Intravascular Large B‐Cell Lymphoma Presenting With Urinary and Fecal Incontinence: A Case Report

ABSTRACT

Intravascular large B‐cell lymphoma (IVLBCL) can present with neurological symptoms such as urinary and fecal incontinence. A failure to recognize this association may delay the diagnosis, especially as imaging does not always reveal lesions. Clinicians must maintain a high index of suspicion for IVLBCL in patients with unexplained neurological symptoms, persistent fever, and elevated interleukin‐10, even when imaging is non‐specific. Early biopsy and multidisciplinary evaluation are essential for timely diagnosis and management.

Key Clinical Message

Intravascular large B‐cell lymphoma may present as isolated incontinence with normal neuroimaging. High suspicion and early biopsy are critical for timely diagnosis and management.

1. Introduction

Intravascular large B‐cell lymphoma (IVLBCL) is a rare form of extra‐nodal non‐Hodgkin lymphoma and is classified as a distinct subtype of diffuse large B‐cell lymphoma [1]. Pathologically, it is characterized by the proliferation and aberrant accumulation of malignant B lymphocytes within the lumina of small vessels, specifically capillaries and venules [2]. IVLBCL is highly aggressive and can affect multiple organ systems, with central nervous system (CNS) and skin involvement being the most common [3].

Neurological manifestations, which are highly heterogeneous, occur in approximately 35% of IVLBCL patients. These range from sensory and motor deficits, neuropathies, and aphasia to seizures and altered consciousness [4]. Notably, a significant proportion of patients (76%) exhibit signs related to the CNS, while 38% show involvement of the spinal cord and nerve roots during the disease course [5]. While presentations such as cauda equina or conus medullaris syndrome have been documented, the combined cauda equina–conus medullaris syndrome is exceedingly rare, with only two previously reported cases. Both patients presented with a characteristic triad of paraparesis, sensory disturbances, and sphincter dysfunction [6, 7].

We herein report a case of a 57‐year‐old male diagnosed with IVLBCL, whose predominant and presenting symptoms were isolated urinary and fecal incontinence, accompanied by negative spinal magnetic resonance imaging (MRI), hemophagocytic syndrome (HPS), and extremely elevated interleukin‐10 (IL‐10) levels, underscoring this unusual clinical presentation of the disease.

2. Case History/Examination

A 57‐year‐old Chinese man was admitted with a four‐month history of persistent fever and more than 1 month of progressive urinary and fecal incontinence and bilateral lower limb numbness and swelling. There was no hemiplegia nor cognitive dysfunction, and there was no prior history of neurologic disorders nor connective tissue disease. On examination, he had bilateral pitting edema of the lower extremities and numerous telangiectasias on erythematous upper abdominal skin. His lower limb strength was impaired (level 4), while upper limb strength was normal. Babinski sign was positive bilaterally, with no plane of paresthesia.

Laboratory tests revealed anemia (hemoglobin 76 g/L), thrombocytopenia (platelets 30 × 10⁹/L), hypoalbuminemia (albumin 15 g/L), and markedly elevated serum lactate dehydrogenase (LDH, 855 U/L), ferritin (1,728 ng/mL), and cytokines (IL‐10 > 1,000 pg/mL, with a normal reference value of < 9.1 pg/mL). Cerebrospinal fluid (CSF) analysis revealed a mildly increased protein of 0.7 mg/dL, but cytology was normal. MRI of the lumbar and sacral spine demonstrated mild disc bulging at L3‐S1, but no compressive lesions (Figure 1A). There was no evidence of intracranial pathology on head MRI, and Positron Emission Tomography‐Computed Tomography (PET‐CT) did not reveal abnormalities except mild splenomegaly.

FIGURE 1.

(A) MRI of the lumbar and sacral spine showing mild disc bulging at L3‐S1 but no compressive lesions; (B) Atypical large lymphoid cells within the lumina of small blood vessels (HE staining×400); (C) CD20‐positive neoplastic lymphoid cells (×400); (D) Tumor cells entirely confined within CD34‐stained vascular lumina (×400).

3. Differential Diagnosis, Investigations, and Treatment

The initial suspicion was infectious disease; however, multiple blood and urine cultures, cerebrospinal fluid metagenomic next‐generation sequencing, cytomegalovirus/Epstein–Barr virus (EBV) Deoxyribonucleic Acid (DNA) detection, and tuberculosis and fungal‐related screenings were all negative, and empirical antibiotic treatment had no effect, thus ruling out infectious etiologies. Due to cytopenia, persistent fever without evidence of infectious or immunologic disease, persistently elevated serum LDH and cytokine levels, and the rapid development of hemophagocytic syndrome after admission to our hospital, intravascular lymphoma was suspected. To confirm this, random cutaneous biopsies were taken, which revealed CD20‐positive neoplastic lymphoid cells within the small vessels of the deep dermis and subcutaneous fat Figure 1B–D, securing a diagnosis of intravascular large B‐cell lymphoma (IVLBCL). Immunohistochemical staining showed Paired box gene 5 (PAX‐5) (+), B‐cell lymphoma 2 (Bcl‐2) (90%+), B‐cell lymphoma 6 (Bcl‐6) (60%+), multiple myeloma oncogene 1 (MUM‐1) (90%+), and a nuclear antigen Ki‐67 (Ki‐67) proliferation index of 90%; tumor protein p53 (p53) was expressed in wild‐type. CD31 and CD34 highlighted vascular involvement. CD3, CD5, and CD10 were negative. Epstein–Barr virus‐encoded RNA (EBER) in situ hybridization was negative. The patient was discharged with a corticosteroid pre‐phase followed by R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. Treatment restored bowel and bladder continence, and his fever settled.

4. Outcome and Follow‐Up

The patient was followed up regularly at the Department of Hematology and completed a total of 7 cycles of the R‐CHOP. During the treatment course, serum IL‐10 levels were monitored repeatedly; the level first decreased to the lower limit of the normal range and then rose again to 28.6 pg/mL, suggesting an increased risk of early disease recurrence. Six months after the completion of initial treatment, the patient presented with fever again, accompanied by a significant increase in serum IL‐10 level. A repeat PET‐CT scan confirmed disease recurrence.

5. Discussion

IVLBCL is a rare large B‐cell lymphoma characterized by the proliferation of neoplastic cells within the lumina of small blood vessels. It commonly involves the nervous system, manifesting as dementia, stroke‐like episodes, focal deficits, multiple intracranial lesions, or encephalopathy with cognitive deterioration [8]. However, it is rare to present with fecal and urinary incontinence, which, in the absence of imaging abnormalities, makes prompt diagnosis challenging. Additionally, the lack of typical lymphadenopathy and specific tumor markers further increases clinical diagnostic difficulty [9], while serum cytokine detection provides a new approach for diagnosis and disease monitoring.

According to the World Health Organization classification, IVLBCL has classic, hemophagocytic syndrome‐associated, and isolated cutaneous subtypes, plus Asian and Western variants by clinical and geographical features. The Asian variant mainly involves liver, spleen, and bone marrow (often with HPS), while the Western variant tends to involve skin and CNS [10]. The core of this case is its unique phenotype: Isolated urinary/fecal incontinence as the initial neurological manifestation, normal spinal MRI, and HPS with IL‐10 > 1,000 pg/mL, enriching the understanding of Asian‐type IVLBCL heterogeneity.

IL‐10 is a characteristic cytokine secreted by IVLBCL tumor cells, with its diagnostic and monitoring value verified by this case and Zhang et al.'s (2020) cohort study [11]. With a cut‐off value of 95.65 pg/mL, it has 80% sensitivity and 100% specificity for IVLBCL. Its dynamic changes correlate with treatment response, as shown by the “> 1,000 pg/mL (normal: 28.6 pg/mL)” trend of this case. Mechanistically, elevated IL‐10 reflects abnormal tumor proliferation and mediates immunosuppression. For differential diagnosis, IL‐10 is mostly < 200 pg/mL in infections (e.g., EBV infection, tuberculosis), rarely > 100 pg/mL in autoimmune diseases, but often a thousand‐fold elevated in IVLBCL [11].

There have been a few reports of IVLBCL with combined urinary and fecal incontinence, described as two main patterns. The first pattern was with cauda equina/conus medullaris syndrome seen as neuroforaminal narrowing of the lumbar spine on MRI. In a series of 24 IVLBCL cases presenting as cauda equina/conus medullaris syndrome, two had normal brain and spinal MRI, and eight had normal spinal MRI 42 days after symptom onset [12]. Its pathological basis is tumor cell infiltration of the cauda equina nerve roots or conus medullaris blood vessels, leading to local blood supply disorders. In the second pattern, IVLBCL presents with both peripheral and central nervous system involvement, initially as urinary and bowel incontinence mimicking encephalomyeloradiculoneuropathy. In this pattern, the disease directly affects the spinal cord and disrupts central neural pathways involved in urination and bowel control, such as the basal ganglia, sometimes with normal brain imaging [9]. Moreover, urinary and fecal continence can be influenced by indirect neural factors that may not be apparent on imaging, such as neuropathy secondary to partial denervation, pelvic floor weakness, chronic strain, or increased intra‐abdominal pressure [13].

As there are no specific pathognomonic neuroradiological findings for IVLBCL, relying solely on imaging for its diagnosis can be misleading. In our case, despite the absence of overt radiographic abnormalities to fully explain the incontinence, the constellation of significantly elevated LDH and IL‐10 levels, hyperinflammation, typical skin biopsy findings, and response to treatment is consistent with central or peripheral nervous system involvement with IVLBCL. The pathological mechanism may involve tumor cells selectively infiltrating small blood vessels in spinal autonomic nerve conduction pathways—mainly accumulating in capillary and venule lumina. When infiltration is limited to the autonomic nerve regulation area above the conus medullaris, only sphincter dysfunction occurs without obvious spinal parenchymal injury or signal changes. The conventional treatment for IVLBCL is mainly rituximab combined with chemotherapy; with the advancement of immunotherapy, Chimeric Antigen Receptor T‐Cell Immunotherapy has become an important option for this disease, and PET‐CT can be used to monitor treatment response, as supported by relevant literature [14].

This case has limitations: Lack of objective neurofunctional assessments (e.g., urodynamic examination, anal sphincter tone measurement) may affect judging neurological involvement details; short follow‐up requires further observation of long‐term prognosis and neurological sequelae. However, its unique phenotype and clinical experience provide important reference for identifying atypical IVLBCL, improving its clinical spectrum, and developing treatment strategies.

In conclusion, this case defines a unique position in the IVLBCL clinical spectrum by highlighting the rare Asian‐type phenotype: “negative MRI + isolated sphincter dysfunction + HPS + markedly elevated IL‐10.” As a core biomarker, IL‐10 is critical for differential diagnosis, treatment efficacy monitoring, and recurrence prediction. For patients with unexplained fever, cytopenia, and acute neurological symptoms (even with normal imaging findings), IVLBCL should be suspected, and timely IL‐10 testing and random skin biopsy are recommended.

Author Contributions

Yu He: conceptualization, writing – original draft. Liyunian Bai: conceptualization, writing – original draft. Yang Jiao: conceptualization, supervision, writing – review and editing.

Funding

This work was supported by the China Medical Board (Grant Nos. 20–384 and CMB–JYCXGG04). This research was funded by the China Medical Board (Grant Nos. 20–384 and CMB‐JYCXGG04).

Ethics Statement

Our study has been granted an exemption from review by the Ethics Review Board of Peking Union Medical College Hospital.

Consent

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Conflicts of Interest

This case report was previously posted as a preprint on Authorea (DOI: 10.22541/au.176440517.73366432/v1, URL: https://doi.org/10.22541/au.176440517.73366432/v1). The current version of the manuscript has been revised and updated from the preprint version for submission to the journal.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.