Unique case of atraumatic splenic rupture in a patient with chronic lymphocytic leukaemia with Richter’s transformation

Abstract

Though rare, atraumatic rupture of the spleen can be a complication in certain leukaemias and lymphomas. We present a unique case of atraumatic rupture of the spleen in a patient with chronic lymphocytic leukaemia. The patient presented to the emergency department with abdominal pain; he had been on ibrutinib therapy but stopped taking the medication abruptly 6 days prior. On evaluation, he was found to have a ruptured spleen with a haemoperitoneum. Pathology of the excised spleen showed infiltration of the spleen with hyperproliferated CD5+ intermediate-to-large cells, consistent with B-cell lymphoma and favouring Richter’s transformation. There are only a few available reports of patients with similar presentations identified in our literature review.

Background

The most common cause of rupture of the spleen is trauma, which can be an immediate manifestation or a delayed presentation following blunt abdominal trauma.¹ Atraumatic rupture of the spleen can be spontaneous or pathological.² Several aetiologies like neoplasms, infections, inflammations and medications have been linked to splenic rupture.³ Splenic rupture is a clinical diagnosis confirmed by a CT scan or intraoperatively. The mortality rate of atraumatic splenic rupture is around 12.2%.³ While pathological rupture of the spleen is a well-known complication of infectious mononucleosis and malaria, it is seldom associated with haematological malignancies.¹ We report a patient with chronic lymphocytic leukaemia (CLL) on ibrutinib therapy presenting with abdominal distention and pain after abruptly stopping the medication. His CT scan revealed a subcapsular splenic haematoma and a haemoperitoneum. Laparotomy revealed splenic rupture, and the histopathology was consistent with Richter’s transformation (RT) of CLL to CD5+ large cell lymphoma.

Case presentation

A 69-year-old man with a medical history of CLL on ibrutinib therapy, non-ischaemic cardiomyopathy, heart failure with reduced ejection fraction, hypertension, hyperlipidaemia and tobacco dependence presented to the emergency department (ED) with a 1-week history of vague abdominal pain, distension and a 3-day history of watery diarrhoea.

The patient was initially diagnosed with CLL 10 years prior to presentation by peripheral blood flow cytometry consistent with CD5, CD19, CD19 lambda, CD20, CD23, CD38 positive and CD10 negative B cell population. Fluorescence in situ hybridisation (FISH) studies and cytogenetics of the peripheral blood showed positivity for trisomy 12. Two years later, a CT of the chest, abdomen and pelvis showed bulky adenopathy in both axillae, enlarged lymph nodes in the mediastinum, paraaortic, pancreatic and right inguinal lymph nodes, along with significant splenomegaly. He received two cycles of rituximab for extensive bulky lymphadenopathy and achieved clinical remission. Five years after diagnosis, he was noted to have an increase in White Blood Cells (WBC)counts along with painful adenopathy. He was then started on ibrutinib at a reduced dose of 140 mg as the patient reported of joint swelling and was reluctant to take a full dose of the medication. He was on the reduced dose, but he discontinued the treatment 1 week prior to presentation due to acute diarrhoea. A comprehensive metabolic panel was obtained at that time and revealed acute renal failure with a creatinine of 370 µmol/L and Blood Urea Nitrogen (BUN) 16.43 mmol/L. He was requested to get admitted to the hospital for further evaluation. On arrival to the ED, he was afebrile with a heart rate of 72 beats per minute and blood pressure of 117/58 mm of Hg. His physical examination, including cardiopulmonary examination, was unremarkable without any notable jugular venous distention, pulmonary crackles, pedal oedema or hepatomegaly. Laboratory studies were significant for leucocytosis of 17.2 ×10⁹/Lwith an absolute lymphocyte count of 11 500 cells/mm³, acute anaemia with a haemoglobin of 9.51 g/dL and a platelet count of 97 ×10⁹/L. One month prior, his laboratory studies showed creatinine of 136.17 µmol/L and a haemoglobin of 14 g/dL. A CT scan of the abdomen revealed splenomegaly with a ruptured subcapsular splenic haematoma, haemoperitoneum and lymphadenopathy (figures 1 and 2). On review, serial CT examinations demonstrated splenomegaly for several years with a maximum length of 17.6 cm 7 years prior to presentation. His spleen at the time of the rupture measured about 16.4 cm, including the subcapsular haematoma.

Figure 1.

CT of the abdomen and pelvis showing blood in the pelvis and abdomen (white arrows).

Figure 2.

CT of the abdomen showing the subcapsular splenic haematoma (white arrows).

The patient underwent an emergent exploratory laparotomy, revealing massive haemoperitoneum and splenic rupture treated with splenectomy and a partial omentectomy (figure 3), requiring four units of packed red blood cells and one unit of platelets intraoperatively. The postoperative course was uneventful, and the patient recovered without any complications.

Figure 3.

Gross images showing splenomegaly and ruptured spleen.

Surgical pathology was consistent with extensive infiltration of the spleen with malignant cells. Impression on H&E staining was non-Hodgkin's lymphoma with large cell/high-grade features (figures 4–6). Immunohistochemical staining was positive for CD19, CD20, CD23, CD79a, PAX5 and weak CD5 positivity. The FISH analysis was negative for MYC, BCL6 and BCL2 rearrangement ruling out double-hit lymphoma.

Figure 4.

H&E stain at 1000× magnification showing extensive lymphocytic infiltrate, demonstrating large cells with irregular nuclei and some cells with prominent nucleoli.

Figure 5.

CD20 B-cell stain at 40× magnification, showing positive staining (brown) with nodular and diffuse pattern of B-cell infiltrates.

Figure 6.

Ki-67 proliferation rate stain (MIB-1) at 400× magnification showing increased expression.

The patient was finally diagnosed with RT in CLL and was recommended chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). The patient refused R-CHOP and was continued on ibrutinib 140 mg daily. He was elaborately counselled about the side effect profile of the drug and the importance of medication compliance.

Outcome and follow-up

Escalation of therapy with R-CHOP was suggested after RT. Stem cell transplant would be the subsequent therapy in line after R-CHOP. Given that the patient refused R-CHOP therapy, he is not a candidate for stem cell transplant. During a follow-up, 6 months after his splenectomy, the patient reported compliance with the current reduced dose of ibrutinib without any side effects. R-CHOP therapy was offered again; however, the patient continued to refuse it.

Discussion

The most common cause of rupture of the spleen is trauma. Atraumatic splenic rupture is a rare occurrence.⁴ Though unusual, pathological rupture of the spleen can be observed in haematological malignancies. According to a systematic review conducted by Aubrey-Bassler and Sowers, a review of 613 cases of splenic rupture from 1950 to 2011, only 84 were secondary to haematological malignancies.¹ The most common cause of haematological neoplasm leading to splenic rupture was non-Hodgkin’s lymphoma, acute lymphoblastic leukaemia, followed by chronic and acute myelogenous leukaemias.^{1 5} Therefore, patients with haematological malignancies presenting with acute abdomen warrant assessment for splenic rupture.

Patients with haematological malignancies are known to have splenomegaly secondary to malignant cell infiltration. Splenic rupture is not only due to infiltration of the spleen but also possibly due to splenic infarcts, chemotherapy and cytoreductive agents.²

Our patient discontinued ibrutinib therapy abruptly, attributing to the side effects. According to the study conducted by Hampel et al, 25% of 202 patients with CLL had rapid progression of the disease within 2 years.⁶ Initially, cessation of the therapy was considered the most likely cause of splenic rupture in our patient. A few case reports support the hypothesis that sudden cessation of ibrutinib can cause a reversal of chemokine inhibition and trigger a sudden influx of malignant cells into the spleen, which can lead to rupture.⁷ However, the surgical pathology demonstrated RT. WHO defines RT as an aggressive lymphoma arising in the background of CLL.^{8 9} The majority of patients with RT from CLL transform into activated B-cell type. However, a few transforms into classical Hodgkin’s lymphoma or other non-Hodgkin’s lymphomas.¹⁰ The incidence of RT in the USA ranges from 2% to 10%, and the median time to transformation from CLL was noted to be 2–4 years.^{11 12} Based on several individual systematic reviews, RT in CLL can occur in about 5%–10% of the patients.^13–15 Although the mechanism is poorly understood, several immunological and genetic factors are considered to lead to this transformation.¹³ According to a review by Thyagarajan et al, molecular profiling of 84 patients revealed TP53 disruption and c-MYC abnormalities as the most common genetic lesions in 47.1% and 26.2% of the patients, respectively, leading to RT.¹³ Patients usually present with hepatosplenomegaly, lymphadenopathy and an elevated serum lactate dehydrogenase.¹³ RT has a rapidly progressive clinical course with a poor prognosis. The median survival is 62 months in clonally unrelated RT and 8–10 months in clonally related RT.¹³ Historically, R-CHOP has been the treatment of choice in these patients.¹⁶ Our patient refused R-CHOP and hence is being continued on ibrutinib.

Irrespective of the aetiology, splenic rupture is a life-threatening condition that needs prompt medical and surgical intervention. It might be a diagnostic challenge in cases with no trauma and warrants more vigilance, especially in patients with haematological malignancies.

Learning points.

• Splenic rupture is a life-threatening condition. A high degree of suspicion is required to make a timely clinical diagnosis when there is no trauma involved.

• Even though rare, splenic rupture should be considered in the differential diagnosis of all cases of acute abdomen, especially in a setting of leukaemia or lymphoma.

• Patients with chronic lymphocytic leukaemia are at the risk of Richter’s transformation and need periodic blood tests and imaging surveillance.

• This case report reiterates the importance of medication compliance and emphasises the need for additional research on cytoreductive therapy and the effects of abrupt cessation.

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