Primary splenic diffuse large B-cell lymphoma (PS-DLBCL) is a relatively rare malignancy, and there are no optimal approaches for diagnosis and management. There are less invasive splenic biopsies that effectively obviate diagnostic and elective splenectomies. We report a man in his 50s with 2-day history of pain in the abdomen and who was found to have a splenic mass on PET-CT. A CT-guided core needle splenic biopsy confirmed the diagnosis of PS-DLBCL. He was managed with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) alone, without splenectomy. The patient attained complete remission, and he is disease free at 6 years of follow-up.
- haematology (incl blood transfusion)
- cancer intervention
- malignant and benign haematology
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- haematology (incl blood transfusion)
- cancer intervention
- malignant and benign haematology
Differentiating the pathological origins of isolated splenomegaly between primary splenic and those associated with hepatic or underlying systemic diseases is a diagnostic challenge. Malignant lymphomas account for a significant yet underestimated number of isolated splenomegaly.1 Primary splenic diffuse large B-cell lymphoma (PS-DLBCL) is a comparatively uncommon disease, accounting for 1% of all malignant lymphomas.2 Initially, primary splenic lymphomas were interpreted as being restricted to the hilar nodes and spleen.3 Later PS-DLBCL was suggested as the disease that commenced in the spleen or had the bulk of disease confined to the spleen.4 5
Diffuse large B-cell lymphomas (DLBCLs) of the spleen are aggressive tumours similar to the ones originating from the lymph nodes and other extranodal locations, and this is the rationale behind treating splenic DLBCL based on the general guidelines suggested for DLBCL.1 6 Although permutations of splenectomy, systemic chemoimmunotherapy and radiation have been found useful, there is no concordance in treatment approaches. Splenectomy’s diagnostic and therapeutic role has not been thoroughly investigated. A multi-database study demonstrates that the use of splenectomy has plummeted from 82% (pre-rituximab era) to 72% (rituximab era) following the approval of rituximab in 2006 by the US Food and Drug Administration.5 We present a case where we used CT-guided core needle splenic biopsy to diagnose the primary splenic DLBCL, and the patient attained complete remission with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone).
A man in his 50s presents with 2-day history of excruciating pain in the left hypochondrium radiating to the left shoulder. The physical examination did not show lymphadenopathy or hepatosplenomegaly.
Laboratory examinations for complete blood count, liver and renal functions were within the normal limits. An ultrasound of the abdomen revealed a hypoechoic splenic lesion measuring 9.1×7.1 cm without signs of vascularity. A CT scan of the abdomen revealed splenic enlargement with a focal lesion measuring 9.5×7.4 cm with a mild heterogeneous postcontrast lesion. The mass caused minimal displacement of the splenic vein. A month later, the patient reported to us and the CT abdomen and pelvis (figure 1) showed splenomegaly measuring 11.6×11.4×7.9 cm with a large heterogeneously enhancing necrotic mass lesion with an exophytic component of 10.3×9.9×7 cm in the antero-inferior aspect of spleen. On fluorodeoxyglucose positron emission tomography (FDG PET) scan, the mass was enhancing heterogeneously with central necrotic metabolically active areas likely suggestive of a neoplastic aetiology.
Bone marrow showed no involvement. A fine needle aspiration cytology (FNAC) revealed a haemorrhage. A CT-guided core biopsy was performed to evaluate the splenic lesion further, and it confirmed a haematolymphoid malignancy. Histopathology revealed DLBCL with a monomorphous population of lymphoid cells and a few large lobulated cells infiltrating in a trabecular and diffuse pattern the sclerotic fibrocollagenous stroma. Large areas of necrosis were present. Immunohistochemistry showed CD45, CD20, CD79a, CD10, positivity (figure 2), and negative for CD 3, CD5, thus confirming PS-DLBCL (stage IE-Ann Arbour staging system).
Here in our case, there are four differential diagnoses discerned from the initial radiological reports which are haemangioma, angiosarcoma, lymphoma and splenic metastasis. Haemangioma is further classified into two: typical and atypical. Typical haemangioma of the spleen presents as a peripheral nodular enhancement with centripetal filling, whereas atypical haemangioma is difficult to diagnose. Atypical haemangioma requires FNAC for confirmation. Dynamic imaging eliminated typical haemangioma, and biopsy eliminated atypical haemangioma. Angiosarcoma presents with a heterogeneous large rapidly growing lesion. This can be eliminated because, in our case, the lesion was slowly progressing. Metastasis to the spleen is ruled out by the absence of other local lesions.
The patient received six cycles of R-CHOP with each cycle at an interval of 21 days, and there was 95% regression (4.2×3.1×2.8 cm from 10.3×9.9×7 cm) of the splenic lesion on completing the first four cycles. A PET-CT done 1 month postchemoimmunotherapy showed a complete anatomic and metabolic response.
Outcome and follow-up
The patient is alive and disease free on 6 years (2015–2021) of follow-up.
The early 2000s witnessed numerous clinical trials demonstrating rituximab’s efficacy, a chimeric anti-CD20 IgG1 monoclonal antibody, when used in combination with CHOP in previously untreated aggressive non-Hodgkin lymphoma patients.7 Rituximab’s addition to CHOP enhanced the response rate and event-free survival in stage I DLBCL patients; the complete response rates were better with R-CHOP compared with CHOP (77% vs 61.5%, p=0.001).8 Although there are no optimal approaches to managing PS-DLBCLs, the general practice is to administer systemic chemoimmunotherapy, either alone or postsplenectomy. Splenectomy is not mandatory; however, it is commonly performed for diagnosis.9 There are safe, effective and minimally invasive alternatives that obviate the need for diagnostic splenectomies, such as image-guided percutaneous FNAC, core needle biopsy and laparoscopic biopsy.10–12
While core biopsy has not been traditionally recommended considering spleen’s fragility and the risk of postcore biopsy complications, there were studies conducted in the 1950s (300 patients), 1960s (500 patients) and 1970s (800 patients) that reported splenic biopsies were relatively safe with only four to five minor complications.13–15 Furthermore, institutional reviews and meta-analysis on core needle splenic biopsy report a diagnostic yield of 92.3% and a low rate of complications (5.8%).12 13 16 Currently, core biopsy is used as a routine diagnostic technique in splenic lesions, and a multi-centre study reported a 100% diagnostic accuracy of core needle biopsy in splenic lymphoma.17–19 Splenic biopsy has a favourable complication rate compared with splenectomy and is a safe alternative.16
Stage I PS-DLBCL patients who underwent splenectomy had increased disease-specific (HR=0.51, 95% CI=0.17–1.08; p=0.04 in the pre-rituximab era vs HR=0.62, 95% CI=0.25–1.38; p=0.53 in the rituximab era) and overall survival rates (HR=0.66, 95% CI=0.32–1.14; p=0.03 in the pre-rituximab era vs HR=0.74, 95% CI=0.37–1.43, p=0.45 in the rituximab era) only in the pre-rituximab era.5 Furthermore, elective splenectomy on malignant lymphomas has a higher complication rate compared with elective splenectomies on benign pathology. The most common potential complications of elective splenectomy are bleeding, infections and venous thromboembolism.20 Additionally, it is an irreversible surgical procedure with the loss of several immunohaematological functions.5 An observational study, which included splenic lymphomas diagnosed in the USA between 2004 and 2013, illustrated a notable decline (from 77% to 62%) in the use of splenectomy in DLBCLs. Besides, they did not find any association between overall survival and splenectomy.21 There are no prospective randomised controlled trials that have investigated the usefulness of splenectomy. Hence it is not definite whether splenectomy is obligatory in the rituximab era. The use of splenectomies in stage I splenic DLBCL has decreased with the introduction of rituximab (82% vs 72%, p=0.03).5
In conclusion, our study reports a case of PS-DLBCL diagnosed using CT-guided core needle splenic biopsy and managed with six cycles of R-CHOP. The patient attained complete anatomic and metabolic remission 1 month after completing the chemoimmunotherapy. He is alive and relapse free, 6 years from the diagnosis. Splenic preservation’s clinical benefit is that potential postoperative complications and immunosuppression can be obviated without any change in the survival outcomes. Future studies need to confirm the clinical benefits of managing primary splenic DLBCL using R-CHOP without splenectomy.
The interventional radiologist who performed the core biopsy was indeed a godsend for me. There were multiple differentials, but an oncologist, pathologist and radiologist helped me get to the right diagnosis. Although we (my family and I) were taken aback by the diagnosis of cancer, we trusted in the treatment plan. We were relieved to see a massive reduction in the cancer size during the mid chemotherapy cycles. Thankful that the cancer shrinked with the chemotherapy itself, and I did not have to go through surgery. In retrospect, I am grateful to the right calls the physicians took.
Splenectomy’s diagnostic and therapeutic role in stage I-primary splenic diffuse large B-cell lymphoma (PS-DLBCL) has not been thoroughly investigated.
Based on prior reports and our experience, image-guided core splenic biopsy is recommended in stage I PS-DLBCL for its efficiency, low rate of complications and high overall diagnostic accuracy.
Image-guided splenic biopsy could be a safe alternative to diagnostic splenectomy in stage I PS-DLBCL, and by obviating splenectomy, we preserve the haematological and immunological functions and avoid potential surgical complications.
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Twitter @TaraRajendran, @JR_Kini
Contributors TR did the conceptualisation, methodology, data curation and original draft preparation. JRK wrote the pathology section of the original draft and AA wrote the radiology section of the manuscript. KP did the investigation, supervision, reviewing and editing.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests KP has stock and other ownership interests at Merck and NATCO and receives honoraria from AstraZeneca; Cipla; DR.REDDYS; Mylan.
Provenance and peer review Not commissioned; externally peer reviewed.