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. 2009 May 25;2009:bcr08.2008.0696. doi: 10.1136/bcr.08.2008.0696

Contribution of the 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography to the diagnosis of primary osseous Hodgkin lymphoma

Florence Breibach 1, Anne Julian 2, Camille Laurent 1, Eric Anglade 3, Arnaud Constantin 4, Nicolas Sans 5, Jean-Louis Tricoire 6, Pierre Brousset 1, Marie-Bernadette Delisle 7, Anne Gomez-Brouchet 7
PMCID: PMC3029632  PMID: 21686679

Abstract

Hodgkin lymphoma typically presents as a nodal lesion and infrequently involves extra nodal sites. Although cases of primary extra-nodal Hodgkin lymphoma have been reported previously, the reality of the primitive nature of the disease was difficult to authenticate with traditional high resolution imaging techniques, such as computed tomography or magnetic resonance imaging, because they cannot evaluate the spread of the disease throughout the whole body. We report here a case of primary osseous Hodgkin lymphoma, regarded as stage I extranodal IE thanks to the important contribution of a new imaging technique, the 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography/ computed tomography (18F-FDG-PET/CT). PET enables systemic Hodgkin lymphoma with secondary bone invasion to be distinguished from primitive osseous Hodgkin lymphoma. This technique is highly specific in demonstrating the isolated osseous localisation of the tumour and should be recommended in all patients with putative osseous lymphoma.

BACKGROUND

Hodgkin lymphoma (HL) typically involves the lymphatic system at one or more sites.1 Primary extra-nodal HL without lymph node involvement is rare.2,3 Several primary cases have been described in different sites such as lungs,4–8 oral mucosa,9 salivary glands,10,11 oesophagus,12 stomach,13 rectum,14–16 thyroid gland,17,18 central nervous system,19,20 testicles21 and kidneys.22 Most primary Hodgkin cases reported previously are in fact secondary cases in a context of systemic Hodgkin’s disease.

Extra nodal HL is considered at stage I according to Ann Arbor classification. This case must be distinguished from systemic HL with secondary bone invasion, which corresponds to stage IV of the disease.23–26 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT) is a new, functional, highly sensitive imaging technique, which allows concomitant investigation of malignant tumour locations and examination of the whole body.27–29 Here we present a case of primary osseous HL. 18F-FDG-PET/CT proved that the bone tumour was primitive and unique, and thus confirmed that it was a stage I unifocal osseous HL. Such accurate diagnosis was crucial for proposing the most appropriate treatment.

CASE PRESENTATION

A 17-year-old female patient without any previous history presented with deep, continuous restricted low back pain that began 3 months earlier. There was no traumatic factor related to the apparition of pain. The patient presented with only night sweats. There was neither fever nor weight loss. Physical examination did not show any pathological lymph node. Severe pain was elicited upon clinical examination of the left sacral region.

INVESTIGATIONS

Laboratory values showed a mild inflammatory syndrome (C reactive protein 20 UI), a fluctuating elevated eosinophilic rate (from 500 to 3500 cells/mm3) and a slightly elevated IgE rate. The bacteriological, mycological and parasitological tests remained negative.

Radiographs of the lumbar spine and pelvis were normal. CT scan showed an osteolytic lesion in the left hemisacrum (fig 1). Magnetic resonance imaging (MRI) of the pelvis showed a diffuse infiltration of the left hemisacrum. Following gadolinium injection, MRI revealed a significant enhancement of the left hemisacrum. A CT scan of the neck, chest, abdomen and pelvis did not show any other lesion. A whole body 18F-FDG-PET/CT also showed a marked tracer uptake in the left part of the sacrum, which was even more intense at tumour periphery (fig 2). No pathological tracer uptake was found elsewhere.

Figure 1.

Figure 1

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Osteolytic lesion of the left hemisacrum with blurred borders and moderate sclerotic changes in periphery in computed tomography scan.

Figure 2.

Figure 2

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From left to right: transversal views with non-attenuation corrected 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography (dedicated FDG-PET), contrast enhanced computed tomography (CT), and FDG-PET/CT fusion. PET showed an intense FDG uptake at the sacral lesion periphery whereas FDG uptake was reduced within this lesion.

A primary histopathological examination of a CT guided needle biopsy was inconclusive as it showed osseous fibrosis infiltrated with inflammatory cells such as lymphocytes and eosinophilic granulocytes. Therefore, a surgical biopsy followed by a microscopic examination was performed. The lesions were characterised by a fibrosis developing in bone marrow spaces, which was infiltrated with diffuse and nodular layers of lymphocytes, plasma cells, histiocytes, and eosinophilic and neutrophilic granulocytes. Lacunar cells and rare typical binucleated Reed–Sternberg cells (RS), with large cytoplasms and prominent eosinophilic nucleoli, were scattered in the reactive infiltrate. Areas of acidophilic necrosis were found (fig 3). Immunohistochemistry showed an isolated staining of the atypical cells with anti-CD30 and anti-CD15 antibodies. These cells did not express CD20, EMA, CD79a, PS100 and CD1A (fig 4). Epstein–Barr virus (EBV) status was negative. Taken together, these morphological and immunological data were consistent with a classical Hodgkin’s lymphoma.

Figure 3.

Figure 3

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Typical binucleated Reed–Sternberg cells in the reactive infiltrate.

Figure 4.

Figure 4

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CD 30 Reed–Sternberg cells staining.

DIFFERENTIAL DIAGNOSIS

A neoplastic or infectious osseous disease, such as tuberculosis, was first suggested based on traditional high resolution imaging techniques because the lesion exhibited destructive and aggressive behaviours: lytic and heterogeneous lesion with extension into soft tissues. 18F-FDG-PET/CT proved that the bone tumour was primitive and unique. The true diagnosis, however, could not be done solely with radiological examinations. Microscopic analysis of a surgical biopsy was necessary. The microscopic diagnosis of an osseous location of HL may be difficult since fibrosis and granulomatous infiltration most often predominate while masking the rare diagnostic RS cells. The most frequent misdiagnosis is other primary or metastatic bone tumours, eosinophilic granuloma and osteomyelitis. In our case, eosinophilic granuloma could be clinically evoked due to the low age of the patient, its high frequency, and the unique bone location. Similarly, osteomyelitis, secondary to osseous parasitological, mycobacterial or banal germ infection, could have been suggested. In the latter cases, immunohistochemical analyses are mandatory to distinguish X cells of eosinophilic granuloma from RS cells.

OUTCOME AND FOLLOW-UP

All the imaging and histopathological data enabled us to establish the diagnosis of a primitive osseous HL at stage I according to the Ann Arbor classification. The patient was given three cycles of MOPP chemotherapy (methylchlorethamine, vincristine, procarbazine, prednisone), and 1 year later she is in a good shape. Functional symptoms disappeared and osseous lesions diminished. One year later the patient is considered to be in complete clinical remission.

DISCUSSION

Classical HL is usually almost entirely confined to the lymph nodes. The disease is characterised, on microscopic examination, by the presence of Reed–Sternberg cells residing in a mixture of non-neoplastic reactive cells.1 HL is usually supra-diaphragmatic with contiguous spread often occurring predictably from one nodal group to the next along the lymphatic pathways. Extra nodal involvement is much less common in HL than in non-Hodgkin lymphoma. Numerous authors described cases of primary extra-nodal HL, but many of these appeared to have concurrent and/or subsequent nodal involvement. Few cases of primary pulmonary Hodgkin disease with no hilar or mediastinal node disease,4–8 primary involvement of different organs of the gastrointestinal tract,12–16 of the parotid10,11 and the thyroid17,18 glands have been described. Others locations such as the central nervous system,19,20 testicles21 or kidneys22 have been reported.

What makes our case original is that this is the first report of bone HL whose primary and unifocal characters were confirmed by the whole body 18F-FDG-PET/CT. Primary lymphomas of bone are uncommon malignancies, representing 3–7% of malignant bone tumours and 1–3% of extranodal malignant lymphomas. Most of them are large B cell lymphoma.30,31 Fewer than 20 patients with HL presenting as a primary bone tumour have been previously reported in the literature. Diagnosed before 1960, most of these patients had very limited evaluations, compared with current standards. The reality of the osseous manifestations of HL could not be proved because of the limited explorations carried out at that time.2 Only three solitary osseous tumours and two multifocal osseous HL have actually been identified as real primitive bone diseases. Most of the lesions were located on axial skeleton or on long bones. While standard x rays show an osteolytic lesion, traditional high resolution imaging techniques, such as CT or MRI, allow a better definition of both the location and local extension of the lesions. The general spread of the disease could not be evaluated on the whole body. One of these cases had been explored by 18F-FDG-PET/CT imagery. Contrary to x ray imaging which is essentially anatomic, 18F-FDG-PET is a functional imaging process since it measures the FDG avidity of the tissues.27 Moreover, it allows an exploration of the whole body in the same step. Many studies showed that 18F-FDG-PET was more sensitive than whole body CT for evaluating the spread of lymphoma (79–99% and 65–90%, respectively).27–29 Still, it has also some drawbacks: a poor spatial resolution (4 mm) and good but not very high specificity, since some other benign lesions with a high glucidic metabolism, like inflammations, granulomas and infections, can show an increase of the FDG uptake.32,33 Recently, the fusion of isotopic and x ray imaging permitted the combination of anatomic and functional data, improving the specificity of the 18F-FDG-PET. Several studies proved that the efficacy of the combination 18F-FDG-PET/CT was better than PET alone in the same application.34–36 18F-FDG-PET/CT is therefore currently the best tool to establish the unique and primitive characteristic of a lesion in primitive osseous HL.

LEARNING POINTS

  • Primary extra-nodal Hodgkin lymphoma (HL) is rare and primary bone HL is even rarer.

  • 18F-FDG-PET/CT is the best imaging technique that confirms osseous primary HL.

  • Diagnosis with 18F-FDG-PET/CT ameliorates therapeutic management.

Footnotes

Competing interests: none.

Patient consent: Patient/guardian consent was obtained for publication

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