The Potential Prognostic and Therapeutic Implications of Prolactin Receptor and Growth Hormone-releasing Hormone Receptor Expression in Uterine Leiomyosarcomas.

The management of uterine leiomyosarcomas (uLMS) remains challenging. The rate of recurrence and metastasis is high, with 5-yr survival reaching only 40% to 50% in patients with tumor confined to the uterus (FIGO stage I or II). Prolactin receptor (PRLR) and growth hormone-releasing hormone receptor (GHRHR) have been implicated in the carcinogenesis of malignant tumors of the breast, endometrium, ovary, liver, and prostate. GHRHR antagonists inhibit in vitro growth of many human tumors and the expression of PRLR is associated with resistance to chemotherapy. The immunohistochemical expression of PRLR and GHRH in 24 primary and 2 recurrent uLMS was evaluated. Representative sections were stained with PRLR and GHRHR antibodies and immunoreactivity was calculated using H -score. The results were correlated with clinicopathologic data using Kaplan-Meier survival and multivariable Cox proportion hazard regression analyses. All tumors were positive for both markers with predominantly moderate to strong expression of PRLR (89%) and GHRHR (82%). Patients with tumors showing moderate to strong expression of PRLR were significantly less likely to achieve disease-free survival ( P =0.004) and significantly more likely to have a poor overall survival ( P =0.049). No significant difference in mean PRLR expression was found between tumors with higher mitotic counts (>20/10 hpf) and lower mitotic counts (20 or less/10 hpf). Furthermore, in 2 patients where the primary and recurrent tumors were tested, there was stronger expression of PRLR in the recurrence compared with the primary. This correlation was not found with GHRHR. Both PRLR and GHRHR may play a role in carcinogenesis in uLMS, as they do in other malignant neoplasms. To our knowledge, this study is the first evaluating the expression of these receptors in uLMS. Moderate or high expression of PRLR may serve as a prognostic marker associated with recurrences and increased mortality in uLMS patients.

Prosigna® breast cancer assay: histopathologic correlation, development, and assessment of size, nodal status, Ki-67 (SiNK™) index for breast cancer prognosis.

The Prosigna® assay is a United States Food and Drug Administration (US-FDA) cleared molecular test for prognostic use in hormone receptor-positive stage I/II breast cancer in postmenopausal women. We analyzed histopathologic features of 79 cases with Prosigna® assay results and found a significant correlation between tumor size, grade, and Ki-67 labeling index with Prosigna® score (0-40, 41-60, and 61-100) and Prosigna® risk categories. Since the Prosigna® risk stratification is influenced by lymph node status, we designed an index that included lymph node status and the two most correlated variables (size and Ki-67 labeling index). This was termed the size, nodal, and Ki-67 (SiNK™) index and is calculated as follows: (size in mm) + (pN × 10) + (Ki-67 labeling index). The SiNK™ index was divided into ≤40 and >40 to test its prognostic significance in a well-characterized dataset of 106 ER+/HER2-negative stage I-II invasive breast cancers treated with standard multi-modality therapy with long term follow-up (average 101 months follow-up). Patients with SiNK™ ≤40 showed significantly improved distant recurrence-free survival (96% distant recurrence-free survival in SiNK™ ≤40 compared to 81% in SiNK™ >40; log-rank test p value: 0.0027). SiNK™ provides strong prognostic information in ERo+/HER2-negative breast cancers. SiNK™ index is simple to calculate using data from routine pathology reports. This should be further evaluated in larger datasets.

Follow-up Findings in Postconservative Treatment Surveillance for Women With Cervical Adenocarcinoma In Situ.

OBJECTIVES: The risks of adenocarcinoma in situ (AIS) recurrence or progression after conservative treatment are uncertain. The aim of this study was to examine the role of high-risk human papillomavirus (hrHPV) and cytology in the posttreatment surveillance of AIS patients. MATERIALS AND METHODS: Follow-up results of hrHPV status, cytology results, and clinicopathological features of 207 patients were retrospectively analyzed, in whom AIS was initially treated by loop electrosurgical excision procedure (LEEP)/cone biopsy between September 2009 and June 2018. RESULTS: Among 207 patients diagnosed AIS on LEEP/cone biopsy, 30.9% (64/207) had positive margins. Persistent/recurrent AIS rate was substantially higher in the patients with positive margins than in those with negative margins (47.2% vs 9.3%, p < .001). Of 74 patients with hrHPV surveillance, 17 (17/74, 23.0%) were found to have positive hrHPV and 4 (4/17, 23.5%) had the persistent/recurrent AIS regardless of margin status. On the contrast, no AIS were found in negative surveillant hrHPV patients (23.5% vs 0%, p < .001). Lastly, 27.8% patients (22/79) were reported atypical glandular cells on surveillant cytology, and 9 persistent/recurrent AIS cases were further identified on second biopsy or hysterectomy with a positive detection rate of 40.9%. CONCLUSIONS: In this study, we concluded the positive margin on LEEP/cone biopsy in AIS patients was associated with a significantly greater risk of disease persistence or recurrence. The posttreatment surveillance by cytology and adjunct hrHPV would be an ideal strategy in predicting AIS persistence and recurrence, which will warrant further treatments.

Spectrum of tau pathologies in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant disorder caused by a trinucleotide expansion in the huntingtin gene. Recently, a new role for tau has been implicated in the pathogenesis of HD, whereas others have argued that postmortem tau pathology findings are attributable to concurrent Alzheimer's disease pathology. The frequency of other well-defined common age-related tau pathologies in HD has not been examined in detail. In this single center, retrospective analysis, we screened seven cases of Huntington's disease (5 females, 2 males, age at death: 47-73 years) for neuronal and glial tau pathology using phospho-tau immunohistochemistry. All seven cases showed presence of neuronal tau pathology. Five cases met diagnostic criteria for primary age-related tauopathy (PART), with three cases classified as definite PART and two cases as possible PART, all with a Braak stage of I. One case was diagnosed with low level of Alzheimer's disease neuropathologic change. In the youngest case, rare perivascular aggregates of tau-positive neurons, astrocytes and processes were identified at sulcal depths, meeting current neuropathological criteria for stage 1 chronic traumatic encephalopathy (CTE). Although the patient had no history of playing contact sports, he experienced several falls, but no definitive concussions during his disease course. Three of the PART cases and the CTE-like case showed additional evidence of aging-related tau astrogliopathy. None of the cases showed significant tau pathology in the striatum. In conclusion, while we found evidence for tau hyperphosphorylation and aggregation in all seven of our HD cases, the tau pathology was readily classifiable into known diagnostic entities and most likely represents non-specific age- or perhaps trauma-related changes. As the tau pathology was very mild in all cases and not unexpected for a population of this age range, it does not appear that the underlying HD may have promoted or accelerated tau accumulation.

HPV-Associated Atypical Mitotic Figures in Squamous Intraepithelial Lesions of the Lower Female Genital Tract.

OBJECTIVES: Atypical mitoses with rod and dot-shaped extra pieces of chromosomes separate to the main spindle are commonly seen in HPV-associated intraepithelial lesions. To determine the reproducibility and correlation of HPV-associated atypical mitoses (HAM) with histological diagnosis and p16 status, we performed a retrospective study. METHODS: A total of 100 consecutive cervical biopsies, 10 vulvar HSIL (usual VIN), 10 differentiated VIN, 10 vulvar condylomata, 5 normal proliferative endometrial, and 5 normal ovarian follicles were assessed. The first 10 mitoses were examined in the cervical biopsies, and the case recorded as positive when one HAM was identified. The first 50 mitoses in the vulvar cases and controls were examined, and the percentage of HAM was calculated. RESULTS: HAM were found in 62.5% of HSIL, 14.7% of LSIL, and 0% of benign cervical biopsies. When p16 was positive, 62.7% showed HAM, and when p16 was negative, 12.5% showed HAM. HAM were commonly found in vulvar HSIL, 12% of all mitoses, but extra dots of chromosome were also occasionally found in the mitoses of differentiated VIN (1%) and rarely in normal controls (0.2%). No HAM were found in condylomata. CONCLUSIONS: HAM was useful to confirm SIL, but the incidence was too low for absence to exclude SIL. Although HAM are more common in HSIL, they cannot be relied upon to distinguish HSIL from LSIL. The dot form of HAM is less reliable than the rod form, as extra dots of chromosomes may be occasionally seen in differentiated VIN and rarely seen in normal proliferative endometrium.

A comprehensive review of anal cancer-with a special focus on anal cytology.

The diagnosis of anal cancer is relatively uncommon, but its incidence has been steadily increasing in high-risk populations. In the 2001 Bethesda System for Reporting Cervical Cytology, anal cytology was introduced as a component. Since then, it has been recognized as a potential tool for screening anal cancer, often in conjunction with high-resolution anoscopy. There are notable similarities between anal cancer and cervical cancer, including the causative role of human papillomavirus. However, there are also significant differences, particularly in terms of disease prevalence. Anal cytology may be used as a primary screening test, and in the event of abnormalities, patients are subsequently directed for high-resolution anoscopy. However, the best approach for anal cancer screening is yet to be determined and uniformly implemented. This comprehensive review article provides an in-depth analysis of the epidemiology and incidence of anal precursor and malignant lesions. It explores the various methods of sample procurement, preparation, interpretation (including sensitivity and specificity), and reporting terminology in anal cytology. The article also addresses the significance of concurrent high-risk human papillomavirus screening in anal cytology and its role in screening programs. Furthermore, it discusses the follow-up, prevention, and subsequent management strategies for anal cancers. By synthesizing current knowledge in these areas, this review aims to provide a comprehensive understanding of anal cytology and its implications in the early detection, prevention, and management of anal neoplasia and cancer.

Cytopathology in the era of social media.

In today's medical landscape, social media (SoMe) platforms have expanded their reach beyond mere communication and entertainment, making a significant impact in the pathology field, including cytopathology. In recent years, SoMe platforms have become increasingly adopted by cytopathologists, facilitating continued education, professional networking, enhancing patient engagement, and entertainment. This adoption has influenced the professional growth of cytopathologists, and at its best, has led to the establishment of a robust professional online presence and ultimately contributed to leadership positions, fellowship opportunities, and academic promotions. Moreover, the integration of SoMe into the academic field has shown a profound impact on the visibility of academic journals and has provided a platform for lower-impact factor journals to expand their reach, ultimately increasing article citation rates and positively contributing to journal impact factor growth. SoMe platforms created a modern avenue for conference networking that has revolutionized knowledge dissemination and enhanced real-time engagement. The advantages of SoMe have extended to a global scale, positively enhancing professional expertise sharing, facilitating effective communication and teleconsultation worldwide, and reaching developing countries. Drawing insights from the recent medical literature and the practical insight from the experts' personal experience, this article provides a comprehensive review of how SoMe and cytopathology intersect to create new opportunities, facilitating informed discussions, global collaboration, and advancements in the field of cytopathology. This article also delves into the challenges surrounding SoMe platform navigation and addresses ethical and regulatory concerns, providing guidelines on what to post and what not to post on SoMe platforms.

Interobserver Variability in HER-2 Immunostaining Interpretation of Metastatic HER2 Low Breast Cancers in Cytology Specimens.

BACKGROUND: Approximately, 55% of breast carcinomas are reported to be HER-2 low breast carcinomas. Trastuzumab-Deruxtecan is a new FDA-approved targeted therapy for HER-2 low metastatic breast carcinomas, making it essential that all efforts are made to identify these tumors in specimens submitted for pathologic examination. Cytology specimens are often the first and only modality of this assessment due to the ease of specimen procurement. This study aimed to determine the variability in HER-2 immunostaining interpretation among observers using cytologic specimens from metastatic sites. DESIGN: A pathology database search was made to identify metastatic breast carcinoma reported in cytology specimens. A manual search was then done to identify cases of HER-2 low category, H&E cell block and HER-2 neu immunostain slides were retrieved for a total of 50 cases. Reviewer #1 and #2 independently interpreted HER-2 immunostain of all 50 cases. Only discordant cases were sent for reviewer-3 interpretation. All three were blinded by the metastatic site, and original HER-2 interpretation. RESULTS: Of 50 cases, 11 cases (22%) were reported as concordant scores between reviewer #1 and reviewer #2 but had a discordant original IHC report. Additionally, 4 cases (8%) had discordant reporting of HER2 IHC stain between reviewer #1 and reviewer #2 making a total of 15 cases (30%) with overall discordant results. CONCLUSION: This study highlights the interobserver variability of HER-2 immunostain interpretation for HER-2 low category of breast carcinomas. We recommend the need for more robust laboratory techniques including molecular for uniform identification of these unique targetable metastatic breast carcinoma groups.

A six-year comprehensive review of eye cytology cases received at a tertiary level hospital.

BACKGROUND: Ocular cytology is an effective method of diagnosing infective, benign, and malignant ocular disease processes due to easy accessibility and rapid turnaround time. However, these specimens pose significant diagnostic challenges due to rarity of the specimen type, sparse diagnostic material available for ancillary workup, and unfamiliarity of the diagnostic entities by the cytopathologist. METHODS: This study conducted a 6-year comprehensive review of 65 eye cytology cases received at a tertiary level hospital. Cytopathologic diagnoses of "negative for malignancy" and "atypical" were categorized as negative findings (70.8%, n = 46) and diagnoses of "suspicious for malignancy" and "positive for malignancy" were categorized as positive findings (23.1%, n = 15). A 44.6% (n = 29) of cases had subsequent histopathology and/or flow cytometry diagnoses. Premalignant and malignant lesions detected on histopathology were considered as significant findings. Statistical analysis was performed to evaluate the concordance of ocular cytology with associated histopathology and/or flow cytometry diagnoses. RESULTS: The accuracy of final cytology-histopathology and/or cytology-flow cytometry diagnoses in this cohort of cases is 86.2%. The sensitivity and specificity of ocular diagnosis by cytology are 66.6% and 100%, respectively. The positive and negative predictive values of ocular diagnosis by cytology are 100% and 80.9%, respectively. CONCLUSION: Ocular cytology is a fast, effective, and sensitive method for diagnosing ocular pathology specimens. Familiarity with these specimen types by cytopathologists can help in diagnosing ocular diseases effectively on small, challenging cytologic preparations.

Reliably making the primary diagnosis of mesothelioma utilizing serous fluid cytology specimens: an institutional experience.

INTRODUCTION: The diagnosis of mesothelioma has historically been challenging, especially on serous fluid cytology (SFC). Distinguishing between reactive and neoplastic mesothelial cells can be difficult on cytomorphology alone. However, additional ancillary tests, such as BRCA1 associated protein-1 immunohistochemistry and fluorescence in situ hybridization for cyclin-dependent kinase inhibitor 2A deletion, can provide a sensitive and highly specific method of proving malignancy. MATERIALS AND METHODS: SFC specimens diagnosed as mesothelioma, suspicious for mesothelioma (SM), and atypical mesothelial cells (AMCs) since 2012 were identified by querying the laboratory information system. Clinical data and pathologic parameters were gathered. RESULTS: One hundred ten cases of mesothelioma, SM, and AMC were identified. Of these, 61 cases had a definitive diagnosis of mesothelioma on SFC. Average age at SFC diagnosis was 67 years (26-87 years), with most patients being male (67%). Out of the 61 cases, 11 cases (18%) had an initial diagnosis of mesothelioma made on SFC specimens, with 5 of these 11 cases being in patients that never received a histologic diagnosis of mesothelioma. Ancillary studies were utilized in all 11 cases. An initial diagnosis of metastatic mesothelioma was made on SFC in 9 cases (15%). For 6 of these 9 cases, the SFC diagnosis was the sole diagnosis of metastatic mesothelioma without a companion histologic diagnosis. In addition, 15 cases were diagnosed as SM, with 11 of these cases following a definitive mesothelioma diagnosis. Thirty-four cases were diagnosed as AMC, with 27 cases following a definitive mesothelioma diagnosis. CONCLUSIONS: The diagnosis of mesothelioma can be reliably made on SFC with the appropriate cytomorphology criteria and/or confirmatory ancillary testing.

Ten Years of Pathology on Twitter (X): Landscape and Evolution of Pathology on Twitter From 2012 to 2023.

CONTEXT.­: Social media is a powerful tool in pathology education and professional networking that connects pathologists and pathology trainees from around the world. Twitter (X) appears to be the most popular social media platform pathologists use to share pathology-related content and connect with other pathologists. Although there has been some published research on pathology-related activity on Twitter during short time frames, to date there has not been published research examining pathology-related Twitter activity in totality from its earliest days of activity to recently. OBJECTIVE.­: To comprehensively evaluate the use of pathology on Twitter (X) during the last 10 years. DESIGN.­: Pathology-related tweets were systematically scraped from Twitter from January 2012 to January 2023 using pathology hashtags as a surrogate measure for all pathology content on Twitter. COVID-related tweets were approximated by tweets containing the term "COVID." RESULTS.­: There were 591 812 unique pathology-related tweets identified during the time period, with #pathology being the most common hashtag used and #PathTwitter becoming more popular since 2020. There has been positive annual growth of pathology Twitter, with peaks in use during major pathology conferences. During the initial phases of the COVID-19 pandemic a sustained increase in pathology tweets was observed. CONCLUSIONS.­: Pathology Twitter has grown during the last 10 years and has become increasingly popular for pathology education and networking. With the changing landscape of social media platforms this study provides an understanding of how pathology medical education and professional networking uses of social media are used and evolve over time.

CytoLyt fixation impedes insulinoma-associated protein 1 (INSM1) immunoreactivity compared to formalin fixation.

INTRODUCTION: Insulinoma-associated protein 1 (INSM1) is an immunohistochemical marker commonly used to confirm cytomorphological concordant neuroendocrine tumors/carcinomas (NETs/NECs), demonstrating high utility in small samples. Previous reports have suggested comparable INSM1 staining in CytoLyt-fixed cell blocks and formalin-fixed surgical pathology specimens. This study aimed to assess INSM1 immunoreactivity using both fixation methods and investigate potential factors contributing to its variable expression. MATERIALS AND METHODS: A retrospective query was performed (03/31/21-05/31/22) for NET/NEC cases that had both formalin- and CytoLyt-fixed cell blocks. We collected clinical data and reporting of immunostains for each case. INSM1 staining was evaluated in both fixation methods, and reported as positive, negative, or equivocal. Equivocal INSM1 staining was further scored as a percentage of 1%-100% and intensity of weak (faint staining), moderate (darker staining), and strong (dense staining). RESULTS: Our search identified 20 cases from diverse body sites, including mediastinal lymph nodes (40%), pancreas (35%), lung (20%), and porta hepatis lymph nodes (5%). All cases exhibited a widespread positivity (over 90%) in formalin-fixed cell blocks. In contrast, CytoLyt fixed cells showed a negative stain in 65% of cases and 30% exhibited an equivocal positivity. CONCLUSIONS: While INSM1 is previously reported as a sensitive (75%-100%) and specific (82.7%-100%) marker for NET/NECs, our study found a reduced immunohistochemical staining in CytoLyt-fixed cell blocks. Consequently, false negative INSM1 immunohistochemical results in CytoLyt-fixed cell block material may pose a pitfall in the diagnosis of NET/NEC.

Staphylococcus aureus adapts to exploit collagen-derived proline during chronic infection.

Staphylococcus aureus is a pulmonary pathogen associated with substantial human morbidity and mortality. As vaccines targeting virulence determinants have failed to be protective in humans, other factors are likely involved in pathogenesis. Here we analysed transcriptomic responses of human clinical isolates of S. aureus from initial and chronic infections. We observed upregulated collagenase and proline transporter gene expression in chronic infection isolates. Metabolomics of bronchiolar lavage fluid and fibroblast infection, growth assays and analysis of bacterial mutant strains showed that airway fibroblasts produce collagen during S. aureus infection. Host-adapted bacteria upregulate collagenase, which degrades collagen and releases proline. S. aureus then imports proline, which fuels oxidative metabolism via the tricarboxylic acid cycle. Proline metabolism provides host-adapted S. aureus with a metabolic benefit enabling out-competition of non-adapted strains. These data suggest that clinical settings characterized by airway repair processes and fibrosis provide a milieu that promotes S. aureus adaptation and supports infection.

Significance of concurrent HPV testing with unsatisfactory Papanicolaou test for prediction of follow-up HPV, Papanicolaou test, and biopsy results.

OBJECTIVES: Approximately 1% to 2% of routine cytologic specimens collected for Papanicolaou testing are unsatisfactory for evaluation. The American Society for Colposcopy and Cervical Pathology 2019 guidelines recommend repeat testing within 2 to 4 months of an unsatisfactory Papanicolaou test (UPT) result. METHODS: We evaluated the utility of follow-up Papanicolaou testing, human papillomavirus (HPV) testing, and biopsy in 258 cases of UPTs. RESULTS: High-risk HPV testing was positive in 17.4% (n = 45) and negative in 82.6% (n = 213) of cases at the time of initial UPT; 8.1% (n = 21) of cases had discordant HPV test results. Similarly, 3.8% (n = 8) of initially HPV-negative cases were reported to be HPV-positive on follow-up; 28.9% (n = 13) of initially HPV-positive cases were reported to be HPV negative on follow-up. In total, 27.1% (n = 70) of cases underwent biopsy. Biopsies with significant findings were present in 40% (n = 12) of HPV-positive cases and 7.5% (n = 3) of HPV-negative cases. Low-grade squamous intraepithelial lesion (LSIL) (low-grade cervical intraepithelial neoplasia [CIN-1]) was the most significant finding in all 3 HPV-negative biopsies; 58.3% (n = 7) of HPV-positive biopsies showed LSIL (CIN-1), 13.3% (n = 4) showed HSIL (high-grade CIN), and 3.3% (n = 1) showed invasive carcinoma. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of concurrent HPV testing at the time of UPT for predicting follow-up HPV test result within 1 year of initial UPT are 80.0%, 94.0%, 71.1%, and 96.2%, respectively. The sensitivity, specificity, PPV, and NPV of initial HPV test results for predicting follow-up Papanicolaou test results are 67.7%, 89.7%, 48.8%, and 95.0%, respectively. RESULTS: Concurrent HPV testing in the setting of UPT can be a sensitive tool for predicting follow-up HPV status and significant findings of squamous intraepithelial lesions on follow-up Papanicolaou tests and biopsy.

Staphylococcus aureus stimulates neutrophil itaconate production that suppresses the oxidative burst.

Neutrophils are critical in the host defense against Staphylococcus aureus, a major human pathogen. However, even in the setting of a robust neutrophil response, S. aureus can evade immune clearance. Here, we demonstrate that S. aureus impairs neutrophil function by triggering the production of the anti-inflammatory metabolite itaconate. The enzyme that synthesizes itaconate, Irg1, is selectively expressed in neutrophils during S. aureus pneumonia. Itaconate inhibits neutrophil glycolysis and oxidative burst, which impairs survival and bacterial killing. In a murine pneumonia model, neutrophil Irg1 expression protects the lung from excessive inflammation but compromises bacterial clearance. S. aureus is thus able to evade the innate immune response by targeting neutrophil metabolism and inducing the production of the anti-inflammatory metabolite itaconate.

Ketogenesis promotes tolerance to Pseudomonas aeruginosa pulmonary infection.

Pseudomonas aeruginosa is a common cause of pulmonary infection. As a Gram-negative pathogen, it can initiate a brisk and highly destructive inflammatory response; however, most hosts become tolerant to the bacterial burden, developing chronic infection. Using a murine model of pneumonia, we demonstrate that this shift from inflammation to disease tolerance is promoted by ketogenesis. In response to pulmonary infection, ketone bodies are generated in the liver and circulate to the lungs where they impose selection for P. aeruginosa strains unable to display surface lipopolysaccharide (LPS). Such keto-adapted LPS strains fail to activate glycolysis and tissue-damaging cytokines and, instead, facilitate mitochondrial catabolism of fats and oxidative phosphorylation (OXPHOS), which maintains airway homeostasis. Within the lung, P. aeruginosa exploits the host immunometabolite itaconate to further stimulate ketogenesis. This environment enables host-P. aeruginosa coexistence, supporting both pathoadaptive changes in the bacteria and the maintenance of respiratory integrity via OXPHOS.

Reassessing the optimal volume for malignancy detection in serous fluid cytology.

BACKGROUND: The international system for reporting serous fluid cytopathology (TIS) recommends submitting at least 50-75 mL of serous fluid to decrease false-negative results. However, prior studies did not agree on specific volume requirements or consensus adequacy criteria. Our study aims to assess whether fluid volume affects the adequacy rate and to assess the minimum volume necessary for optimal adequacy in pleural and peritoneal fluids. METHODS: A total of 8530 serous fluid cytology cases were identified in the laboratory information system. Differences in mean fluid volume received in the laboratory were compared using an ANOVA Games-Howell test based on TIS category. The percentage of malignant diagnoses across the volume ranges of 0 to 5 mL, 5 to 10 mL, 10 to 25 mL, 25 to 50 mL, 50 to 75 mL, 75 to 100 mL, 100 to 150 mL, 150 to 250 mL, 250 to 500 mL, 500 to 2000 mL was compared in pleural and peritoneal fluids using a chi-square test, and a SiZer analysis was performed. RESULTS: Mean fluid volume in inadequate, atypical, and negative cases was significantly lower compared to positive cases. A SiZer analysis showed a positive relationship between the malignancy fraction of pleural and peritoneal fluids and fluid volume. The percentage of malignant diagnoses in pleural and peritoneal fluid samples increased significantly up to a volume range of 75-100 mL. CONCLUSIONS: There is a significant relationship between fluid volume, adequacy and detection of malignancy in serous effusion cytopathology. The malignancy fraction increases with larger fluid volumes but at least 75-100 mL of fluid should be submitted for optimal diagnosis of malignancy in pleural and peritoneal fluids.

Klebsiella pneumoniae induces host metabolic stress that promotes tolerance to pulmonary infection.

K. pneumoniae sequence type 258 (Kp ST258) is a major cause of healthcare-associated pneumonia. However, it remains unclear how it causes protracted courses of infection in spite of its expression of immunostimulatory lipopolysaccharide, which should activate a brisk inflammatory response and bacterial clearance. We predicted that the metabolic stress induced by the bacteria in the host cells shapes an immune response that tolerates infection. We combined in situ metabolic imaging and transcriptional analyses to demonstrate that Kp ST258 activates host glutaminolysis and fatty acid oxidation. This response creates an oxidant-rich microenvironment conducive to the accumulation of anti-inflammatory myeloid cells. In this setting, metabolically active Kp ST258 elicits a disease-tolerant immune response. The bacteria, in turn, adapt to airway oxidants by upregulating the type VI secretion system, which is highly conserved across ST258 strains worldwide. Thus, much of the global success of Kp ST258 in hospital settings can be explained by the metabolic activity provoked in the host that promotes disease tolerance.

The practice of cytopathology during the era of COVID-19: challenges and changes.

This paper reviews the challenges faced by cytology laboratories during the COVID-19 pandemic. Various safety guidelines regarding collection, handling, transport and sampling in cytology laboratory are presented. A brief literature overview of adapted changes regarding new safety techniques, processing, sampling techniques implemented by the cytology laboratories in this part of the world is presented. The use of cytology in COVID-19 patients is discussed. The authors have also tried to present the challenges and changes faced for training and education during this time. Migration from multi-headed scope in-person sign-out to digital based platforms were adapted to continue medical education. The potential long-term implications of these adaptations on cytology services are also touched upon.

Educational Case: High-Grade Serous Carcinoma of the Ovary.

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, seehttp://journals.sagepub.com/doi/10.1177/2374289517715040.1.