A Rare Case of Cutaneous Diffuse Large B-cell Lymphoma Presenting as a Chronic “Infectious” Skin Ulcer
Cutaneous diffuse large B-cell lymphoma (DLBCL) usually manifests as papules, nodules, or plaques. A rare case of a patient with a chronic skin ulcer and signs and symptoms of infection, including fever and large amounts of yellow wound exudate, is presented.
Fifteen (15) months before diagnosis, a 43-year-old otherwise healthy man noted soreness without apparent cause in his upper chest and a palpable 2 cm x 2 cm focal lump. The patient developed frequent fevers, and the lump enlarged over time, producing purulent exudate. For 14 months, the patient was examined and treated at 5 hospitals, but biopsies, smears, cultures, and various types of nucleic acid testing were negative. Antibiotics to treat the suspected but nonclassified infection were ineffective. Ultimately, debridement and pathological examination of necrotic tissue from the deep sinus revealed DLBCL. The patient was provided chemotherapy, surgical debridement, and negative pressure wound therapy. Wounds started to reduce in size once chemotherapy was initiated. The wound was surgically closed with a split-skin graft, and the patient was discharged 93 days following admission to the authors’ facility. This case illustrates the possibility of cutaneous DLBCL in patients with chronic skin ulcers and infectious manifestation that do not respond to antibiotic therapy. Prompt deep tissue debridement and pathological examination of deep tissue will help confirm the presence of cutaneous DLBCL and guide required chemotherapy.
Chronic skin ulcers are a common complication of diabetes, peripheral vascular disease, infection, and neoplasia. Local ulcer care will be successful only if the underlying cause is correctly identified and medical steps are taken to reverse it. Diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, accounts for ~30% to 40% of non-Hodgkin’s lymphoma.1 Skin is the second most common site of extranodal non-Hodgkin B-cell lymphomas, with an estimated incidence of 0.3/100 000/year.2 Cutaneous DLBCL usually manifests as papules, nodules, or plaques; abscesses or ulcers develop only in rare cases.3 The authors’ review of the literature revealed few cases of B-cell lymphomas associated with cutaneous ulceration, and none of them presented as a chronic “infectious” abscess per the case reported herein. The purpose of this case study is to document the presentation of cutaneous DLBCL as a nonhealing wound with signs and symptoms of infection.
History. Mr. J, a 43-year-old otherwise healthy man (no underlying disease), was admitted to the authors’ facility, a large comprehensive hospital with 2900 beds, with a nonhealing ulcer on his left chest that was discharging purulent drainage. The patient had begun to feel soreness without apparent cause in his upper left chest 15 months earlier, and a focal lump (2 cm × 2 cm) without tenderness could be palpated. Approximately 1 month later, the mass gradually enlarged, and Mr. J experienced intermittent fever and was hospitalized successively in different hospitals where lymph node biopsy and ulcer exudate, as well as smears, microbial culture, acid-fast staining, and tuberculous/nontuberculous mycobacteria nucleic acid testing, were negative for bacterial or fungal infection.
Several pathological examinations of the wound and adjacent lymph nodes involving immunohistochemical staining and biopsy revealed vascular proliferation accompanied by the infiltration of inflammatory cells. After incision and drainage, Mr. J’s chest and neck wounds failed to heal but large amounts of yellowish exudate were present and samples were sent for microbiological cultures to look for possible bacteria or fungi, with negative results. Mr. J was treated successively with antibiotics including cephalosporin, quinolone, and antituberculosis drugs appropriate to the infectious manifestations but he still developed intermittent fever. A sterile gauze sponge was applied for drainage and the wound was dressed with gauze, foam, alginate, and silver dressings in succession; nothing brought about wound healing.
After approximately 14 months of treatment in 5 hospitals, Mr. J was transferred to the authors’ hospital. Mr. J was running an intermittent body temperature of 36.4˚ C to 38.5˚ C, his vital signs were stable, he was conscious, and the wound did not affect activities of daily living. He reported only mild pain from the chest wound according to visual analogue scale assessments, and he had no comorbidities. Wound exudate was sent for bacterial and fungal cultures multiple times and all returned negative. On day 5 of admission, thoracic and abdominal computed tomography (CT) examinations showed a left cervicothoracic abscess, splenic abscess, and right axillary lymph node enlargement. Splenic puncture and abscess drainage were performed under CT guidance. No bacteria or fungi were found in the drained fluid, and only inflammatory cells were detected in the pathological examination.
On day 11 of admission, bone marrow biopsy results showed active hematopoiesis with prominent myeloid hyperplasia and blood tests showed significantly elevated indicators of infection (white blood cell and neutrophil counts [27.42 x 109/L], C-reactive protein [185.59 mg/L], and erythrocyte sedimentation rate [107 mm/hour]). After anti-infection treatments (eg, penicillin, azithromycin, ceftazidime, imipenem, and metronidazole) were provided in succession in the appropriate dosage and according to the manufacturer instructions, the aforementioned indices did not change significantly. The yellowish exudate from the ulcer increased and sinus depth was 6 cm to 9 cm; neither improved after dressing changes (2 to 3 times every day) or use of sterile gauze sponges in the sinuses to drain the exudate (see Figure 1A).
On day 15 of admission, Mr. J was still experiencing intermittent fever and his blood pressure began to drop, indicating septic shock (lowest blood pressure was 79/42 mm Hg). After antishock therapy with noradrenalin, Mr. J’s blood pressure returned to normal. The following day, the wounds were debrided under general anesthesia and intraoperative exploration revealed deep chest sinuses reaching to the ribs and parietal pleura, with a large amount of cheese-like necrotic tissue packed on the sinus wall. Negative pressure wound therapy (NPWT) was initiated in the operating room and continuously applied at a setting of -100 mm Hg for 6 to 7 days. Mr. J had no fever after the surgery, and the infection indexes gradually decreased to normal. Tissue culture showed no growth of bacteria or fungi.
Diagnosis. Pathological examination of sampled tissues suggested lymphohematopoietic malignancies in the necrotic tissue deep inside the chest wall and lymphoid tissues of the left neck (see Figure 2). Taking into account the morphological and immunological phenotypes and a history of long-term skin ulcers, the diagnosis of DLBCL associated with chronic inflammation was confirmed. A positron emission tomography-CT (PET-CT) examination revealed increased fluorodeoxyglucose (FDG) uptake in the cervicothoracic and right axillary lymph nodes and spleen, indicating invasive lymphoma.
Treatment. Mr. J was provided rituximab, vindesine, epirubicin, cyclophosphamide, and prednisolone (R-CHOP) chemotherapy for 7 days, repeated every 3 weeks in the department of hematology. After 3 rounds of chemotherapy, a follow-up PET-CT scan showed FDG uptake in cervicothoracic soft tissues was reduced significantly in both intensity and scope and the nodular FDG uptake in the spleen also decreased significantly. During the period of chemotherapy, Mr. J’s left cervicothoracic wound gradually decreased in size; deep sinuses in the wounds closed after several surgical debridements and NPWT treatments.
Approximately 11 weeks after admission, the left thoracic wound was debrided and a split-skin graft was applied, after which the cervicothoracic wound healed (see Figure 1B). Mr. J was discharged on day 93 after admission.
In this case, the patient had received long-term anti-infection treatments in different hospitals because infection is still a primary consideration when a patient presents with long-term fever, heavy wound exudate, significantly increased inflammatory indices, an early-stage wound biopsy indicating only infiltration of inflammatory cells, and long-term administration of systemic antibiotics have a negligible therapeutic effect. After Mr. J underwent surgical removal of necrotic tissue from his deep lesions, pathological examination led to an unexpected diagnosis of DLBCL. After R-CHOP chemotherapy, the disease was controlled and wounds started to decrease in size. This case suggests DLBCL should be considered in patients with prolonged nonhealing ulcers with local or systemic manifestations of infection that fail to respond to anti-infection therapy.
Prompt treatment (ie, once the patient’s symptoms or clinical examinations are associated with the wounds) if the wound is unresponsive to standard care surgical procedures for the removal of necrotic tissue from deep lesions, along with pathological examination, can help confirm the etiology. The authors believe the yellowish exudate from the wound yielded negative microbiological culture results because it was not the result of an infectious process but rather liquefaction of the lymphoma. The authors’ theory cannot be confirmed because, to the best of their knowledge, this is the first documented case of a cutaneous DLBCL presenting as a chronic skin ulcer with infectious manifestation.
DLBCL can be divided into germinal center cell-like (GCB) and non-GCB subtypes for prognosis assessment according to immunohistochemistry results.4 In the current case, the multiple myeloma oncogene 1 (MUM1), CD138, C-myc, and PAX-5 all were positively expressed. MUM1 and CD138 usually are used as non-GCB subtype markers, while C-myc and PAX-5 also indicate poor prognosis.5 In addition, PET-CT scans not only improve the accuracy of diagnosis of DLBCL but also help assess treatment efficacy. Numerous studies6,7 reported patients with a negative scan showed both a better progression-free and a better overall survival rate; these results helped physicians make further treatment decisions. However, the PET scan’s prognostic value has not been consistently proven to surpass the prognostic potential of the International Prognostic Index6,7 (IPI), a clinical tool developed by oncologists to help predict the prognosis of patients with aggressive non-Hodgkin’s lymphoma. The IPI assigns 1 point for each of the following risk factors: age >60 years; stage III or IV disease; elevated serum lactate dehydrogenase; Eastern Cooperative Oncology Group/Zubrod performance status (a measure of patient cancer status) of 2, 3, or 4; and >1 extranodal site. The sum of the points allotted correlates with the following risk groups: low risk (0–1 points) — 5-year survival of 73%; low-intermediate risk (2 points) — 5-year survival of 51%; high-intermediate risk (3 points) — 5-year survival of 43%; high risk (4–5 points) — 5-year survival of 26%. The IPI was not applied in this case. However, according to the assessment standards, had the IPI been applied, it would indicate low-intermediate risk. Of note, either PET or IPI is valuable for prognosis of DLBCL, which does not affect the therapeutic measures.
Ideally, surgery on patients with DLBCL should be limited to a biopsy to establish the correct histological diagnosis, leaving the treatment with curative intent to radiotherapy and chemotherapy.8 In this case, the patient received several surgical debridements combined with NPWT drainage along with chemotherapy. The deep sinuses gradually closed, and the ulcer healed after split-skin grafting.
The possibility of cutaneous DLBCL should be considered in patients with chronic skin ulcers and infectious manifestation that do not respond to antibiotic therapy. Early debridement and pathological examination of tissues from the deep lesion can help determine an accurate diagnosis and prompt treatment that includes surgical debridement and skin grafting after chemotherapy to close ulcers caused by DLBCL.
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Potential Conflicts of Interest: This project was supported by National Natural Science Foundation of China (81571900).
Dr. Song is an attending doctor, Dr. Gong is a laboratorian, and Dr. Yan and Dr. Zhang are chief physicians, State Key Laboratory of Trauma, Burns, and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing, China. Please address correspondence to: Jiaping Zhang, MD, Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing, China; email: firstname.lastname@example.org.