Tumori

Results. Thirty-four cancers were detected among 31 subjects. One patient refused magnetic resonance imaging because of claustrophobia. Compared with sporadic disease, hereditary cancer showed some differences, in terms of biologic attitude and semeiotic patterns. These differences were mainly registered for magnetic resonance imaging, where the most frequent radiological variant was represented by the very high T2 signal intensity (73%). Moreover, the size of 8 of the neoplasms showed a significant increase in less than one year, 5 of them in less than 6 months. Six lesions were in BRCA1 patients and the remaining in BRCA2. Furthermore, cancers with a high growth rate also demonstrated a significant increment in T2 signal intensity.

Conclusions. Our results confirmed the high growth rate within BRCA-related breast cancers, especially for BRCA1 mutation carriers. In our experience, we found a specific imaging phenotype, represented by the high T2 signal intensity of hereditary breast cancer. To our knowledge, this is the first report that points out this new semeiotic parameter, which is usually typical of benign lesions. Considering the correlation between high growth rate and high T2 signal intensity, the former seems to be related to the absence of induction of a desmoplastic reaction that could somehow restrict cancer growth. Free full text available at www.tumorionline.it

In the 1990s the concept of inherited breast cancer was focused on. In fact, two breast-related cancer genes, BRCA1 and BRCA2, were identified. Mutations in these genes are responsible for a markedly increased risk to develop breast cancer, even at a young age, which is often multiple. Women BRCA carriers face almost a 60% life-long risk of breast cancer.

The optimal management of this increased risk is still under intense investigation, which includes screening, risk-reducing surgery and chemoprevention^1,2. Surveillance has been traditionally based on regular clinical examination and mammography, which currently represents the most effective screening method in the general population. Nevertheless, first reports on the aptitude of mammography in the detection of breast cancer in high-risk women showed a huge percentage of false-negative results^3-5.

Owing to its high spatial and contrast resolution and no X-ray correlation, magnetic resonance imaging (MRI) has been progressively included in screening protocols. The superior sensitivity of the technique for the detection of breast cancer even at an early stage has been unanimously established^4,6-10.

At our Institute, between June 2000 and September 2009, 227 women at high genetic risk entered a protocol of diagnostic surveillance: 34 breast cancers were diagnosed in 32 patients. One of them was only diagnosed at mammography and ultrasound because the patient refused MRI examination. During this period, we noticed some differences between the biologic behavior of hereditary cancer compared with sporadic disease.

First of all, we noted that the growth of breast cancer in high-risk patients can be very fast. We registered 8 (23%) cases in which the size of the suspected lesion markedly increased in less than one year, 5 of them in less than 6 months and 2 within 6 months.

Secondly, according to the traditional MRI semeiotic phenotype, we encountered some morphologic or dynamic aspects of the BRCA-related neoplasm that could not be considered as typical for cancer, particularly for the T2 signal intensity (SI), which was very high, as we usually find in benign diseases of the general population. Conventional imaging also registered some differences as regards sporadic cancers.

The aim of the study was to verify the high speed of growth of inherited breast cancer, to study their T2 SI besides kinetic and morphologic aspects, and to analyze whether there was any difference in the MRI phenotype between BRCA1, BRCA2 carriers and women at high familial risk.

Materials and methods

Between June 2000 and May 2009, 230 women – BRCA1 (136) and BRCA2 carriers (61), or first degree relatives of BRCA1 (4) and BRCA2 (4) carriers, or with high familial risk of breast cancer (25) – were annually screened with clinical examination, mammography, ultrasound and MRI.

Women were classified as BRCA1 or BRCA2 carriers if genetic testing identified a disease-causing mutation. Women belonging to families where no mutation was identified or in whom the test was not performed were classified as high familial risk, according to previously established criteria. Informed consent was obtained from each subject enrolled in the study.

Mammography was performed in craniocaudal and mediolateral oblique projections. Spot compression, magnification, and additional views were obtained as needed (Hologic Selenia, direct digital mammography). Ultrasound of the breast was performed with high frequency probes (12-5 MHz, 50 mm) (Philips HDI 5.000).

MRI examinations were performed on a 1.5 T magnet (n. 23 with Magneton Vision and n. 12 with Magneton Avanto, Siemens, Erlangen, Germany) using a dedicated double breast surface coil. For premenopausal patients, MRI was performed between the 7th and the 14th day of the menstrual cycle. Our imaging protocol consisted of a previous T2 inversion recovery (IR) sequence (TR/TE 5770/73) followed by a three-dimensional, gradient-echo, T1-weighted dynamic images (TR/TE 7.8/4.7, flip angle 25°, slice thickness 1.8 mm without gap, no. of sections 88, matrix 410 x 512, FOV 340 x 100 cm, TA 55 sec) obtained once before and five times after injection of 0.2 mmol/kg gadolinium DTPA and followed by a saline flush of 20 ml.

Informed consent was obtained before each MRI examination.

Histopathological confirmation was obtained at vacuum-assisted core-needle biopsy with mammography, ultrasound or MRI guidance.

Two dedicated radiologists analyzed mammographic and sonographic aspects of each lesion (Table 1). Another radiologist expert in breast MRI, blinded to the results of conventional analysis, described both morphologic and dynamic aspects of each enhancing region (Table 2). For morphologic characteristics, the analysis was performed on image subtraction of the precontrast images from early and late postcontrast images in order to obtain the suppression of fat and nonenhancing parenchyma and to distinguish the enhancing aspects. Lesion shape (mass like, non-mass like [irregular shape], ductal), dendritic enhancement and margins were evaluated.

For dynamic aspects, a region of interest (ROI) was placed within the tumor-suspected enhancement and the SI-to-time curve was calculated. The shape of the curve (type I, persistent; type II, plateau; type III, washout)¹¹ was also evaluated. Further patterns of MRI analysis were the modality of uptake of contrast medium (homogeneous, heterogeneous, with rim enhancement) and the T2 SI (optically judged as high, intermediate, or low).

For each breast cancer we measured the maximum diameter in case of mass-like enhancement. In case of irregular or dendritic shape enhancement or when multiple small contiguous foci were present, we measured their overall maximum extension, whereas we took the length and the breadth in case of ductal-like enhancement. As the T2 SI did not change when a recall was requested, we quantified T2 SI only on the last MRI examination. When interesting changes in size occurred for the same breast cancer in two different examinations, we measured the two main perpendicular diameters.

The radiographic tumor size ranged from 4 mm to 3 cm.

To quantify the optical brightness of T2 SI, we first applied the “pixel lens value” function (Table 3). On the T2-weighted IR fat-suppressed sequence, we scheduled a mean SI value of each lesion by computing 3 measurements and deriving the mean SI mean. Despite the well-known overall nonhomogeneity of breast parenchyma, we tried to relate the SI of the lesion to that of the mammary gland. In order to accomplish this, we choose to draw 3 pixel lens values within the normal tissue surrounding the lesion, irrespective of its content, then derived the mean value. We kept a distance of 10 mm as regards the lesion to avoid any overlap with eventual neoangiogenetic vessels or desmoplastic reactions. The mean results were compared to calculate the ratio between the T2 SI of the lesion and that of the surrounding breast (LPS, lesion-to-parenchyma signal score).

On T2-weighted IR fat-suppressed sequences, we also calculated a mean SI value by means of an ROI (Table 3). For this second procedure, we applied the evaluation on the pectoralis major muscle in the region of its major thickness and on the suspected neoplastic lesion. Since the lesion size of our cohort ranged from 5 mm to 3 cm, we selected two different ROIs with a mean diameter of 5.0 ± 0.1 mm for each lesion, then averaged the SI results. Only for one lesion no larger than 2 mm was the ROI diameter small enough to fit the right size of the lesion in analysis. Final values were calculated by dividing the lesion SI by the SI of the major pectoral muscle (LMS, lesion-to-muscle signal score).

In order to yield uniform results, we held the same ROI diameter for analysis of the T2 SI of the pectoralis major muscle. In this second case, the mean results were also compared and final values were calculated by dividing the T2 SI value of the lesion by that of the pectoralis major muscle.

Once all the ratio scores were calculated, we determined some threshold values to quantify optical impressions. When a suspected finding was seen at only MRI despite ultrasound second look, recall of the patient was recommended. The recall was mainly advised because of the very small diameter of the lesions at their presentation, because of the occurrence of benign morphologic-kinetic features for some cases, and because of the unavailability of the MRI-guided biopsy device until April 2009.

Between June 2000 and May 2009, 227 women at high genetic risk were enrolled in the study. During this period, 34 breast cancers were diagnosed in 31 women. Nineteen breast cancers were detected in 19 BRCA1 carriers (19/34, 61%), 9 in 6 BRCA2 carriers (9/34, 29%), and 6 in 6 women at high familial risk (6/34, 19%). Patient 5 and patient 11 were submitted to conventional analysis at another hospital and directed to MRI in our Institution (patient 11 had two enhancing lesions in the left and one in the right breast). For another woman, cancer was diagnosed only by means of conventional imaging as the patient refused MRI because of claustrophobia (patient 13). The 34th neoplasm was detected in a carrier who had a contralateral breast cancer 5 years after mastectomy. Of the 34 diagnosed breast cancers of our cohort, only 33 were evaluated by means of MRI because 1 patient refused the examination.

All of the 33 breast cancers submitted to MRI analysis were detected by this modality. For one of these patients, conventional imaging was not available but was reported as negative. Nine cancers were detected also with mammography, and 3 cancers became suspect at the recall (12/34, 35.2%). Eighteen cancers were detected also with ultrasound and 4 become recognizable at the recall (22/34, 64.7%). Nine women had already developed cancer in the contralateral breast before enrollment, and 4 had an ipsilateral breast cancer.

MRI registered 3 false-positive results (patients 33, 34, 35); 2 were found to be adenosis, and 1 was a complex dysplasia at histological examination. Conventional imaging registered 3 false-positive reports, not confirmed at MRI and histology (patients 36, 37 and 38).

In one case, MRI and ultrasound disclosed a focus of lobular carcinoma in situ (LCIS) (patient 32). According to the international guidelines, this case was not considered as a true carcinoma.

Table 4 summarizes the histological features of the 34 detected breast cancers. Of these, 18 were pure invasive cancers, 2 were pure ductal carcinoma in situ (DCIS), 1 was a DCIS and LCIS, and 11 were invasive carcinomas with in situ components. Histological type was not available in one patient for whom invasive carcinoma not otherwise specified was reported (patient 19). Moreover, patient 11 had bilateral pathological features at imaging; she was treated after our diagnosis at another institution, where following left lesion biopsy she received chemotherapy; subsequent MRI evaluation showed good regression of the disease in both breasts. The patient underwent left mastectomy and continued her further follow-up at the other institution .

Within the invasive group, the most common histological type was ductal carcinoma (IDC), described in 25/34 cases (73%). IDC was present in 17 of the 19 cancers in BRCA1 carriers, in 5 of 8 cancers in BRCA2 carriers, and in 3 of 6 cancers in high-familial-risk patients. IDC were mostly grade III (20/34, 59%), and only 2 cases were grade I (one in the tubular carcinoma and one in an IDC of a BRCA2 carrier).

Although receptor and Her2-neu status was not available for all cases, we found 9 triple negatives, 8 of which were in tumors of BRCA1 carriers.

Mammographic findings

Twenty-five (25/34, 73.5%) breast cancers occurred in women with normal mammograms. For 1 of these patients, mammography was not available but was reported as negative. Of 12 recalls requested on the basis of MRI findings, 3 mammographies disclosed positive findings (3/12, 25%).

Eight cancers appeared as a mass, none with smooth margins (Table 1). Four cancers were detected because of microcalcifications with/without association to a true mass. None of these cancers appeared as an architectural distortion; 2 of them appeared as an asymmetrical thickening. None of them had a typically benign appearance like a fibroadenoma, and only 1 showed benign calcifications.

The mammographic density patterns in women with invasive or intraductal breast cancer and false-negative findings on mammograms was not significantly different from those in women with true-positive results.

Sixteen (16/34, 47%) breast cancers occurred in women with normal or benign aspects within the parenchyma. For 1 of these patients, ultrasound was not available but was reported as negative. Of 12 recalls requested on the basis of MRI findings, 4 ultrasound examinations disclosed positive findings (4/12, 33%). All of the 16 cancers appeared as a solid mass with an irregular shape and margins (Table 1). None of these cancers appeared as fibroadenoma-like lesions, round or oval in shape, with posterior acoustic enhancement (Table 1).

As regards false-positive results of conventional imaging, for patient 36, mammography gave negative results within a P2 glandular context. Ultrasound showed a highly suspect ill-defined hypoechoic mass in a high-familial-risk patient, without MRI correspondence. Histology was negative for cancer.

For patient 37 (BRCA1-mutated), mammography showed the onset of suspected microcalcifications within a P2 mammographic pattern. MRI did not disclose suspicious findings. Histology revealed stromal fibrosis. Patient 38 was negative at mammography but in a P2 glandular pattern. Ultrasound detected a hypoechoic mass with circumscribed margins, considered as iconographically benign, but worthy of biopsy because of the clinical context. In this case, MRI showed a round mass-like enhancement of 6 mm in the same position, with a very high T2 SI, but with an aspecific dynamic curve, which induced the MR radiologist to advice simple follow-up. Histology revealed a phyllodes tumor.

Of the 34 diagnosed breast cancers of our cohort, only 33 were evaluated by means of MRI because 1 patient refused the examination. For one of these lesions (patient 11, right breast), we do not have histology, but the suspect enhancing area showed the same morphologic-kinetic aspects as the biopsied disease of the contralateral breast.

None of the 33 MRI-evaluated cancers occurred in a benign or negative context, hence MRI did not register false-negative results. However, we considered as suspect and sent to biopsy 2 cases of adenosis and 1 complex dysplasia.

Of malignant lesions, the most frequent morphologic pattern was enhancing mass-like in 26 patients (26/33, 78%), round or oval shape, single or more than one contiguous foci, each one a few millimeters in size in the second case (Table 2). Of these 26, 11 (11/26, 42%) lesions showed smooth margins and homogeneous internal enhancement. One of these converted to an irregular shape made by several contiguous dendritic aspects, irregular borders and hence heterogeneous enhancement (patient 16). It was an IDC combined with a DCIS, in a mutated-BRCA1 patient. Another lesion converted to irregular borders but still with homogeneous uptake at the recall (patient 30). It was also an IDC combined with a DCIS, but in a BRCA2 carrier. For the remaining 9, 4 were pure IDC, 1 was invasive cancer not otherwise specified, 3 were IDC commixed with DCIS, and 1 was DCIS and LCIS. Of these 11 malignancies arising with smooth margins and homogeneous internal enhancement, 9 were in BRCA1 and 2 in BRCA2 carriers.

The T2 SI in these mass-like lesions with smooth margins and homogeneous internal enhancement was high in 9 (9/11, 81%) and of intermediate intensity in 1, whereas the T2 IR sequence resulted not done in 1 (Table 2). When of intermediate intensity, histology revealed IDC and DCIS.

Of the 26 tumors with a morphologic mass-like pattern, 15 (55.5%) demonstrated irregular borders: 9 were pure IDC, 1 was invasive tubular carcinoma, 1 was ILC and LCIS, 1 was IDC and LCIS, 2 were IDC and DCIS, and the last was IDC and ILC. Eight of these breast cancers belonged to BRCA1-mutated women, 4 to BRCA2-mutated women, and 3 to women at high familial risk.

The T2 SI in mass-like lesions with irregular borders was very high in 10 (10/15, 66.6%), of intermediate intensity in 2, low in an IDC, and not done in 2. When of intermediate intensity, histology revealed IDC in one and IDC and LCIS in the other. Of these 15 lesions with irregular borders, 6 were associated to the rim pattern (Table 2).

Seven of 33 MRI-detected cancers did not show a typical mass-like morphologic enhancement (7/33, 21%). Four of them arose as an irregular shape with speculated borders; 2 as dendritic, ductal but very irregular, with speculated edges and a branched aspect; and 1 as a more linear, ductal-like enhancement.

Irregular shapes with irregular margins mainly occurred in in situ carcinomas (1 DCIS, 1 not submitted to biopsy but with the same shape as in the contralateral DCIS, and 1 DCIS and LCIS) except for 1 IDC: 2 of the women were at high familial risk and the remaining were BRCA2-mutated. T2 SI was low in those not biopsied, of intermediate intensity in the case of DCIS and LCIS, and very high in one DCIS and one IDC. None of the lesions characterized by an regular shape at presentation showed any morphological transformation at the recall.

Dendritic aspects were present in BRCA1 subjects and histology disclosed DCIS in one case and IDC in the other. T2 was of intermediate intensity in intraductal disease and of high intensity in invasive cancer. Both of the diseases characterized by dendritic morphology at presentation demonstrated a transformation at the recall: the lesions converted into a mass-like enhancement in both subjects. These mass-like entities were always combined with irregular margins, but with homogeneous uptake in one and rim enhancement in the other (Table 2).

Ductal enhancement was associated to a BRCA2-mutated patient with IDC and ILC (Table 2). T2 SI was of low intensity. The lesion converted into several contiguous round small mass-like enhancements at the recall.

As regards false-positive MRI results, morphologic pattern was that of an enhancing mass, with smooth margins and homogeneous enhancement combined with a plateau curve in one case of adenosis, where T2 was very high and the patient was BRCA1 mutated. One case showed an irregular area of enhancement with very irregular margins and heterogeneous enhancement and a steady curve. The T2 SI was isointense compared to normal parenchyma; the patient was BRCA1 mutated. The third case, in a BRCA1-mutated patient, was an irregular area of enhancement, irregular in shape, with homogeneous uptake, with a plateau curve and T2 SI of intermediate intensity.

Concerning dynamic aspects, of 33 MRI-analyzed cancers, 21 were associated with a washout curve shape (21/33, 63.6%). In 1 case the washout curve showed a delayed aspect as may happen in the lobular histotype¹². In another one, the washout curve was commixed with a steady curve at presentation but converted to a washout type, the only kinetic aspect at the recall (Table 2). A third lesion registered a washout type at presentation but converted into a steady type at the recall.

Seven other neoplasms were associated with a plateau curve shape (7/33, 21%) and 5 (5/33, 15%) to a steady curve shape, one of which converted to a washout shape at the recall (Table 2).

Of the 21 washout curves, 13 (13/21, 61.9%) belonged to pure invasive carcinoma, 5 (5/21, 23.8%) to invasive carcinoma combined with intraductal disease, and 3 (3/21, 14%) to in situ disease alone. This curve shape was found in 10 BRCA1-mutated, 6 BRCA2-mutated, and 5 high-familial-risk patients.

Of the 7 plateau type curves, 4 (4/7, 57%) were found in pure invasive carcinoma, 2 (2/7, 28.5%) belonged to invasive carcinoma combined with intraductal disease, 1 corresponded to the lesion not submitted to biopsy, and none was associated to intraductal disease. Of these 7, 5 were found in BRCA1- and 2 in BRCA2-mutated women.

Of the 5 steady curves, 2 (2/5, 40%) were invasive carcinoma, 2 (2/5, 40%) belonged to invasive carcinoma combined with intraductal disease, and 1 (1/5, 20%) was present in intraductal disease. They were found in 4 BRCA1- and 1 BRCA2-mutated women.

Benign disease was never associated with a washout curve and always found in BRCA1-mutated women.

Considering the 33 MRI-detected cancers, T2 IR sequence was not applied in 3 cases. Of the other 30, we accounted for 22 breast cancers with very high T2 SI (22/30, 73%), 5 breast cancers showed T2 SI of intermediate intensity (5/30, 16.6%), and 3 cancers were associated to low T2 SI (3/30, 0.1%) (Table 2). Of the 3 MRI false-positive cases, 1 was isointense on T2 sequence, 1 showed intermediate intensity and 1 showed high T2 SI.

Of the 22 neoplasms with high T2 SI, 13 were found in BRCA1-mutated (13/22, 59%), 7 in BRCA2-mutated (7/22, 31,8%), and 2 in high-familial-risk patients (2/22, 0.1%). Of the 5 lesions with T2 intermediate intensity, 4 were associated to BRCA1 mutation and 1 to high familial risk.For the 3 low intensity T2 SI cancers, 2 were associated to BRCA2 and 1 to BRCA1 mutation.

Of the 22 with high T2 SI, 14 (14/22, 63.6%) were pure invasive carcinoma, 3 (3/22, 13.6%) were pure intraductal disease, and 5 (5/22, 22,7%) were invasive carcinoma associated to intraductal disease. Of the 5 cancers with intermediate T2 SI, 2 were pure in situ disease, 1 was pure IDC, and 2 were invasive combined with intraductal disease. Lastly, of the 2 lesions with low T2 SI, 1 was IDC and the other was not submitted to biopsy.

To evaluate the brightness of SI on T2 IR sequences, we quantified T2 SI of the lesion by means of two functions: first the pixel lens value, second an ROI. The former compared the SI of the lesion to the one of the surrounding parenchyma, the latter to the SI of the pectoralis major muscle.

As regards the LPS, in our cohort we found that optical low SI corresponded to a value ≤1.2, whereas intermediate SI ranged from 1.2 to 2.5 and high SI over 2.5 (Table 3). As regards the lesion-to-muscle score (LMS), we also registered some basal thresholds (Table 3). Many overlaps occurred in this case between the numeric results. In detail, optical low SI ratio values between SI of the lesion and the pectoralis major muscle ranged from 1.4 to 2.5. One patient with cancer relapse over a previous surgical scar had a score of 5.9 in low optical SI. Optical middle SI numerical scores ranged from >1.5 to <4; and high SI between 3.1 and 18.8 (Table 3).

Several overlaps occurred between numerical scores of middle and high SI. Low SI values were between 1.4 and 2.5, with the exception of one lesion arising over a previous surgical scar that registered an optical low T2 SI but with a corresponding LMS score of 5.9 (patient 10). The highest SI scores were found in patients 24, 26, 28 and 30 (Tables 2 and 3). Corresponding optical brightness was cystic-like for all the lesions, two of which also showed rapid growth. Only one lesion arose over a previous scar. Two of these were pure IDC, grade III; one was IDC and ILC, grade II; the last was DCIS and IDC, grade II.

Patients 8, 11 (right), 15 and 20 exhibited some discrepancies. The tumor of patient 8 showed optically intermediate T2 intensity with an LMS score of 1.5, like lower LMS general scores. However, it was a DCIS. For patient 11, the tumor (on the right) was of low optically T2 intensity but with a 2.5 LMS score, like intermediate LMS scores. We do not know the histology of the lesion. The tumor of patient 15 demonstrated an optically high T2 but the LMS score was of the intermediate group, and the lesion was an IDC and DCIS, grade III. The tumor of patient 20 showed an optically intermediate T2 intensity, but the LMS score was of the lower LMS general scores. Again, the lesion was an IDC and DCIS, grade III.

Of the 31 women affected by breast cancer, 1 refused MRI because of claustrophobia and the disease was detected only with mammography and ultrasound. In 15 patients, the diagnosis of breast disease was made after the first MRI examination was performed (and 5 of these had previously been evaluated only by means of conventional analysis). Sixteen had the onset of disease during the screening program, and the cancer arose after an interval of 3 years for one woman and of 1 to 2 years for the others. Two different expert radiologists reviewed previous MRI of these women and confirmed the absence of morphologic or dynamic indications of a tumor.

For 9 of the group already enrolled in the surveillance program (9/16, 56.3%), MRI examinations preceding the onset of the disease were completely negative, with bilateral darkness of both breasts on early and late subtracted images. For the remaining 7 (7/16, 43.7%), the former MRI showed a dysplastic pattern, with bilateral multiple foci of enhancement almost of the same size, as is frequently seen in young women.

Owing to the possibility of false-positive results of MRI, when an MRI examination was suspect but without corresponding findings on mammography or ultrasound, the patients were deferred to follow-up. This happened for 12 cases (Table 2). As we had previously noted that some changes may occur in mammary parenchyma of BRCA-mutated women within short periods, we reduced the period of follow-up to a few months. Only one of these patients with suspicious aspects on MRI but with no correspondence on conventional imaging delayed the MRI control to one year because of claustrophobia.

On the last recall (Table 2), only 4 of the 12 (4/12, 33.3%) had no change, whereas we noted a volume increase besides some morphological or dynamic changes of the disease in the other 8 (8/12, 66.6%) cases. Changes occurred for periods ranging from 3 months to 1 year. Of patients who had a phenotypic evolution, 6 were BRCA1 mutated (6/8, 75%), 2 were BRCA2 mutated (2/8, 25%), and none were at high familial risk. Tumors with unchanged morphological and dynamic aspects were from patients at high familial risk in 2 cases, BRCA1 mutated in 1, and BRCA2 mutated in the remaining subject. All changes that occurred in 3 months were in BRCA1-mutation carriers.

Of the 8 tumors that experienced an MRI phenotype evolution (Table 2), 2 had an impressive volumetric increase of nearly 1 cm, respectively at 3 months and 1 year (patients 19 and 24). Both of them were BRCA1-mutation carriers, and the cancer histotype was invasive carcinoma not otherwise specified in the first and IDC in the second. Their age was 44 and 54 years. For the first woman, morphology evolved from a small focus of enhancement, smooth margins and homogeneous uptake of contrast medium to a larger enhancing mass, with a rim pattern and speculated margins, highly suggestive of an infiltrative behavior. The diameters changed from 6 to 14 mm in 3 months (Figure 1). In this case, mammography remained unsuspicious at the recall, whereas ultrasound depicted a structural nonhomogeneity as a focal architectural distortion without typical characteristics for cancer on the basis of MRI findings. Mammographic glandular pattern was P2 according to the Wolfe Classification ¹³.

The second woman had a dendritic impregnation (ductal like with speculated-branched margins) at the beginning, with speculated borders and heterogeneous enhancement, and the evolution was towards a single larger mass-like lesion, again with irregular margins and a rim pattern. Hence in this case, besides the volumetric increase, also morphologic phenotype showed a transformation in a short time. The size of the lesion changed from 5 x 18 mm to 12 x 18 mm within 12 months (Figure 2). Mammographic glandular pattern was again P2, and conventional imaging (both mammography and ultrasound) remained unsuspicious at the recall. In contrast, dynamic parameters did not show any transformation between the first MRI examination and the recall.

Considering the high speed of growth, it was expected that the most typical malignant feature in terms of kinetics occurred in the 2 cases. Surprisingly, both diseases were not associated to a washout curve but to a steady-curve type in the first and a plateau type in the second case. Another interesting morphologic pattern was the T2 SI, which was very high in both cases from the beginning.

Also for the tumor of patient 23 (Figure 3), there was a volumetric increase in a mass-like enhancement, ill-defined margins, and homogeneous uptake of 11 x 13 mm in a morphologically unchanged enhancing mass of 13 x 20 mm. Changes occurred within 3 months. In this case, besides the volumetric increase, we noted the onset of two further pathological foci of 7 and 6 mm (Figure 3). The main lesion was not associated with a rim pattern. Also in this case, the patient showed BRCA1 mutation and was 47 years old. The mammographic glandular pattern was P1. Conventional imaging was also positive in this case, but the patient refused surgery for 3 months. Mammography showed a mass with indistinct margins. Ultrasound depicted an ill-defined hypoechoic mass. In this subject, kinetic aspects also showed an evolution and once again, surprisingly, the change was from washout to a steady shape of the dynamic curve. T2 SI was again very high. Histology showed IDC for the major lesion. Regarding the smaller lesions, one belonged to an IDC and ILC and the second to a benign mastopathy.

Similar morphologic evolution but with a smaller diameter occurred in patient 8 (Figure 4). In this case, tumor growth was of a few mm, the T2 SI was of intermediate intensity, and histology revealed a pure DCIS. The lesion arose as a tiny dendritic enhancement of 2 x 10 mm, ductal like with speculated borders, and converted to a single mass of 15 mm in 3 months, with speculated margins without a rim pattern. T2 SI was in this case of intermediate intensity. In contrast, dynamic parameters did not show any change like the washout type. Glandular pattern was N1. On occasion of the recall, ultrasound did not reveal any abnormal finding, whereas mammography disclosed the onset of some calcifications within an asymmetric structural thickening, where MRI showed the suspicious enhancement. However, morphology and density of calcifications where not typical of malignancy. The patient was BRCA1 mutated, 63-years old, and histology disclosed DCIS. In this case, chemotherapy could be avoided.

For another patient (patient 17), we registered a smaller increase in the medio-lateral diameter, resulting from a numerical increase in some contiguous enhanced ducts, suggestive of endoductal proliferation. Diameters converted from 2 x 8 mm to 4 x 10 mm in 6 months. Margins of the region of enhancement were speculated from the beginning. Dynamic parameters did not show any change like the washout type. T2 SI was also very high in this case. The mammographic pattern was N1, but conventional imaging remained unsuspicious at the recall. The patient was BRCA2 mutated, 48-years old, and histology disclosed IDC and ILC.

Patient 16 experienced an onset of the disease represented by several small round foci, smooth borders and homogeneous enhancement along a ductal-like extension. Within only 3 months, the disease showed both a volumetric increase and a morphologic phenotype evolution, converting from 5 x 18 to 10 x 18 mm and becoming a non-mass-like irregular area of enhancement in which several contiguous branches of almost dendritic enhancement were represented (Figure 5). The mammographic glandular pattern was P2. Despite MRI findings, also in this case mammography continued to give negative results at the recall, whereas ultrasound disclosed a nonhomogeneous but non-specific area within the same quadrant. The dynamic parameter remained a washout type, T2 SI was very high, and the patient, 56-years old, was BRCA1 mutated with DCIS and IDC.

Another patient had onset of the disease with some contiguous round foci of enhancement (patient 31), but in this case they were not distributed along a linear orientation but already with a branched pattern. The small foci had irregular borders and the growth resulted in an increase in their number, thus in a larger area of enhancement. The growth occurred within 4 months. The maximum diameter evolved from 16 mm to 30 mm. The curve shape, a washout type, did not change between the beginning and the recall. The T2 SI was very high. Histology disclosed DCIS and IDC (Figure 6). Radiographic pattern for the woman was P2, and conventional imaging remained unsuspicious at the recall. The patient was BRCA1-mutated and 39-years old.

The last woman with morphologic phenotype evolution had a single round mass at the beginning, smooth margins and homogeneous enhancement (patient 30). The evolution was towards a tiny volumetric increase, still homogeneous but with irregular margins, surrounded by an irregular weak flare of enhancement. The diameters changed from 8 to 12 mm in 6 months. In this case, the kinetic patterns also changed from steady to the washout type (Figure 7). The glandular pattern was P2. Mammography and ultrasound both gave negative results at the recall, but ultrasound showed the onset of a highly suspect axillary lymph node. The patient was BRCA2 mutated and 52-years old. Histology revealed the presence of DCIS and IDC.

Among the remaining 4 patients in follow-up because of suspicious MRI findings, in one the tumor remained almost unchanged in volume, morphology and dynamic aspects for 7 months (patient 14). The lesion was a 6-cm regional enhancement in a 50-year-old woman who had previously been submitted to left mastectomy for multiple foci of DCIS associated with LCIS. The region of enhancement was anterior to an esthetic prosthesis of the remaining breast. The margins of the enhancement were speculated and the curve was a classical washout type mixed with a delayed washout type, which is possible to find in lobular carcinoma ¹². Distribution of the enhancement involved homogeneously all the parenchyma, thus raising doubt of just a highly vascularized stroma, but it could not be compared with the contralateral breast because of the mastectomy. Owing to the presence of the prosthesis, evaluation by mammography did not detect any abnormality within the parenchyma, whereas ultrasound disclosed the presence of a single small mass of 1 cm behind the nipple. The mammographic glandular pattern was dysplastic. The patient was a high-risk woman with DCIS and LCIS.

Another patient remained almost unchanged in 4 months, with a volumetric increase of only a few millimeters (patient 29). The morphologic pattern was of an irregular area of homogeneous enhancement and speculated margins. In this case, it was the dynamic curve shape that showed partial evolution. In fact, at the beginning the ROI on the enhancing region showed steady type mixed with a washout curve, whereas at the recall the curve was only a washout type. Here mammography was not suspicious, whereas ultrasound revealed a poorly defined hypoechoic mass dubious for cancer at the first examination. This area corresponded to an MRI region of enhancement. The same region became more suspect at the recall. The glandular pattern was dysplastic. The patient belonged to the high-familial-risk group, and histology revealed the presence of IDC.

For 2 patients (patients 6 and 25) submitted to recall, an intraductal development of enhancement was detected at the beginning with some contiguous small foci, with speculated margins for the first case and smooth margins for the second. The morphological aspects, the size and the dynamic curve shape (washout type) remained the same at the diagnosis and at the recall, respectively after 5 and 4 months. Despite an N1 pattern for the first case, no suspicious findings appeared at the first analysis, whereas a mass with indistinct margins appeared at mammography. Only at the recall did ultrasound reveal a small, suspicious mass. With an N1 glandular pattern for the second case, ultrasound continued to give negative results, whereas for the recall some malignant calcifications appeared at mammography. These women were BRCA1 and BRCA2 mutated with respectively IDC and DCIS and LCIS.

All cancers with a more rapid speed of growth (patients 16, 19, 24 and 31) were from BRCA1 mutation carriers (Table 2).

Schrading and Kuhl¹⁴ described how the location of a breast cancer may become an important predictor of malignancy. They discovered that women with BRCA1 mutation or high familial risk tend to develop breast cancer in the posterior part of the breast.

In our group of 33 MRI-detected breast cancers, 13 lesions were located in the posterior portion of the breast, 11 of them in the prepectoral region. Of these 13 tumors, 7 were from BRCA1-mutated and 4 from BRCA2-mutated patients, and 2 were high-familial-risk patients.

There is emerging evidence that tumors in BRCA carriers, compared to sporadic cancers, exhibit different biological and morphological features. BRCA1 breast cancers are frequently poorly differentiated, with higher mitotic counts, negative for estrogen and progesterone receptors, p185 negative and p53 positive. Tumors from BRCA2-mutated women as well as those arising in high-familial-risk women show pathologic features similar to those of sporadic cases^15-17.

Tilanus-Linthorst et al.^15,17 also reported the same tumor behavior we observed in the present study. In fact, they described faster tumor growth in women with BRCA mutation than in the general population and estimated a tumor doubling time of 45 days for mutation carriers. Furthermore, they reported major tumor growth in women with BRCA1 mutation and in patients aged <40 years of age.

In accord with these findings, in our study we noted that an impressive volumetric increase occurred in a short time. Tumors that showed the most rapid growth were in 4 BRCA1 carriers (patients 16, 19, 24 and 31), whereas the age of these patients was 56, 44, 54 and 37 years, respectively. Considering the longest diameter of each enhancing lesion, the increase in size was estimable respectively as 8 mm in 3 months, 8 mm in 4 months, 7 mm in 12 months, and 17 mm in 4 months. Histology was indicative of invasive carcinoma in all 4 cases; except for one case, the tumors were all grade III. Evaluation of hormone receptor was not available in one case, while 2 cases were triple negative and the last one showed Er+PgR-p1850 parameters.

However, it has been observed that radiological phenotype may be different in hereditary breast cancer. In fact, such tumors frequently show morphological and kinetic aspects commonly seen in benign lesions^5,14,18,19. Schrading and Kuhl¹⁴ pointed out a major number of differences in BRCA1-associated cancers. In fact, they did not find calcifications associated with invasive cancer or intraductal disease.

Concerning our cohort, we found 3 intraductal carcinomas (patients 8, 14 and 25), but only one of them, whose histology described DCIS and LCIS, was associated to suspected calcifications (patient 25). For the only pure ductal in situ carcinoma (patient 8), tiny, aspecific calcifications were observed, whereas in the remaining case of DCIS and LCIS calcifications were not detectable at mammography because of the presence of a breast prosthesis (Table 1). The first case was a BRCA1 carrier, the second a high-familial-risk woman, and the third a BRCA2 carrier.

Within our group, we detected only 3 cases of pathological calcifications, and these were related to invasive carcinomas (patients 3, 7 and 13) (Table 1). Two of these patients were BRCA1 mutated and the third was at high familial risk.

Tilanus-Linthorst et al.⁵and Kuhl et al.¹⁸ also described how BRCA1-associated cancers may exhibit “pushing”, well-circumscribed margins, homogeneous internal architecture, and low echogenicity.

In our patients (Table 1), we noted that when no suspicious findings were detected at mammography mainly because of a glandular pattern, ultrasound could more easily depict pathologic aspects with a higher sensitivity before and after MRI. However, when detectable by means of conventional imaging, breast cancers of our group did not significantly differ from sporadic cancers. In fact, the percentage of hereditary breast cancers with typically benign aspects was very low in our study. As regards MRI, Schrading and Kuhl ¹⁴ reported a high percentage of invasive cancers with a non-mass enhancement and a benign kinetic aspect.

Morphologic patterns are usually of eminent relevance in the radiological interpretation. Smooth borders have often been associated with a negative predictive value for malignancy^9,20, whereas irregular contour, nonhomogeneous enhancement and rim pattern have been reported as highly indicative of malignancy¹⁵. Tilanus-Linthorst et al.¹⁵stated that the association of rim enhancement with central necrosis can be an indicator for the growth rate of tumors. Jimenez et al.²¹ reported that centrally necrotizing carcinomas had an accelerated clinical course and early systemic metastasis. This is in agreement with Tilanus-Linthorst et al.¹⁵, who also found mitotic count to be significantly high in tumors from gene-mutation carriers. Regarding our cohort, only 9 of 33 (27%) malignancies showed pure smooth margins: 12 (36%) arose with speculated borders, and 3 neoplasm – initially with smooth margins – converted to irregular margins at the recall.

The higher rate of sharp tumor margins and eventual rim enhancement may thus be explained by the more aggressive nature of tumors in BRCA-mutated carriers.

As regards the correlation with curve shape, the washout type was detected in 21 of the 33 malignancies of our study (21/33, 63.6%). As regards histology, the washout curve was prevalent in invasive carcinoma, but we also found the same curve in intraductal disease. The same curve shape was more often detected in BRCA1-mutated subjects than in the other subjects, but the high number of BRCA1-mutated subjects in our cohort needs to be taken into account. Hence, we can consider the washout curve as highly predictive of malignancy, but without a significant difference between sporadic and hereditary cancers.

For false-positive MRI findings, all the patients were BRCA1 mutated and the morphologic shapes were very suspicious. We did not find the typical washout curve but saw other invasive lesions with the same kinetic aspects. Isointensity of T2 SI should have more favorably directed the diagnosis in one case of adenosis.

Mammography frequently gave false-negative results despite breast density and tumor diameters. One possible explanation could be the major aggressiveness of hereditary cancers, which may reduce the incidence of microcalcifications as an indicator of subclinical, still intraductal lesions.

Moreover, Tilanus-Linthorst et al.⁵ described for the first time the phenomenon of prominent pushing margins of breast cancer in BRCA carriers. They observed that when pushing margins are prominent, the fibrotic reaction of the connective tissue adjacent to the tumor and responsible for distortion and spiculated margins is absent. This phenomenon could explain possible false-negative mammograms.

In our experience, the main MRI semeiotic variance that we observed in the group of neoplasms arising in mutation carriers was the T2 SI, which could differ significantly from that of sporadic breast cancers. In fact, it is known that in the general population, T2 SI is of an intermediate intensity for breast cancer, of a higher intensity for benign lesions^5,22,23, and of an even greater intensity for cystic entities. The almost constant pattern of an MRI semeiotic aspect that we encountered in positive women of our surveillance program was the high or even very high SI of hereditary cancers (Table 3). Kuhl et al.⁴ reported that such behavior may occur in mutated cancers.

In another study, carried out on the general population, Kuhl et al.²³ observed that breast cancers displayed a low SI on T2-weighted turbospin echo (TSE) images in 88/101 cases (87%), whereas 13/101 (13%) cases had an increased SI. They also concluded that the T2 TSE pulse sequence without fat suppression was the only one suitable for lesion characterization, whereas they did not obtain the same significant results on corresponding T2-weighted SPIR (spectral presaturation inversion recovery) TSE images (with fat suppression).

More recently, Ballesio et al.²² calculated the ratio between the SI of the nodule and the pectoralis major muscle with an ROI analysis on T2-weighted IR sequences. Within the general population, they described a lower T2 SI belonging to malignancies, with 82.4% sensitivity, 77.4% specificity, 80% positive predictive value and negative predictive value.

In our experience, carried out on a population at high risk of inherited breast cancer and on mutated women, we found 34 malignant lesions, 33 were submitted to MRI analysis, only 30 of which were also evaluated with T2 IR sequences. Of these 30 T2 IR evaluated cancers, we found that 22 (22/30, 73.3%) displayed an unmistakable hyperintensity: 59% of these T2 very high SI was associated to BRCA1 mutation, whereas only 39% of them was <50 years old. Also that patient with LCIS in BRCA1 mutation showed very high T2SI. MRI false-positive cases showed T2 isointensity and hyperintensity in 2 cases of adenosis and intermediate intensity in one case of dysplasia.

Of the 22 neoplasms with high T2 SI, only 59% were pure invasive carcinomas. The pattern was also found in 3 pure in situ carcinomas, 31% were invasive combined with intraductal disease, and the overall medullary aspects were found only in 3 cases. Therefore, it seems that high T2 IR SI cannot be considered as a specific index of a selective histotype, nor an indicator of a medullary or mucinous component only.

If we refer to the phenomenon of “prominent pushing margins”, arising from the analysis of BRCA1/2-related cancers⁵ and described by Lakhani et al.^24,25 as a front of tumor cells not separated by connective tissue, we can make some interesting considerations. According to MRI semeiotic parameters, connective tissue shows low to intermediate T2 SI both on T2 TSE and T2 IR sequences because of the scarcity of water. Considering hereditary breast cancers, the T2 SI should thus become higher and increase to major levels if connective structure and desmoplastic reaction are lacking.

In our study, the tumors with a fast growth (patients 16, 19, 24 and 31) consistently demonstrated a very high T2 SI, which was similar to that of cystic matrix. It seems that the absence of connective architecture within the tumor and the absence of the desmoplastic reaction surrounding the lesions reduces the possibility to restrict cancer growth, thus allowing a major aggressiveness. In addition, we found high T2 SI mainly in invasive carcinomas of mutation carriers, but this aspect was also the most frequent in intraductal disease. Consequently, in our cohort, high T2 SI cannot be considered as a pattern specific of invasive cancer. However, all of the cancers with high T2 SI and rapid evolution occurred in BRCA1 carriers (patients 16, 19, 24 and 31). It would thus be interesting to know whether hereditary breast cancer has a peculiar structure, combined with a different induction to the desmoplastic reaction of the surrounding parenchyma, that could explain these new radiological patterns.

In addition to optical impression, to quantify T2 SI we also calculated the mean SI value of each lesion and related the SI of the lesion to that of the parenchyma (LPS, parenchyma SI) and to that of the pectoralis major muscle (LMS, muscular SI) by means of two different functions: the pixel lens value for the former and an ROI for the latter (Table 3). As regards LPS, parenchymal SI was different in each patient (range, 30-960), but the results of numerical scores proved to be coherent with optical level of brightness (Table 3). For one tumor (patient 24), optical T2 SI was very high, similar to that of cystic lesions, but the ratio score was at a intermediate level (i.e., 2.4). The lesion had an impressive volumetric growth, containing a necrotic center. The numerical score should therefore be considered as an additional index of its internal nonhomogeneity.

As regards LMS (Table 3), muscular SI was less heterogeneous than parenchymal SI. We noted that they remained at lower levels when the examinations had been performed with a Vision device and on higher levels when performed with Avanto. There were several overlaps between numerical scores of intermediate and high SI for LMS. It may be that the quantification of a mean SI value by means of a ROI is more sensitive to the heterogeneity of the internal structure of a lesion than the computation of the mean SI value by means of several pixel lens values taken from different sites of the same lesion. This is even more evident for larger diameters.

However, LPS and LMS analyses both had the limitation of the small number of subjects examined. Further evaluations are needed to improve the new interpretation models. We therefore deduce that the SI calculated on T2 images (LPS and LMS) should be considered as an adjunct parameter for differential diagnosis of doubtful lesions, but in clinical practice they should not be considered alone. LPS and LMS should be used to confirm a diagnosis ruled out on the basis of established breast MRI criteria, such as dynamic enhancement and morphological data.

BRCA carriers face a high lifetime risk of developing breast cancer. However, evidence indicating whether overall prognosis is worse for women with BRCA-related cancer has not been conclusive. Several studies have shown that annual screening in BRCA-mutated or high-risk women can be significantly helpful to detect breast cancer early^4,7-10,26,27. It has also been demonstrated that in multimodality surveillance programs the accuracy of MRI is higher than that of conventional imaging and that combination of the two techniques is needed to avoid unnecessary biopsies^4,28-33.

Tumor size and nodal status represent the most important prognostic factors in breast cancer^31,32. The survival rates of women with breast cancers <1 cm in diameter and with negative lymph nodes are high, and mortality risk may be appreciably reduced by early tumor detection. However, data on the real impact of an early diagnosis are essential, considering that a high proportion of BRCA1-mutated tumors displays negative prognostic factors such as triple-negative status, and lack of a correlation between tumor stage and metastatic spread has been reported in these patients ³³. Although caution is needed, early detection should be offered to women with a gene mutation or with a increased familial risk of breast cancer.

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erB-2
erlotinib
errors in radiation deliv
erythroleukoplakia
Erythropoietin
Esophageal adenocarcinoma
Esophageal cancer
Esophagogastroscopy
Esophagus
esophageal cancer
esthesioneuroblastoma
estrogen receptor
estrogen-progesterone rec
Ethics
Ethics committees
Ethmoid cancer
Ethnic distribution
European Union
euthanasia
event tree model
evidence-based medicine
Ewing sarcoma
Ewing's sarcoma
Ewing’s sarcoma
Ewing’s sarcoma family
exemestane
Exercise testing
exonic splicing enhancers
exosomes
experimental
extended cholecystectomy
External beam radiotherap
Extra-abdominal metastasi
Extracapsular extension
Extracellular matrix prot
Extradonal non-Hodgkin's
Extragonadal germ cell tu
extramedullary plasmacyto
Extranodal lymphoma
extranodal MALT lymphoma
Extraosseous Ewing's sarc
extraosseous sarcoma
Extrapulmonary small cell
Extravasation
eyelid
ezrin
facial nerve
false positive
Familial adenomatous poly
Familial polyposis
families
family
Fas/FasL
fatigue
FDG-PET
feasibility
febrile neutropenia
Female
fetal dose
FHIT gene
Fibroma
fibromatosis
fibronectin
fibrosis
filgrastim
Finasteride
fine-needle aspiration cy
FISH
Fistula
fixed-dose-rate infusion
FLIPI
Floxuridine
fluorescence
Fluoropyrimidine-pretreat
Fluorouracil
FMF
focal adhesion kinase
Focal nodular hyperplasia
folate
FOLFIRI
folfox
FOLFOX IV/LV5FU2 chemothe
FOLFOX regimen
folinic acid
Follicular carcinoma
Follicular lymphoma
follicular thyroid cancer
follow-up
Food
Forearm
foregut neuroendocrine ca
Four or more positive axi
Fractionated stereotactic
fractionation
fraud
fullerenes
fulminant liver failure
G-CSF
galectin-1
galectin-3
Gallbladder
Gallbladder carcinoma
Gamma probe
Gamma-glutamyltransferase
gastrectomy
Gastric cancer
Gastric carcinoma
Gastric melanoma
gastric myoepithelial ham
gastrointestinal carcinoi
gastrointestinal interven
Gastrointestinal lymphoma
Gastrointestinal neoplasm
Gastrointestinal stromal
Gastrointestinal stromal
gastrointestinal stromal
gastrointestinal stromal
Gemcitabine
Gender differences
Gene expression
gene expression profile
gene polymorphism
gene therapy
General practitioners
Genetic research
genetic susceptibility
Genetic testing
Genetic tests
Genomic instability
genomics
genomics
GEP neuroendocrine tumors
germ cell tumor
germ cell tumors
Germline mutations
gestational trophoblastic
giant basal cell carcinom
giant follicles
giant keratoacanthoma
Giant mixed retroperitone
Giemsa
GIST
glioblastoma
Glioblastoma multiforme
Gliofibroma
Glioma
gliosarcomas
Glottic cancer
glucagon
glucose-6-phosphate dehyd
glutamine
glutathione S-transferase
glycoproteins
Gonadoblastoma
good clinical practice
Good's syndrome
GPI
granular cell tumor
granulocyte-colony stimul
granulocytic sarcoma
Granulomatous angiopannic
Granulomatous gastritis
Graves' disease
growth inhibitory peptide
growth rate
GSTP1
guidelines
Guillain-Barré syndrome
Gynecomastia
Gynecomastia and hormone
Gynecomastia and prostate
H. pylori
Hadron therapy
hairy cell leukemia
half-body irradiation
hamartoma
Hand-foot syndrome
Hashimoto’s thyroiditis
HBV/HCV infections
HCV
HDR brachytherapy
Head and neck
Head and neck cancer
Head and neck carcinoma
Head and neck malignancie
head and neck neoplasms
head and neck tumor
Head trauma
Health-related quality of
healthy donors
Heart
heart failure
heart transplantation
heat
heat shock protein 70
heavily pretreated
Hemangioendothelioma
Hemangiopericytoma
Hemangiosarcoma
Hematological malignancie
hematological malignancy
Hematopoietic stem cell t
hematuria
Hemodialysis
Hemoglobin levels
hemoperitoneum
hemophilia A
Hep-2 cells
Heparin
Hepatic adenosquamous car
Hepatic arterial infusion
Hepatic arterial infusion
Hepatic artery
hepatic tumor
Hepatitis B virus
hepatitis B virus (HBV)
Hepatitis B virus integra
Hepatitis C virus infecti
hepatoblastoma
Hepatocellular
Hepatocellular carcinoma
hepatocellular carcinoma
hepatocyte growth factor
HER-2
HER-2 receptor
HER-2/neu
HER2
HER2-positive metastatic
Herceptin
Hereditary breast cancer
hereditary non-polyposis
HEY1
high dose
High dose chemotherapy
high dose rate
high genetic risk
high-dose boost
High-dose chemotherapy
high-dose epirubicin
High-dose rate brachyther
high-grade glioma
High-grade squamous intra
high-risk medulloblastoma
Histogenesis
histological diagnosis
Histological score
HIV
hMLH1
hMLH1 hypermethylation
HNPCC
Hodgkin disease
Hodgkin's disease
Hodgkin's disease (HD)
Hodgkin’s disease
Home palliative care serv
homocysteine levels
Horizontal growth phase m
Hormone receptor status
Hormone refractory
hormone replacement thera
Hormone therapy
Hormone-refractory prosta
Hormonorefractory
Hormonotherapy
Hospital
Hospital-based population
HPV
Hrthle cell carcinoma
hTERT
hu-PBL/SCID chimera
huge hepatocellular carci
Human
human carboxylesterase-2
Human chorionic gonadotro
Human Epo receptor (EpoR)
Human G-CSF receptor
Human immunodeficiency vi
Human papilloma virus
Human papillomavirus
human sarcoma
Human tumor cell lines
hur
hydration
hydrocele
Hydrogen peroxide
hydronephrosis
Hypercoagulable state
Hypereosinophilic idiopat
Hyperfractionated radioth
Hyperfractionation
Hyperparathyroidism
Hypersensitivity reaction
Hypertermic tissue ablati
hyperthermia
Hypocalcemia
Hypofractionation
Hypoparathyroidism
hypopharyngeal cancer
hypothyroidism
ICCC-3
ICD-10
Id2 protein
Idiopathic thrombocytopen
IFN-a-2a
Ifosfamide
IgR
IHH
IL-12
IL-2
ileal carcinoid
ileal mucosa
image analysis
image fusion
Image probing
image-guided intensity-mo
Image-guided radiotherapy
imaging
imatinib
Imatinib mesylate
imiquimod
immune host response
Immunity
immunocompetent host
immunocytochemistry
Immunodeficiency
immunohistochemical analy
Immunohistochemical marke
Immunohistochemistry
Immunoradiometric assays
Immunoscintigraphy
Immunotherapy
impact factor
Implantable port
IMRT
in vivo imaging
in vivo small animal magn
inappropriate doses of ch
incentives
Incidence
incidence rates
Independent studies
induced lymphoma
induction chemotherapy
induction therapy
infant
infantile myofibromatosis
infection
Infections
infectious agents
infiltrating ductal carci
Inflammation
Inflammatory bowel diseas
Inflammatory breast carci
Inflammatory mechanism
Inflammatory metastatic c
inflammatory myofibroblas
inflammatory pseudotumor
Informed consent
infrastructures
infusion reaction
Infusional chemotherapy
infusional therapy
Inguinal canal
Inguinal hernia
Inoperable bowel obstruct
insular
Insular thyroid carcinoma
Insurance
integral dose
Integrated radiotherapeut
integration
integrin beta 3
intensity modulated radia
Intensity-modulated exter
Intensity-modulated radia
Intensity-modulated radia
intensity-modulated radio
Interaction
Interactive computer grap
Interferon
interferon beta
Interleukin-2
Interleukin-6
interleukins
Intermediate emetogenic c
internal mammary node met
international collaborati
international cooperation
International Prognostic
internet
Interobserver agreement
Interpectoral (Rotter's)
interstitial pneumonitis
interval cancer
interval cancers
interval censoring
Interventional radiology
intestinal permeability
intestinal pouch
intima-media thickness
Intra-arterial chemothera
intra-operative radiother
Intraabdominal tumor mass
Intracranial tumors
Intraductal carcinoma
Intrahepatic cholangiocar
Intrahepatic cholestasis
intramedullary metastases
intramedullary tumor
intraoperative pathologic
Intraoperative radiothera
intraosseous hemangioma
Intraperitoneal chemother
intraperitoneal chemoth
Intraperitoneal hyperther
intratumoral lymphocyte
Intravascular lymphomatos
Invasion
Invasive ductal carcinoma
invasiveness
Ionizing irradiation
IORT
Iran
Irinotecan
iris metastasis
iron oxide nanoparticle
isolated splenic metastas
isothiocyanates
Italian cancer burden
Italian cancer control
Italian EPIC population
Italian Sarcoma Group
Italy
jaw
jaws
jejunal intussusception
Job's syndrome
joinpoint analysis
Juvenile granulosa cell t
K-ras
k-ras codon 12 mutation
Kaposi's sarcoma
Kaposi’s sarcoma
keratin
Keratin/genetics
keratoacanthoma
Ki-67
Ki-67 antigen
Ki-ras gene
Ki67
Kidney
kidney transplantation
KIT
kit protein
Korea
Krukenberg tumor
Kyphoplasty
lab-on-chip
labelling
Lacrimal sac
Lactulose-mannitol test
Laminin
lamivudine
Laparoscopic cholecystect
laparoscopic splenectomy
Laparoscopic surgery
laparoscopy
Large breast
laryngeal cancer
laryngeal chondrosarcoma
Laryngeal neoplasm
larynx
Larynx carcinoma
late brain metastases
late complication
Late effects
late effects of cancer tr
late relapse
Late side effects
Late toxicity
latent membrane protein 1
Leading cancer sites
Leiomyosarcoma
leptomeningeal metastases
Leucovorin
Leydig cell tumor
Li-Fraumeni syndrome
life tables
Life-style
Life-style questionnaire
Limited stage
lipid-rich carcinoma
Liposarcoma
Liposomal doxorubicin
Liposomes
Liquid-based cytology
literature review
Liver
liver cancer
liver failure
Liver malignancies
Liver metastases
Liver metastasis
liver neoplasm
Liver resection
Liver transplantation
Liver tumors
lobectomy
Lobular carcinoma
lobular carcinoma in situ
lobular neoplasia
Local control
Local recurrence
local tumor recurrence
local-regional recurrence
localized carcinoma of th
localized gastrointestina
localized non-Hodgkin's l
Locally advanced
Locally advanced breast c
Locally advanced breast t
Locally advanced disease
locally advanced lung can
Locoregional chemotherapy
Locoregional radiotherapy
Lomustine
Long-surviving patient
long-term complications
long-term follow-up
Long-term outcome
Long-term remission
Long-term survival
Long-term-survivors
loss of heterozygosity
loss of heterozygosity (L
Loss of heterozygosity,
low dose intensity
low dose rate
lumpectomy
Lung
Lung adenocarcinoma
Lung cancer
lung cancer prognosis
Lung carcinoma
Lung metastases
lung metastasis
Lung neoplasm
Lung neoplasms
lung resection
lung toxicity
lymph node
lymph node diameter
Lymph node excision
Lymph node failure
Lymph node metastases
lymph node sampling
Lymph node status
Lymph node-negative breas
Lymph nodes
Lymphadenectomy
Lymphangioleiomyomatosis
lymphatic mapping
lymphocytes
lymphofollicular infiltra
Lymphoma
Lymphoscintigraphy
MAb CIBCgp185
macrophage
Magnetic resonance
Magnetic resonance imagin
maintenance chemotherapy
major surgery
Male breast cancer
Male breast carcinoma
Malignancy
malignant breast disease
malignant fibrous histioc
Malignant fibrous histioc
malignant giant cell tumo
malignant glioma
malignant gliomas
malignant infiltration of
Malignant melanoma
malignant mesenchymoma
malignant mixed mesoderma
Malignant pericardial tum
malignant peripheral nerv
Malignant pleural Mesothe
malignant thymoma
Malignant transformation
Malnutrition
MALT lymphoma
mammary phyllodes tumor
Mammography
mammography screening
Mandibular metastasis
Mandibular tumors
manifestation
mantle cell lymphoma
Margin involvement
mastalgia
mastectomy
matrix metalloproteinase-
matrix producing carcinom
Mature cystic teratoma
maxillary sinus
MCC
Mediastinal radiotherapy
mediastinal staging
Mediastinum
medical choice
Medical ethics
medical oncologist’s tr
medullary breast cancer
medullary carcinoma
Medullary thyroid cancer
Medullary thyroid cancer
Medullary thyroid cancer
Medullary thyroid carcino
Medullary thyroid carcino
Medullary thyroid carcino
Megestrol acetate
Melanin
melanocytoma
melanoma
Melanoma prevention
Membranous glomerulonephr
MEN 2 syndromes
MEN 2A
MEN 2B
meningeal carcinomatosis
Meningeal hemangiopericyt
Meningioma
Menopause
Menstrual cyles
menstrual induction
mental adaptation to canc
Merkel cell carcinoma
mesenchymal chondrosarcom
mesenchymal tumor
mesenteric cyst
Mesenteric fibromatosis
Mesenteric paraganglioma
Mesenteric thrombosis
mesentery
Mesothelioma
Meta-analysis
metacarpal bone
metachronous metastasis
metaiodobenzylguanidine s
Metaiodobenzylguanidine t
metallic implants
metalloproteinase
metallothioneins
Metanephrines
metaplastic carcinoma
metastasectomy
Metastases
Metastasis
metastasis of unknown ori
metastasis to stomach
Metastatic bone disease
Metastatic breast cancer
Metastatic cancer
metastatic cancers
Metastatic colorectal can
metastatic gastric cancer
metastatic liver disease
metastatic non-small cell
metastatic ovarian tumor
Metastatic prostate carci
Metastatic spinal cord co
metatarsal bones
methodological approaches
methylation
Methylene blue
metronomic therapy
MGMT
mice
microcalcification
Microcalcifications
Microenvironment
micropapillary
Microvascular density
Midline lymphoma
Minimal change disease
minors
Mismatch repair genes
mitogen-activated protein
mitomycin C.
mitomycin-C
Mitoses
mitotic catastrophe
Mitotic index
Mitoxantrone
Mixture models
MLH1
MMP
mobility
molecular diagnostics
Molecular follow-up
Molecular markers
monoclonal antibody
mononuclear cell migratio
Morbidity
morbidity-mortality
Mortality
Moschcowitz's disease
Motility
MRI
MSH2
MTA
MTHFR
mucinous adenocarcinoma
mucinous tumors
Mucosa-associated-lymphoi
mucosal damage
mucosuria
multi-drug resistance
multi-drug resistance pro
multicentric trial
multidisciplinary treatme
multiendocrine failure
multikinase inhibitor
multileaf collimator
Multimodality therapy
multimodality treatment
multiple bladder-prostate
multiple endocrine neopla
Multiple lymphangiomas
multiple malignancies
Multiple malignancy
Multiple myeloma
multiple primary cancers
multiple sclerosis
Multipurpose surveys
Multivariate analysis
Muscle cell proliferation
mutation
myasthenia
mycosis fungoides
myelodysplastic syndrome
myeloid markers
myocardial metastasis
myocardial perfusion defe
myocardial perfusion scin
myoepithelial cells
myoid
Na+-I- symporter
nanomedicine
nanoparticles
nanotechnology
nanomedicine
nanoparticles
nasal septum
Nasopharyngeal cancer
Nasopharyngeal carcinoma
nasopharyngeal neoplasm
Nasopharynx
National survival estimat
Natural killer cells
Neck
neck dissection
neck mass
neck metastases
Neck's tumors
necrosis
negative second-look lapa
neoadjuvant
neoadjuvant chemoradiatio
Neoadjuvant Chemotherapy
neoadjuvant radiotherapy
Neoadjuvant therapy
neoadjuvant,Taxotere
Neoplasm
Neoplasm circulating cell
neoplasm metastasis
Neoplasms
neopterin.
Neovascularization
nephrectomy
Nephrotic syndrome
nephrotoxicity
Nerve-sparing
Network
networks
neural tissue
neurilemmoma
Neuroanatomy
neuroblastoma
neuroendocrine carcinoma
Neuroendocrine differenti
Neuroendocrine tumor
Neuroendocrine tumors
neurofibromatosis 2
neurogliocytoma
Neurological state
Neuron-specific enolase
Neuropathic pain
neurosurgery
neurotoxicity
neutropenia
neutropenic enterocolitis
New bisphosphonates
new schedule
NF-ÛB
NF1
nipple-sparing mastectomy
NIS expression
NIS therapy
Nitric oxide
NK activity
NK cells
NK lymphoma
nm23
Nodal regions
nomograms
Non-functioning adrenocor
non-Hodgkin disease
Non-Hodgkin lymphoma
non-Hodgkin lymphomas
non-Hodgkin’s lymphoma
non-melanoma skin cancers
non-non-Hodgkin's lymphom
Non-palpable breast lesio
Non-palpable thyroid nodu
non-pegylated doxorubicin
Non-platinum chemotherapy
Non-profit clinical trial
non-seminoma
Non-smal cell lung cancer
Non-small cell lung cance
non-small cell type
non-small-cell lung cance
non-viral vectors
Nongestational choriocarc
nonlinear resonance inter
nonpigmented ciliary epit
nonseminomatous germ cell
norcholesterol scintigrap
Nosocomial infections
Nottingham prognostic
novel mutations
NSCLC
Nuclear medicine therapy
nucleic acid delivery
nutrient mixture
nutritional status
Obesity
obscure digestive bleedin
Occult blood
Occult primary
occult/obscure gastrointe
occupational exposure
octreoscan
Octreotide
Ocular
ocular adnexal lymphoma
odontogenic tumors
off-label
older population
oligonucleotides
omentum
Omentum.
Oncocytic neoplasm
oncogene
oncogenes
Oncogenomics
Oncology
Opioid consumption
opportunistic screening
optical biopsy of cancer
optical imaging
optical neuritis
Optimized screening
oral cancer
oral cavity
Oral mucositis
oral precancerous conditi
oral UFT (tegafur-uracil)
oral vinorelbine
orbit
Orbital involvement
Orbital metastasis
Orbital surgery
organisation of care
Orgotein
Oropharynx
Orthovoltage therapy
osteo-oncology
Osteoclastic activation
osteonecrosis
osteopetrosis
osteopontin
Osteosarcoma
osteosarcoma of the kidne
osteosarcomatous differen
outcome
outpatient regimen
Ovarian cancer
Ovarian carcinoma
ovarian endometriosis
ovarian malignancy
ovarian psammocarcinoma
ovarian teratoma
Ovarian tumor
Ovary
over-treatment
overall survival
Overdose
Overexpression
Oxaliplatin
oxidative phosphorylation
p105
p14
p16
p185HER2
p27Kip1
p53
p53 antibodies
p53 gene
p53 mutation
p53 protein
p57Kip2
p63
p73
Pacemaker
Paclitaxel
Paclitaxel-carboplatin
Paget’s disease
PAI-1
Pain mechanisms
painful lipomas
palliative care
palliative care in oncolo
Palliative chemotherapy
palliative radiation ther
palmar-plantar erythrodys
palonosetron
pancreas
Pancreatic cancer
pancreatic carcinoma.
pancreatic cyst
pancreatic ductal adenoca
pancreatic heterotopy of
pancreatic intraductal pa
Pancreatic metastases
pancreatic neoplasm
pancreatic neoplasms
Pancreatic resection
pancreaticoduodenectomy
panitumumab
Pap smear history
Pap smear screening
Pap smears
Papillary carcinoma
Papillary fibroelastoma
papillary thyroid carcino
Paraganglioma
paralytic ileus
parametric model
paranasal sinuses
Paraneoplastic nephrotic
Paraneoplastic neurologic
Paraneoplastic syndrome
Paraplegia
Paraspinal tumors
Parathyroid
parathyroid adenoma
Parathyroid carcinoma
Parathyroid hormone (PTH)
Parathyroidectomy
Parenteral nutrition
parotid carcinoma
parotid gland
parotid neoplasm
partial laryngectomy
pathology
Pathology related markers
Pathway
patient satisfaction
patient-physician relatio
patterns of care
Patterns of failure
paxillin
PCR
PDGF
PEComa
pediatric
pediatric oncology
pediatric tumors
pegfilgrastim
Pegylation
Pelvic CT
Penile metastases
perfusion
Periampullary stromal tum
perineal prostatectomy
Perioperative radiotherap
Peripheral blood progenit
peripheral blood stem cel
peripheral leukocytes
peritoneal carcinomatosis
Peritoneal mesothelioma
Peritonealcancer
Peritonectomy
Peritoneovenous shunt
Peritoneum
peritumoral hepatic tissu
perivascular epithelioid
Permanent prostate Brachy
PET
PET sensitivity
PET.
PET/CT
Pharmaceutical industries
pharmacoeconomics
Pharmacoeconomy
pharmacogenetics
Pharyngolaryngeal squamou
Phase I
Phase II study
Pheochromocytoma
Pheochromocytoma treatmen
Phosphoinositide 3-kinase
photo excitation
Photofrin
Photosensitizer
phyllodes tumor
Physical activity
Physicians
physiotherapy
Pituitary adenoma
pituitary gland
pituitary gland metastasi
placental site trophoblas
planning study
Plasma fatty acid
plasmacytoid
Plasmacytoma
Plastic ring
Plastic surgery
Platinum
pleomorphic adenoma
Pleura
Pleural neoplasms
pleural small cell carcin
Pleurocentesis
Ploidy
Pneumonectomy
point mutations
point-of-care
Pollution
poly(butyl cyanoacrylate)
poly(lactide-co-glycolic
Polyamines
polychemotherapy
polycystic liver disease
Polymerase chain reaction
polymorphism
polymorphous
polysomy
ponicidin
population surveillance
Population survey
Population surveys
population-based
Population-based study
population-based survey
Porphyrins
port site recurrence
Positron emission tomogra
positron-emission tomogra
Post-irradiation sarcoma
Post-radiation osteosarco
Post-remission treatment
Post-traumatic glioma
Post-traumatic meningioma
Post-treatment CIN
Postoperative chemoradiat
postoperative radiochemot
Postoperative radiotherap
Postoperative therapy
PP1 inhibitor
PR
Practice guidelines
pRb
pre-operative chemotherap
Predictive value
Prednisone
Pregnancy
Preoperative chemoradiati
preoperative diagnosis
preoperative immunotherap
preoperative radiochemoth
Preoperative radiotherapy
pretreatment tumor lysis
Prevalence
prevalence of use of comp
prevention
Prevention and control
Priapism
Primary
primary adenocarcinoma
primary bilateral adrenal
primary central nervous s
primary chemotherapy
primary cultures
primary duodenal adenocar
primary hepatic leiomyosa
primary hyperparathyroidi
primary lung tumors
primary osteosarcoma
primary pancreatic lympho
primary systemic therapy
Primitive neuroectodermal
proctocolectomy
progesterone receptor
Prognosis
Prognostic factor
Prognostic factors
Prognostic markers
prognostic parameter
Prognostic score
proliferating trichilemma
Proliferation
proliferation index
prone position
Prophylactic total thyroi
Prospective cohort study
Prospective longitudinal
Prospective study
prostaglandin-endoperoxid
Prostate
Prostate adenocarcinoma
prostate biopsy
Prostate cancer
Prostate carcinoma
prostate neoplasms
Prostate specific antigen
prostate-specific antigen
Prostatectomy
Prostatic ducts
Prostatic neoplasm
prostatic neoplasms
protection
Protein microarray
Protein S
Proteomics
Proteomics technologies
Proton beams
proton therapy
PSA test
Pseudomyxoma peritonei
Psoriasis
psychosexuality
psychosocial
Psychosocial adjustment
psychosocial support
PTCA
PTEN
Pulmonary
Pulmonary adenocarcinoma
Pulmonary blastoma
Pulmonary fibrosis
Pulmonary lymphoma
pulmonary non-Hodgkin’s
Pulmonary valve
Pylethrombosis
pyogenic liver abscess
Pyrene
quality assurance
quality indicators.
quality of care
Quality of life
quality score system
Quantification
quantitative real time po
questionnaire
questionnaires
Radiation
Radiation safety
Radiation therapy
Radiation-induced meningi
Radiation-induced tumors
Radiation-induced
Radical hysterectomy
Radical nephrectomy
radical surgery
radiochemotherapy
Radiofrequency ablation
Radiograph
Radioguided surgery
Radioiodine therapy
radiologic diagnosis
radiologically dense brea
radiometabolic therapy
Radionecrosis
Radionuclide therapy
radioprotection
radiosensitivity
Radiosensitizer
radiosensitizing
Radiosurgery
Radiotherapy
Radiotherapy fractionatio
radiotherapy treatment
Radiotherapy treatment pl
radiochemotherapy
Raloxifene
Ralstonia pickettii
Raltitrexed
ramosetron
Random sample
randomized controlled cli
Randomized controlled stu
Randomized controlled tri
randomized phase III tria
RARb
rare entity
rash
RASSF1A tumor suppressor
RCC
Re-irradiation
reactive lymphoid hyperpl
reactive oxygen species
Recall colitis
receptor
receptors
recognization
recombinant human growth
Recombinant human thyrotr
record-and-verify systems
Rectal adenocarcinoma
Rectal cancer
rectal fistula
rectal injury
Rectal lymphomas
rectal neoplasms
Rectovaginal fistula
Rectovaginal septum
Rectum
rectus abdominis muscle
Recurrence
Recurrent
Recurrent carcinoma
Recurrent high-grade glio
recurrent ovarian cancer
Recurrent rectal carcinom
Reflux esophagitis
Regional chemotherapy
regional medical programs
Regional program
registries
regression
regression analysis
reirradiation
Relapse
relative survival
relative value
Renal cancer
Renal carcinoma
Renal cell cancer
Renal cell carcinoma
Renal failure
Renal metastasis
renal osteosarcoma
renal papillary carcinoma
Renomedullary interstitia
Reproductive factors
Resection
residual lesion
Resistant
resources
respiratory failure
RET oncoproteins
Ret tyrosine kinase
RET/PTC
Retinal metastases
retro-orbital granulocyti
Retroperitoneal liposarco
retroperitoneal mass
retroperitoneal tumor
retrorectal hamartoma
retrorectal tumors
retrospective study
review
rewards
rhabdomyosarcoma
Rheumatoid arthritis
rhuCD40L,TRAF
ring and tandem
risk factor
risk factors
Risk of cancer
RNA
RNA interference
Runx2
S-100 protein
s-phase fraction
S-phase fraction.
sacroplasty
Salivary gland
Salvage radiotherapy
salvage therapy
Sampling bias
Sarcoma
sarcomatoid renal cell ca
Sarcomatosis
Scalene lymph node
scalp
scalp cooling
Schwann cell
Schwannoma
SCID mice
Sclerosing hemangioma
Scoring
Screening
seasonality
Second line
Second malignancies
second primary cancer
second primary tumors
second-hand smoke
second-line
Second-line chemotherapy
secondary breast angiosar
secondary hemicolectomy
Secondary malignancies
secondary prevention
Secondary sarcomas
SEER program
Segmental duodenal resect
selection criteria
Selective estrogen recept
selective internal radiat
self-expanding stent
self-report assessment
seminal vesicle invasion
seminoma
Sensitivity
sentinel lymph node
Sentinel lymph node biops
Sentinel lymph node mappi
Sentinel node
Sentinel node mapping
sequence
sequence variant
sequence-specific primer
sequential chemotherapy
serum
Serum lactate dehydrogena
sestamibi
setup uncertainty
sex cord stromal tumor
Sex-specific rates
sexual dysfunction
SF-36 questionnaire
shoe worker
shoulder movement
shoulder syndrome
Signs
Silver staining
simple cholecystectomy
simultaneous care
simultaneous thyroid carc
Single agent
single nucleotide polymor
single nucleotide polymor
single strand conformatio
single-strand conformatio
single-strand conformatio
sinonasal cancer
siRNA
Sister Joseph's nodule
size
skeletal muscle
skin
skin cancer
Skin metastases
Skin neoplasms
skin squamous cell carcin
skin toxicity
Smac/DIABLO
Small bowel
Small cell carcinoma
Small cell lung cancer
Small cell lung carcinoma
Small intestine adenocarc
Small melanocytic skin le
Small melanoma
Small-cell lung cancer
Smoking
smoking ban
Smoking cessation
Smoking habits
social class
Socio-economic data valid
Sodium iodide
soft tissue sarcoma
Soft tissue sarcomas
soft tissue tumor
soft-tissue tumor
solid pseudopapillary neo
solid tumor
solitary fibrous tumor
Solitary plasmacytoma
somatostatin analogs
Somatostatin analogues
Somatostatin receptor sci
Somatostatin receptors
sorafenib
Sox9
Spain
Specificity
Sphincter saving procedur
sphincter-saving procedur
sphincter-saving surgery
spinal accessory nerve
spinal cord
spindle cell
spindle-cell carcinoma
spleen.
Splenectomy
splenic lymphangioma
splenic metastases
Splenic rupture
Splenomegaly
splenopancreasectomy
Spontaneous internal jugu
Squamous cell carcinoma
squamous cell carcinoma a
squamous cell carcinoma o
Squamous cell carcinoma,V
Squamous cell laryngeal c
stage
stage III
Staging
Standard incidence ratio
statistical method.
Statistical model
Stealth liposomes
stem cell transplantation
stenosis
Stereotactic
stereotactic body radiati
stereotactic radiosurgery
Sternberg tumor
Sternum
Steroid receptors
Steroids
Stevens-Johnson syndrome
Stomach
stomach cancer
stool test
stop-flow
Subcutaneous mastectomy
subdural hematoma
Subdural osteomas
Subgroup analysis
Sugar industry
Suicide
Suicide thoughts
sulfur compounds
Sunburn
sunitinib
Superficial therapy
Superior hypogastric plex
superior mediastinal synd
superior vena cava syndro
supernumerary breast
Superoxide dismutase
supraclavicular adenopath
supraclavicular lymphaden
supraclavicular radiother
supraventricular tachycar
Surgery
surgical complications
Surgical margins
surgical mortality
surgical oncology
surgical procedures
Surgical resection
surgical strategy
surgical treatment
Suriname
Survey
Survival
Survival analysis
SV40
Swiss albino mice
Sympathetic cervical chai
Sympathetic chain
Symporter (NIS)
Symptom management
symptom-to-treatment inte
Symptoms
Synaptophysin
synchronous cancer
Synchronous multicentric
Synchronous presentation
synchronous triple cancer
Synchronous tumors
synergistic effect
synovial sarcoma
systemic chemotherapy
T2 signal intensity
Tamoxifen
Tangential irradiation
tanshinone II-A
target coverage
Target delineation
target therapies
target therapy
Target volume
targeted contrast materia
targeted drug delivery
targeting
taxane
Taxol
Taxotere
TCF regimen
tcr-gamma
Technetium-99m
technique investigation
tectal glioma
telemedicine
Telomerase activity
telomerase RNA
Temozolomide
temozolomide refractory
teratoma
terebrant ulcer
terminal cancer patients
terminal patient
terminally ill
test
testicular cancer
Testicular seminoma
Testicular tumors
Testis
Testosterone,Wistar rats
tetrandrine
thalidomide
Therapeutic guidelines
therapeutic strategies
therapy
therapy-related leukemia
thiamine
Thiols
third-line chemotherapy
Three-dimensional conform
three-dimensional conform
Thrombocytopenia
thrombophilic screening
Thrombosis
Thrombotic thrombocytopen
Thymic carcinoid
thymolipoma
Thymoma
thymus
Thyroglobulin
Thyroglobulin (Tg)
Thyroglossal duct cyst
Thyroglossal duct remnant
Thyroid
Thyroid cancer
Thyroid cancer scintigrap
Thyroid carcinoma
thyroid gland
thyroid lesions
thyroid metastases
thyroid metastasis
Thyroid neoplasms
thyroid nodule
thyroid squamous cell car
thyroid surgery
thyroid tumor
thyroidectomy
time trends
Time-intensity dynamic pr
TIMP3
Tissue remodelling
tobacco
Tobacco smoking
tomotherapy
Tongue
tongue cancer
tonsil
tonsil metastasis
topoisomerase IIa
total colectomy
Total dermatoscopic score
total gastrectomy
total parental nutrition
Toxicity
TP53
TPS commissioning
TRAIL
training
tram
transanal excision
Transarterial chemoemboli
transcatheter arterial ch
Transitional cell carcino
translational research
Transplant-related compli
Transrectal ultrasonograp
transverse colon
trastuzumab
Treatment
Treatment guidelines
treatment monitoring
treatment response predic
treatment verification
Trends
trends in smoking
TRIMprobTM
Triphenylethylenes
triplet
triplet regimen
Trisomy 21
TSPAN1
TTF-1
Tuberculosis
Tumor
tumor and nontumor lesion
tumor bank
tumor burden
tumor cells
Tumor lysis syndrome
Tumor marker
Tumor marker CA 15-3
Tumor markers
tumor metastasis
tumor response
tumor sample
tumor seeding
tumor size
tumor stage
Tumor staging
Tumor-associated mononucl
Tumor-like lesion
tumor-like multiple scler
Tumorigenesis
Tumorlets
Tumors macrophages
Turkish breast cancer sur
tuscany
twins
type-1 neurofibromatosis
Tyrosine kinase
tyrosine kinase inhibitor
ultrasonography
Ultrasound
Ultrasound-guided fine-ne
Umbilical nodule
unconventional cancer tre
undertreatment
undifferentiated esophage
undifferentiated nasophar
uniscale assessment
unknown primary
unknown primary site
unknown primary tumors
unresectable
Unusual metastatic sites
uPA,TIMP
upper aerodigestive cance
Upregulation
Urachal carcinoma
Urbanization
urethane
Urinary bladder metastase
urinary tract
urokinase plasminogen act
urothelial cancer
Urothelial carcinoma
Urothelial carcinoma of t
urothelium.
usage of cam
uterine cervical cancer
uterine cervix cancer
uterine cervix carcinoma
uterine metastasis
Uterine neoplasms
Uterine sarcoma
uterine serous cancer
Uterus
Uveal melanoma
UW-QOL
Vaccination
Vacuum-assisted core biop
Vaginal cancer
validation
validity
Vascular endothelial grow
vascular proliferation
Vascular tumor
vascular tumors
VE-cadherin,VEGF
vectorization
Venous thromboembolic com
Vertebral compression fra
Vertebral tumor
vertebroplasty
videoconference
Vinblastine
Vinorelbine
virtual bio repository
vitamin A
Vitamin D analogs
VM26
vocal fold paralysis
vocal folds
voice disorder
VP3
Weekly administration
Weekly docetaxel
weekly docetaxel and gemc
Weekly paclitaxel therapy
Weekly therapy
Wernicke's encephalopath
WHO histopathological cla
whole abdominal irradiati
whole brain radiotherapy
wnt signaling
Wnt-5a
women
Woringer-Kolopp disease
X-ray computed tomography
X-rays
Xenograft
yolk sac tumor
young
youth smoking
yttrium-90
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