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: Current guidelines offer limited strategies for managing recurrent/persistent oesophageal adenocarcinoma (EAC). Salvage endoscopic mucosal/submucosal resection (ER) shows promise in oesophageal squamous cell carcinoma, however its success in EAC is limited. We aimed to elucidate histological characteristics influencing salvage ER success in patients with low-stage, pretreated EAC.
Methods: We retrospectively reviewed 272 EAC tumours postoesophagectomy from five US centres and collected clinicopathological data including discontinuous growth (DG), defined as separate tumour foci ≥2 mm from the main tumour. We selected 101 patients with low-stage disease and divided them into treatment-naïve (n=70) and neoadjuvant therapy (n=31) groups. We compared the two groups and differences in clinical, histological and outcome characteristics were identified.
Results: In the entire cohort (n=272), DGs were identified in 22% of cases. Multivariate analysis revealed DGs as an independent prognostic factor for recurrence and positive oesophagectomy margins. Lymphovascular invasion (LVI) and background intestinal metaplasia predicted DG presence and absence, respectively. Compared with the treatment-naïve low T-stage subgroup, the pretreated subgroup exhibited higher incidence of poorly differentiated carcinoma (16% vs 46%, p=0.007), larger tumours (14 vs 30 mm, p<0.001), higher tumour, node, metastases stage (7% vs 30%, p=0.004), more nodal disease (7% vs 36%, p<0.001) and frequent DGs (1% vs 13%, p=0.030).
Conclusions: In treated low T-stage EACs, DGs may contribute to suboptimal outcomes following salvage ER. Presence of LVI (as a surrogate for DGs) and poor differentiation in the absence of intestinal metaplasia in biopsy samples may serve as histological poor prognosticators in treated patients with EAC being considered for salvage ER.
Aims: In intraoperative frozen tissue section laboratories (FS laboratories) conventional practice for mounting coverslips on tissue slides involves the use of xylene-based mounting agents, such as Pertex. However, toxic vapours pose a risk to biomedical laboratory scientists (BLS) and pathologists who handle the wet slides to provide fast and urgent diagnostic results to surgeons during operations. Our study aims to evaluate non-toxic mounting agents to substitute Pertex, preferably with a fast curing time suitable for the demands of the new digital era in pathology.
Methods: Five non-toxic mounting agents were purchased and tested through six different protocols and compared to xylene-based Pertex as our gold standard. With light microscopy, tissue slides were quality assessed by BLS. Mounting agents, which were evaluated comparable to Pertex, were also evaluated by a pathologist, hence scanned digitally and re-evaluated.
Results: The protocols for Eukitt UV, Eukitt UV R-1 and Eukitt UV R-2 had significantly more artefacts (bubbles) compared to gold standard Pertex (p<0.0001, p=0.004 and p<0.0001, respectively) and assessed inadequate as replacements. Neo-Mount and Tissue Mount were assessed applicable regarding quality, but curing times were long. Tek Select UV showed promising results in both quality and fast curing time (protocol was <2 min).
Conclusions: Toxic mounting agents need replacement to health guard professionals, and also digital pathology is revolutionising laboratories. A digitalized FS laboratory requires fast dry/cured slides for digital scanning. Therefore, a substitute for the FS laboratory should have the qualities of being non-toxic to handle and having a fast curing time, and a UV-based mounting agent may solve both requirements.
Aims: The International Association for the Study of Lung Cancer (IASLC) has proposed a new histological grading system for invasive lung adenocarcinoma (LUAD). However, the efficacy of this grading system in predicting distant metastases in patients with LUAD remains unexplored. This study aims to assess the potential of the IASLC grading system in predicting the occurrence of brain and bone metastases in patients with resectable LUAD, thereby identifying individuals at high risk of post-surgery distant metastasis.
Methods: We retrospectively analysed clinical data and pathological reports of 174 patients with early-stage LUAD who underwent surgical resection between 2008 and 2015 at our cancer center. Patients were monitored for 5 years, and their bone and brain metastasis-free survival rates were determined.
Results: 28 out of 174 patients developed distant metastases in 5 years with a median overall survival of 60 months for metastasis-free patients and 38.3 months for patients with distant metastasis. Tumour grading of all samples was evaluated by both IASLC grading and predominant pattern-based grading systems. Receiver operating characteristic (ROC) curves were used to evaluate the predictive capabilities of the IASLC grading system and tumour stage for distant metastasis. Compared with the predominant pattern-based grading system, the IASLC grading system showed a better correlation with the incidence of distant metastasis and lymphovascular invasion. ROC analyses revealed that the IASLC grading system outperformed tumour stage in predicting distant metastasis.
Conclusions: Our study indicates that the IASLC grading system is capable of predicting the incidence of distant metastasis among patients with early-stage invasive LUAD.
Aims: Diagnosis of IgG4-related ophthalmic disease (IgG4-ROD) rests on the correlation of clinical features, serological testing and histopathology, using internationally accepted diagnostic criteria for objective interpretation; however, several mimickers of IgG4-RD overlap in clinical presentation and histopathology. We assess histopathological features in a series of presumptive IgG4-ROD cases, with emphasis on histopathological mimics and comparison of three IgG4-ROD diagnostic/classification criteria (organ-specific (OS), revised comprehensive diagnostic (RCD) and American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) criteria).
Methods: The histopathology database was screened for cases with clinical/histopathological suspicion of IgG4-ROD. Slides were reviewed, OS, RCD and ACR/EULAR criteria were applied, and the final clinicopathological diagnosis was recorded.
Results: 37 patients (24 females, 13 males; 19-73 years) were diagnosed as either IgG4-ROD (n=18) or non-IgG4-related disease (n=19). Non-IgG4-related disease group showed elevated serum IgG4 (55.5%), fibrosis (100%), dense lymphoplasmacytic inflammation (92.8%), with an increase in tissue IgG4+plasma cells (57.1%) and elevated IgG4:IgG+plasma cell ratio (14.3%). ACR/EULAR missed 50% (9/18, sensitivity-52.8%) of true IgG4-ROD cases, while OS and RCD criteria missed 11.1% (2/18, sensitivity-88.9%) of IgG-ROD cases. ACR/EULAR criteria mislabelled 7.14% (1/14, specificity-90.9%) while OS and RCD criteria wrongly categorised 71.4% (10/14, specificity-47.4%) and 50% (7/14, specificity-63.2%) specific non-IgG4-ROD cases as IgG4-ROD. Storiform fibrosis, obliterative phlebitis, increased IgG4:IgG+plasma cell ratio and elevated serum IgG were statistically significant in distinguishing IgG4-ROD from its mimics.
Conclusion: ACR/EULAR criteria showed high specificity but were cumbersome and sensitivity was low, while RCD and OS criteria showed low specificity. Stringent clinicopathological correlation to exclude mimics is critical in avoiding diagnostic errors in IgG4-ROD.
Aims: Phyllodes tumours (PTs) are relatively common fibroepithelial tumours comprising epithelial and stromal component. Usually, PTs show a spindle cell morphology with a fibroblast phenotype, while some tumour cells exhibit epithelioid morphological features and sarcomatoid transformation. However, the molecular characteristics of this morphology subset remain unclear. This study aimed to summarise the clinicopathological, morphological and molecular characteristics of seven cases of PT with epithelioid features.
Methods: Morphological and clinicopathological characteristics were observed and retrieved. Immunohistochemistry, immunofluorescence and electron microscope were performed on seven cases of epithelioid PT to explore immunophenotypic and ultrastructural characteristics. Transcriptomic and proteomic analyses were conducted to compare differentially expressed genes and proteins between epithelioid PT and classical PT.
Results: Patients with epithelioid PT exhibit a high recurrence rate (42.8%). Morphologically, in addition to having epithelioid cytological features, neoplastic stromal cells exhibit moderate to marked atypia and often exhibit sarcomatoid transformation, similar to the characteristics of borderline PT. Transcriptomic and proteomic analyses demonstrated that epithelioid PTs are distinct from classical PTs in gene expression and protein abundance levels. Immunohistochemical analysis showed that among all differentially expressed proteins, epithelioid PT showed abnormal p16/retinoblastoma expression patterns, similar to those of malignant PT.
Conclusions: Epithelioid PT has unique morphological characteristics, biological behaviour and protein expression profile, which meets the diagnostic criteria of borderline PT and is prone to sarcomatoid transformation. It may be a special morphological subgroup of borderline PT and has partial characteristics of malignant PT, which should be taken seriously in pathological diagnosis and clinical management.