Phyllodes tumour of the breast and margins: How much is enough

Summary: Phyllodes breast tumours are fairly uncommon, and they can be benign, borderline or malignant. General surgeons usually encounter them following the surgical excision of a breast lump that had the appearance of a fibroepithelial lesion. The surgeon is then faced with the question of what to do to establish an acceptable treatment margin. In this discussion, we recommend a plan for the management of Phyllodes tumours based on a review of the recent literature, confirmed by a retrospective review of the results from our centre. A negative margin is acceptable treatment following a lumpectomy for Phyllodes tumours. Only patients with a positive margin should undergo a revision.

Breast intraductal papillomas without atypia in radiologic-pathologic concordant core-needle biopsies: Rate of upgrade to carcinoma at excision.

BACKGROUND: The surgical management of mammary intraductal papilloma without atypia (IDP) identified at core-needle biopsy (CNB) is controversial. This study assessed the rate of upgrade to carcinoma at surgical excision (EXC). METHODS: This study identified women with a CNB diagnosis of intraductal papilloma without atypia or carcinoma at a cancer center between 2003 and 2013. Radiologic-pathologic concordance was assessed for all cases, and discordant cases were excluded. The radiologic and clinicopathologic features of patients with a CNB diagnosis of IDP were correlated with an upgrade to carcinoma at EXC. RESULTS: The study population consists of 189 women with 196 IDPs; 166 women (171 IDPs) underwent EXC. The upgrade rate was 2.3% (4 of 171). The upgraded lesions were 2 invasive lobular carcinomas and 2 cases of ductal carcinoma in situ (DCIS). One case of DCIS involved the residual IDP, whereas the other 3 carcinomas were ≥ 8 mm away. Twenty-four women (25 IDPs) did not undergo EXC and had stable imaging on follow-up (median, 23.5 months). CONCLUSIONS: The upgrade rate at EXC for IDPs diagnosed at CNB with radiologic-pathologic concordance was 2.3%. These findings suggest that observation is appropriate for patients with radiologic-pathologic concordant CNB yielding IDP, regardless of its size. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2819-2827. © 2016 American Cancer Society.

Endometrial sarcomas: an immunohistochemical and JAZF1 re-arrangement study in low-grade and undifferentiated tumors.

The current World Health Organization classification divides endometrial sarcomas into low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma. Recent studies suggest undifferentiated endometrial sarcoma is a heterogeneous group and a subgroup with uniform nuclei is more akin to low-grade endometrial stromal sarcoma in terms of morphologic, immunohistochemical and genetic features. We classified endometrial sarcomas treated at our institution from 1998 to 2011 into low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma, the latter being further categorized into a group with either uniform or pleomorphic nuclei. Morphological features, immunoprofile and fluorescence in situ hybridization rearrangements of JAZF1 and PHF1 genes were correlated with tumor category and outcome. A total of 40 cases were evaluated comprising 23 low-grade endometrial stromal sarcomas, 10 undifferentiated endometrial sarcomas with nuclear uniformity and 7 undifferentiated endometrial sarcomas with nuclear pleomorphism. Low-grade endometrial stromal sarcomas were more often estrogen and progesterone receptor positive (83%) compared with undifferentiated endometrial sarcoma with nuclear uniformity (10%) or with nuclear pleomorphism (0%) (P<0.001). Positivity for p53 was restricted to undifferentiated endometrial sarcomas with more frequent expression in the group with nuclear pleomorphism (57%) than with nuclear uniformity (10%) (P=0.06). Ki-67 proliferation index in >10% of tumor cells more frequent in undifferentiated endometrial sarcoma than low-grade endometrial stromal sarcoma (P=<0.001). JAZF1 rearrangement was detected in 32% of low-grade endometrial stromal sarcomas and in none of the undifferentiated sarcomas. Rearrangement of PHF1 was found in two patients, one with JAZF1-PHF1 fusion. There were no significant differences in clinical behavior between undifferentiated endometrial sarcoma with nuclear uniformity versus nuclear pleomorphism. In conclusion, we found undifferentiated endometrial sarcoma subtypes and low-grade endometrial stromal sarcoma have distinct immunohistochemical and cytogentic profiles. Our data do not show any difference in clinical behavior between subgroups in undifferentiated sarcomas.

Cutaneous myoepithelioma arising within hidradenoma of the scalp.

A 62-year-old man presented with a 2-year history of a 2-cm cystic mass involving his occiput. There had been recent enlargement, and the clinical impression was that of a pilar cyst. Histopathological sections showed a partially dermal solid and cystic proliferation. The tumor contained areas of glandular differentiation with cuboidal to columnar cells lining luminal and cystic spaces. A concurrent spindle cell proliferation was seen interspersed between glands and also formed broad, cellular sheets of cells. The stroma was sclerotic and without chondroid or myxoid elements. Immunohistochemistry showed that the spindled cells expressed S100 protein, cytokeratin and smooth muscle myosin. The immunohistochemical profile and the relationship with ductal elements supported myoepithelial differentiation. The proliferation warranted the diagnosis of myoepithelioma arising from a hidradenoma, which to our knowledge has not been previously described. In addition to discussing this case, we provide a brief review of epithelial-myoepithelial neoplasms encountered in the skin.

The Use of Optical Coherence Tomography for Gross Examination and Sampling of Fixed Breast Specimens: A Pilot Study.

Thorough gross examination of breast cancer specimens is critical in order to sample relevant portions for subsequent microscopic examination. This task would benefit from an imaging tool which permits targeted and accurate block selection. Optical coherence tomography (OCT) is a non-destructive imaging technique that visualizes tissue architecture and has the potential to be an adjunct at the gross bench. Our objectives were: (1) to familiarize pathologists with the appearance of breast tissue entities on OCT; and (2) to evaluate the yield and quality of OCT images of unprocessed, formalin-fixed breast specimens for the purpose of learning and establishment of an OCT-histopathology library. METHODS: Firstly, 175 samples from 40 formalin-fixed, unprocessed breast specimens with residual tissue after final diagnosis were imaged with OCT and then processed into histology slides. Histology findings were correlated with features on OCT. RESULTS: Residual malignancy was seen in 30% of tissue samples. Corresponding OCT images demonstrated that tumor can be differentiated from fibrous stroma, based on features such as irregular boundary, heterogeneous texture and reduced penetration depth. Ductal carcinoma in situ can be subtle, and it is made more recognizable by the presence of comedo necrosis and calcifications. OCT features of benign and malignant breast entities were compiled in a granular but user-friendly reference tool. CONCLUSION: OCT images of fixed breast tissue were of sufficient quality to reproduce features of breast entities previously described in fresh tissue specimens. Our findings support the use of readily available unprocessed, fixed breast specimens for the establishment of an OCT-histopathology library.

Efficacy of GATA3 Versus BRST2 for the Identification of Metastatic Breast Carcinoma in the Upper GI Tract: Which Performs Better?

Distinguishing primary diffuse-type gastric carcinoma (PDGC) versus gastric involvement by metastatic breast carcinoma (mBC), particularly the lobular subtype, is difficult on histology alone. Both can appear morphologically similar. GATA3, a novel transcription factor, is used in certain scenarios as an immunohistochemical marker of breast origin. Our objective was to investigate the efficacy of GATA3 in differentiating PDGC and mBC and how it compares to another breast marker, BRST2. We retrospectively stained 40 cases of PDGC and 10 control cases of mBC from upper gastrointestinal tract specimens for antibodies: GATA3, BRST2, CDX2, and estrogen receptor. Staining of tumor cells was semiquantified with a modified Allred score. GATA3 and BRST2 were positive in 17.5% and 12.5% of PDGC cases, respectively, and in 100% of mBC cases. Allred scores for GATA3 were significantly greater in mBC cases compared with PDGC (P=0.001). Allred scores were not significantly different for BRST2 due to low levels of staining in mBC cases. Although sensitivity and specificity were similar, differences in staining between PDGC and mBC were more decisive for GATA3 versus BRST2 and thus easier to interpret. In addition, 50% of PDGC cases were positive for CDX2 and none for estrogen receptor. Overall, our results show that GATA3 can reliably and correctly identify cases of mBC to the upper gastrointestinal tract. However, because a minority of PDGC were positive for GATA3, it should still be used within an antibody panel to resolve this diagnostic dilemma.

Assessing the Impact of Color Normalization in Convolutional Neural Network-Based Nuclei Segmentation Frameworks.

Image analysis tools for cancer, such as automatic nuclei segmentation, are impacted by the inherent variation contained in pathology image data. Convolutional neural networks (CNN), demonstrate success in generalizing to variable data, illustrating great potential as a solution to the problem of data variability. In some CNN-based segmentation works for digital pathology, authors apply color normalization (CN) to reduce color variability of data as a preprocessing step prior to prediction, while others do not. Both approaches achieve reasonable performance and yet, the reasoning for utilizing this step has not been justified. It is therefore important to evaluate the necessity and impact of CN for deep learning frameworks, and its effect on downstream processes. In this paper, we evaluate the effect of popular CN methods on CNN-based nuclei segmentation frameworks.

A case of recurrent, multifocal anastomosing haemangiomas.

Anastomosing haemangiomas are relatively rare lesions, with a renal predilection, and which, given their imaging and pathologic appearance, mimic aggressive malignancies such as angiosarcoma. The imaging characteristics of this case are informative when evaluating a vascular lesion of the adrenal gland.

Papillary lesions of the breast: impact of breast pathology subspecialization on core biopsy and excision diagnoses.

BACKGROUND: Classifying papillary lesions of the breast on core biopsy (CB) is challenging. Although traditionally all such lesions were surgically excised, at present, conservative management of benign lesions is being advocated; therefore, accurately classifying papillary lesions on CB is all the more imperative. The extent to which subspecialty training in breast pathology might mitigate such difficulties in diagnosis has not yet been reported. We investigated change in diagnoses from CB to surgical excision according to subspecialist training in breast pathology and interobserver agreement between specialized breast pathologists (BPs) and nonbreast pathologists (NBPs) in classifying these lesions. DESIGN: CBs of 281 papillary lesions from 266 patients diagnosed between 2000 and 2010 were classified by both a BP and NBP into benign, atypical, ductal carcinoma in situ/encapsulated papillary carcinoma, or invasive carcinoma categories. Rates of change in diagnostic category in the surgical excision specimen were calculated on the basis of: (i) the original diagnosis, (ii) diagnosis made by the BP, and (iii) diagnosis made by the NBP. Comparisons were made using the χ test. Kappa values were calculated for interobserver agreement. RESULTS: Of 162 lesions with subsequent excision, 90 were originally diagnosed as benign, 38 as atypical, 25 as ductal carcinoma in situ/encapsulated papillary carcinoma, and 9 as invasive on CB. The upgrade rate for benign papillomas to an atypical or malignant lesion on surgical excision was 22.2% according to the original diagnosis. This rate fell to 16.3% when the BP diagnoses were considered, compared with 26.3% for the NBP diagnoses. There was no significant difference between BPs and NBPs in the rate of upgrade from a benign to an atypical/malignant diagnosis, although downgrades from atypical/malignant to benign papillomas were more commonly seen among NBPs (P=0.002). Overall, the BP diagnosis on CB was less likely to differ from the excision diagnosis (P=0.0001). Benign papillomas upgraded on excision were more likely to occur with larger radiologic mass size (P=0.033) compared with those that were not upgraded. Of 8 benign papillomas upgraded to a malignant lesion on excision, 7 were discordant on radiology. Interobserver agreement between BP and NBP diagnoses was in the "fair agreement" range (κ=0.38), with perfect agreement in 66.4% of cases. CONCLUSIONS: Correlation between CB and excision diagnoses for breast papillary lesions is significantly greater for BPs than for NBPs. This is largely because of a tendency to overcall atypia or malignancy on CB by NBPs. However, upgrades from benign to atypical or malignant did not significantly differ according to subspecialization. With accurate pathologic assessment and radiologic-pathologic correlation, the upgrade rate of benign papillomas to malignancy can be minimized significantly.