PET Scan Evaluation of Thymic Mass After AutologousPeripheral Blood Stem-cell Transplantation in an Adult with

Non-Hodgkin’s Lymphoma

FRANCESCA PAGLIAIa, LUIGI RIGACCIa,*, VITTORIO BRIGANTIb, CATIA DINIc, ANTONIO CASTAGNOLIb,LUCA VAGGELLIb and ALBERTO BOSIa

aHaematology Department of Florence, Azienda Ospedaliera Careggi and Universita degli Studi, Policlinico Careggi Viale Pieraccini, 85, 50132,Florence, Italy; bNuclear Medicine, Azienda Ospedaliera Careggi, Florence, Italy; cRadiodiagnostic Unit, Azienda Ospedaliera Careggi, Florence,

Italy

(Received 30 December 2002)

We report the case of a 31-year-old man with anaplastic large-cell lymphoma successfully treated withchemotherapy who showed mediastinal widening 5 months after autologous stem-cell transplantation.CT scan and PET evaluations were consistent with the diagnosis of benign thymic hyperplasia. Becauseof the rapid and aggressive course of this type of lymphoma, and the progressive widening of the massat CT scan, we performed a mediastinal biopsy that confirmed these findings, showing normal thymictissue. This is the first case of benign thymic hyperplasia defined with FDG-PET and confirmed byhistologic evaluation.

Keywords: Pet scan; Thymic mass; Thymic hyperplasia; Post stem cell transplant; Non-Hodgkin’slymphoma

INTRODUCTION

Treatment of NHL frequently results in residual masses

detected radiologically [1]. Mediastinal enlargement

after intensive chemotherapy or haematopoietic stem-

cell transplantation in a patient with haematologic

malignancy, particularly with lymphoma, represents a

very problematic finding because it might indicate a

recurrent disease, a second neoplasm, a primary thymic

tumour or a benign thymic hyperplasia. Here, we

describe the case of a 31-year-old man with a diagnosis

of high grade non-Hodgkin’s lymphoma, who under-

went to induction therapy followed by autologous

peripheral blood stem-cell transplantation as consolida-

tion treatment.

CASE REPORT

A 31-year-old man with no medical history was presented

with asymptomatic lymphadenopathy in March 2001.

Physical examination showed bilateral cervical and left

supraclavicular adenopathy. CT scan revealed anterior

mediastinal, left paratracheal and retrosternal

lymphadenopathy. A biopsy of a supraclavicular lymph

node was performed with the diagnosis of anaplastic

large-cell lymphoma with Hodgkin’s like appearance

(ALK negative). After staging, the patient was classified

as stage IIA, IPI 0.

He was treated according to the MACOP-B protocol

[2] (Cyclophosphamide, Adriamycin, Methotrexate,

Vincristine, Bleomycin, Prednisone). After 6 weeks he

successfully performed a PBPC harvest after mobilisation

with mega-CHOP [3] (Cyclophosphamide, Adriamycin,

Vincristine, Prednisone) and G-CSF; then he completed

the other 6 weeks of MACOP-B protocol. The total dose

of prednisone administered was 100 mg/day for about 3

months. At the end of the course he achieved a complete

remission, as evaluated by CT scan and PET analysis. On

28th September 2001, he performed peripheral blood

stem-cell transplantation. The conditioning regimen

(ICE) consisted of Vepeside 600 mg/m2/day for 3 days,

ISSN 1042-8194 print/ISSN 1029-2403 online q 2003 Taylor & Francis Ltd

DOI: 10.1080/1042819031000083307

*Corresponding author. Tel.: þ39-055-4277476. Fax: þ39-055-412098. E-mail: l.rigacci@dfc.unifi.it

Leukemia & Lymphoma, Vol. 44, No. 11 (November 2003), pp. 2015–2018

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Ifosfamide 3 g/m2/day for 4 days and Carboplatin

500 mg/m2/day for 3 days. Sustained myeloid engraftment

was achieved by day 10, and the patient was discharged

from hospital on day 13.

During the routine follow-up, 2 months after HSCT,

the CT scan of the chest showed the presence of

anterior superior mediastinal mass (Fig. 1). After 1

month, a PET evaluation resulted in a mild diffuse

hyperactivity around the aortic arch, with a chimney

aspect and a SUV of 2.7 possibly consistent with

thymic hyperplasia (Fig. 2). On the basis of PET

results, we decided to perform another CT scan 1-

month later, that revealed an enlargement of the

previous finding, resulting in an anterior mediastinal

mass in correspondence with the thymic lodge. Due to

the very aggressive histology of this lymphoma, we

could not wait for a radiological monitoring and we

decided for a histological evaluation. One month later,

the patient underwent to an open biopsy by anterior

thoracotomy. Postoperative recovery was uneventful.

Histologic examination showed normal thymic tissue.

MATERIAL AND METHODS

PET Imaging Procedure

18F-FDG was produced using an automated 18F-FDG

synthesis system with a small cyclotron. PET

scanning was performed with an Advance System

(General Electric Medical System). The physical

characteristics of this scanner have been described in

detail by DeGrado et al. [4].

PET Data Analysis

The 18F-FDG image was visually interpreted from

the monitor and films and carefully correlated with CT

study. As an index of 18F-FDG uptake, after correction for

FIGURE 1 Computed tomography of the chest. Anterior mediastinal mass.

FIGURE 2 FDG-PET scan shows mediastinal activity compatible with thymic hyperplasia.

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radioactive decay, the standardized uptake value (SUV)

was calculated according to the following formula:

SUV ¼ radioactivity in ROI (Bq/cm3)/injected dose

(Bq)/body weight (g). The PET scan in this patient

showed a weak hyperactivity of the mediastinal mass

with a border line semiquantitative value (Fig. 2).

Computed Tomography (CT) Analysis

CT scan of the chest showed an anterior superior

mediastinal mass consistent with thymic hyperplasia or

lymphoadenopathy (Fig. 1).

DISCUSSION

The analysis of active lymphoma after chemotherapy or

radiotherapy has a great clinical impact. In this patient,

CT scan provides an accurate definition of the

mediastinal mass, but it was not possible to discriminate

between active disease and hyperplasia. PET scan

provided an accurate definition of glucose metabolism,

showing faint hyperactivity of the mass with a

semiquantitative value ðSUV ¼ 2:7Þ which was consist-

ent with thymic hyperplasia instead of active disease.

Benign thymic hyperplasia has been reported in children

and young adults after chemotherapy for testicular

tumours, or haematologic malignancies, particularly for

Hodgkin’s lymphoma, and less frequently for non-

Hodgkin’s lymphoma since 1980 [5]. This phenomenon

has been described also after chemotherapy or radio-

therapy for other malignancies, such as osteogenic

sarcoma, Wilms’ tumour, rhabdomyosarcoma, malignant

fibrous histiocytoma, Ewing’s sarcoma, metastatic

malignant histiocytoma, acute myeloid leukaemia, after

high-dose chemotherapy followed by autologous stem-

cell transplantation in patients with breast cancer, and in

a child affected by ALL after allogeneic bone marrow

transplantation [6–9]. Thymic hyperplasia may also

occur in non systemically treated, newly diagnosed

testicular cancer patients or in healthy children and in

several clinical situations, such as discontinuation of

corticosteroids, hyperthyroidism, following recovery

from burns, infections and after cardiovascular surgery

[7,8,10,11]. There are cases in which thymic regrowth

after chemotherapy is 50% greater than baseline volume,

phenomenon known as thymic rebound. The thymus

appears to be atrophic during the administration of

chemotherapy and regrows during the recovery phase.

This happens more frequently in children and younger

patients because of the physiological involution of the

gland during adolescence [9–12]. In the literature, cases

in 40-years-old adults have been described, but the

majority is observed in children and adolescents. Choyke

et al. [6] described 20 patients with various haematologic

and solid tumours who showed thymic atrophy and

regrowth in response to chemotherapy in a total of 29

patients two were 35-years-old [13,14]. Further cases

following treatment of HD or NHL have been described

in adults of 40 years of age [15,16].

As demonstrated by several studies, the absence of

concurrent lymph node enlargement or other signs of

relapsing lymphoma is the major radiological clue

favouring the diagnosis of thymic hyperplasia.

To differentiate thymic rebound from recurrent disease

may be difficult in patients following chemotherapy for

lymphoma. Functional imaging with Gallium has the

capability to discriminate active disease, but false

positives have been reported, mainly in children, but

also in young adults. F18DG, which with PET scan is

reported to be more sensitive in lymphoma patients, is

taken up by the normal thymus in children, but seems to

disappear after puberty. Brink et al. [9] reported FDG

uptake related to thymus hyperplasia in 5% of adults after

chemotherapy. In this retrospective study Brink con-

sidered the classical triangular shape and moderate uptake

at both visual inspection and semiquantitative analysis as

well ðSUV , 4Þ; the criterion for potentially benign FDG

thymus uptake. In the case reported here, we have

observed an identical PET scan result and we have

demonstrated the hypothesis of thymus hyperplasia

histologically. To our knowledge, this is the first case of

thymic hyperplasia identified utilizing PET scan and

subsequently successfully confirmed by histological

analysis.

Acknowledgements

We are grateful to Barbara Scappini for revision of the

manuscript.

References

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PET SCAN OF THYMIC MASS IN NHL 2017

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