Watchful waiting for some children with a mediastinal mass: the potential role for 18 F-fluorodeoxyglucose positron emission tomography: a case report and review of the literature

  • Rosa Nguyen1Email author,

    Affiliated with

    • Jamie L Coleman2,

      Affiliated with

      • Scott C Howard3, 4 and

        Affiliated with

        • Monika L Metzger3, 4

          Affiliated with

          BMC Pediatrics201313:103

          DOI: 10.1186/1471-2431-13-103

          Received: 29 January 2013

          Accepted: 27 June 2013

          Published: 10 July 2013

          Abstract

          Background

          Benign hyperplastic thymus is a rare but important differential diagnosis of anterior mediastinal lesions. Histological and radiological criteria are used to distinguish this benign condition from other malignant diseases but have their limitations, and biopsy of mediastinal masses can be risky. We report for the first time the diagnostic value of fluorodeoxyglucose 18 F positron emission tomography for patients with incidentally identified anterior mediastinal masses to avoid biopsy in some cases.

          Case presentation

          A 2 year old girl presented with new onset of emesis and constipation leading to the incidental discovery of an anterior mediastinal mass on radiograph. Chest computed tomography revealed cystic components within the mass concerning for a malignancy. Biopsy of the lesion and bone marrow aspiration and biopsy were negative but there was concern that the mediastinal biopsy may have missed the malignant component of the lesion. Hence, a positron emission tomography scan was obtained that showed mild homogeneous fluorodeoxyglucose 18 F avidity within the mass similar to that of normal thymus. The diagnosis of benign hyperplastic thymus was made.

          Conclusion

          The differential diagnosis of an incidentally found anterior mediastinal mass includes malignancy, but benign lesions such as benign hyperplastic thymus must also be considered, particularly when the complete blood count and biochemical profile are normal. Fluorodeoxyglucose 18 F positron emission tomography can help guide a clinician’s decision for further interventions and treatment.

          Keywords

          Mediastinal disease Mediastinum Positron-emission tomography Thymus hyperplasia

          Background

          Potential etiologies of anterior mediastinal masses in children include benign and malignant tumors whose incidences vary by patient age and symptoms at presentation. Benign hyperplastic thymus (BHT) is a rare condition that occurs mainly in infants and usually resolves spontaneously by 3 years of age, while it seldom occurs in older children and never in adults [13]. BHT is characterized by an increase in size of the thymus with normal histological architecture [15]. Hence, BHT must be distinguished from follicular hyperplasia in association with Graves’ disease, rebound thymus hyperplasia in cancer patients after chemotherapy, or thymoma and thymolipoma, which do not meet histological criteria for BHT and are mainly seen in adolescents and adults, respectively [1, 6, 7].

          Diagnoses such as germ cell tumor, thyroid cancer, and lymphomas (Hodgkin and non-Hodgkin) must be ruled out during diagnostic workup. BHT spontaneously resolves over time, without specific treatment or surveillance; thus, prognosis and management differ from that of malignant etiologies [1, 8]. Fine-needle aspiration cytology and imaging studies (e.g., chest radiograph, ultrasound, and computed tomography [CT]) are used to diagnose BHT in a minimally invasive manner but may result in inadequate biopsy specimens or inconclusive radiologic findings, requiring more invasive and potentially dangerous procedures [911]. In one study of 54 children and adults who underwent mediastinal biopsy, the procedure-related morbidity was 6%, and fatalities have been reported [12].

          Here we describe a child whose diagnosis of BHT was based on CT-guided core needle biopsy and supported by conventional imaging and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scan. PET can help differentiate BHT from other conditions associated with an anterior mediastinal mass.

          Case presentation

          A 2-year-old girl with no significant past medical history was in her usual state of health when she developed non-bloody and non-bilious emesis associated with constipation. A review of other systems was negative. She did not take any medications and family history was non-contributory. In the emergency room, she appeared well and in no acute distress, with a normal physical examination. Weight, height, and vital signs were normal for age and gender. A chest/abdominal radiograph to evaluate her constipation showed no intra-abdominal pathology but demonstrated mediastinal widening (Figure 1A). A CT scan revealed a 10.3 cm × 6.6 cm × 6.3 cm heterogeneous, right-sided anterior mediastinal mass with a single hypodense area likely representing necrosis, and compression of bronchovascular structures. Laboratory tests showed no hematologic or metabolic derangements.
          http://static-content.springer.com/image/art%3A10.1186%2F1471-2431-13-103/MediaObjects/12887_2013_839_Fig1_HTML.jpg
          Figure 1

          Diagnostic imaging studies of the presented patient. (A) Anteroposterior chest radiograph reveals a large predominately right-sided mass. (B) PET image shows that activity within the mass (black arrow) is indistinguishable from that in the normal thymus (white arrow). (C) Fused transaxial 18 F-FDG PET/CT shows only low-intensity, homogeneous 18 F-FDG avidity within the mass, with photopenia corresponding to the cystic/necrotic area (white arrow).

          The patient underwent CT-guided core needle biopsy of the lesion, bilateral bone marrow aspirates and biopsies to rule out a malignancy. Hematoxylin and eosin staining and immunohistochemical studies of the mediastinal mass biopsy showed preservation of thymic architecture, with sheets of variably mature small- to intermediate-sized lymphoid cells and few Hassall's corpuscles, consistent with benign thymic tissue. Flow cytometry revealed T-lymphocytes with a full spectrum of orderly thymic maturation patterns, and bone marrow aspirates and biopsies showed normocellular marrow (80%) with trilineage hematopoiesis without evidence of leukemia or lymphoma.

          However, the inhomogeneous area within the mass on CT imaging is not a typical finding of BHT and raised concern for a malignancy such as teratoma or lymphoma, which may present with such features (Table 1). PET-CT scan of the large anterior mediastinal mass showedareas of low-intensity, and diffuse, homogeneous FDG avidity, similar to the normal thymus (Figure 1B). Central low-attenuation areas by CT within the mass lacked FDG activity and are suggestive of necrosis (Figure 1C). The standardized uptake value of the lesions ranged from 2.3 to 2.5 MBq/kg, except for the cystic area, which had values less than 2 MBq/kg.
          Table 1

          Differential diagnosis of mediastinal masses in children

          Differential diagnosis

          Diagnostic imaging modality

          Comments

          Computed tomography

          Magnetic resonance

          PET scan

           

          Normal thymus

          Quadrilateral with convex or straight margins in infants, triangular with concave or straight margins in older children

          Bilobed, convex at birth, straight during puberty, concave in old age, greater generalized T1-weighted and fast spin-echo T2-weighted hyperintensity and diminishing intermediate T1- and T2-signal soft tissue with fatty involution

          Homogeneous low-intensity uptake

          Age-dependent change in appearance

          Benign Etiologies

          Benign thymic hyperplasia

          Symmetrically enlarged, typically homogeneous

          Enlarged, thymus characteristics similar to normal thymus (see above)

          Typically homogeneous low-intensity uptake

          Idiopathic

          Thymic follicular hyperplasia

          Symmetrically enlarged, normal sized in 25%-50%

          Enlarged, thymus characteristics similar to normal thymus (see above)

          Homogeneous uptake.

          Chronic inflammatory states, autoimmune conditions, myasthenia gravis (65%-75%)

          Rebound hyperplasia

          Symmetrically enlarged, normal sized in 25%-50%

          Enlarged, thymus characteristics similar to normal thymus (see above)

          Increased homogeneous uptake

          After chemotherapy

          Thymolipoma

          Pericardial fatty mass with fibrous septa

          Hyperintense T1-signal resembling subcutaneous fat and area with intermediate intensity soft of tissue attenuation

          Resembling uptake in fatty tissue and normal thymus

          Mainly in adolescents and young adults

          Malignant Etiologies

          Lymphoma

          Homogeneous or heterogeneous, nodular, hemorrhage, necrosis, cystic components

          Homogeneous low-signal on T1-weighted images, high-signal or intermixed areas (low and high) intensity on T2-weighted images

          Heterogeneous intense uptake

          Peak incidence in adolescence

          Teratoma

          Well-circumscribed, displacing mass, calcification (80%), fat-fluid levels, cystic, heterogeneous changes in lung parenchyma, pleura, or pericardium (tumor rupture)

          Hyperintense fat on T1-weighted images within fluid of low signal intensity (cystic changes), hyperintense mass on T2-weighted images

          Heterogeneously avid

          Tissue from germ-cell layers

          Seminoma

          Large and lobular, homogenous

          High-intensity mass with with septal structures in T2-weighted images

          Heterogeneously avid

          Most common primary solid tumor of the mediastinum

          Non-seminomatous tumor

          Large, lobulated, heterogeneous masses with large (>50%) areas of low attenuation, hemorrhage, necrosis

          Internal heterogeneous intensities with areas of high signal intensity reflecting degenerative cystic changes on T2-weighted images.

          Heterogeneously avid

          Highly aggressive

          Thyroid carcinoma

          Well-defined, smooth or lobuated, tracheal deviation, contrast-enhancing, calcifications

          Most tumors are hyperintense of markedly hyperintense on T2-weighted images

          Heterogeneously avid

          Ectopic thyroid

          The diagnosis of BHT was made based on histology and lack of FDG avidity on PET scan. The patient continues routine follow up almost a year after original diagnosis with stable mediastinal mass and no further problems or complaints.

          Discussion

          As the scope of diagnostic imaging broadens, there is greater likelihood of incidental detection of anterior mediastinal masses. Lymphomas and germ cell tumors are the most common malignant tumors of the anterior mediastinum in children; whereas, thymomas seldom occur in this age group [13]. Thymolipomas may occur in young adolescents and adults and occasionally children. Although their radiographic appearance may resemble BHT, thymolipomas present on MRI as mainly fatty masses with inhomogeneous areas that represent thymus tissue [14, 15]. BHT is a rare but important benign condition and must be differentiated from malignant and other benign tumors.

          To date, 53 patients with BHT have been reported (Table 2); 34 (64%) of them had respiratory symptoms, and imaging studies revealed a mediastinal mass. In the remaining 19 (36%) patients, the mediastinal lesion was an incidental finding. In either scenario, further diagnostic workup was warranted to rule out a malignancy; however, the implication of malignancy together with imaging findings and parental fear may have led to use of invasive interventions for diagnostic confirmation. Indeed, 79% (15/19) of asymptomatic patients underwent open biopsy and only 26% (9/34) of symptomatic patients were observed clinically without biopsy. In symptomatic patients, open biopsy can be diagnostic and therapeutic, but less invasive procedures are preferred [16].
          Table 2

          Reported cases of benign thymic hyperplasia

          Reference

          Case no*

          Sex

          Age

          Size

          Presenting symptoms

          Diagnostic imaging

          Pathology

          Course

          Comments/Follow up

          Symptomatic cases

          Oh [17]

          1

          F

          15

          15 × 10 × 2 cm, 102 g

          Pulmonary infection

          Fluoroscopy, angiography

          Histology

          Open resection

          None

          2

          F

          14

          8.4 × 2.8 × 1.4 cm, 20 g

          Upper respiratory infection

          Fluoroscopy

          Histology

          Open resection

          None

          Ruco [5]

          -

          M

          5

          950 g

          Dyspnea

          None

          Histology

          Open resection

          None

          O'Shea [18]

          -

          M

          1

          420 g

          Dyspnea, lymphocytosis

          CXR

          FNA, histology

          Steroids, open resection

          5 months

          Barcia [19]

          2

          M

          4

          47-92 g

          Pulmonary infection

          CXR

          Histology

          Open resection

          1 month

          3

          M

          1

          47-92 g

          Pulmonary infection

          CXR

          Histology

          Open resection

          1 month

          11

          F

          9

          47-92 g

          Chest discomfort

          CXR

          Histology

          Steroids, open resection

          1.5 years

          Rasore-Quintino [20]

          -

          M

          4

          800 g

          Pulmonary infection

          99Technetium scan

          Histology

          Open resection

          None

          Lack [6]

          2

          M

          11

          15.2 cm,

          324 g

          Mild dyspnea, URI

          CXR

          Histology

          Open resection

          9 years

          Lamesch AJ [21]

          -

          M

          6/12

          230 g

          Respiratory distress

          CXR

          Histology

          Ventilation, steroids, open resection

          6 years

          Parker [11]

          -

          M

          1 3/12

          200 g

          Pulmonary infection

          CXR, US, fluoroscopy, CT

          Histology

          Open resection

          None

          Kobayashi [22]

          1

          M

          1/12

          -

          Respiratory distress, lymphocytosis

          CXR, CT

          None

          Observation, steroids

          Intensive care unit admission, no follow-up

          2

          M

          2/12

          -

          Respiratory distress, lymphocytosis

          CXR, CT

          None

          Observation, steroids

          None

          3

          M

          4/12

          -

          Pulmonary infection, lymphocytosis

          CXR, CT

          None

          Observation, steroids

          None

          4

          F

          1/12

          -

          Respiratory distress, lymphocytosis

          CXR, CT

          None

          Observation

          None

          Nezelof [23]

          1

          F

          10

          93 g

          Cough

          CXR

          Histology

          Open resection

          None/uneventful follow up

          Judd [24]

          -

          M

          12

          13 × 8 × 3.5 cm, 245 g

          Wheezing, dysphagia

          CXR

          Basic laboratory tests, histology

          Open resection

          None

          Ricci [2]

          3

          M

          14

          850 g

          Dyspnea, altered LFTs, atelectasis

          CXR, CT

          ECG, LFTs, histology

          Open resection

          9 years

          4

          M

          5

          950 g

          Dyspnea

          CXR, CT

          ECG, EMG, LFTs, biopsy ×2, histology

          Open partial resection

          Wound infection, osteomyelitis, lung atelectasis/1 month

          Linegar [8]

          1

          F

          2/12

          220 g

          URI, lymphocytosis, splenomegaly

          CXR, CT

          Histology

          Open resection

          3 months

          2

          M

          3

          18 × 10 × 6 cm, 855 g

          Recurrent URI, lymphocytosis

          CXR

          Histology

          Open resection

          None

          3

          M

          6

          1260 g

          Wheezing, dyspnea, respiratory distress

          CXR, CT

          FNA, histology

          N/A

          None

          4

          M

          3

          100 g

          Recurrent URI

          CXR

          Histology

          Open resection

          None

          Lee [25]

          1

          F

          3/12

          -

          Persistent URI, lymphocytosis

          CT

          Open biopsy, histology

          Observation

          1 year

          2

          M

          11/12

          500 g

          URI, lymphocytosis, mediastinal shift

          CT

          Histology

          Open resection

          None

          Bangerter [9]

          8

          M

          1/12

          5x6 cm

          Acute airway obstruction

          Imaging not further specified

          U/S guided FNA, histology

          Steroids

          Death 10 months after diagnosis of unknown cause/8 months

          Hoerl [10]

          -

          M

          5/12

          4.6 cm AP

          Choking

          CT

          FNA, histology

          Observation

          1 year

          Tareen [26]

          1

          M

          3/12

          -

          Persisting URI

          CT, CXR, US

          None

          Steroids, observation

          6 months

          2

          M

          8/12

          -

          Recurrent URI, dyspnea, tachypnea

          CXR, CT

          FNA, histology

          Open resection

          6 months

          Sosothikul [27]

          -

          M

          4

          -

          Dyspnea, wheeze

          CXR, CT

          BMA, histology

          Observation

          Involution/1 month

          Gow [28]

          -

          F

          6/12

          N/A

          Respiratory symptoms

          Imaging not further specified

          Flow cytometry, histology

          Open resection

          1 year

          Piednoir [29]

          -

          M

          3/12

          -

          Anesthesia related respiratory distress, incidental finding

          CT

          None

          Observation

          Involution/2 years

          Szarf [30]

          -

          M

          2

          830 g

          Fever, dry cough and dyspnea

          CXR, CT

          Alpha-FP, beta-HCG, FNA, histology

          Steroids, open resection

          Reoccurrence of symptoms

          Tan [31]

          -

          F

          9/12

          17.5 × 11 × 5

          Upper respiratory infection

          CXR, MRI

          FNA, histology

          Steroids, open resection

          None

          Asymptomatic cases

          Oh [17]

          3

          F

          10

          80 g

          Incidental finding

          Fluoroscopy

          Basic laboratory tests, histology

          Open resection

          None

          Katz [32]

          -

          M

          7/12

          9 × 8 × 6 cm, 224 g

          Incidental finding, lymphocytosis

          CT, upper GI, IV pyelography

          Immunologic studies, BMA, histology

          Open resection

          Hypogamma-globulinemia/4 years

          Barcia [19]

          1

          M

          4

          47-92 g

          Incidental finding

          CXR

          Histology

          Open resection

          1 year

          5

          F

          11

          47-92 g

          Incidental finding

          CXR

          Histology

          Steroids, open resection

          3 months

          6

          F

          3

          47-92 g

          Incidental finding

          CXR

          Histology

          Open resection

          3 months

          7

          M

          4

          47-92 g

          Incidental finding

          CXR

          Histology

          Open resection

          1 year

          8

          M

          4

          47-92 g

          Incidental finding

          CXR

          Histology

          Open resection

          2 years

          9

          F

          7

          47-92 g

          Incidental finding

          CXR

          Histology

          Steroids, open resection

          1.5 years

          10

          M

          13

          47-92 g

          Incidental finding

          CXR

          Histology

          Open resection

          4 months

          Lee [33]

          -

          F

          2

          19 × 12 × 4.5 cm

          Incidental finding

          CXR

          Histology

          Oral steroids, open resection

          None

          Lack [6]

          1

          M

          14

          490 g

          Incidental finding, lymphocytosis

          CXR

          Histology

          Open resection

          17 years

          Nezelof [23]

          2

          F

          5

          N/A

          Incidental finding

          CXR, mediastinoscopy

          Basic laboratory tests, biopsy, histology

          Observation

          None/uneventful follow up

          3

          F

          11

          N/A

          Incidental finding

          CXR, mediastinoscopy

          Biopsy, histology

          Observation

          None

          Arliss [34]

          -

          M

          15

          17 × 16 × 6 cm, 680 g

          Incidental finding, lymphocytosis

          CXR, CT

          Histology

          Open resection

          1 4/12 years

          Ricci [2]

          1

          M

          16

          13 cm,

          250 g

          Incidental finding

          CXR, CT

          ECG, EMG, LFTs, histology

          Open resection

          12 years

          2

          M

          12

          7.5 cm,

          120 g

          Incidental finding

          CXR, CT

          ECG, EMG, LFTs, histology

          Open resection

          7 years

          Rice [3]

          -

          M

          10

          482 g

          Incidental finding

          MRI

          BMA, histology

          Open resection

          None

          Bangerter [9]

          1

          F

          5

          3 × 5

          N/A

          Imaging not further specified

          U/S guided FNA, histology

          N/A

          9 years

          6

          F

          8

          1.5 × 1

          N/A

          Imaging not further specified

          U/S guided FNA, immunopheno-typing, histology

          N/A

          8 months

          Current case

          -

          F

          2

           

          Incidental finding

          CRX, CT, PET

          Core needle biopsy

          Observation

           

          * If number of patients with benign thymus hyperplasia and patients with other conditions is provided in report.

          CT Computed tomography, CXR Chest radiograph, ECG Electrocardiogram, EMG Electromyogram, FNA Fine needle aspiration, LFTs Liver function tests, MRI Magnetic resonance imaging, N/A Not applicable, PET Positron emission tomography, URI Upper respiratory tract infection, U/S Ultrasound.

          The primary goal while assessing a mediastinal mass is to rule out oncologic emergencies (anatomic, metabolic, or hematologic) that require immediate medical attention. Workup includes patient’s history, physical examination, routine laboratory tests, and anatomic imaging (Figure 2). After excluding oncologic emergencies, further tests are needed to diagnose the mediastinal lesion.
          http://static-content.springer.com/image/art%3A10.1186%2F1471-2431-13-103/MediaObjects/12887_2013_839_Fig2_HTML.jpg
          Figure 2

          Flow chart for the workup of a mediastinal mass in an otherwise asymptomatic child.

          Physiologic imaging, most often PET-CT, is recommended in the diagnostic process when uncertainty about the malignant versus benign nature of the mass persists (Figure 2) [35].

          The pattern and intensity of uptake within such lesions on PET and morphologic appearance on CT can help differentiate benign from malignant etiologies [36] (also see Table 1). To accurately interpret BHT in PET studies, FDG uptake patterns in the normal thymus and pathologic entities involving the thymus need to be known [37]. Normal thymic tissue and benign conditions such as BHT after chemotherapy (so called “thymic rebound”), comparable to our patient, demonstrate diffuse, low-intensity, homogeneous FDG avidity (Table 1) [38, 39].

          Malignant conditions show intense FDG avidity that is usually heterogeneous in distribution [40]. The appearance of our patient’s lesion was similar to the normal thymus without focality, suggesting its benign nature (Figure 1B), [41] despite the cystic and necrotic areas within the mass [36, 42]. The morphology and uptake pattern on 18 F-FDG PET are more meaningful than the SUV. There is an overlap in SUV range between normal thymus and other malignant anterior mediastinal tumor entities [43]. Although a very high SUV may be indicative of malignancy, an average SUV does not exclude malignancy [36, 43].

          Conclusion

          In conclusion, for incidentally found anterior mediastinal masses in otherwise healthy children, we recommend that clinicians expeditiously rule out oncologic emergencies then perform a diagnostic workup. PET scans can help differentiate BHT from other more serious conditions and may spare patients invasive diagnostic procedures.

          Further studies including large pediatric series are needed to evaluate the importance of 18 F-fluorodeoxyglucose positron emission tomography in patients with suspected benign hyperplastic thymus.

          Consent

          Written informed consent was obtained from the patient’s mother for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

          Abbreviations

          BHT: 

          Benign hyperplastic thymus

          BMA: 

          Bone marrow aspiration

          CT: 

          Computed tomography

          FDG: 

          18 F- fluorodeoxyglucose

          PET: 

          Positron emission tomography

          SUV: 

          Standardized uptake value.

          Declarations

          Acknowledgments

          This research study is supported by the National Institutes of Health Cancer Support Core Grant (CA-21765 to MLM) and the American Lebanese Syrian Associated Charities (ALSAC to JLC and MLM).

          We thank Vani Shankar from St Jude for final editorial assistance as it relates to grammar and style.

          Authors’ Affiliations

          (1)
          Department of Pediatrics, University of Maryland
          (2)
          Department of Radiological Sciences, St. Jude Children’s Research Hospital
          (3)
          Department of Oncology, St. Jude Children’s Research Hospital
          (4)
          University of Tennessee Health Sciences Center

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          44. Pre-publication history

            1. The pre-publication history for this paper can be accessed here:http://​www.​biomedcentral.​com/​1471-2431/​13/​103/​prepub

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