Multiple Myeloma Presenting as Lower Gastrointestinal Bleeding: A Case Report.

Abbreviations

Gastrointestinal

Multiple Myeloma

Body Mass Index

International Normalized Ratio

Positron Emission Tomography–Computed Tomography

Intravenous

Immunoglobulin G

Bortezomib, Lenalidomide, and Dexamethasone regimen

Monoclonal Gammopathy of Unknown Significance

Smoldering Multiple Myeloma

National Comprehensive Cancer Network

Magnetic Resonance Imaging

Free Light Chain

Hyperviscosity Syndrome

Immunoglobulin

Introduction

Gastrointestinal (GI) bleeding most commonly arises from primary GI conditions such as peptic ulcer disease, acute gastric mucosal injury, neoplasms of the digestive tract, or esophageal varices secondary to hepatic cirrhosis. However, patients with hematologic malignancies may also develop GI bleeding, with reported incidence rates ranging from 10% to 30% [ 1 ]. The underlying mechanisms are typically multifactorial, including direct infiltration of malignant hematopoietic cells, mucosal injury, immunodeficiency‐related infections, coagulation abnormalities, and pre‐existing peptic ulcer disease [ 1 ].

Multiple myeloma (MM) is a malignant proliferation of a single clone of plasma cells, leading to the overproduction of structurally homogeneous immunoglobulins. The classic clinical features include anemia, renal dysfunction, skeletal destruction, recurrent infections, and hypercalcemia. Nevertheless, MM may present with atypical or extramedullary manifestations [ 2 ]. Among GI presentations, MM has been reported to cause acute or chronic pancreatitis, mesenteric ischemia secondary to amyloidosis, acute abdomen, and hepatosplenomegaly [ 2 ]. GI bleeding as an initial symptom remains extremely rare.

Case History/Examination

A 46‐year‐old Asian man with no known chronic illnesses presented with a three‐day history of fresh, bright red rectal bleeding, accompanied by generalized fatigue and myalgia. He also reported a dull, non‐localized headache that was worse in the mornings and unrelieved by paracetamol tablets. There was no history of similar episodes, change in bowel habits, fever, weight loss, abdominal pain, or urinary symptoms. He denied the use of nonsteroidal anti‐inflammatory drugs (NSAIDs), anticoagulants, or recreational drugs, and had no significant past medical, surgical, or family history.

The patient worked at a gold shop and reported a good appetite prior to symptom onset. He smoked several cigarettes daily and consumed alcohol occasionally.

On admission, he appeared pale and fatigued but was alert and oriented. His blood pressure was 165/100 mmHg; other vital parameters were within normal limits. The body mass index was 24.2 kg/m 2 . Physical examination revealed signs of volume depletion without external bleeding. Cardiovascular and respiratory examinations were unremarkable. The abdomen was soft with mild central tenderness but no guarding or organomegaly. Neurological and peripheral examinations were normal. Digital rectal examination showed no active bleeding, melena, or masses.

Differential Diagnosis, Investigations and Treatment

Initial investigations on March 10, 2025, revealed severe normocytic anemia (hemoglobin 5.5 g/dL) and a mildly prolonged INR of 1.4. Intravenous fluids, proton pump inhibitor infusion, analgesia, and transfusion of three units of packed red blood cells were initiated. The gastroenterology team was consulted and scheduled a colonoscopy. The following day, the patient's hemoglobin rose to 7.9 g/dL post‐transfusion. Key hematologic and biochemical findings on admission and after one week are summarized in Table 1 .

Laboratory tests demonstrated markedly elevated total serum protein (> 120 g/L), hypoalbuminemia (18 g/L), and a peripheral smear with rouleaux formation and plasmacytoid lymphocytes, suggesting hyperviscosity. Colonoscopy on March 13 revealed a small sessile rectal polyp, which was removed via cold snare, and internal hemorrhoids, with no other significant bleeding source identified. Despite these findings, anemia persisted, raising suspicion of systemic disease.

Conclusion and Results

Hematology consultation on March 14 raised suspicion for plasma cell dyscrasia, particularly MM. Workup included serum protein electrophoresis (SPEP), urine immunofixation, β2‐microglobulin testing, and skeletal survey. On March 15, results confirmed a monoclonal IgG kappa spike and IgG kappa paraproteinuria. Bone marrow aspiration showed clonal plasma cell proliferation, confirming the diagnosis of MM. To minimize the risk of worsening hyperviscosity, further transfusions were avoided unless strictly necessary.

Between March 17 and 18, a PET‐CT and skeletal survey confirmed multiple lytic bone lesions. Chemotherapy was initiated on March 20 with the VRd protocol (bortezomib, lenalidomide, and dexamethasone), along with supportive care including intravenous fluids, analgesia, and nutritional optimization. Sequential laboratory results at the start of chemotherapy, during transaminitis, and at discharge are presented in Table 2 .

On March 24, the patient received zoledronic acid after dental clearance for bone disease management. Although bleeding symptoms resolved, anemia persisted, requiring ongoing monitoring. Between March 25 and 31, the patient developed transaminitis, likely secondary to lenalidomide and other hepatotoxic agents. These drugs were temporarily held, resulting in the gradual normalization of liver enzymes. Between April 1 and 9, the patient remained clinically stable, with slow improvement in hemoglobin levels. Supportive therapy, including hydration, proton pump inhibitors, and nutritional support, was maintained, and lenalidomide reintroduction was planned for the next chemotherapy cycle.

By April 10, the patient remained stable, with no further bleeding or symptoms of hyperviscosity. He was deemed fit for discharge and referred for outpatient hematology follow‐up to continue therapy. A detailed summary of the patient's hospital course is provided in Table 3 .

Discussion

Plasma cell dyscrasias encompass a spectrum of disease, which includes asymptomatic premalignant proliferation of plasma cells (monoclonal gammopathy of unknown significance (MGUS)) and asymptomatic MM (smoldering MM (SMM)) to malignant disease (MM and plasma cell leukemia) with end‐organ damage and associated significant patient morbidity [ 3 ].

MM is a clonal plasma cell proliferative disorder characterized by the abnormal increase of monoclonal immunoglobulins. Unchecked, the excess production of these plasma cells can ultimately lead to specific end‐organ damage. It presents with a wide variety of symptoms, known as CRAB symptoms, with C—hypercalcemia (13%), R—renal failure (20%–40%), A—anemia (70%), and B—lytic bone lesions (80%), in addition to weight loss (24%) and recurrent infections [ 4 ]. The National Comprehensive Cancer Network (NCCN) criteria for the diagnosis of active MM include clonal bone marrow plasma cells ≥ 10%, the presence of biopsy‐confirmed bony or extramedullary plasmacytoma, and one or more myeloma‐defining events such as hypercalcemia (> 1 mg/dL higher than the upper limit), renal failure (creatinine > 2 mg/dL or creatinine clearance < 40 mL/min), anemia (hemoglobin < 10 g/dL or hemoglobin > 2 g/dL below the lower limit of normal), one or more osteolytic bone lesions on skeletal radiography, one or more focal ≥ 5 mm lesions on MRI scans, clonal bone marrow plasma cells ≥ 60%, and an abnormal serum‐free light chain (FLC) ratio ≥ 100 (involved kappa) or < 0.01 (involved lambda) [ 5 ].

In the present study, the patient presented with a history of rectal bleeding for 3 days and a low hemoglobin level. Colonoscopy was insignificant; although a polyp was identified on colonoscopy, it showed no evidence of active bleeding, stigmata of recent hemorrhage, or surrounding mucosal abnormalities. No other bleeding sources were identified during the procedure. Hemoglobin was still low, and the peripheral smear showed normocytic normochromic anemia with remarkable rouleaux formation. Other lab values showed low albumin with high protein; the patient was investigated for possible hyperviscosity syndrome.

Bone marrow aspiration and biopsy demonstrated clonal plasma cell proliferation, consistent with MM, and PET scan showed multifocal lytic lesions with low‐grade metabolic activity in keeping with MM. Treatment was commenced for the patient.

MM is the second most prevalent hematological malignancy, representing 2% of all cancer mortalities. Although usually restricted to the bone marrow, extramedullary involvement of this disease can occur in up to 20% of cases. The most common extramedullary site is the upper respiratory tract, including the oropharynx, nasopharynx, nasal cavities, sinuses, and larynx. Cases of MM with GI features are not uncommon. Reported GI manifestations include nausea, vomiting, and abdominal pain, while overt bleeding is exceedingly rare [ 6 ]. There are very few reported cases of MM presenting with GI hemorrhage [ 1 , 7 ].

Pathogenesis of GI bleeding in MM is through several pathways, including direct plasma cell infiltrations in the form of plasmacytomas, amyloid infiltration of the gut wall resulting in increased capillary fragility, platelet or coagulation abnormalities, and preceding peptic ulcers, which may sometimes be secondary to treatment with anti‐inflammatory medications and corticosteroids [ 7 , 8 ].

In this patient with MM, the prolonged INR with slightly prolonged aPTT, low functional fibrinogen, reduced antithrombin activity, protein S deficiency, and normal d dimer level—despite normal liver function tests, normal platelet count, and normal abdominal ultrasound—argue against liver disease or overt DIC. The findings are best explained by paraprotein‐related coagulation interference, particularly acquired dysfibrinogenemia.

In MM, monoclonal immunoglobulins can bind to fibrinogen and impair its conversion to fibrin or disrupt fibrin polymerization, producing a qualitative fibrinogen defect. This leads to defective clot formation and bleeding, often with prolonged PT and reduced functional fibrinogen levels. Paraproteins may also interfere with clot‐based laboratory assays, causing apparently low antithrombin and protein S activity without true severe deficiency. Overall, the pattern is most consistent with paraprotein‐mediated dysfibrinogenemia rather than hepatic failure or consumptive coagulopathy [ 9 , 10 ].

In this patient, there were no clinical or investigative features to suggest systemic amyloidosis as the primary process. He had no organomegaly on imaging, echocardiography was normal without features of restrictive cardiomyopathy, and colonoscopy showed no mucosal infiltrates or wall thickening. There was no overt proteinuria to suggest renal involvement, and whole‐body FDG PET‐CT demonstrated only multiple lytic bone lesions without evidence of soft‐tissue or visceral deposition. Taken together, the absence of clinical, biochemical, and radiologic indicators of organ infiltration makes systemic amyloidosis a low‐probability explanation in this case.

Hyperviscosity syndrome [HVS] results from a high blood viscosity due to an abnormal protein or cellular element increase, frequently secondary to plasma cell disorders with immunoglobulin (Ig). The clinical triad of HVS includes mucosal bleeding (epistaxis, gum), visual abnormalities (blurring, papilledema, retinal bleeding, venule thrombosis), and neurological abnormalities (drowsiness, ataxia, cerebral bleeding) [ 11 ].

Management consists of plasmapheresis (reduces serum viscosity by 20%–30%) with the definitive therapy being bortezomib‐based regimens and supportive care. Bortezomib and high‐dose steroids are associated with an immunomodulatory drug like thalidomide, lenalidomide, or alkylating agents like cyclophosphamide or melphalan [ 9 ]. This patient responded well to treatment, and his m protein improved. Coagulation test parameters also improved well on treatment.

This case highlights an uncommon initial presentation of MM with overt lower GI bleeding in a relatively young patient, underscoring the need to broaden the differential when endoscopic findings are nondiagnostic and hematologic clues suggest a plasma cell disorder. Early recognition of potential hyperviscosity and prompt hematology involvement are key to successful management. The patient's favorable response to VRd with adjunctive bone protection, alongside vigilant monitoring for treatment‐related hepatotoxicity and appropriate drug holds, demonstrates that timely, protocolized care can achieve bleeding control and clinical stabilization. Clinically, this report emphasizes three practical signals that should trigger myeloma workup in unexplained GI bleeding: disproportionate anemia, unexplained protein gap, and peripheral smear rouleaux. While limited by its single‐patient design, the case reinforces a simple pathway for front‐line teams: stabilize, screen for plasma cell dyscrasia when red flags exist, avoid unnecessary transfusions in suspected hyperviscosity, and start myeloma‐directed therapy early with close biochemical surveillance.

Author Contributions

Ahmed Arabi: conceptualization, data curation, investigation, methodology, writing – original draft, writing – review and editing. Naseem Ambra: conceptualization, data curation, investigation, methodology, writing – review and editing. Asgad Mohamed Ahmed Eltigani: methodology, writing – original draft. Asma Ahmed Yousif: methodology, writing – original draft. Abdelkarim Hashim Mohamed: supervision, writing – original draft.

Funding

The authors have nothing to report.

Consent

Written informed consent was obtained from the patient for publication of their medical information described in this case report.

Conflicts of Interest

The authors declare no conflicts of interest.

Arabi A., Ambra N., Eltigani A. M. A., Yousif A. A., and Mohamed A. H., “Multiple Myeloma Presenting as Lower Gastrointestinal Bleeding: A Case Report,” Clinical Case Reports 14, no. 5 (2026): e72340, 10.1002/ccr3.72340.

Ahmed Arabi and Naseem Ambra co‐principal investigator.

Data Availability Statement

Data is available upon reasonable request to the corresponding author.

References

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Associated Data

Data Availability Statement

Data is available upon reasonable request to the corresponding author.