Skip Navigation

Japanese Journal of Clinical Oncology 2004 34(7):429-431; doi:10.1093/jjco/hyh069
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Papantoniou, V.
Right arrow Articles by Zerva, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Papantoniou, V.
Right arrow Articles by Zerva, C.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2004 Foundation for Promotion of Cancer Research

Scintimammographic Findings of Phyllodes Tumor of the Breast in a Double-phase Study with Tc-99m (V)DMSA and Tc-99m MIBI: a Case Report

Vassilas Papantoniou1, John Koutsikos1, Maria Sotiropoulou2, Ekaterini Mainta1, Dimitrias Lazaris3, Spyridon Tsiouris1 and Cherry Zerva1,+

Departments of 1 Nuclear Medicine, 2 Pathology and 3 Obstetrics and Gynecology, Alexandra University Hospital, Athens, Greece


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 CASE REPORT
 DISCUSSION
 REFERENCES
 
We present a case of phyllodes tumor of the breast in a 78-year-old woman evaluated with Tc-99m (V)DMSA and Tc-99m MIBI scintimammography, acquired in separate sessions (10 and 60 min post-injection). Tc-99m (V)DMSA was accumulated intensely within the mass [tumor to background ratio (T/B) >3], whereas Tc-99m MIBI had significantly lower uptake (T/B 1.9). Histology revealed a phyllodes tumor (maximum diameter 15 cm) and approximately three mitoses over 10 fields of view (FOV) x40, foci of epithelial hyperplasia and apocrine metaplasia. Stromal Ki-67 expression was 7%. The tumor was considered to be benign and the patient underwent mastectomy. One year later the patient presented with local malignant recurrence of the disease with over 15 mitoses per 10 FOV. Tc-99m (V)DMSA seems to have an advantage over Tc-99m MIBI in detecting mesenchymal tumors with unforeseen biological behavior and Ki-67 over-expression, such as phyllodes tumors, even with primary negative histological findings.


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 CASE REPORT
 DISCUSSION
 REFERENCES
 
Phyllodes tumors represent 0.5–1.8% of breast tumors and only 2.5% of fibroepithelial tumors. It is constituted from a combination of epithelial and stromal components surrounding the ductal mesenchymal (1).

These kinds of tumors present in women aged 35–55 years. Patients are referred with a palpable and quickly growing mass of size >4 cm. Phyllodes tumors are classified as benign [<3 mitoses per 10 fields of view (FOV)] and malignant low and high grade (>3 mitoses per 10 FOV). The biological behavior of phyllodes tumors is unpredictable and local recurrence and even malignant transformation may occur in high-grade malignant phyllodes tumors. Clinical examination, history and mammography can easily lead to a safe diagnosis, but there is no good predictor for the prognosis and the progression of such a tumor. A high mitotic index, Ki-67, hormonal receptor status, stromal overgrowth, measurement of sarcomatous component and necrosis are considered to be the most significant histological and immunohistochemical parameters to assess the prognostic outcome of the disease (2).

Tc-99m pentavalent DMSA [(V)DMSA] and Tc-99m MIBI scintimammography have been used in detecting breast cancer and its lymph node involvement and even more in precancerous lesions with high risk of progression to malignancies (35). Tc-99m (V)DMSA and Tc-99m MIBI appear to have different mechanisms of accumulation in tumors, which have not yet been completely clarified. Tc-99m MIBI is concentrated in cancer cells by an energy-requiring transport mechanism and transmembrane electronegative potential, in addition to non-specific mechanisms, and is stored within the mitochondria. The mechanism of accumulation of Tc-99m (V)DMSA has been thought to be related to the structural similarity between Tc-99m (V)DMSA core and PO43–, which is avidly taken up by some cancer cells (6,7). In a poorly differentiated breast cancer model, it is reported that uptake of Tc-99m (V)DMSA was more than twofold greater than that of Tc-99m MIBI (8). It is also reported that Tc-99m (V)DMSA uptake by tumors was related to glucose-mediated acidosis (9). This study was performed to evaluate and compare the abilities of Tc-99m (V)DMSA and Tc-99m MIBI to visualize tumors with unknown biological behavior, such as phyllodes tumors, especially those related to increased cell proliferation activity.


    CASE REPORT
 TOP
 ABSTRACT
 INTRODUCTION
 CASE REPORT
 DISCUSSION
 REFERENCES
 
A 78-year-old woman with a mammography showing extensive opacity occupying the whole left breast (Fig. 1) underwent scintimammography (before surgery) with Tc-99m (V)DMSA and Tc-99m MIBI with a 48 h time interval between the two tests.



View larger version (125K):
[in this window]
[in a new window]
 
Figure 1. The whole left breast is occupied by an extensive opacity in the mammogram.

 
Lateral prone and anterior supine early and late images (at ~10 and ~60 min, respectively) were acquired, after intravenous administration of 555–740 MBq of each radiotracer. Acquisitions were obtained using a special positioning pad (PBI-2 Scintimammography Pad Set®, Pinestar Technology, Greenville, PA).

Scintimammography was performed using a single-head g camera (Sophycamera DS7®, Sopha Medical Vision International, Buc, France), equipped with a high-resolution parallel hole collimator connected to a dedicated computer (Sophy NxT®, Sopha Medical Vision International). The matrix was 256 x 256 pixels and the photo peak was focused at 140 keV with a symmetric 10% window.

Tc-99m (V)DMSA scintigraphy showed increased concentration with tumor to background ratio (T/B) >3 in both early and delayed images. Tc-99m MIBI also showed increased concentration but with lower T/B ratio (1.9) (Fig. 2).



View larger version (111K):
[in this window]
[in a new window]
 
Figure 2. (A) Early (10 min post-injection) and late (60 min post-injection) left lateral images of Tc-99m MIBI scintimammography in prone position. Slight increase (arrow) in MIBI uptake (T/B ratio = 1.9). (B) Early (10 min post-injection) and late (60 min post-injection) left lateral images of Tc-99m (V)DMSA scintimammography in prone position. Significant increased concentration (arrow) (T/B ratio >3).

 
The patient underwent mastectomy and the histology revealed a phyllodes tumor (maximum diameter 15 cm) and approximately three mitoses over 10 FOV, foci of epithelial hyperplasia and apocrine metaplasia (Fig. 3).



View larger version (140K):
[in this window]
[in a new window]
 
Figure 3. Phyllodes tumor: nuclear polymorphism with stromal mitotic activity, epithelial hyperplasia.

 
Ki-67 was found to be over-expressed in the first evaluation. It was 7% in stromal and 5% in epithelial hyperplasia.

One year later, the patient underwent a second surgery due to local recurrence of the disease. Over 15 mitoses per 10 FOV x40 were observed in surgical specimens.


    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 CASE REPORT
 DISCUSSION
 REFERENCES
 
Moffat et al. (10) reported that 17% of benign and 27% of malignant phyllodes tumors in a group of 1600 patients with phyllodes tumors presented with recurrence of the disease. The biological behavior of phyllodes tumors seems unpredictable. Stromal overgrowth, necrosis, type of sarcomatous component, high malignant grade, increased cell proliferation index, increased cellularity and stromal atypia are the more significant histological parameters of grave prognosis.

Imaging characteristics with mammography and ultrasonography in differentiating between benign and malignant phyllodes tumors have not been described (11). Katayama et al. (12) reported cases evaluated with Tc-99m MIBI and Tc-99m MDP to estimate and distinguish between benign and malignant types of phyllodes tumors. Ohta et al. (13) reported that the early appearance of a phyllodes tumor is related to a benign tumor.

Tc-99m (V)DMSA and to a lesser extent Tc-99m MIBI, as we reported previously, can be effective in visualizing preinvasive lesions such as DCIS/LCIS and epithelial hyperplasia (14,15). Tc-99m (V)DMSA seems to be related to cell proliferative activity in cancerous (5,16) and even more in precancerous cell populations such as DCIS/LCIS and epithelial hyperplasia.

The potential reasons for differences between Tc-99m (V)DMSA and Tc-99m MIBI tumor accumulation are probably based on the different mechanisms of tracer concentration in tumors, as mentioned before.

In the present case, Ki-67 was slightly increased in the stromal (7%) and in the epithelial (5%) component of the tumor. In theoretically benign lesions, a slight increase in the cell proliferation index appears to be a significant risk factor in the process of carcinogenesis (1721). Although increased Ki-67 expression has been reported to be related to a higher uptake of Tc-99m (V)DMSA in epithelial hyperplasia, it is still uncertain whether stromal overgrowth or epithelial hyperplasia is the cause of increased Tc-99m (V)DMSA concentration, although it has no special clinical significance.

Tc-99m (V)DMSA was found to be related to proliferative activity in invasive and preinvasive breast lesions (22,23), which is directly related to tumor grade. Tc-99m MIBI’s lower uptake is probably due to the non-dependence of this tracer on cell proliferation index. Obviously, this is the reason for the low MIBI uptake in the present case.

This case indicates that histologically proven benign phyllodes tumor does not safely exclude a malignant transformation. We consider that Tc-99m (V)DMSA scintimammography could offer useful information regarding the probable outcome of the disease.


    FOOTNOTES
 
+ For reprints and all correspondence: John Koutsikos, Department of Nuclear Medicine, Alexandra University Hospital, 80 Vas. Sofias Ave. & Lourou, Athens 11527 Greece. E-mail: jtkoutsik{at}yahoo.gr Back


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 CASE REPORT
 DISCUSSION
 REFERENCES
 
1 Tavassoli FA. Pathology of the Breast. New York: Elsevier 1992;442–65.

2 Rossen PP, Oberman HA. Tumors of the Mammary Gland. 3rd edition. Washington, DC: Armed Force Institute of Pathology 1993;107–14.

3 Papantoniou V, Sotiropoulou M, Stipsaneli E, Louvrou A, Feda H, Christodoulidou J, et al. Scintimammographic findings of in situ ductal breast carcinoma in a double-phase study with Tc-99m (V)DMSA and Tc-99m MIBI. Value of Tc-99m (V)DMSA. Clin Nucl Med 2000;25:434–9.[CrossRef][Web of Science][Medline]

4 Papantoniou V, Christodoulidou J, Papadaki E, Valotassiou V, Stipsanelli A, Louvrou A, et al. 99mTc-(V)DMSA scintimammography in the assessment of breast lesions: comparative study with 99mTc-MIBI. Eur J Nucl Med 2001;28:923–8.[CrossRef][Web of Science][Medline]

5 Palmedo H, Hensel J, Reinhardt M, Von Mallek D, Matthies A, Biersack HJ. Breast cancer imaging with PET and SPECT agents: an in vivo comparison. Nucl Med Biol 2002;29:809–15.[CrossRef][Web of Science][Medline]

6 Yokoyama A, Saji H. Tumor diagnosis using radioactive metal ions and their complexes. In: Siegel H, editor. Metal Ions in Biological Systems, vol. 10. New York: Marcel Dekker 1980;313–40.

7 Wulfrank D, Schelstraete K, Small F, Charles F. Analogy between tumor uptake of technetium-99m-(V) dimercaptosuccinic acid (DMSA) and technetium-99m-MDP. Clin Nucl Med 1989;14:588–93.[CrossRef][Web of Science][Medline]

8 Palmedo H, Hensel J, Bender H, Wagner U, Bangard M, Biersack HJ. 18F-FDG, 99mTc-(V)DMSA and 99mTc-MIBI in an animal breast cancer-model: comparison of tumor-uptake and correlation with scintigraphic and PET-detection [abstract]. Eur J Nucl Med 2000;27:1130.

9 Horiuchi K, Saji H, Yokoyama A. Tc(V)-DMS tumor localization mechanism: a pH-sensitive Tc(V)-DMS-enhanced target/non-target ratio by glucose-mediated acidosis. Nucl Med Biol 1998;25:549–55.[CrossRef][Web of Science][Medline]

10 Moffat CJ, Pinder SE, Dixon AR, Elston CW, Blamey RW, Ellis IO. Phyllodes tumours of the breast: a clinicopathogical review of thirty-two cases. Histopathology 1995;27:205–18.[Web of Science][Medline]

11 Liberman L, Bonaccio E, Hamele-Bena D, Abramson AF, Cohen MA, Dershaw DD. Benign and malignant phyllodes tumors: mammographic and sonographic findings. Radiology 1996;198:121–4.[Abstract/Free Full Text]

12 Katayama N, Inoue Y, Ichikawa T, Harada M, Itoh T, Shimoyamada K, et al. Increased activity in benign phyllodes tumor on Tc-99m MDP scintimammography. Clin Nucl Med 2000;25:551–2.[CrossRef][Web of Science][Medline]

13 Ohta H, Komibuchi T, Nishio T, Kitai T, Yamamoto S, Ukikusa M, et al. Technetium-99m-sestamibi scintimammography of benign and malignant phyllodes tumors. Ann Nucl Med 1997;11:37–9.[Medline]

14 Papantoniou V, Sotiropoulou M, Stipsanelli A, Souvatzoglou M, Valotassiou V, Koutsikos I, et al. Tc-99m (V)DMSA breast uptake in usual type hyperplasia (HUT) and apocrine metaplasia (AM) in relation with cell proliferation index (Ki-67) and the presence of estrogen receptors. Comparative study with Tc-99m MIBI [abstract]. Eur J Nucl Med Mol Imag 2003;Suppl 2:S290.

15 Maunda KY, Chande H, Mselle TFA, Bomanji JB. 99mTc sestamibi scintimammography in the diagnosis of palpable breast masses. Nucl Med Commun 2003;24:141–4.[CrossRef][Web of Science][Medline]

16 Papantoniou VJ, Souvatzoglou MA, Valotassiou VJ, Louvrou AN, Ambela C, Koutsikos J, et al. Relationship of cell proliferation (Ki-67) to 99mTc-(V)DMSA uptake in breast cancer. Breast Cancer Res 2004;6:R56–62.[CrossRef][Web of Science][Medline]

17 Solcia E. Histological Typing of Endocrine Tumours, 2nd ed. WHO International Histological Classification of Tumours. Springer: Berlin 2000.

18 Kocova L, Skalova A, Fakan F, Rousarova M. Phyllodes tumour of the breast: immunohistochemical study of 37 tumours using MIB1 antibody. Pathol Res Pract 1998;194:97–104.[Web of Science][Medline]

19 Dacic S, Kounelis S, Kouri E, Jones MW. Immunohistochemical profile of cystosarcoma phyllodes of the breast: a study of 23 cases. Breast J 2002;8:376–81.[CrossRef][Medline]

20 Niezabitowski A, Lackowska B, Rys J, Kruczak A, Kowalska T, Mitus J, et al. Prognostic evaluation of proliferative activity and DNA content in the phyllodes tumor of the breast: immunohistochemical and flow cytometric study of 118 cases. Breast Cancer Res Treat 2001;65:77–85.[CrossRef][Web of Science][Medline]

21 Shaaban AM, Sloane JP, West CR, Foster CS. Breast cancer risk in usual ductal hyperplasia is defined by estrogen receptor-alpha and Ki-67 expression. Am J Pathol 2002;160:597–604.[Abstract/Free Full Text]

22 Papantoniou V, Stipsaneli A, Arka A, Louvrou A, Lazaris D, Nakopoulou L, et al. Immunohistologic assessment of 99mTc-(V)DMSA and 99mTc-MIBI uptake in breast cancer [abstract]. Eur J Nucl Med 1999;26:977.

23 Papantoniou V, Nakopoulou L, Christodoulidou J, Papadaki E, Souvatzoglou M, Stipsaneli A, et al. Correlation and multivariate regression analysis between 99mTc (V)DMSA and 99mTc MIBI uptake and steroid receptors, proliferation index, tumor size, age, malignant grade, p53 and c-erbB-2 in primary breast cancer [abstract]. Eur J Nucl Med 2001;28:1120.

Received January 25, 2004; accepted March 29, 2004


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Papantoniou, V.
Right arrow Articles by Zerva, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Papantoniou, V.
Right arrow Articles by Zerva, C.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?