Primary Splenic Diffuse Large B-Cell Lymphoma: A Case Report and Literature Review of a Rare Condition.

Introduction: Primary splenic lymphoma is a rare lymphoproliferative disorder that involves the spleen, exhibits diverse clinical presentations, and lacks a clear consensus in terms of management strategies. Case Presentation: We present the case of a 52-year-old patient with a complex medical history marked by multiple chronic medical conditions. The patient was diagnosed with primary splenic lymphoma, specifically the diffuse large B-cell subtype. Treatment for our patient involved a shortened course of chemotherapy (4 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] followed by two doses of rituximab) due to issues related to compliance and treatment-related complications. This was followed by consolidative radiotherapy without resorting to splenectomy. Conclusion: Remarkably, despite using a shortened course of R-CHOP, the patient achieved complete resolution, and a positron emission tomography scan conducted at the end of the 6-month posttreatment period confirmed sustained complete remission.

Atypical diffuse large B-cell lymphoma, primary splenic lymphoma variant; a case report.

INTRODUCTION AND IMPORTANCE: Primary splenic lymphoma (PSL) is characterized by lymphoma involvement confined to the spleen and hilar lymph nodes, without evidence of liver involvement or other sites. This condition is extremely uncommon, accounting for approximately 1 % of non- Hodgkin lymphomas (NHLs) and <2 % of all lymphomas. Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of both PSLs and all NHLs. DLBCL encompasses an aggressive heterogeneous entity with distinct morphological variants. CASE PRESENTATION: A 68 year-old gentleman presented to the office with a 10-month history of vague left sided upper abdominal pain. Clinical examination revealed a tender left upper quadrant, evidenced with splenomegaly on radiological evaluation. The patient proceeded with a splenectomy with subsequent pathological and immunohistochemical analysis, confirming a final diagnosis of germinal center type DLBCL. CLINICAL DISCUSSION: Primary splenic DLBCL is a rare variant of DLBCL, characterized by exclusive involvement of the spleen. It requires a comprehensive diagnostic evaluation to exclude lymphoma involvement in other organs and lymph nodes. Splenectomy followed by appropriate adjuvant therapy has been demonstrated as the definitive treatment strategy. This case report emphasizes the importance of considering primary splenic DLBCL as a differential diagnosis in patients presenting with splenomegaly and highlights the significance of multidisciplinary collaboration for accurate diagnosis and optimal management of this uncommon entity. CONCLUSION: Primary Splenic DLBCL, an exceptionally rare B-Cell neoplasm variant, requires precise diagnosis due to its unique splenic involvement. Splenectomy's efficacy, adjuvant therapy, multidisciplinary collaboration, and ongoing research are crucial for optimal management.

Primary Splenic Diffuse Large B-Cell Lymphoma: A Case Report.

Primary splenic lymphoma (PSL) is a rare disease and an improbable cause of splenomegaly or splenic nodules. On the contrary, splenic secondary involvement as part of an advanced lymphoproliferative disorder is more common. The authors present the case of a 49-year-old woman with a primary splenic diffuse large B-cell lymphoma (PS-DLBCL), in which the absence of other organs' involvement determined an ultrasound-guided biopsy of the spleen to achieve a definitive diagnosis. With this case the authors intend to emphasise the extensive differential diagnosis of splenomegaly, splenic nodules or infiltrates, the usefulness of splenic biopsy in establishing the diagnosis and recall a rare disease, with non-specific presenting symptoms, in which the diagnostic workup is challenging. LEARNING POINTS: The differential diagnosis of splenic nodules or infiltrates is vast and challenging, and it includes haematological diseases, systemic infectious diseases but also non-malignant infiltrative diseases.Although some lymphomas frequently present with splenomegaly, this is not the case of DLBCL, with the exception of PS-DLBCL.PS-DLBCL is a very rare pathology, accounting for 1% of all DLBCL and less than 1% of all NHL.

The role of splenectomy in management of splenic B-cell lymphomas.

INTRODUCTION: Splenic B-cell lymphomas are rare and understudied entities. Splenectomy is frequently required for specific pathological diagnosis in patients with splenic B-cell lymphomas other than classical hairy cell leukemia (cHCL), and can be effective and durable therapy. Our study investigated the diagnostic and therapeutic role of splenectomy for non-cHCL indolent splenic B-cell lymphomas. METHODS: Observational study of patients with non-cHCL splenic B-cell lymphoma undergoing splenectomy between 1 August 2011 and 1 August 2021 at the University of Rochester Medical Center. The comparison cohort was patients categorized as having non-cHCL splenic B-cell lymphoma who did not undergo splenectomy. RESULTS: Forty-nine patients (median age 68 years) had splenectomy (SMZL n = 33, HCLv n = 9, SDRPL n = 7) with median follow up of 3.9 years post splenectomy. One patient had fatal post-operative complications. Post-operative hospitalization was ≤ 4 days for 61% and ≤ 10 days for 94% of patients. Splenectomy was initial therapy for 30 patients. Of the 19 patients who had previous medical therapy, splenectomy changed their lymphoma diagnosis in 5 (26%). Twenty-one patients without splenectomy were clinically categorized as having non-cHCL splenic B-cell lymphoma. Nine required medical treatment for progressive lymphoma and of these 3 (33%) required re-treatment for lymphoma progression compared to 16% of patients following first line splenectomy. CONCLUSION: Splenectomy is useful for the diagnosis of non-cHCL splenic B-cell lymphomas with comparable risk/benefit profile and remission duration to medical therapy. Patients with suspected non-cHCL splenic lymphomas should be considered for referral to a high-volume center with experience in performing splenectomies for definitive diagnosis and treatment.

Prognostic nomogram for primary splenic lymphoma: a SEER database-based study.

This study aimed to establish a nomogram model based on the clinicopathological factors affecting the prognosis of patients with primary splenic lymphoma (PSL) to predict the overall survival (OS) and cancer-specific survival (CSS) of patients. A total of 4074 patients diagnosed with PSL were included in this study. Among them, 4052 cases from the SEER (Surveillance, Epidemiology, and End Results) database were randomized into a training set and an internal validation set in a 7:3 ratio. Another 22 patients from the First Affiliated Hospital of Xi'an Jiaotong University were used as an external validation set. The prognostic factors affecting the OS and CSS of patients were analyzed using univariate and multivariate Cox regression models. Survival analysis was performed using Kaplan-Meier (KM) method and compared by Log-rank test. Then, a nomogram model was established to predict OS and CSS. Finally, the model was validated both internally and externally using the concordance index (C-index), receiver operating characteristic curve (ROC), and calibration curve to evaluate its predictive value, and the decision curve analysis (DCA) was conducted to assess its clinical utility. Our results showed that the model displayed a good prediction ability. In the training set, the OS rates at 1, 3, and 5 years were 85.9%, 75.8% and 70.1%, respectively, while the CSS rates at 1, 3, and 5 years were 91.9%, 86.2% and 82.3%, respectively. Predictors in the prediction model of OS included age, sex, marital status, Ann Arbor stage, histology, surgery, chemotherapy and year at diagnosis. On the other hand, predictors in the model of CSS included age, Ann Arbor stage, histology, chemotherapy, and year at diagnosis. Internal and external validation of the nomogram model showed that the C-index for predicting OS was 0.678 (0.662, 0.694) in the training set, 0.672 (0.648, 0.696) in the internal validation set, and 0.704 (0.565, 0.843) in the external validation set; the C-index for predicting CSS was 0.685 (0.661, 0.709) in the training set, 0.683 (0.650, 0.716) in the internal validation set, and 0.676 (0.488, 0.864) in the external validation set. The calibration curves for several groups showed good consistency, and DCA suggested its clinical usability. In conclusion, the nomogram constructed in this study has a good predictive value for the survival of patients with PSL, and can be a clinically applicable and practical prediction tool, facilitating rapid and accurate individualized predictions of the patient survival.

An Unusual Differential Diagnosis of Gastric Haemorrhage: A Rare Case of Gastrosplenic Fistula.

A gastrosplenic fistula is a rare complication of primary splenic lymphoma and a rare cause of massive upper gastrointestinal haemorrhage. We report a case of a spontaneous gastrosplenic fistula secondary to splenic large B-cell lymphoma. The patient was admitted to the emergency department with haematemesis. Oesophagogastroduodenoscopy showed a deep gastric ulcer, and a subsequent CT scan revealed a gastrosplenic fistula. Gastric biopsy demonstrated gastric mucosa with infiltration by large lymphoid cells. A multidisciplinary discussion on the management of this case was conducted. Primary surgical treatment of the fistula was not deemed indicated because the bleeding had stopped. The patient was stabilized, transfused, and then transferred to the oncology unit for chemotherapy. During hospitalization, lung metastases were found but the progressive worsening of the patient's general condition contraindicated chemotherapy. She was transferred to a hospice and died 2 months later of neoplastic cachexia. Gastrosplenic fistula is a rare condition. Prompt recognition of the underlying pathology can save the patient's life. We aim to highlight this rare complication of splenic lymphoma, discuss the presenting signs and symptoms, and explore the management options. LEARNING POINTS: A gastrosplenic fistula is a rare complication of primary splenic lymphoma.It can cause massive upper gastrointestinal haemorrhage.Our patient was managed without surgery but died 2 months later from neoplastic cachexia.

The Role of Contrast-Enhanced Ultrasound in Differentiating Splenic Tuberculosis From Splenic Lymphoma.

Aim: To summarize the features of splenic tuberculosis and splenic lymphoma by contrast-enhanced ultrasound (CEUS) and examine the application of CEUS in differentiating splenic tuberculosis from splenic lymphoma. Methods: The ultrasound and CEUS manifestations of 30 cases of splenic tuberculosis and 19 cases of splenic lymphoma were retrospectively analyzed, and the number of lesions, degree of splenomegaly, internal echogenicity, color blood flow signal, and CEUS manifestations of the two diseases were statistically determined. Results: A significant difference was noted in the internal echogenicity between splenic tuberculosis and splenic lymphoma lesions, particularly the strip-shaped hyperechoic areas of the lesions. The ultrasound features of perisplenic, retroperitoneal, and superficial lymph node enlargement were found to overlap (p < 0.05). Splenic tuberculosis showed heterogeneous enhancement and non-enhancement, whereas lymphoma showed low enhancement and high enhancement, and CEUS findings were statistically significant in distinguishing both, p < 0.05. Conclusion: Splenic tuberculosis is characterized by a lack of blood supply, mostly heterogeneous enhancement, and non-enhancement noted in CEUS. Splenic lymphoma lesions are often characterized by a rich blood supply and homogeneous enhancement on CEUS. CEUS can help identify the microcirculation of lesions in both patients with splenic lymphoma and patients with splenic tuberculosis. Thus, CEUS has great application value.

Profuse telangiectasias in an immunocompetent patient misleading presentation revealing a hepatosplenic-Tγδ-cell lymphoma.

Here we present the case of an hepato-splenic-Tγδ-cell lymphoma interestingly occurring in a non-immunocompromised patient, with profuse telangiectasias giving originally misleading orientation towards the diagnosis of B angiotropic lymphoma.

Unusual Rapid Growth of Primary Splenic Diffuse Large B-Cell Lymphoma with Extensive Necrosis.

The primary splenic lymphoma is extremely uncommon with an incidence rate of <1% of all the lymphomas under the strict criteria for diagnosis expounded by Das Gupta et al. Clinical presentations of nonspecific symptoms are weight loss, weakness, fever, and left upper quadrant pain or discomfort due to enlarged spleen. Abdominal ultrasound and CT are the most widely used imaging modality for the assessment of lymphoma. The imaged features of splenic lymphoma are nonspecific; typical lymphoma presents as a diffusely enlarged spleen. The abdominal CT scan in our case showed a large cystic splenic mass measuring 14 cm without enhancement after contrast medium. Lymphoma is often described as an aggressive tumor because its rapid doubling time can quickly increase the size of a tumor. In our case, the tumor grew to more than 100 times its original size in 4 months. So, we present this unusual rapid growth of primary splenic lymphoma.

Identification of secondary splenic lymphoma with contrast-enhanced ultrasound in the pediatric population. A case report.

Contrast-enhanced ultrasound scan (CEUS) is the application of ultrasound contrast agents (UCAs) to traditional ultrasound. Our aim is to report the use of CEUS for a prompt assessment of a suspected secondary splenic lymphoma in a child, which, in our experience, has allowed an accurate description of the parenchymal perfusion and vascularization pattern, leading to a confident diagnosis. We suggest that CEUS will replace Magnetic resonance imaging (MRI) or Computed tomography (CT) as standard imaging option for differential diagnosis of spleen lesions in pediatric population. As a result this will lead to decreasing the overall use of ionizing radiation and reducing the time interval to a certain diagnosis.

How to Diagnose and Treat CD5-Positive Lymphomas Involving the Spleen.

Patients with CD5-expressing lymphomas presenting with splenomegaly are frequently diagnosed with chronic lymphocytic leukemia. The most important differential diagnosis is mantle cell lymphoma, both in its classical and leukemic, non-nodal forms, given its prognostic and therapeutic implications. Other small B-cell neoplasms that frequently involve the spleen and occasionally express CD5 include the splenic marginal zone lymphoma, hairy cell leukemia and, rarely, lymphoplasmacytic lymphoma. The frequency of CD5 positivity depends in part on the sensitivity of the detection methods employed. Usually, a combination of morphological, immunophenotypic and molecular findings allows for a precise sub-classification of CD5-positive, low-grade B-cell lymphomas of the spleen. Some of these tumors may display a mixture of small and larger B cells, raising the possibility of more aggressive lymphomas, such as diffuse large B-cell lymphomas (DLBCL). Approximately 5-10% of DLBCL are CD5-positive and some may manifest as primary splenic lesions. When available, the morphology of DLBCL in the splenic tissue is distinctive and a leukemic picture is very rare. In conclusion, the appropriate morphological and clinical context assisted by flow cytometry panels and/or immunohistochemistry allows the differential diagnosis of CD5-positive, non-Hodgkin, B-cell lymphomas involving the spleen.

A Review on Splenic Diffuse Red Pulp Small B-Cell Lymphoma.

Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is a rare disease, representing <1% of all non-Hodgkin lymphomas (NHL). The most common clinical manifestations include splenomegaly, lymphocytosis, and hemocytopenia. A diagnosis of SDRPL can be challenging, as it shares multiple clinical and laboratory features with splenic marginal zone lymphoma (SMZL), hairy cell leukemia (HCL), and HCL variant (HCL-v). Obtaining splenic tissue remains the gold standard for diagnosis. In the cases where splenic tissue is not available, diagnosis can be established by a review of peripheral blood and bone marrow studies. SDRPL is characterized by a diffuse involvement of the splenic red pulp by monomorphous small-to-medium sized mature B lymphocytes effacing the white pulp. The characteristic immunophenotype is positive for CD20, DBA.44 (20 to 90%), and IgG, and typically negative for CD5, CD10, CD23, cyclin D1, CD43, annexin A1, CD11c, CD25, CD123, and CD138. The Ki-67 proliferative index is characteristically low. Cyclin D3 is expressed in the majority of SDRPL in contrast with other types of small B-cell lymphomas, thus facilitating the recognition of this disease. There is no standard treatment regimen for SDRPL. Initial treatment options include splenectomy, rituximab monotherapy, or a combination of both. Chemoimmunotherapy should be considered in patients with advanced disease at baseline or progression.

The effect of surgery on primary splenic lymphoma: A study based on SEER database.

BACKGROUND: Although primary splenic lymphoma (PSL) is rare, it ranks first among splenic primary malignant cancers, and the incidence of lymphoma of spleen has gradually increased in recent years. However, the efficacy of surgery for PSL has not been clinically verified by large sample data, which has affected the formulation of relevant guidelines. AIM: To assess whether surgery can enhance the prognosis PSL patients. METHODS: Extracted the data of patients with PSL from The Surveillance, Epidemiology, and End Results (SEER) database, and divided the patients into surgery and non-surgery group. Kaplan-Meier curves and log-rank tests were used to compare the overall survival (OS) and cancer-specific survival (CSS). The propensity score matching (PSM) was used to match the data, then compared the OS and CSS again. The COX proportional hazard regression model was used for univariate and multivariate analysis. Finally, we performed subgroup analysis in different Ahmann stages. RESULTS: A sum of 2207 patients with PSL were enrolled, of which 1062 (48.1%) patients received surgery, and 1145 (51.9%) patients did not undergo surgery. Overall, patients in the surgery group had better OS and CSS. After the propensity scores matching, surgery was not statistically significant in OS and CSS. In the subgroup analysis, surgery was a protective factor for the OS and CSS in Ahmann I/II. However, surgery was no statistical significance in OS and CSS in Ahmann III. In patients with Ahmann Ⅰ/Ⅱ SMZL, surgery was a protective factor for OS and CSS. In patients with Ahmann Ⅲ SMZL, surgery was also statistically significant of OS and CSS. CONCLUSIONS: Surgery can significantly improve the prognosis of patients with Ahmann Ⅰ/Ⅱ primary splenic lymphoma, but there was no survival difference in the Ahmann Ⅲ patients with or without surgery. For patients with SMZL, surgery was effective for improving OS and CSS.

Clinical Characteristics, Treatment and Evolution of Splenic and Nodal Marginal Zone Lymphomas-Retrospective and Multicentric Analysis of Portuguese Centers.

INTRODUCTION: Treatment of Splenic (SMZL) and Nodal (NMZL) Marginal Zone Lymphoma is not consensual. Histologic transformation (HT) to aggressive lymphoma is a poorly understood event, with an unfavorable outcome. OBJECTIVES: Describe the clinical characteristics, treatment, outcomes and incidence of HT. METHODS: Characteristics of patients with SMZL and NMZL consecutively diagnosed in 8 Portuguese centers were retrospectively reviewed. Endpoints were overall survival (OS), time to first systemic treatment (TTFST), frequency of HT and time to transformation (TTT). RESULTS: This study included 122 SMZL and 68 NMZL, most of them received systemic treatment: 55.4% and 76.5%, respectively. Splenectomy was performed in 58.7% of patients with SMZL. Different treatment protocols were used. OS or TTFST did not differ significantly according to treatments. Given the small sample size, no conclusion can be made concerning the role of Rituximab in the treatment of NMZL and SMZL based in these results. HT was documented in 18 patients, mainly in SMZL, with a cumulative incidence at 5 years of 4.2%. We confirmed that age is a prognostic factor. CONCLUSION: Randomized prospective trials are needed to standardize treatment in MZL. Patients with HT did appear to have shorter OS in comparison with those who did not experience HT (OS 5 years of 68.4% vs. 80.4%), but the number of HT was too small to reach statistical significance.

Differentiating Primary Pancreatic Lymphoma Versus Primary Splenic Lymphoma: A Case Report.

Background: Both primary pancreatic lymphoma (PPL) and primary splenic lymphoma (PSL) represent rare entities. PPL typically arises in the head of the pancreas but may arise in other locations also. PSL usually presents with nonspecific symptoms, including left upper quadrant pain, weight loss, and fever. This report describes a patient with a large left upper quadrant mass, which initially was believed to be a primary pancreatic mass, but which on final pathology appeared to be consistent with a PSL. Presentation: The patient is a 64-year-old woman who initially presented with symptoms of left upper quadrant abdominal pain and distension; she subsequently was found to have an 18 cm heterogeneous mass arising from the pancreatic tail. She underwent a distal pancreatectomy with splenectomy. Final pathology confirmed a diffuse large B cell lymphoma arising from the splenic parenchyma. Conclusions: Both PPL and PSL are rare causes of left upper quadrant masses. In this case, we describe a large lymphoma that appeared to arise from the tail of the pancreas, but on final pathology was found to be splenic in origin. Differentiating these two clinical entities is important for prognostication and treatment. A multimodal approach with surgical resection followed by chemotherapy is preferred.

Primary splenic anaplastic variant of diffuse large B-cell lymphoma: a case report.

BACKGROUND: Primary splenic lymphoma represents a rare entity that constitutes less than 1% of non-Hodgkin lymphomas, and less than 2% of all lymphomas. Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of primary splenic lymphomas. DLBCL encompasses a heterogeneous entity with distinct morphological variants. The anaplastic variant of DLBCL was first defined in the 2017 World Health Organization classification as a rare histological subtype that constitutes less than 3.4% of DLBCL cases. CASE PRESENTATION: A 65-year-old Syrian man presented to our hospital with constant dull localized left upper quadrant abdominal pain for about 20 days accompanied by general weakness, loss of appetite, and rapid weight loss. Clinical examination revealed isolated splenomegaly and left upper abdominal tenderness. Following physical, laboratory, and radiologic examinations, the patient underwent splenectomy. Interestingly, pathological and immunohistochemical examinations of the resected spleen confirmed the diagnosis of a primary anaplastic variant of DLBCL. CONCLUSIONS: Herein, we aimed to present an unusual combination of a rare splenic neoplasm and a unique lymphoma subtype. Furthermore, we aimed to highlight the difficulties in differential diagnosis and the importance of histological and immunohistochemical examinations with clinical correlation.

Splenic lymphoma with complex gastro-spleno-diaphragmatic fistula: 3D laparoscopic multivisceral resection. The first literature case report.

INTRODUCTION: Gastrosplenic fistula is a rare disease involving stomach and spleen that can lead to dangerous complications like massive gastrointestinal bleeding. Diffuse large B-cell lymphoma (DLBC) is the principal pathological cause of gastrosplenic fistula. CASE REPORT: We report a case of A 76-year-old caucasian woman came to the emergency room with fever for two week and gravative pain in left upper quadrant of the abdomen. CT scan of thorax and abdomen demonstrated an inhomogeneous hypodense large lymphomatous mass (10 × 6 cm) of upper pole of the spleen deformating medial profile and infiltrating gastric fundus and left diaphragm. with the diagnosis of complex gastro-splenic-diaphragmatic fistula we performed an en-block resection using a 3D laparoscopic vision system. DISCUSSION: Gastrosplenic fistula is a rare complication of several clinical conditions. Among the different causes diffuse large B-cell lymphoma is the most frequent although diffuse histiocytic lymphoma, Hodgkin's lymphoma and extranodal NK/T-cell lymphoma are also described. After a literature review we found less then 30 cases of gastrosplenic fistula secondary to lymphoma. In our case report we do the first description of three-organs fistula envolvement, stomach, spleen and diaphragmatic dome, managed with 3D laparoscopic approach. CONCLUSION: Gastrosplenic fistula can represent a fatal evolution of splenic or gastric lymphoma independently from chemotherapy treatment. The diagnosis of this condition is very difficult and related to its rarity. To our opinion, laparoscopy represents a valid and safe alternative to open surgery in management of these patients.

Rare Causes of Isolated and Progressive Splenic Lesions: Challenges in Differential Diagnosis, Evaluation, and Treatment of Primary Splenic Lymphomas.

The spleen is among the most common extranodal sites for Hodgkin and non-Hodgkin lymphomas (NHLs); however, among lymphomas arising from the spleen, primary splenic lymphomas (PSLs) are rare. The group of PSLs includes primary splenic diffuse large B-cell lymphoma (PS-DLBCL), splenic red pulp small B-cell lymphoma, splenic marginal zone lymphoma (SMZL), and a splenic hairy cell leukemia variant. Delineating between the PSL variants can be challenging, especially as fine-needle aspirate and core needle biopsy of the spleen are not routinely offered at most medical centers. Herein, we describe the clinical course of 2 representative patients who presented with non-specific gastrointestinal symptoms, the first who was diagnosed with PS-DLBCL and the second who was diagnosed with SMZL. We review and contrast the clinical presentations, imaging techniques, and laboratory findings of these discrete lymphoma variants and offer strategies on how to delineate between these varied splenic processes. We also examine the use of splenectomy and splenic needle biopsy as diagnostics and, in the case of splenectomy, a therapeutic tool. Finally, we also briefly review treatment options for these varied lymphoma sub-types while acknowledging that randomized trials to guide best practices for PSLs are lacking.

No Stones, Some Groans, and Psychiatric Overtones with "Non-specific" Splenomegaly.

Hypercalcemia is a potentially life-threatening electrolyte imbalance that is commonly caused by hyperparathyroidism, supplement or medication use, and/or malignancy. Splenomegaly is commonly a non-specific finding, but in the setting of hypercalcemia, may provide diagnostic insight into the underlying pathology and warrant further evaluation. A 70-year-old man presented from his outpatient provider with serum calcium > 15 mg/dL with complaints of one-month fatigue, weakness, poor oral intake, 10 lbs. unintentional weight loss, and periodic confusion noted by his wife. He received an extensive inpatient workup which was non-diagnostic. Splenomegaly was observed on radiographic imaging and reported as "nonspecific". Following discharge, denosumab was required to manage the hypercalcemia. Eventually, a diagnosis of primary splenic lymphoma was made months later. Laparoscopic splenectomy was planned but was advanced to an open laparotomy intraoperatively due to the rapid growth of the neoplasm. Early and close investigation of the spleen is warranted when splenomegaly presents in the setting of hypercalcemia and, as in this case, may prevent significant therapeutic burden.