Pleomorphic Calcifications Research Articles

Abstract PO4-20-07: Dense Breast Tissue in a High-Risk African-American Woman with DCIS and Nodal Metastasis of Intra-ductal Carcinoma: A Case Report and Discussion on the Current USPSTF Draft Recommendation

Abstract Introduction and objectives: The incidence of breast cancer (BC) in younger women has increased in recent years, raising the discussion on adjustments to screening recommendations. This past May, a new draft recommendation to the USPSTF guidelines for BC screening adjusted the age of screening from 50 to 40. However, there is still insufficient evidence to recommend adjusted screening guidelines for patients at increased risk including ethnic minorities with higher mortality and women with dense breasts. The paucity of trials and reviews for many of these at-risk groups may be leading to later diagnosis and poorer outcomes. This case highlights the importance of clinical judgment when screening patients whose presentation lies outside the guidelines. Clinical Case: A 29-year-old AAW with past medical history of bipolar disorder presents to her primary care physician in April 2023 with concern for left breast mass. Patient was previously on risperidone and Depakote for her bipolar disorder one year prior which resulted in drug-induced amenorrhea and breast tenderness with evidence of elevated prolactin. She was taken off her medication with return of her menses, but breast tenderness persisted for three months. During this time, she noticed a palpable breast mass. Family history is not significant for breast cancer. Breast ultrasound and mammography revealed “extremely dense” breast tissue bilaterally. Imaging significant for 7.6 × 6.2 × 6.3 cm irregular mass in the lower inner quadrant of the left breast with pleomorphic calcifications. Biopsy subsequently performed with breast pathology significant for ER+/PR- ductal carcinoma in situ. However, lymph node pathology showed evidence of invasive ductal carcinoma raising question of diagnosis of possible occult breast cancer versus breast cancer with axillary metastasis. PET CT did not show evidence of metastatic disease. She was started on neoadjuvant chemotherapy. Discussion and Conclusion: It is well known that African American women (AAW) are at increased risk for mortality due to BC, aggressive secondary BC, and for high-risk tumor biology. Additionally, AAW generally have more dense breast tissue, another risk factor for BC. Dense breast tissue can make it more difficult to characterize high-risk lesions on screening modalities. In regard to this patient, her dense breast tissue may obfuscate characterization of areas of possible primary cancer being the cause of her nodal metastasis. Current guidelines do not take these well-known associations and risk factors into account. A separate treatment algorithm may be required to work up a patient from high-risk groups such as this patient case. It is crucial that future guidelines on screening should incorporate specific risk factors which would help detect BC earlier in vulnerable populations. Citation Format: Vinita Akula, Jessica Jones. Dense Breast Tissue in a High-Risk African-American Woman with DCIS and Nodal Metastasis of Intra-ductal Carcinoma: A Case Report and Discussion on the Current USPSTF Draft Recommendation [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-20-07.

Abstract PO3-20-08: Case Studies on Detecting Ductal Carcinoma in Situ Using Contrast-Enhanced Spectral Mammography and Predictive Indicators for Underestimation

Abstract Purpose: To introduce clinical cases of ductal carcinoma in situ (DCIS) underestimation focusing on additional benefits of contrast-enhanced spectral mammography (CESM). Background: DCIS, a noninvasive breast cancer, is often underestimated during diagnosis. Predicting which cases will upgrade to invasive cancer is crucial. CESM offers superior diagnostic performance compared to mammography and mammography with targeted ultrasound (US). Its low-energy images improve microcalcification conspicuity, enable accurate tumor extent measurement, and provide information on enhancements associated with nonmass microcalcifications. Enhanced areas on CESM can be easily compared with mammographic microcalcifications, for they are obtained during the same session. Indicators heralding DCIS underestimation 1. Detectability: underestimated DCIS is more likely to be detected on CESM and mammogram than pure DICS, whereas detection rates do not statistically differ on US and MRI. 2. Lesion type: underestimated DCIS mostly presents as enhancing mass or nonmass lesions on CESM and calcifications on low-energy conventional mammography. 3. Disease extent: on CESM, pure DCIS show smaller tumor extent than the underestimated ones. 4. CESM gray value (CGV) of the lesion on recombined image: the pure DCIS types show lower mean, standard deviation, maximum, and difference values, whereas the underestimated types demonstrate lower minimum values, and vice versa. Case 1: Screen detected pure DCIS without postsurgical upgrade in an asymptomatic 44-year-old woman. US-guided core biopsy yielded DCIS, intermediate nuclear grade with necrosis. Postsurgical pathology confirmed a 1.5 cm pure ductal carcinoma in situ, intermediate nuclear grade with necrosis. (A) US shows a 1.3 cm irregular hypoechoic mass in the right breast. (B) Routine mammography demonstrates no definite abnormality in the right breast. (C) CESM shows a 1.2 cm irregular enhancing mass in the upper central portion of right breast and CGV was 2034 AU. (D) Contrast-enhanced MR images show a 2.1 cm irregular enhancing mass in 12 o’clock direction of the right breast. Case 2: Screen detected DCIS with postsurgical upgrade to microinvasive ductal carcinoma in a 64-year-old woman with nonspecific discomfort in her right breast. US-guided core biopsy yielded DCIS, high nuclear grade with necrosis. Postsurgical pathology confirmed a 2.8 cm sized microinvasive ductal carcinoma, high nuclear grade, histologic grade 3 with necrosis. (A) US demonstrates a 1.9 cm irregular hypoechoic mass with calcifications in 9 o’clock direction 2.1 cm from the nipple in the right breast. (B) Right magnification view shows a 2.5 cm-extent segmentally distributed fine pleomorphic calcifications in the right breast. (C) CESM shows a 3 cm irregular enhancing mass with calcifications in the right breast, and CGV was 2045 AU. (D) Contrast-enhanced MR images shows a 2.3 cm irregular enhancing mass in the right breast. Case 3: Screen detected DCIS with postsurgical upgrade to invasive ductal carcinoma with DCIS in a 47-year-old woman who had a family history of breast cancer. US-guided core biopsy yielded DCIS, intermediate nuclear grade with necrosis. Postsurgical pathology confirmed a 0.2 cm invasive ductal carcinoma with 2.4 cm DCIS. (A) US demonstrates a 2.3 cm irregular hypoechoic mass in the left breast. (B) Routine mammography shows asymmetry in the upper portion of the left breast. (C) CESM shows a 3 cm enhancing mass in the left breast, and CGV of the lesion on MLO-recombined image was 2072 AU. (D) Contrast-enhanced MR image shows a 6 cm irregular enhancing mass in the upper portion of the left breast. Conclusion: CESM provides added advantages over mammography and breast US in detecting underestimated DCIS, and it is comparable to breast MRI. Key indicators to consider include detectability, enhancing lesion, larger tumor extent, higher mean CGV on CESM. Citation Format: Minji Song, Hee Jung Shin. Case Studies on Detecting Ductal Carcinoma in Situ Using Contrast-Enhanced Spectral Mammography and Predictive Indicators for Underestimation [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-20-08.

A Challenging Case of Atypical Papillary Proliferation of Nipple with Loss of Myoepithelial Layer Cells; a Diagnostic Dilemma

Abstract Introduction/Objective Papillary breast lesions are comprised of a broad spectrum of entities ranging from benign conditions like intraductal papilloma to invasive carcinoma. These lesions account for less than 3% percent of breast tumors and less than 2% of breast malignancies. The wide range and overlap in the clinical, imaging, and histologic characteristics of these lesions can often make them difficult to classify. Here we present a case of a challenging neoplastic nipple papillary lesion with a differential diagnosis ranging from nipple adenoma with atypia to papillary carcinoma. Methods/Case Report 48-year-old female with history of left nipple mass for 6 months, presented to the emergency department with mild bleeding from the left nipple for two hours. Breast ultrasound showed a group of fine pleomorphic calcifications within a mass arising from the left nipple, highly concerning for Paget's disease. Histopathology revealed papillary proliferation of well-formed round structures within a variably fibrous/hemorrhagic stroma. The nodules exhibited papillary fronds with epithelial hyperplasia of monotonous low-grade cells, and scattered mitoses, forming relatively rigid/luminal structures with polarization. No desmoplasia or conventional infiltrative pattern was seen. Immunohistochemical staining showed strong expression for estrogen receptor (ER). Cytokeratin 5/6, p63 and calponin did not highlight the myoepithelial layer in the papillary elements or around the round structures. A diagnosis of atypical papillary proliferation was rendered to warrant an excision. Subsequently, the patient underwent total mastectomy, which revealed conventional invasive ductal carcinoma with lymphovascular space invasion. Results (if a Case Study enter NA) NA Conclusion Atypical papillary lesions of the nipple are difficult to classify in a limited biopsy material. The loss of myoepithelial cell layer makes interpretation even more challenging. Extreme caution should be taken in assigning neoplastic nature to the lesions in biopsy which eventually guide the surgeon in making decision to preserve the nipple or not.

Recurrence Yield of Stereotactic Biopsy of Suspicious Calcifications After Breast Conservation Therapy.

AimTo analyze the histopathological outcome of stereotactic biopsies of newly developed suspicious calcifications at lumpectomy scar site in patients with breast conservation surgery (BCS) to determine the incidence of malignancy and the association of mammographic appearance of recurrent microcalcification and their distribution. We also determined the association of disease recurrence with the presence of calcifications in original tumor and lumpectomy resection margins with the risk of recurrence.Materials and methodsThis study is a retrospective review of mammograms of patients with breast cancer from 2010 to 2021 who underwent stereotactic biopsy of newly developed suspicious calcifications at scar site appreciated on annual follow-up mammogram after breast conservation surgery (BCS) with no mass on correlative ultrasound. The radiological and pathological features of the patients' primary tumor and new calcifications were obtained from the hospital's electronic patient record system.ResultsA total of 84 patients with breast cancer developed suspicious microcalcifications at the lumpectomy scar site detected on follow-up mammograms after BCS, and 28.6% showed malignant histopathological outcomes. All malignant cases demonstrated pleomorphic morphology. All amorphous (9.5%) and coarse heterogeneous (54.8%) calcifications were benign. The distribution pattern of recurrent malignant calcifications was grouped in 9.5%, regional in 2.4%, linear in 9.5%, and segmental in 7.1%. Calcifications in primary tumors were found in 20.2% of cases. Positive margins were found in 7.1% of these malignant cases. Statistically, there was a strong association between calcification morphology, calcification distribution, presence of calcifications on baseline mammogram, and tumor resection margins. The presence of calcifications in primary tumors and positive resection margins were identified as significant independent risk factors of malignant recurrent calcifications in the logistic regression model and marginal statistical significance in the multivariable logistic regression (MLR) model.ConclusionThe interval development of pleomorphic calcifications after BCS with either linear or segmental pattern, positive resection margins, and associated calcifications in primary tumors was related to the increase in the risk of recurrence. Although amorphous and coarse heterogeneous morphology with grouped distribution showed benign outcomes, stereotactic biopsy is recommended to exclude disease recurrence in this high-risk patient population.

Calciphylaxis and Ulcerative Lesions of Bilateral Nipple–Areolar Complex Due to Alcoholic Liver Disease

When faced with eczematous lesions involving the nipple–areolar complex (NAC), Paget's disease is assumed to be the diagnosis, anything else being considered a “Zebra” necessitating its exclusion on pathology. A middle-aged lady presented with synchronous asymmetrical ulceration of bilateral NAC with pleomorphic calcifications on mammography and simultaneous extensive vascular calcification in bilateral breasts that suggested systemic cause. Calciphylaxis is a rare diagnosis occurring usually due to underlying end-stage renal disease or hyperparathyroidism. There are very few case reports of calciphylaxis due to alcoholic liver disease and no cases to the best of our knowledge involving NAC. We report an extremely rare case of breast and NAC calciphylaxis due to alcoholic liver disease, highlighting need to consider benign etiology when bilateral involvement is present.

The Influence on Image Reconstruction Methods on Digital Breast Tomosynthesis Guided Vacuum-assisted Biopsy for Clustered Microcalcifications

In this study, we verified the targeting time and coordinates of stereotactic vacuum-assisted biopsy (STVAB) and digital breast tomosynthesis-guided vacuum-assisted biopsy (DBTVAB). We used 23 fabricated phantom samples that consisted of small round, amorphous, and pleomorphic clustered microcalcifications, and two types of image reconstruction methods: filtered back projection (FBP) and iterative super-resolution reconstruction (ISR). Regarding targeting time, DBTVAB tended to be shorter than STVAB in the two image reconstruction methods and the targeting time was significantly shorter for the amorphous and pleomorphic calcifications using DBTVAB with FBP compared to that using STVAB (p=0.022 for amorphous, p=0.041 for pleomorphic). The targeting time for small round calcifications was longer using DBTVAB with ISR compared to that using STVAB (p=0.013). For targeting coordinates, using DBTVAB with FBP showed a significant difference only for pleomorphic calcifications but using DBTVAB with ISR showed no significance. The findings of this study suggest that FBP is more suitable than ISR to be used as an image reconstruction method, and DBTVAB can shorten the targeting time compared to STVAB.

Ipsilateral microcalcifications after breast-conserving surgery: is it possible to differentiate benign from malignant calcifications?

To analyse stereotactic biopsies of microcalcifications in patients with previous ipsilateral breast-conserving surgery (BCS) to identify the positivity rate, assess for an association between the patient's primary cancer or mammographic appearances of the microcalcifications, and the risk of recurrence. Relevant patients from 2018-2020 were identified via a retrospective review of the prospectively maintained radiological procedure database. Clinicopathological features of the patients' primary tumour and new calcifications were obtained from the hospital electronic patient record system and the national integrated medical imaging system. Thirty-one percent of recurrences post-ipsilateral BCS presented as isolated microcalcifications on mammography. Fifty-three percent of patients undergoing stereotactic biopsy of ipsilateral calcifications had recurrence. A positive margin status was associated with new or recurrent malignancy. There was no significant correlation between oestrogen-receptor status, sentinel lymph node status, adjuvant radiotherapy or chemotherapy and the risk of recurrence. Calcifications within the tumour bed were more likely to be benign while calcifications within the same quadrant but remote from the tumour bed were more likely malignant. All coarse calcifications were benign while 67% of fine linear/fine linear branching and 89% of fine pleomorphic calcifications were malignant. Increased time since diagnosis, positive margin status, fine pleomorphic and fine linear calcifications in the same quadrant as the tumour bed were associated with malignancy. Patients with coarse calcifications and calcifications within the tumour bed may avoid stereotactic biopsy and undergo short-interval surveillance.

Molecular Subtypes of Breast Cancer: A Review for Breast Radiologists.

Gene expression profiling has reshaped our understanding of breast cancer by identifying four molecular subtypes: (1) luminal A, (2) luminal B, (3) human epidermal growth factor receptor 2 (HER2)-enriched, and (4) basal-like, which have critical differences in incidence, response to treatment, disease progression, survival, and imaging features. Luminal tumors are most common (60%-70%), characterized by estrogen receptor (ER) expression. Luminal A tumors have the best prognosis of all subtypes, whereas patients with luminal B tumors have significantly shorter overall and disease-free survival. Distinguishing between these tumors is important because luminal B tumors require more aggressive treatment. Both commonly present as irregular masses without associated calcifications at mammography; however, luminal B tumors more commonly demonstrate axillary involvement at diagnosis. HER2-enriched tumors are characterized by overexpression of the HER2 oncogene and low-to-absent ER expression. HER2+ disease carries a poor prognosis, but the development of anti-HER2 therapies has greatly improved outcomes for women with HER2+ breast cancer. HER2+ tumors most commonly present as spiculated masses with pleomorphic calcifications or as calcifications alone. Basal-like cancers (15% of all invasive breast cancers) predominate among "triple negative" cancers, which lack ER, progesterone receptor (PR), and HER2 expression. Basal-like cancers are frequently high-grade, large at diagnosis, with high rates of recurrence. Although imaging commonly reveals irregular masses with ill-defined or spiculated margins, some circumscribed basal-like tumors can be mistaken for benign lesions. Incorporating biomarker data (histologic grade, ER/PR/HER2 status, and multigene assays) into classic anatomic tumor, node, metastasis (TNM) staging can better inform clinical management of this heterogeneous disease.

Postoperative Imaging Appearance of an Implantable Three-dimensional Bioabsorbable Tissue Marker After Breast Surgery: Initial Experience at a Single Institution.

Three-dimensional bioabsorbable tissue marker (BTM) placement during breast surgery is performed for the purpose of improved surgical cavity delineation for radiotherapy and improved cosmetic outcome. The purpose of this study is to evaluate the postsurgical imaging findings of BTM. This Institutional Review Board-approved retrospective review included all patients implanted with BTM at breast surgery from January 2017 to September 2018. Demographics, tumor characteristics, imaging, and histologic findings were evaluated. Medical records were reviewed during a three-year period to evaluate for tumor recurrence. Ninety-seven patients had BTM implanted, of which 76 patients had imaging follow-up of at least 1 year. Of the 76 patients who had mammographic follow-up, 3 (3.9%) developed suspicious microcalcifications requiring biopsy, yielding ductal carcinoma in-situ in 2 patients and benign calcifications in 1 patient. Of 61 patients who had sonographic follow-up, 44 (72.1%) patients had complex fluid collections containing avascular, heterogeneously hyperechoic solid components, which remained stable or decreased in size over time; no recurrent tumors were found in this group. One patient (1.6%) had a vascular solid mass, which yielded recurrent papilloma. Four (6.6%) patients developed irregular hypoechoic masses at the surgical site, one of which corresponded with a developing asymmetry mammographically; biopsy yielded fibromatosis. Tissue sampling of the remaining three cases yielded invasive ductal carcinoma, fat necrosis, and radiation changes, respectively. Accurate identification of the expected postoperative imaging appearance of BTM may prevent unnecessary biopsy. Suspicious findings necessitating biopsy are pleomorphic calcifications, developing asymmetry and vascular and irregular hypoechoic masses.

Diffuse midline glioma of the cervical spinal cord with H3 K27M genotype phenotypically mimicking anaplastic ganglioglioma: a case report and review of the literature

Here, we report on a 28-year old male patient presenting with neck and shoulder pain, dysesthesia of all four limbs and hypesthesia of both hands, without motor deficits. Magnetic resonance imaging showed an intradural, intramedullary mass of the cervical spinal cord of 6.4 cm length and 1.7 cm diameter. The patient underwent surgical resection. Histological and immunohistochemical evaluation showed pleomorphic glial tumor cells, mitoses, calcifications, and atypical ganglioid cells compatible with the morphology of anaplastic ganglioglioma (WHO Grade III). Extensive molecular workup revealed H3F3A K27M, TERT C228T and PDGFRα Y849C mutations indicating poor prognosis. The H3F3A K27M mutation assigned the tumor to the molecular group of diffuse midline glioma (WHO Grade IV). Epigenome-wide methylation profiling confirmed the methylation class of diffuse midline glioma. Thus, this is a very rare case of malignant glioma with H3 K27M genotype phenotypically mimicking anaplastic ganglioglioma. This case emphasizes the importance of comprehensive morphological and molecular workup including methylome profiling for advanced patient care.

Treatment of Pregnancy-Associated Breast Cancer.

KS is a 33-year-old Caucasian married woman who works full time as an accountant and has one daughter who is 2 years old. She enjoys reading and exercising in her spare time. She initially presented in July 2015 at the age of 31 years with a 1-cm breast mass in the left inner breast, which prompted a mammogram to be obtained. The mammogram revealed diffuse and occasionally grouped left breast calcifications. Additionally, there was focal edema at the site of the mass.A follow-up mammogram was recommended to document stability in 6 months, which demonstrated an interval increase in number and size of segmental pleomorphic calcifications in the lower inner breast spanning 6 cm in size. A stereotactic core needle biopsy was completed and revealed high-grade ductal carcinoma in situ (DCIS) that was estrogen receptor (ER) and progesterone receptor (PR) positive.Surgical TreatmentKS underwent genetic testing due to her young age at diagnosis of noninvasive breast cancer. She was tested with the breast/ovarian cancer panel, which was negative for mutation.She preceded to bilateral nipple-sparing mastectomy with left sentinel node biopsy and immediate implant reconstruction in February 2016. The operative pathology revealed 3.3 cm of high-grade DCIS. The surgical margins were negative (less than 1 mm posteriorly and less than 2 mm anteriorly). There was 1 sentinel node and 2 nonsentinel nodes negative for malignancy. The right breast was negative for cancer and both retro areolar margins were negative.KS did well during the ensuing routine follow-up every 6 to 12 months in surgical oncology at an academic medical center. She was not recommended to take adjuvant endocrine therapy given the benefit of bilateral mastectomy.In 2017, at a routine oncology follow-up visit, she expressed a desire to have more children. After a negative clinical exam, she and her husband were advised that future contraception may be pursued.Pregnancy-Associated Breast Cancer DiagnosisKS was in her usual state of good health when she noticed a left breast mass in the inferior reconstructed breast in June 2017. She presented to the nurse practitioner (NP) in the surgical oncology clinic for evaluation. At that time, she was 17 weeks pregnant and being seen in the same facility for high-risk obstetrics and gynecology care. KS had no other concerning symptoms for recurrent cancer, and her pregnancy had been progressing smoothly.The surgical oncology NP noted a 1-cm firm superficial mass in the breast at 6 o’clock. She had no other bilateral breast findings or adenopathy. Upon review of systems, she denied new persistent headache, shortness of breath, abdominal pain, weight loss, night sweats, or fatigue.Due to her pregnancy and the superficial presentation of the breast mass, a left breast ultrasound was ordered. It revealed an 8-mm irregular hypoechoic mass 7 cm from the nipple at the 6 o’clock position in the reconstructed breast.A diagnostic workup ensued with a left breast ultrasound-guided core needle biopsy. KS was given a diagnosis of clinical stage T1b, N0, grade 2 invasive micropapillary carcinoma: ER positive (Allred 6), PR positive (Allred 8), HER2/neu, immunohistochemistry 3+, and fluorescence in situ hybridization amplified.After discussion of this recurrent cancer diagnosis, her team opted for a bilateral diagnostic mammogram (with abdominal shielding) and bilateral axillary and breast ultrasound to evaluate the contralateral breast and lymph nodes. There was no adenopathy, a small amount of accessory breast tissue in the right axillary tail region, and a biopsy clip was noted in the left inferior breast at 6 o’clock. The new cancer was not seen on mammogram, likely due to the proximity to the implant.

Qualitative Radiogenomics: Association Between BI-RADS Calcification Descriptors and Recurrence Risk as Assessed by the Oncotype DX Ductal Carcinoma In Situ Score.

Treatment of ductal carcinoma in situ (DCIS) is controversial given the variable recurrence and progression to invasive carcinoma. Identifying women who would benefit from adjuvant radiation therapy on the basis of their recurrence risk may allow more individualized management strategies. The Oncotype DX Breast DCIS Score-which we refer to here as the "DCIS score"-is a validated surrogate marker of local recurrence. This study evaluated the association between BI-RADS mammographic calcification descriptors and the DCIS score. Fifty-eight women diagnosed with DCIS presenting with calcifications who had Oncotype DX Breast DCIS assay results were identified. Pretreatment BI-RADS mammographic calcification features were collected including morphology, distribution, and maximum span. The association between calcification descriptors and DCIS score was assessed with logistic regression modeling. Mean DCIS scores were calculated for calcification features significantly associated with DCIS score. All analyses were adjusted for patient age, DCIS grade, and progesterone receptor status. Of the suspicious calcifications that proved to represent DCIS, 19.0% were amorphous; 25.9%, coarse heterogeneous; 39.7%, fine pleomorphic; and 15.5%, fine linear or fine linear branching in morphology. The mean DCIS scores by calcification morphology were 22.3, 35.5, 36.7, and 44.1, respectively. Amorphous calcification morphology had a significantly lower adjusted mean DCIS score compared with fine pleomorphic morphology (p = 0.01) and fine linear or fine linear branching morphology (p = 0.02). The adjusted odds ratio (OR) of intermediate or high risk of recurrence (defined as a DCIS score ≥ 39) was significantly higher for women with fine pleomorphic calcifications (OR = 53.1, p = 0.01) and for those with fine linear or fine linear branching calcifications (OR = 24.0, p = 0.04) than for women with amorphous calcifications. Women with amorphous calcification morphology had the lowest DCIS scores compared with women with fine pleomorphic and fine linear or fine linear branching morphologies. Both fine pleomorphic and fine linear or fine linear branching morphologies were associated with higher odds of intermediate or high risk of recurrence. These findings suggest mammographic features are potential biomarkers of DCIS recurrence and could help individualize treatment decisions.

Pleomorphic Lobular Carcinoma In Situ: Imaging Features, Upgrade Rate, and Clinical Outcomes.

Pleomorphic lobular carcinoma in situ (PLCIS) is an aggressive subtype of lobular carcinoma in situ treated similarly to ductal carcinoma in situ. The purpose of this study was to determine the imaging findings, upgrade rate of PLCIS at core needle biopsy (CNB), and the treatment and outcomes of these patients. This retrospective single-institution study included women with PLCIS at CNB or excisional biopsy without concomitant DCIS or invasive carcinoma between January 1, 1999, and July 20, 2016. Imaging findings, detection mode, treatment, and outcomes were reviewed. Retrospective review of the images was performed. Upgrade rate to ductal carcinoma in situ or invasive carcinoma at lumpectomy was calculated. Twenty-one patients had a finding of PLCIS at CNB (n = 16) or excisional biopsy (n = 5). Four of 15 (27%; 95% CI, 4-49%) cases of PLCIS at CNB were upgraded to DCIS (two cases) or invasive lobular cancer (two cases) at lumpectomy (one patient declined excision). No unique mammographic features were predictive of need to upgrade or extent of disease. Among the patients with pure PLCIS (not upgraded), 13 of 16 (81%) presented with fine pleomorphic calcifications on screening mammograms, 1 of 16 (6%) with distortion and calcifications, 1 of 16 (6%) with a mass, and 1 of 16 (6%) with nonmass enhancement at MRI. The median imaging size was 11 mm (mean, 14 mm; range, 3-47 mm). Twelve of 16 (75%) patients were treated with lumpectomy and 4 of 16 (25%) with mastectomy. Eight of 16 (50%) patients received adjuvant hormonal therapy, and 2 of 16 (17%) received radiation. There were no local recurrences. PLCIS most commonly presented as fine pleomorphic calcifications on mammograms and had a high upgrade rate after CNB. CNB diagnosis of PLCIS requires surgical excision.

Deep Learning or Fundamental Descriptors?

HomeRadiologyVol. 287, No. 2 PreviousNext CommunicationsFree AccessLetters to the EditorDeep Learning or Fundamental Descriptors?Daniel B. Kopans Daniel B. Kopans Author AffiliationsDepartment of Radiology, Breast Imaging Division, Massachusetts General Hospital, Harvard Medical School, 15 Parkman St, Suite 219, Boston, MA 02114e-mail: [email protected]Daniel B. Kopans Published Online:Apr 18 2018https://doi.org/10.1148/radiol.2017173053MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked InEmail Editor:Having placed great hope on computer-aided detection (CAD) back in the 1990s only to be disappointed in its ultimate failure to add much in breast imaging, I am still hopeful, but have a healthy skepticism, about “deep learning,” which is simply CAD on steroids. The article by Dr Bahl and colleagues (1) in the March 2018 issue of Radiology is interesting, but by mixing too many “high-risk lesions” (HRLs) together in the evaluation, as well as not analyzing the reasons for the computer results, the real value of the analysis is in question. As Dr Bahl and colleagues point out, the categories of lesions lumped (sorry) together reduces the ability to understand the value of the test. The HRLs included are widely differing in their etiology and histology as well as their risk for developing breast cancer and “upgrade” with excision. For example, the risk of upgrade for atypical ductal hyperplasia is much higher than that for flat epithelial atypia or a benign papilloma. This is clear in a recent article by two of the same authors (probably including many of the same patient lesions) showing that the upgrade rate for flat epithelial atypia by itself was extremely low at less than 3% (2). I suspect that they grouped the various HRLs together so that they had enough cases to be able to “train” the computer algorithms and then test them.What is not provided is the fact that if a trained radiologist reviewed the same cases and was asked to guess the rate of upgrade for each lesion, she or he would have likely done as well as the computer for many of the lesions. For example, if you performed a core biopsy of segmentally distributed pleomorphic calcifications and the pathologic examination revealed “atypical ductal hyperplasia” you would be fairly certain that the upgrade would reveal at least ductal carcinoma in situ. If, on the other hand, you biopsied and removed five or six borderline round calcifications that produced “atypical ductal hyperplasia,” you would likely be correct if you bet that the surgical excision would not lead to an upgrade.It is worth investigating the use of more powerful computers, but we need to remain skeptical until the data show a clear advantage. I would urge that investigators not simply report results, but be required to analyze histopathologically distinct lesions, separately, and not group lesions together as in this analysis. I would also urge that they try to understand what the computer was adding to a trained radiologist. It may be that simply by reading “pleomorphic” and “segmental” a computer algorithm will call for excision, and “deep learning” is not as deep as we would hope!Disclosures of Conflicts of Interest: disclosed no relevant relationships.

Diagnostic value of breast imaging reporting and data system combined with wire-guided localization biopsy for breast microcalcifications in impalpable breast cancer

Objective To explore the diagnosis value of X-ray breast imaging reporting and data system (BI-RADS) combined with wire-guided localization biopsy for breast microcalcifications in impalpable breast cancer. Methods 192 palpation negative patients with 205 microcalcification lesions were detected by mammography. All lesions were classified according to BI-RADS descriptors for calcification and were categorized by the BI-RADS. The patients with BI-RADS category 4a and above underwent X-ray positioning guide wire-guided biopsy and pathological diagnosis. Results In 205 microcalcification lesions, 74 (36.1%) were malignant lesions, 131 (63.9%) were less than benign lesions. The positive predictive value of malignant breast lesions in clustered, segmental, regional linear branching calcifications were higher [83.3% (5/6), 100.0% (11/11), 100.0% (1/1)], followed by clustered, linear, segmental, regional pleomorphic calcifications [55.9% (38/68), 50.0% (1/2), 40.0% (8/20) and 33.3% (4/12), respectively]. The positive predictive values of malignant in linear branching calcifications and pleomorphic calcifications were significantly higher than those of coarse heterogeneous calcifications, amorphous or indistinct calcifications (χ2 values were 34.44, 51.87, 16.71, 29.86, all P < 0.05). The linear branching calcification had the highest possibility. The proportions of malignant lesions in four different types of glands were extremely dense 40.5% (30/74), heterogeneously dense39.2% (29/74), scattered areas of fibroglandular density 10.8% (8/74) and fat 9.5% (7/74), respectively. Conclusions BI-RADS categorization for breast microcalcification lesions can improve the detection rate of impalpable breast cancer. Linear branching calcification has higher predictive value for malignant lesions. Dense breast is the risk factors of breast cancer, which should be attached great importance. Key words: Mammography; Microcalcification; Biopsy; Palpation; Breast neoplasms

Correlating mammographic and pathologic findings in clinical decision support using natural language processing and data mining methods.

A key challenge to mining electronic health records for mammography research is the preponderance of unstructured narrative text, which strikingly limits usable output. The imaging characteristics of breast cancer subtypes have been described previously, but without standardization of parameters for data mining. The authors searched the enterprise-wide data warehouse at the Houston Methodist Hospital, the Methodist Environment for Translational Enhancement and Outcomes Research (METEOR), for patients with Breast Imaging Reporting and Data System (BI-RADS) category 5 mammogram readings performed between January 2006 and May 2015 and an available pathology report. The authors developed natural language processing (NLP) software algorithms to automatically extract mammographic and pathologic findings from free text mammogram and pathology reports. The correlation between mammographic imaging features and breast cancer subtype was analyzed using one-way analysis of variance and the Fisher exact test. The NLP algorithm was able to obtain key characteristics for 543 patients who met the inclusion criteria. Patients with estrogen receptor-positive tumors were more likely to have spiculated margins (P = .0008), and those with tumors that overexpressed human epidermal growth factor receptor 2 (HER2) were more likely to have heterogeneous and pleomorphic calcifications (P = .0078 and P = .0002, respectively). Mammographic imaging characteristics, obtained from an automated text search and the extraction of mammogram reports using NLP techniques, correlated with pathologic breast cancer subtype. The results of the current study validate previously reported trends assessed by manual data collection. Furthermore, NLP provides an automated means with which to scale up data extraction and analysis for clinical decision support. Cancer 2017;114-121. © 2016 American Cancer Society.

Lobular neoplasia diagnosed on breast Core biopsy: frequency of carcinoma on excision and implications for management.

The appropriate follow-up and treatment for patients with a core biopsy diagnosis of lobular neoplasia (atypical lobular hyperplasia or lobular carcinoma in situ) remains controversial. Several studies have attempted to address this issue, with recommendations ranging from close clinical follow-up or surveillance to mandatory surgical excision in all cases. We report the findings at our institution, where virtually every core needle biopsy diagnosis of lobular neoplasia results in follow-up excision. The goal of the study was to identify potential predictors of upgrade to a more significant lesion. We identified 76 patients over a 15-year period with a core biopsy diagnosis of pure lobular neoplasia and no other high-risk lesions. Subsequent surgical excision identified 10 cases (13%) that were upgraded to carcinoma. Upgrade diagnoses included invasive ductal carcinoma (n=1), invasive lobular carcinoma (n=4), ductal carcinoma in situ (n=3), and pleomorphic lobular carcinoma in situ (n=2). All 10 upgraded cases had imaging findings suspicious for malignancy including irregular masses, asymmetric densities, or pleomorphic calcifications. Of the 10 upgraded cases, 7 were diagnosed as lobular carcinoma in situ on core biopsy. The data support a role for radiologic-pathologic correlation in the evaluation of suspicious breast lesions and suggest that the extent of lobular neoplasia in core biopsy specimens may be an indicator of the likelihood of upgrade to carcinoma.

Molecular subtypes and imaging phenotypes of breast cancer.

During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

Abstract P4-01-01: A case series of the Milky Way sign: A diagnostic finding of ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IDC) on digital breast tomosynthesis (DBT)

Abstract Purpose: we have previously described the "Milky Way Sign", which manifests as microcalcifications overlying noncalcified band-like density, best seen in digital breast tomosynthesis (DBT), in a patient with ductal carcinoma in situ (DCIS). Here, we describe a series of patients with DCIS, IDC, and rarely, Atypical Ductal Hyperplasia (ADH) with this sign. Materials and Methods: we performed a systemic search of all stereotactic core biopsies for suspicious calcifications performed at our institution from April 15, 2014, when we first implemented DBT with synthesized 2D mammogram, to October 2, 2014, and identified all cases that were diagnosed as DCIS, IDC, or high-risk lesions (such as ADH, atypical lobular hyperplasia (ALH), and intraductal papilloma) on pathology. From 89 biopsied performed in 87 patients, a total of 13 cases of DCIS, IDC, or IDC with DCIS were identified in 12 patients. 17 cases of high-risk lesions were identified in 16 patients, including 10 ADH in 9 patients, 4 ALH, two intraductal papillomas, and one atypical columnar cell change. Results: Among the 30 cases of suspicious calcifications with a diagnosis of DCIS, IDC, or high-risk lesions, 37% demonstrated the Milky Way Sign (11/30), including 71% of DCIS cases (5/7), 60% of cases of IDC (3/5), 100% of DCIS/IDC (1/1), and 12% of high-risk lesions (2/17). Both high-risk lesions with the Milky Way sign were ADH from the same patient. Among the 11 cases with the Milky Way sign, the breast density at the site of calcifications is either scattered (6/11) or heterogeneously dense (5/11), whereas the density at 1 cm surrounding the calcifications is either fatty (8/11) or scattered (3/11). The breast is less dense surrounding the calcifications in all but one case. The calcifications seen in the Milky Way cases are predominantly fine pleomorphic calcifications except one case of fine linear and linear branching calcifications. The calcifications are grouped (6/11), linear (3/11), or segmental (2/11) in distribution. Five patients also had contrast-enhanced breast MRIs. Among them, three (one each with the diagnosis of DCIS, IDC or DCIS/IDC) had non-mass enhancement on breast MRI that correlated to the Milky Way sign seen on mammogram. The other two patients (one with DCIS and one with IDC) had post biopsy change instead of Non-mass enhancement were seen in the corresponding areas. Conclusion: The Milky Way sign, in the context of DBT, is a novel diagnostic sign for both DCIS and IDC. It may occasionally be seen in ADH cases as well. Features that often associate with the Milky Way sign include less dense tissue surrounding the calcifications, calcifications that are fine pleomorphic in morphology and grouped or linear in distribution. Preliminary results also suggest that the Milky Way sign may correspond to non-mass enhancement seen on contrast-enhanced breast MRI. Clinical Relevance Statement: We hope that the Milky Way sign will facilitate detection of both DCIS and IDC in the context of DBT. Citation Format: Allison K, Xu Y, Liu YI, Miyake KK, Downey JR, Lipson JA, Ikeda DM. A case series of the Milky Way sign: A diagnostic finding of ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IDC) on digital breast tomosynthesis (DBT). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-01-01.

Microcalcification-Associated Breast Cancer: Presentation, Successful First Excision, Long-Term Recurrence and Survival Rate

Introduction: In this study we evaluated mammographic, histological and immunohistochemical findings for microcalcification-associated breast cancer with regards to breast-conserving therapy, recurrence and survival rate. Patients and Methods: We retrospectively analyzed 99 consecutive, non-palpable and microcalcification-associated breast cancers (94 women) that were treated surgically between January 2002 and December 2003 at a national academic breast cancer center. Calcifications were classified according to the Breast Imaging Reporting and Data System (BI-RADS). Descriptors, surgical outcome and histological findings were assessed. Recurrences and survival rates were evaluated based on medical records, standardized patient questionnaires and/or contacting the physician. Results: 42 of the 99 lesions (42.4%) were invasive carcinomas, 57 (57.6%) were pure ductal carcinoma in situ (DCIS). 6 out of 99 (6.1%) lesions were triple negative, and 29 (29.3%) were HER2/neu positive. Successful first excision rate was 76/99 lesions (76.8%). Breast conservation was achieved in 73.7% (73/99). 10 women showed local recurrences without negatively impacting survival. The recurrences included round/punctate, amorphous, fine pleomorphic, and fine linear or fine-linear branching descriptors. The breast cancer-specific long-term survival rate was 91/94 (96.8%) for a mean follow-up of 81.4 months. The 3 patients who died due to breast carcinoma showed fine pleomorphic calcifications, and had nodal-positive invasive carcinoma at diagnosis. Conclusion: Microcalcification-associated breast cancers are frequently treated with breast-conserving therapy. Continuous clinical and mammographic follow-up is recommended for all descriptors.