CASE REPORT

Incidental carcinomas detected by PET/CT scans in patientswith malignant lymphoma

Kazuya Sato • Katsutoshi Ozaki • Shin-ichiro Fujiwara •

Iekuni Oh • Tomohiro Matsuyama • Ken Ohmine • Takahiro Suzuki •

Masaki Mori • Tadashi Nagai • Kazuo Muroi • Keiya Ozawa

Received: 22 July 2010 / Revised: 2 September 2010 / Accepted: 27 September 2010 / Published online: 26 October 2010

� The Japanese Society of Hematology 2010

Abstract According to the international working group

response criteria for malignant lymphoma revised in 2007,

18F-fluorodeoxyglucose positron emission tomography

(18FDG-PET) combined with or without computed tomog-

raphy (CT) is recommended for pre-treatment staging and

response assessment among patients with diffuse large

B-cell lymphoma and Hodgkin lymphoma. Recently, along

with the widespread use of PET/CT, unexpected uptake and

accumulation of 18FDG has been reported. Discussed in the

present report are patients with malignant lymphoma and

second primary carcinomas that were incidentally found by

PET/CT. A total of 497 consecutive PET/CT were performed

on 290 patients with malignant lymphoma in our institution

from April 2008 through March 2010. Eight patients (2.8%)

had pathologically confirmed second primary carcinomas

consisting of 4 colon cancers, 3 lung cancers, and 1 pan-

creatic cancer. Two cases were diagnosed at the initial

staging, and the others were detected after treatment for

lymphoma. It is noteworthy that PET revealed high accu-

mulations of 18FDG in 5 (62.5%) of the 8 patients without

corresponding tumors in conventional CT. All of the 4

patients with colon carcinoma underwent curative surgery.

The present study suggests that incidental findings by PET in

malignant lymphoma can lead to early detection and suc-

cessful treatment of second malignancies.

Keywords Malignant lymphoma � PET/CT � 18FDG �Incidental findings

1 Introduction

18F-Fluorodeoxyglucose positron emission tomography

(18FDG-PET) and computed tomography (CT) have been

widely used as essential assessment modalities in the field

of oncology. In cases of malignant lymphoma, PET/CT is

recommended for pre-treatment staging and response

assessment in patients with diffuse large B-cell lymphoma

(DLBCL) and Hodgkin lymphoma (HL), according to the

international working group (IWG) response criteria for

malignant lymphoma revised in 2007 [1]. Before the wide

use of PET, it had been extremely difficult to assess the

activity of the residual tumor masses, especially in patients

with bulky masses. In this regard, a major advantage of

PET/CT over conventional radiologic imaging techniques

is the functional ability to distinguish malignant diseases

from benign tumors, necrotic lesions, or fibrosis. In fact,

the emergence of PET eliminated the concept of the

complete remission/unconfirmed, which had been estab-

lished by the IWG in 2004 [1, 2]. 18FDG PET/CT has been

extremely important recent advancements in lymphoma

assessment. However, these modalities are also associated

with false-positive findings (attributed to infection or

inflammation), and are known to be affected by glucose

metabolism. Moreover, depending on the histological types

of lymphoma, the body-wide distribution of non-Hodgkin

lymphoma (NHL) can be quite variable and often unex-

pected. In addition, incidental findings of carcinomas have

K. Sato (&) � K. Ozaki � S. Fujiwara � I. Oh � T. Matsuyama �K. Ohmine � T. Suzuki � M. Mori � T. Nagai � K. Muroi �K. Ozawa

Division of Hematology, Jichi Medical University,

3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan

e-mail: kazuya@jichi.ac.jp

S. Fujiwara

e-mail: sfujiwara@jichi.ac.jp

I. Oh

e-mail: norma@jichi.ac.jp

123

Int J Hematol (2010) 92:647–650

DOI 10.1007/s12185-010-0702-x

been reported during routine interpretation of PET/CT

[3–7]. Therefore, the purpose of this study was to evaluate

second primary carcinomas incidentally detected by PET/

CT for more accurate assessment of patients with malig-

nant lymphoma.

2 Case reports

Retrospective analysis was performed on 290 patients (155

male and 135 female) with a mean age of 61 years (range of

16–93 years) with malignant lymphoma who underwent a

total of 497 consecutive PET/CT in our institution from

April 2008 through March 2010. All PET/CT for initial

staging, restaging, response monitoring (mid-treatment) and

post-therapy surveillance were included in this study.

Twenty-six patients (9.0%) had HL, and 264 patients

(91.0%) had NHL, including 137 with DLBCL, 57 with

follicular lymphoma, 22 with nodal or extranodal marginal

zone lymphoma, 28 with other B-cell lymphoma and 20

with T or NK-cell NHL. Brief clinical information includ-

ing patient characteristics, disease status and treatments

were provided to radiologists in advance.

Of the 290 patients, 14 (4.8%) were recommended by

radiologists for further investigation in order to evaluate

suspicious new abnormalities on the basis of PET/CT find-

ings. Two of the 14 cases did not receive further investi-

gation in view of hematologist’s judgment (PET-positive

lesions were considered reactive lymph nodes). A 93-year-

old female patient, who was strongly suspected to have an

additional primary carcinoma (pancreatic tumor), was not

further investigated because of her poor general condition,

as surgery was thought not to be applicable. Three cases had

pathologically proven benign tumors (granuloma, leiomy-

oma and adenomatous change in thyroid). The remaining 8

patients (2.8%, 8 of 290) had pathologically confirmed

second primary carcinomas (Table 1). The overall diag-

nostic accuracy for PET/CT to identify second primary

carcinomas was 72.7% (8 of 11). The biopsy sites for the

diagnosis of the second primary carcinomas included colon

(4), lung (3) and pancreas (1). Only 1 patient was diagnosed

at the first staging PET/CT (case 4), and the others were

detected after the chemotherapy for lymphoma. CT did not

initially reveal any lesions corresponding to the 18FDG

uptakes revealed by PET in all of the colon cancers and one

lung cancer. One patient died due to an incidentally detected

lung cancer (squamous cell carcinoma) despite complete

remission of lymphoma (case 1). The others underwent

curative surgery or were observed because of the advanced

status of malignant lymphoma. Among them, no clinical

symptoms associated with the incidental lesions were evi-

dent. The main reasons for suspicion of second malignancy

were either new 18FDG uptake despite good responses in

other lymphoma lesions or incidental findings in organs

atypical for lymphoma (e.g., pancreas).

In the present series, a 72-year-old male (case 1) was

diagnosed with DLBCL. Pre-treatment PET/CT detected

involvement of lymph nodes in the bilateral neck, supra-

clavicular area, hilum, and upper pharynx (Fig. 1, left).

Bone marrow examination revealed no infiltration of lym-

phoma cells (clinical stage II). The patient received four

cycles of conventional R-CHOP (rituximab combined with

cyclophosphamide, adriamycin, vincristine and predniso-

lone) chemotherapy. The PET/CT for response assessment

revealed disappearances of pre-existing uptakes only except

for a right hilar lymph node [maximum standardized uptake

value (SUVmax) = 11.09], suggesting a partial response

(Fig. 1, center). Lactate dehydrogenase (LDH) and soluble

IL-2 receptor, which were evaluated above normal range

before chemotherapy, became within normal range. All

tumor markers of lung cancer including carcinoembryonic

antigen (CEA), squamous cell carcinoma antigen (SCC),

Table 1 Patient characteristics

Patient number Age/sex Histological type

of lymphoma

Disease status Purpose for PET Incidental carcinoma

(histology)

1 72M DLBCL CR Therapy monitoring Lung (squamous cell)

2 73M LPL SD Post-therapy surveillancea Lung (large cell)

3 60M BCL – Staging Colon (adenocarcinoma)

4 76M BCL CR Post-therapy surveillancea Pancreas (adenocarcinoma)

5 79M DLBCL PR Therapy monitoring Colon (adenocarcinoma)

6 60M DLBCL CR Therapy monitoring Colon (adenocarcinoma)

7 81M DLBCL PR Therapy monitoring Colon (adenocarcinoma)

8 54F DLBCL CR Therapy monitoring Lung (small cell carcinoma)

DLBCL diffuse large B-cell lymphoma, LPL lymphoplasmacytic lymphoma, BCL B-cell lymphoma (unclassified), CR complete response, PRpartial response, SD stable diseasea 14 and 20 months past after final chemotherapy, respectively

648 K. Sato et al.

123

neuron-specific enolase (NSE), soluble fragment of cyto-

keratin 19 (CYFRA) and pro-gastrin-releasing peptide (pro-

GRP) were within normal ranges. After an additional 4

courses of R-CHOP (for a total of 8 cycles), significantly

increased 18FDG uptake corresponding to right lymph node

of hilum on PET scan was identified (SUVmax = 18.75)

(Fig. 1, right), and CT scan revealed out a speculated

nodule with diffuse thickening of bronchi (Fig. 2). A

transbronchial lung biopsy (TBLB) confirmed the final

diagnosis of squamous cell carcinoma.

3 Discussion

The characteristics of incidental carcinomas detected by

PET/CT among patients with malignant lymphoma are

investigated in the present report. Even with the widespread

use of PET/CT, unexpected findings have been uncommon.

Because of the high incidence of extranodal involvements

and the variable distribution of malignant lymphoma, it is

potentially difficult to distinguish other primary lesions

from extranodal lymphoma using PET/CT. The prevalence

of incidental carcinomas in patients with malignant dis-

eases has been reported from 0.8 to 4.1%, comparable with

2.8% in the present study [3–6]. PET scans for cancer

screening among asymptomatic healthy individuals have

been reported to discover malignant tumors in 2.1% of

individuals [7]. No remarkable differences are detectable

between healthy individuals and those with malignant

disease in this regard.

In patients with previously known carcinomas, inci-

dental co-existence of additional primary malignancies

could be misdiagnosed, as with the case we have shown

here. However, with a few exceptions, the accuracy for

detection of the second carcinomas by PET/CT in the

present study was excellent (72.7%). No patients had any

symptoms due to second carcinomas. PET revealed high18FDG accumulations in 5 (62.5%) of 8 patients who did

not exhibit anatomical changes in conventional CT.

Recently, it has been reported that most carcinomas

detected by PET in asymptomatic patients were at early

curable stages [7]. From the present data, unexpected

uptakes by PET scans should be carefully dealt with, even

if no obvious lesions or unusual uptakes are detected by

conventional anatomical imaging. Of note, all of focal

intensities in the colon were identified as colon carcinomas

(adenocarcinoma) (Table 1), and all patients underwent

potentially curative surgery or endoscopic resection. PET/

CT has been reported to have a high sensitivity and spec-

ificity for detecting colon carcinomas [8], and in the stag-

ing of primary colon carcinomas, PET/CT has been known

to be superior to conventional modalities [8]. Taken toge-

ther, in the case of incidental detection of a focal intensity

Fig. 1 Pre-treatment (left), mid-treatment (center) and post-treatment (right) PET revealed an increasing uptake corresponding to right hilum

despite good responses in other lymphoma lesions

Fig. 2 Post-chemotherapy CT demonstrated a suspicious hilar lung

lesion with thickened bronchial walls

Incidental carcinomas in malignant lymphoma patients 649

123

in the colon, endoscopic intervention should be performed

if at all possible.

Unfortunately, 1 patient in the present report died of the

incidentally detected secondary primary tumor (squamous

cell carcinoma of the lung), despite achieving a complete

remission of DLBCL. Serological tests, including all lung

tumor markers, were within the normal ranges and no

pulmonary symptoms were seen when PET/CT for mid-

treatment assessment of lymphoma was performed (Fig. 1,

center). The diagnosis could have been difficult due to the

invasive tendency along the inner cavities of bronchi in the

patient. However, careful retrospective review of the PET

scans showed a slight increase in SUVmax at the right

hilum compared to the pre-treatment SUVmax (elevated

from 5.50 to 11.09). Although mediastinal uptakes have

been known to be one of the most variable lesions revealed

by PET because of the various causes of mediastinal

uptakes (e.g., smoking, infection and chronic inflamma-

tion) [9], the discrepancy between rapid disappearance of

the uptakes at other co-existing sites and increasing hilum

uptake should be considered. Even if invasive procedures

like TBLB might not be indicated, short-interval follow up

using conventional CT scans and sputum cytology could

provide more prompt information.

Unexpected uptakes of 18FDG in patients with malignant

lymphoma have been a dilemma for hematologists. The

present study suggests that early diagnostic intervention can

potentially achieve detection and cure of second malig-

nancies that are incidental findings by PET in malignant

lymphoma. In indolent lymphomas, the ‘‘watchful waiting’’

concept has been the standard option. However, it should be

considered that the incidence of co-existing and unexpected

second carcinomas is approximately more than 1 out of 50

patients with malignant lymphoma. The present study was

limited to a small number of patients and was retrospec-

tively performed in a single institute. Further prospective

studies for interpretation of unexpected uptakes in PET/CT

are required for the optimal use in patients with malignant

lymphoma.

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