Journal of Clinical Pathology最新文献

Aims: Programmed death-ligand 1 (PD-L1) is known to be highly expressed in various malignancies, including head and neck squamous cell carcinoma (HNSCC). We aimed to determine the prevalence of PD-L1 expression in recurrent or metastatic HNSCC (R/M HNSCC) among Chinese patients.

Methods: This multicentre, retrospective analysis of data from six centres in China included patients with R/M HNSCC treated from 9 August 2021 to 28 February 2022. PD-L1 expression in tumour tissue was assessed and represented using a combined positive score (CPS). The χ² and Cochran-Mantel-Haenszel χ² tests were used to compare the prevalence of different PD-L1 expression statuses according to related co-variables.

Results: For all 402 examined patients with R/M HNSCC, 168 cases (41.8%) had PD-L1 expression with a CPS ≥20, and 337 cases (83.8%) had PD-L1 expression with a CPS ≥1. Between the PD-L1 CPS ≥20 group and PD-L1 CPS <20 group, statistically significant differences were observed for variables of sex (p<0.001), smoking habit (p=0.0138 for non-smokers vs current smokers) and primary tumour site (p<0.001 for hypopharynx vs oral cavity and p=0.0304 for larynx vs oral cavity, respectively).

Conclusion: PD-L1 with CPS ≥20 was expressed in about 41.8% of cases with R/M HNSCC among Chinese patients, and PD-L1 expression was significantly associated with sex, smoking history and primary tumour site. Our findings regarding the variables related to PD-L1 expression level provide insight for clinical practice and a solid basis for future research on immunotherapy in HNSCC.

Trial registration number: ISRCTN10570964.

Even though the average surgical pathologist reviews far more non-neoplastic orthopaedic pathology on a daily basis, most current research focuses on rare tumours and their even less frequent molecular events. Our experiences among consults and focused conferences strongly suggest that there remains a practice gap regarding knowledge and diagnosing specific non-neoplastic orthopaedic conditions. One of the most frequent intraoperative consultations performed in the USA, among both academic and private institutions, relates to revision arthroplasty and the determination of infection in periprosthetic joints. Pathologists play a critical role in this algorithm, helping determine intraoperatively whether patients require antibiotic spacers prior to reimplantation. Many pathology departments have abandoned the examination of arthroplasty specimens because they (and their surgeons) mistakenly believe there is little clinically relevant information to be gained by thorough pathological examination. However, recent literature has challenged this concept, emphasising the importance of distinguishing avascular necrosis (from osteoarthritis/degenerative joint disease with secondary osteonecrosis), subchondral insufficiency fracture, septic arthritis (from so-called 'sterile' osteomyelitis/pseudoabscesses), underlying crystalline diseases and incidental/occult neoplasia. Histological evaluation of historically insignificant orthopaedic specimens, such as tenosynovium from carpal tunnel syndrome/trigger finger, is now seen as valuable in early diagnosis of cardiac amyloidosis. Not infrequently, orthopaedic conditions like haemosiderotic synovitis, osteocartilaginous loose bodies or rheumatoid nodules, may histologically mimic bona fide neoplasms, notably diffuse tenosynovial giant cell tumour, synovial chondromatosis and epithelioid sarcoma, respectively. Here is a review of the more common non-neoplastic orthopaedic conditions, those likely to be examined by the practising surgical pathologist, with updates and guidelines for establishing clinically relevant diagnoses.

Aims: Structured reporting in pathology is not universally adopted and extracting elements essential to research often requires expensive and time-intensive manual curation. The accuracy and feasibility of using large language models (LLMs) to extract essential pathology elements, for cancer research is examined here.

Methods: Retrospective study of patients who underwent pathology sampling for suspected hepatocellular carcinoma and underwent Ytrrium-90 embolisation. Five pathology report elements of interest were included for evaluation. LLMs (Generative Pre-trained Transformer (GPT) 3.5 turbo and GPT-4) were used to extract elements of interest. For comparison, a rules-based, regular expressions (REGEX) approach was devised for extraction. Accuracy for each approach was calculated.

Results: 88 pathology reports were identified. LLMs and REGEX were both able to extract research elements with high accuracy (average 84.1%-94.8%).

Conclusions: LLMs have significant potential to simplify the extraction of research elements from pathology reporting, and therefore, accelerate the pace of cancer research.

An insufficient/inadequate diagnosis on fine-needle aspiration cytology (FNAC) of the breast is not an uncommon diagnostic dilemma. This study aims to review the rate and clinical features predicting an informative or actionable diagnosis on repeating breast aspiration after an insufficient aspirate.

Methods: Unsatisfactory/insufficient/inadequate or equivalent breast aspirates were retrieved from the involved institutions, and those with a repeat aspiration performed within 365 days were included. Clinical and radiological information were retrieved. Available cytological slides were reviewed.

Results: Totally 539 paired aspirates were retrieved, with 61.2% (n=330/539) and 10.9% (n=59/539) cytological diagnosis being informative (not insufficient) and actionable (not insufficient nor benign) on repeat aspiration. Younger age (p=0.005) was associated with an informative diagnosis and prior radiotherapy (p=0.097) and insufficient aspirates performed under free-hand (p=0.097) trended with an actionable diagnosis. Radiological findings of calcification (p=0.026) and hyperechogenicity (p=0.045), a small lesion size on initial (p=0.037) and repeat (p=0.059) radiological assessment and interval size increment (p=0.019) correlated with informative/actionable diagnoses. Cytomorphological parameters, except for a trend with crushing artefact (p=0.063), do not correlate with the cytologic diagnosis of the repeat aspirate.

Conclusions: Repeating breast FNAC on patients after an insufficient diagnosis yields an informative ('sufficient') result in over 60% of cases. Small lesions with calcification, hyperechogenicity and/or interval size increment are more likely to yield diagnostic results on repeat aspiration and indicate select patients suitable for repeat FNAC over more invasive procedures. The lack of associations with cytomorphological parameters cautions against overinterpretation of insufficient breast aspirates.

Aims: Special histomorphological subtypes of colorectal low-grade intraepithelial neoplasia (LGIN) with variable prognostic impact were recently described in patients with inflammatory bowel disease (IBD) referred to as non-conventional dysplasia. However, they can also be found in patients without IBD. We aimed to analyse the reproducibility, frequency and prognostic impact of non-conventional colorectal LGIN in patients with and without IBD.

Methods: Six pathologists evaluated 500 specimens of five different LGIN-cohorts from patients with and without IBD. Non-conventional LGIN included hypermucinous, goblet cell-deficient, Paneth cell-rich and crypt cell dysplasia. A goblet cell-rich type and non-conventional LGIN, not otherwise specified were added. Results were compared with the original expert-consented diagnosis from archived pathology records.

Results: Four or more pathologists agreed in 86.0% of all cases. Non-conventional LGIN was seen in 44.4%, more frequently in patients with IBD (52%; non-IBD: 39.3%, p=0.005). In patients with IBD non-conventional LGIN associated with more frequent and earlier LGIN relapse (p=0.006, p=0.025), high-grade intraepithelial neoplasia (p=0.003), larger lesion size (p=0.001), non-polypoid lesions (p=0.019) and additional risk factors (p=0.034). Results were highly comparable with expert-consented diagnoses. In patients without IBD, non-conventional LGIN may indicate a higher risk for concurrent or subsequent colorectal carcinoma (CRC, p=0.056 and p=0.061, respectively). Frequencies and association with high-grade intraepithelial neoplasia or CRC varied between the different LGIN subtypes.

Conclusions: Non-conventional histomorphology in colorectal LGIN is frequent and highly reproducible. Our results indicate an increased risk for CRC in patients with non-conventional LGIN, probably independent of IBD. We recommend reporting non-conventional LGIN in routine pathology reports.

Aims: Progesterone receptor (PR) is a crucial prognostic marker in breast cancer. However, achieving consistent results in PR immunohistochemistry (IHC) remains challenging due to the lack of well-defined low-positive controls. This study aimed to identify benign tissues with consistent low-level PR expression to serve as ideal controls for IHC.

Methods: We evaluated PR expression in the squamous epithelium of the uterine cervix, nipple smooth muscle and pancreatic islets. QuPath digital image analysis was employed to compare the intensity and quantity of PR staining in target cells within a 2×2 mm area.

Results: The squamous epithelium of the secretory phase cervix, nipple smooth muscle and pancreatic islets displayed appreciable weak PR expression, with mean values of 73, 55 and 60 cells, respectively. Notably, 62% (8/13) of the 2×2 mm areas in the atrophic cervix were completely negative for PR expression. The coefficients of variation for weak PR-expressing cells in pancreatic islets (57.4%) and nipple smooth muscle (65.0%) were lower than those observed in the cervix (96.2%-222.0%). The squamous epithelium of the cervix, especially during the secretory phase, exhibited weak positivity confined to the basal layers, providing another viable control option. However, variations in PR expression may be influenced by physiological factors, such as hormonal fluctuations.

Conclusions: Pancreatic islets and nipple smooth muscle, with their consistent low-level PR expression, offer a promising solution to the challenges associated with PR IHC. This approach may help minimise variations resulting from differing staining methods across laboratories.

Aims: Concerns over population-level immunity have been heightened with each successive wave of COVID-19, prompting questions about whether it is primarily derived from vaccination efforts or from previous natural infections with the virus. We wished to determine the seroprevalence of SARS-CoV-2 antibodies among healthcare workers (HCWs) in Pretoria (Tshwane), South Africa, and to establish whether they were derived from vaccination or natural infection.

Methods: Serum samples were collected from HCWs during the fourth wave of COVID-19 between 1 December 2021 and 13 March 2022. The samples were tested using the Abbott SARS-CoV-2 Spike IgG (S-IgG), IgM (S-IgM) and the SARS-CoV-2 Nucleocapsid IgG (NC-IgG) kits.

Results: Of the 221 participants, 76% (n=168) were women and 24% (n=53) were men. A total of 96.4% (n=213) of the participants were vaccinated. Natural infection-derived antibodies were detected in 23% (n=51) of participants, and vaccine-derived antibodies in 74% (n=164) of the HCWs.

Conclusions: Even after three waves of COVID-19, HCWs derived most of their detectable antibodies from vaccination. Vaccination remains an essential tool to protect HCWs and patients from SARS-CoV-2 infection.

Aims: To reveal clinicopathological characteristics of alcoholic foamy degeneration (AFD)-an uncommon form of alcoholic liver injury.

Methods: Clinicopathological features of AFD (n=9) were examined in comparison to those of severe alcoholic hepatitis (SAH; n=12).

Results: Patients with AFD presented with either biochemical liver dysfunction (n=1) or clinical jaundice (n=8). One case had undergone liver transplantation for alcohol-related cirrhosis and hepatocellular carcinoma 2 years and 3 months before presentation. AFD cases were histologically classified into three groups. The non-jaundiced case had mixed macro- and microvesicular bland steatosis. Seven jaundiced cases showed more complex microscopic features with lobular inflammation, acidophilic bodies, cholestasis and lobular distortion. Hepatocytes were pleomorphic, some extensively enlarged with clear cytoplasm, somewhat resembling ballooning degeneration; however, it was mainly due to accumulated lipid droplets ('pseudoballooning'). The remaining case also had predominant changes of AFD, but a few foci showed classical ballooning hepatocytes and Mallory-Denk bodies, in keeping with mixed AFD and steatohepatitis. When compared with patients with SAH, those with AFD had lower white blood cell and neutrophil counts and higher cholesterol levels (all p<0.001). On imaging, ascites and varices were less common in AFD than in SAH (11% vs 75%, p=0.014; 0% vs 67%, p=0.008, respectively). All seven patients with AFD who successfully abstained from alcohol experienced rapid improvement in liver function.

Conclusions: Microscopic findings of AFD are more complex than currently thought, and some cases may be mistaken for steatohepatitis. AFD may also develop in conjunction with steatohepatitis or following liver transplantation.

Aims: Establishment of a protocol for routine single-molecule localisation microscopy (SMLM) imaging on formalin fixed paraffin embedded (FFPE) tissue using medical renal disease including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS).

Methods: Protocol for normal and diseased renal FFPE tissue was developed to investigate the clinical diagnostic potential of SMLM. Antibody concentrations were determined for confocal microscopy and transferred to SMLM. Different fixatives and lengths of fixation were studied. To reduce autofluorescence, additional quenching and UV bleaching steps were compared. Optimal SMLM acquisition settings were established. SMLM data were imaged, digitally captured, stored, visually inspected and analysed quantitatively.

Results: Protocol was established on normal renal FFPE tissue and then applied to clinical diseased tissue with single and multiple markers. Antibodies against key diagnostic proteins including podocin, nephrin, collagen, laminin, synaptopodin, CD31, IgG, IgM and IgA antibodies were established for MCD, FSGS and immune-mediated renal disease. We found important characteristic differences in the renal diseases listed above.

Conclusions: We established a routine super-resolution microscopy protocol for clinical FFPE material on medical renal biopsies, which could visualise fluorescently labelled proteins in all glomeruli present with a precision of approximately 10-20 nm, with a turnaround under 48 hours. We visualised and quantitated specific protein distributions in different conditions. SMLM opens subcellular microscopy in FFPE to histopathologists on routine FFPE tissue, which can in the future be an adjunct and, in some aspects, a rapid superior alternative to electron microscopy.