Archives of pathology & laboratory medicine最新文献

Context.—: Lymph node (LN) involvement (LNI) is not infrequently observed in ovarian serous borderline tumors (SBTs) but is not considered equivalent to malignant tumor metastasis, as it reportedly does not impact recurrence or survival in patients with SBT. However, the reasons underlying the insignificant clinical impact of LNI remain unclear.

Objective.—: To determine whether histologic reaction patterns (HRPs) are associated with SBT prognosis.

Design.—: We compared HRPs around tumor cell clusters in LNs of patients with SBT and low-grade serous carcinoma. HRPs were classified into 4 categories (HRP 1-HRP 4) based on tumor cell location in LNs, the presence of their adhesion to surrounding lymphoid tissue, or pericellular desmoplastic reactions.

Results.—: Although LNI itself was linked to reduced recurrence-free survival (RFS), no recurrence was observed in patients with HRP 1 or 2, characterized by freely floating tumor cells in the lumens of afferent/efferent lymphatics or intranodal sinus with surrounding free spaces. Conversely, HRP 3 or higher, characterized by firm tumor cell adhesion to lymphoid tissue (HRP 3) or peritumoral desmoplastic reaction (HRP 4), independently impacted RFS, albeit not overall survival.

Conclusions.—: The prognosis of SBT with LNI is not uniformly favorable, and HRPs around the LNI significantly influence patient outcomes. Patients with firm tumor cell adhesion to surrounding tissue, with or without peritumoral desmoplastic reaction (HRP ≥3), independently experience decreased RFS, although this does not correlate with reduced overall survival.

Context.—: Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) rarely exhibits a predominant tubulocystic architecture with few other components. RCC with pure tubules and cysts lined by eosinophilic tumor cells with prominent nucleoli would raise the diagnosis of tubulocystic RCC. It is important to differentiate the 2 entities because they lead to different outcomes.

Objective.—: To address this concern, a multicenter study was implemented to explore useful clinicopathologic features in differentiation between tubulocystic FH-deficient RCC and tubulocystic RCC.

Design.—: Clinical factors included age, sex, tumor size, and outcome. Morphologic factors included cell morphology, presence or absence of a nontubulocystic component, and stromal findings. Immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing were performed to explore the protein expression and molecular profiles of the 2 entities.

Results.—: We evaluated 6 patients with tubulocystic RCC and 10 patients with tubulocystic FH-deficient RCC. Tubulocystic RCC exhibited a small size (<4.0 cm, pT1a), low Ki-67 index (<5%), retained FH, and negative 2SC expression. Tubulocystic FH-deficient RCC had a relatively large size and a high Ki-67 index. Perinucleolar haloes, loss of FH, and 2SC positivity were always observed. Pure tubulocystic architecture was not observed in FH-deficient RCC, because focal nontubulocystic components can always be seen.

Conclusions.—: We emphasized multiple sectioning to identify a nontubulocystic architecture to exclude tubulocystic RCC. Moreover, tumor size, FH/2SC staining, and the Ki-67 index can differentiate tubulocystic FH-deficient RCC from tubulocystic RCC. The diagnosis of tubulocystic RCC was not recommended in renal mass biopsy because of the limited tissues sampled.

Context.—: M-type phospholipase A2 receptor (PLA2R) is the major autoantigen of membranous nephropathy (MN). As the specific antibodies of MN, the correlation between serum PLA2R antibody (sPLA2R-Ab) levels and PLA2R-associated MN (PMN) risk stratification is still controversial.

Objective.—: To apply the time-resolved fluorescence immunoassay (TRFIA) method on urine PLA2R-Ab (uPLA2R-Ab), detect, and then establish a more sensitive method of combined serum and urine PLA2R-Ab detection for PMN hazard stratification.

Design.—: A highly sensitive TRFIA method was used to detect the initial serum and urine samples of patients with PMN. Patients were grouped into remission and nonremission groups according to the outcomes after 12 months of treatment and the data were analyzed.

Results.—: The cutoff values of sPLA2R-IgG (sPLA2R-immunoglobulin G), uPLA2R-IgG, sPLA2R-IgG4, and uPLA2R-IgG4 for distinguishing between remission and nonremission groups were 50 relative units (RU)/mL, 3.51 RU/mL, 6835 ng/mL, and 143.4 ng/mL, respectively. The average value in the remission group for sPLA2R-IgG, uPLA2R-IgG, sPLA2R-IgG4, and uPLA2R-IgG4 was 37.39 RU/mL, 1.10 RU/mL, 3498.99 ng/mL, and 33.83 ng/mL, respectively. The average value in the nonremission group for sPLA2R-IgG, uPLA2R-IgG, sPLA2R-IgG4, and uPLA2R-IgG4 was 279.96 RU/mL, 45.36 RU/mL, 25762.47 ng/mL, and 1383.89 ng/mL, respectively. For sPLA2R-Ab as the primary factor, in combination with uPLA2R-Ab, the high-risk predictive value of combined detection of serum and urine PLA2R-IgG and of serum and urine PLA2R-IgG4 was upgraded from 54.55% to 100% and from 75% to 100%, respectively.

Conclusions.—: A highly sensitive TRFIA method was applied in this study; the combined detection of serum and urine PLA2R-Ab improves the efficiency of PMN risk stratification, and can provide a better assessment of PMN monitoring.

Context.—: Test-ordering practices vary widely between and within health care organizations, and methods used to benchmark test utilization data are unstandardized.

Objective.—: To develop and apply standardized methodology to compare inpatient test utilization data submitted by laboratories enrolled in a College of American Pathologists Q-Probes study.

Design.—: Participating laboratories provided inpatient test volumes for 50 designated analytes and total inpatient days for 2019 or a recent 12-month period. Test utilization patterns were characterized by studying test volumes standardized per 1000 inpatient days. Test volume variability used the standardized median absolute deviation; standardized test volumes were evaluated by calculating comparative ranges for each analyte. Standardized test volumes falling outside their respective comparative ranges are referred to as outliers in this study. Volume data were tested for association with stewardship practices and institutional demographics.

Results.—: Methodology using standardized test volume data identified test groups that are commonly used in the inpatient setting and efficiently identified volume outliers. High test volume outliers included creatine kinase myocardial band, free prostate-specific antigen, myoglobin, serotonin release assay, and hepatitis B serologies; no low-volume outliers were observed. Among 33 participants, 13 (39%) had no test volume outliers, while 5 (15%) showed multiple tests (13-34) with comparatively high volumes. No statistically significant relationships were found between stewardship practices and test-ordering patterns.

Conclusions.—: Our approach can be used to measure inpatient test volume data across organizations and for identifying test volumes falling outside of the standardized comparative ranges that may require interventions to change test utilization practices.

Context.—: Genomic reports are primarily organized in a narrative and unstructured format with variations in content and format. Regulatory requirements and professional guidelines for genetic test reporting exist but provide little guidance for effective communication of information.

Objective.—: To assess clinical genomic reporting practices across 5 disciplines within molecular diagnostics, including germline, somatic solid tumors, somatic hematologic malignancies, pharmacogenomics, and prenatal cell-free DNA screening.

Design.—: Reporting practices were assessed by using a structured review of clinical genomic reports from multiple laboratories in 5 molecular disciplines spanning different practice settings. Report content was reviewed by the presence/absence of from 27 to 44 elements, including 23 elements required by the College of American Pathologists and/or the Clinical Laboratory Improvement Amendments of 1988 (CLIA). If present, the element's location on the report was recorded.

Results.—: A total of 69 genomics reports from 31 laboratories were reviewed. Overall, the reports were compliant with regulatory requirements but showed variability in both format and content. Six of 7 required reporting elements (per CLIA, 42 CFR [Code of Federal Regulations] 493.1291) were included in 90% of the reports. However, these elements were often located in different report sections. Only patient demographics were always found in a specific report section (header).

Conclusions.—: These results show that reports are overall compliant with regulatory requirements, despite some reporting elements being less consistently reported. The lack of consistent presentation of the data elements presents an opportunity to improve the communication of molecular testing results to clinicians and patients.

Context.—: Opportunities to improve transfusion safety occur at lower hemoglobin (Hgb) thresholds and single-unit transfusions. Efforts to improve compliance with transfusion guidelines and single-unit transfusion practices reduce transfusions and lead to improved outcomes.

Objective.—: To evaluate demographic and practice characteristics associated with lower Hgb thresholds and single red blood cell (RBC) unit transfusion practices.

Design.—: This study used the College of American Pathologists (CAP) Q-Probes format with the recent 2020 and 2017 surveys of participating institutions.

Results.—: High rates of transfusion review and compliance were observed with institutions reporting RBC transfusions meeting institutional guidelines. CAP inspection participants and those with a formal policy to encourage single-unit transfusions showed a trend toward greater compliance. Comparison of 2020 and 2017 survey results showed favorable downward trends in the Hgb threshold for transfusion compliance review and pretransfusion and posttransfusion Hgb values. Institutions reporting initiatives to decrease transfusions, teaching hospitals, and those with updated guidelines in alignment with recent literature reported lower pretransfusion Hgb levels in both studies. The 2020 study showed greater single-unit transfusion use among hospitals with patient blood management programs, larger institutions, and those training pathology residents. Single-unit transfusion rates varied by hospital service, with highest rates reported within hematology/oncology (99 of 138 [71.7%]), intensive care (147 of 215 [68.4%]), and medicine (419 of 666 [62.9%]) services.

Conclusions.—: Transfusion practice improvement programs to decrease RBC transfusions include the use of single-unit transfusions and lower institutional pretransfusion Hgb thresholds. Opportunities to lower transfusion thresholds and increase single-unit transfusions exist in surgical and obstetrics services.

Context.—: The aim of the study was to determine the impact of peripheral blood (PB) smear review by a pathologist when requested by a technologist or provider to measure the rate of pathologist-detected clinically relevant findings.

Objective.—: To report and analyze the results of clinically relevant morphologic findings on PB smears that were pathologist reviewed because of either a request from a technologist or an order from a provider.

Design.—: During a 4-week study period, participants enrolled in the College of American Pathologists Q-Probes program submitted data on PB smear reviews including review request source, reason for review request, and if the pathologist's review resulted in a clinically relevant morphologic finding.

Results.—: Twenty-two institutions submitted data on 835 eligible PB smears. Pathologists identified clinically relevant findings on a median 53.4% of technologist-requested PB smear reviews and a median 14.3% of provider-ordered PB smear reviews .The most frequently identified pathologist finding on technologist-requested PB smear reviews was "blasts" in 91 of 532 (17.1%) followed by "atypical (possibly neoplastic) lymphocytes" in 74 of 532 (13.9%); the most frequent finding on provider-ordered reviews was "other" in 55 of 315 (17.5%) followed by "immature cells/left shift in myeloid cells or monocytes" in 12 of 315 (3.8%). Pathologists agreed with technologists' indications for review in 458 of 513 requested reviews (89.3%). Institutions that conducted postanalytic follow-up on previously reviewed PB smears had a higher rate of clinically relevant findings detected on technologist-requested smears.

Conclusions.—: Pathologist review of PB smears flagged by technologists for review frequently yielded clinically relevant findings. This was higher in institutions that conducted postanalytic reviews. Provider-ordered reviews resulted in clinically relevant findings in a median of 14.3% of smears.

Context.—: Cardiac and pulmonary allograft recipients represent a unique population, frequently interacting with support groups and exhibiting intense curiosity about their pathology. Like other solid organ transplant patients, they have enduring and frequent interaction with the laboratory for routine allograft surveillance.

Objective.—: To address patient requests to understand what happens to their explanted organ and to better understand their disease while simultaneously improving awareness of pathologists' role in their continuing care.

Design.—: At routine follow-up appointments, transplant nurse coordinators offer each allograft recipient the opportunity to interact with a pathologist in our "On My Path" program. Organ viewing occurs in a private setting, in a specialized room. Relevant pathology is discussed, and questions are answered, with documentation in the medical record. The patient is subsequently gifted a 3-dimensional model of their explanted organ. Transplant coordinators were surveyed for their feedback on the experience.

Results.—: One hundred fifty-eight interactions have been documented (2017-2022), including patients who underwent cardiac transplant (96, 61%), single or bilateral lung transplant (54, 34%), or combination lung and heart transplant (8, 5%). Transplant coordinators reported an increase in patient understanding of their disease and emotional closure related to the disease through the On My Path program.

Conclusions.—: Pathologists providing direct patient care is a feasible model that addresses currently unmet desires of the transplant population to better understand their pathology. Providing a 3-dimensional model helps to empower patients and drives satisfaction. These interactions also improve awareness about pathology as a discipline and its importance in the continued care of transplant recipients.

Context.—: Lymphangioleiomyomatosis is a rare multisystem disorder belonging to the family of neoplasms exhibiting perivascular epithelioid differentiation. It primarily affects women of childbearing age. The disease is characterized by a proliferation of smooth muscle-like cells (lymphangioleiomyomatosis cells) within all lung compartments, leading to cystic parenchymal destruction and, in some cases, respiratory failure. These cells carry mutations in one or both tuberous sclerosis (TSC) genes and coexpress smooth muscle and melanocytic markers. Female hormones, particularly estrogens, influence the course of the disease. Symptoms of lymphangioleiomyomatosis vary significantly among patients, ranging from exertional dyspnea and coughing to chest pain and recurrent pneumothorax.

Objective.—: To present the latest advancements in the understanding of disease pathogenesis and diagnosis, illustrate the pathologic and radiologic findings, provide a reference for pathologists and other health care professionals, briefly discuss recent evidence-based therapeutic approaches, and emphasize the importance of adopting a multidisciplinary approach to diagnosis and optimization of patient care.

Data sources.—: A comprehensive review of pertinent medical literature published in the last 30 years, focusing on publications written in the English language, was performed.

Conclusions.—: Despite the recent significant advancements in the understanding and management of lymphangioleiomyomatosis, there are still significant gaps in our knowledge of its pathophysiology and the role of the immune system in the genesis and progression of the disease. The current changes in diagnostic algorithms favor the adoption of minimally invasive procedures as the standard of care. As a result, the clinical laboratory will play a larger role in the diagnosis of lymphangioleiomyomatosis, and surgical pathologists will likely be less involved in the diagnosis of pulmonary lymphangioleiomyomatosis than they currently are.

Context.—: The use of hormonal therapy and gender-affirming surgery in the transgender community has been rising during the last several years. Although it is generally safe, hormonal therapy's link to testicular cancer remains uncertain.

Objective.—: To review the incidence of testicular cancer in specimens from gender-affirming orchiectomies at our institution and evaluate the tumors for histologic and genetic alterations.

Design.—: Pathology reports for gender-affirming orchiectomies (January 1, 2018, to August 1, 2023) were reviewed for testicular neoplasms, with additional analysis for chromosome 12 abnormalities. Incidence and chromosome variations were compared with those in the general population.

Results.—: Among 458 cases during 5.5 years, 5 germ cell neoplasms in 4 patients emerged. Our institution's annual incidence rate (159 per 100 000) is 26.5 times higher than the National Cancer Institute's previous report (6.0 per 100 000). Although they were morphologically no different from germ cell neoplasms in the general population, fluorescence in situ hybridization tests showed no i(12p) in 4 of 5 neoplasms (80%) in our cohort.

Conclusions.—: The cause behind this rise in incidence remains uncertain but may be due to long term pretreatment with hormones or blockers. The lower isochromosome 12p frequency suggests an alternative mechanism driving tumor development, which requires more detailed molecular studies.