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.

EWSR1 is the most commonly rearranged gene in mesenchymal neoplasia, and its myriad chimeric oncoproteins drive widely disparate neoplasms. Here, we survey selected EWSR1 rearrangements, including well-described EWSR1 fusions with CREB family members, ATF1 and CREB1, as well as fusions in emerging entities such as mesenchymal neoplasms with EWSR1::PATZ1 and EWSR1::NFATC2 fusions. We also discuss recent data demonstrating the imperfect specificity of EWSR1::WT1 and, possibly, EWSR1::FLI1 fusions.

UNASSIGNED: The risk of malignancy in nonvisualized ovaries on pelvic ultrasound is presumed to be close to zero per imaging correlation; the goal of this manuscript is to define the risk of malignancy in nonvisualized ovaries on pelvic ultrasound as defined by surgical pathology. Records for patients with pelvic ultrasound and surgical pathology containing the word \"ovary\" or \"ovaries\" performed at our institution between 10/1/2015 and 9/30/2021 were reviewed. Data for ovarian visualization were extracted from the radiology report and correlated with surgical pathology results within each ovary. Eighty-seven ovaries in 71 patients out of 422 ovaries (20.6%) in 215 eligible patients were not visualized on ultrasound. Twenty ovaries were excluded because imaging showed large pelvic mass, and 19 ovaries were excluded because surgical pathology for the ovary of interest was not available. A total of 48 ovaries in 37 patients were nonvisualized and had available surgical pathology. Out of 48 nonvisualized ovaries, 31 were normal on surgical pathology and 17 had abnormalities, with 15 benign lesions (12 of which were ≤1 cm in size). Two ovaries in 1 patient contained malignant lesions; although the ovaries were not visualized on ultrasound, the scan demonstrated peritoneal carcinomatosis. In conclusion, a high proportion of ovaries (20.6%, 87/422) are not visualized on pelvic ultrasound, and surgical pathology reveals ovarian lesions in 35.4% (17/48) of nonvisualized ovaries on pelvic ultrasound, with the majority being subcentimeter benign lesions. In the absence of peritoneal carcinomatosis, nonvisualized ovaries had no malignant lesions.

OBJECTIVE: 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.

OBJECTIVE: Surgical pathology reports play an integral role in postoperative management of head and neck cancer patients. Pathology reports of complex head and neck resections must convey critical information to all involved clinicians. Previously, we demonstrated the utility of 3D specimen and defect scanning for communicating margin status and documenting the location of supplemental margins. We introduce a newly designed permanent pathology report which improves documentation of intraoperative margin mapping and extent of corresponding supplemental margins harvested.
METHODS: We test the hypothesis that gaps in understanding exist for head and neck resection pathology reports across providers. A cross-sectional exploratory study using human-centered design was implemented to evaluate the existing permanent pathology report with respect to understanding margin status. Pathologists, surgeons, radiation oncologists, and medical oncologists from United States-based medical institutions were surveyed. The results supported a redesign of our surgical pathology template, incorporating 3D specimen / defect scans and annotated radiographic images indicating the location of inadequate margins requiring supplemental margins, or indicating frankly positive margins discovered on permanent section.
RESULTS: Forty-seven physicians completed our survey. Analyzing surgical pathology reports, 28/47 (60%) respondents reported confusion whether re-excised supplemental margins reflected clear margins, 20/47 (43%) reported uncertainty regarding final margin status, and 20/47 (43%) reported the need for clarity regarding the extent of supplemental margins harvested intraoperatively. From this feedback, we designed a new pathology report template; 61 permanent pathology reports were compiled with this new template over a 12-month period.
CONCLUSIONS: Feedback from survey respondents led to a redesigned permanent pathology report that offers detailed visual anatomic information regarding intraoperative margin findings and exact location/size of harvested supplemental margins. This newly designed report reconciles frozen and permanent section results and includes annotated radiographic images such that clinicians can discern precise actions taken by surgeons to address inadequate margins, as well as to understand the location of areas of concern that may influence adjuvant radiation planning.

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OBJECTIVE: Low-grade oncocytic tumour (LOT) and eosinophilic vacuolated tumour (EVT) are recently described emerging entities, which demonstrate distinct features but are not yet recognised as separate neoplasms in the fifth WHO classification. Published series to date have been largely multi-institutional and based on surgically resected tumours. This study aims to determine the frequency, clinicopathologic features and outcome of LOT and EVT in a single institutional series of oncocytic/eosinophilic renal neoplasms, including patients managed with active surveillance and non-surgical intervention.
RESULTS: Cases were identified from a consecutive institutional series of in-house renal tumours diagnosed on biopsy and/or nephrectomy (2003-2023). Tumours with a diagnosis or differential diagnosis of oncocytoma, chromophobe renal cell carcinoma or oncocytic neoplasm not otherwise specified (including LOT, EVT and tumours with overlapping hybrid features) were retrospectively reviewed and classified/reclassified.In total, 605 oncocytic/eosinophilic renal neoplasms were reviewed, among which 33 LOT (5.5%) and 5 EVT (0.8%) were identified. LOT were CK7+, CD117- and GATA3+ (94%). EVT were CD117+, CK7 focal+ (80%) and cathepsin K+ (80%). At the median follow-up of 34 months (range 2-253) and 56 months (range 8-90) for LOT and EVT, respectively, there was no evidence of recurrence following ablation/surgical resection, metastasis or death from disease for all patients, including the 22 managed with active surveillance (20 LOT and 2 EVT).
CONCLUSIONS: LOT and EVT comprised a minority of oncocytic renal neoplasms in this series. We report a large institutional series including patients managed non-surgically, with no adverse outcome, adding to the existing literature indicating a benign outcome.

Rosai-Dorfman disease (RDD) is a non-Langerhans cell histiocytosis which usually presents as painless lymphadenopathy. Extranodal involvement is known to occur in various organs, and less than ten cases with primary pancreatic involvement have been reported previously. This case report details the clinical course of an elderly female, presenting with upper abdominal discomfort and imaging suggestive of malignancy. Multiple non-diagnostic fine-needle aspirations were followed by surgical intervention. Histopathological evaluation revealed a pancreatic mass with characteristic features of RDD. The large hallmark RDD histiocytes showed pale, watery-clear cytoplasm, central round nucleus, and prominent nucleolus, with and without lymphocyte emperipolesis. The RDD histiocytes showed positive immunostaining for CD68, CD163, S100 (nuclear and cytoplasmic), OCT-2, Cyclin D1 and are negative for CD1a, Factor XIIIa, fascin and langerin. This case underscores the importance of considering RDD in the differential diagnosis of pancreatic masses alongwith comprehensive evaluation, multidisciplinary approach and pancreatic core needle biopsy evaluation.

OBJECTIVE: Colorectal cancer (CRC) is the third most common malignancy worldwide. Accurate pathological diagnosis and predictive abilities for treatment response and prognosis are crucial for patients with CRC. This study aims to analyse the expressions of p21 and EGFR in CRC and their relationships with clinicopathological characteristics and prognosis to enhance diagnostic and prognostic evaluations.
METHODS: This study conducted a retrospective analysis of p21 and EGFR expressions in 12 319 Chinese patients with CRC using immunohistochemistry. The relationships between these expressions and clinicopathological characteristics and survival outcomes were explored through statistical and survival analyses.
RESULTS: Differential expressions of p21 and EGFR in CRC were closely related to clinicopathological characteristics and significantly impacted overall survival (OS). p21 expression was associated with the primary tumour site, mucinous subtype, lymphovascular invasion, perineural invasion, circumferential resection margin, T stage, N stage, tumour, node, metastases (TNM) stage, and mismatch repair status. EGFR expression was related to mucinous subtype, tumour differentiation, lymphovascular invasion, perineural invasion, tumour size, T stage, N stage, TNM stage and BRAF gene mutation. p21 and EGFR expressions were positively correlated (r=0.11). High p21 expression correlated with favourable OS, whereas high EGFR expression predicted poorer OS. A prognostic nomogram incorporating these biomarkers and clinical variables demonstrated robust predictive power for patient survival rates.
CONCLUSIONS: p21 and EGFR serve as potential indicators for pathological diagnosis, risk stratification, and predicting treatment efficacy and prognosis in patients with CRC. The study\'s findings provide valuable references for personalised treatment and prognosis evaluation in clinical practice.

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