Recommendations for diagnosing STIC: a systematic review and meta-analysis

Our understanding of the oncogenesis of high-grade serous cancer of the ovary and its precursor lesions, such as serous tubal intraepithelial carcinoma (STIC), has significantly increased over the last decades. Adequate and reproducible diagnosis of these precursor lesions is important. Diagnosing STIC can have prognostic consequences and is an absolute requirement for safely offering alternative risk reducing strategies, such as risk reducing salpingectomy with delayed oophorectomy. However, diagnosing STIC is a challenging task, possessing only moderate reproducibility. In this review and meta-analysis, we look at how pathologists come to a diagnosis of STIC. We performed a literature search identifying 39 studies on risk reducing salpingo-oophorectomy in women with a known BRCA1/2 PV, collectively reporting on 6833 patients. We found a pooled estimated proportion of STIC of 2.8% (95% CI, 2.0–3.7). We focused on reported grossing protocols, morphological criteria, level of pathologist training, and the use of immunohistochemistry. The most commonly mentioned morphological characteristics of STIC are (1) loss of cell polarity, (2) nuclear pleomorphism, (3) high nuclear to cytoplasmic ratio, (4) mitotic activity, (5) pseudostratification, and (6) prominent nucleoli. The difference in reported incidence of STIC between studies who totally embedded all specimens and those who did not was 3.2% (95% CI, 2.3–4.2) versus 1.7% (95% CI, 0.0–6.2) (p 0.24). We provide an overview of diagnostic features and present a framework for arriving at an adequate diagnosis, consisting of the use of the SEE-FIM grossing protocol, evaluation by a subspecialized gynecopathologist, rational use of immunohistochemical staining, and obtaining a second opinion from a colleague.

Nuclear Morphological Characteristics in Breast Cancer: Correlation with Hormone Receptor and Human Epidermal Growth Factor Receptor 2

Background. Hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) are the common diagnostic/prognostic markers in breast cancer. Few articles have recently reported the correlation between cytology and molecular subtypes. We combined nuclear morphological characteristics with HR and HER2 status to observe the relationship and provide ideas for machine learning. Methods. We reanalyzed fine-needle aspiration cytology samples and core-needle puncture histological specimens from 142 patients with invasive breast cancer between March 2019 and December 2019, and the findings were compared with the two groups (HR+/HER2- and HR-/HER2+) following nuclear cytomorphological features: nuclear/cytoplasmic ratio, difference of nuclear size, nuclear pleomorphism, chromatin feature, nuclear membrane and nucleoli, and Nottingham grading. Results. Two groups were significantly associated with the difference of nuclear size, nuclear pleomorphism, and nucleoli ( P < 0.001 ) and consistent with histological grading ( P < 0.001 ). Moreover, nucleolar characteristics of size and number had obviously statistical significance ( P < 0.001 ). Multiple micro-nucleoli were frequently seen in the HR+/HER2- group compared with the HR-/HER2+ group which mostly were observed centered medium-large nucleoli. We described four interesting nuclear morphologies in the experiment. Conclusions. There were significant differences in nuclear characteristics between two groups. HR and HER2 status not only might be predicted in cytological samples, but some specific nuclear morphological features might have potential value to help us understand molecular function and predict more information.

Large Primary Neuroendocrine Tumor of the Liver in a 57-year-Old Female Presenting With MSSA Bacteremia

Primary neuroendocrine tumors (NETs) are rare forms of malignancy, representing just .5% of known cancers and having an overall incidence of 0.2/100,000. The most common sites of origin are bronchopulmonary and gastrointestinal, most commonly the appendix, pancreas, and ileum. We report the case of a 57-year-old female who was admitted for refractory MSSA bacteremia and several weeks of abdominal pain. CT imaging done on presentation demonstrated a 12.5 x 19.4 x 17.3 cm heterogeneous right liver mass with associated mass effect. The patient was taken to the operating room and a right hepatectomy and cholecystectomy were performed without complication. Histological examination revealed necrotic tumor in sheets and nests with marked nuclear pleomorphism. Immunohistochemistry demonstrated positive staining for pancytokeratin, synaptophysin, chromogranin, and TTF-1, consistent with undifferentiated NET. While rare, NETs can originate from a variety of organs outside the gastrointestinal and bronchopulmonary tract, including the liver.

Correlation of Clinical, Histopathological and Histomorphometric Features of Canine Soft Tissue Sarcomas

Soft-tissue sarcomas (STS) represent a heterogeneous group of tumours with similar histological characteristics and biological behaviour. This study aimed to describe the correlation between clinical, histopathological and histomorphometric features of STS in dogs. Medical records were reviewed to identify all dogs in which an STS was diagnosed between 2006-2017. Thirty cases were included, and tumour samples and medical records were recovered. Most of the dogs were mixed breed (40%) and 80% of the STS were located in the subcutaneous connective tissue. Histopathological classification showed that undifferentiated sarcoma (17%) and peripheral nerve sheath tumour (30%) were the most common STS. Grade I STS were obtained in 50% of cases (15/30), and grade II or III tumours compromised 43% (13/30) and 7% (2/30) respectively. The mitotic index ranged from zero to 26 (5.8 ± 7.5). Increased nucleus:cytoplasm ratio was moderately associated with higher tumour grade (p = 0.05; rS = 0.361) and mitotic index (p = 0.05; rS = 0.355), while the number of microvessels was positively correlated with degree of differentiation (p = 0.05; rS = 0.362) and nuclear pleomorphism (p = 0.036; rS = 0.384). Histomorphometry proved to be useful in the evaluation of STS, representing an additional tool correlated with well-established prognostic factors (histopathological grade, degree of differentiation, nuclear pleomorphism).

Malignant Nodular Hidradenoma of the Fingertip: A Case Report

Malignant nodular hidradenoma (MNH) is an infrequent, highly malignant tumor derived from eccrine sweat glands. MNH usually occurs on the scalp, trunk, and proximal extremities, and rarely on the hand. A 55-year-old male patient visited clinics with a gradually enlarging painless mass at fingertip. It begins a year ago. Recently, it has grown rapidly and starts ulceration, and bleeding over the past 3 weeks. According to the biopsy report, it has focal necrosis, atypia, atypical mitoses, and nuclear pleomorphism suggested that the mass was MNH. After histological diagnosis, tiny bone erosion was observed in the re-read radiographic finding. For the oncologic evaluation, the patient was transferred to the cancer center. Radical amputation was performed to the residual tumor that might remain based on re-reading of radiographs. MNH of the finger is especially difficult to the diagnosis given its rarity and variable histology. When ulcerative skin lesion and radiographic bone erosion are observed, one should suspect malignancy and makes out a proper therapeutic plan after histologic biopsy.

Glassy cell carcinoma of cervix: A case report

Glassy cell carcinoma of the cervix is a rare subtype of adenosquamous carcinoma associated with aggressive course and poor prognosis. It is considered to originate from the subcylindrical reserve cells of the cervix and has been associated with human papillomavirus. Histologically glassy cell carcinoma is composed of nestes of large cells with ground glass cytoplasm and large vesicular nuclei with prominent nucleoli. Nuclear pleomorphism and tumor giant cells are frequently seen. Mitotic activity is brisk. Infiltration by eosinophils and plasma cells with admixture of lymphocytes is a characteristic feature. Focal squamous and glandular differentiation may be seen. The immunohistochemistry markers are positive for squamous cell carcinoma (p63, CK34) and adenocarcinoma(MUC1, MUC2, CEA).Here we present a case of 49 year old female diagnosed as glassy cell carcinoma histologically and immunohistochemically.

Cytology of peritoneal implants of borderline serous tumor of ovaries in ascitic fluid

Objectives: Peritoneal fluid cytology is done routinely in cases with serous carcinoma of ovary. However, morphologic features of borderline serous tumors (BSTs) of ovary in ascitic fluid have been rarely described. The aim of our study was to evaluate the morphologic features of BST with and without ascitic fluid involvement (BST+ and BST-, respectively) and compare with those of serous carcinomas, both in conventional and liquid-based cytology (LBC) smears. Material and Methods: Out of 30 BST cases reported in 3 years, seven cases had BST+. We compared the cytomorphology of seven cases of BST+, seven cases of BST-, and seven cases of serous adenocarcinoma with positive ascitic fluid cytology. Both conventional and LBC smears were studied in all cases and compared. Histopathology of omentum in these cases was also studied. Results: Most cases with BST+ had regular papillary fragment borders with nuclei showing mild-to-moderate pleomorphism, fine nuclear chromatin with small nucleoli as compared with serous carcinomas all of which had irregular borders with moderate-to-severe nuclear pleomorphism, coarse chromatin, and macronucleoli. Conclusion: A combination of cytoarchitectural and nuclear features can help in suspecting BST in ascitic fluid. Ascitic fluid cytology together with tissue histology can increase the rate of the detection of peritoneal implants.

Long-term outcomes and predictors of recurrence in patients with early-stage node negative breast cancer.

e12597 Background: In this study, we aimed to assess the outcomes, and predictors of recurrence in patients with early-stage node-negative breast cancer. Methods: We evaluated data of the patients who were treated between 1988 and 2018 years retrospectively. Demographical, clinical, pathological, and treatment features of the patients were recorded. SPSS 25 version was used for statistical analysis. We used Kaplan-Meier and Cox regression analysis to assess survival analysis. Also, we performed logistic regression and ROC analysis for recurrence predictors. Results: In total, 347 patients were included in the study.The median age was 50 (range, 18-81) at diagnosis. The percent of the patients who had stage 1 and 2 were 86.6% and 13.4%, respectively. The most common histopathological type was invasive ductal carcinoma (71.6%). Estrogen receptor and progesterone receptor positivity were 80.3% and 62.1%, respectively. Her2 receptor positivity was 15.9%. The number of patients who had undergone lumpectomy and mastectomy was 85.5% and 14.5%, respectively. Sentinel lymph node biopsy was performed on 78.7% of the patients, and axillary lymph node dissection 21.3%. Also, the patients received adjuvant radiotherapy (88.7%), adjuvant chemotherapy (48.5%), and adjuvant hormonotherapy (82.1%). Tumor recurrence was occurred in 31 (8.7%) patients (local recurrence-45.2% and metastasis-54.8%). Five-, ten- and twenty-years recurrence ratios were 4.3%, 8%, and 23%. Also, contralateral breast cancer has occurred in 19 (5.3%) patients. During the study period, 30 (8.4%) patients died. Ten-years and twenty-years survival ratios were 91.6% and 76.6%, respectively. In univariate analysis, aged over 65 years (p = 0.004), nuclear pleomorphism (p = 0.049), mitosis (p = 0.003), and necrosis (p = 0.002) were statistically significant for recurrence. In ROC analysis, the tumor's longest size was not statistically significant for recurrence (for over 1.45 cm, p = 0.07). Conclusions: In this study, we determined thirty-years outcomes in patients with early-stage node-negative breast cancer. In the follow-up, we detected the recurrences ratios, between ten and twenty years, were more common than the first ten-years. Despite a small number of patients who had a recurrence, we showed that being age over 65 years and pathological features (nuclear pleomorphism, mitosis, and necrosis) were statistically significant for disease recurrence in univariate analysis.

Pathogenic tau disrupts the cellular program that maintains neuronal identity

Neurons in human Alzheimer’s disease acquire phenotypes that are also present in various cancers, including over-stabilization of the cytoskeleton, nuclear pleomorphism, decondensation of constitutive heterochromatin, and aberrant activation of the cell cycle. Unlike in cancer, in which cell cycle activation drives tumor formation, activation of the cell cycle in post-mitotic neurons is sufficient to induce neuronal death. Multiple lines of evidence suggest that abortive cell cycle activation is a consequence of pathogenic forms of tau, a protein that drives neurodegeneration in Alzheimer’s disease and related “tauopathies.” We have combined network analysis of human Alzheimer’s disease and mouse tauopathy with mechanistic studies in Drosophila to discover that pathogenic forms of tau drive abortive cell cycle activation by disrupting the cellular program that maintains neuronal identity. Mechanistically, we identify Moesin, a prognostic biomarker for cancer and mediator of the epithelial-mesenchymal transition (EMT), as a major effector of tau-induced neurotoxicity. We find that aberrant activation of Moesin in neurons acts through the actin cytoskeleton to dysregulate the cellular program that maintains neuronal identity. Our study identifies mechanistic parallels between tauopathy and cancer and sets the stage for novel therapeutic approaches.