7International Journal of Myeloma vol. 9 no. 2 (2019)

Endoscopic ultrasound-guided fine-needle aspiration in the diagnosis of multiple myeloma accompanied

by 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 high 18F-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 is

less 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 patients

with unfavorable prognoses.

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

Introduction

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

characterized by bone marrow infiltration of clonal plasma

cells with clinical features such as hypercalcemia, renal

insufficiency, anemia, and bone lesions. Extramedullary

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

the time of diagnosis, and the presence of EMPs is associated

with poor prognosis in both newly diagnosed and relapsed

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

tinal tract, pleura, testis, skin, peritoneum, liver, endocrine

glands, and lymph nodes [1, 2]. It was reported that fewer than

1% of patients with newly diagnosed symptomatic MM have

lymphadenopathy [3]. We report a case of MM diagnosed by

endoscopic ultrasound (EUS)-guided fine-needle aspiration

(FNA) of the swollen lymph nodes in the hepatic portal region.

Case Report

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

malignant lymphoma. He had a history of hypertension

and insomnia and had undergone abdominal computed

tomo graphy (CT) due to occult blood in the urine detected

in a mass screening. The CT images demonstrated swelling of

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

physical examination was normal, and no surface lymph node

was palpable. The laboratory data showed slight elevation of

serum uric acid, but no myeloma-related events such as hyper-

calcemia, renal failure, and anemia, and levels of serum lactate

dehydrogenase (LDH) and soluble interleukin (IL)-2 receptor

were normal (Table 1). Total-body CT, esophago-

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

Received: March 28, 2019, accepted: April 24, 2019Department of Hematology, Nippon Medical School, Tokyo, Japan

Corresponding author: Hideto TAMURA, MD, PhDDepartment of Hematology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, JapanE-mail: tam@nms.ac.jp

CASE REPORT

International Journal of Myeloma vol. 9 no. 2 (2019)8

MORIYA et al.

denum revealed marked swelling of lymph nodes in the

hepatic portal region, and FNA yielded an adequate sample.

The biopsy specimen showed small-sized lymphocytes and

plasma cells (Fig. 2A), which were positive for CD38 (Fig. 2B),

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

cytometric and chromosomal analyses were not performed

because the amount of aspirated sample obtained by EUS-FNA

was insufficient. These findings indicated that the lymph

nodes contained plasmacytomas, and thus we performed

bone marrow examination and positron emission tomography

(PET)-CT to detect myeloma cells and bone lesions, respec-

tively. The bone marrow contained 15% clonal plasma cells

(Fig. 2C), which were CD19–CD56+CD45+MPC-1+CD20+/– cyto-

plasmic lambda-positive cells in CD38 high-positive fractions

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

Table 1. Patient’s laboratory data at diagnosis

WBC 6000/μL AST 24 IU/L Ca 9.4 mg/dL

Stab 0% ALT 17 IU/L TP 7.0 g/dL

Seg 64.0% LDH 146 IU/L Alb 4.6 g/dL

Eo 0.5% ALP 261 IU/L CRP 0.19 mg/dL

Ba 0.5% gGTP 19 IU/L Glu 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 Cre 0.73 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

Ret 8‰ Cl 106 mEq/L

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).

9International Journal of Myeloma vol. 9 no. 2 (2019)

EUS-FNA in the diagnosis of myeloma

as shown by flow cytometric analysis. Adverse chromosomal

abnormalities such as t(4;14), t(14;16), and 17p- were not

detected by fluorescence in situ hybridization. PET-CT

demonstrated high 18F-fluorodeoxyglucose (FDG) uptake by

lymph nodes of the hepatic portal region and several

bone lesions of the right scapula and thoracic vertebrae

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

electrophoresis showed monoclonal lambda light-chain

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

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

diagnosed Bence Jones lambda type MM in Durie & Salmon

stage IIIA and International Scoring System stage II.

The patient was treated with bortezomib plus dexameth-

asone (BD) with concurrent radiotherapy of the vertebrae

because of lumbago with high FDG uptake. After 1 course of

BD therapy, the serum free light-chain kappa/lambda ratio

normalized (Fig. 4). After four courses of BD were administered,

abdominal CT demonstrated no swelling of lymph nodes in

the hepatic portal region. High-dose melphalan treatment

with autologous peripheral blood stem cell transplantation

(APBSCT) was performed, and the patient continued to show

a complete response for 4.3 years after transplantation with

no maintenance therapy.

Discussion

In our patient, histological diagnosis of swollen lymph

nodes in the portal region was needed because no myeloma-

defining signs were evident in the laboratory blood test

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

which contributed to the early start of treatment and resulted

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

prognosis.

The diagnosis of EMPs requires the demonstration of

monoclonal plasma cell proliferation in the tumor site.

Minimally invasive surgical procedures are preferred, especially

for elderly patients, and CT-guided core needle biopsy (CTNB)

is a common procedure to obtain tumor samples. However, it

is sometimes difficult to perform CTNB because of the high

risk of pneumothorax, hemorrhage, and air embolism in some

patients. In some cases, plasmacytoma biopsy is performed in

invasive procedures such as open surgical biopsy, although

EUS-FNA is a less invasive, well-established technique. There

have been several reports of EMPs in the pancreas, omentum,

liver, and gallbladder, as well as of mediastinal and mass

lesions near the aortoiliac bifurcation diagnosed by EUS-FNA

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

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 by lymph nodes and bone with an osteolytic lesion (yellow arrows).

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

International Journal of Myeloma vol. 9 no. 2 (2019)10

MORIYA et al.

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

used in FNA. However, the small amount of sample obtained is

a disadvantage of EUS-FNA, which may result in difficulty in

pathophysiological diagnosis and biological/genetic ana-

lyses in hematology area. On the other hand, the diagnostic

accuracy of lymph nodes for metastatic pancreatic cancer is

very high when combined with radiologic evaluation, and

some studies showed that EUS-FNA has a sensitivity of 79–98%

and a specificity of 98–100% in diagnosing mediastinal and

intraabdominal lymphadenopathies [12]. It is difficult to

diagnose some lymphomas in detail, but it was reported that

the accuracy of EUS-FNA in combination with flow cytometry

in diagnosing lymphoma was 94.2% [13], and therefore

EUS-FNA is a useful tool in the diagnosis of lymphadenopathy.

The incidence of extramedullary lesions in MM is 7–15% at

initial diagnosis, and the majority of those cases have a single

plasmacytoma [1, 3]. Patients with EMPs at diagnosis have

shorter 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 of

bortezomib-based combination therapy in extramedullary

MM, 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 of

EMPs was significantly higher in younger than in elderly

patients [17, 18]. Transplant-eligible patients with EMPs should

be treated with triplet induction therapy followed by high-

dose melphalan with APBSCT and triplet consolidation therapy

[19]. However, our patient did not receive triplet induction/

consolidation therapy because the triplet regimen was not

standard at the time of treatment.

In summary, EUS-FNA has some disadvantages such as the

small amount of specimen yielded, but it is very useful for the

diagnosis of early-stage high-risk MM accompanied by EMPs.

In our patient, EUS-FNA led to the diagnosis of MM and made

urgent 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 of

the patient.

Conflicts of Interest

The authors declare no competing financial interests.

References

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 J Haematol 2004;73:402–6.

3. Wu P, Davies FE, Horton C, Jenner MW, Krishnan B, Alvares CL, et al. The combination of cyclophosphamide, thalidomide and dexamethasone is an effective alternative to cyclophosphamide - vincristine - doxorubicin - methylprednisolone as induction chemotherapy 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: A case 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 to diagnose 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 by endoscopic 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 aspiration of 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 of endoscopic ultrasound-guided fine-needle aspiration in eval-uating mediastinal and intra-abdominal lymphadenopathies of unknown origin. Oncol Lett 2018;15:6991.

11International Journal of Myeloma vol. 9 no. 2 (2019)

EUS-FNA in the diagnosis of myeloma

15. Ali R, Ozkalemkas F, Ozkan A, Ozkocaman V, Ozcelik T, Ozan U, et al. 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 in 72 patients with multiple myeloma who were younger than 40

years. 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.