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Lobular Breast Carcinoma A Case of Rare Possible

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F-FDG PET/CT and Bone Scan False Negative

Anna Margherita Maffione, MD,* Laura Camilla Lisato, MD,Þ Annalisa Rasi, MD,Þ Maria Cristina Marzola, MD,* Patrick M. Colletti, MD,þ and Domenico Rubello, MD* Abstract: A patient with diffuse osteosclerotic bone metastases from invasive lobular breast carcinoma is presented with both 18F-FDG PET/CT and bone scans negative for hypermetabolic lesions. Skeletal metastases were documented by CT and bone marrow biopsy, and high increased CA 15-3 level was recorded. This case report points to the potential risk of false-negative FDG PET and bone scans examination in lobular carcinoma type. Key Words: PET/CT, 18F-FDG, lobular carcinoma, breast cancer, bone scan, false negative (Clin Nucl Med 2015;40: e134Ye136)

Received for publication February 13, 2014; revision accepted March 10, 2014. From the Departments of *Nuclear Medicine, PET Unit, and †Pathology, Santa Maria della Misericordia Hospital, Rovigo, Italy; and ‡Department of Radiology, University of Southern California, Los Angeles, CA. Conflicts of interest and sources of funding: none declared. Reprints: Anna Margherita Maffione, MD, Department of Nuclear Medicine, Santa Maria della Misericordia Hospital, Viale Tre Martiri, 140, 45100 Rovigo, Italy. E-mail: [email protected]. Copyright * 2014 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0363-9762/15/4002Ye134

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REFERENCES 1. Groheux D, Giacchetti S, Moretti JL, et al. Correlation of high 18F-FDG uptake to clinical, pathological and biological prognostic factors in breast cancer. Eur J Nucl Med Mol Imaging. 2011;38:426 Y 435. 2. Crippa F, Seregni E, Agresti R, et al. Association between [18F]fluorodeoxyglucose uptake and postoperative histopathology, hormone receptor status, thymidine labelling index and p53 in primary breast cancer: a preliminary observation. Eur J Nucl Med. 1998;25:1429Y1434. 3. Avril N, Menzel M, Dose J, et al. Glucose metabolism of breast cancer assessed by 18F-FDG PET: histologic and immunohistochemical tissue analysis. J Nucl Med. 2001;42:9Y16. 4. Buck A, Schirrmeister H, Ku¨hn T, et al. FDG uptake in breast cancer: correlation with biological and clinical prognostic parameters. Eur J Nucl Med Mol Imaging. 2002;29:1317Y1323. 5. Heudel P, Cimarelli S, Montella A, et al. Value of PET-FDG in primary breast cancer based on histopathological and immunohistochemical prognostic factors. Int J Clin Oncol. 2010;15:588Y593. 6. Inoue T, Yutani K, Taguchi T, et al. Preoperative evaluation of prognosis in breast cancer patients by [(18)F]2-deoxy-2-fluoro-D-glucose-positron emission tomography. J Cancer Res Clin Oncol. 2004;130:273Y278. 7. Avril N, Rose´ CA, Schelling M, et al. Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations. J Clin Oncol. 2000;18:3495Y3502. 8. Bos R, van Der Hoeven JJ, van Der Wall E, et al. Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol. 2002;20:379Y387. 9. Buck AK, Schirrmeister H, Mattfeldt T, et al. Biological characterisation of breast cancer by means of PET. Eur J Nucl Med Mol Imaging. 2004;31: S80YS87. 10. Cristofanilli M, Gonzalez-Angulo A, Sneige N, et al. Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes. J Clin Oncol. 2005;23:41Y 48. 11. Koolen BB, Vrancken Peeters MJ, Wesseling J, et al. Association of primary tumour FDG uptake with clinical, histopathological and molecular characteristics in breast cancer patients scheduled for neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging. 2012;39:1830Y1838. 12. Brown B, Laorr A, Greenspan A, et al. Negative bone scintigraphy with diffuse osteoblastic breast carcinoma metastases. Clin Nucl Med. 1994;19:194 Y196. 13. Koizumi M, Yoshimoto M, Kasumi F, et al. What do breast cancer patients benefit from staging bone scintigraphy? Jpn J Clin Oncol. 2001;31:263Y269.

Clinical Nuclear Medicine

& Volume 40, Number 2, February 2015

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Clinical Nuclear Medicine

& Volume 40, Number 2, February 2015

Lobular Breast Carcinoma

FIGURE 1. A 78-year-old white woman affected by breast carcinoma underwent left mastectomy in 2009. Pathology revealed an infiltrating lobular carcinoma (ILC) pT2 pN2 Mx; estrogen receptor (ER), 90%; progesterone receptor, 90%; Ki-67, 6%; and human epidermal growth factor receptor 2, negative. Progressively, an increase of CA 15-3 level was observed (357 U/mL; reference values, G31.1 U/mL), and the patient was scheduled for a bone scan, a thoracic contrast-enhanced CT, and a whole-body 18 F-FDG PET/CT. A, bone window contrast-enhanced CT scan of the pelvis demonstrates diffuse osteosclerotic micronodular and macronodular bone lesions, in keeping with diffuse metastasis. B, fused 18F-FDG PET/CT scan of the pelvis (bone window for CT) demonstrates the absence of significant increased tracer uptake. Diffuse osteosclerotic nodular bone changes were reported suggesting a metastatic disease involvement. C, Maximum intensity projection of 18F-FDG PET scan shows the whole-body absence of noteworthy radiopharmaceutical uptake. D, Anterior view and (E) posterior view of bone scan demonstrate the absence of significant radiopharmaceutical uptake of oncologic relevance. In consideration of the unusual appearance of the disease due to the substantial negativity of PET and bone scan, a bone marrow biopsy was performed revealing metastasis from lobular carcinoma; ER, 100%; progesterone receptor, 70%; Ki-67, 2%; and human epidermal growth factor receptor 2 ++. Lower FDG uptake in ILC than in infiltrating ductal carcinoma has already been reported by some studies1Y6; the justification could be found in a minor tumor cell concentration, a spread infiltration of adjacent tissue, a low proliferation rate, and a decreased level of GLUT1 expression in ILC.7Y9 Some authors have found that ILCs are usually ER positive and of histological grade 2,10 2 situations that could be correlated with a relatively low FDG PET sensitivity.11 Regarding scintigraphy, in spite of a single case reported in literature of a patient with diffuse osteoblastic metastases from ILC with negative bone scan,12 there is no scientific evidence about a low sensitivity of bone scan for ILC.13 All these findings are translated in clinical practice as a potential risk of false-negative FDG PET/CT and bone scan examinations in ILC, both in staging and restaging for metastatic setting.

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Clinical Nuclear Medicine

& Volume 40, Number 2, February 2015

FIGURE 2. A, bone marrow trephine biopsy section showing infiltration of the bone marrow by metastatic lobular carcinoma of the breast growing in aggregates (hematoxylin-eosin, 200). B, bone marrow trephine biopsy section showing low Ki-67 proliferative rate of metastatic lobular carcinoma (Ki-67 immunoperoxidase stain, 200). In this particular case, it can be hypothesized that the low proliferative rate of the tumor can be the cause of the very low glycolytic bone marrow metabolism.

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* 2014 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

CT and bone scan false negative.

A patient with diffuse osteosclerotic bone metastases from invasive lobular breast carcinoma is presented with both F-FDG PET/CT and bone scans negati...
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