever, diarrhea and abdominal pain. He was scheduled for laparatomy with presumptive diagnosis of acute appendicitis. At exploratory laparatomy, a normal-looking appendix and multiple mesenteric lymphadenopathies were detected. The lymph node biopsies and appendectomy specimen revealed leukemic infil- tration (figure 2). His BM examination and CSF analysis were normal, and systemic re- induction chemotherapy was started. He was then put on maintenance chemotherapy till May, 2008. He was disease-free at the time of writing this report (mid 2011).
Leukemic infiltration of the appendix, which was first described over one hundred years ago by Askanazy,8 is recently more prevalent.
The results of autopsies have revealed a fre- quency of 10-40% in different studies.2 How- ever, leukemic involvement of the appendix
diagnosed antemortem has been rarely seen. In an extensive review of the literature using PubMed and Embase databases with appen- dix, leukemic infiltration, appendicitis and ap- pendectomy as keywords, about 20 cases of acute leukemia with the involvement of the appendix as the sole extramedulary organ, or accompanied by other organs including uterus, cervix, ovaries and other pelvic soft tissue
Both cases of the present study presented with signs and symptoms of acute abdomen, and were scheduled for laparatomy with pre-
sumptive diagnosis of acute appendicitis. They
were found to have leukemic infiltration of the appendix, while their BM was in complete re- mission. The relapses occurred late in the courses of the disease (3 and 7 years after initial diagnosis of ALL for case one and two, respectively).
Given that the patients, especially case 1, had multiple relapses in different organs in- cluding ovaries, bowel, intra-abdominal lymph nodes, liver and CNS, while their BM was in complete remission, the appendix should be considered as a sanctuary area like CNS, tes- tes and kidneys, in which the presence of leu-
kemic cells have been reported.1
We believe that the reason for the frequent relapses of the first case, despite the administration of appropriate chemotherapeutic agents, was the presence of dormant leukemic cells in sanctuaries. These cells could escape the effects of chemotherapy, and repopulate in other organs including ovaries, bowel and finally BM. It should be kept in mind that BM remission does not imply the complete clearance of leukemic cell from the body.3 Furthermore, the increasing survival of leukemia patients with the aid of modern chemotherapy regimens justifies further detection of extramedulary relapses even in unusual sites like the appendix.
The sign, symptoms and findings of the two
cases suggest that leukemic infiltration of the appendix should be considered in differential diagnosis of known cases of leukemia, who present with signs and symptoms of acute ap- pendicitis.
We would like to express our special thanks to Dr. N. Shokrpoor for editorial assistance and Mrs. M. Farahmandi for typing this manuscript.
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Figure 1: A microscopic section from appendiceal wall showing diffuse infiltration of leukemic cells (H&E ×250
Figure 2: leukemic infiltratin of appendix in case 2.