Splenic Marginal Zone Lymphoma as a Vascular-Appearing Mass in a Patient With Sustained Virologic Response to Hepatitis C Therapy

Introduction

Marginal zone lymphoma is an indolent subtype of non-Hodgkin lymphoma, accounting for 7% of all mature non-Hodgkin lymphomas. Splenic marginal zone lymphoma (SMZL) is an even rarer subtype, accounting for 20% of marginal zone lymphomas [1,2]. It is associated with chronic hepatitis C virus (HCV) infection [1], and imaging features usually demonstrate massive splenomegaly rather than a focal mass due to the typical diffuse global infiltration of the splenic red pulp and marginal zones [3]. Following the advent of highly effective antiviral therapies, viral eradication is now recognized as an effective lymphoma treatment that can induce disease regression in HCV-associated cases.

Focal splenic lesions with vascular enhancement patterns are more associated with vascular tumors such as sclerosing angiomatoid nodular transformation (SANT) or hemangiomas [4,5]. Presentation of SMZL as a focal splenic mass is rare and poses a diagnostic challenge. Distinguishing benign vascular lesions from malignant mimics is clinically critical, as an inaccurate diagnosis can drastically alter management from safe observation to unnecessary radical surgery or delayed systemic therapy. We report a highly atypical case of SMZL presenting as a vascular-appearing focal splenic mass that demonstrated delayed interval enlargement despite successful HCV eradication. By exploring the diagnostic pitfalls and atypical imaging features of this case, we aim to increase clinical awareness, prevent potential misdiagnoses, and highlight the critical need for clinicopathologic correlation when evaluating indeterminate splenic lesions.

Case Report

A 60-year-old man with no significant past medical history presented with generalized pruritic rash and change in bowel habits of a few weeks. He denied abdominal pain, gastrointestinal bleeding, weight loss, fever, or other constitutional symptoms. There was no history of trauma or recent travel. Physical examination was unremarkable, with no abdominal tenderness, palpable mass, or clinically appreciable splenomegaly. There was also no peripheral lymphadenopathy.

Initial serum hematology and biochemistry performed in the emergency department showed a hemoglobin level of 16.2 g/dL, leukocytosis of 16.02×109/L, and a normal platelet count (182×109/L). Subsequent biochemistry lab values were also within normal range. Liver function tests demonstrated mildly elevated transaminase levels [alanine aminotransferase (ALT) 62 U/L, aspartate aminotransferase (AST) 60 U/L] with borderline serum albumin (37 g/L), although these normalized on subsequent follow-up visits. Lactate dehydrogenase and β2-microglobulin were not routinely drawn at initial presentation. Bedside abdominal ultrasound demonstrated a hypoechoic splenic lesion, without associated free fluid, splenic hematoma, or features of acute infarction. The patient was admitted for further evaluation.

Contrast-enhanced computed tomography (CT) of the abdomen and pelvis performed during admission to evaluate the splenic lesion showed a 3.1×3.3-cm hypodense splenic lesion (Figure 1). This was deemed to be indeterminate, with differential causes of infection or neoplasm raised. Imaging follow-up was recommended. Incidental morphologic features of hepatic cirrhosis were also seen on the CT scan. There was no lymphadenopathy or evidence of extrasplenic disease. The patient was subsequently discharged with outpatient gastroenterology follow-up.

Further evaluation by gastroenterology included additional laboratory investigations, which showed normal tumor markers. Viral serology revealed chronic HCV infection, genotype 1A, with an initial viral load of 6.82 log IU/mL. Hepatitis B serology indicated immunity. Antiviral therapy with sofosbuvir/velpatasvir was initiated and completed by January 2020. Sustained virologic response was achieved, with hepatitis C viral load remaining undetectable on follow-up assessments, including post-treatment at 24 weeks and on subsequent surveillance testing.

Serial imaging surveillance with ultrasound of the hepatobiliary system was performed at approximately 6-month intervals from August 2019 to December 2020, demonstrating splenic lesion stability. On surveillance ultrasound performed in June 2021, approximately 18 months following documentation of undetectable hepatitis C viral load, there was a sudden interval increase in size of the lesion, prompting further evaluation (Figure 2).

A dedicated multiphasic CT of the abdomen confirmed enlargement of the splenic lesion from 3.1×3.3 cm to 5.7×5.7 cm. The lesion was hypoenhancing relative to the background splenic parenchyma on the arterial phase (Figure 3A), with progressive peripheral-to-central enhancement. On delayed phase imaging, there was central hypodensity, while the peripheral rim of the lesion was isodense relative to the non-lesional splenic parenchyma (Figure 3B). No wedge-shaped hypodensity to suggest an infarction, perisplenic collection, or hematoma was identified. The remainder of the splenic parenchyma demonstrated relative homogeneity, and the splenic artery and vein were patent.

Due to the sudden interval growth and the absence of a classical imaging pattern to suggest a specific diagnosis, the case was discussed with a multi-disciplinary tumor board. Specifically, a benign vascular lesion such as a SANT was heavily considered given the enhancement characteristics. However, a primary splenic sarcoma or lymphoma could not be entirely excluded. The multidisciplinary tumor board concluded that the rapid enlargement predisposed the patient to a high risk of spontaneous rupture and bleeding, and was concerning for sinister pathology. As a primary splenic malignant process could not be definitively excluded, surgical resection was recommended instead of percutaneous biopsy. This decision took into account the bleeding risk in the setting of portal hypertension (which was seen as esophageal varices on upper gastrointestinal endoscopy) and uncertain diagnostic yield. Preoperative staging with CT of the thorax did not show any metastatic disease.

An elective laparoscopic splenectomy was performed following a pre-operative vaccination protocol. The patient had an uncomplicated postoperative recovery and was discharged with a long-term vaccination surveillance plan. The patient was also referred for routine hematology surveillance. The gross specimen of the spleen weighed 390 g, corresponding to mild to moderate splenic enlargement, and contained a focal mass measuring 6 cm.

Histopathological examination of the splenectomy specimen showed SMZL with extensive organized infarction and associated epithelioid granulomatous reaction (Figure 4). The white pulp demonstrated a characteristic biphasic appearance, with expansion of the marginal zone surrounding a relatively darker inner mantle zone, in keeping with SMZL (Figure 5A). Additional stains and molecular testing for infectious organisms, including Mycobacterium tuberculosis, were negative. No features of aggressive transformation were identified. Immunohistochemical analysis also confirmed the diagnosis, demonstrating marginal zone expansion and CD20-positive B-cell populations (Figure 5B–5D).

Discussion

DIFFERENTIAL DIAGNOSIS:

There remains a diagnostic challenge when patients present with focal splenic lesions demonstrating vascular or progressive enhancement, as both benign vascular lesions and malignant processes may exhibit overlapping imaging features, as in the present case. Distinguishing among these entities based on imaging alone can be difficult, even with multimodality assessment, and may necessitate surgical resection for definitive diagnosis.

Benign vascular lesions of the spleen represent an important consideration in this setting, as they may demonstrate variable signal characteristics and enhancement patterns on magnetic resonance imaging (MRI) that overlap with malignant entities. To illustrate this diagnostic dilemma, Table 1 compares the classical features of these entities against the specific findings observed in our case that caused diagnostic confusion. Additionally, a companion image of a histologically proven benign splenic hemangioma (Figure 6) is included to demonstrate vascular enhancement features which remained radiologically indeterminate, highlighting the difficulty in differentiating such benign lesions from the malignancy, similar to our case.

Primary splenic malignancy, including lymphoma or rare vascular sarcoma, must also be considered in the differential diagnosis of a focal splenic lesion demonstrating interval enlargement and indeterminate enhancement characteristics.

In this case, imaging findings alone were insufficient to reliably distinguish between benign and malignant etiologies, reflecting the inherent overlap in appearance of focal vascular-appearing splenic lesions. Temporal evolution on follow-up imaging and integration of clinical context was therefore important in guiding further management.

Conclusions

SMZL may, rarely, present as a focal splenic mass and mimic benign vascular lesions on imaging, even in the absence of marked splenomegaly. When indeterminate splenic lesions demonstrate interval growth, particularly in patients with relevant clinical risk factors, reliance on imaging alone may be insufficient. In such scenarios, multidisciplinary discussion and consideration of histological confirmation are essential to establish a definitive diagnosis and avoid delays in management. Clinicians should maintain a low threshold for diagnostic splenectomy in patients with rapidly enlarging, indeterminate splenic lesions, even if they have achieved a sustained virologic response for HCV. Future clinical protocols should prioritize the development of advanced functional imaging criteria or validated molecular biomarkers to better differentiate atypical SMZL from benign vascular mimics pre-operatively.