Lymphoma-associated deep vein thrombosis mimicking cellulitis in an elderly patient with diabetes: A case report

Abstract

BACKGROUND

Cellulitis is a common bacterial skin and soft tissue infection. Misdiagnosis of cellulitis and its mimics may lead to unnecessary antibiotic use and surgical intervention.

CASE SUMMARY

We report the case of an elderly patient with diabetes mellitus, hypertension, chronic kidney disease, and chronic obstructive pulmonary disease who presented with right leg swelling and was initially diagnosed with cellulitis. Further evaluation revealed a large abdominal follicular lymphoma encasing the aorta and inferior vena cava, associated with deep vein thrombosis of the right common femoral vein.

CONCLUSION

In elderly patients with diabetes who present with persistent leg ulcers and edema, infection is often presumed while thrombosis may be overlooked. A detailed history and thorough physical examination are essential to distinguish cellulitis from its mimics.

Key Words: Lymphoma; Deep vein thrombosis; Cellulitis; Venous ulcer; Diabetic foot ulcer; Case report

Core Tip: This case highlights an unusual cellulitis mimic in an elderly diabetic patient with a chronic nonhealing leg ulcer and progressive unilateral leg swelling. Although initially treated as cellulitis, further evaluation revealed deep vein thrombosis of the right common femoral vein caused by massive abdominal follicular lymphoma encasing the inferior vena cava and iliac vessels. The resulting venous obstruction led to chronic venous insufficiency and ulceration, contributing to delayed wound healing and unnecessary antibiotic treatment and surgical intervention. In elderly patients with persistent unilateral edema and nonhealing ulcers, clinicians should consider deep vein thrombosis, malignancy-related venous obstruction, and other cellulitis mimics.

INTRODUCTION

Cellulitis is a common bacterial infection of the skin characterized by poorly demarcated erythema, edema, warmth, and tenderness. However, approximately one-third of patients initially diagnosed with cellulitis are ultimately found to have alternative conditions[1-4]. Misdiagnosis of cellulitis and its mimics can lead to unnecessary antibiotic therapy and surgical intervention.

The conditions most commonly mistaken for cellulitis include eczema/contact dermatitis, lymphedema and chronic venous insufficiency-related stasis dermatitis or lipodermatosclerosis (Table 1). Deep vein thrombosis (DVT) may also be difficult to distinguish from cellulitis, as it can present with unilateral lower extremity edema accompanied by mild warmth, erythema, and tenderness. The presence of DVT risk factors in the patient’s history should raise clinical suspicion, particularly active malignancy or recent extremity immobilization.

Table 1 Non-infectious causes of cellulitis mimics.

Venous/lymphantic diseases	Allergic dermatitis/eczema	Rheumatologic diseases/arthritis	Malignancy associated disorders
(1) Deep vein thrombosis (phlegmasia cerulea dolens); (2) Chronic venous insufficiency; (3) Venous ulcer; (4) Stasis dermatitis; (5) Lipodermatosclerosis; (6) Superficial thrombophlebitis; (7) Lymphedema; (8) Erythromelalgia/erythermalgia; and (9) Calciphylaxis	(1) Asteatotic eczema; (2) Contact dermatitis; (3) Fixed drug eruption; (4) Eosinophilic cellulitis (Wells’ syndrome); (5) Urticaria, Angioedema; and (6) Insect bites, foreign body reaction, Injection reaction	(1) Gout, pseudogout; (2) Rheumatoid arthritis, spondyloarthropathy; (3) Adult-onset Still’s disease; (4) Vasculitis; (5) Familial mediterranean fever; (6) Panniculitis, erythema nodosum/erythema induratum; (7) Tenosynovitis; (8) Sarcoidosis; (9) Pyoderma gangrenosum; and (10) Popliteal (Baker’s) cyst	(1) Carcinoma erysipeloides; (2) Subcutaneous panniculitis-like T cell lymphoma; (3) Paget’s disease; (4) Sweet syndrome; and (5) Radiation recall

Here, we report the case of an elderly patient with non-Hodgkin lymphoma-associated right leg DVT caused by massive lymphadenopathy encasing the aorta and inferior vena cava, initially presenting as lower extremity cellulitis.

CASE PRESENTATION

Chief complaints

An 80-year-old man was admitted for a nonhealing wound following a traffic accident and progressive swelling of the right leg for 1 month.

History of present illness

The patient was initially diagnosed with cellulitis in the emergency department and empirically treated with oxacillin. However, DVT was also suspected because the degree of ipsilateral leg edema could not be fully explained by cellulitis alone.

History of past illness

The patient had a history of type 2 diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease and chronic obstructive pulmonary disease, all under regular medical treatment.

Personal and family history

No significant personal or family history was reported.

Physical examination

Physical examination revealed right leg edema with a nonhealing wound. In addition, left supraclavicular lymphadenopathy and splenomegaly were noted on palpation.

Laboratory examinations

Laboratory testing showed normal antithrombin III, protein C, protein S, and von Willebrand factor activity, with no evidence of antiphospholipid antibodies[5].

Imaging examinations

Peripheral venous Doppler ultrasonography demonstrated near-total occlusion of the right common femoral vein (Figure 1A). Abdominal magnetic resonance imaging (MRI) was performed to evaluate for a pelvic mass contributed to thrombosis formation and revealed a large mass involving the para-aortic, paraspinal, and right pelvic regions, encasing the abdominal aorta, inferior vena cava, and right iliac vessels (Figure 1B).

Figure 1 Imaging examinations. A: Doppler showed total occlusion of the right common femoral vein; B: Magnetic resonance imaging showed a huge mass over the paraaortic, paraspinal and right pelvic region encasing abdominal aorta, inferior vena cava, right iliac artery and vein.

MULTIDISCIPLINARY EXPERT CONSULTATION

Lymphoma was suspected, and an excisional biopsy of the left supraclavicular lymph node confirmed grade 2 B-cell follicular lymphoma (Figure 2). Bone marrow examination further demonstrated bone marrow involvement. Because of the persistent nonhealing ulcer, the patient underwent fasciectomy, debridement and skin grafting performed by the plastic surgery team (Supplementary Figure 1).

Figure 2 Pathology of a left supraclavicular lymph node excisional biopsy. Follicular lymphoma, grade 2 (hematoxylin-eosin, 400 ×).

FINAL DIAGNOSIS

Massive abdominal grade 2 follicular B-cell lymphoma encasing the abdominal aorta and inferior vena cava, associated with DVT of the right common femoral vein.

The chronic nonhealing wound was determined to be a venous ulcer secondary to lymphoma-associated DVT and chronic venous insufficiency. The thrombosis was considered to be primarily caused by tumor encasement and compression of the inferior vena cava and iliac vein.

TREATMENT

The patient initially refused further treatment and returned 6 months later with progressive enlargement of the left supraclavicular lymphadenopathy and a 30-kg body weight loss.

A positron emission tomography scan was performed for staging and demonstrated findings consistent with lymphoma involving the head and neck, mediastinal, abdominal/pelvic, bilateral inguinal, and axillary regions, with additional involvement of the bone marrow and spleen (Figure 3).

Figure 3  Positron emission tomography showed lymphoma in head and neck, mediastinum, abdominal/pelvic regions, bilateral inguinal and axillary regions, as well as bone marrow and spleen involvement.

The patient received one cycle of the cyclophosphamide, vincristine, and prednisone regimen, followed by six cycles of rituximab, cyclophosphamide, vincristine, and prednisone chemotherapy. The tumor responded favorably to treatment[6].

OUTCOME AND FOLLOW-UP

Ultimately, the patient and his family elected to pursue hospice care because of his poor performance status. The overall-case timeline, from diagnosis through treatment, is shown in Figure 4.

Figure 4 Timeline of the overall diagnosis and treatment course. ER: Emergency room; DVT: Deep vein thrombosis; LN: Lymph node; BW: Body weight; PET: Positron emission tomography; COP: Cyclophosphamide, vincristine, and prednisone; R-COP: Rituximab, cyclophosphamide, vincristine, and prednisone.

DISCUSSION

Venous thromboembolism (VTE) is a clinically important complication in patients with malignancy and is particularly relevant for lymphoma. Elderly patients have a higher baseline risk of VTE, with incidence exceeding 1% per year[7]. In patients with lymphoma, the risk of VTE varies according to histologic subtype, disease burden, treatment phase, and patient-related factors. In aggressive and indolent lymphoma, the annual incidences of VTE have been reported as 4.2% and 1.4%, respectively; moreover, factors that have been found to be associated interpedently with increased VTE risk are diffuse large B-cell lymphoma, peripheral T-cell lymphoma, Hodgkin lymphoma, primary mediastinal B-cell lymphoma, advanced-stage disease, body mass index ≥ 30, constitutional symptoms, and doxorubicin-based chemotherapy[8]. Although follicular lymphoma is generally classified as an indolent lymphoma, the present case demonstrates that extensive tumor burden and anatomical vascular involvement may substantially increase thrombotic risk. In addition to systemic cancer-associated hypercoagulability, which may involve tumor-related activation of coagulation, inflammatory cytokines, endothelial dysfunction, platelet activation, and reduced mobility, local mechanical factors may also play a decisive role in thrombosis formation. For our patient, the thrombophilia workup provided no evidence of inherited or autoimmune thrombophilia; therefore, the DVT was deemed most likely to have been acquired and to be related to the combined effects of lymphoma-associated hypercoagulability and direct venous compression.

The anatomical relationship between the lymphoma and the venous system provides a logical explanation for the clinical progression in this patient. Abdominal MRI demonstrated a large para-aortic, paraspinal, and right pelvic mass encasing the abdominal aorta, inferior vena cava, and right iliac vessels. Such encasement can narrow the venous lumen, reduce venous flow velocity, and produce venous stasis in the ipsilateral lower extremity. According to Virchow’s triad, venous stasis, endothelial dysfunction, and hypercoagulability act together to promote thrombus formation. The right common femoral vein thrombosis in our patient can therefore be understood as the downstream consequence of impaired iliocaval venous drainage caused by a retroperitoneal lymphomatous mass. Once thrombosis had occurred, the venous outflow obstruction became further aggravated, resulting in sustained venous hypertension of the right lower extremity[9,10].

This sustained venous hypertension itself explains the subsequent development of chronic venous insufficiency and a nonhealing venous ulcer. In chronic venous insufficiency, elevated venous pressure is transmitted to the superficial venous and capillary systems. Increased capillary pressure then promotes leakage of plasma proteins and erythrocytes into the interstitium, leading to edema, hemosiderin deposition, leukocyte recruitment, and chronic inflammation. Fibrin cuff formation around capillaries, growth factor trapping, impaired oxygen diffusion, microcirculatory dysfunction, and tissue hypoxia further compromise skin nutrition and repair capabilities. When a local wound occurs, as in our patient, following trauma, the already compromised venous and microvascular environment then serves to impair granulation, epithelialization, and wound closure. Thus, our patient’s chronic leg ulcer was not merely a diabetic wound nor a persistent soft tissue infection but rather the final manifestation of a pathological sequence: Retroperitoneal lymphoma encasement of major veins, venous outflow obstruction, secondary DVT, chronic venous hypertension, chronic venous insufficiency, and intractable venous ulceration[11,12].

Retroperitoneal lymphomatous masses may also create diagnostic confusion because their presentations can mimic infectious, inflammatory, or vascular disorders. Bulky retroperitoneal lymphadenopathy may present with nonspecific systemic symptoms, abdominal or back discomfort, lower-extremity edema, renal dysfunction, or thrombotic events, depending on the structures compressed. When venous compression produces unilateral leg swelling, warmth, erythema, and tenderness, the presentation may closely resemble cellulitis. Conversely, when imaging shows vessel encasement or thrombosis, the underlying lymphoma may initially be overlooked in favor of a primary vascular diagnosis. The case presented herein, therefore, has educational value because it illustrates that cellulitis-like lower-limb inflammation may be the visible distal manifestation of an occult proximal malignant process.

The initial clinical differential diagnosis in our patient included cellulitis, DVT, and venous stasis-related changes. Cellulitis was clinically plausible because the patient had diabetes mellitus, a trauma-induced wound, leg swelling, and local inflammatory changes, all of which are common triggers for empirical antibiotic therapy. However, cellulitis alone did not fully explain the degree and persistence of unilateral edema, the chronic nonhealing course, nor the presence of systemic findings such as supraclavicular lymphadenopathy and splenomegaly. Venous stasis dermatitis and chronic venous insufficiency were also important considerations because they can present with erythema, edema, skin texture changes, pigmentation, scaling, and ulceration, and are among the most common noninfectious mimics of cellulitis[1-4]. DVT was appropriately suspected because the unilateral leg swelling was out of proportion to the local infection, prompting evaluation for a venous obstruction. Ultimately, Doppler ultrasonography confirmed the near-total occlusion of the right common femoral vein and subsequent abdominal MRI identified the bulky lymphoma encasing the inferior vena cava and iliac vessels, both of which were critical to establishing a correct diagnosis in this case.

Such misdiagnosis is a particular risk in elderly diabetic patients. Diabetes predisposes patients to skin breakdown, impaired wound healing, neuropathy, peripheral vascular disease, and recurrent soft tissue infection; consequently, clinicians may anchor prematurely on diabetic foot infection or cellulitis when erythema and ulceration are present. Moreover, in elderly patients’ pain may be blunted, symptoms may be nonspecific, and comorbidities such as chronic kidney disease, immobility, edema, or vascular disease may obscure a true underlying cause. Conventional diagnostic thinking may also overemphasize visible local skin findings while underemphasizing proximal venous obstruction, malignancy-associated thrombosis, and systemic signs such as lymphadenopathy, splenomegaly, unexplained weight loss, or failure to respond to antibiotics. Importantly, this case highlights the limitations of an infection-centered approach to chronic lower-extremity wounds and supports a more systematic diagnostic strategy.

CONCLUSION

When presumed cellulitis does not improve as expected, the diagnosis should be actively reconsidered. Persistent unilateral edema, disproportionate swelling, chronic or recurrent ulceration, poor response to antibiotics, absence of clear systemic infection, and the presence of malignancy-related clues should prompt examination by venous Doppler ultrasonography and when proximal obstruction is suspected cross-sectional imaging of the pelvis and abdomen. Early recognition of DVT and malignancy-related venous compression may prevent unnecessary antibiotic exposure and repeated surgical procedures, while facilitating timely oncologic evaluation and management. In elderly diabetic patients with chronic nonhealing leg ulcers, clinicians should therefore consider not only infection but also DVT, chronic venous insufficiency, malignancy-associated venous obstruction, and other cellulitis mimics.