International Journal of Myeloma 9(2): 7–11, 2019
©Japanese Society of Myeloma

CASE REPORT

Endoscopic ultrasound-guided fine-needle aspirationin the diagnosis of multiple myeloma accompaniedby portal extramedullary plasmacytomas
Keiichi MORIYA, Hideto TAMURA, Masahiro OKABE, Toshio ASAYAMA,
Mika SUNAKAWA, Yasuko KURIBAYASHI and Koiti INOKUCHI
A 67-year-old man presented with plasmacytomas in the hepatic portal region, as diagnosed with endoscopic
ultrasound-guided fine-needle aspiration (EUS-FNA). Laboratory blood tests showed no myeloma-related
symptoms such as hypercalcemia, renal failure, and anemia, and normal levels of serum immunoglobulins. However,bone marrow examination demonstrated approximately 15% of atypical plasma cells in bone marrow mononuclear
cells, and serum tests showed an abnormal serum free light-chain ratio and monoclonal protein of Bence Jones
lambda upon immunoelectrophoresis. Positron emission tomography/computed tomography demonstrated high18

F-fluorodeoxyglucose uptake in the portal hepatic tumors and several bone lesions accompanied by osteolysis.

The patient was treated with bortezomib plus dexamethasone followed by high-dose melphalan with autologous
stem cell transplantation, resulting in a complete response.
Lymph nodes are common sites of extramedullary myeloma disease associated with poor prognosis. EUS-FNA isless invasive than open surgical biopsies and thus it is recommended in the differential diagnosis of plasmacytoma
in cases such as ours. EUS-FNA may enable early treatment, resulting in a good response even in myeloma patientswith unfavorable prognoses.
Key words:

multiple myeloma, extramedullary disease, endoscopic ultrasound-guided fine-needle aspiration

Introduction

endoscopic ultrasound (EUS)-guided fine-needle aspiration(FNA) of the swollen lymph nodes in the hepatic portal region.

Multiple myeloma (MM) is a mature B-cell malignancy

Case Reportcharacterized by bone marrow infiltration of clonal plasma
cells with clinical features such as hypercalcemia, renal
insufficiency, anemia, and bone lesions. Extramedullary

A 67-year-old man visited our hospital with suspected

plasmacytomas (EMPs) are seen in 7–15% of MM patients at

malignant lymphoma. He had a history of hypertension

the time of diagnosis, and the presence of EMPs is associatedand insomnia and had undergone abdominal computedwith poor prognosis in both newly diagnosed and relapsed

tomo­graphy (CT) due to occult blood in the urine detected

MM patients [1]. Common sites of EMPs are the gastrointes­

in a mass screening. The CT images demonstrated swelling oftinal tract, pleura, testis, skin, peritoneum, liver, endocrine

multiple lymph nodes in the hepatic portal region (Fig. 1). The

glands, and lymph nodes [1, 2]. It was reported that fewer thanphysical examination was normal, and no surface lymph node

1% of patients with newly diagnosed symptomatic MM have

was palpable. The laboratory data showed slight elevation oflymphadenopathy [3]. We report a case of MM diagnosed byserum uric acid, but no myeloma-related events such as hypercalcemia, renal failure, and anemia, and levels of serum lactate

Received: March 28, 2019, accepted: April 24, 2019
Department of Hematology, Nippon Medical School, Tokyo, Japan
Corresponding author: Hideto TAMURA, MD, PhD
Department of Hematology, Nippon Medical School, 1-1-5 Sendagi,
Bunkyo-ku, Tokyo 113-8603, Japan
E-mail: tam@nms.ac.jp

dehydrogenase (LDH) and soluble interleukin (IL)-2 receptor
werenormal(Table1).

Total-bodyCT,esophago­gastroduodenoscopy, and colonoscopy were performed,
although they showed no tumor or abnormal mass lesion
except for the previously detected lymph nodes. Biopsy of
the lymph nodes by laparotomy was deemed too invasive,
and thus diagnostic EUS-FNA was performed. EUS at the duo-International Journal of Myeloma

vol. 9 no. 2 (2019)7MORIYA et al.

Table 1.
WBC

Patient’s laboratory data at diagnosis

6000/μL

AST

24 IU/LCa

9.4 mg/dL

Stab0%ALT

17 IU/L

TP

7.0 g/dL

Seg

64.0%

LDH

146 IU/LAlb

4.6 g/dL

Eo

0.5%

ALP

261 IU/L

CRP

0.19 mg/dL

Ba

0.5%

gGTP

19 IU/LGlu

102 mg/dL

Mo

8.0%

T-Bil

0.5 mg/dL

sIL-2R

464 U/mL

Lym

27.0%

UA

7.6 mg/dL

IgG

877 mg/dL

RBC

409 × 104/μL

BUN

13.3 mg/dL

IgA

113 mg/dL

Hb

13.8 g/dL

Cre0.73 mg/dL

IgM

39 mg/dL

Ht

39.9%

Na

144 mEq/L

β2MG

4.7 mg/dL

Plt

21.3 × 104/μL

K

4.0 mEq/L

Ret8‰

Cl106 mEq/L

Figure 1. CT image at diagnosis. Coronal slice of the portal areashows swelling of two lymph nodes (yellow arrow).

Figure 2. Microscopic images. The EUS-FNA sample smear shows proliferation of plasma cells with HE staining (A) and these were CD38+ in
immunohistochemistry (B). A bone marrow aspiration sample smear shows proliferation of plasma cells with Wright-Giemsa staining (C).

denum revealed marked swelling of lymph nodes in thewas insufficient. These findings indicated that the lymph

hepatic portal region, and FNA yielded an adequate sample.

nodes contained plasmacytomas, and thus we performed

The biopsy specimen showed small-sized lymphocytes andbone marrow examination and positron emission tomography

plasma cells (Fig. 2A), which were positive for CD38 (Fig. 2B),(PET)-CT to detect myeloma cells and bone lesions, respec­

CD56, and CD138, and lambda light-chain restriction. Flow

tively. The bone marrow contained 15% clonal plasma cells

cytometric and chromosomal analyses were not performed(Fig. 2C), which were CD19–CD56+CD45+MPC-1+CD20+/– cyto­

because the amount of aspirated sample obtained by EUS-FNA

plasmic lambda-positive cells in CD38 high-positive fractions

8International Journal of Myeloma

vol. 9 no. 2 (2019)

EUS-FNA in the diagnosis of myeloma

Figure 3. PET-CT images at diagnosis. Coronal slices of the same area in Figure 1 (left) and pulmonary hilum area (right) show FDG uptake bylymph nodes and bone with an osteolytic lesion (yellow arrows).

Figure 4. Clinical course from induction therapy to autologous stem cell transplantation.

Discussion

as shown by flow cytometric analysis. Adverse chromosomal
abnormalities such as t(4;14), t(14;16), and 17p- were notdetected by fluorescence in situ hybridization. PET-CT
18

In our patient, histological diagnosis of swollen lymph

F-fluorodeoxyglucose (FDG) uptake bynodes in the portal region was needed because no myeloma-lymph nodes of the hepatic portal region and several

defining signs were evident in the laboratory blood testbone lesions of the right scapula and thoracic vertebrae

results. EUS-FNA revealed MM accompanied by portal EMPs,

accompanied by some osteolysis (Fig. 3). Serum and urinary

which contributed to the early start of treatment and resulted

electrophoresis showed monoclonal lambda light-chain

in a good response in this case of myeloma with an unfavorable

protein with serum free light-chain kappa/lambda 141/1730

prognosis.

demonstrated highmg/L, and serum β2MG was 4.7 mg/dL. We therefore

The diagnosis of EMPs requires the demonstration ofdiagnosed Bence Jones lambda type MM in Durie & Salmon

monoclonal plasma cell proliferation in the tumor site.

stage IIIA and International Scoring System stage II.

Minimally invasive surgical procedures are preferred, especially

The patient was treated with bortezomib plus dexameth­for elderly patients, and CT-guided core needle biopsy (CTNB)

asone (BD) with concurrent radiotherapy of the vertebrae

is a common procedure to obtain tumor samples. However, itbecause of lumbago with high FDG uptake. After 1 course ofis sometimes difficult to perform CTNB because of the highBD therapy, the serum free light-chain kappa/lambda ratio

risk of pneumothorax, hemorrhage, and air embolism in somenormalized (Fig. 4). After four courses of BD were administered,patients. In some cases, plasmacytoma biopsy is performed in

abdominal CT demonstrated no swelling of lymph nodes ininvasive procedures such as open surgical biopsy, although

the hepatic portal region. High-dose melphalan treatment

EUS-FNA is a less invasive, well-established technique. Therewith autologous peripheral blood stem cell transplantation

have been several reports of EMPs in the pancreas, omentum,(APBSCT) was performed, and the patient continued to show

liver, and gallbladder, as well as of mediastinal and massa complete response for 4.3 years after transplantation withlesions near the aortoiliac bifurcation diagnosed by EUS-FNA

no maintenance therapy.

[4–11]. Furthermore, the incidence of complications with

International Journal of Myeloma

vol. 9 no. 2 (2019)9

MORIYA et al.

EUS-FNA is lower than with CTNB because of the fine needle

Referencesused in FNA. However, the small amount of sample obtained isa disadvantage of EUS-FNA, which may result in difficulty inpathophysiological diagnosis and biological/genetic ana­lyses in hematology area. On the other hand, the diagnostic
accuracy of lymph nodes for metastatic pancreatic cancer isvery high when combined with radiologic evaluation, andsome studies showed that EUS-FNA has a sensitivity of 79–98%
and a specificity of 98–100% in diagnosing mediastinal andintraabdominal lymphadenopathies [12]. It is difficult todiagnose some lymphomas in detail, but it was reported thatthe accuracy of EUS-FNA in combination with flow cytometry
in diagnosing lymphoma was 94.2% [13], and therefore­EUS-FNA is a useful tool in the diagnosis of lymphadenopathy.
The incidence of extramedullary lesions in MM is 7–15% atinitial diagnosis, and the majority of those cases have a single
plasmacytoma [1, 3]. Patients with EMPs at diagnosis haveshorter progression-free survival compared with others.
Solitary plasmacytomas are usually treated with radiation [14],but there is no standard therapy for patients with multiple
EMPs. Because there were several reports on the efficacy ofbortezomib-based combination therapy in extramedullaryMM, our patient was administered BD as induction therapy,achieving a significant therapeutic effect [15, 16]. Several
reports mentioned that high-dose chemotherapy followed by
APBSCT can overcome the negative impact of EMPs on
prognosis [1, 3]. Previous studies found that the prevalence ofEMPs was significantly higher in younger than in elderly
patients [17, 18]. Transplant-eligible patients with EMPs shouldbe treated with triplet induction therapy followed by highdose melphalan with APBSCT and triplet consolidation therapy[19]. However, our patient did not receive triplet induction/
consolidation therapy because the triplet regimen was notstandard at the time of treatment.
In summary, EUS-FNA has some disadvantages such as thesmall amount of specimen yielded, but it is very useful for thediagnosis of early-stage high-risk MM accompanied by EMPs.
In our patient, EUS-FNA led to the diagnosis of MM and madeurgent treatment possible.

Authorship
K.M. and H.T. analyzed the clinical status of the patient,analyzed the data, and prepared the manuscript; M.O., T.A.,
M.S., Y.K., and K.I. analyzed the data and the clinical status ofthe patient.

Conflicts of Interest
The authors declare no competing financial interests.
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vol. 9 no. 2 (2019)

1. Varettoni M, Corso A, Pica G, Mangiacavalli S, Pascutto C, Lazzarino
M. Incidence, presenting features and outcome of extramedullary
disease in multiple myeloma: a longitudinal study on 1003
consecutive patients. Ann Oncol 2010;21:325–30.
2. Damaj G, Mohty M, Vey N, Dincan E, Bouabdallah R, Faucher C,
et al. Features of extramedullary and extraosseous multiple
myeloma: a report of 19 patients from a single center. Eur JHaematol 2004;73:402–6.
3. Wu P, Davies FE, Horton C, Jenner MW, Krishnan B, Alvares CL,
et al. The combination of cyclophosphamide, thalidomide anddexamethasone is an effective alternative to cyclophosphamide- vincristine - doxorubicin - methylprednisolone as induction­chemotherapy prior to autologous transplantation for multiple
myeloma: a case-matched analysis. Leuk Lymphoma 2006;47:2335–8.
4. Padda MS, Milless T, Adeniran AJ, Mahooti S, Aslanian HR.
Pancreatic and Gastric Plasmacytoma Presenting with Obstructive
Jaundice, Diagnosed with Endoscopic Ultrasound-Guided Fine
Needle Aspiration. Case Rep Gastroenterol 2010;4:410–5.
5. Roh YH, Hwang SY, Lee SM, Im JW, Kim JS, Kwon KA, et al.
Extramedullary plasmacytoma of the pancreas diagnosed using
endoscopic ultrasonography-guided fine needle aspiration. Clin
Endosc 2014;47:115–8.
6. Kim JH, Paik WH, Joo M, Kim JG, Kim JW, Bae WK, et al.
Extramedullary plasmacytoma mimicking pancreatic cancer: Acase report and literature review. Endosc Ultrasound 2017;6:269–72.
7. Muddana V, Goyal A, Chahal P. Endoscopic ultrasound-guided
fine needle aspiration and diagnosis of omental plasmacytoma.
Endosc Ultrasound 2017;6:278–9.
8. Husney J, Guttmann S, Anyadike N, Mayer I, Rahmani R.
Endoscopic ultrasound-fine needle aspiration: A novel way todiagnose a solitary extramedullary plasmacytoma of the liver.
Endosc Ultrasound 2016;5:134–6.
9. St Romain P, Desai S, Bean S, Jiang X, Burbridge RA.
Extramedullary plasmacytoma of the gallbladder diagnosed byendoscopic ultrasound fine needle aspiration (EUS-FNA). J
Gastrointest Oncol 2015;6:E7–9.
10. Mallo R, Gottlieb K, Waggoner D, Wittenkeller J. Mediastinal
plasmacytoma detected by echocardiography and biopsied with
EUS-FNA. Echocardiography 2008;25:997–8.
11. Doi S, Yasuda I, Nakashima M, Kawaguchi J, Yamauchi T, Iwashita
T, et al. Endoscopic ultrasound-guided fine-needle aspirationof lesions near the aortoiliac bifurcation via an upper gastro­
intestinal approach. J Gastroenterol Hepatol 2011;26:1717–20.
12. Caers J, Paiva B, Zamagni E, Leleu X, Blade J, Kristinsson SY,et al. Diagnosis, treatment, and response assessment in solitary
plasmacytoma: updated recommendations from a European
Expert Panel. J Hematol Oncol 2018;11:10.
13. Kim TH. How to improve the diagnostic accuracy of EUS-FNA
in abdominal and mediastinal lymphadenopathy? Clin Endosc
2019;52:93.
14. Wang J, Chen Q, Wu X, Wang Y, Hou W, Cheng B. Role ofendoscopic ultrasound-guided fine-needle aspiration in eval­uating mediastinal and intra-abdominal lymphadenopathies of
unknown origin. Oncol Lett 2018;15:6991.

EUS-FNA in the diagnosis of myeloma

15. Ali R, Ozkalemkas F, Ozkan A, Ozkocaman V, Ozcelik T, Ozan U, etal. Bortezomib and extramedullary disease in multiple myeloma:
the shine and dark side of the moon. Leuk Res 2007;31:1153–5.
16. Blade J, Fernandez de Larrea C, Rosinol L, Cibeira MT, Jimenez R,Powles R. Soft-tissue plasmacytomas in multiple myeloma:
incidence, mechanisms of extramedullary spread, and treatment
approach. J Clin Oncol 2011;29:3805–12.
17. Blade J, Kyle RA, Greipp PR. Presenting features and prognosis in72 patients with multiple myeloma who were younger than 40years. Br J Haematol 1996;93:345–51.
18. Huang SY, Yao M, Tang JL, Lee WC, Tsay W, Cheng AL, et al.
Epidemiology of multiple myeloma in Taiwan: increasing
incidence for the past 25 years and higher prevalence of
extramedullary myeloma in patients younger than 55 years.
Cancer 2007;110:896–905.
19. Touzeau C, Moreau P. How I treat extramedullary myeloma. Blood
2016;127:971–6.

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