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Research ArticleCLINICAL INVESTIGATIONS

99mTc-MIBI Imaging in the Presurgical Characterization of Thyroid Follicular Neoplasms: Relationship to Multidrug Resistance Protein Expression

Enrico Saggiorato, Tiziana Angusti, Rosy Rosas, Morena Martinese, Monica Finessi, Federico Arecco, Edoardo Trevisiol, Nicoletta Bergero, Barbara Puligheddu, Marco Volante, Valerio Podio, Mauro Papotti and Fabio Orlandi
Journal of Nuclear Medicine November 2009, 50 (11) 1785-1793; DOI: https://doi.org/10.2967/jnumed.109.064980
Enrico Saggiorato
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Tiziana Angusti
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Rosy Rosas
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Morena Martinese
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Monica Finessi
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Federico Arecco
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Edoardo Trevisiol
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Nicoletta Bergero
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Barbara Puligheddu
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Marco Volante
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Valerio Podio
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Mauro Papotti
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Fabio Orlandi
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  • FIGURE 1. 
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    FIGURE 1. 

    Thyroid 99mTc-MIBI scan. (A and B) Representative positive case (RI, 71.76) of solitary cold thyroid nodule in right lobe histologically diagnosed as nononcocytic solid/trabecular poorly differentiated carcinoma. (A) Early image with tracer accumulation in nodule (ER, 2.62). (B) Delayed image with tracer retention in lesion (DR, 4.50). (C and D) Representative negative case (RI, −40.64) of solitary cold thyroid nodule in left lobe that proved to be microfollicular goiter. (C) Early image with tracer increase uptake in nodule (ER, 2.81). (D) Delayed image with nearly complete tracer washout from nodule (DR, 1.67).

  • FIGURE 2. 
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    FIGURE 2. 

    MDR1 expression in thyroid nodules with cytologic result of follicular neoplasm. (A) No P-gp immunoreactivity of follicular cells in nononcocytic emblematic case (follicular adenoma). (B and C) MRP1 membranous apical immunoexpression in case of nononcocytic microfollicular goiter (B) and in case of nononcocytic follicular variant of papillary carcinoma (C), both with negative RI indices. Cytoplasmic immunoreactivity with granular pattern is seen. (D) No MRP1 membranous apical labeling in case of nononcocytic solid/trabecular papillary carcinoma with positive RI value. Cytoplasmic immunoreactivity with granular pattern is seen. Arrows show linear membranous apical immunoreactivity. Immunoperoxidase with Mayer solution counterstain was used (magnification, ×160; insets: magnification, ×630).

  • FIGURE 3. 
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    FIGURE 3. 

    Proposed decision tree for thyroid follicular neoplasms combining 99mTc-MIBI scanning with molecular marker panel that we previously described (8). For cytologic diagnosis of oncocytic follicular neoplasm, we propose evaluation of galectin-3 and cytokeratin-19. Conversely, for nononcocytic follicular neoplasms, semiquantitative 99mTc-MIBI scintigraphy could be performed when galectin-3 and HBME-1 are negative. Negative results for both markers (galectin-3 and HBME-1) and for 99mTc-MIBI scanning indicate that close follow-up is needed. If molecular testing or 99mTc-MIBI scintigraphy results are positive, patient should be referred for thyroidectomy. HBME-1 = cell surface mesothelial antigen HBME-1.

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    TABLE 1

    Clinicopathologic Data of Patients with Thyroid Follicular Lesions, Visual 99mTc-MIBI Results, and MRP1 Expression

    Visual pattern*Apical expression†
    Sex (M/F)Median age and range (y)Median tumor size and range (cm)NegativePositiveNegativePositive
    Lesion typen0123−++++++
    Nononcocytic
     Microfollicular goiter93/659; 54–692.00; 1.20–4.00342—1152
     Follicular adenoma121/1148; 35–711.85; 1.00–3.50192—3261
     Minimally invasive follicular carcinoma20/239.5; 36–433.65; 3.50–3.80——2—1—1—
     Follicular variant of papillary carcinoma123/951; 28–621.35; 1.00–3.00—48—10—2—
     Poorly differentiated carcinoma11/0724.00——1—1———
    Oncocytic
     Microfollicular goiter51/460; 46–652.50; 1.00–3.00——414—1—
     Follicular adenoma61/546.5; 36–681.75; 1.00–2.90—1413—3—
     Follicular variant of papillary carcinoma30/369; 42–701.60; 1.10–1.60——3—3———
     Insular carcinoma11/0728.00——1—1———
    • ↵* Visual 99mTc-MIBI images were assessed using the following scoring system: pattern 0, no increased uptake of the nodule in either early or delayed images; pattern 1, increased uptake by nodule only in early images; pattern 2, increased uptake by nodule both in early and in delayed images; and pattern 3, increased uptake by nodule only in delayed images. For statistical analysis, visual scintigraphic patterns 0 or 1 and 2 or 3 were considered negative and positive, respectively.

    • ↵† MRP1 apical immunoreactivity was analyzed using the following scale: −, no reactivity; +, <25% positive follicular cells; ++, 25%−50% positive follicular cells; and +++, >50% positive follicular cells. For statistical analysis, MRP1 was considered positive when apical membrane immunoreactivity was observed in >25% of tumor cells (++ and +++).

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    TABLE 2

    Discrimination Between Malignant and Benign Nononcocytic Thyroid Lesions by 99mTc-MIBI Analyses

    Type of analysisSensitivity (%)Specificity (%)Positive predictive value (%)Negative predictive valuePositive likelihood ratioAccuracy
    Visual73.33% (44.91–92.05)80.95% (58.08–94.44)73.33% (44.91–92.05)80.95% (58.08–94.44)3.85 (1.51–9.79)77.78%
    Semiquantitative*100% (78.03–100)90.48% (69.58–98.55)88.24% (63.52–98.20)100% (82.20–100)10.50 (2.81–39.24)94.44%
    • ↵* RI threshold level = −11.94.

    • Data in parentheses are confidence intervals.

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    TABLE 3

    Semiquantitative 99mTc-MIBI Analysis Results

    BenignMalignant (carcinoma)
    CaseDiagnosisERDRRI*CaseDiagnosisERDRRI†
    Nononcocytic lesions
     TH-01Goiter1.191.3210.81TH-22Follicular1.832.7047.52
     TH-02Goiter2.722.25-17.28TH-23Follicular6.797.206.04
     TH-03Goiter2.811.67-40.64TH-24Papillary0.580.6817.97
     TH-04Goiter1.090.87-20.41TH-25Papillary0.400.4513.64
     TH-05Goiter2.501.40-44.00TH-26Papillary2.012.5325.82
     TH-06Goiter0.840.72-14.91TH-27Papillary2.823.8837.62
     TH-07Goiter1.501.27-15.15TH-28Papillary2.683.0012.15
     TH-08Goiter5.534.67-15.66TH-29Papillary1.942.5028.91
     TH-09Goiter9.753.75-61.54TH-30Papillary1.431.8831.92
     TH-10Adenoma2.324.67101.25TH-31Papillary1.361.8233.97
     TH-11Adenoma3.923.45-11.94TH-32Papillary1.491.6812.73
     TH-12Adenoma1.960.78-60.25TH-33Papillary2.183.0037.50
     TH-13Adenoma1.570.80-49.09TH-34Papillary1.241.23-0.81
     TH-14Adenoma1.800.83-53.70TH-35Papillary1.381.34-2.89
     TH-15Adenoma0.930.81-12.72TH-36Poorly differentiated2.624.5071.76
     TH-16Adenoma0.680.58-14.68
     TH-17Adenoma1.351.18-12.78
     TH-18Adenoma0.440.25-43.75
     TH-19Adenoma1.541.15-25.10
     TH-20Adenoma1.551.25-19.12
     TH-21Adenoma1.140.89-22.22
    Oncocytic lesions
     TH-37Goiter3.003.258.33TH-48Papillary1.241.4113.63
     TH-38Goiter1.692.0018.68TH-49Papillary2.252.365.05
     TH-39Goiter2.123.0041.67TH-50Papillary0.701.0043.33
     TH-40Goiter0.390.5539.39TH-51Insular3.103.8423.84
     TH-41Goiter1.201.4217.88
     TH-42Adenoma1.171.6541.02
     TH-43Adenoma2.905.6795.29
     TH-44Adenoma2.682.07-22.67
     TH-45Adenoma4.003.00-25.00
     TH-46Adenoma2.234.1786.78
     TH-47Adenoma1.761.9611.65
    • ↵* For benign nononcocytic lesions, all but 2 cases showed negative RI values. The 2 RI-positive cases had negative MRP1 apical expression (−). For benign oncocytic lesions, all but 2 cases showed positive RI values. The 2 RI-negative cases had positive MRP1 apical expression (++).

    • ↵† For malignant nononcocytic lesions, all but 2 cases showed positive RI values. The 2 RI-negative cases had positive MRP1 apical expression (++). For malignant oncocytic lesions, all cases showed positive RI values and had negative MRP1 apical expression (−).

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Journal of Nuclear Medicine: 50 (11)
Journal of Nuclear Medicine
Vol. 50, Issue 11
November 2009
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99mTc-MIBI Imaging in the Presurgical Characterization of Thyroid Follicular Neoplasms: Relationship to Multidrug Resistance Protein Expression
Enrico Saggiorato, Tiziana Angusti, Rosy Rosas, Morena Martinese, Monica Finessi, Federico Arecco, Edoardo Trevisiol, Nicoletta Bergero, Barbara Puligheddu, Marco Volante, Valerio Podio, Mauro Papotti, Fabio Orlandi
Journal of Nuclear Medicine Nov 2009, 50 (11) 1785-1793; DOI: 10.2967/jnumed.109.064980

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99mTc-MIBI Imaging in the Presurgical Characterization of Thyroid Follicular Neoplasms: Relationship to Multidrug Resistance Protein Expression
Enrico Saggiorato, Tiziana Angusti, Rosy Rosas, Morena Martinese, Monica Finessi, Federico Arecco, Edoardo Trevisiol, Nicoletta Bergero, Barbara Puligheddu, Marco Volante, Valerio Podio, Mauro Papotti, Fabio Orlandi
Journal of Nuclear Medicine Nov 2009, 50 (11) 1785-1793; DOI: 10.2967/jnumed.109.064980
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