==== Front Intern Med Intern Med Internal Medicine 0918-2918 1349-7235 The Japanese Society of Internal Medicine 36104190 10.2169/internalmedicine.0035-22 Case Report Incidentally Detected Extramedullary Plasmacytoma of the Gallbladder: A Case Report and Literature Review Ono Hideki 1 Iwatsu Shinichi 1 Otsuka Eiichi 2 Kato Yuji 1 1 Department of Gastroenterology, Oita Prefectural Hospital, Japan 2 Department of Hematology, Oita Prefectural Hospital, Japan Correspondence to Dr.　Hideki Ono, spgh6299@dune.ocn.ne.jp 13 9 2022 15 4 2023 62 8 11451149 28 3 2022 24 7 2022 Copyright © 2023 by The Japanese Society of Internal Medicine https://creativecommons.org/licenses/by-nc-nd/4.0/ The Internal Medicine is an Open Access journal distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view the details of this license, please visit (https://creativecommons.org/licenses/by-nc-nd/4.0/). Extramedullary plasmacytoma (EMP) can rarely occur in conjunction with multiple myeloma (MM). EMPs are usually detected in the upper aerodigestive tract (UAD) but can also occur along the digestive tract. However, the involvement of gallbladder is uncommon. Gastrointestinal tract symptoms often lead to the diagnosis of EMP in the gallbladder. An 81-year-old man was referred to our hospital with suspected primary gallbladder carcinoma. He was subsequently operated on, and the pathological findings showed EMP of the gallbladder without MM. plasmacytoma gallbladder multiple myeloma ==== Body pmcIntroduction Multiple myeloma (MM) is a common hematologic malignancy characterized by intramedullary clonal plasma cell proliferation. Extramedullary plasmacytoma (EMP) involves any tissue outside the skeleton and is rarely seen in patients with MM (1,2). On preoperative imaging, it is difficult to distinguish gallbladder EMP from gallbladder carcinoma, the most common malignant gallbladder tumor (2). We herein report a case of incidentally detected gallbladder EMP without MM. Case Report An 81-year-old man was admitted to our hospital because of an asymptomatic gallbladder tumor detected by transabdominal ultrasonography (TAUS) at a periodic health checkup. He had a history of appendectomy, pulmonary emphysema, and prostate hypertrophy but no malignant neoplasms, including a hematopoietic organ tumor. An initial blood examination revealed slightly low hemoglobin (11.9 g/dL) and normal urea and electrolyte levels. The levels of tumor markers CEA and CA19-9 were within the normal range. Myeloma protein (M protein) was undetected in blood and urine samples. TAUS and endoscopic ultrasonography (EUS; convex array type) revealed a low-echoic mass with an extended base and asymmetric shape (Fig. 1A, B). The hyperechoic outer layer of the gallbladder was thin (Fig. 1B) following EUS. However, the common bile duct was normal. Computed tomography (CT) revealed an enhanced gallbladder mass (Fig. 2A, B). Gadoxetic acid-enhanced magnetic resonance imaging (GA-MRI) revealed a gallbladder nodule, and diffusion-weighted imaging revealed a nodule with extension in the gallbladder (Fig. 3A, B, C, and D). However, there was no evidence of invasion of the liver or tumors in other abdominal or pelvic organs. Esophagogastroduodenoscopy and total colonoscopy revealed no malignancy. We therefore diagnosed him with primary gallbladder carcinoma and referred the patient for open cholecystectomy. Figure 1. Images of TAUS and EUS. TAUS revealed a low echoic mass with an extent base and asymmetry shape (A). In EUS, the outer layer of the gallbladder was thinning (B, arrows). TAUS: transabdominal ultrasonography, EUS: endoscopic ultrasonography Figure 2. Contrasted CT revealed an enhanced mass in the gallbladder. Simple CT (A) and contrasted CT (B, arrows). CT: computed tomography Figure 3. MRI findings of the patient. Simple MRI (A). Ga-enhanced MRI (B, 20 seconds and C, 120 seconds) and diffusion-weighted imaging (D). A tumor nodule with smooth extension in the gallbladder wall was confirmed (D, arrows). MRI: magnetic resonance imaging, DWI: diffusion-weighted imaging After the operation, the resected specimen revealed a protruded tumor in the gallbladder (Fig. 4A). The cut surface of the specimen showed infiltrating gallbladder serosa, and a microscopic examination revealed abnormal plasma cells infiltrating the gallbladder serosa (Fig. 4B, C). In addition, an immunohistochemistry analysis confirmed positivity for CD138 (Fig. 4D, yellow quadrangle in Fig. 4C) and kappa light chain and negativity for CD20, CD3, CD4, CD5, CD8, and CD19. No liver invasion or lymph node metastasis was noted. Furthermore, bone marrow aspirate revealed normocellular marrow. Positron emission tomography-CT showed no abnormal accumulation in other organs. Therefore, the final diagnosis for the patient was gallbladder EMP without MM. The patient had no remarkable complications after surgery and has a follow-up evaluation scheduled for 26 months. Figure 4. Pathological findings of the patient. A macroscopic protruded tumor was noted in the gallbladder (A). The tumor was macroscopically recognized as infiltrating the gallbladder serosa at the cut surface of the specimen (B, arrows). The tumor contained abnormal plasma cells infiltrating the serosa of the gallbladder (C). The abnormal plasma cells were positive on immunoperoxidase stain for CD138, a plasma cell marker (400×) (D). Discussion EMP accounts for 3% of MM cases, with an age range at the diagnosis of 55-60 years old (3). Most solitary EMPs are in the head and neck, primarily in the upper aerodigestive tract (UAD) (4). Holler et al. summarized 1,134 cases of EMP from 1999 to 2021, and 131 cases of EMP were observed (about 11%) in the gastrointestinal tract (4). The liver accounted for 9% of 226 EMP cases reported in Bladé et al.'s study (5). Cases of EMP of the pancreas have been reported in the PubMed database. We searched the PubMed database for all relevant studies published until May 31, 2022, using the search term [plasmacytoma] AND [gallbladder] and found nine case reports (Table). Abughanimeh et al. (6) cited two other cases of gallbladder EMP with MM (7, 8; lower Table row). Gallbladder EMP can present with gastrointestinal symptoms, and the 11 total cases showed some symptoms or were associated with MM (1-3,6-13). In addition, case reports by St Romain et al., Fakhri et al., and Abt et al. incidentally detected gallbladder EMPs with MM (1,2,7). Table. Reference Year Age/Sex Background MM Presenting gastrointestinal symptoms (5) 1995 53/M Yes Painless obstructive jaundice (4) 2007 66/M Yes Right upper quadrant pain (5) 2008 70/M Yes Right upper quadrant pain (due to cholecystitis) (8) 2010 63/F No Epigastric pain, jaundice (6) 2012 69/M No Right upper quadrant pain (5) 2015 53M Yes Incidental imaging findings (CT) (3) 2016 65/F Yes Incidental imaging findings (PET-CT) (5) 2018 66/F Yes Right upper quadrant pain (3) 2019 77/F Yes Sepsis to biliary source (2) 1969 53/F Yes Asymptomatic gallbladder stone (4) 2012 80/M Yes Obstructive jaundice Our case 2021 81/M No Incidental imaging findings (TAUS) MM: multiple myeloma, CT: computed tomography, PET-CT: positron emission tomography/computed tomography, TAUS: transabdominal ultrasonography Conversely, our case was asymptomatic and showed no evidence of MM. CT in previous cases reportedly detected a thickened gallbladder wall, dilated biliary ducts, or enlarged lymph nodes in gallbladder EMP or biliary ducts (2,6). In addition, primary gallbladder adenocarcinoma, the most common primary gallbladder polyp, shows similar radiological findings. While MRI was not performed in all 11 cases, a tumor nodule with smooth extension in the gallbladder wall was confirmed by diffusion-weighted MRI in our case. Although the differential diagnosis between primary gallbladder carcinoma and EMP of the gallbladder without histopathological findings remains challenging, MRI findings may aid in the preoperative diagnosis of EMP of the gallbladder. EUS fine-needle aspiration (FNA) has been widely used for biliary tract lesions. St Romain et al. reported a case of gallbladder EMP with MM diagnosed by EUS-FNA (1). EUS-FNA for biliary tract lesions should be performed with care due to risks such as biliary fistula and membrane dissemination (14). Majerović et al. and Hwang et al. reported cases of gallbladder EMP without MM that were surgically treated and had a good course (3,9). In Holler et al.'s report, patients with EMP who received radiation, surgery, a combination of surgery and radiation, and another therapy showed an overall local recurrence rate of 12.8%, with MM developing in 10.2% (4). Furthermore, among patients with EMP of the UAD undergoing surgery alone, 5% developed MM, whereas among those with EMP of non-UAD regions, 3.4% developed MM. Whether or not cholecystectomy alone contributes to a good course in patients with gallbladder EMP without MM is uncertain (10). Wirk et al. reported that EMP non-progressive of MM is usually indolent (15). To our knowledge, this is the first report of a rare case of asymptomatic gallbladder EMP without MM. Therefore, EMP should be considered in the differential diagnosis of gallbladder tumors, regardless of MM. The authors state that they have no Conflict of Interest (COI). Acknowledgement The authors wish to thank Dr. Haruka Sato from the Department of Radiology for her support in the diagnostic imaging. ==== Refs 1. St Romain P , Desai S , Bean S , Jiang X , Burbridge RA . Extramedullary plasmacytoma of the gallbladder diagnosed by endoscopic ultrasound fine-needle aspiration (EUS-FNA). J Gastrointest Oncol 6 : 7-9, 2015. 2. Fakhri AA , Rodrigue PD , Fakhri AF . Extramedullary plasmacytoma of the gallbladder detected on fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography. J Clin Imaging Sci 6 : 40, 2016.27761300 3. Majerović M , Bogdanić B , Drinković N , Kinda SB , Jakić-Razumović J , Gašparović V . Extramedullary plasmacytoma imitating neoplasm of the gallbladder fossa after cholecystectomy. Coll Antropol 36 : 331-333, 2012.22816242 4. Holler A , Cicha I , Eckstein M , et al . Extramedullary plasmacytoma: tumor occurrence and therapeutic concepts -a follow up. Cancer Med. Forthcoming. 5. Bladé J , Beksac M , Caers J , et al . Extramedullary disease in multiple myeloma: a systemic literature review. Blood Cancer J 12 : 45, 2022.35314675 6. Abughanimeh O , Qasrawi A , Abu Omar M , Bahaj W , Abu Ghanimeh M . A case of multiple myeloma associated with extramedullary plasmacytoma of the gallbladder manifesting as acute cholecystitis. Cureus 10 : e2688, 2018.30050743 7. Abt AB , Deppisch LM . Multiple myeloma involving the extrahepatic biliary system. J Mt Sinai Hosp NY 36 : 48-54, 1969. 8. Fukatsu H , Hiramatsu Y , Takagi S , Morishita H . Multiple myeloma involving the extrahepatic bile duct. Intern Med 52 : 829-830, 2013.23545686 9. Hwang DW , Lim CS , Jang JY , et al . Primary hematolymphoid malignancies involving the extrahepatic bile duct or gallbladder. Leuk Lymphoma 51 : 1278-1287, 2010.20572800 10. Mouchli M , Grider DJ , Yeaton P . Gallbladder metastasis: a report of two cases. Case Rep Oncol 19 : 235-240, 2019. 11. Kondo H , Kainuma O , Itami J , Minoyama A , Nakada H . Extramedullary plasmacytoma of maxillary sinus with later involvement of the gall bladder and subcutaneous tissues. Clin Oncol 7 : 330-331, 1995. 12. Schuster D , Klosterhalfen B , Fiedler C , Prescher A . Metastasis of medullary plasmacytoma as the cause of acute cholecystitis. Dtsch Med Wochenschr 132 : 612-615, 2007 (in German).17357904 13. Heckmann M , Uder M , Grgic A , Adrian N , Bautz W , Heinrich M . Extraosseous manifestation of multiple myeloma with unusual appearance in computed tomography - case report. Röntgenpraxis 56 : 249-253, 2008.19294871 14. Tanaka K , Katanuma A , Hayashi T , Kin T , Takahashi K . Role of endoscopic ultrasound for gallbladder disease. J Med Ultrasonic 48 : 187-198, 2021. 15. Wirk B , Wingard JR , Moreb JS . Extramedullary disease in plasma cell myeloma: the iceberg phenomenon. Bone Marrow Transplant 48 : 10-18, 2013.22410751