Clinical Contribution of Next-Generation Sequencing Multigene Panel Testing for BRCA Negative High-Risk Patients With Breast Cancer.

BACKGROUND: Breast cancer is the most common malignancy in women and thought to be hereditary in 10% of patients. Recent next-generation sequencing studies have increased the detection of pathogenic or likely pathogenic (P/LP) variants in genes other than BRCA1/2 in patients with breast cancer. This study evaluated pathogenic variants, likely pathogenic variants, and variants of unknown significance in 18 hereditary cancer susceptibility genes in patients with BRCA1/2-negative breast cancer. PATIENTS AND METHODS: This retrospective study included 188 high-risk BRCA1/2-negative patients with breast cancer tested with a multigene cancer panel using next-generation sequencing. RESULTS: Among 188 proband cases, 18 variants in 21 patients (11.1%) were classified as P/LP in PALB2 (n = 6), CHEK2 (n = 5), MUTYH (n = 4), ATM (n = 3), TP53 (n = 2), BRIP1 (n = 1), and MSH2 (n = 1). Three novel P/LP variants were identified. An additional 28 variants were classified as variants of unknown significance and detected in 30 different patients (15.9%). CONCLUSION: This is one of the largest study from Turkey to investigate the mutation spectrum in non-BRCA hereditary breast cancer susceptibility genes. A multigene panel test increased the likelihood of identifying a molecular diagnosis in patients with BRCA 1/2-negative breast cancer at risk for a hereditary breast cancer syndrome. More studies are needed to enable the clinical interpretation of these P/LP variants in hereditary patients with breast cancer.

Imaging characteristics of male breast disease.

The purpose of the study was to describe the imaging findings of male breast disease. One hundred and sixty-four male patients, who underwent mammography and ultrasonography (US) between January 1999 and December 2008, were retrospectively evaluated. Seventy-five patients (46%) underwent biopsy, and 89 patients (54%) were diagnosed radiologically. The radiologic and pathologic diagnoses in 164 cases of this series were 13 cancers (8%), including one ipsilateral and one contralateral breast cancers, 147 cases of gynecomastia (90%), one fibroadenoma (0.6%), two cases of fibrocystic disease of the breast (1.2%), and one epidermoid inclusion cyst (0.6%). Three mammographic patterns were adequate to describe all 147 cases of gynecomastia in our series: 53 patients (36%) had nodular gynecomastia, 46 patients (31%) had dendritic gynecomastia, and 48 patients (33%) had diffuse gynecomastia. Gynecomastia was unilateral in 65% of cases (n=95), and bilateral in 35% of cases (n=52). On physical examination, two of the malignant lesions had no clinic features of malignancy (15%). On mammography, 11 of 13 malignant masses were demonstrated (85%). A mass with microcalcifications was seen on mammograms in one case (9%). The contours of the masses were irregular in nine cases (82%), well-circumscribed in two cases (18%). The location of the masses was retroareolar in seven cases (64%) and eccentric to the nipple in four cases (36%). The size of the masses varied between 0.5 cm and 5 cm (mean 2.4 cm). Nipple retraction was evident in five cases (45%), and skin thickening in four cases (36%). All of the malignant masses were demonstrated on ultrasound; however, one of them was seen retrospectively after mammography. All of the masses were hypoechoic and solid, the contours were well-defined and smooth in two masses (15%), and irregular in 11 masses (85%), and five masses (39%) had posterior prominent shadowing. Axillary lymphadenopathia was detected in two cases (15%). One patient had a previous contralateral breast cancer, and one had an ipsilateral. On mammography, breast cancer characteristically exhibits an irregular subareolar mass, nipple retraction, and skin ulceration or thickening, but sometimes breast cancer has a well-circumscribed contour and punctuated microcalcifications. Ultrasonography is essential and useful for further characterization and helpful for demonstrating lymphadenopathies of the axillary region.

Prolactin levels and examination with breast ultrasound or mammography.

OBJECTIVE: Stresses including surgery, exercise, nipple stimulation, and chest wall injury such as mechanical trauma, burns, surgery, herpes zoster of thoracic dermatomes, hypoglycaemia and acute myocardial infarction cause significant elevation of prolactin levels. The aim of the present study was to evaluate the changes in prolactin level during mammography and ultrasonographic examination. MATERIALS AND METHODS: Seventy-four premenopausal (mean age, 32.1+/-7.3 y) and 81 post-menopausal women (mean age, 48.3+/-8.9 y) were enrolled into the study. Premenopausal women were evaluated with ultrasound (Senographe 600 T [General Electric]) and post-menopausal women were examined with mammography (Mammomat 3000 [Siemens]). Blood samples for prolactin were taken prior to ultrasound or mammography and 15, 30 and 45 min after ultrasound or mammography. RESULTS: Mean baseline serum prolactin level was 7.2+/-0.9 ng/ml in premenopausal women before ultrasound. Mean baseline serum prolactin level was 5.4+/-0.4 ng/ml in post-menopausal women before mammography. It was found that there were no significant changes in prolactin levels after ultrasound or mammography (P > 0.05). Mean levels of baseline prolactin were statistically significant higher in premenopausal than in post-menopausal women (P = 0.03). CONCLUSION: Mammography and ultrasonographic examination have no acute effect on serum prolactin levels in either group. There is no need to wait before measuring the prolactin level after mammographic or ultrasonographic breast examination.

Management of microcalcifications developing at the lumpectomy bed after conservative surgery and radiation therapy.

OBJECTIVE: The purpose of our study was to determine whether the mammographic features (morphology and distribution) of new microcalcifications that develop in women treated with lumpectomy and radiation therapy can allow differentiation of benign changes from recurrent neoplasm. MATERIALS AND METHODS: A retrospective review of mammograms of 402 patients who were treated with conservative surgery and radiation therapy between 1987 and 2005 revealed 68 cases of new calcifications (in 66 patients) with follow-up (n = 55) or biopsy (n = 13) results. Analysis included the time between completion of radiation therapy and the appearance of calcifications; location of calcifications relative to the site of the original lesion; the morphology and distribution of calcifications; and changes in number, density, morphology, and rate of change of calcifications. RESULTS: The median rate of development after lumpectomy was 24 months (range, 6-84 months) for benign and 52 months (range, 20-90 months) for malignant calcifications. In 63 cases (93%), the new calcifications developed in the same quadrant as the primary tumor. None of the calcifications initially interpreted as BI-RADS category 2 (n = 40/68; 59%) and category 3 (n = 19/68; 28%) represented recurrent disease. Nine (13%) of 68 calcifications were initially classified as BI-RADS category 4 or 5; six (67%) of the nine were malignant and three (33%) were benign at biopsy. CONCLUSION: Newly occurring calcifications in the treated breast are usually benign, and they can be managed conservatively in many cases by using morphology and pattern of distribution as a guide.

Tubular carcinoma of the breast: mammographic, sonographic, clinical and pathologic findings.

PURPOSE: To determine and quantitate the radiological characteristics of tubular carcinoma of the breast, to report clinical and pathologic findings and to define findings at follow-up. MATERIALS AND METHODS: A retrospective review of records of 2872 women who received a diagnosis of breast carcinoma between January 1988 and January 2006 revealed 32 histopathologically proven pure tubular carcinoma of the breast. Analysis included history; findings at physical examination, mammography, and sonography (US) at the time of diagnosis and in postoperative follow-up and histopathological results. RESULTS: Fifty-nine percent of the patients (n=19) presented with a palpable mass. The mammographic findings were a mass in 23 (72%), a mass with microcalcifications in 2 (6%), asymmetric focal density in 1 (3%), architectural distortion in 1 (3%) and negative in 5 (16%) of the 32 patients. Most (96%) masses had spiculated margins. US depicted 30 masses in 29 patients, all of which were hypoechoic, mostly (n=27, 90%) with posterior acoustic shadowing. The cancer was clinically occult in 41% (n=13), mammographically occult in 16% (n=5), and sonographically occult in 6% (n=2) of the patients. Histologically, the tumor was multifocal in 3% (n=1) of the patients. Four (13%) patients developed contralateral breast carcinoma at follow-up. CONCLUSION: Tubular carcinoma has a variety of presentations, but it is mostly seen on mammography as a small spiculated mass, and on sonography as an irregular mass with posterior acoustic shadowing. Although tubular carcinoma is known as a well-differentiated tumor with excellent prognosis, the mammographic follow-up of the contralateral breast is important.

Tubulolobular carcinoma of the breast: clinical, mammographic and sonographic findings.

PURPOSE: To determine and quantitate radiologic characteristics of tubulolobular carcinoma of the breast and to report clinical and pathologic findings. MATERIALS AND METHODS: A retrospective review of records of 2872 women who received a diagnosis of breast carcinoma between January 1988 and January 2006 revealed 26 histopathologically proven tubulolobular carcinoma of the breast. Analysis included history; findings at physical examination, mammography, and sonography (US) at the time of diagnosis and in postoperative follow-up, and histopathological results. RESULTS: At physical examination, palpable mass was present in 85% (n=22) of the patients. The mammographic findings were mass in 17 (65%), asymmetric focal density in 2 (8%), architectural distortion in 2 (8%) and negative mammograms in 5 (19%) of the 26 patients. US depicted 25 masses in 24 patients, all of which were hypoechoic, with spiculated (n=13) or microlobulated (n=12) margins. The cancer was clinically occult in 12% (n=3), mammographically occult in 19% (n=5), and radiologically occult in 4% (n=1) of the patients. Histologically, the mean size of the tumor was 1.7cm and 18 (69%) patients were node negative. CONCLUSION: Tubulolobular carcinoma of the breast usually manifests clinically as a firm, immobile mass and mammographically as a spiculated or ill-defined, irregular, isodense mass without microcalcifications. Common findings on sonography include a homogeneously hypoechoic, spiculated or microlobulated mass with posterior acoustic shadowing or normal acoustic transmission. Tubulolobular carcinoma should be included in the differential diagnosis for breast masses with these imaging features.

Paget's disease of the breast: clinical, mammographic, sonographic and pathologic findings in 52 cases.

PURPOSE: To determine and quantitate radiologic characteristics of Paget's disease of the breast and to report clinical and pathologic findings. MATERIALS AND METHODS: A retrospective review of records of 2872 women who received a diagnosis of breast carcinoma between January 1988 and January 2006 revealed 52 histologically proved Paget's disease of the breast. Analysis included history, findings at physical examination, mammography and sonography (US) and histologic type of Paget's disease. RESULTS: At physical examination, palpable mass (n=33, 63%), nipple erythema-eczema-ulceration (n=17, 33%) and blood-stained nipple discharge (n=5, 10%) were noted. Among 17 patients who had clinically evident Paget's disease, the mammographic findings were isolated microcalcifications in 3 (18%), mass associated with microcalcifications in 5 (29%), mass in 2 (12%) and negative in 7 (41%) patients. In the 35 patients with clinically inevident Paget's disease, these mammographic findings were 43% (n=15), 34% (n=12), 20% (n=7) and 3% (n=1), respectively. US depicted 43 masses in 35 patients, all of which were lobulated or irregularly contoured, mostly (n=41, 95%) without posterior acoustic shadowing. The cancer was clinically occult in 10% (n=5), mammographically occult in 15% (n=8) and radiologically occult in 13% (n=7) of the 52 patients. Histologically, the tumor was multifocal and/or multicentric in 11 (21%) patients. CONCLUSION: The clinical features of Paget's disease are characteristic and should alert the clinician to the likelihood of an underlying carcinoma, which should be evaluated radiologically. However, as Paget's disease is primarily a clinical diagnosis and mammograms may be negative, screening programs without clinical examination may result with delay in diagnosis. As a result, both clinical and imaging findings are complementary and should be correlated to confirm or exclude a diagnosis of Paget's disease.

Male breast disease: clinical, mammographic, and ultrasonographic features.

PURPOSE: To describe and quantitate the radiological (mammographic and ultrasonographic) characteristics of male breast disease and to report the clinical and pathological findings. MATERIALS AND METHODS: Two-hundred-thirty-six male patients with different male breast diseases, diagnosed at our institution between January 1990 and July 2001, were retrospectively evaluated. The history, physical examination, mammographic and ultrasonographic findings were analyzed. RESULTS: The spectrum of the disease in 236 male patients were gynecomastia (n=206), primary breast carcinoma (n=14), fat necrosis (n=5), lipoma (n=3), subareolar abscess (n=2), epidermal inclusion cyst (n=1), sebaceous cyst (n=1), hematoma (n=1), myeloma (n=1), and metastatic carcinoma (n=2). The distribution of patterns of gynecomastia were; 34% (n=71) nodular, 35% (n=73) dendritic and 31% (n=62) diffuse glandular. Gynecomastia was unilateral in 55% (n=113) and bilateral in 45% (n=93) of the patients. Male breast cancer presented as a mass without microcalcifications in 86% (n=12) and with microcalcifications in 7% (n=1) of patients. The mass was obscured by gynecomastia, partially in two, totally in one patient. The location of the mass was retroareolar in 46% (n=6) and eccentric to the nipple in 54% (n=7) of patients. On ultrasonography (US), the contours were well-circumscribed in 20% (n=3) and irregular in 80% (n=12) of the masses. CONCLUSION: Male breast has a wide spectrum of diseases, some of which have characteristic radiological appearances that can be correlated with their pathologic diagnosis. In the evaluation of the male breast, mammography and US are essential and should be performed along with physical examination.

Sclerosing adenosis: mammographic and ultrasonographic findings with clinical and histopathological correlation.

OBJECTIVE: To evaluate the mammographic and ultrasonographic findings of sclerosing adenosis, a relatively uncommon entity which may sometimes mimic carcinoma. MATERIALS AND METHODS: A retrospective review of the records of 33,700 women, who have undergone mammographic examination at our institution between January 1985 and July 2001 revealed 43 histopathologically proven sclerosing adenosis. The history, physical examination, mammographic and ultrasonographic findings were analyzed in all patients. In 30 patients, the nonpalpable lesions were preoperatively localized by the needle-hookwire system under the guidance of mammography (n=22) or ultrasonography (US) (n=8). Radiological features were correlated with histopathological findings. RESULTS: The age of the patients varied between 32 and 55 years (mean, 43.7 years). Only two patients had a family history of breast cancer. In six patients, the presenting complaint was mastalgia. A palpable mass was present in 13 cases. The mammographic findings were; microcalcifications in 24 (55.8%) (clustered in 22, diffuse in two), mass in five (11.6%), asymmetric focal density in three (6.9%), and focal architectural distortion in three (6.9%) patients. Four of the masses were irregularly contoured, while one was well-circumscribed. On US, focal acoustic shadowing without a mass configuration was noted in the three patients who showed asymmetrical focal density on mammography. In eight patients, who showed normal mammograms, a solid mass was detected on US. Two masses had discrete well-circumscribed oval or lobulated contours, while six showed microlobulation and irregularity. In one case, the irregularly contoured mass had marked posterior acoustic shadowing. Two of the three patients, who had focal architectural distortion on mammograms, had an irregularly contoured solid mass, while the third presented as focal acoustic shadowing without a mass configuration. CONCLUSION: Sclerosing adenosis mostly presents as a nonpalpable lesion with different mammographic and sonographic appearances. The most common finding is microcalcifications on mammograms. Awareness of the possible imaging features will enable us to consider sclerosing adenosis in the differential diagnosis. The radiological features may sometimes mimic malignancy, so histopathologic examination is mandatory for definite diagnosis.

The role of breast MRI in planning the surgical treatment of breast cancer.

PURPOSE: To determine the frequency by which breast magnetic resonance imaging (MRI) provides information that influences the surgical management of patients with breast cancer. MATERIALS AND METHODS: From August 2006 to December 2008, contrast-enhanced bilateral breast MRI was performed on 68 patients, all of whom exhibited highly suspicious imaging findings (BI-RADS category 4 or 5). Patients were grouped according to their histopathological diagnosis and type of breast parenchyma. All of the enrolled patients were believed to be candidates for breast conservation on the basis of physical examination, mammography, and ultrasonography. The patients were reevaluated with the MRI examination as to whether they were still candidates for breast conservation therapy. RESULTS: The MRI findings changed the previous management plans in 19.1% of the 68 patients. With respect to the surgical approach, no statistically significant difference was observed between the histopathology groups (P = 0.403). In terms of the breast parenchymal pattern, however, surgical planning was changed in 53.8% of the patients who exhibited a dense pattern, which was significantly different from the rates of the other groups (P = 0.006). The sensitivity, specificity, positive predictive value, and negative predictive value of the MRI for additional malignant lesion detection and identification were 85%, 98%, 92%, and 96%, respectively. The agreement test revealed 86% agreement (very good) between the additional findings observed on the MRI and the histopathological results. CONCLUSION: If breast-conserving surgery is planned, an MRI should be performed in all women with suspected breast cancer, especially those exhibiting dense or heterogeneously dense breast parenchyma, for which the sensitivity of both ultrasonography and mammography is low.

Mammographic features of the sternalis muscle.

PURPOSE: To evaluate the mammographic findings of the sternalis muscle and discuss appropriate diagnostic approaches. MATERIALS AND METHODS: Ten years of records from our mammography unit were retrospectively examined for the presence of the sternalis muscle. This variant was seen in 10 women out of the 52,930 examined, and the mammograms of these patients were reevaluated. The size, shape and contours of the muscle were reviewed on the craniocaudal (CC) and mediolateral oblique (MLO) views. Yearly mammograms were assessed to evaluate follow-up changes. Extra examinations were reviewed, including ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI). RESULTS: The prevalence of the sternalis muscle was 0.018%. Its contours were well-defined, irregular or spiculated, and the diameter ranged from 3-4 mm to 15 mm. The shape of the muscle varied from slightly bulging to round or triangular. The muscle was detected on MLO projections in three patients as an inferior soft tissue density at the posterior edge of the breast, continuous with the pectoralis muscle. Distinct pulling of the breast led to variations in the appearance of the muscle on yearly mammograms. US examinations were normal in all patients. CT and MRI showed the muscle clearly. CONCLUSION: The appearance of the sternalis muscle may vary on CC views. It may also be detected on MLO projections. The ability to visualize the muscle depends on proper positioning. Knowledge of its detectability on mammograms will prevent the misdiagnosis of a mass and prevent further unnecessary investigations.

[Temporal bone CT and MRI in cochlear implant candidates]. / Kohlear implant adaylarinda temporal kemik BT ve MRG.

PURPOSE: Hearing can be restored by cochlear implantation in patients with sensorineural hearing loss, who have a normal seventh cranial nerve. The aim of imaging in cochlear implant candidates is to determine the etiology of the hearing loss, congenital malformations and variations that may cause difficulty during the operation, patency of the cochlea and the presence of the seventh, cranial nerve. The aim of this study is to review the literature and to discuss the imaging findings that may affect the type and success of the operation. MATERIALS AND METHODS: 33 cochlear implant candidates, who underwent high resolution computed tomography, were included in the study. High resolution fast spin echo T2 weighted and constructive interference in steady state sequences were performed in 23 patients with a 1.5 Tesla magnetic resonance unit. RESULTS: Computed tomography and magnetic resonance imaging were normal in 16 patients. Unilateral or bilateral labyrinthine ossification was detected in 4 patients. Variations of the temporal bone, congenital malformations, sequelae of chronic otitis and trauma were detected in 13 patients. Cochlear implantation was performed in 5 patients. Operative difficulty, complications and postoperative outcome were noted in these 5 patients. CONCLUSION: High resolution computed tomography and magnetic resonance images obtained by high resolution T2 weighted fast spin echo sequence and constructive interference in steady state sequence help the surgeon in planning the operation and predict potential complications in cochlear implant candidates.

Inflammatory breast carcinoma: mammographic, ultrasonographic, clinical, and pathologic findings in 142 cases.

PURPOSE: To determine and quantitate radiologic characteristics of inflammatory breast carcinoma and to report clinical and pathologic findings. MATERIALS AND METHODS: A retrospective review of records of 2,733 women who received a diagnosis of breast carcinoma between January 1988 and May 2000 revealed 142 histologically proved inflammatory carcinomas. Analysis included history; findings at physical examination, mammography, and ultrasonography (US); and histologic type of inflammatory carcinoma. RESULTS: At physical examination, skin changes (n = 115, 81%) were the most common findings. A palpable mass was noted in 62% (n = 88), with axillary lymph node involvement in 68% (n = 96) of the carcinomas. Mammography revealed findings in carcinomas: skin thickening, 84% (n = 119); diffusely increased density, 37% (n = 53); trabecular thickening, 81% (n = 115); mass, 16% (n = 23); asymmetric focal density, 61% (n = 87); microcalcifications, 56% (n = 80); nipple retraction, 43% (n = 61); and axillary lymphadenopathy, 24% (n = 34). US showed changes in carcinomas: skin thickening, 96% (n = 136); parenchymal echogenicity changes, 73% (n = 104); dilated lymphatic channels, 68% (n = 96); solid mass, 80% (n = 114); pectoral muscle invasion, 10% (n = 14); focal areas of parenchymal acoustic shadowing, 37% (n = 52); and axillary lymphadenopathy, 73% (n = 104). CONCLUSION: Presence of isolated inflammatory signs is sufficient to suggest inflammatory breast carcinoma clinically. Inflammatory breast carcinoma has a mammographic pattern of inflammatory changes, such as skin thickening and stromal coarsening and/or diffusely increased breast density with or without an associated mass and/or malignant-type microcalcifications. US is helpful not only in depiction of masses masked by the edema pattern but also in demonstration of skin and pectoral muscle invasion and axillary involvement.

Metaplastic carcinoma of the breast: clinical, mammographic, and sonographic findings with histopathologic correlation.

OBJECTIVE: The purpose of this study was to investigate the mammographic and sonographic findings of metaplastic carcinoma of the breast and to correlate the radiologic features with clinical and histopathologic findings. CONCLUSION: Metaplastic carcinoma of the breast often manifests as a rapidly growing, palpable mass that has high density on mammography and may be microlobulated on sonography. Complex echogenicity with solid and cystic components may be seen sonographically and is related to necrosis and cystic degeneration found histopathologically. Although it is a rare breast malignancy and these features are not unique, metaplastic carcinoma should be included in the differential diagnosis for breast masses with these imaging features.

Neuroendocrine differentiated breast carcinoma: imaging features correlated with clinical and histopathological findings.

The aim of this study was to describe the imaging features of neuroendocrine differentiated breast carcinoma (NEDBC) and to correlate the radiological findings with the clinical and histopathological findings. A retrospective review of the mammograms of 1845 histopathologically proven breast cancer cases revealed five NEDBC. The clinical, imaging, and histopathological findings were analyzed. On mammography, a high-density mass was seen in all patients. The shape of the mass was round in 4 and irregular in 1 patient. The margins were spiculated in 2, indistinct in 1, microlobulated in 1, and partially obscured in 1 patient. On sonography, 4 patients had homogeneously hypoechoic masses with normal sound transmission. In 1 patient the mass was heterogeneously hypoechoic with mild posterior acoustic enhancement. The margins were microlobulated in 2, irregular in 2, and well-circumscribed in 1 patient. Neuroendocrine differentiated breast carcinoma should be included in the differential diagnosis of mammographically dense, round masses with predominantly spiculated or lobulated margins. Sonographically, they mostly present as irregular or microlobulated, homogeneously hypoechoic masses with normal sound transmission.

Invasive micropapillary carcinoma of the breast: clinical, mammographic, and sonographic findings with histopathologic correlation.

OBJECTIVE: The purpose of our study was to investigate the imaging features of invasive micropapillary carcinoma of the breast, which is a recently described, rare variant of infiltrating ductal carcinoma. CONCLUSION: Invasive micropapillary carcinoma of the breast usually manifests as a firm, immobile mass. Findings on mammography are of a spiculated, irregular or round, high density mass with or without associated microcalcifications. On sonography, the common findings are of a homogeneously hypoechoic, irregular or microlobulated mass with posterior acoustic shadowing or normal sound transmission. Axillary lymph nodes are frequently involved. Although these findings are not specific and may be seen with other breast malignancies, invasive micropapillary carcinoma should be included in the differential diagnosis for breast masses with these imaging features. Also, radiologic findings may help in the histopathologic differentiation of cases that are difficult to diagnose, such as metastatic tumors.

Breast metastasis from low-grade endometrial stromal sarcoma after a 17-year period.

Metastases to the breast are rare with an incidence of 0.5-3% of patients with extramammary carcinomas. We report a unique case of an endometrial stromal sarcoma metastasizing to the breast after a 17-year-period. Mammographic and ultrasonographic findings with histopathological correlation are described.