What is the likely cause and treatment for hepatomegaly, prominent spleen, bilateral renal enlargement with obstructive hydronephrosis, and retroperitoneal lymphadenopathy?

Lymphoproliferative Disorder: Likely Non-Hodgkin Lymphoma

The constellation of hepatomegaly, prominent splenomegaly, bilateral renal enlargement with obstructive hydronephrosis, and retroperitoneal lymphadenopathy is most consistent with a diffuse lymphoproliferative process, specifically non-Hodgkin lymphoma (NHL), and requires urgent tissue diagnosis followed by systemic chemotherapy. 1, 2, 3

Diagnostic Approach

Immediate Essential Workup

• Complete blood count with differential to assess for cytopenias (particularly thrombocytopenia from hypersplenism or bone marrow involvement), leukocytosis, and presence of circulating lymphoblasts 1, 2
• Comprehensive metabolic panel including liver function tests, serum creatinine (to assess renal function given hydronephrosis), and lactate dehydrogenase (LDH), which is elevated in aggressive lymphomas 1
• Serum β2-microglobulin as a prognostic marker in lymphoma 1
• Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) testing before initiating anti-CD20 monoclonal antibody therapy, as hepatitis B reactivation is a significant risk 1

Critical Imaging Studies

• CT chest with contrast to evaluate for mediastinal lymphadenopathy and assess disease extent 1
• The existing abdominal/pelvic CT already demonstrates retroperitoneal lymphadenopathy and bilateral hydronephrosis; this should be reviewed for specific characteristics including size of lymph nodes, degree of renal obstruction, and presence of hepatosplenic lesions 1, 3

Tissue Diagnosis - The Definitive Step

Lymph node biopsy is essential and preferred over other tissue sampling methods to establish the specific lymphoma subtype, which determines treatment strategy 1. The retroperitoneal lymphadenopathy provides an accessible target for image-guided core needle biopsy 4.

The biopsy must include:

• Immunophenotypic analysis using flow cytometry and/or immunohistochemistry with Pan-B and Pan-T cell antigens 1
• Cytogenetic or molecular genetic analysis to identify characteristic chromosomal translocations 1
• FISH for major translocations depending on suspected subtype 1

Additional Essential Tests

• Bone marrow biopsy with aspirate is essential whenever treatment is considered, as bone marrow involvement occurs in 36-39% of intermediate-grade lymphomas and affects prognosis 1
• Serum protein electrophoresis to assess for hypergammaglobulinemia 1

Most Likely Diagnosis

Diffuse Large B-Cell Lymphoma (DLBCL)

DLBCL is the most probable diagnosis given the aggressive presentation with massive organomegaly and obstructive complications 5, 3. This subtype accounts for the majority of cases presenting with peritoneal, omental, and mesenteric involvement 3.

Key supporting features from the evidence:

• Peritoneal lymphomatosis (which can cause retroperitoneal lymphadenopathy) is most frequently seen in DLBCL 3
• Hepatosplenomegaly with retroperitoneal lymphadenopathy was observed in the majority of DLBCL cases in a series of peritoneal lymphoma 3
• Bilateral renal involvement can occur in ALL and lymphoma, though less common than other sites 6

Important Differential Considerations

Burkitt lymphoma should be considered given the potential for rapid growth and abdominal involvement, though it is less common 3. Follicular lymphoma typically has a more indolent course but can present with massive retroperitoneal adenopathy 4.

Management of Obstructive Hydronephrosis

Urgent urological consultation is required to address the bilateral obstructive hydronephrosis, which threatens renal function 1.

Options include:

• Bilateral percutaneous nephrostomy tubes as a temporizing measure before initiating chemotherapy 1
• Bilateral ureteral stent placement if technically feasible 1

The hydronephrosis will likely improve with effective lymphoma treatment, but acute kidney injury must be prevented in the interim 1.

Treatment Strategy

For Diffuse Large B-Cell Lymphoma (Most Likely)

In physically fit patients, the combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard first-line treatment 5. This regimen should be initiated promptly after tissue diagnosis is confirmed 1, 5.

• MUGA scan or echocardiogram must be performed before initiating anthracycline-containing regimens to assess baseline cardiac function 1
• Five to six cycles of R-CHOP are typically administered 5
• Prophylactic intrathecal chemotherapy should be considered given the high tumor burden and risk of CNS involvement 5

For Patients with Comorbidities

If significant cardiac dysfunction or renal insufficiency is present, dose-reduced regimens or alternative chemotherapy protocols should be considered 1.

Role of Splenectomy

Splenectomy is NOT the primary treatment for lymphoma with massive splenomegaly in the modern era 5. However, it may be considered in select cases for:

• Symptomatic relief from massive splenomegaly causing mechanical compression 5
• Obtaining definitive tissue diagnosis when other biopsy sites are inaccessible 5
• Severe hypersplenism causing life-threatening cytopenias 5

Chemotherapy remains the definitive treatment, and splenectomy, if performed, should be followed by systemic chemotherapy 5.

Prognostic Considerations

The presence of retroperitoneal lymphadenopathy is an adverse prognostic factor in some malignancies, though this is best studied in renal cell carcinoma rather than lymphoma 7. The extensive disease burden with multiple organ involvement suggests advanced stage disease (likely Stage IV) 1.

Elevated LDH, presence of B symptoms (fever, night sweats, weight loss), and performance status are critical prognostic factors that should be documented 1.

Critical Pitfalls to Avoid

• Do not delay tissue diagnosis by pursuing extensive additional imaging; the priority is obtaining histologic confirmation 1
• Do not assume this is a benign process such as autoimmune lymphoproliferative syndrome (ALPS), which requires chronic lymphadenopathy >6 months and elevated TCR-αβ⁺ DNT cells ≥1.5% of total lymphocytes—features not mentioned in this acute presentation 1
• Do not overlook the obstructive uropathy; bilateral hydronephrosis can rapidly progress to acute kidney injury and must be addressed urgently 1
• Do not initiate treatment without hepatitis B screening, as reactivation can be fatal 1
• Do not perform renal biopsy before excluding hematologic malignancy with less invasive testing, as bone marrow aspiration should be done first 6