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Benign proliferative breast diseases are well recognized in young females. Benign biphasic proliferation of epithelial and myoepithelial cells has been observed, among which adeno-myoepithelial adenosis is one of the rare morphologies published in the literature with the tendency to recur and poses a risk for low-grade malignant transformation. Here, we report a case of a young female who had a history of recurrent breast lump mimicking phyllodes tumor and eventually diagnosed as adeno-myoepithelial adenosis on histopathological examination. Benign proliferative breast diseases are well recognized in young females. Benign biphasic proliferation of epithelial and myoepithelial cells has been observed, among which adeno-myoepithelial adenosis is one of the rare morphologies published in the literature with the tendency to recur and poses a risk for low-grade malignant transformation. Here, we report a case of a young female who had a history of recurrent breast lump mimicking phyllodes tumor and eventually diagnosed as adeno-myoepithelial adenosis on histopathological examination.

Fibrocystic disease of breast is characterized by lumpiness and discomfort. Our 48-year-old perimenopausal patient had a painless progressively enlarging non-tender lump in her right breast since 1 year. On physical examination a 10 × 8 cm firm non-tender lump was observed occupying almost the whole breast, whose surface was nodular though not fixed. The operative specimen appeared like a honeycomb with multiple cavities filled with yellowish firm material typical of tuberculosis. Surprisingly, histology found neither this nor malignancy. Radical breast excision is never warranted except if the latter is confirmed.

Background: Distinguishing benign breast diseases (BBDs) from malignant breast diseases is a worrisome entity and should also have knowledge of the pattern of occurrence of the disorders in their geographical location. This research aimed to study the clinical and histopathological pattern of BBD in Indian patients., Materials and Methods: The study was conducted on 153 specimens from lumpectomy, core needle biopsy, and mastectomy. Data regarding patients' age, sex, presenting complaints, duration of the complaints, and history of menstrual cycles and lactation were collected from the biopsy requisition forms and case papers. The tissue bits were processed and stained with hematoxylin and eosin, and a histopathological examination was performed., Results: Most of the patients in the present study were females (n = 151, 98.7%). The mean age of the patients was 30.45 years. Most of the BBD cases (n = 118, 77.14%) were benign, of which fibroadenoma (101 cases) accounted for 66%. Majority of the lesions were in the upper outer quadrant (39.22%). Of the 153 cases, 94 cases of fibroadenoma, one case of breast abscess, nine cases of fibrocystic change, four cases of phyllodes, three cases of lipoma, and one case of gynecomastia diagnosed clinically correlated well with histopathology (n = 112, 73%)., Conclusion: BBDs are mostly seen in female patients in the age group of 21-30 years. Fibroadenoma is the most common BBD. Clinical assessment followed by histopathological examination provided an accurate diagnosis. The clinical diagnosis correlated well with histopathology., Competing Interests: None

Background: Fibroadenomas are the most common benign breast lesions in women. They present as a unilateral mass and can rapidly enlarge in size through hormonal changes. Fibroadenomas could be classified as small or giant, and as simple or complex. They are classified as 'giant' when the size exceeds 5 cm and/or weight 500 gram; and as 'complex' if one of the following characteristics is present: cysts with a size >3 mm, epithelial calcifications, sclerosing adenosis and papillary apocrine metaplasia. Giant fibroadenomas can cause compression of surrounding breast tissue or breast asymmetry, requiring surgical excision in order to preserve a normal breast shape., Case: A 26-year-old pregnant woman was referred with a palpable mass of her right breast. The mass rapidly increased in size to a diameter of 13 cm during the second trimester of her pregnancy. A tru-cut biopsy confirmed a fibroadenoma. The rapid growth and compression of normal breast tissues indicated a lumpectomy during her pregnancy. The mass was easily excised without any consequences for the pregnancy. Pathological examination showed a complex giant fibroadenoma., Conclusion: A unique case of a pregnant woman with rapid progression of a fibroadenoma that met the criteria of a complex and giant fibroadenoma, was presented. This case emphasizes the importance of timely surgical intervention, even during pregnancy, to prevent permanent breast tissue damage.

The presented case describes the difficulties of diagnosis of the breast microglandular adenosis (MGA), taken by clinicians for a malignant process due to the nature of growth and large size. Criteria for histological and immunohistochemical diagnosis and differentiation of MGA with malignant neoplasms, in particular, with tubular breast carcinoma, are presented. Taking into account the rarity of the pathology and the absence of described cases in the Russian-language literature, the observation is of interest to pathologists and clinicians.

Classification of breast tumors has been evolving in the last decade. Uncommon types of breast neoplasms have been increasingly recognized. While the pathogenesis of a subset of these tumors remains to be ascertained, integration of state-of-the-art knowledge from molecular advancements and clinical practice has enhanced our understanding of these diseases, be they unique to the breast or more frequently seen in other organs. Furthermore, these lesions may have diverse clinical outcomes despite of similar histopathologic and immunophenotypic characteristics or even molecular alterations, thus warranting different clinical management. Therefore, recognizing their salient histologic features and judicious use of ancillary studies is essential to reach the correct diagnosis in the pursuit of personalized medicine. This review provides an update on selective special types of breast neoplasms, with emphasis on their salient clinicopathologic features, diagnostic pitfalls, controversies, and recent molecular genetic advances., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Microglandular adenosis (MGA)-related lesions, including atypical MGA (AMGA) and carcinoma involving MGA (C-MGA), are characterized by epithelial atypia, negative hormone receptors, and HER2 status, and can mimic invasive triple negative breast cancer (TNBC) in core needle biopsies (CNB) resulting in selection for treatment with neoadjuvant chemotherapy (NAC). We identified 12 cases of AMGA and/or C-MGA in post-NAC excision specimens (EXC) and analyzed their morphologic and immunohistochemical (IHC) features. All CNBs were initially diagnosed as containing TNBC. Upon re-review, TNBC was confirmed in nine cases. In three CNBs AMGA and/or C-MGA had been interpreted as TNBC. AMGA was initially recognized in only one case but AMGA and/or C-MGA were present in an additional nine CNBs. At EXC, no residual TNBC was present in 5 of 9 EXCs and all 12 cases showed residual AMGA and/or C-MGA. Similar to conventional MGA, AMGA, and C-MGA were positive for S-100, laminin and collagen IV and negative for calponin and p63. Following NAC, these lesions retained their typical staining pattern despite acquiring treatment-related morphologic alterations, most notably of which were areas of single cell growth pattern seen in eight EXCs. This study is the first to report the effects of NAC on AMGA and C-MGA. Our data showed no response of the AMGA and/or C-MGA following NAC in contrast to the high response rate of conventional TNBC. In particular, the infiltrative single cell pattern of post-NAC MGA-related lesions closely mimicked residual TNBC. The persistence of AMGA and C-MGA following NAC supports the notion that these lesions are distinct from conventional TNBC. Our findings also highlight the challenges in recognizing AMGA and C-MGA in CNBs which may lead to unwarranted treatment with NAC in the absence of conventional TNBC.

Competing Interests: The authors declare no conflicts of interest.

Proliferative epithelial lesions are risk factors for breast cancer. They are a heterogeneous group of lesions in which the presence of atypia is related to varying degrees of risk. They should be considered in the differential diagnosis with benign lesions, in situ ductal carcinoma and infiltrating carcinoma. An accurate histopathological diagnosis is important in choosing the best therapeutic option, including vacuum assisted biopsy and surgery. We revise diagnostic criteria and the differential diagnosis of usual ductal hyperplasia, radial scar and complex sclerosing lesions, distinct types of adenosis, papillary lesions, atypical ductal hyperplasia, flat epithelial atypia and lobular neoplasia in situ. Furthermore, we summarize the degree of risk associated with the different conditions and management possibilities., (Copyright © 2020 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Sclerosing adenosis (SA) is a benign lesion with complicated pathological components and could mimic breast carcinoma in both clinical palpation and medical imaging findings. The present study was conducted to assess the value of ultrasound (US) characteristics in diagnosing SA and their differentiation from breast carcinoma., Methods: We retrospectively reviewed the medical records of 305 women (347 lesions) with invasive ductal carcinoma (IDC) and 54 women with single SA lesion, who had breast excision between April 2016 and July 2018. US BI-RADS atlas and elastography were applied and their associated characteristics were compared between SA and IDC., Results: The mean age of SA was younger than that of IDC (43.6 ± 7.4 vs 53.2 ± 10.3, P < 0.001). Compared to IDC, SA had more frequency of parallel orientation (94.44% vs 71.76%, P < 0.001) and circumscribed margin (48.15% vs 4.90%, P < 0.001), less frequency of irregular shape (64.81% vs 95.97%, P < 0.001), hypoechoic echotexture (88.89% vs 98.27%, P = 0.002), calcification (12.96% vs 55.04%, P < 0.001), and posterior acoustic changes (3.70% vs 53.89%, P < 0.001) or associated features (architectural distortion, 3.70% vs 59.65%, P < 0.001; duct changes, 18.52% vs 63.40%, P < 0.001). Vascularity absence was more common in SA compared to IDC (35.19% vs 6.63%, P < 0.001). And the elasticity score was lower in SA (2.38 ± 0.60 vs 3.91 ± 0.81, P < 0.001). After adjusting for age, we found spiculated margin, posterior shadowing, calcification, architectural distortion, and vascularity could independently identify the differences between these two entities. After involving elasticity score, the calcification and vascularity could still be independent indicators for differential diagnosis., Conclusion: Understanding SA imaging features will enable radiologists to communicate results to the referring physician consistently, which could benefit a reliable assessment and specific management recommendations. A systematic evaluation of the US BI-RADS atlas together with breast elastography may be a powerful tool to identify SA and differentiate it from breast cancer.

Breast cancer is the most diagnosed cancer among women around the world. The development of computer-aided diagnosis tools is essential to help pathologists to accurately interpret and discriminate between malignant and benign tumors. This paper proposes the development of an automated proliferative breast lesion diagnosis based on machine-learning algorithms. We used Tabu search to select the most significant features. The evaluation of the feature is based on the dependency degree of each attribute in the rough set. The categorization of reduced features was built using five machine-learning algorithms. The proposed models were applied to the BIDMC-MGH and Wisconsin Diagnostic Breast Cancer datasets. The performance measures of the used models were evaluated owing to five criteria. The top performing models were AdaBoost and logistic regression. Comparisons with others works prove the efficiency of the proposed method for superior diagnosis of breast cancer against the reviewed classification techniques., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Habib Dhahri et al.)

Introduction: Sclerosing adenosis is a form of adenosis characterized by lobulocentric architecture, glandular and stromal proliferation in which the stromal component compresses and distorts the glandular structures. Atypical epithelial proliferations such as atypical lobular hyperplasia, lobular carcinoma in situ, and ductal carcinoma in situ may accompany areas of sclerosing adenosis. We present a case of ductal carcinoma in situ and sclerosing adenosis with metastatic carcinoma on sentinel lymph node., Case Description: A 40-year-old woman presented with a palpable mass in her left breast. Radiologic studies showed a lesion suggesting malignancy in the left breast and atypical lymph node in the left axillary region. Left lumpectomy and sentinel lymph node biopsy was performed. Histopathologic examination revealed lobulocentric lesions with glandular proliferation and hyalinizing stroma in between. Foci of high-grade cribriform and solid type ductal carcinoma in situ were observed. Sentinel lymph node biopsy showed micrometastasis in one lymph node section. Based on these findings, the patient was diagnosed with high-grade ductal carcinoma in situ with sclerosing adenosis. However, the presence of micrometastasis in the lymph node suggested occult invasion that we were not able to detect., Conclusion: Ductal carcinoma in situ with sclerosing adenosis can mimic invasive carcinoma both radiologically and histologically. It should be kept in mind that there may be occult invasive carcinoma in patients with ductal carcinoma in situ whether the lesion is accompanied by sclerosing adenosis or not. Multiple sections and immunohistochemical studies can be of help.

Delayed terminal duct lobular unit (TDLU) involution is associated with elevated mammographic breast density (MD). Both are independent breast cancer risk factors among women with benign breast disease (BBD). Prior digital analyses of normal breast tissues revealed that epithelial nuclear density (END) and TDLU involution are inversely correlated. Accordingly, we examined associations of END, TDLU involution, and MD in BBD clinical biopsies. This study included digitized images of 262 representative image-guided hematoxylin and eosin-stained biopsies from 224 women diagnosed with BBD, enrolled within the cross-sectional BREAST-Stamp project that were visually assessed for TDLU involution (TDLU count/100 mm 2 , median TDLU span and median acini count per TDLU). A digital algorithm estimated nuclei count per unit epithelial area, or END. Single X-ray absorptiometry of prebiopsy ipsilateral craniocaudal digital mammograms measured global and localized MD surrounding the biopsy region. Adjusted ordinal logistic regression models assessed relationships between tertiles of TDLU and END measures. Analysis of covariance examined mean differences in MD across END tertiles. TDLU measures were positively associated with increasing END tertiles [TDLU count/100 mm 2 , OR T3vsT1 : 3.42, 95% confidence interval (CI), 1.87-6.28; acini count/TDLU T3vsT1 , OR: 2.40, 95% CI, 1.39-4.15]. END was significantly associated with localized, but not, global MD. Relationships were most apparent among patients with nonproliferative BBD. These findings suggest that quantitative END reflects different but complementary information to the histologic information captured by visual TDLU and radiologic MD measures and merits continued evaluation in assessing cellularity of breast parenchyma to understand the etiology of BBD., (©2019 American Association for Cancer Research.)

Microglandular adenosis (MGA) of the breast is exceedingly rare, with only a few case reports and series published to date. Previous studies have elegantly demonstrated the progression of benign MGA to atypical MGA to MGA-in situ carcinoma to invasive carcinoma and therefore suggest MGA as a possible non-obligate precursor lesion to a subset of breast carcinomas. Immunohistochemically, MGA is negative for estrogen receptor (ER), progesterone receptor (PR), and HER2-neu oncoprotein expression, and carcinomas arising in the setting of MGA are often reported to be triple negative. In this article, we present a unique case of an ER+/PR+/HER2- invasive carcinoma associated with MGA and atypical MGA. Our case highlights the diagnostic pitfall of MGA and suggests that MGA is a heterogeneous group of lesions with potential for either luminal-type or basal-type differentiation during progression to breast carcinoma.

The exact mechanism of endometriosis is unknown. The recommendation system (RS) based on item similarities of machine learning has never been applied to the relationship between diseases. The study aim was to identify diseases associated with endometriosis by applying RS based on item similarities to insurance data in South Korea. Women aged 15 to 45 years extracted from the Korean Health Insurance Review & Assessment Service National Inpatient Sample (HIRA-NIS) 2009-2015. We used the RS model to extract diseases that were correlated with an endometriosis diagnosis. Among women aged 15 to 45 years, endometriosis was defined as a diagnostic code of N80.x and a concurrent treatment code. A control group was defined as women who did not have the N80.x code. Benign breast diseases, cystitis, and non-toxic goitre were extracted by the RS. A total of 1,730,562 women were selected as the control group, and 11,273 women were selected as the endometriosis group. In logistic regression analysis adjusted for age per 5 years, data year, and socioeconomic status, benign neoplasm of breast (odds ratio (OR): 2.58; 95% confidence interval (CI): 1.90-3.50), other cystitis (OR: 2.63; 95% CI: 1.56-4.44), and non-toxic single thyroid nodule (OR: 1.62; 95% CI: 1.14-2.32) were statistically significant. Endometriosis was associated with benign breast disease, cystitis, and non-toxic goitre.

Background: Cystic hypersecretory carcinoma is a rare subtype of breast cancer. It is a member of cystic hypersecretory lesions, which include a series of pathological disease lineages: cystic hypersecretory hyperplasia (CHH), CHH with atypia, cystic hypersecretory carcinoma (CHC) and invasive CHC. It was found that most cystic hypersecretion lesions were in situ carcinoma, and only 19 cases of invasive cystic hypersecretion carcinoma were reported., Case Presentation: We are reporting a case of a 63-year-old female who had a lump in her left breast for 3 years. A modified radical mastectomy was done and morphological diagnosis of invasive CHC with axillary node metastasis was made., Conclusions: Owing to a smaller number of reported cases, little is known about the biological behavior, prognosis and molecular study of cystic hypersecretion lesions. Therefore, more cases with follow-up data are needed to reveal the biological behavior of this rare tumor.

- The aim of the study was to assess the role of the estradiol and progesterone relationship during the late luteal phase and the occurrence of fibrocystic breast disease (FBD). The concentration of estradiol/progesterone was measured in the group of women with FBD as study group (n=50) and control group of women without FBD (n=40). All women had regular ovulation cycles. Blood samples for estradiol (E2), progesterone (P) and prolactin determination were obtained in the morning at 8 am on days 21 and 24 of menstrual cycle. Significant mastalgia and mastodynia history in women with FBD was obtained with yes or no questionnaire. FBD diagnosis was confirmed with ultrasound (size and number of simple cysts). In the control group, a reduced E2/P ratio was noticed from day 21 to day 24 of the cycle (from 14.8±11.5 pg/mL to 9.1±6.1 pg/mL; p<0.05), which was not recorded in the group of women with FBD (study group). Even the slightest disturbance of the E2/P ratio may contribute to the occurrence of FBD with clinical manifestations of mastalgia and mastodynia.

Some fibroepithelial lesions (FEL) of the breast are difficult to classify as cellular fibroadenoma (CFA) or benign phyllodes tumor (BPT) due to overlapping histologic features. This indeterminate group is histologically characterized by prominent stromal cellularity, mild atypia, and mitotic activity. The local recurrence potential of cellular FEL (CFEL) has been insufficiently studied. The objective of this study was to evaluate the histologic features, characterize the long-term follow-up and recurrence rate of CFEL, and compare this data with the recurrence rate of definitive BPT. Ninety CFEL that were <4 cm were recovered from the benign breast disease cohort. The control group comprised of 10 randomly selected patients with BPT. Cases were classified based on a combination of mitotic activity, intracanalicular growth, stromal atypia, stromal prominence, and fat infiltration. None of the CFEL was widely excised. Of the 90 CFEL cases, there were 22 BPT-like, 35 CFA, and 33 indeterminate. The mean age of the patients was 40.1 years. The mean tumor size was 2.4 cm. All patients had at least two years of follow-up (median 27). None of the patients with BPT-like CFEL showed ipsilateral recurrence. Five of the 35 patients with CFA had recurrent ipsilateral CFA. This occurred within 1 to 11 years after the initial diagnosis. One of 33 patients with indeterminate type had a recurrent ipsilateral lesion five years after the initial diagnosis with histologic features of CFA. None of the patients in control group had any recurrence. In conclusion, as a group, CFEL have a low proclivity for recurrence, even when enucleated with close or positive margins. The presence of histologic features of BPT did not correlate with an increased potential for recurrence., (Copyright © 2018. Published by Elsevier Inc.)

Multiphoton microscopy has attracted increasing attention and investigations in the field of breast cancer, based on two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG). However, the incidence of breast benign diseases is about 5 to 10 times higher than breast cancer; up to 30% of women suffer from breast benign diseases and require treatment at some time in their lives. Thus, in this study, MPM was applied to image fibroadenoma and fibrocystic lesion, which are two of the most common breast benign diseases. The results show that MPM has the capability to identify the microstructure of lobule and stroma in normal breast tissue, the interaction of compressed ducts with surrounding collagen fiber in fibroadenoma, and the architecture of cysts filled with cystic fluid in fibrocystic disease. These findings indicate that, with integration of MPM into currently accepted clinical imaging system, it has the potential to make a real-time diagnosis of breast benign diseases in vivo, as well as breast cancer.

Crystallizing galactocele is a very rare entity which yields a viscous, chalky material on Fine Needle Aspiration Cytology (FNAC). FNAC is used both for diagnosis as well as treatment of this condition. We present here a case of 26 years old lactating female who presented with swelling in the right breast for 8 months. The swelling was firm, discrete, non-tender and mobile involving the upper inner quadrant of right breast. A diagnosis of benign breast disease, possibly fibroadenoma was made clinically. FNAC of the lesion yielded thick, milky and chalky material. Cytological smears showed numerous semitransparent crystals of varying size and shapes with angulated borders in a background of granular and amorphous debris along with frothy appearing micelles. These crystals show positive birefringence. Based on clinical history of lactation and typical cytological findings, a diagnosis of crystallizing galactocele was made. We report this case because of rarity of this condition and to the best of our knowledge, till date only five cases of crystallizing galactocele has been reported in medical literature.

Aim: We aimed to compare the tru-cut biopsy and postoperative pathology results of breast lesions with suspicion of malignancy. Furthermore we aimed to determine the efficacy, specificity and sensitivity of the tru-cut biopsy., Methodology: 140 patients who were operated due to breast mass following tru-cut biopsy were retrospectively evaluated. Patients' demographic characteristics, imaging findings, biopsy and histopathology results were compared., Results: The mean age of 140 patients was 51.3 (Ranged: 17-83 ages). Malignancy was statistically more common in patients older than 45 years old. According to tru-cut biopsy results 103 (73.5%) lesions were malign, 32 (23%) benign, and 5 (3,5%) suspicious. Histopathological evaluation established 113 (% 80.7) malign and 27 (19,3%) benign lesions. Tru-cut biopsy had a sensitivity, specifity, positive predictive value, negative predictive value and diagnostic accuracy of 93.5%, 95.4%, 99%, 75% and 80%, respectively in this study., Conclusions: Our findings have confirmed that tru-cut biopsy is an accurate, reliable and as effective as open surgery for breast cancer diagnosis. The higher success rates may achieve by accordance of triple assessment which includes clinical, radiological and pathological evaluation with tru-cut biopsy., Key Words: Breast cancer, Core needle biopsy, Preoperative evaluation, Tru-cut biops.

We report the case of Ms. A.A, a primiparous woman aged 21 years presenting (4 months after delivery) with an increase in left breast volume occurred 1 week after delivery associated with fever. The patient was put on amoxicillin, protected by suspending breast-feeding for several weeks without improvement. Clinical examination showed febrile patient with a temperature of 39°, an increase in left breast volume, inflammatory signs especially at the level of internal quadrants (A). Palpation showed a painful, hot collection adherent to the skin, measuring 16 cm, at the level of the internal quadrants, invading the external quadrants, without axillary adenopathies, suggesting breast abscess. Ultrasound (B) showed voluminous solidocystic predominantly liquid echogenic mass with thick walls and buds up to 46 mm, classified as ACR4. Puncture biopsy collected grayish green liquid, sent for bacteriological examination; antibiotic therapy with quinolones was started. Follow up of patient, after 3 days, showed reduction of the inflammatory signs and bacteriological examination of the liquid found no germ. After 15 days of antibiotic therapy, the inflammatory signs had disappeared and the volume of the mass had reduced enough, hence the indication for cystectomy. Cystectomy with simple enucleation was performed (C); surprisingly, the histological examination showed cystic fibroadenoma (D).

Apocrine change in the breast is an extremely common finding. In most cases, the benign or malignant nature of the lesion is easily recognized. Apocrine adenosis is used to describe sclerosing adenosis with apocrine change. The term apocrine atypia is used when there is significant cytologic atypia in apocrine cells, characterized by a 3-fold nuclear enlargement, prominent/multiple nucleoli, and hyperchromasia. Atypical apocrine adenosis is diagnosed when apocrine adenosis and apocrine atypia are superimposed. However, there are no definite criteria to distinguish atypical apocrine adenosis from apocrine ductal carcinoma in situ. Immunohistochemical markers can be confounding and may lead to erroneous diagnoses. Atypical apocrine features in sclerosing lesions may be misinterpreted as invasive carcinoma if the underlying lesion is not recognized. In the absence of definite features of malignancy, the diagnosis of apocrine ductal carcinoma in situ may be extremely difficult. In the present article, we review atypical apocrine adenosis focusing on diagnostic challenges and their implications on clinical management.

Apocrine adenosis (AA) and atypical apocrine adenosis (AAA) are uncommon findings in breast biopsies that may be misinterpreted as carcinoma. The clinical significance and risk implications of AAA diagnosed on core biopsy are not well established. This study aimed to determine the frequency of carcinoma on follow-up excision in patients with a diagnosis of AA or AAA on core biopsy. Forty-one breast core biopsies of AA (n=29) and AAA (n=12) were identified during a study period of 12 years. Of the 41 core biopsies with AA or AAA, 10 biopsies showed coexisting/concurrent atypical hyperplasia or carcinoma. In the absence of coexisting/concurrent atypical hyperplasia or carcinoma in core biopsy, none of the follow-up excision specimens after a diagnosis of AA or AAA showed ductal carcinoma in situ or invasive carcinoma. In conclusion, AA or AAA by itself is an uncommon core biopsy diagnosis that may not require surgical excision., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Though fibroadenoma is the most common benign tumor of the breast and is more common under the age of 30, giant fibroadenoma is rare representing less than 4% of all fibroadenomas. A 12 years old girl presented with rapidly enlarging well-circumscribed firm, non-tender mass in right breast for 2 months which was painless and with no history of trauma, nipple discharge, fever, anorexia, weight loss or axillary lymphadenopathy. There was no family history of neoplasms. Clinically, the lump was about 12 × 12 cm and not fixed to skin or underlying structures with the absence of nipple retraction or discharge. There was no axillary lymphadenopathy. Fine needle aspiration cytology showed a benign proliferative breast disease. Total excision of mass was done preserving nipple and areola having weight of 535 gm with histopathological features suggestive of giant fibroadenoma. Giant fibroadenoma is a benign breast disease that may mimic rare malignant lesion. So, breast and nipple conserving surgery should always be performed irrespective of size of tumor as in this case.

Background: Accurate clinical diagnosis of fibroadenoma in young females is desirable because of the possibility of nonoperative treatment for those desiring it., Objectives: To determine the accuracy of the clinical diagnosis of fibroadenoma in patients aged ≤ 25 years., Patients and Methods: A prospective study of all patients with breast disease presenting to the breast clinic was conducted from January 2004 to December 2008., Results: During the study period, 145 patients aged ≤25 years presented with breast lumps. In this group, a clinical diagnosis of fibroadenoma was made in 100 (69.0%), fibrocystic disease in 32 (22.1%), breast cancer in 4 (0.03%) patients, the remaining were benign lesions. Excision biopsy was done for 81 (55.9%) patients. Of these 81 patients, only 62 (76.5%) returned with histology report. The histological diagnosis was fibroadenoma in 45 (72.5%) patients with a mean age of 21.4 years. Their ages range from 18 to 25 years. The histological diagnosis was fibrocystic disease in 9 (14.5%) and malignant phyllodes in 1 (1.6%) patient. The remaining 7 (11.3%) patients had other types of benign lesions. For fibroadenoma, true positive cases were 42, false positive 7 and false negative 3, and true negative 10. Therefore, the sensitivity of clinical diagnosis of fibroadenoma was 93.3%, while specificity was 58.8%., Conclusion: The sensitivity of clinical diagnosis of fibroadenoma in patients aged ≤25 years was good, though specificity is low.

Radial scar (RS) has been recognized as a risk factor for developing breast cancer, and excision is recommended for patients with RS identified on core needle biopsy (CNB). However, recent literatures suggest that the increased risk may be caused by concurrent proliferative lesions on the biopsy, rather than radial scar itself. In this study, we investigated the follow-up excision (FUE) results for patients with RS on CNB with no history of a prior or a concurrent breast cancer or atypical proliferative lesions (APLs). A total of 113 RS cases including 32 cases with APLs or carcinoma and 81 cases without APLs on CNB were included in this study. Forty cases (49%) without APLs had FUE. No significant difference in radiologic and clinical findings was identified between cases with FUEs and cases without FUEs. Of the 40 cases with FUE, 9 cases (22.5%) were upgraded including 3 atypical ductal hyperplasias, 4 lobular neoplasias, 1 flat epithelial atypia, and 1 atypical apocrine adenosis. However, no case was upgraded to invasive carcinoma or ductal carcinoma in situ. All cases with mammotome CNBs were not upgraded. Our data suggest that conservative follow-up with imaging rather than surgical excisions may be more appropriate for patients with only RS on biopsy, especially for patients with mammotome CNBs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To compare the diagnostic accuracy of touch imprint cytology and frozen section in the diagnosis of malignant breast lumps keeping histopathological diagnosis as the gold standard., Methods: The cross-sectional validation study was conducted at Foundation University Medical College, Islamabad, from February 2011 to February 2012, and comprised patients undergoing mastectomy/lumpectomy. The specimens were collected from the operation theatre of Fauji Foundation Hospital, Rawalpindi. After tissue fixation, three representative sections were processed and the slides were stained with haematoxylin and eosin stain. The person analysing touch imprint cytology slides was blinded to the frozen section and histopathological slide results and vice-versa. Data was analysed using SPSS 17., Results: Out of 76 patients with a mean age of 49±15.14 years, 61(80%) were diagnosed with malignant breast diseases. The sensitivity, specificity, positive predictive value, negative predictive value and true positives of touch imprint cytology were 96.72%, 100%, 100%, 88.24% and 96.72% respectively. The corresponding values of the frozen section were 100% each. The diagnostic accuracy calculated for touch imprints and frozen section was 97.37% and 100% respectively., Conclusions: The diagnostic accuracy of frozen section was better than touch imprint cytology in rapid intra-operative diagnosis. However, touch imprints can safely be used as an alternative intra-operative procedure to ensure satisfactory results.

Objective: Breast cysts are common, often discovered incidentally or subsequently to pain or palpable mass. The purpose of these recommendations is to describe the sonographic findings for classifying breast cystic lesions, to analyze the value and contribution of various imaging techniques and sampling and to provide a management strategy., Materials and Methods: Literature review conducted by a small group and then reviewed and validated by the group designated by the Collège national des gynécologues et obstétriciens français (CNGOF) to make recommendations for clinical practice for benign breast lesions., Results: Breast cysts are classified in 3 categories: simple cysts, complicated cysts and complex cysts. For simple cysts, after ultrasound, no further imaging is necessary, cytology is to consider only as analgesic. For complicated cysts, a control at 4-6 months is recommended; the use of cytology depends on the context (familial risk, difficulty of follow-up). In case of complex cyst, sampling by cytology or biopsy is recommended. More assessments of other imaging tests are reported., Conclusion: The sonographic characterization is essential for management of breast cyst., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

The purpose of this study was to verify the utility of second-look ultrasonography (US) in evaluating nonmass enhancement (NME) lesions detected on breast magnetic resonance imaging (MRI) by analysing its correlation and imaging features. From July 2008 to June 2012, 102 consecutive MRI-detected NME lesions were subsequently evaluated with US. Lesions were evaluated according to the established Breast Imaging Reporting and Data System (BI-RADS) lexicon. The correlation between MRI-detected NME lesion characteristics, lesion size, histopathological findings and features at second-look US were analysed. Second-look US identified 44/102 (43%) of the NME lesions revealed by MRI. A US correlate was seen in 34/45 (76%) malignant lesions compared with 10/57 (18%) benign lesions (p < 0.0001). The likelihood of malignancy was significantly higher for NME lesions with a US correlate than lesions without: 34/44 (77%) versus 11/58 (19%) (p < 0.0001). The malignancy of the 44 (43%) MRI-detected NME lesions with a US correlate was significantly associated with US lesion margins and BI-RADS categories (p = 0.001 and 0.002 respectively). Second-look US of MRI-detected NME lesions is useful for decision-making as part of the diagnostic workup. Familiarity with the US features associated with malignancy improves the utility of US in the workup of these NME abnormalities., (© 2015 Wiley Periodicals, Inc.)

Background: Monocentric cohorts suggested that radiation-induced CD8 T-lymphocyte apoptosis (RILA) can predict late toxicity after curative intent radiotherapy (RT). We assessed the role of RILA as a predictor of breast fibrosis (bf +) after adjuvant breast RT in a prospective multicenter trial., Methods: A total of 502 breast-cancer patients (pts) treated by conservative surgery and adjuvant RT were recruited at ten centers. RILA was assessed before RT by flow cytometry. Impact of RILA on bf + (primary endpoint) or relapse was assessed using a competing risk method. Receiver-operator characteristic (ROC) curve analyses were also performed in intention to treat. This study is registered with ClinicalTrials.gov, number NCT00893035 and final analyses are presented here., Findings: Four hundred and fifty-six pts (90.8%) were included in the final analysis. One hundred and eight pts (23.7%) received whole breast and node irradiation. A boost dose of 10-16 Gy was delivered in 449 pts (98.5%). Adjuvant hormonotherapy was administered to 349 pts (76.5%). With a median follow-up of 38.6 months, grade ≥ 2 bf + was observed in 64 pts (14%). A decreased incidence of grade ≥ 2 bf + was observed for increasing values of RILA (p = 0.012). No grade 3 bf + was observed for patients with RILA ≥ 12%. The area under the ROC curve was 0.62. For cut-off values of RILA ≥ 20% and < 12%, sensitivity and specificity were 80% and 34%, 56% and 67%, respectively. Negative predictive value for grade ≥ 2 bf + was equal to 91% for RILA ≥ 20% and positive predictive value was equal to 22% for RILA < 12% where the overall prevalence of grade ≥ 2 bf + was estimated at 14%. A significant decrease in the risk of grade ≥ 2 bf + was found if patients had no adjuvant hormonotherapy (sHR = 0.31, p = 0.007) and presented a RILA ≥ 12% (sHR = 0.45, p = 0.002)., Interpretation: RILA significantly predicts the risk of breast fibrosis. This study validates the use of RILA as a rapid screening test before RT delivery and will change definitely our daily clinical practice in radiation oncology., Funding: The French National Cancer Institute (INCa) through the "Program Hospitalier de Recherche Clinique (PHRC)".

The purpose of this study is to examine the breast cancer risk overall among women with simple fibroadenoma or complex fibroadenoma and to examine the association of complex fibroadenoma with breast cancer through stratification of other breast cancer risks. The study included women aged 18-85 years from the Mayo Clinic Benign Breast Disease Cohort who underwent excisional breast biopsy from 1967 through 1991. Within this cohort, women who had fibroadenoma were compared to women who did not have fibroadenoma. Breast cancer risk (observed versus expected) across fibroadenoma levels was assessed through standardized incidence ratios (SIRs) by using age- and calendar-stratified incidence rates from the Iowa Surveillance, Epidemiology, and End Results registry. Analyses were performed overall, within subgroups of involution status, with other demographic characteristics (age, year of biopsy, indication for biopsy, and family history), and with histologic characteristics, including overall impression [nonproliferative disease, proliferative disease without atypia (PDWA), or atypical hyperplasia]. Fibroadenoma was identified in 2136 women [noncomplex, 1835 (85.9%); complex, 301 (14.1%)]. SIR for noncomplex fibroadenoma was 1.49 (95% CI 1.26-1.74); for complex fibroadenoma, it was 2.27 (95% CI 1.63-3.10) (test for heterogeneity in SIR, P = .02). However, women with complex fibroadenoma were more likely to have other, concomitant high-risk histologic characteristics (e.g., incomplete involution and PDWA). In analyses stratified by involution status and PDWA, complex fibroadenoma was not an independent risk marker for breast cancer. Complex fibroadenoma does not confer increased breast cancer risk beyond other established histologic characteristics.

We report four cases of adenoma of the nipple, a rare benign epithelial benign tumor occurring under the nipple and areola. Clinically, erosion findings of the nipple require discrimination from Paget's disease. In addition, a mass found in the nipple warrants discrimination from ductal carcinoma. Two cases underwent aspiration biopsy cytology and the other underwent tumor imprint cytology, respectively, revealing a large number of epithelial cell populations in the necrotic background material. These large cell clusters had a papillary or sheet structure and exhibited decreased cell cohesiveness at the cluster part. In addition, small clusters and solitary epithelial cells were also present. Furthermore, a two-cell pattern comprising both duct epithelial and myoepithelial cells was observed in the cell clusters. Two other cases underwent nipple brush cytology, revealing a few small papillary clusters with isolated epithelial cells in the hemorrhagic background. The clusters appeared as benign duct proliferative lesions such as papilloma, papillomatosis, and adenosis. An accurate diagnosis warrants the recognition of regular nuclei with bland chromatin and myoepithelial cells and the identification of the lesion location., (© 2015 Wiley Periodicals, Inc.)

Mammographic studies have documented a number of architectural changes occurring around breast biopsy sites. These changes are well described in the radiological literature, but similar studies do not appear to be present in the pathology literature. We reviewed 100 consecutive mastectomy specimens from women who had undergone prior core needle or excisional biopsies. Multiple sections of the needle tract or excisional biopsy site were reviewed and morphologic findings reported. Hemorrhage, fat necrosis, granulation tissue, necrosis of fibrous tissue, and epithelium along with fibrosis and foreign body type giant cells were common features. Less frequent were areas of synovial metaplasia, atypical spindle cells, atypical duct-like structures, single atypical cells, squamous metaplasia, proliferations of abnormal blood vessels, and hemosiderin deposition. The misinterpretation of atypical spindle cells, single atypical cells, atypical duct-like structures and squamous metaplasia could result in the false-positive diagnosis of residual malignancy. Careful attention to the reactive nature of these changes aids in their distinction from carcinoma., (© 2015 Wiley Periodicals, Inc.)

Objective: This study aimed to discuss the differences of malignant findings in breast lesions diagnosed with Breast Imaging-Reporting and Data System for Ultrasonography (BI-RADS-US) category 4C to determine which malignant findings are more important., Materials and Methods: A total of 159 cases of breast lesions diagnosed with BI-RADS-US category 4C were analyzed retrospectively. All patients got pathological results (81 cases of benign; 78 cases of breast cancer). Two doctors scanned and diagnosed the patients, with another doctor recording ultrasonographic findings retrospectively. The differences were compared by means of the Chi-square (χ2) test., Results: Phyllodes and acoustic attenuation had statistical differences in the comparison of breast lesions (p < 0.05). Irregular shape, indistinct boundary, poorly-defined margin, penetrating or tortuous surrounding vessels, RI ≥ 0.7, and microcalcification had no statistical differences in the comparison of benign and malignant breast lesions., Conclusions: Phyllodes and acoustic attenuation are the more important malignant ultrasonographic findings of breast cancer. The malignant ultrasonographic findings are not unique for breast cancer.

The aim - to determine the role of single nucleotide polymorphism PvuII of the gene EsRα as an indicator of proliferative activity in benign breast dysplasia (BBD) and its effect on receptor status of breast tissue for expression EsRα. Defined genotype PvuII polymorphism EsRα, the expression level in remote EsRα among patients with BBD. For these patients, and morphological parameters samples are divided into groups and compared. It is shown that there is a connection between the PvuII-gene polymorphism EsRα with the degree of proliferation (χ2=43,142; p<0,0001) and the expression level EsRα (χ2=51,041; p<0,0001) in breast tissue at BBD in patients with homozygous (C/C) polymorphism PvuІІ of the gene EsRα. Addition to the standard morphological study justified immunohistochemical study with the definition of the expression level of EsRα due to the fact that the increase in the level of expression associated with an increase in cell proliferation in tumors with BBD (χ2=7,370; p=0,007). An algorithm for the diagnosis of proliferative forms BBD.

Diabetic mastopathy is an uncommon, benign breast condition seen in type 1 and less frequently type 2 diabetic patients. It is characterized by a dense fibrous stromal proliferation of breast tissue, clinically mimicking cancerous masses, thus leading to worrisome investigations. Clinicians and pathologists must distinguish this benign condition from malignant causes because surgery may worsen the case as these lesions tend to recur more extensively at the site of resection. We present the case of a young woman with type 1 diabetes with typical diabetic mastopathy and summarize the literature to increase awareness of this troublesome but benign disorder., (Copyright © 2014 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

A 37-year-old female was indicated to have a non-mass lesion in her left breast on ultrasonography (US) and visited our outpatient clinic. Mammography showed no findings of masses or microcalcification. Dynamic magnetic resonance imaging (MRI) showed a segmental enhanced lesion consisting of nodular and ring enhancement. A US-assisted vacuumed needle biopsy was performed, and the histological findings revealed sclerosing adenosis and apocrine metaplasia. After 1 year of follow-up, the MRI findings suggested both a benign lesion and ductal carcinoma in situ, and surgical excision was performed. We used a new device to evaluate the surgical margin on MRI. The non-mass lesion was excised according to the device-guided margin under local anesthesia. The histological findings revealed the features of mastopathy. Following excision, MRI showed no residual non-mass lesions, and the shape of the patient's left breast was maintained.

IgG4-related sclerosing disease was first identified and defined in the twenty-first century. In this pathology, the serum IgG4 level increases and IgG4-positive plasma cells and lymphocytes infiltrate organs such as the pancreas, salivary glands, lacrimal glands, kidneys, and the retroperitoneum. Presented in this report is a case of IgG4-related sclerosing disease that occurred in the breast and was treated successfully with steroid therapy. A 51-year-old woman presented with bilaterally swollen eyelids and an elevated serum IgG4 concentration. Screening CT revealed a lesion in her right breast but no other lesions. Mammography, ultrasonography, and MRI could not rule out malignancy, so a core needle biopsy was performed. Histologically, the lesion was composed of papilloma with fibrosis, adenosis, and severe lymphoplasmacytic infiltration. No malignant features were observed. Many plasma cells within the lesion were immunohistochemically positive for IgG4. IgG4-related sclerosing disease of the breast was diagnosed, and steroid therapy was initiated. During 4 weeks of steroid treatment the lesion became smaller in size, and at 7-months follow-up the lesion showed no new growth. Since steroid therapy is effective for this disease, IgG4-related sclerosing disease should be considered in the differential diagnosis of breast lesions in order to avoid unnecessary surgery.

Fibroadenomatoid hyperplasia of the breast (FAHB) is a rare benign breast lesion and its clinical features are similar to fibroadenoma and fibrocystic changes. FAHB has been previously termed sclerosing lobular hyperplasia, fibroadenomatosis, fibroadenomatoid change, or fibroadenomatoid mastopathy. Typically, FAHB is derived from stroma and epithelia. The pathologic characteristics of FAHB are microfocal lobulocentric proliferation of stroma accompanied by epithelial and myoepithelial components resembling similar histological changes, as found in fibroadenoma, apocrine hyperplasia, intraductal hyperplasia, and lobular hyperplasia. FAHB could be present as a localized or diffused pattern in pathology. Most cases show no well-circumscribed mass lesions and no apparent capsules; it is usually identified as an incidental finding in other benign lesions or in random sampling in cancerous breast tissues. FAHB is categorized as a benign proliferative breast disease and it has previously been reported; however, the authors believe this study may be the first case with two giant masses reported. Fiber adenoma hyperplasia is a rare cystic hyperplasia of breast pathology and its ultrasonographic manifestations are easily confused with breast cancer. Comparative MRI ultrasound analysis will help make the differential diagnosis., (© 2014 S. Karger AG, Basel.)

Microglandular adenosis is a rare glandular lesion of the breast, which can mimic well-differentiated invasive carcinoma, and is characterized by a haphazard proliferation of uniform small round glands with open lumina and lacking a myoepithelial cell layer. This lesion has a rather unique immunohistochemical profile characterized by expression of cytokeratins and S-100, and lack of estrogen receptor (ER) and progesterone receptor (PR). The role of microglandular adenosis as a potential precursor of invasive breast cancer has long been a matter of controversy; however, recent molecular analyses have demonstrated that these lesions are heterogeneous at the genetic level, and that at least a subset of microglandular adenosis are clonal and display gene copy number alterations. Importantly, the pattern of genetic aberrations found in microglandular adenosis differs from that of other non-obligate precursors of ER-positive breast cancer. Carcinomas arising in microglandular adenosis are mostly of triple-negative phenotype (i.e. lack of ER, PR and HER2) and express S100, similar to microglandular adenosis. Genetic alterations found in microglandular adenosis have been shown to be similar to those found in synchronous invasive carcinomas. Here we review the clinical, morphological, and molecular features of microglandular adenosis, with an emphasis on its role as a non-obligate precursor of triple-negative breast cancer, and discuss areas for future research endeavors to clarify the clinical and biological significance of these fascinating lesions.

The information from radiologists was utilized in the proposed computer-aided diagnosis (CAD) for breast tumor classification. The ultrasound (US) database used in this study contained 166 benign and 78 malignant masses. For each mass, six quantitative feature sets were used to describe the radiologists' grading of six Breast Imaging Reporting and Data System (BI-RADS) categories including shape, orientation, margins, lesion boundary, echo pattern, and posterior acoustic features on breast US. The descriptive abilities were between 76% and 82% and the predicted descriptors were then used for tumor classification. Using receiver operating characteristic curve for evaluation, the area under curve (AUC) of the proposed CAD was slightly better than that of a conventional CAD based on the combination of all quantitative features (0.96 vs. 0.93, p=0.18). The partial AUC over 90% sensitivity of the proposed CAD was significantly better than that of the conventional CAD (0.90 vs. 0.76, p<0.05). In conclusion, the computer-aided analysis with qualitative information from radiologists showed a promising result for breast tumor classification., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The technology of building an expert system for diagnosing malignant nature of invasive tumors of the mammary gland based on a set of quantitative features of the cell nuclei has been developed. Its peculiarity was the presence of weighting coefficients in all the features. Quantitative features were obtained by transforming the initial morphometric data with the help of simple (evaluation of mean values and building of histograms) and complex (regression analysis) mathematical operations. The expert system consisted of one-dimensional X-matrix used for investigations and two-dimensional standard S-matrix. The X-matrix elements were assigned for filling with the quantitative features of the studied sample with a nonestablished diagnosis. The S-matrix elements contained threshold values of quantitative features from the system of diagnostic decision criteria for malignant forms of diseases and their weighting coefficients. Threshold values of nuclear features (larger or smaller) were determined taking into account the range of their values in the groups of malignant and benign pathology. Significance of quantitative features in diagnosing diseases has been assessed. The presence of weighting coefficients allowed diagnosing malignant and benign pathology in a quantitative form by the diagnostic index value. Diagnostic index was calculated by the sum of weighting coefficients of features of the studied sample, which fell within the range of system of the S-matrix diagnostic decision criteria. Clinical trials revealed high efficiency of the developed approach while diagnosis of breast cancer invasive forms at a preoperative stage., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Non-cancerous diseases of the breast have assumed increasing importance because of the public awareness of breast cancer. These benign diseases are a recognized important risk factor for later breast cancer which can develop in either breast. The risk estimate of these benign breast diseases has not been well established in sub Saharan Africa. Women with benign proliferative or atypical breast lesions have a two- fold risk of developing breast cancer in western populations. The purpose of this study therefore was to determine the prevalence of proliferative disease ( BPBD) with and without atypia among Ugandan Black women., Methods: A cross-sectional descriptive study conducted at Mulago Hospital Breast Clinic between January 2012 and June 2012; 208 women aged 12 years and above with palpable breast lumps were screened. Fine needle aspiration biopsies were taken for cytological examination., Results: Of the 208 women with benign breast lumps screened, 195 were recruited in the study. The prevalence of BPBD was 18% (35/195). BPBD with atypia was 5.6% (11/195). The mean age and body mass index (BMI) were 28.4 years and 23.26 kg/m2 respectively. The commonest lesions were fibroadenomas for 57%, (111/195), and fibrocystic change were 21% (40/195). Most BPBD with atypia lesions were in the fibrocystic category., Conclusions: Benign proliferative breast diseases are common, found mostly among premenopausal women. A significant proportion of BPBD had atypical proliferation. An accurate breast cancer risk estimate study for BPBD is recommended.

Background: Diabetic mastopathy is a rare condition, which is clinically not easily to differentiate from breast cancer., Case Description: A 32-year-old woman, with a long-standing history of insulin-dependent diabetes mellitus presented at the breast outpatient clinic with a firm palpable, painless mass in her right breast. Mammography and ultrasound examination showed, respectively, slight asymmetry with dense glandular tissue and a hypoechoic area with posterior shadowing. MR mammography showed no suspicious abnormalities. Histopathological examination revealed fibrous tissue with lymphocytic inflammation. The combination of clinical presentation, history of diabetes mellitus, and histological findings led to a diagnosis of diabetic mastopathy., Conclusion: A palpable breast abnormality in a woman with diabetes mellitus can be caused by diabetic mastopathy. Knowledge of this condition by the disciplines involved can prevent over-diagnosis and unnecessary interventions.