The benign mimickers of carcinoma on breast MRI

The similarity between benign and malignant pathologies on magnetic resonance imaging (MRI) and a wide-ranging variability of the lesions from benign proliferative changes to invasive breast carcinoma cause a lower and wide-ranging specificity of breast MRI relative to its surpass sensitivity. A wide range of tissue components such as the skin, the adipose tissue, vascular and neural tissues, connective tissues, glandular tissues, ducts, and muscle tissues are found here all together. This pictorial review was aimed at deliberating benign mimickers of breast carcinoma on MRI and trying to call attention to the overlapping and distinctive features

A Case of an Invasive Lobular Carcinoma with Extracellular Mucin: Radio-Pathological Correlation

A case of 77-year-old female with an invasive lobular carcinoma with extracellular mucin is presented. She felt palpable mass in her left breast. Then, she came to our hospital for further examination. Mammography of right in full view revealed architectural distortion in left upper portion. And ultrasonography demonstrated low-echoic mass about 2 cm in diameter and invasion of the fat tissue was observed. Hence, malignancy was suspected and magnetic resonance imaging (MRI) was performed. MRI findings showed irregular shaped and margined mass with small T2-high-signal intensity. These findings suggested invasive carcinoma with mucin. Because the cancer lesion was not large, partial mastectomy was performed. Interestingly, pathological diagnosis was invasive lobular carcinoma with extracellular mucin. Extracellular mucinous lesion was concordant with small T2-high-signal intensity. This type of carcinoma was previously reported only in three cases, and rare but important, because the treatment and prognosis might change by histological subtypes. We suggest one of the MRI special features of our case is not only irregular shaped and margined mass but also small T2-high-signal intensity. These MR findings might be one of the valuable findings for the diagnosis and differentiation between this type of carcinoma from other tumors

A study of diagnostic accuracy in benign breast disease with special reference to recent diagnostic tools

INTRODUCTION: Benign breast disease is a common disorder. It is atleast 10 times more common than breast cancer in hospital clinics. The histological changes of benign breast disease are in reality part of the spectrum of changes that occur in the life time of breast tissue. These histological charges do not proceed as a smooth continuum; the individual elements often occur simultaneously and can give rise to anatomical (palpable) abnormalities such as nodularity (or) cystic change, which may initiate referral to hospital, but are not disease in the true sense of word. However an increasing interest in histology of the normal human breast with studies of autopsy and biopsy material, is providing a background which allowed a better understanding of what is normal and what is abnormal, thus helping to correct the tendency to overrate the malignant potential of benign Breast disease. The term benign breast disease encompasses a wide range of clinical and pathological entities. Up to 30% of women may suffer from a benign breast disorder requiring treatment at sometime in their life. In general population on examination of breast grossly evident cystic changes were found in 20% but histological evidence of cystic changes were found in 59% of women(2). In patients attending breast clinic for various breast problems, 40% of patients were found to be having fibrocystic changes and about 7% having fibroadenoma. Hence benign breast disease requires imaging studies for evaluations. Mammography and ultrasound are the most useful tools for this purpose. Mammography is used as a primary tool in benign breast disease and also as a screening tool to detect early breast cancer. Ultrasound is used to differentiate cystic lesions from solid lesions and particularly useful in dense breast seen in young women. Both of these tools are also useful in localizing to lesion and in guiding biopsy. Hence both ultrasound and Mammography are the pillars on which the edifice of this study is built. AIM OF THE STUDY 1. To compare the utility of mammography and sonography in the diagnosis of benign breast diseases. 2. To study the utility of 3D Ultrasound in the evaluation of Benign Breast lesions. MATERIALS AND METHODS: Female patients in the pre, peri and post menopausal age groups with benign breast disorders who underwent breast ultrasound and mammography from September 2003 were included in this study. Patients with features of malignancy were excluded from the study. Standard nomenclature for characterization of the lesions on mammography and ultrasound were used. Subsequently all the patients underwent histopathological examinations of lesions in the form of excision biopsy or true cut biopsy. Patients in whom histopathology could not be done due to practical reasons Fine Needle Aspiration Cytology was done. In correlation with the clinical diagnosis and FNAC final diagnosis was arrived and patients were treated accordingly. RESULTS: Sixty nine patients were included in this study. All patients underwent ultrasound of the breast and mammography. All the 69 patients underwent FNAC. Histopathological examinations were done for 49 patients. In Our study out of 69 patients histopathological confirmation was possible in 49 patients. Of the remaining patients, 10 patients were not willing for surgery because of the small size of the lesions and for cosmetic objections and another 10 patients did not require biopsy and were conservatively treated. Out of the 49 patients in whom histopathological confirmation and FNAC were done, result of the FNAC did not correlate with the HPE in 5 patients. Because of difficulty in finding out location of the lesion in 3 patients FNAC was negative. In 2 cases of phylloids tumour FNAC was unable to diagnose correctly. All other cases FNAC was consistent with histopathological examination. Out of the 49 patients Ultrasound showed positive diagnosis for 46 patients with a sensitivity of 93.9%. Whereas mammography was positive was only in 33 patients with a sensitivity of 67.3%. Statistical test of proportion showed that Z value is 3.3 with the corresponding p value less than 0.001. Hence it is concluded that ultrasound produces statistically significant higher sensitivity compared to mammography. We compared sensitivity of ultrasound and mammography keeping gold standard as histopathological examination. It is found that ultrasound in general shows the sensitivity of 92.8% (positive results for 64 patients out of 69 examined), whereas mammography showed the sensitivity of 66.7% (Positive results for 46 out of 69 patients examined). This difference is statistically significant because the z value is 3.8. Hence the corresponding p value is less than 0.001. CONCLUSION: Mammography is superior to ultrasound in the detection of Microcalcification. Sonography is complementary to mammography in patients with palpable abnormalities of the breast. Sonography’s superiority over mammography is in its ability to show the presence and extent of lesions that are obscured by Dense breast tissue and in characterising palpable lesions that are mammographically not visible or occult. Ultrasonogram is most helpful in characterising cystic Lesions and studying the internal component of these lesions. Three dimensional ultrasound is helpful in additionally Characterising most of the lesions that cause greater degrees Of architectural distortion. Compression pattern proves to be more specific for benign Lesions. Three dimensional ultrasound is not very specific for Lesions causing lesser degrees of architectural distortion

Diagnostic Challenge of Invasive Lobular Carcinoma of the Breast: What Is the News? Breast Magnetic Resonance Imaging and Emerging Role of Contrast-Enhanced Spectral Mammography

Invasive lobular carcinoma is the second most common histologic form of breast cancer, representing 5% to 15% of all invasive breast cancers. Due to an insidious proliferative pattern, invasive lobular carcinoma remains clinically and radiologically elusive in many cases. Breast magnetic resonance imaging (MR) is considered the most accurate imaging modality in detecting and staging invasive lobular carcinoma and it is strongly recommended in pre-operative planning for all ILC. Contrast-enhanced spectral mammography (CESM) is a new diagnostic method that enables the accurate detection of malignant breast lesions similar to that of breast MR. CESM is also a promising breast imaging method for planning surgeries. In this study, we compare the ability of contrast-enhanced spectral mammography (CESM) with breast MR in the preoperative assessment of the extent of invasive lobular carcinoma. All patients with proven invasive lobular carcinoma treated in our breast cancer center underwent preoperative breast MRI and CESM. Images were reviewed by two dedicated breast radiologists and results were compared to the reference standard histopathology. CESM was similar and in some cases more accurate than breast MR in assessing the extent of disease in invasive lobular cancers. Further evaluation in larger prospective randomized trials is needed to validate our preliminary results

Ultrasound evaluation of biopsy proven malignant breast mass

Background: Breast cancer is the most common malignancy in female worldwide. Ultrasound (US) is a safe and easily available modality for evaluation of breasts in females of all age groups. It can detect characteristic features of breast malignancy with high degree of accuracy. This study was undertaken with the aims to evaluate the ultrasonographic features of malignant breast mass, to identify the most commonly encountered gray scale ultrasound findings and to study the role of Doppler ultrasound in those cases.Methods: The study was conducted in Dr B. Borooah Cancer Institute, Guwahati from January 2018 to January 2019. Gray scale ultrasound including Doppler study was done in all the female patients coming with palpable breast lump or with nipple discharge and images were archived. The archived images of a total number of 108 patients with biopsy report positive for malignancy were retrospectively studied and the ultrasound findings were evaluated.Results: Most common gray scale ultrasound features for malignant breast masses were hypoechoic mass, taller than wide, irregular shape, having spiculated margins, neither posterior acoustic enhancement nor shadowing, presence of intralesional microcalcifications and surrounding echogenic halo. Hypervascularity, noticeable difference in waveform pattern between central and peripheral vessels, high resistance flow pattern with absent or reversal of diastolic flow were the common Doppler findings.Conclusions: Combination of Doppler with gray scale ultrasound has emerged as a very important technique in diagnosing malignant breast mass with high accuracy

Third International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions)

The heterogeneous group of B3 lesions in the breast harbors lesions with different malignant potential and progression risk. As several studies about B3 lesions have been published since the last Consensus in 2018, the 3rd International Consensus Conference discussed the six most relevant B3 lesions (atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), radial scar (RS), papillary lesions (PL) without atypia, and phyllodes tumors (PT)) and made recommendations for diagnostic and therapeutic approaches. Following a presentation of current data of each B3 lesion, the international and interdisciplinary panel of 33 specialists and key opinion leaders voted on the recommendations for further management after core-needle biopsy (CNB) and vacuum-assisted biopsy (VAB). In case of B3 lesion diagnosis on CNB, OE was recommended in ADH and PT, whereas in the other B3 lesions, vacuum-assisted excision was considered an equivalent alternative to OE. In ADH, most panelists (76%) recommended an open excision (OE) after diagnosis on VAB, whereas observation after a complete VAB-removal on imaging was accepted by 34%. In LN, the majority of the panel (90%) preferred observation following complete VAB-removal. Results were similar in RS (82%), PL (100%), and FEA (100%). In benign PT, a slim majority (55%) also recommended an observation after a complete VAB-removal. VAB with subsequent active surveillance can replace an open surgical intervention for most B3 lesions (RS, FEA, PL, PT, and LN). Compared to previous recommendations, there is an increasing trend to a de-escalating strategy in classical LN. Due to the higher risk of upgrade into malignancy, OE remains the preferred approach after the diagnosis of ADH

MALDI Mass Spectrometry Imaging for the Discovery of Prostate Carcinoma Biomarkers

The elucidation of new biological markers of prostate cancer (PCa) should aid in the detection, and prognosis of this disease. Diagnostic decision making by pathologists in prostate cancer is highly dependent on tissue morphology. The ability to localize disease-specific molecular changes in tissue would help improve this critical pathology decision making process. Direct profiling of proteins in tissue sections using MALDI imaging mass spectrometry (MALDI-IMS) has the power to link molecular detail to morphological and pathological changes, enhancing the ability to identify candidates for new specific biomarkers. However, critical questions remain regarding the integration of this technique with clinical decision making. To address these questions, and to investigate the potential of MALDI-IMS for the diagnosis of prostate cancer, we have used this approach to analyze prostate tissue for the determination of the cellular origins of different protein signals to improve cancer detection and to identify specific protein markers of PCa. We found that specific protein/peptide expression changes correlated with the presence or absence of prostate cancer as well as the presence of micro-metastatic disease. Additionally, the over-expression of a single peptide (m/z = 4355) was able to accurately define primary cancer tissue from adjacent normal tissue. Tandem mass spectrometry analysis identified this peptide as a fragment of MEKK2, a member of the MAP kinase signaling pathway. Validation of MEKK2 overexpression in moderately differentiated PCa and prostate cancer cell lines was performed using immunohistochemistry and Western Blot analysis. Classification algorithms using specific ions differentially expressed in PCa tissue and a ROC cut-off value for the normalized intensity of the MEKK2 fragment at m/z 4355 were used to classify a blinded validation set. Finally, the optimization of sample processing in a new fixative which preserves macromolecules has led to improved through-put of samples making MALDI-IMS more compatible with current histological applications, facilitating its implementation in a clinical setting. This study highlights the potential of MALDI-IMS to define the molecular events involved in prostate tumorigenesis and demonstrates the applicability of this approach to clinical diagnostics as an aid to pathological decision making in prostate cancer

Gastrointestinal tract plasmablastic lymphoma in HIV infected adults: a histopathological audit.

Masters Degree. University of KwaZulu-Natal, Durban.Background: Plasmablastic lymphoma (PBL) is an aggressive B-cell lymphoma that is characterised by the expression of plasma cell antigens and loss of pan B-cell antigens. The neoplasm is extensively reported in the oral cavity and anorectal region but rarely in the gastrointestinal tract where only isolated case reports and small case series exist. In the current study, morphologic, immunohistochemical and molecular features of 17 cases of gastrointestinal tract PBL were reviewed. Materials and Methods: Ten-year retrospective study that reappraised the histomorphological and immunophenotypic features of HIV-associated PBLs in the gastrointestinal tract that were diagnosed and coded as ‘plasmablastic lymphoma’. Results: The average age of the study patients was 41 years with a 3:1 ratio of males to females. The most frequent site of involvement was the small intestine (42%). Majority of the cases showed a predominant diffuse (82%) growth pattern. Immunoblasts and plasmablasts were observed in all cases. Sixty-five percent (65%) of the cases exhibited scattered centroblasts and one case demonstrated predominance of centroblasts. Other features observed include pseudo-alveolar growth pattern, plasmacytic differentiation, scattered multinucleated giant cells, focal clear cell change, high mitotic activity with high proliferative indices (Ki-67 >90%), apoptotic bodies and necrosis. Immunohistochemistry revealed absence of pan B-cell antigens and expression of plasma cell antigens. Epstein-Barr virus-encoded RNA was expressed in 53% of the cases. Conclusion: This study highlights the spectrum of histopathological features of gastrointestinal tract PBLs. Additional observations not previously described or emphasised in literature includes pseudo-alveolar growth pattern, centroblast-predominance, multinucleated giant cells and clear cell change. Awareness of this entity in the gastrointestinal tract and its histopathological features and immunohistochemical profile is essential for making an accurate diagnosis and avoiding potential diagnostic errors. Keywords: Plasmablastic lymphoma; HIV-related lymphoma; AIDS-related lymphoma; gastrointestinal tract; stomach; small intestine; colon

Improving biomarker assessment in breast pathology

The accuracy of prognostic and therapy-predictive biomarker assessment in breast tumours is crucial for management and therapy decision in patients with breast cancer. In this thesis, biomarkers used in clinical practice with emphasise on Ki67 and HER2 were studied using several methods including immunocytochemistry, in situ hybridisation, gene expression assays and digital image analysis, with the overall aim to improve routine biomarker evaluation and clarify the prognostic potential in early breast cancer. In paper I, we reported discordances in biomarker status from aspiration cytology and paired surgical specimens from breast tumours. The limited prognostic potential of immunocytochemistry-based Ki67 scoring demonstrated that immunohistochemistry on resected specimens is the superior method for Ki67 evaluation. In addition, neither of the methods were sufficient to predict molecular subtype. Following this in paper II, biomarker agreement between core needle biopsies and subsequent specimens was investigated, both in the adjuvant and neoadjuvant setting. Discordances in Ki67 and HER2 status between core biopsies and paired specimens suggested that these biomarkers should be re-tested on all surgical breast cancer specimens. In paper III, digital image analysis using a virtual double staining software was used to compare methods for assessment of proliferative activity, including mitotic counts, Ki67 and the alternative marker PHH3, in different tumour regions (hot spot, invasive edge and whole section). Digital image analysis using virtual double staining of hot spot Ki67 outperformed the alternative markers of proliferation, especially in discriminating luminal B from luminal A tumours. Replacing mitosis in histological grade with hot spot-scored Ki67 added significant prognostic information. Following these findings, the optimal definition of a hot spot for Ki67 scoring using virtual double staining in relation to molecular subtype and outcome was investigated in paper IV. With the growing evidence of global scoring as a superior method to improve reproducibility of Ki67 scoring, a different digital image analysis software (QuPath) was also used for comparison. Altogether, we found that automated global scoring of Ki67 using QuPath had independent prognostic potential compared to even the best virtual double staining hot spot algorithm, and is also a practical method for routine Ki67 scoring in breast pathology. In paper V, the clinical value of HER2 status was investigated in a unique trastuzumab-treated HER2-positive cohort, on the protein, mRNA and DNA levels. The results demonstrated that low levels of ERBB2 mRNA but neither HER2 copy numbers, HER2 ratio nor ER status, was associated with risk of recurrence among anti-HER2 treated breast cancer patients. In conclusion, we have identified important clinical aspects of Ki67 and HER2 evaluation and provided methods to improve the prognostic potential of Ki67 using digital image analysis. In addition to protein expression of routine biomarkers, mRNA levels by targeted gene expression assays may add further prognostic value in early breast cance