Matthew Hanna

Overview of contemporary guidelines in digital pathology: what is available in 2015 and what still needs to be addressed?

As technological advancements continue to transform the practice of pathology, new adopters of these technologies will look to guidelines on how best to incorporate them with an eye to preserving and enhancing patient safety and diagnostic quality. Telepathology, using a variety of digital pathology modalities, has tremendous potential to achieve that goal. Pathology departments are increasingly looking to implement different digital pathology platforms, whole slide imaging (WSI) systems in particular, for a broad range of applications in patient care. WSI allows for the acquisition, management and review of completely digitised slides as would be done with a light microscope. WSI also facilitates image analysis that cannot be carried out by a pathologist using traditional microscopy. Over the last few years, the Digital Pathology Association, The Royal College of Pathologists, College of American Pathologists, Canadian Association of Pathologists, the American Telemedicine Association and the Society of Toxicologic Pathology have published guidelines for validating and implementing digital pathology systems. This review summarises, compares and contrasts these published guidelines and discusses pertinent issues that need to be addressed as the guidelines are revised in the future.

Correlation of Oncotype DX Recurrence Score with Histomorphology and Immunohistochemistry in over 500 Patients

Oncotype Dx is used to determine the recurrence risk (RR) in patients with estrogen receptor positive (ER+) and lymph node negative (LN−) breast cancer. The RR is divided into low (0–17), intermediate (18–30), and high (31) to predict chemotherapy benefit. Our goal was to determine the association between histomorphology, immunohistochemistry, and RR. We retrospectively identified 536 patients with ER+ and LN− breast cancers that underwent Oncotype testing from 2006 to 2013. Tumor size ranged from 0.2 cm to 6.5 cm (mean = 1.3 cm) and was uniform in all 3 categories. The carcinomas were as follows: ductal = 63.2%, lobular = 11.1%, and mixed = 35.7%. The RR correlated with the Nottingham grade. Increasing RR was inversely related to PR positivity but directly to Her2 positivity. Of the morphologic parameters, a tubular(lobular) morphology correlated only with low-intermediate scores and anaplastic type with intermediate-high scores. Other morphologies like micropapillary and mucinous were uniformly distributed in each category. Carcinomas with comedo intraductal carcinoma were more likely associated with high RR. Forty-four patients with either isolated tumor cells or micrometastases were evenly distributed amongst the 3 RR. While there was only 1 ER discrepancy between our immunohistochemistry (3+ 80%) and Oncotype, up to 8% of PR+ cases (mean = 15%, median = 5%) and 2% of HER2+ cases were undervalued by Oncotype.

Augmented Reality Technology Using Microsoft HoloLens in Anatomic Pathology

Context Augmented reality (AR) devices such as the Microsoft HoloLens have not been well used in the medical field. Objective To test the HoloLens for clinical and nonclinical applications in pathology. Design A Microsoft HoloLens was tested for virtual annotation during autopsy, viewing 3D gross and microscopic pathology specimens, navigating whole slide images, telepathology, as well as real-time pathology-radiology correlation. Results Pathology residents performing an autopsy wearing the HoloLens were remotely instructed with real-time diagrams, annotations, and voice instruction. 3D-scanned gross pathology specimens could be viewed as holograms and easily manipulated. Telepathology was supported during gross examination and at the time of intraoperative consultation, allowing users to remotely access a pathologist for guidance and to virtually annotate areas of interest on specimens in real-time. The HoloLens permitted radiographs to be coregistered on gross specimens and thereby enhanced locating important pathologic findings. The HoloLens also allowed easy viewing and navigation of whole slide images, using an AR workstation, including multiple coregistered tissue sections facilitating volumetric pathology evaluation. Conclusions The HoloLens is a novel AR tool with multiple clinical and nonclinical applications in pathology. The device was comfortable to wear, easy to use, provided sufficient computing power, and supported high-resolution imaging. It was useful for autopsy, gross and microscopic examination, and ideally suited for digital pathology. Unique applications include remote supervision and annotation, 3D image viewing and manipulation, telepathology in a mixed-reality environment, and real-time pathology-radiology correlation.

Re-evaluating the role of sentinel lymph node biopsy in microinvasive breast carcinoma

The role of sentinel lymph node biopsy in microinvasive breast carcinoma is unclear. We examined the incidence of lymph node metastasis in patients with microinvasive carcinoma who underwent surgery at our institution. Retrospective review of our pathology database was performed (1994–2012). Of 7000 patients surgically treated for invasive breast carcinoma, 99 (1%) were classified as microinvasive carcinoma. Axillary staging was performed in 81 patients (64, sentinel lymph node biopsy; 17, axillary lymph node excision). Seven cases (9%) showed isolated tumor/epithelial cells in sentinel nodes. Three of these seven cases showed reactive changes in lymph nodes, papillary lesions in the breast with or without displaced epithelial cells within biopsy site tract, or immunohistochemical (estrogen receptor, progesterone receptor, and HER2) discordance between the primary tumor in the breast and epithelial cells in the lymph node, consistent with iatrogenically transported epithelial cells rather than true metastasis. The remaining four cases included two cases, each with a single cytokeratin-positive cell in the subcapsular sinus detected by immunohistochemistry only, and two cases with isolated tumor cells singly and in small clusters (<20 cells per cross-section) by hematoxylin and eosin and immunohistochemistry. The exact nature of cytokeratin-positive cells in the former two cases could not be determined and might still have represented iatrogenically displaced cells. In the final analysis, only two cases (3%) had isolated tumor cells. Three of these four cases had additional axillary lymph nodes excised, which were all negative for tumor cells. At a median follow-up of 37 months (range 6–199 months), none of these patients had axillary recurrences. Our results show very low incidence of sentinel lymph node involvement (3%), only as isolated tumor cells, in microinvasive carcinoma patients. None of our cases showed micrometastases or macrometastasis. We recommend reassessment of the routine practice of sentinel lymph node biopsy in patients with microinvasive carcinoma.

Predictive nuclear chromatin characteristics of melanoma and dysplastic nevi

Background: The diagnosis of malignant melanoma (MM) is among the diagnostic challenges pathologists encounter on a routine basis. Melanoma may arise in patients with preexisting dysplastic nevi (DN) and it is still the cause of 1.7% of all cancer-related deaths. Melanomas often have overlapping histological features with DN, especially those with severe dysplasia. Nucleotyping for identifying nuclear textural features can analyze nuclear DNA structure and organization. The aim of this study is to differentiate MM and DN using these methodologies. Methods: Dermatopathology slides diagnosed as MM and DN were retrieved. The glass slides were scanned using an Aperio ScanScopeXT at ×40 (0.25 μ/pixel). Whole slide images (WSI) were annotated for nuclei selection. Nuclear features to distinguish between MM and DN based on chromatin distributions were extracted from the WSI. The morphological characteristics for each nucleus were quantified with the optimal transport-based linear embedding in the continuous domain. Label predictions for individual cell nucleus are achieved through a modified version of linear discriminant analysis, coupled with the k-nearest neighbor classifier. Label for an unknown patient was set by the voting strategy with its pertaining cell nuclei. Results: Nucleotyping of 139 patient cases of melanoma (n = 67) and DN (n = 72) showed that our method had superior classification accuracy of 81.29%. This is a 6.4% gain in differentiating MM and DN, compared with numerical feature-based method. The distribution differences in nuclei morphology between MM and DN can be visualized with biological interpretation. Conclusions: Nucleotyping using quantitative and qualitative analyses may provide enough information for differentiating MM from DN using pixel image data. Our method to segment cell nuclei may offer a practical and inexpensive solution in aiding in the accurate diagnosis of melanoma.

Why is digital pathology in cytopathology lagging behind surgical pathology

Dr. Hanna is a clinical instructor of pathology informatics at the University of Pittsburgh. He completed his residency training at the Mount Sinai Hospital in New York City and currently is a pathology informatics fellow at the University of Pittsburgh Medical Center. Dr. Hanna serves as a junior editor of the Journal of Pathology Informatics. He has strong interests in pathology and clinical informatics, as well as women’s health pathology.