British Journal of Radiology (2005) 78, 758-761
© 2005 British Institute of Radiology
doi: 10.1259/bjr/55106848
Gluteal injection site granulomas: false positive finding on FDG-PET in patients with non-small cell lung cancer
H Prosch, MD1,
S Mirzaei, MD2,
E Oschatz, MD1,
G Strasser, MD1,
M Huber, MD3 and
G Mostbeck, MD1
1 Otto Wagner Hospital, Department of Radiology, Sanatoriumsstra
e 2, 1140 Vienna, 2 Wilhelminenspital, Institute of Nuclear Medicine, Montleartstrae 37, 1160 Vienna and 3 Otto Wagner Hospital, Department of Pathology, Sanatoriumsstrae 2, 1140 Vienna, Austria
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Abstract
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Positron-emission-tomography (PET) with fludeoxyglucose F-18 ([18F] fluoro-2-deoxy-D-glucose, FDG) has become an established imaging modality in patients with lung cancer for mediastinal lymph node staging and the detection of extrathoracic metastases. However, tracer accumulations are not limited to malignant tissue but are also found in muscles and benign inflammatory processes. We report on two patients with lung cancer in whom FDG-PET revealed suspicious tracer accumulations in the buttock. Ultrasound (US) revealed a hyperechogenic nodule with poorly defined margins in both patients. On specific inquiry both patients reported on repeated "intramuscular" gluteal injections. Histology after US guided biopsy showed an accumulation of macrophages within fibrous tissue, compatible with injection site granulomas. The reported cases underline that 18F-FDG may accumulate in benign, ancillary processes that have to be distinguished from distant metastases. Tracer accumulation in the buttocks may be highly suggestive of injection site granulomas, especially if the patient reports on "intramuscular" injections. In this setting, US is a widely available modality to distinguish metastasis from adipose tissue necrosis.
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Introduction
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The last decade whole-body positron emission tomography (PET) with fludeoxyglucose F-18 ([18F] fluoro-2-deoxy-D-glucose, FDG) has become an established imaging modality in oncology. High sensitivity and the high negative predictive value led to its important role in patients with lung cancer for mediastinal lymph node staging as well as the detection of extrathoracic metastases [1]. However, 18F-FDG uptake is not exclusively by malignant tissue but is also found in muscles and inflammatory processes. There is a growing number of reports on physiological processes and benign entities that have to be distinguished from metastases PET staging [2]. It is essential to be aware of normal variants, artefacts and other causes of false positive studies.
We report on two patients with lung cancer in whom FDG-PET revealed suspicious tracer accumulations in the gluteal region.
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Case reports
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PET studies in both cases were performed on a ECAT EXACT PET scanner (CTI/Siemens, Knoxville, TN) 1 h after intravenous injection of 355 MBq and 325 MBq 18F-FDG, respectively. Ultrasound (US) examinations were performed on an ATL HDI 5000 ultrasound device (Philips, The Netherlands) using a linear array – small part scanhead.
Case 1
A 57-year-old female patient with a 30 month history of non-small cell lung cancer (NSCLC) (squamous cell carcinoma, T4 N3 M0) was admitted to our hospital for a re-evaluation after five cycles of chemotherapy. Prior to radiation therapy distant metastases had to be excluded.
FDG-PET showed hypermetabolic foci in the right lower lung and the right hilum, corresponding to the residual NSCLC and lymph node metastases. Additionally, a hypermetabolic focus could be detected in the right dorsal pelvic region (Figure 1a
). Further evaluation of the hypermetabolic focus with US revealed a poorly marginated, inhomogeneous lesion with a maximal diameter of 1.5 cm within the adipose tissue of the buttock (Figure 1b). On specific inquiry the patient reported to have received several injections of vitamin B preparations and the analgesic tramadol in this area in the past, the last injection some 3 months ago. US guided biopsy of the lesion was performed. The histological work-up demonstrated adipose tissue necrosis and an accumulation of macrophages.
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Figure 1. (a) 57-year-old woman with lung cancer. FDG-PET scan demonstrating pathological tracer accumulation in the right lower dorsal lung (arrowhead) and a hypermetabolic focus in the right dorsal pelvic region (arrows). (b) Ultrasound of the right buttock. Inhomogeneous, partly hyperechogenic and partly hypoechogenic (compared with the surrounding fat) lesion with poorly defined margins (arrowheads) and a maximal diameter of 1.5 cm within the adipose tissue.
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Case 2
A 71-year-old male patient had undergone lobectomy of the left lower lobe (NSCLC, squamous cell carcinoma, T2 N0 M0) 6 months previously. He was now admitted for the evaluation of a suspected tumour recurrence based on clinical findings and a CT scan of the chest. The FDG-PET scan showed hypermetabolic foci in the left upper and left lower lung and a small hypermetabolic focus in the right upper mediastinum suggesting tumour recurrence and mediastinal adenopathy. In addition, focal increased uptake of FDG was found in the soft tissues of the right dorsal pelvic region (Figure 2a). US examination demonstrated a poorly marginated, round hyperechogenic lesion (1.9 cm maximum diameter) which was surrounded by an unsharp hypoechogenic rim (Figure 2b) within the adipose tissue. On request, this patient reported repeated "intramuscular" injections of a non-steroidal anti-inflammatory drug (phenylbutazone) in the gluteal region in the past. The last injection he had received was 1 year prior to the FDG-PET examination. US guided biopsy was performed. Histologically, necrotic adipose tissue with focal scar formation and accumulation of macrophages (Figure 2c) was found.
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Figure 2. (a) 71-year-old man with lung cancer. FDG-PET demonstrating hypermetabolic foci in the left upper and left lower lung suggesting tumour recurrence (mediastinal adenopathy not shown). Hypermetabolic focus on the right side corresponds to posterior parts of the liver. In addition there is a hypermetabolic focus in the right buttock (arrows). (b) US of the right buttock. Poorly marginated, hyperechogenic lesion (1.9 cm diameter) surrounded by a less echogenic rim. (c) Histological image showing an accumulation of macrophages (arrows) within fibrous tissue. Immunostaining for anti-human macrophage CD 68 ( x 250).
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Discussion
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Although in the presented cases the 18F-FDG uptake in the buttocks was likely to be benign, the referring physicians wanted to exclude distant metastases or a second malignancy. Metastases to the subcutaneous tissue are observed in up to 9% of cancer patients [4]. The most frequent tumours causing subcutaneous metastases are melanoma, lung cancer and breast cancer [4]. Sonographically, subcutaneous metastases usually appear as hypoechogenic, well demarcated nodules with a polycyclic shape within the subcutaneous fat. Using colour Doppler ultrasound, these metastasis demonstrate hypervascularity with multiple feeding vessels [4]. In contrast, injection site granulomas appear as hyperechogenic nodules with heterotopic calcifications and poorly defined borders [5]. In addition, clinical history and the localization of the lesion in the subcutaneous fat in the upper outer quadrant of the buttock are suggestive for an injection site granuloma.
Injection site granulomas are caused by repeated injections of drugs into the subcutaneous fat [6]. The tissue reaction depends on the site and number of injections and the composition of the injected drug. However, despite the high incidence of injection site granulomas due to "intralipomatous" injection, no reports on FDG tracer accumulations were found in the medical literature. There is only one report on an increased uptake in an In-111 Octreoscan in a patient who had undergone repeated "intramuscular" Sandostatin injections [7].
In both of our patients these injection site granulomas were proven histologically. Histology in injection site granulomas may demonstrate stages in the transition from necrosis of fat cells to formation of dense fibrous tissue with inflammatory changes, with or without foreign-body giant cells [8]. The accumulation of macrophages – as shown in our patients – within the lesions may be an explanation for the 18F-FDG accumulation. Inflammatory cells have been reported to have an increased uptake of 18F-FDG [2]. One may speculate that 18F-FDG tracer accumulations are limited to "active" injection site granulomas were activated macrophages are present. However, the time interval between FDG-PET and the last injection was up to 1 year in our patients, indicating that "activity" of these granulomas may last long.
The reported cases underline that 18F-FDG tracer may accumulate in benign, ancillary processes that have to be distinguished from distant metastases. 18F-FDG accumulations in the buttocks are highly suggestive of injection site granulomas, especially if the patient reports on recent "intramuscular" injections. In this setting, US may be a widely available modality to distinguish metastasis from adipose tissue necrosis. In addition, the combination of PET and CT may further help to clarify the precise anatomical location and benign nature of this potential pitfall.
Received for publication September 28, 2004.
Revision received March 2, 2005.
Accepted for publication March 14, 2005.
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References
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Abstract
Introduction
