□ CASE REPORT □Giant Septic Lymphadenitis with Marked Gas Formation
Caused by Bacteroides fragilis in a Patient with Adult
T-cell Leukemia/lymphoma
Takeaki Tomoyose 1, Sawako Nakachi 1,2, Yukiko Nishi 1, Kazuho Morichika 1, Iori Tedokon 1,Keita Tamaki 1, Natsuki Shimabukuro 1,2, Taeko Hanashiro 1, Hironori Samura 3,Takuya Fukushima 4 and Hiroaki Masuzaki 1

Abstract
Adult T-cell leukemia/lymphoma (ATL) sometimes causes opportunistic infections. A 53-year-old woman
with systemic lymphadenopathies was diagnosed with ATL by inguinal lymph node biopsies and underwent
oral chemotherapy. Two months later, high grade fever, lower abdominal pain and lymphadenopathy recurred.
Computed tomography revealed the presence of lymphadenopathy with marked gas formation in the pelvic
lesion. Blood cultures were suggestive of septic lymphadenitis by Bacteroides fragilis (BF). This represents
the first demonstration of giant lymphadenitis with gas formation caused by BF in a patient with ATL. Notably, septic lymphadenitis is pivotal in the differential diagnosis of systemic lymphadenopathy in ATL.
Key words: adult T-cell leukemia/lymphoma, lymphadenitis, Bacterodes fragilis, gas formation(Intern Med 54: 2919-2922, 2015)(DOI: 10.2169/internalmedicine.54.4324)

Introduction
Adult T-cell leukemia/lymphoma (ATL) provokes a variety of opportunistic infections, especially Strongyloides stercoralis, Pneumocystis jiroveci, cytomegalovirus, Toxoplasma
gondii, Mycobacterium tuberculosis, Mycobacterium avium
complex and fungal infections (1). In patients with ATL, thedysfunction of infected T-cells sometimes causes a series ofopportunistic infections.
Bacteroides fragilis (BF) is an anaerobe, which usuallycolonizes the colon and female genital tracts. The major
types of anaerobic infection are localized in the tissues of
the intra-abdominal area, the pelvis, the skin, soft tissue, thepleuropulmonary region, and the female genital tract (2).
Anaerobic infections are often associated with tissue necrosis and abscess formation. However, anaerobic bacterial

lymphadenitis is rare. Therefore, to precisely diagnose pelvic
lymphadenopathy, we need to explore the possibility of bacterial lymphadenitis, malignancies, autoimmune lymphadenopathy and a variety of inflammatory diseases. After thediagnosis of malignant lymphoma, we sometimes fail to exclude the possibility of bacterial lymphadenitis, in the seeming absence of neutropenia. We herein report an extremelyrare case of pelvic lymphadenitis with gas formation caused
by BF in a 53-year-old Japanese woman with ATL.

Case Report
A 53-year-old Japanese woman represented systemic lymphadenopathy. Anti-human T-cell lymphotrophic virus type 1(HTLV-1) antibody was detected. A pathological investigation via a left inguinal lymph node open biopsy revealed thepresence of pleomorphic lymphoma cells which were CD4

１Division of Endocrinology, Diabetes and Metabolism, Hematology and Rheumatology, Second Department of Internal Medicine, Graduate
School of Medicine, University of the Ryukyus, Japan, ２Center of Bone Marrow Transplantation, Ryukyu University, Japan, ３Unit of Organ Oriented Medicine, Division of Digestive and General Surgery, First Department of Surgery, Graduate School of Medicine, University of theRyukyus, Japan and ４Laboratory of Immunohematology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, JapanReceived for publication October 20, 2014; Accepted for publication April 12, 2015
Correspondence to Dr. Takeaki Tomoyose, ttomoyos@ryudai2nai.com

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Figure 1. Abdominal CT on day 13 of the first cycle of CHOP
showed a lymph node with air bubble-like structures and two
cystic lymph nodes. The maximum size of the lymph nodes wasaround 6×5 cm.

positive and CD8 negative. The prevalence of the ATL cells
was over 5% in the peripheral blood. Based on the laboratory findings, the patient was diagnosed with acute-type
ATL. Her systemic lymphadenopathy exacerbated and theprevalence of ATL cells in peripheral blood reached around
20% after 5 months. The serum level of lactate dehydrogenase (LDH) was increased from 600 to 2,600 IU/L. Aftershe rejected treatment with intensive combination chemotherapy, because she did not have any symptoms (except forlymphadenopathy), we decided to initiate the administrationof oral combined chemotherapy, which included etoposideand prednisolone for 4 months. Three weeks after the initiation of oral combined chemotherapy, the patient’s lymphadenopathy was ameliorated and her level of serum LDH decreased from 2,600 to 1,200 IU/L. Her lymphocyte and ATL
cells decreased from 40 to 8% and 25 to 3%, respectively.
She appeared in the emergency service with high fever andleft lower abdominal pain, accompanied by a prominent tender mass in the area of the left lower abdomen. Her whiteblood cell (WBC) count was within the normal range, while
her neutrophil count was elevated (WBC count, 7.7×109/L;
neutrophils, 98%) without a left shift. Neither lymphocytes
nor ATL cells were detected. The serum levels of LDH andsoluble interleukin-2 receptor (IL-2R) were markedly elevated at 2,500 IU/L and 29,000 U/L, respectively. There wasno elevation of the patient’s C-reactive protein level. As
computed tomography (CT) revealed the presence of systemic lymphadenopathy, especially of the pelvic lymph
nodes, which were reminiscent of central necrosis without
infectious findings. Clinically, she did not present cellulitis
and the left inguinal site where lymph node biopsy was performed was stable. Because of the ATL progression, she wasreceived CHOP (cyclophosphamide 750 mg/m2 on day 1,doxorubicin 50 mg/m2 on day 1, vincristine 1.4 mg/m2 on
day 1 and prednisolone 60 mg/m2 on day 1-5). One week
after the chemotherapy, there was a marked improvement ofher systemic lymphadenopathy, however, the left lower abdominal pain continued. When her leukocyte count dropped

to 0.5×109/L, she developed a high fever with shivering. Cefepime was administered for febrile neutropenia. BF was detected in one of blood culture bottles. The antimicrobial susceptibility test showed resistance to 4th generation cephalosporins, but carbapenem, clindamycin, and quinolone sensitivity. We thus changed the antibiotic therapy to imipenem/
cilastatin, clindamycin, and levofloxacin combined with hyperbaric oxygen therapy. CT on day 13 of the first cycle of
CHOP detected three enlarged lymph nodes in the pelvic region (Fig. 1). The size of the largest one was 6×5 cm. Air
bubble-like structures were observed. Taken together withthe pathophysiological findings, she was diagnosed with BFinduced pelvic lymphadenitis and resultant sepsis. We attempted to aspirate and drain the lymphadenitis, but did notsucceed. The discharge was very limited and no bacteria
were detected in the culture. Her fever was reduced, but theinflammation of the three lymph nodes did not improve withantibiotics. She subsequently presented a severe headacheand vomiting. ATL cells were detected in her cerebrospinal
fluid, but no bacteria were found. Since her persistent headache was attributed to ATL-invasive meningitis, of anticancer drugs (methotrexate 15 mg, cytarabine 20 mg, and prednisolone 20 mg) were administered intrathecally, one monthafter the first cycle of CHOP. Two days after the IT administration of the anticancer drugs, the three swollen lymph
nodes were successfully removed (Fig. 2a). The resected
lymph nodes were not adhesive around the tissues and werecapsulated without rupture. The cut surfaces of extirpatedlymph nodes consisted mainly of solid necrotic tissues andmodest lymphoid tissues without a foul smell. The bacterial
and fungal cultures of the removed lymph nodes were negative. Pathologic examination of the lymph nodes revealed
necrosis and the presence of neutrophil-filled abscesses. ATL
cells were not detected (Fig. 2b). She was received a second
cycle of CHOP chemotherapy two months after the first cycle CHOP (Fig. 3). The pelvic lymphadenitis was not considered to have recurred during the subsequent chemotherapies, because she did not have persistent febrile abdominal
pain.

Discussion
The current patient was a case of ATL represented by
septic lymphadenitis with gas formation in the pelvic region
due to BF. In general, septic lymphadenitis caused by BF isdiagnosed by CT imaging of the lymph node gas formation
and blood culture. In the present case, there were two manifestations to be highlighted. First, the size of lymph nodes
in the lymphadenitis was extraordinarily large. Second, theinfection was provoked in a patient who was T-cell immunocompromised. It is noteworthy that certain groups ofimmunocompromised subjects, including patients with diabetes mellitus, the elderly, patients undergoing steroid treatment, patients with HIV-infection, and transplantation recipients sometimes experience infections in unusual anatomicalsites (3). An abscess is a unique biologic phenomenon re-2920

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bFigure 2. The analysis of the resected lymph nodes: (a) macroscopic findings; yellowish necroticfoci were noted on the cut surface of the nodes, (b) microscopic findings; the lymph nodes were necrotic with neutrophil-filled abscesses. ATL cells were not detected.

Figure 3. The representative findings on the CT. (a) The initial state, (b) after oral combined chemotherapy, (c) on emergency admission, (d) after CHOP therapy, and (e) after resection of the three affected lymph nodes.

flecting the combination of pathological processes and thehost’s defensive mechanisms. Within the fibrous capsule ofa well-formed abscess, bacteria and neutrophils coexist. The
animal models of intra-abdominal sepsis are employed toidentify cells responsible for abscess formation. Experimentswith αβ TCR knockout mice have suggested that T-cells
play a critical role in abscess formation in response to
BF (4).
A line of studies suggests that the activation of CD4positive T-cell and the resultant production of interleukin-17
play a critical role in the formation of abscesses caused by
BF (5). HTLV-1 infection suppresses the immunity of thehost and induces various types of opportunistic infections
such as Strongyloides stercoralis, Pneumocystis jirovecii, cytomegalovirus, Mycobacterium tuberculosis (1). Bacterial
pathogens of BF induce abscess formation by CD4 positiveT-cells and neutrophils (6). It should be noted that abscessformation is made not only by neutrophils but also by CD4
positive T-cells. It is likely that in the current case, the abscesses were formed in the lymph nodes for over 2 weeks,
because abscess formation requires a long period of time toinactivate T-cells and neutrophils through HTLV-1 infection
and chemotherapy. As the patient’s T-cell count was over0.2×109/L from day 7 of the first cycle CHOP, the abscessformation on CT was clarified on day 13 of the first cycle
CHOP. To our knowledge, the present case is the first demonstration of giant pelvic lymphadenitis with gas formation
caused by BF in a patient with ATL.
Common types of anaerobic infections occur through endogenous bacterial flora. Anaerobes are involved in infections of the intraperitoneal cavity, thoracic cavity, the female
genital organs, the skin/soft tissues, the nervous system(brain, epidural tissue and subdural tissue), the oral cavity
and the neck. A comprehensive knowledge of the common
sites of anaerobic colonization by anaerobes is critical to determine the pathogens as well as to estimate their routes ofinvasion. It has been shown that major sites of BF colonization include the colon, the oral cavity, the thoracic cavity,
the female genital organs, and the urological tract, but not
the skin. In accordance with this notion, the major origins of
BF bacteremia are considered to be the gastrointestinal tract,
the female genital tract, the skin/soft tissue, the urologicaltract, and the respiratory tract (7). Without the occurrence ofcellulitis, it is considered unlikely that an inguinal open biopsy caused the pelvic lymphadenitis on the same side as it
was performed. Furthermore, the current patient presented
no other infectious signs and symptoms.
The predisposing factors for anaerobic bacteremia include
malignant neoplasms, hematologic disorders, transplantationof organs, recent gastrointestinal or obstetric surgery, intestinal obstruction, diabetes mellitus, post-splenectomy, the useof cytotoxic agents or corticosteroids, and the presence of anundrained abscess (8). Our patient had multiple risk factors
including hematological malignancy, post chemotherapy, andthe use of corticosteroids. However she did not have theother major risk factors, especially diabetes mellitus, intestinal obstruction, or HIV infection.
BF is often isolated not only from pus secretions, puncture fluids, and dialysis fluids but also from blood. Anaerobic blood culture-positive patients sometimes have underly-2921

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ing diseases included malignant tumors, gastrointestinal/hepatobiliary diseases, and surgical complications (8). Although we could not identify ATL cells nor BF in the resected lymph nodes, it crucial to consider the possibility ofopportunistic infections by BF in the differential diagnosisof lymphadenopathy in patients with ATL.
The authors state that they have no Conflict of Interest (COI).
Financial Support
This work was supported in part by the Project of Establishing
Medical Research Base Networks against Infectious Diseases in
Okinawa (2012-2014), the Takeda Science Foundation (Specified
Research Grant: 2010-2013), and the project “Establishing a research hub toward the development of an intellectual cluster in
Okinawa Prefecture, Japan” (2011-2014).

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Ⓒ 2015 The Japanese Society of Internal Medicine
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