American journal of clinical pathology最新文献

Objective: NUT carcinoma (NC) is a rare epithelial malignancy caused by a rearrangement of the nuclear protein in testis gene (NUTM1), with fewer than 200 cases reported worldwide to date. The majority of cases have occurred in young patients (ie, ≤25 years of age), most commonly in the thoracic and head and neck regions. This case marks the first documented occurrence of NC in the hepatobiliary system.

Methods: A 35-year-old woman presented with abdominal pain radiating to the back that has persisted for 2 weeks. Liver tests revealed obstructive jaundice. An abdominal magnetic resonance imaging scan demonstrated diffuse intrahepatic bile duct dilatation resulting from a stricture at the biliary confluence. Subsequent endoscopic retrograde cholangiopancreatography biopsy confirmed an invasive, poorly differentiated carcinoma, and a stent was placed in the left hepatic duct. Following right portal vein embolization, the patient underwent an extended right hepatectomy.

Results: Pathology revealed a firm 2.5-cm gray-white mass at the hepatic duct bifurcation. The initial diagnosis was a biliary carcinoma characterized by mass formation and a periductal infiltrating pattern. The tumor exhibited distinctive features, such as nested architecture, open vesicular chromatin, focal squamous differentiation, and perineural vascular invasion. Positive immunohistochemistry for CK7, CK19, P40, P63, and NUT protein and identification on DNA sequencing of a BRD3::NUTM1 fusion led to a final diagnosis of NC. Despite adjuvant chemotherapy, the patient succumbed to recurrent disease 18 months after surgery.

Conclusions: This case highlights the importance of recognizing NC in atypical locations and emphasizes the need for a thorough investigation in young patients with malignancies that display squamous differentiation. This report expands our understanding of biliary NC and underscores the challenges associated with its diagnosis and management.

Objective: Accurate blood staging in mycosis fungoides (MF)/Sézary syndrome (SS) is essential for precise diagnosis, prognostication, and effective management. Through 3 illustrative cases, we highlight the complexity of blood staging of MF/SS caused by expanded CD4-positive T-cell large granular lymphocyte (T-LGL) populations that mimic malignant involvement and complicate accurate disease assessment.

Methods: We identified 3 patients with MF/SS and more than 250/µL of CD4-positive, CD7-negative and/or CD4-positive, CD26-negative T cells in blood but with discordant T-cell receptor profiles between blood and skin samples. We also analyzed 100 consecutive T-cell blood flow cytometry panels ordered for patients evaluated in our cutaneous lymphoma clinic to determine the frequency of such populations.

Results: Each case demonstrated expanded CD4-positive T-LGL populations in the blood characterized by at least partial CD8, CD56, and CD57 expression and absent or decreased CD26 and/or CD7 expression. Blood from these patients exhibited distinct clonotypes from skin lesions, suggesting a reactive rather than malignant origin. Analysis of 100 consecutive cutaneous lymphoma staging blood flow cytometry cases identified similar CD4-positive, CD57-positive T cells of 250/μL or more in 3 of 100 cases, plus 1 atypical case of SS with partial, dim CD57 expression.

Conclusions: The presence of expanded T-LGL populations in blood can confound accurate staging of MF/SS, potentially leading to misclassification and ineffective or unnecessary treatment. These cases exemplify how comprehensive molecular and immunophenotypic profiling, including multicolor flow cytometry and T-cell receptor comparisons, along with morphologic evaluation of blood ensure accurate disease assessment to inform better clinical decision-making in MF/SS.

Objective: To assess the appropriateness and clinical indication of ordering the heparin-induced thrombocytopenia (HIT) platelet factor 4 (PF4) tests (based on the 4T score) for the diagnosis of HIT.

Methods: We retrospectively analyzed 261 PF4/polyvinylsulfonate (PVS)-enzyme-linked immunosorbent assay (ELISA) tests performed for 261 patients between January 2020 and June 2022. Patients were divided into 2 groups: 4T score less than 4 (unindicated HIT test requests) and 4T score of 4 or more (appropriately indicated HIT test requests). Clinical characteristics, test results, and treatment decisions were compared between groups.

Results: Only 136 (52.11%) of 261 tests were indicated by a 4T score or 4 or higher, whereas 125 (47.89%) of 261 tests were performed in low-probability patients (4T score <4). The PF4/PVS-ELISA positivity rate did not differ significantly between groups (11.03% vs 5.6%, P = .125). Patients with indicated testing had higher baseline platelet counts, longer time to platelet drop, and a greater percent drop in platelets (all P < .001). Among the 22 PF4/PVS-ELISA positive cases, only 10 had serotonin release assay (SRA) testing performed, of which 2 were SRA-positive. Among patients with low clinical probability, 75.20% (94/125) had heparin discontinued, despite the minimal risk.

Conclusions: Most HIT testing was inconsistent with guideline recommendations of the American Society of Hematology. Overtesting may lead to unnecessary anticoagulation, and undertreatment may have occurred in high-risk cases. These findings underscore the need for improved implementation of 4T-based decision tools to guide HIT evaluation and treatment.

Objective: Several studies analyzed the "reprogramming" of germ cell tumors of the testis (GCTT), known to be an epigenetic process that results in the preservation of stem cell features and/or differentiation of GCTT. EZH2 is a methyltransferase involved in the epigenetic regulation of tumors and has become a promising therapeutic target, but few studies have analyzed its expression in GCTT, germ cell neoplasia in situ (GCNIS), and adjacent testis.

Methods: We tested 131, 36, and 29 GCTT components, GCNIS, and adjacent testes, respectively. EZH2 expression was evaluated by H-score and compared between different subgroups by adopting median values and the Fisher exact test.

Results: We found that EZH2 was more highly expressed by adjacent testis/GCNIS rather than by GCTT (P < .001), with adjacent testis showing the highest values and being statistically significant compared to GCNIS (P < .001). In adjacent testis, EZH2 expression was mainly detected in spermatocytes (primary and secondary) and spermatids, with scattered positive spermatogonia. Seminoma/embryonal carcinoma showed statistically significantly higher EZH2 expression compared to the other nonseminomatous GCTT (P = .027).

Conclusions: EZH2 is differentially expressed during GCTT reprogramming (adjacent testis [very high levels] → GCNIS [high levels] → seminoma/embryonal carcinoma [moderate levels] → other nonseminomatous GCTT [low/absent levels]), supporting its involvement in the epigenetic regulation for determining the fate of GCTT.

Objective: Choline transporter (ChT) immunohistochemistry (IHC) is a new ancillary test that aids in the diagnosis of Hirschsprung disease in newborns and infants. The behavior of this stain in older children (greater than 1 year of age) with chronic constipation, where Hirschsprung disease is clinically unlikely, has not been investigated. The aim of our study was to determine the behavior of ChT IHC in rectal biopsies performed on older children with chronic constipation.

Methods: We performed ChT IHC on 54 endoscopically obtained mucosal biopsies from 41 patients with chronic constipation. For comparison, ChT IHC was also performed on 12 endoscopically obtained mucosal biopsies from 8 nonconstipated children, 11 rectal suction biopsies from 9 infants, and 6 full-thickness biopsies from 5 older children with confirmed Hirschsprung disease. We reviewed the ChT IHC staining and quantified the number of positive staining neurites in the muscularis mucosae.

Results: Of the 54 rectal biopsies from children with chronic constipation, 13 (24%) showed an aganglionic staining pattern, and 7 (13%) showed equivocal staining. The number of immunoreactive neurites in the muscularis mucosae in constipated children without Hirschsprung disease, however, was substantially lower than seen in patients with Hirschsprung disease. In comparison, in children without constipation, most biopsies showed a ganglionic pattern (11/12 [92%]). All biopsies from the Hirschsprung disease group demonstrated an aganglionic pattern.

Conclusions: In our cohort, ChT IHC showed an abnormal/aganglionic or equivocal pattern in 37% of patients with chronic constipation. As such, ChT IHC results should be interpreted with caution when performed on rectal biopsies in chronically constipated children.

Objective: Targeted therapy in non-small cell lung cancer (NSCLC) is now often included as first-line treatment in the neoadjuvant and adjuvant settings. Delays in optimizing treatments based on biomarker status can affect outcomes. Therefore, we assessed the turnaround time (TAT) of reflex biomarker testing for all NSCLCs clinical stage 1B and greater.

Methods: A next-generation sequencing (NGS) and PD-L1 immunohistochemistry reflex protocol for NSCLC clinical stage 1B and greater was implemented. Turnaround time intervals between procedure date, pathology sign-out, date received in the molecular laboratory, and date of NGS sign-out were calculated. Median and IQR of each interval before and after implementation of the reflex protocol were calculated and compared using the Mann-Whitney U test.

Results: In total, 492 lung cancer NGS cases were identified, 351 before and 141 after implementation of the reflex protocol. The prereflex cases, after exclusion of biomarker testing ordered on older blocks and outside consults (n = 165), demonstrated a 22-day median time from procedure to NGS sign-out (range, 11-70 days; IQR, 9; mean, 24 days), compared to a 20-day median time (range, 13-54 days; IQR, 4.5; mean, 21 days) postimplementation (n = 120) (P < .000103).

Conclusions: Reduction in median TAT from procedure to NGS sign-out was statistically significant after implementation of reflex biomarker testing in NSCLC samples.

Objective: The successful diagnosis and classification of lymphoid neoplasms in blood and bone marrow is the responsibility of the practicing pathologist. This guide provides a general "roadmap" for this process, from initial case recognition to final classification.

Methods: The integration of hematologic, morphologic, immunophenotypic, and genetic features for the full spectrum of precursor and mature B-cell, T-cell, and natural killer-cell neoplasms that typically manifest in blood and bone marrow is included.

Results: Classification systems for lymphoid neoplasms provide criteria for pathologists to render a diagnosis that is optimal for patient care, treatment, and outcome prediction.

Conclusions: This guide provides diagnostic strategies for lymphoid neoplasms encountered in blood and bone marrow specimens using both the International Consensus Classification and the World Health Organization fifth edition classification systems. Key tips are provided for each entity along with testing requirements, differential diagnosis, nonneoplastic mimics, and other unique features based on the experience of the Bone Marrow Pathology Group members.

Objective: Cytology samples can harbor clinically significant microorganisms; however, cytopathologists can be challenged by the interpretation of special stains and the description or classification of microorganisms. This study aimed to highlight the value of medical microbiologist consultations on cytology specimens.

Methods: This quality assurance project retrospectively reviewed all medical microbiologist consultations on cytology specimens from 2018 to 2024. Special stains used, consultation findings, associated clinical microbiology laboratory studies, and the clinical significance of identified microorganisms were extracted from cytology reports and the electronic medical record.

Results: Medical microbiologist consultations were requested on 152 cytology samples from 139 patients. Thoracic sources comprised most cases (110/152, 72%). Clinically significant microorganisms were identified in 30% (45/152), of which most were fungi. The medical microbiologist confirmed artifacts or mimics in 24% (36/152). The microbiologist assisted cytopathologists in the care of 15 patients with clinically significant pathogens but for whom relevant clinical microbiology laboratory studies were negative or not performed.

Conclusions: Medical microbiologists and the clinical microbiology laboratory are important resources for the diagnosis of infectious diseases in cytology specimens. This project uniquely documents the consultative and collaborative relationship between cytopathologists and medical microbiologists at a major academic medical center and highlights its positive impact on patient care.

Objective: The number of orthotopic heart transplants (OHTs) performed each year continues to increase, as does the post-transplant survival rate. Little is known, however, about the morphologic changes in the liver after the patient has undergone an OHT. In this study, we retrospectively reviewed liver pathology in patients following OHT to comprehensively describe the histopathologic changes, particularly fibrosis.

Methods: Three pathologists retrospectively reviewed liver biopsy samples in patients who had undergone OHT using a standardized checklist format.

Results: In our cohort of 19 biopsies, the morphologic features of hepatic injury noted were in the form of vascular outflow obstruction (9 biopsies), portal inflammation (13 biopsies), cholestasis (8 biopsies), and steatosis/steatohepatitis (5 biopsies). There was no evidence of nodular regenerative hyperplasia. Five of 9 patients with vascular outflow obstruction had sinusoidal fibrosis. Of 8 patients with clinical suspicion of portal hypertension and cirrhosis, only 3 demonstrated advanced fibrosis.

Conclusions: This is the first comprehensive account of histopathologic changes in the liver following OHT. This information will be beneficial for clinical decision-making when monitoring hepatic function and fibrosis in patients with OHT.

Objective: Interference caused by hemolysis, icterus, and lipemia (HIL) are a common source of preanalytical errors during coagulation testing. Stago has developed a specific module on its coagulation analyzers to standardize the detection of HIL.

Methods: The aims of this study were to evaluate the accuracy, carryover, and cross-interference of HIL measurement and compare results with those obtained on cobas 8000 modular analyzer series devices (Roche Diagnostics). These evaluations were carried out using Clinical and Laboratory Standards Institute guidance and regulatory study requirements.

Results: We demonstrated the absence of sample carryover through the HIL measurement chamber and excellent accuracy between HIL theoretical and measured concentrations, with an R2 above 0.99 in all cases. We did not detect any cross-interference of bilirubin and lipids to hemoglobin, of hemoglobin and lipids to bilirubin, or for hemoglobin and bilirubin to lipids. We found excellent agreement between HIL on the Stago STA R Max3 and cobas 8000 platforms, with κ coefficients ranging from 0.928 to 0.963.

Conclusions: These results support the implementation of the Stago Expert Preanalytical Check module for HIL interference measurement in routine coagulation laboratory testing.