Primary gastric plasmacytoma evolving to non-secretory multiple myeloma: A case report.

1. Introduction

Extramedullary plasmacytoma is a localized monoclonal plasma cell neoplasm arising outside the bone marrow and accounts for fewer than 5% of plasma cell neoplasms. [ 1 , 2 ] Most lesions occur in the upper aerodigestive tract, whereas gastrointestinal involvement is relatively uncommon, and primary gastric involvement is particularly rare. [ 2 , 3 ]

Although approximately 100 cases of gastric plasmacytoma have been reported, most evidence is derived from individual case reports and small case series, resulting in substantial heterogeneity in clinical presentation, endoscopic findings, and treatment strategies. [ 2 , 4 ] The endoscopic appearance of gastric plasmacytoma is variable and often nonspecific, typically presenting as a protruding or subepithelial lesion, ulcerative lesion, or mucosal irregularity, and frequently leading to an initial differential diagnosis of gastric adenocarcinoma, mucosa-associated lymphoid tissue (MALT) lymphoma, or gastrointestinal stromal tumor. [ 1 , 2 , 5 ] Accurate diagnosis, therefore, requires histopathologic confirmation of monoclonal plasma cell proliferation and exclusion of systemic disease. [ 1 , 2 , 6 , 7 ]

Given the limited and heterogeneous nature of the available literature, management strategies for gastric plasmacytoma remain diverse. Reported approaches include endoscopic resection for superficial lesions, surgical resection for more extensive disease, and radiotherapy (RT) as an organ-preserving option, with systemic therapy reserved for selected cases. [ 8 – 11 ] RT is generally effective due to the radiosensitivity of plasma cell neoplasms; however, histologic response may not parallel the initial clinical or endoscopic response, and delayed histologic remission or persistent residual disease has been described. [ 11 – 13 ] Although primary gastric plasmacytoma is generally regarded as a localized disease, progression to multiple myeloma has been reported in a small number of patients, emphasizing the importance of long-term surveillance. [ 8 , 14 – 17 ]

Here, we report a patient with primary gastric plasmacytoma who initially fulfilled the diagnostic criteria for localized disease and was treated with definitive radiotherapy. Despite delayed histologic remission of the primary gastric lesion, the patient subsequently developed biopsy-confirmed skeletal plasma cell neoplasm and was ultimately managed as non-secretory multiple myeloma. This case highlights the importance of integrating sequential clinicopathologic findings during follow-up and illustrates that long-term surveillance remains essential even when the initial staging supports localized disease.

2. Case presentation

The Institutional Review Board of Chungbuk National University Hospital approved the study (IRB No: 2026-04-029), and this study was performed with written informed consent and adhered to the guidelines established by the Declaration of Helsinki.

A 75-year-old man with no significant past medical or family history underwent screening esophagogastroduodenoscopy in February 2024. This revealed an approximately 3-cm protruding mass located on the posterior wall of the gastric body (Fig. 1 A). The lesion was initially suspected to represent advanced gastric carcinoma, and a biopsy was performed at an outside institution. Physical examination revealed no remarkable findings.

Endoscopic findings of primary gastric plasmacytoma. (A) Initial esophagogastroduodenoscopy demonstrating an approximately 3-cm protruding mass located on the posterior wall of the gastric body. (B) Follow-up endoscopy performed approximately 3 mo after radiotherapy showing marked regression of the lesion with residual mucosal irregularity. (C) Follow-up endoscopy performed approximately 9 mo after radiotherapy demonstrating near-complete resolution of the lesion.

The outside pathology report described a malignant tumor with differential diagnoses including poorly differentiated adenocarcinoma, malignant lymphoma, and neuroendocrine tumor. Slide review at our institution demonstrated atypical plasmacytoid cell proliferation, raising concern for a plasma cell neoplasm, including plasmacytoma or MALT lymphoma with marked plasmacytic differentiation.

Repeat endoscopic biopsy performed at our institution showed diffuse infiltration of monotonous plasmacytoid cells within the lamina propria (Fig. 2 A). The tumor cells exhibited eccentric nuclei, clumped chromatin, and moderate eosinophilic cytoplasm. No significant nuclear pleomorphism, prominent nucleoli, or high-grade cytologic atypia were identified. In addition, lymphoepithelial lesions and a significant small B-cell component were not observed.

Histologic and immunohistochemical findings at the initial diagnosis. (A) Hematoxylin and eosin staining showing diffuse infiltration of plasmacytoid cells within the lamina propria (×200). (B) Immunohistochemical staining for CD138 demonstrating diffuse expression in the neoplastic plasma cells (×200). (C) Immunohistochemical staining for kappa light chain showing monotypic expression (×200). (D) Immunohistochemical staining for lambda light chain showing absence of expression, confirming light-chain restriction (×200).

Immunohistochemical staining demonstrated CD138 positivity and kappa light-chain restriction with negative lambda staining (Fig. 2 B–D). CD20 immunohistochemistry showed only scattered background B lymphocytes. The Ki-67 labeling index was approximately 30%. Taken together, the morphologic and immunophenotypic findings were consistent with a plasma cell neoplasm and were most compatible with plasmacytoma in the appropriate clinical context.

Comprehensive systemic evaluation was subsequently performed. Bone marrow biopsy revealed normocellular marrow without evidence of plasma cell neoplasm, with plasma cells accounting for 4.7% of marrow cellularity. Serum and urine protein electrophoresis and immunofixation studies demonstrated no monoclonal protein. Serum free light-chain analysis showed mildly elevated free κ light chains (23.61 mg/L) with a normal κ/λ ratio (1.17). Baseline laboratory evaluation showed a hemoglobin level of 13.0 g/dL, serum calcium of 8.8 mg/dL, and serum creatinine of 0.94 mg/dL.

Positron emission tomography/computed tomography (PET/CT) demonstrated increased uptake confined to the gastric lesion, without evidence of systemic disease (Fig. 3 A and B). Based on these findings, the patient was diagnosed with solitary gastric plasmacytoma.

Baseline positron emission tomography/computed tomography findings. (A) Whole-body maximum intensity projection image demonstrating no abnormal hypermetabolic lesions outside the stomach. (B) Axial fused PET/CT image demonstrating focal hypermetabolic activity along the gastric wall corresponding to the primary lesion. PET/CT = positron emission tomography/computed tomography.

After multidisciplinary discussion, definitive RT was selected as an organ-preserving treatment. Radiotherapy was delivered to the stomach using intensity-modulated radiotherapy with volumetric modulated arc therapy to a total dose of 45 Gy in 25 fractions over approximately 5 weeks. Treatment was well tolerated without acute toxicity.

Follow-up endoscopy demonstrated marked regression of the lesion at 3 months and near-complete resolution at 9 months after RT (Fig. 1 B and C). Histologic examination of the 3-month follow-up biopsy demonstrated persistent plasma cell infiltration on H&E sections with diffuse CD138 positivity and persistent kappa light-chain restriction (Fig. 4 A–D). In contrast, the 9-month follow-up biopsy showed only sparse residual plasma cells on H&E sections without light-chain restriction, demonstrating a polytypic kappa/lambda pattern consistent with histologic remission (Fig. 5 A–D).

Three-month follow-up biopsy after definitive radiotherapy. (A) Hematoxylin and eosin staining showing residual plasma cell infiltration (×200). (B) CD138 immunohistochemistry demonstrating persistent plasma cell infiltration (×200). (C) Kappa light-chain immunohistochemistry showing persistent monotypic expression (×200). (D) Lambda light-chain immunohistochemistry showing absence of expression, consistent with persistent light-chain restriction (×200).

Nine-month follow-up biopsy after definitive radiotherapy. (A) Hematoxylin and eosin staining showing marked regression of the plasma cell infiltrate (×200). (B) CD138 immunohistochemistry demonstrating only scattered residual plasma cells (×200). (C) Kappa light-chain immunohistochemistry showing loss of monotypic expression (×200). (D) Kappa and lambda light-chain immunohistochemistry demonstrating a polytypic staining pattern, consistent with histologic remission (×200).

During surveillance, contrast-enhanced CT performed in February 2026 demonstrated multifocal osteolytic lesions involving the spine, which were initially interpreted as possible metastatic disease (Fig. 6 A and B). Subsequent PET/CT performed in April 2026 demonstrated multifocal hypermetabolic lesions involving the maxillae and extensive skeletal sites, including the clavicle, vertebral column, sternum, ribs, pelvis, and femur (Fig. 7 A and B). Biopsy of the L5 vertebral lesion confirmed a plasma cell neoplasm showing CD138 positivity, kappa light-chain restriction, a Ki-67 labeling index of approximately 30%, and negativity for CD20 and CD56 (Fig. 8 A–D). Despite biopsy-confirmed plasma cell neoplasm with multifocal skeletal involvement, serum and urine protein electrophoresis and immunofixation remained negative. Serum free light-chain analysis demonstrated an increase in free κ light chains to 64.77 mg/L, whereas free λ light chains remained 17.54 mg/L. At the time of systemic progression, the hemoglobin level was 10.8 g/dL, serum calcium 9.0 mg/dL, and serum creatinine 0.88 mg/dL (Table 1 ).

Table 1 Serial clinicopathologic findings from diagnosis to systemic progression. Parameter Baseline (March 2024) Systemic progression (February–April 2026) Final diagnosis (June 2026) Bone marrow plasma cells 4.7% Not repeated Not repeated Serum protein electrophoresis No M-spike No M-spike No M-spike Serum immunofixation Negative Negative Negative Urine immunofixation Negative Negative Negative Free κ light chain (mg/L) 23.61 64.77 – Free λ light chain (mg/L) 20.13 17.54 – Hemoglobin (g/dL) 13.0 10.8 11.9 Serum calcium (mg/dL) 8.8 9.0 10.1 Serum creatinine (mg/dL) 0.94 0.88 1.28 Imaging PET/CT: localized gastric uptake CT: multifocal osteolytic lesions PET/CT: multifocal hypermetabolic skeletal lesions Pathologic clavicular fracture Pathology Gastric plasmacytoma L5 biopsy: plasma cell neoplasm Non-secretory MM Serial laboratory, imaging, and pathologic findings from diagnosis to systemic progression. Bone marrow examination was performed only at diagnosis and was not repeated after the development of skeletal lesions. Serum and urine electrophoresis and immunofixation remained negative throughout follow-up, despite progressive skeletal disease. PET/CT = positron emission tomography/computed tomography.

Serial clinicopathologic findings from diagnosis to systemic progression.

Serial laboratory, imaging, and pathologic findings from diagnosis to systemic progression. Bone marrow examination was performed only at diagnosis and was not repeated after the development of skeletal lesions. Serum and urine electrophoresis and immunofixation remained negative throughout follow-up, despite progressive skeletal disease.

PET/CT = positron emission tomography/computed tomography.

Contrast-enhanced computed tomography demonstrating multifocal osteolytic skeletal lesions. (A) Coronal reformatted contrast-enhanced CT image demonstrating multifocal osteolytic lesions involving the thoracolumbar spine. (B) Representative axial contrast-enhanced CT image showing one of the lumbar osteolytic lesions. These lesions were initially interpreted as possible metastatic disease but were retrospectively recognized as the earliest radiologic manifestation of evolving multiple myeloma. CT = computed tomography.

Follow-up positron emission tomography/computed tomography demonstrating systemic skeletal involvement. (A) Whole-body maximum intensity projection image showing multifocal hypermetabolic lesions involving the maxillae and multiple skeletal sites. (B) Axial fused PET/CT image demonstrating intense fluorodeoxyglucose uptake in the L5 vertebral body corresponding to the biopsy site. PET/CT = positron emission tomography/computed tomography.

Histologic and immunohistochemical findings of the L5 vertebral biopsy. (A) Hematoxylin and eosin staining demonstrating diffuse plasma cell infiltration replacing the normal bone marrow (×200). (B) CD138 immunohistochemistry highlighting the neoplastic plasma cells (×200). (C) Kappa light-chain immunohistochemistry showing monotypic expression (×200). (D) Lambda light-chain immunohistochemistry showing absence of expression, confirming kappa light-chain restriction (×200).

Subsequently, the patient developed a pathologic fracture of the left clavicle. Following multidisciplinary reassessment by the hematology service, the patient was ultimately managed as non-secretory multiple myeloma, and systemic therapy with bortezomib, lenalidomide, and dexamethasone (VRd) was initiated. A schematic overview of the patient’s clinical course is presented in Figure 9 .

Clinical timeline illustrating the evolution from localized gastric plasmacytoma to non-secretory multiple myeloma. The timeline summarizes the initial diagnosis, definitive radiotherapy, delayed histologic remission, subsequent skeletal progression, and final clinical diagnosis of non-secretory multiple myeloma.

3. Discussion

Primary gastric plasmacytoma is a rare plasma cell neoplasm that may clinically and endoscopically mimic gastric carcinoma, lymphoma, or subepithelial tumors, often making diagnosis challenging and requiring repeated biopsy with careful histopathologic evaluation. [ 1 , 4 , 17 , 18 ] In the present case, the initial biopsy performed at an outside institution was interpreted as a malignant tumor with differential diagnoses including poorly differentiated adenocarcinoma, malignant lymphoma, and neuroendocrine tumor, illustrating the diagnostic difficulty of this rare entity.

Histopathologic examination combined with immunophenotyping is therefore essential for establishing the diagnosis. The most important differential diagnosis is MALT lymphoma with marked plasmacytic differentiation. [ 1 , 6 ] In the present case, the lesion showed a relatively uniform proliferation of plasmacytoid cells without lymphoepithelial lesions or a significant small B-cell component, findings that favored plasmacytoma over MALT lymphoma.

A critical step in the diagnosis of gastric plasmacytoma is distinguishing a truly localized lesion from systemic disease. Contemporary diagnostic recommendations emphasize comprehensive staging, including bone marrow examination, serum and urine protein electrophoresis with immunofixation, serum free light-chain analysis, and whole-body imaging, because extramedullary plasmacytoma may represent the initial manifestation of multiple myeloma rather than an isolated lesion. [ 7 , 19 ] At the time of initial diagnosis, our patient fulfilled the diagnostic criteria for solitary gastric plasmacytoma. Bone marrow examination demonstrated only 4.7% plasma cells without evidence of plasma cell neoplasm; serum and urine electrophoresis and immunofixation studies were negative; serum free light-chain analysis showed only mildly increased free κ light chains with a normal κ/λ ratio; and PET/CT demonstrated uptake confined to the stomach without evidence of systemic disease. These findings supported an initial diagnosis of localized gastric plasmacytoma.

The association between gastric plasmacytoma and Helicobacter pylori infection remains controversial. Although regression following eradication therapy has been reported in some patients, persistence of disease despite successful eradication has also been described, suggesting that chronic antigenic stimulation is unlikely to account for all cases. [ 3 , 6 , 20 ] In the present case, Helicobacter pylori infection was excluded by Giemsa staining.

To better contextualize the present case, we reviewed previously published reports of primary gastric plasmacytoma identified through a PubMed search using the keywords “gastric plasmacytoma” and “stomach plasmacytoma.” Representative reports describing clinicopathologic features, treatment, and follow-up were preferentially reviewed and compared with the present case. Rather than viewing the literature as isolated case reports, the published cases suggest several recurring clinical patterns. First, some cases are initially misdiagnosed as gastric carcinoma, lymphoma, or submucosal tumors and are subsequently reclassified as plasmacytoma after repeated biopsy or surgical resection. [ 1 , 2 , 17 ] Second, superficial or mucosa-confined lesions have been successfully treated with endoscopic mucosal resection or endoscopic submucosal dissection, suggesting that minimally invasive approaches are feasible in carefully selected early lesions. [ 5 , 9 , 10 , 21 ] Third, localized gastric plasmacytomas have been successfully managed with definitive radiotherapy as an organ-preserving strategy, although reported outcomes range from complete remission to delayed histologic clearance, persistent residual disease, and radiation-resistant tumors. [ 11 – 13 ] Finally, although most reported gastric plasmacytomas remained localized after local therapy, progression to multiple myeloma has been reported in a small number of cases, highlighting the importance of long-term surveillance even in patients initially classified as having localized disease. [ 8 , 15 – 17 ]

Radiotherapy remains the preferred organ-preserving treatment for localized extramedullary plasmacytoma because plasma cell neoplasms are generally highly radiosensitive. [ 7 ] Histologic response after radiotherapy, however, may not parallel the initial clinical or endoscopic response. Among the published cases treated with definitive radiotherapy, Tan et al described 2 patients who both achieved durable clinicopathologic remission despite different response kinetics. [ 11 ] In one patient, a biopsy performed 3 months after radiotherapy still demonstrated persistent monoclonal plasma cells despite marked endoscopic regression, with complete histologic remission documented on subsequent follow-up. A similar phenomenon has also been reported in more recent cases, in which residual disease after radiotherapy prompted additional local treatment such as endoscopic submucosal dissection, while other patients exhibited persistent radiation-resistant disease requiring systemic therapy. [ 12 , 13 ]

The present case further expands this spectrum of post-radiotherapy response. Residual monoclonal plasma cells with persistent kappa light-chain restriction were identified on a biopsy performed 3 months after radiotherapy despite marked endoscopic regression. However, the 9-month biopsy demonstrated loss of light-chain restriction with a polytypic kappa/lambda pattern, indicating histologic remission without additional local treatment. These findings suggest that early post-radiotherapy biopsy should be interpreted cautiously because histologic clearance may lag behind clinical and endoscopic response, and residual plasma cells do not necessarily indicate treatment failure.

Beyond the variable histologic response after radiotherapy, this case also illustrates the diagnostic challenges associated with subsequent disease evolution. Although the patient fulfilled the diagnostic criteria for solitary gastric plasmacytoma at the time of initial diagnosis, based on the absence of bone marrow involvement, negative serum and urine electrophoresis and immunofixation studies, a normal serum free κ/λ ratio, and PET/CT findings confined to the stomach, the subsequent clinical course demonstrated evolution to non-secretory multiple myeloma. [ 7 , 19 ]

In retrospect, the multifocal osteolytic lesions identified on contrast-enhanced CT in February 2026 most likely represented the earliest radiologic manifestation of systemic disease. At the time, however, these lesions were not initially attributed to plasma cell neoplasia because there was no biochemical evidence of multiple myeloma and no clinical suspicion of disease recurrence. Even after biopsy of the L5 vertebral lesion confirmed plasma cell neoplasm in April 2026, the findings were initially interpreted as recurrent plasmacytoma rather than multiple myeloma. Only after the subsequent development of a pathologic clavicular fracture did the overall clinical picture become consistent with evolving non-secretory multiple myeloma, prompting the initiation of systemic therapy.

According to current IMWG diagnostic criteria, the development of multifocal osteolytic bone lesions fulfilled a myeloma-defining event despite persistently negative serum and urine electrophoresis and immunofixation studies. [ 7 , 19 ] This interpretation is further supported by the gradual increase in serum free κ light-chain levels during follow-up. Although these biochemical abnormalities were insufficient to establish a diagnosis of multiple myeloma at the time, they became more meaningful when considered together with the patient’s subsequent clinical progression. Repeat bone marrow examination was not performed after systemic skeletal involvement became evident, representing a limitation of the present report. Nevertheless, the sequential integration of imaging findings, biopsy confirmation, laboratory trends, and subsequent clinical progression strongly supported the clinical diagnosis of non-secretory multiple myeloma. Solitary plasmacytoma represents part of the spectrum of plasma cell disorders, and the present case illustrates that apparently localized disease may evolve into multiple myeloma despite an initially favorable response to local therapy. This case underscores that persistently negative serum and urine electrophoresis or immunofixation should not preclude careful evaluation of newly detected skeletal lesions, particularly when accompanied by evolving clinical findings.

4. Conclusions

Primary gastric plasmacytoma is a rare plasma cell neoplasm that is typically localized at presentation and generally responds well to definitive radiotherapy. This case demonstrates that histologic remission may be delayed after radiotherapy and that systemic progression to non-secretory multiple myeloma may occur despite the absence of systemic disease at initial staging. Although such progression appears to be uncommon, long-term surveillance integrating clinical, radiologic, and pathologic findings remains essential, and early post-treatment biopsy findings should be interpreted in the context of the overall clinical course.

Acknowledgments

The authors used an artificial intelligence–assisted language tool to support manuscript organization and language editing. The authors reviewed and approved the final content and take full responsibility for the manuscript.

Author contributions

Conceptualization: Chang Gok Woo, Seung-Myoung Son.

Data curation: Yong-Pyo Lee, Jun Su Lee.

Investigation: Yong-Pyo Lee, Jun Su Lee, Gyu Sang Yoo, Chang Gok Woo.

Resources: Gyu Sang Yoo, Chang Gok Woo.

Supervision: Seung-Myoung Son.

Writing – original draft: Yong-Pyo Lee, Seung-Myoung Son.

Writing – review & editing: Yong-Pyo Lee, Jun Su Lee, Gyu Sang Yoo, Chang Gok Woo, Seung-Myoung Son.