Lymphoplasmacytic lymphoma following splenectomy in a patient with Gaucher disease: a case report

¹Department of Internal Medicine, Mohammed VI, University Hospital of Oujda, Oujda, Morocco, ²Immunohematology and Cellular Therapy Laboratory, Medical School of Oujda, Mohammed First University of Oujda, Oujda, Morocco

^&Corresponding author
Ismail Belefqih, Department of Internal Medicine, Mohammed VI, University Hospital of Oujda, Oujda, Morocco

Introduction    

Gaucher disease represents a rare cause of splenomegaly that can easily be overlooked. Splenectomy is sometimes performed in order to manage some complications, such as restrictive pulmonary syndrome, and refractory cytopenias. But it may worsen the prognosis by compound accumulation in cellular lysosomes in multiple organ systems including visceral organs, bone marrow, neurologic, and skeletal [1]. Independently of Gaucher disease, splenectomy is also associated with an increased risk of cancer [2]. As malignancy represents one of the major causes of death among Gaucher patients, splenectomy in Gaucher disease may further increase the risk of developing a malignancy [3].

Patient and observation     

Patient information: we present the case of a 60 years-old female patient, with no underlying comorbidities who complained of a mild upper left quadrant abdominal discomfort.

Clinical findings: initial physical evaluation found a stable patient on hemodynamical, neurological, and respiratory evaluation, afebrile and anicteric. Abdominal examination revealed a palpable splenomegaly without collateral venous circulation. Moreover, there was no hepatomegaly nor peripheral lymphadenopathies.

Diagnostic assessment: initial laboratory evaluation showed a normal complete blood count with a hemoglobin at 14 g/dl, a platelet count at 250000 elements/mL, and leucocyte count at 5500 element/ml and peripheral blood smear did not reveal any abnormal cell. Serum protein electrophoresis (SPEP) was normal, and both serum and urine immunofixation were negative. C-reactive protein (CRP) and sedimentation rate were within the normal range. Antinuclear antibodies, as well as rheumatoid factor, were negative. Serologies of HIV, hepatitis C, and hepatitis B were negative.

A computer tomography (CT) scan confirmed the presence of splenomegaly of 170 mm on its coronal axis, without signs of portal hypertension nor liver disease. Moreover, there were no lymphadenopathies nor solid malignancy. Bone marrow biopsy did not reveal any malignant infiltration. The patient decided to have a second opinion from another healthcare institution, which warranted and performed a diagnostic splenectomy, before receiving the results of the remaining non-invasive investigation. Histological examination of the spleen showed a fibro-congestive spleen with necrotic reshuffles, and no lymphomatous infiltration.

Two months after the splenectomy, the patient complained of dyspnea and the chest X-ray revealed a unilateral pleural effusion. Initial pleural fluid analysis showed an exudate and the pleural biopsy revealed a lymphoid infiltrate of lymphomatous nature expressing CD20, and negative for CD5, CD10, CD23, cyclin D1, which is compatible with a lymphoplasmacytic lymphoma. A computed tomography (CT) scan was ordered, and revealed the onset of deep lymphadenopathies on both sides of the diaphragm. Serum protein electrophoresis (SPEP) revealed a monoclonal gammopathy and serum immunofixation was positive for IgM. The diagnosis of Waldenstrom's macroglobulinemia was then established. Simultaneously initial splenomegaly workup revealed a low activity of beta-glucosidase enzyme at 3.4 units (normal level: 6.5-10.5 units). The diagnosis of Gaucher disease was then established.

Therapeutic interventions and outcome: the decision was to initiate treatment with rituximab monotherapy. After two cycles, the patient presented an infectious pneumonia with septic shock, for which she was admitted to the intensive care unit and died shortly after.

Informed consent: the patient provided a clear and well informed written consent for the publication of the case.

Discussion     

Splenomegaly represents a frequently encountered affection in internal medicine and general practice, with a variety of underlying causes, dominated by portal hypertension, malignancy, and infection. The usual investigations therefore consist of a portal system exploration, microbiology testing, and neoplastic investigations, such as a CT scan, SPEP, Bone marrow biopsy, and JAK2 mutation. When the initial workup is negative, or when clinical settings are suggestive, other causes, such as rheumatic diseases and infiltrative diseases are sought. When non-invasive testing does not identify the cause, a splenectomy can be performed as a diagnostic tool. The procedure does not come without potential complications, especially of malignancy, and thus as tempting as it might be, splenectomy should only be sought after a full non-invasive investigation. Studies following up veterans who underwent splenectomy for traumatic causes, found a subsequent increase in malignancy risk of hematologic and solid nature [2].

As for Gaucher disease, splenectomy was and still is considered to be a therapeutic option especially before the arrival of enzyme replacement therapy. It was then used to manage deep cytopenias, and restrictive pulmonary syndrome or recurrent splenic infarction, in the instance of a very large spleen. But as the spleen is one of the major storages of substrates, its removal is associated with an increase in substrate infiltration of other organs [1]. Immunomodulatory abnormalities seem to be playing a major role in the development of hematologic malignancy [4]. As an example, a study following 2742 patients with Gaucher disease found a significant increase in the relative risk of multiple myeloma of 5,9 fold [5]. More alarming, studies following patients with Gaucher disease found that asplenic patients had a greater incident, not only for one, but for multiple malignancies compared to Gaucher patient with a spleen [6].

Conclusion     

This case portrays the very quick and sudden development of a malignancy after the splenectomy in a patient with Gaucher disease, which should not only prompt physicians to be cautious of ordering the surgery before completing the non-invasive workup, but also should question the implication of the splenectomy in the management of Gaucher disease. As the major cause of deaths among Gaucher patients is represented by secondary cancers, caution should be exerted to limit risk factors, but also to employ meticulous screening of different cancers.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Patient management: Ismail Belefqih, Habiba Alaoui, Khalid Serraj. Manuscript revision: Habiba Alaoui, Khalid Serraj. All authors have read and agreed to the final manuscript.

References