Deep Learning Provides Rapid Screen for Breast Cancer Metastasis with Sentinel Lymph Nodes.

OBJECTIVE: Deep learning has been shown to be useful in detecting breast cancer metastases by analyzing whole slide images (WSI) of sentinel lymph nodes; however, it requires extensive analysis of all the lymph node slides. Our deep learning study attempts to provide a rapid screen for metastasis by analyzing only a small set of image patches to detect changes in tumor environment. METHODS: We designed a convolutional neural network to build a diagnostic model for metastasis detection. We obtained WSIs of Hematoxylin and Eosin-stained slides from 34 cases with equal distribution in positive/negative categories. Two WSIs were selected from each case for a total of 69 WSIs. From each WSI, 40 image patches (100x100 pixels) were obtained to yield 2720 image patches, from which 2160 (79%) were used for training, 240 (9%) for validation, and 320 (12%) for testing. Interobserver variation was also examined among 3 users. RESULTS: The test results showed excellent diagnostic results: accuracy (91.15%), sensitivity (77.92%), and specificity (92.09%). No significant variation in results was observed among the 3 observers. CONCLUSION: This preliminary study provided a proof of concept for conducting a rapid screen for metastasis rather than an exhaustive search for tumors in all fields of all sentinel lymph nodes.

The value of SOX2 in the differential diagnosis of SMARCA4 (BRG1)-deficient uterine neoplasms.

SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4/BRG1)-deficient undifferentiated uterine sarcoma (SDUS) is a recently described uterine sarcoma. It is characterized by predominantly rhabdoid or large epithelioid cells with abundant cytoplasm and varying components of small and spindle cells, resembling the 'large cell variant' of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). In addition, SMARCA4-inactivating mutations have been described as the driver mutations in SDUS. However, undifferentiated endometrial carcinoma (UDEC) and dedifferentiated endometrial carcinoma (DDEC) may show some clinical and morphological overlaps with SDUS, and about 20% of reported UDEC/DDEC cases also have loss expression of SMARCA4. SDUS is a very aggressive disease and universally lethal in all reported cases. Differentiating SDUS from UDEC/DDEC is relevant for the prognosis, pathogenesis, and possible targeted therapies for the disease. In this study, we compared the clinical, morphological, immunohistochemical, and molecular characteristics of 10 tumors including 2 SDUS, 2 SCCOHT, 1 uterine carcinoma with neuroendocrine differentiation (UDEC?), and 5 UDEC/DDEC. All 5 UDEC/DDEC cases showed strong and diffuse nuclear positivity for SOX2, while all SCCOHT and SDUS cases were completely negative. We concluded that SOX2 could be a useful marker for the differential diagnosis between SDUS and UDEC/DDEC.

Educational Case: Mantle Cell Lymphoma.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Educational Case: Systemic Mastocytosis with an Associated Hematological Neoplasm.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

The predictive and prognostic value of Foxp3+/CD25+ regulatory T cells and PD-L1 expression in triple negative breast cancer.

Recent significant developments in cancer immunotherapy have led to important breakthroughs and paradigm shifts in the treatment of malignancy. Although breast cancer traditionally has been considered less immunogenic, triple-negative breast cancer (TNBC) is the most immunogenic subtype with more stromal tumor-infiltrating lymphocytes (TILs) and higher programmed death-ligand 1 (PD-L1) expression. The goal of this study is to evaluate regulatory T cells (Tregs) and PD-L1 expression in TNBC, as well as their associations with clinicopathologic features and the outcomes. Tissue microarrays (TMA) of biopsy and resection specimens of 43 TNBC patients who underwent breast biopsy, neoadjuvant chemotherapy, and mastectomy were prepared. The number of Foxp3+ Tregs, Foxp3+/CD25+ Tregs, and expression of PD-L1 in tumor cells (PD-L1 TCs) and TILs (PD-L1 TILs) were assessed by immunohistochemistry. PD-L1 expression combined positive score (PD-L1 CPS) was calculated according to the manufacturer's guidelines. PD-L1 expression was detected in 72% of the cases, and it expressed in a higher percentage and higher intensity in TILs than TCs in TNBC (p = 0.006 and 0.0005, respectively). PD-L1 TCs, PD-L1 TILs, and PD-L1 CPS were all positively associated with pathologic complete response (pCR) (p = 0.04, 0.03, and 0.02, respectively). PD-L1 TILs and PD-L1 CPS also correlated with TILs and tumor infiltrating lymphocyte volume (TILV). Foxp3+ Tregs and Foxp3+/CD25+ Tregs had strong positive correlation (r = 0.89), and they were positively associated with TILs, TILV, and PD-L1 expression. Foxp3+/CD25+ Tregs, PD-L1 TCs, and PD-L1 CPS were positively correlated with better overall survival (p = 0.04, 0.04 and 0.01, respectively).

Therapy-related myeloid neoplasms with isolated del(20q): comparison with cases of de novo myelodysplastic syndrome with del(20q).

The isolated deletion of chromosome 20q [del(20q)] has been observed in both de novo and therapy-related cases of myelodysplastic syndrome (MDS). The clinicopathologic features of de novo MDS with isolated del(20q) are well characterized. However, relatively little is known about therapy-related myeloid neoplasms (t-MNs) with isolated del(20q). In this study, we identified five cases of t-MN and 26 cases of de novo MDS with isolated del(20q) over a 10-year period. All cases had a long latency interval from the treatment of the primary malignancy to the onset of t-MN, and all were associated with frequent bone marrow dysplasia. The del(20q) was the sole abnormality detected at the time of diagnosis of t-MN in three cases, six years prior to diagnosis in one case, and at the time of relapse of acute myeloid leukemia (AML) in one case. Three patients with therapy-related MDS (t-MDS) had a relatively indolent clinical course, whereas two patients presented with AML or developed AML shortly after t-MDS. The patients with de novo MDS with isolated del(20q) presented frequently with anemia and thrombocytopenia which were associated with bone marrow dysplasia. The median overall survival was 64 months. In all cases, del(20q) was present at the time of diagnosis.

Changing trends in human papillomavirus-associated head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) continues to be a significant disease with varying rates of incidence and mortality worldwide. Numerous studies have demonstrated that human papillomavirus (HPV) is etiologically linked with a subset of HNSCC, independent of tobacco and alcohol use. This subset of tumor shows increased sensitivity to radiation therapy and association with better outcomes. The study aims to determine the HPV burden and trend among patients with HNSCC in the southern region of the United States over the past 10 years. Of 142 cases from 2000 to 2004, 18 (13%) were positive for high-risk HPV. Nine of these were oropharyngeal tumors, including 4 cases from the tonsil. These constitute 38% (9/24) of all oropharyngeal tumors and 57% (4/7) of tonsillar tumors. Of 35 cases from 2009 to 2010, 14 (40%) were positive for high-risk HPV. Thirteen of these were oropharyngeal tumors, including 9 cases from the tonsil. These constitute 59% (13/23) of oropharyngeal tumors and 64% (9/14) of tonsillar tumors. When data from the 2 periods are combined, the results show that African American patients are less likely to have HPV-associated disease compared with white patients (9% vs 22%). Human papillomavirus-positive and oropharyngeal HNSCC are more likely to be nonkeratinizing (P < .0001). In conclusion, the HPV detection rate in oropharyngeal squamous cell carcinoma increased from 38% to 59% between the 2000-to-2004 and 2009-to-2010 periods.

Human papillomavirus in metastatic lymph nodes from unknown primary head and neck squamous cell carcinoma.

OBJECTIVE: Determine human papillomavirus (HPV) incidence in unknown primary squamous cell carcinomas (SCCa) of the head and neck and assess if HPV status influenced survival. STUDY DESIGN: Historical cohort study. SETTING: Tertiary care center. SUBJECTS: Patients with unknown primary SCCa despite a complete workup who underwent neck dissection or excisional biopsy and postoperative comprehensive ± chemoradiotherapy between 2002 and 2009. METHODS: HPV fluorescence in situ hybridization (FISH) and p16(INK4a) immunohistochemistry (p16 IHC) were performed. Results were compared with survival, age, race, gender, tobacco use, alcohol use, and nodal stage. RESULTS: Twenty-five patients met the inclusion criteria, of whom 88% were >10 pack year tobacco users. Twenty-eight percent were HPV-positive defined by both p16+ and FISH+. Five-year overall survival was 66.7% in HPV-positive and 48.5% in HPV-negative patients (P = .35). Similarly, 5-year disease-free survival rates were 66.7% in HPV-positive and 48.5% in HPV-negative patients (P = .54). All 3 HPV-positive nonsmokers were survivors, but this was not significant because of the small sample size (P > .05). No other characteristics were associated with survival (P > .05). CONCLUSION: Twenty-eight percent of metastatic lymph nodes from occult primary tumors were HPV positive. There was no survival difference associated with HPV status. Most of the HPV-positive patients in this study were tobacco users who had similar survival to HPV-negative patients, so caution should be used in interpreting HPV status in these patients.