Introduction
Solitary plasmacytoma (SP) is an infrequent condition marked by the localized growth of monoclonal plasma cells. There are two identified forms of localized plasma cell neoplasms: solitary plasmacytoma of bone (SBP) and primary extraosseous/extramedullary plasmacytoma (EMP). EMP accounts for only 3-5% of plasma cell malignancies and typically occurs at extranodal sites, with 90% of cases found in the head and neck region [ 1 ]. Gastrointestinal involvement is rare, representing less than 5% of all EMP cases [ 2 ]. This entity is usually localized but may progress to multiple myeloma depending on marrow involvement, with a 10% risk of progression to multiple myeloma at three years if no clonal plasma cells are present in the bone marrow, and a 20% risk of progression at three years if there is minimal marrow involvement (<10% clonal plasma cells)[ 2 ]. The most common clinical presentation is gastrointestinal bleeding or peptic ulcers that do not improve with conventional treatment [ 3 , 4 , 5 ].
Herein, we report a case of a patient initially diagnosed with gastric adenocarcinoma. Surgical pathology unexpectedly revealed dual primary tumors: gastric adenocarcinoma and gastric plasmacytoma (GP). The latter is an example of primary extraosseous plasmacytoma (EMP), illustrating the importance of considering EMP in differential diagnoses of gastric tumors.
Case presentation
A 63-year-old female presented with recent-onset epigastric pain accompanied by unintentional weight loss of 2 kg. She denied any associated gastrointestinal symptoms, including changes in bowel habits, nausea, vomiting, or signs of gastrointestinal bleeding. Her vital signs were within normal limits. The abdominal examination was normal, with no masses or adenopathy palpated. Her past medical history was unremarkable, with no known chronic illnesses or prior significant medical conditions. A contrast-enhanced abdominal CT scan was performed, revealing a solid mass suggestive of malignancy in the posteromedial wall of the gastric fundus, accompanied by nearby neoplastic lymphadenopathy. Figure 1 illustrates a contrast-enhanced abdominal computed tomography (CT) scan.
An upper gastrointestinal endoscopy was conducted, revealing subepithelial solid masses in the gastric fundus. Biopsies were taken during the procedure, and subsequent histopathological examination confirmed the presence of tubular gastric adenocarcinoma stage IIA disease. Helicobacter pylori testing yielded negative results. The patient underwent a perioperative FLOT chemotherapy (docetaxel, oxaliplatin, and fluorouracil/leucovorin) followed by gastrectomy.
In the surgical pathology examination, surprisingly, high-grade gastric dysplasia/adenocarcinoma in situ (tumor size: 0.5 cm in largest diameter) without infiltrating component was found, coexisting with morphological and immunohistochemical findings compatible with involvement by plasma cell neoplasia (tumor size approximately: 11 x 7 x 4 cm) and six out of 21 perigastric lymph nodes involved by plasma cell neoplasia. Immunohistochemical analysis of the tumor cells showed positivity for CD38 and monotypic expression of a kappa light chain, without an expression of a lambda light chain; confirming plasmacytic lineage. As shown in Figure 2 , a detailed morphological and immunohistochemical analysis of the tumor lesion was performed.
Serum protein electrophoresis showed a monoclonal protein peak. Molecular analysis revealed deletion of TP53 and rearrangement of IgH, indicative of high-risk neoplasia associated with adverse prognosis and increased mortality.
Furthermore, serum and urine immunofixation assays detected monoclonal protein band IgG kappa. Bone marrow biopsy yielded negative results for clonal plasma cells or other aberrations, no lytic lesions were observed on the low-dose whole-body CT scan, and there were no findings of hypercalcemia or anemia.
Following gastrectomy, an 18-FDG PET/CT scan was performed, revealing no evidence of infiltrative pathology at the surgical site or elsewhere anatomically; also, an immunofixation assay was negative for monoclonal protein bands. Considering the primary nature of the completely resected GP and the absence of clonal plasma cell involvement in the bone marrow, the patient was deemed to be in remission. However, stringent monitoring with serum protein electrophoresis with immunofixation, and 18-FDG PET/CT scan was also recommended for ongoing surveillance.
Discussion
The importance of defining active treatment versus monitoring lies in the fact that patients with SP have a higher risk of developing symptomatic multiple myeloma (MM) in the next 10 years (60% SBP and 20% EMP) [ 4 , 6 ]. One of the prognostic factors in SBP for progression to MM is bone marrow infiltration by clonal plasma cells at diagnosis. Another predictor of progression is the presence at diagnosis of serum-free light chains (sFLC) and positivity after treatment. Progression of an SP is defined as local relapse, the appearance of additional lesions without signs of MM, or progression to MM [ 4 ]. Table 1 presents the diagnostic criteria for SB and related disorders.
Table 1
Diagnostic criteria for solitary plasmacytoma and overlapping disorders EMP: extraosseous/extramedullary plasmacytoma, PC: plasma cell, BM: bone marrow, MM: multiple myeloma, SBP: solitary bone plasmacytoma, PET-CT: positron emission tomography-computed tomography Adapted from [ 7 ]
| Plasmacytoma | Serum monoclonal protein | Bone marrow | End organ damage | Work-up PET-CT | Risk of progression to MM | Primary Treatment | Additional Treatment Options | ||
| Solitary plasmacytoma | Solitary plasmacytoma | Present | Not required for diagnosis, but a monoclonal protein may be present. | Negative | Not required | No other lesions | 10% will progress to MM within 3 years | Local radiotherapy | Surgery (if accessible and resectable) |
| Solitary plasmacytoma with minimal bone marrow involvement | Present | Not required for diagnosis, but a monoclonal protein may be present. | Monoclonal PC infiltration < 10% | Absent | No other lesions | 60% with SBP or 20% with EMP will progress to MM within 3 years | Local radiotherapy and close monitoring | Chemotherapy (if progression occurs) | |
| Multiple myeloma | Macrofocal myeloma | Present and multiple | Not required for diagnosis, but a monoclonal protein may be present. | Monoclonal PC infiltration < 10% | Possible but Limited systemic symptoms | Multiple bone or other organ lesions | 30% to 50% over a period of 2 to 5 years. | Combination chemotherapy | Autologous stem cell transplant, radiotherapy for focal lesions |
| Multiple myeloma | Not required but can occur | Present but may be absent in the case of non-secretory myeloma | Monoclonal PC infiltration ≥ 10% | Present | Multiple bone or other organ lesions | Meets criteria for multiple myeloma | Combination chemotherapy | Autologous stem cell transplant |
Most patients with GPs are elderly with nonspecific symptoms, including anorexia, weight loss, epigastric discomfort, or gastrointestinal bleeding [ 6 ]. During endoscopy, GPs often appear as nodular masses, which typically leads to differential diagnoses such as gastrointestinal stromal tumors (GISTs) or lymphomas. Frequently, the findings on endoscopy simulate a carcinoma when the mass is ulcerated or a linitis plastica when mucosal folds are diffusely thickened [ 6 , 7 ].
Among the therapeutic possibilities for a solitary SP is fractionated localized radiotherapy with doses between 40-50 Gy, this being currently the standard of care, with good response rates evidenced in retrospective analyzes, but without randomized controlled trials comparing this approach with best supportive care or chemotherapy. Another therapeutic option is surgical resection, usually followed by radiotherapy due to the risk of relapse. This option is recommended in SBP only if a surgical approach is required due to bone pathology. In EMP, it is recommended only in cases of defined, large lesions. Chemotherapy as a post-radiation adjuvant treatment is controversial [ 7 , 8 ].
Post-treatment follow-up is recommended in the case of measurable diseases according to the International Myeloma Working Group (IMWG) criteria; in the case of non-measurable diseases, the Response Evaluation Criteria in Solid Tumours (RECIST) criteria are added [ 7 ]. Table 2 presents case reports of plasmacytomas located in the gastrointestinal tract, detailing their characteristics and treatment approaches. We have compared the management of our patient with these standard approaches documented in the literature, and as shown in Table 2 , our approach is aligned with established practices. This is the first reported case of the coexistence of gastric adenocarcinoma in situ and GP. To date, no standard clinical care protocol for this combination is defined in the literature. For gastric adenocarcinoma in situ, treatment typically involves endoscopic resection or surgical intervention, depending on the extent and localization of the disease. However, the management of cases with concurrent plasmacytoma is not well established.
Table 2
Published case reports of intra-abdominal extramedullary plasmacytoma
| Study | Country | Patient | Anatomical location | Presentation | Therapy | ||
| Age (years) | Sex | Operative | Non-operative | ||||
| Park et al., 2014 [ 9 ] | South Korea | 70 | Male | Stomach | Dyspepsia | Endoscopic submucosal resection | Thalidomide, dexamethasone |
| Zhao et al., 2014 [ 10 ] | China | 79 | Male | Stomach | Epigastric pain | Total gastrectomy, subtotal pancreatectomy, splenectomy | None |
| Han et al., 2014 [ 11 ] | South Korea | 62 | Male | Stomach | Periumbilical pain | Gastric bypass (palliative) | None |
| Fukuhara et al., 2016 [ 12 ] | Japan | 36 | Male | Stomach | Dyspnea, fatigue | Total gastrectomy, extended lymphadenectomy | Bortezomib, cyclophosphamide, dexamethasone |
| Ammar et al., 2010 [ 13 ] | USA | 69 | Female | Duodenum | Fatigue, melaena | Percutaneous transhepatic biliary drainage | Extracorporeal radiotherapy |
| Ariyarathenam et al., 2013 [ 14 ] | UK | 58 | Male | Ileum | Intussusception, small bowel obstruction | Segmental small bowel resection | None |
| Gabriel et al., 2014 [ 15 ] | USA | 62 | Male | Ileum, caecum | Melaena | Endoscopic submucosal resection (failed), right hemicolectomy | None |
| Weidenbaum, 2020 [ 16 ] | USA | 83 | Female | Stomach | Anemia | None | Extracorporeal radiotherapy and bortezomib, cyclophosphamide, dexamethasone |
| Jeong Lee et al., 2020 [ 17 ] | South Korea | 63 | Female | Stomach | Abdominal pain | Surgical resection | None |
| Vara-luis et al., 2024 [ 18 ] | Portugal | 71 | Female | Stomach | Dyspepsia | Surgical resection | None |
Conclusions
The simultaneous presentation of gastric adenocarcinoma in situ and primary gastric extraosseous plasmacytoma is unprecedented in the medical literature, underscoring the exceptional nature and clinical importance of this case. There is no consensus on a standardized treatment protocol for EMP. Existing studies indicate that the most common treatments are surgery or radiation therapy, sometimes combined with chemotherapy. In addition, there are no long-term follow-up studies specifically focusing on GPs.
Disclosures
Human subjects: Consent was obtained or waived by all participants in this study.
Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following:
Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work.
Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work.
Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.
Author Contributions
Concept and design: Sergio A. Bolivar, Humberto Martinez-Cordero, Maria Cynthia Fuentes, German Salguedo
Acquisition, analysis, or interpretation of data: Sergio A. Bolivar, Patricia Medina, Maria Cynthia Fuentes, German Salguedo
Drafting of the manuscript: Sergio A. Bolivar, Humberto Martinez-Cordero, Patricia Medina, Maria Cynthia Fuentes, German Salguedo
Critical review of the manuscript for important intellectual content: Sergio A. Bolivar, Humberto Martinez-Cordero, Patricia Medina, Maria Cynthia Fuentes, German Salguedo
Supervision: Sergio A. Bolivar, Humberto Martinez-Cordero, German Salguedo
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