Case 285: Primary Breast Lymphoma.

History A 25-year-old woman was referred to our breast clinic for assessment of a palpable mass in her left breast that developed quickly in 2 weeks. She denied any associated fever, chills, redness, or pain. She had no relevant medical or surgical history; no evidence of recent pregnancy, abortion, or breastfeeding; and no family history of breast cancer. Clinical examination enabled confirmation of a firm mass occupying the retroareolar region and the outer quadrant of the left breast with no skin retraction, edema, or erythema. There was no evidence of enlarged axillary lymph nodes. US of the left breast, bilateral breast MRI, and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT were performed.

Is there any added value to substitute the 2D digital MLO projection for a MLO tomosynthesis projection and its synthetic view when a 2D standard digital mammography is used in a one-stop-shop immediate reading mammography screening?

OBJECTIVES: Breast cancer screening consists of batch interpretation of two-view (cranio-caudal CC- and medio-lateral oblique MLO) digital mammography (DM) per breast. The DM-MLO view was substituted by an MLO-digital breast tomosynthesis (DBT) and its synthetic (2D-synthetic mammography (SM)-MLO) view. The performance of this hybrid protocol was evaluated in a one-stop-shop screening visit, providing immediate reading and additional work up. METHODS: Retrospective, observational review, comparing the cancer detection rate (CDR), breast US rates, and biopsy rates in 13,048 women screened with DM from June 2015 to November 2016 and 8639 women screened with SM-DBT/DM from January 2017 to July 2018. Chi-square tests or Fisher's exact tests were used to compare proportions between the two screening imaging methods. RESULTS: SM + DBT/DM significantly increased the overall CDR (10.8‰) versus DM (7.5‰) (p = 0.0120) with more invasive lobular carcinoma (14% versus 4%) (p = 0.0357) detected and overall more invasive cancers among women with breast density type B (p = 0.0411) and those aged between 60 and 70 (p = 0.0306). This was achieved at the expense of additional sonographic examinations performed (33.5% in DBT group versus 26.7% in DM group) (p < 0.0001), more BI-RADS category III assigned (1.8% in SM-DBT/DM group versus 1.5% in DM group) (p = 0.0443) and more biopsy rates (3.0 % in SM-DBT/DM group versus 1.7% in DM group) (p < 0.0001). CONCLUSIONS: Hybrid mammographic protocol replacing 2D-MLO by DBT-MLO and SM-MLO views in a one-stop-shop screening visit improved CDR, at the expense of more sonographic examinations, biopsies, and BI-RADS III lesions. Breast US alone detected 9.2% of all breast cancers in this cohort. KEY POINTS: • Hybrid protocol including MLO (DBT + SM) with 2D DM CC may improve CDR compared to standard 4 views 2D DM in a screening program providing immediate interpretation. • Adding screening breast US, when perceived necessary, in the same visit of a screening mammography, increases cancer detection rate of 9.2%. • Based on our results, hybrid protocol including DBT + SM in MLO plane and DM in CC plane could be safely implemented as a transition towards DBT and SM alone, without any compromise in the cancer detection ability. Our results may vary according to the properties of machines from different vendors.

Medical Cannabis in Oncology: a Valuable Unappreciated Remedy or an Undesirable Risk?

OPINION STATEMENT: The use of the cannabis plant by cancer patients has been rising significantly in the past few years worldwide, primarily driven by public demand. There is an obvious need for more reliable scientific data, pharmacology information, a better understanding of its mode of action, and available clinical evidence supporting its robust use. Physicians must complete a thorough medical assessment, screening for potential drugs, or treatment contraindications before allowing its consumption. In light of the growing popularity of cannabis usage, it is highly essential that, in the near future, the medical community will be able to provide practical recommendations and explicit guidelines, including doses, and that cannabinoid concentrations in the used products are defined regarding its prescription before any medical procedure involving its usage is authorized. Here, we review and describe the favorable outcomes demonstrating the benefits of cannabis as an adjunctive treatment to conventional medicines for chemotherapy-induced nausea, vomiting, and cancer-related pain (primarily refractory chronic or neuropathic pain). Although not yet substantial enough, the treatment of anorexia, insomnia, depression, and anxiety is also seemingly favorable. To date, reports regarding its anti-neoplastic effects or its potent immunosuppressive properties influencing response to immunotherapy are still very conflicting and controversial. Thus, with the current state of evidence, cannabis use is not advisable as initial treatment, as an adjunct or an advanced line of care. In the coming years, we expect that preclinical data and animal models will shift to the clinical arena, and more patients will be recruited for clinical trials, and their reports will advance the field. Thus, physicians should prescribe cannabis only if careful clarification and consideration is provided together with a follow-up response evaluation.

Breast MRI Does Not Help Differentiating Radial Scar With and Without Associated Atypia or Malignancy.

PURPOSE: To review breast magnetic resonance imaging (MRI) features of radial scar (RS) with and without associated atypia/malignancy. METHODS: Twenty-eight (mean age 56.8) patients diagnosed with 30 biopsy-proven RS (n = 25, ultrasound-guided 14-gauge, n = 5, stereotactically guided 9-gauge) subsequently underwent breast MRI followed by surgery. Magnetic resonance imaging protocol included axial T1, axial fat sat T2, and postgadolinium in axial and sagittal planes. Two radiologists reviewed the mammographic and MRI findings in consensus according to the Breast Imaging Reporting and Data System lexicon. RESULTS: Of the 30 RSs excised surgically, 14 (14/30, 47.7%) were not associated with atypia/malignancy while atypia/malignancy was found in 16 (16/30, 53.3%) RSs. Three (3/30, 10%) RS lesions did not enhance on dynamic MR. Mean lesion size on MRI was 1.4 cm (range, 0.5-5 cm). Seventeen (17/30, 56.7%) lesions presented as nonmass enhancement and 9 (9/30, 30%) as masses. Nonmass lesions showed focal distribution (13/17, 76.5%) and heterogeneous enhancement (15/17, 88.2%). Masses showed irregular shape and margins (6/9, 67%) and heterogeneous enhancement (8/9, 89%). Multivariate analysis did not show any significant difference in MRI presentation between RS only and RS associated with atypia/malignancy. CONCLUSION: Breast MRI does not help differentiate between RS with or without associated atypia/malignancy.

Case 285.

History A 25-year-old woman was referred to our breast clinic for assessment of a palpable mass in her left breast that developed quickly in 2 weeks. She denied any associated fever, chills, redness, or pain. She had no relevant medical or surgical history; no evidence of recent pregnancy, abortion, or breastfeeding; and no family history of breast cancer. Clinical examination enabled confirmation of a firm mass occupying the retroareolar region and the outer quadrant of the left breast with no skin retraction, edema, or erythema. There was no evidence of enlarged axillary lymph nodes. US of the left breast (Fig 1), bilateral breast MRI (Fig 2), and fluorine 18 fluorodeoxyglucose PET/CT (Fig 3) were performed.

Comparative Evaluation of Iodine-125 Radioactive Seed Localization and Wire Localization for Resection of Breast Lesions.

PURPOSE: Radioactive seed localization (RSL) uses a titanium seed labeled with iodine-125 energy for surgery of nonpalpable breast lesions. RSL facilitates radiology-surgery scheduling and allows for improved oncoplasty compared with wire localization (WL). The purpose of this work was to compare the 2 techniques. METHODS: We performed a retrospective study of all breast lesions operated with RSL between February 2013 and March 2015 at our university institution, and compared with an equivalent number of surgeries performed with a single WL. Imaging and pathology reports were reviewed for information on guidance mode, accuracy of targeting, nature of excised lesion, size and volume of surgical specimen, status of margins, and reinterventions. RESULTS: A total of 254 lesions (247 women) were excised with RSL and compared with 257 lesions (244 women) whose surgery was guided by WL. Both groups were comparable in lesion pathology, guidance mode for RSL or WL positioning, and accuracy of targeting (98% correct). Mean delay between biopsy and surgery was 84 days for RSL versus 103 after WL (P = .04). No differences were noted after RSL or WL for surgical specimen mean weight, largest diameter, and volume excised. For malignancies, the rate of positive margins was comparable (2.8%-3%), with 5 of 10 women in the RSL group who underwent a second surgery displaying residual malignancy compared with 3 of 9 women in the WL group. CONCLUSIONS: RSL is safe and accurate, and has comparable surgical endpoints to WL. Because RSL offers flexible scheduling and facilitated oncoplasty, RSL may replace WL for resection of nonpalpable single breast lesions.

Imaging Features Associated With Posttraumatic Breast Neuromas.

OBJECTIVE: The aim of this study is to review the clinical and imaging features of patients with a histopathologic diagnosis of posttraumatic breast neuromas. MATERIALS AND METHODS: We report eight biopsy-proven posttraumatic neuromas in six patients with a history of breast surgery. Mammographic, sonographic, and breast MRI examinations were reviewed according to the BI-RADS lexicon. In addition, the tail sign, a specific sign known to be associated with neuromas in other parts of the body, was assessed. RESULTS: Mammographic, MRI, and sonographic examinations were performed in three, four and all six patients, respectively. The neuromas were occult on the three mammograms performed but all of them were identified on ultrasound as hypoechoic masses with parallel orientation; seven of the eight neuromas (87.5%) had an oval shape with circumscribed margins. Strain elastography performed for two patients (three neuromas) showed benign features (benign elasticity scores and fat-to-lesion ratio). Half of the masses showed a tail sign (focal thickening of the nerve adjacent to posttraumatic neuroma, similar to the dural tail sign). Of five lesions investigated by MRI, two were occult on MRI. The remaining three were visible as isointense foci on T1-weighted images, with a benign type 1 enhancement curve. CONCLUSION: In patients who underwent breast surgery, a mass with benign features raises the possibility of a neuroma. Although the tail sign was present in half of the posttraumatic neuromas, imaging-guided biopsy remains the standard of care.

The Added Value of Statistical Modeling of Backscatter Properties in the Management of Breast Lesions at US.

PURPOSE: To develop a classification method based on the statistical backscatter properties of tissues that can be used as an ancillary tool to the usual Breast Imaging Reporting and Data System (BI-RADS) classification for solid breast lesions identified at ultrasonography (US). MATERIALS AND METHODS: This study received institutional review board approval, and all subjects provided informed consent. Eighty-nine women (mean age, 50 years; age range, 22-82 years) with 96 indeterminate solid breast lesions (BI-RADS category 4-5; mean size, 13.2 mm; range, 2.6-44.7 mm) were enrolled. Prior to biopsy, additional radiofrequency US images were obtained, and a 3-second cine sequence was used. The research data were analyzed at a later time and were not used to modify patient management decisions. The lesions were segmented manually, and parameters of the homodyned K distribution (α, k, and µn values) were extracted for three regions: the intratumoral zone, a 3-mm supratumoral zone, and a 5-mm infratumoral zone. The Mann-Whitney rank sum test was used to identify parameters with the best discriminating value, yielding intratumoral α, supratumoral k, and infratumoral µn values. RESULTS: The 96 lesions were classified as follows: 48 BI-RADS category 4A lesions, 16 BI-RADS category 4B lesions, seven BI-RADS category 4C lesions, and 25 BI-RADS category 5 lesions. There were 24 cancers (25%). The area under the receiver operating characteristic curve was 0.76 (95% confidence interval: 0.65, 0.86). Overall, 24% of biopsies (in 17 of 72 lesions) could have been spared. By limiting analysis to lesions with a lower likelihood of malignancy (BI-RADS category 4A-4B), this percentage increased to 26% (16 of 62 lesions). Among benign lesions, the model was used to correctly classify 10 of 38 fibroadenomas (26%) and three of seven stromal fibroses (43%). CONCLUSION: The statistical model performs well in the classification of solid breast lesions at US, with the potential of preventing one in four biopsies without missing any malignancy.

Inhibition of endocannabinoid-degrading enzyme fatty acid amide hydrolase increases atherosclerotic plaque vulnerability in mice.

The role of endocannabinoids such as anandamide during atherogenesis remains largely unknown. Fatty acid amide hydrolase (FAAH) represents the key enzyme in anandamide degradation, and its inhibition is associated with subsequent higher levels of anandamide. Here, we tested whether selective inhibition of FAAH influences the progression of atherosclerosis in mice. Selective inhibition of FAAH using URB597 resulted in significantly increased plasma levels of anandamide compared to control, as assessed by mass spectrometry experiments in mice. Apolipoprotein E-deficient (ApoE(-/-)) mice were fed a high-fat, cholesterol-rich diet to induce atherosclerotic conditions. Simultaneously, mice received either the pharmacological FAAH inhibitor URB597 1mg/kg body weight (n=28) or vehicle (n=25) via intraperitoneal injection three times a week. After eight weeks, mice were sacrificed, and experiments were performed. Vascular superoxide generation did not differ between both groups, as measured by L012 assay. To determine whether selective inhibition of FAAH affects atherosclerotic plaque inflammation, immunohistochemical staining of the aortic root was performed. Atherosclerotic plaque formation, vascular macrophage accumulation, as well as vascular T cell infiltration did not differ between both groups. Interestingly, neutrophil cell accumulation was significantly increased in mice receiving URB597 compared to control. Vascular collagen structures in atherosclerotic plaques were significantly diminished in mice treated with URB597 compared to control, as assessed by picro-sirius-red staining. This was accompanied by an increased aortic expression of matrix metalloproteinase-9, as determined by quantitative RT-PCR and western blot analysis. Inhibition of fatty acid amide hydrolase does not influence plaque size but increases plaque vulnerability in mice.

Case 201: glomus tumor of the breast.

History A 55-year-old woman presented to our breast clinic with 1-year history of lancinating pain in the right breast that was exacerbated by blunt pressure and cold temperature. She denied any family history of breast cancer or any personal history of trauma, infection, or surgery of the breast. On clinical examination, exquisite pain was generated by simple light pressure over the upper outer quadrant of the right breast. Mammography and ultrasounography (US) with Doppler analysis of the right breast were painful but were performed with the least pressure possible.

Molecular classification of infiltrating breast cancer: toward personalized therapy.

Breast cancer is a heterogeneous disease, which comprises several molecular and genetic subtypes, each with characteristic clinicobiologic behavior and imaging patterns. Traditional classification of breast cancer is based on the histopathologic features but offers limited prognostic value. Novel molecular characterization of breast cancer with cellular markers has allowed a new classification that offers prognostic value, with predictive categories of disease aggressiveness. These molecular signatures also open the door to personalized therapeutic options, with new receptor-targeted therapies. For example, invasive cancer subtypes such as the luminal A and B subtypes show better prognosis and response to hormone receptor-targeted therapies compared with the triple-negative subtypes; on the other hand, triple-negative tumors respond better than luminal tumors to chemotherapy. Tumors that display amplification of the oncogene ERBB2 (also known as the HER2/neu oncogene) respond to drugs directed against this oncogene, such as trastuzumab. The imaging aspects of tumors correlate with molecular subgroups, as well as other pathologic features such as nuclear grade. Smooth tumor margins at mammography may be suggestive of a triple-negative breast cancer, and a human epidermal growth factor receptor 2 (HER2)-positive tumor is characteristically a spiculated mass with calcifications. Low-grade ductal carcinoma in situ (DCIS) is better detected with mammography, although magnetic resonance (MR) imaging may allow better characterization of high-grade DCIS. MR imaging diffusion sequences show higher values for the apparent diffusion coefficient for triple-negative and HER2-positive subtypes, compared with luminal A and B tumors. MR imaging is also a useful tool in the prediction of tumor response after chemotherapy, especially for triple-negative and HER2-positive subtypes.

Breast reconstruction: review of surgical methods and spectrum of imaging findings.

Breast reconstruction after mastectomy is often requested by women with breast cancer who are ineligible for breast-conserving therapy and women with a high genetic risk for breast cancer. Current breast reconstruction techniques are diverse and may involve the use of an autologous tissue flap, a prosthetic implant, or both. Regardless of the technique used, cancer may recur in the reconstructed breast; in addition, in breasts reconstructed with autologous tissue flaps, benign complications such as fat necrosis may occur. To detect breast cancer recurrences at a smaller size than can be appreciated clinically and as early as possible without evidence of metastasis, radiologists must be familiar with the range of normal and abnormal imaging appearances of reconstructed breasts, including features of benign complications as well as those of malignant change. Images representing this spectrum of findings were selected from the clinical records of 119 women who underwent breast magnetic resonance (MR) imaging at the authors' institution between January 2009 and March 2011, after mastectomy and breast reconstruction. In 32 of 37 women with abnormal findings on MR images, only benign changes were found at further diagnostic workup; in the other five, recurrent breast cancer was found at biopsy. Four of the five had been treated initially for invasive carcinoma, and one, for multifocal ductal carcinoma; three of the five were carriers of a BRCA gene mutation. On the basis of these results, the authors suggest that systematic follow-up examinations with breast MR imaging may benefit women with a reconstructed breast and a high risk for breast cancer recurrence.

Accuracy of percutaneous core needle biopsy in diagnosing papillary breast lesions and potential impact of sonographic features on their management.

OBJECTIVE: To assess retrospectively the accuracy of core needle biopsy in diagnosing papillary breast lesions and evaluate the prediction of malignant papillary lesions based on sonographic features. METHODS: Review of 130 papillary lesions diagnosed on core needle biopsy (2002-2008) in 110 patients. The biopsy results were compared with final surgical pathology or evolution on imaging follow-up. Lesion size, patient age, type of biopsy needle and guidance, and length of imaging follow-up were documented. Sonographic features were retrospectively reviewed according to the BI-RADS lexicon. Morphology, not part of BI-RADS, was assessed as intraductal, intracystic, or solid. RESULTS: Of the 130 papillary lesions, 6 were sampled with an 11-G vacuum-assisted needle under stereotactic guidance and the remaining 124 were sampled under US guidance with a 14-G (n = 115), 18-G (n = 8), or 10-G (n = 1) needle. Initial core needle biopsy diagnosis was benign (n = 103), showed atypia (n = 20), or malignancy (n = 7). Thirty-seven (36%) benign lesions were surgically excised and 66 (64%) were followed up. On final outcome, 10 benign lesions were upgraded to malignancy (9.7%) and 3 to atypia (3.6%). There was no significant difference in the benign, malignant, and upgraded groups with respect to size, age, or BI-RADS sonographic characteristics. None of the oval-shaped lesions nor the intraductal ones were upgraded. CONCLUSIONS: Although some sonographic features could favor a benign diagnosis, when a core biopsy yields the diagnosis of a papillary lesion, surgical excision is recommended to definitely exclude malignancy.

Foot center of pressure trajectory alteration by biomechanical manipulation of shoe design.

BACKGROUND: Footwear-generated biomechanical manipulations have been shown to alter lower limb kinetics. It has been suggested that this is due to altered trajectory of the foot's center of pressure (COP), conveying a shift in location of the ground reaction force and modifying moments and forces acting on proximal body segments. However, past studies have focused on qualitative association between footwear design and the COP locus. Moreover, this association was calculated via indirect analysis. The purpose of the present study was to directly examine and quantify the correlation between measured footwear biomechanical manipulation and the location of the COP trajectory during gait. METHODS: A novel biomechanical device allowing flexible positioning of 2 convex-shaped elements attached to its sole was utilized. A total of 20 healthy male adults underwent direct in-shoe pressure measurements while walking with the device set at 7 mediolateral configurations. COP data were collected during gait and analyzed with respect to different stance subphases. RESULTS: COP location significantly correlated with a shift of the elements medially or laterally. The linear model describing this correlation was found to be statistically significant. CONCLUSION: There was significant correlation between the plantar orientation of the shoe device configuration and the COP. CLINICAL RELEVANCE: Changes in COP trajectory may be valuable in patients suffering from multiple foot disorders elevating pressure on the foot. Accurate COP control could aid in the manipulation of the forces acting on the proximal joints during gait. In addition, these findings may have implications in the field of biomechanical apparatus design and practice.

Sonographic appearance of invasive ductal carcinoma of the breast according to histologic grade.

OBJECTIVE: The purpose of this study was to compare the efficacy of the sonographic features in the BI-RADS lexicon for predicting malignancy grade of invasive ductal breast carcinoma in women assigned a BI-RADS category of 4 or 5. MATERIALS AND METHODS: Two radiologists retrospectively evaluated 299 consecutive cases of grades 1-3 invasive ductal breast carcinoma presenting as a mass in consensus by using the BI-RADS sonographic lexicon. Histologic grade was established on surgical specimens. Effect sizes were calculated via the Goodman and Kruskal tau, an asymmetric measure of strength of nominal association, and results were interpreted in terms of proportional reduction in error. RESULTS: Thirty-eight lesions (13%) were grade 1, 153 (51%) were grade 2, and 108 (36%) were grade 3, with the majority of all masses showing an irregular shape (84%) and hypoechoic echotexture (82%). Of the sonographic features examined, malignancy grade was best predicted by posterior acoustics (τ = 0.13, p < 0.001), lesion boundary (τ = 0.05, p < 0.001), and margin (τ = 0.04, p = 0.001). Among grade 3 lesions, there were significantly more lesions with posterior enhancement (53 vs 27.6; adjusted standardized residuals (z(res)) = 7; p < 0.001), abrupt interfaces (68 vs 51.2; z(res) = 4; p < 0.001), and microlobulated margins (12 vs 5.8; z(res) = 3; p = 0.001) than would be expected. CONCLUSION: Malignancy grade was slightly to moderately predicted by margin, lesion boundary, and acoustic sonographic features. In particular, grade 3 invasive ductal breast carcinomas were more likely than expected to display microlobulated margins, abrupt interfaces, and posterior enhancement.

Surgical outcome of biopsy-proven lobular neoplasia: is there any difference between lobular carcinoma in situ and atypical lobular hyperplasia?

OBJECTIVE: The aims of our study were to determine the frequency of malignancy after surgical excision of biopsy-proven lobular carcinoma in situ (LCIS) or atypical lobular hyperplasia (ALH) lesions, to assess any difference between pure LCIS and pure ALH lesions regarding their radiologic presentation and the malignancy upgrade rate after surgical excision, and to evaluate the outcome of lesions that were not excised surgically but were followed up. MATERIALS AND METHODS: Radiologic and pathologic records of 14,435 imaging-guided needle biopsies of the breast performed between 2004 and 2008 in three different institutions were retrospectively reviewed. A total of 126 patients (0.9%) had biopsy-proven LCIS or ALH, or both, as the highest-risk lesion. Among the 126 patients, 89 (71%) continued to surgery, and 14 were followed up for more than 24 months. The Mantel-Haensel chi-square test was used for statistical analysis. RESULTS: Cancer upgrade was documented in 17 of the 43 LCIS (40%), 11 of the 40 ALH (27%), and two of the six combined ALH and LCIS lesions (33%) surgically excised, for a total malignancy upgrade rate of 34% (30/89). Both LCIS and ALH lesions presented mammographically in most cases as microcalcifications (p = 0.078). None of the 14 patients followed up for a mean period of 51 months showed development of malignancy. CONCLUSION: No statistically significant difference was found between mammographic presentation and postsurgical outcome of LCIS versus ALH lesions. Surgical excision of these lesions is recommended as long as no evident criteria are provided to differentiate those that might be associated with an underlying malignancy.