Pathologist Computer-Aided Diagnostic Scoring of Tumor Cell Fraction: A Swiss National Study.

Tumor cell fraction (TCF) estimation is a common clinical task with well-established large interobserver variability. It thus provides an ideal test bed to evaluate potential impacts of employing a tumor cell fraction computer-aided diagnostic (TCFCAD) tool to support pathologists' evaluation. During a National Slide Seminar event, pathologists (n = 69) were asked to visually estimate TCF in 10 regions of interest (ROIs) from hematoxylin and eosin colorectal cancer images intentionally curated for diverse tissue compositions, cellularity, and stain intensities. Next, they re-evaluated the same ROIs while being provided a TCFCAD-created overlay highlighting predicted tumor vs nontumor cells, together with the corresponding TCF percentage. Participants also reported confidence levels in their assessments using a 5-tier scale, indicating no confidence to high confidence, respectively. The TCF ground truth (GT) was defined by manual cell-counting by experts. When assisted, interobserver variability significantly decreased, showing estimates converging to the GT. This improvement remained even when TCFCAD predictions deviated slightly from the GT. The standard deviation (SD) of the estimated TCF to the GT across ROIs was 9.9% vs 5.8% with TCFCAD (P < .0001). The intraclass correlation coefficient increased from 0.8 to 0.93 (95% CI, 0.65-0.93 vs 0.86-0.98), and pathologists stated feeling more confident when aided (3.67 ± 0.81 vs 4.17 ± 0.82 with the computer-aided diagnostic [CAD] tool). TCFCAD estimation support demonstrated improved scoring accuracy, interpathologist agreement, and scoring confidence. Interestingly, pathologists also expressed more willingness to use such a CAD tool at the end of the survey, highlighting the importance of training/education to increase adoption of CAD systems.

Donor-derived fulminant herpes simplex virus hepatitis after liver transplantation: Two cases and review of literature.

BACKGROUND: Fulminant herpetic hepatitis due to herpes simplex virus (HSV), serotype 1 or 2, is a rare but often fatal complication after solid organ transplantation (SOT). HSV hepatitis in SOT recipients can occur either due to primary infection acquired post transplantation, viral reactivation in a seropositive patient, or as donor-derived infection. Cases of fatal hepatitis have been reported in the liver as well as in other SOT recipients. The fatal outcome is mostly due to delayed diagnosis and treatment, which is explained by the lack of clinical specificity of HSV hepatitis. METHODS: We report two cases of fatal donor-derived HSV hepatitis in liver-transplanted recipients. We reviewed all published cases of donor-derived HSV infections after SOT with an evaluation of the presence of prophylaxis and outcome. RESULTS: In both liver recipients, the retrospective determination of HSV serostatus was negative, and both cases occurred in the absence of cytomegalovirus or HSV prophylaxis. A review of the literature showed a significant series of cases of severe hepatitis, mostly fatal, as well as the absence of specific preventive therapy guidelines in cases of HSV serology mismatch. CONCLUSIONS: The occurrence of two fatal donor-derived hepatitis made the Swiss Transplant Infectious Diseases working group modify its national recommendations regarding pretransplant serostatus determination and HSV prophylaxis after liver transplantation. Further studies are needed to assess this approach.

The Milan system for reporting salivary gland cytopathology-A single-center study of 2156 cases.

BACKGROUND: Fine-needle aspiration cytology (FNAC) represents an important diagnostic tool for the workup of salivary gland (SG) lesions. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a six-tiered system for standardizing diagnoses and improvement of communication between pathologists and clinicians, providing risk of malignancy (ROM) rates for every category. The aims of the present study were (i) to validate the use of MSRSGC in a large series of SG FNAC in a tertiary center in Switzerland, (ii) to determine ROM for each category and compare them with data from MSRSGC and similar studies, and (iii) to investigate whether there were relevant differences of non-diagnostic results between fine-needle aspirations (FNA) performed by cytopathologists compared to non-cytopathologists. METHODS: The files of the department of Pathology in the University Hospital Zurich (UHZ) were searched for SG FNAC between 2010 and 2019. The MSRSGC guidelines were applied retrospectively. Furthermore, ROM, risk of neoplasia (RON), sensitivity, and specificity were calculated based on the cases with histopathological follow-up. RESULTS: A total of 2156 SG FNAC including 753 cases with histopathological follow-up were evaluated. Generally, ROM was within the range of values provided by MSRSGC, with some minor deviations. Sensitivity was 94.6%, and specificity was 99.3%. CONCLUSIONS: Our study confirms the usefulness of MSRSGC. In addition, it provides a detailed insight into the wide spectrum of SG FNAC. Finally, we showed that the rate of non-diagnostic FNA was significantly lower in FNAs performed by cytopathologists compared to non-cytopathologists.

Fine needle aspiration in COVID-19 vaccine-associated lymphadenopathy.

AIMS: With ongoing intensive vaccination programme against COVID-19, numerous cases of adverse reactions occur, some of which represent rare events. Enlargement of the injection site’s draining lymph nodes is increasingly reported, but is not yet widely recognised as being possibly associated with recent vaccination. As patients at risk of a severe course of COVID-19, indicated by their medical history such as a previous diagnosis of malignancy, receive priority vaccination, newly palpable lymph nodes raise concerns of disease progression. In this case series, we report on five patients who presented with enlarged lymph nodes after COVID-19 vaccination. METHODS: Sonography guided fine needle aspiration (FNA) was performed in five patients presenting with PET-positive and/or enlarged lymph nodes after COVID-19 vaccination with either the Pfizer-BioNTech or Moderna vaccine. RESULTS: COVID-19 vaccination had been carried out in all cases, with an interval of between 3 and 33 days prior to FNA. Three of five patients had a history of neoplasms. The vaccine was administered into the deltoid muscle, with subsequent enlargement of either the cervical, supra-, infra- or retroclavicular, or axillary lymph nodes, in four out of five cases ipsilaterally. In all cases, cytology and additional analyses showed a reactive lymphadenopathy without any sign of malignancy. CONCLUSIONS: Evidence of newly enlarged lymph nodes after recent COVID-19 vaccination should be considered reactive in the first instance, occurring owing to stimulation of the immune system. A clinical follow-up according to the patient’s risk profile without further diagnostic measures is justified. In the case of preexisting unilateral cancer, vaccination should be given contralaterally whenever possible. Persistently enlarged lymph nodes should be re-evaluated (2 to) 6 weeks after the second dose, with additional diagnostic tests tailored to the clinical context. Fine needle aspiration is a well established, safe, rapid and cost-effective method to investigate an underlying malignancy, especially metastasis. Recording vaccination history, including date of injection, site and vaccine type, as well as communicating this information to treating physicians of different specialties is paramount for properly handling COVID-19 vaccine-associated lymphadenopathy.

Synergy of cytological methods in the pathological staging of breast cancer: Axillary fine-needle aspiration and intraoperative scrape cytology of the sentinel lymph node.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has become the standard in breast cancer staging, but it is costly and time-consuming. Fine-needle aspiration cytology (FNAC) under ultrasonographic guidance identifies patients who need axillary lymph-node dissection (ALND), thus reducing costs. As an alternative to frozen sections (FS), intraoperative scrape cytology (ISC) for SLNB is an inexpensive, rapid, accurate and safe technique. We evaluated the synergy of FNAC and SLNB in determining the axillary burden and the performance of the ISC method. METHODS: Over a nine-year period, 894 breast cancer patients were analyzed. Of these, 439 patients with echographic suspicious nodes underwent preoperative FNAC; negative axillary ultrasounds or FNACs resulted in 606 intraoperative SLNB, performed using the ISC technique. The results were compared with histological diagnosis, and sensitivity, specificity, predictive values and accuracy were calculated. RESULTS: Of the 439 FNACs, 121 were positive and underwent immediate ALND, and 242 negative patients underwent intraoperative SLNB (69% sensitivity, 99% specificity). Positive cases often had multiple nodal involvement (55% pN2-3). Of the 606 SLNB-ISC smears, 510 were true negative; 65 true positives allowed for one-step ALND (71% sensitivity, 99% specificity). CONCLUSION: Preoperative positive axillary FNAC predicts a higher disease burden and determines the avoidance of SLNB for patients eligible for immediate ALND. ISC instead of FS is a safe and sensitive technique to identify metastases, indicating completion of ALND. PARTIALLY PRESENTED AT: Joint International Oncology (sentinel node & cancer metastasis) Congress, May 27-29, 2013, San Francisco, California, USA 18 ° International Congress of Cytology (ICC 2013-1161), May 26-30, 2013, Paris, France Convegno Nazionale GISMa - Finalborgo (Savona), Italy,19-20 maggio 2016.

Rare abdominal metastases from occult lobular breast cancer: report of two cases.

Intra-abdominal metastases from breast carcinomas are rarely reported in the literature. Least are those originating from occult breast primary. We report, one case of pancreatic metastasis and one case of metastatic infiltration of the colonic wall, both by occult lobular breast carcinoma. The first patient underwent pancreaticoduodenectomy for obstructive jaundice, with unexpected histological finding of infiltration of distal bile duct, pancreatic gland, portal vein and retroperitoneal soft tissue by lobular carcinoma of the breast. The second patient complained of diffuse abdominal pain associated with constipation and rectal bleeding and underwent endoscopic biopsy of three intestinal strictures, revealing metastatic lobular carcinoma with signet-ring cell morphology. In both cases, a subsequent complete diagnostic work-up demonstrated asymptomatic multiple breast nodules, diagnosed as lobular carcinoma by fine needle aspiration cytology.

Cytologic diagnosis of ocular melanocytoma: a case report.

BACKGROUND: Pigmented lesions of the eye represent a challenging field from both clinical and pathologic approaches. The importance of a correct diagnosis in this case is enhanced by the delicate structures involved and their difficult accessibility. CASE: We report a case of a 51-year-old man with acute vision loss and the feeling of a foreign body in the left eye diagnosed with vitreous hemorrhage. A small, pigmented lesion in the proximity of optic nerve head was detected. After a 9-year follow-up, a definitive diagnosis of melanocytoma was achieved in vitrectomy cytology. Smears showed a population of plump, cohesive melanocytes and elongated cells with cytoplasmic melanin and uniform rounded nuclei. No change in the lesion has occurred 3 years after vitrectomy. CONCLUSION: Fine needle aspiration proved to be helpful and reliable for the correct diagnosis of melanocytoma, which does not require additional treatment.

PAX8 expression in human bladder cancer.

PAX8 is a transcription factor with a role in ontogenesis of the urinary tract. The aim of the present investigation was to investigate PAX8 expression in normal bladder and in non-invasive urothelial tumours. Nine cases of normal urothelial mucosa, 2 cases of papillary urothelial neoplasia of low malignant potential, 12 cases of low grade non-invasive papillary urothelial carcinoma and 16 cases of high grade non-invasive papillary urothelial carcinoma were investigated by immunohistochemistry. PAX8 mRNA expression was evaluated by RT-PCR in a different set of normal bladder mucosas and tumours. In addition, PAX8 expression was evaluated by RT-PCR in bladder from 2 human embryos and in several continuous cell lines derived from bladder tumours (5637, RT-112, TCC-SUP, HT 1376). In immunohistochemical studies, PAX8 was expressed in 28 out of 30 non-invasive urothelial tumours, but not in the normal adult bladders. In RT-PCR studies, PAX8 was expressed in 13 out of 13 bladder tumours but not in the 6 normal bladder mucosa. Contrary to that in adults, PAX8 was expressed in 2 cases of bladder mucosa from 16-week-old embryos. PAX8 was expressed in all the cell lines from bladder tumours. Both in the bladder tumours and cell lines PAX8 expression was highly heterogeneous in terms of the splicing isoforms. Treatment of cell lines with sodium butyrate (NaB) induced several changes of the splicing isoforms. Therefore, only subsets of molecular events that determine the PAX8 mRNA splicing heterogeneity in bladder tumours are sensitive to NaB treatment.