A breast fibroadenoma mimicking an extranodal deposit of Hodgkin s lymphoma in 67 Ga imaging

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1 The British Journal of Radiology, 82 (2009), e58 e62 CASE REPORT A breast fibroadenoma mimicking an extranodal deposit of Hodgkin s lymphoma in 67 Ga imaging 1 E MORALIDIS, PhD, 2 E MANDALA, PhD, 3 I VENIZELOS, PhD, 1 G ARSOS, PhD, 4 E ZAFIRIADU, MD, 5 M GOUTZIOULIS, PhD and 1 C KARAKATSANIS, PhD 1 Department of Nuclear Medicine and 2 4th Department of Internal Medicine, Aristotle University, Hippokration Hospital and Departments of 3 Pathology and 4 Radiology, Hippokration Hospital, and 5 4th Department of Obstetrics and Gynecology, Aristotle University, Hippokration Hospital, Thessaloniki, Greece ABSTRACT. We present the case of a young woman with classical nodular sclerosing Hodgkin s lymphoma (clinical stage IIB). During staging work-up, intense gallium-67 ( 67 Ga) accumulation in a left breast lump raised the suspicion of an extranodal deposit, but biopsy favoured a benign histology. A post-treatment 67 Ga scan showed complete remission of the disease with normal tracer uptake in the left breast. However, a few months after treatment, a faint left mammary concentration of 67 Ga was observed. The breast mass was excised and histopathology was consistent with fibroadenoma. This unusual presentation is a new addition to the literature on false-positive 67 Ga findings and chemotherapy-associated tracer changes. Received 3 December 2007 Revised 30 January 2008 Accepted 5 February 2008 DOI: /bjr/ The British Institute of Radiology Gallium-67 ( 67 Ga) scintigraphy is an acknowledged modality for the evaluation of patients with lymphoma and, over the years, its role in oncology has focused almost exclusively on assessing the response of lymphomas to therapeutic manoeuvres [1]. However, there is a variety of challenges and pitfalls inherent in 67 Ga imaging for lymphoma. We report on a young female patient with Hodgkin s lymphoma in whom 67 Ga scintigraphy showed tracer accumulation in the left breast. Case report A 24-year-old woman presented with cervical lymph node enlargement, a left breast lump and constitutional symptoms. On clinical examination, enlarged, firm and non-tender cervical and supraclavicular lymph nodes were palpated bilaterally. A cm ovoid mass was also noted in the upper inner quadrant of the left breast, which was smooth and tender on palpation and had not been brought to medical attention previously. CT showed numerous enlarged cervical, submandibular and supraclavicular lymph nodes bilaterally, together with mediastinal lymphadenopathy, while the breast lump appeared hyperdense (Figure 1a d). On ultrasound, the breast mass was homogeneously hypoechoic with a sharp contour and a small central necrosis. In 67 Ga citrate imaging, intense tracer accumulation in the left breast was observed, together with active disease in the cervical, supraclavicular and mediastinal lymph nodes Address correspondence to: E Moralidis, Department of Nuclear Medicine, Aristotle University, AHEPA Hospital, 1 Stilp Kyriakidi Str, Thessaloniki , Greece. emoral@hol.gr; emoral@ med.auth.gr (Figure 1e). Biopsy of the breast mass showed components of fibrosis and adenosis, and a mild inflammatory reaction, but no malignancy was detected. Lymph node biopsy showed nodular sclerosing classical Hodgkin s lymphoma, classified as clinical Stage IIB. The patient was submitted to combined modality treatment for early stage unfavourable disease (six courses of ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) and irradiation with 30 Gy of the involved lymph nodes). 7 months later, CT showed complete remission of the disease and no significant change in the left breast mass (Figure 2a d). A 67 Ga scan also demonstrated normal tracer uptake in the affected lymph nodes and the left breast (Figure 2e). In the months following treatment, it was felt clinically that the left breast mass was growing, while faint 67 Ga concentration in the left breast was noted (Figure 3); the patient was referred for breast surgery. The lump was shelled out easily and subjected to histopathological examination, which was consistent with fibroadenoma together with mild periductal inflammation; no evidence of malignancy was found (Figure 4). Discussion Fibroadenoma is the most common solid breast mass in women under the age of 30 years, and is second only to carcinoma in the overall frequency of breast tumours [2]. Its rate of occurrence is reported to be 7 13% in women examined in breast clinics [3]. Fibroadenomas typically are unilateral and variable in size and their growth is moderated by oestrogens, progesterone, pregnancy and lactation; they also undergo atrophic e58 The British Journal of Radiology, March 2009

2 Case report: 67 Ga accumulation in a breast fibroadenoma (a) (b) (c) (d) (e) Figure 1. At baseline assessment, CT showed enlarged (a) cervical, (b) supraclavicular and (c) mediastinal lymph nodes (arrows) and (d) a hyperdense left breast mass (arrow). (e) In gallium-67 ( 67 Ga) imaging, intense tracer accumulation in the left breast was observed (thick arrow), together with abnormal tracer accumulation in cervical, supraclavicular and mediastinal lymph nodes (thin arrows). changes during the menopause [3, 4]. Analyses of the cellular components of fibroadenoma disclose benign hyperplastic processes associated with an aberration of normal development, rather than a true neoplasm [3]. Notably, a normal percutaneous biopsy cannot completely exclude pathology, as it fails to address the mass effects in large fibroadenomas, whereas surgical excision may allow a reliable histological diagnosis [4]. The British Journal of Radiology, March 2009 e59

3 E Moralidis, E Mandala, I Venizelos et al (a) (b) (c) (d) (e) Figure 2. After the completion of therapy, CT showed good resolution of (a) cervical, (b) supraclavicular and (c) mediastinal lymphadenopathy and no significant difference in the appearance of the left breast mass (arrow in d). (e) Gallium-67 ( 67 Ga) scintigraphy showed normal tracer uptake in the left breast, the cervical and supraclavicular regions and the mediastinum. e60 The British Journal of Radiology, March 2009

4 Case report: 67 Ga accumulation in a breast fibroadenoma Figure 3. 1 year after the baseline assessment, faint gallium- 67 ( 67 Ga) concentration in the left breast was noted (arrow). There was no evidence of disease recurrence elsewhere. 99m Tc Positive technetium-99m ( 99m Tc) sestamibi, tetrofosmin, indium-111 ( 111 In) octreotide, F-18-deoxyfluoro-D-glucose positron emission tomography (FDG- PET), 99m Tc thymine and iodine-131 ( 131 I) scans have been reported with fibroadenomas [5 10]. The findings have been attributed to (i) increased cellular activity, (ii) the expression of somatostatin receptors in the local vasculature or (iii) high levels of functionally active sodium iodide symporter protein in fibroadenoma. Many studies have demonstrated the clinical relevance of 67 Ga scintigraphy in patients with Hodgkin s or non- Hodgkin s lymphoma [1]. Its primary role is in monitoring the response to therapy, differentiation of residual viable lesions from non-tumoural fibrotic tissue, and surveillance for disease recurrence. The protocol requires Figure 4. Histopathological examination (haematoxylin and eosin stain, 6100) revealed a biphasic pattern of glandular and connective tissue elements consistent with fibroadenoma, together with mild periductal inflammation. The British Journal of Radiology, March 2009 a pre-treatment 67 Ga scintigraphy to assess the tracer uptake pattern of the individual lymphoma, followed by periodic imaging during and after treatment. There are reports that 67 Ga accumulates in extranodal lymphoma, including breast lesions, and that it is able to detect extranodal deposits with approximately the same sensitivity as it can nodal lymphoma [11 13]. It should be added that primary breast lymphoma is rare, with an incidence of no more than 0.5% of all breast malignancies and 2% of extranodal lymphomas, whereas secondary mammary involvement is slightly more common than primary breast lymphoma [12]. It is also important to note that, unlike lymphoma, breast carcinomas often are not 67 Ga avid [12 14]. There is growing evidence that FDG-PET is remarkably more efficient than 67 Ga scintigraphy for staging and restaging in lymphoma [15]. However, although FDG-PET has gained popularity, it is not yet universally available and many practitioners continue to rely on 67 Ga imaging when evaluating patients with lymphoma. In our case, the suspicion of an extranodal deposit in the breast lump during staging work-up was raised mainly on the basis of earlier data demonstrating accumulation of 67 Ga in breast lymphoma [11 13]. At that time, however, biopsy favoured a benign histology. Despite complete response to treatment of the affected lymph nodes and normalization of mammary tracer uptake, faint 67 Ga accumulation in the breast mass a few months later led to surgical excision and histopathological examination, which documented the presence of a fibroadenoma. Intense 67 Ga accumulation in the breast fibroadenoma may have been caused by increased cellular activity and the co-existing mild inflammation of the lesion. The normalization of mammary tracer uptake immediately after the conclusion of therapy may have been mediated by both the chemotherapy-induced disruption of the menstrual cycle and a direct suppressive effect of treatment. Faint left mammary accumulation of 67 Ga a few months later may have been secondary to (i) the restoration of the menstrual cycle and (ii) increased cellular activity in fibroadenoma and the mild periductal inflammation. This unusual presentation is a new addition to the literature regarding potential false-positive interpretations of 67 Ga scans and tracer uptake changes mimicking response to chemotherapy in young female patients with breast fibroadenoma. These findings are also in agreement with the widely shared experience that unusual presentations of common diseases are more likely than rare pathologies. References 1. Even-Sapir E, Israel O. Gallium-67 scintigraphy: a cornerstone in functional imaging of lymphoma. Eur J Nucl Med 2003;30:S Kepple J, Klimberg S. Management of benign breast mass. Probl Gener Surg 2003;4: Greenberg R, Skornick Y, Kaplan O. Management of breast fibroadenomas. J Gen Intern Med 1998;13: Park CA, David LR, Argenta LC. Breast asymmetry: presentation of a giant fibroadenoma. Breast J 2006;5: Prats E, Banzo J, Merono E, Herranz R, Carril JM. 99m Tc- MIBI scintimammography as a complement of the mam- e61

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