Archives of pathology & laboratory medicine最新文献

Context.—: Superficially invasive squamous cell carcinoma of the anus (SISCCA) is defined as a minimally invasive cancer measuring less than 3 mm in depth and less than 7 mm in horizontal spread. Its subtle morphologic alterations pose a significant challenge for histologic diagnosis.

Objective.—: To evaluate the diagnostic agreement among pathologists for SISCCA and to identify potential areas for improvement.

Design.—: Four gastrointestinal (GI) and 4 gynecologic (GYN) pathologists independently reviewed digitized hematoxylin-eosin images of 20 anal high-grade squamous intraepithelial lesions with suspected early invasion. Participants classified each lesion as either invasive or noninvasive and selected features indicative of invasion from a list compiled from major textbooks. Cohen κ coefficient was calculated to assess interobserver agreement.

Results.—: Of the 20 lesions, 8 (40%) received unanimous diagnoses, while 12 (60%) had discrepancies. Overall agreement was moderate (κ = 0.46; 95% CI, 0.29-0.48), with similar levels between the GI (κ = 0.53; 95% CI, 0.45-0.74) and GYN (κ = 0.46; 95% CI, 0.25-0.48) groups (P > .01). The GYN group diagnosed a higher number of lesions as invasive than did the GI group (median, 14.5 versus 10.5; P > .01). In consensus SISCCA diagnoses, the most commonly noted feature was the presence of small irregular tumor nests, followed by desmoplastic response and paradoxical maturation.

Conclusions.—: Variability in recognizing histologic features indicative of early invasion contributed to the poor reproducibility in the diagnosis of SISCCA. Efforts should focus on refining diagnostic criteria and integrating features that have proved effective in identifying early invasive cancer at other anatomic sites.

Context.—: Infantile pyknocytosis (IP) is an uncommon cause of transient neonatal hemolytic anemia and hyperbilirubinemia occurring in approximately 10% of cases of unexplained neonatal hemolytic anemia.

Objective.—: To study cases of IP with a focus on long-term follow-up, perinatal events, and family history.

Design.—: Cases were prospectively identified during review of peripheral blood smears for neonatal hyperbilirubinemia during an 11-year period. Clinical and laboratory parameters, follow-up data, and family history were recorded.

Results.—: Nine cases of IP were identified from the morphologic recognition of pyknocytes and clinical and laboratory evidence of hemolysis, and included 6 males and 3 females. Age at diagnosis ranged from 1 to 18 days (median, 4 days), and gestational age at birth ranged from 29 to 38 weeks (median, 35 weeks). Hemoglobin nadir ranged from 4.9 to 8.1 g/dL (median, 6 g/dL), and maximum total bilirubin concentration ranged from 7.7 to 27.5 mg/dL (median, 22.0 mg/dL). All 9 patients required phototherapy and transfusions. Hemolysis spontaneously resolved without recurrence in all cases, with time to resolution ranging from 13 to 70 days (median, 33 days) and median follow-up of 7 years (range, 1-11 years). Six patients (67%) had a sibling with neonatal jaundice as well. A similar proportion had significant perinatal events.

Conclusions.—: IP is associated with spontaneous resolution without long-term complications. The underlying etiology is unknown. Perinatal events may expose red blood cells to an overwhelming oxidative stress. Strong family history suggests familial predisposition causing transient red blood cell defect, making them more susceptible to hemolysis.

Context.—: Gestational choriocarcinoma is the most common form of gestational trophoblastic neoplasm. It is characterized by aggressive, destructive growth and a marked tendency for hematogenous spread, leading to high mortality if left untreated. However, with the advent of effective clinical treatment for postmolar gestational trophoblastic neoplasms in recent decades, the clinicopathologic presentation of gestational choriocarcinoma has significantly changed. Today, it more frequently presents at extrauterine sites and/or in an unexpected manner, posing considerable diagnostic challenges for pathologists. Nonetheless, prompt and accurate pathologic diagnosis remains essential for effective clinical management and optimal patient outcomes.

Objective.—: To review the clinical features and pathologic diagnosis of gestational choriocarcinoma, including its early manifestations.

Data sources.—: This review is based on literature and the author's personal diagnostic experience.

Conclusions.—: In the era of precision medicine, gestational choriocarcinoma has become a rare encounter, largely owing to the implementation of postmolar surveillance programs and timely initiation of chemotherapy. Diagnostic recognition of the tumor requires a high index of suspicion, familiarity with its histologic features and early forms, awareness of the unexpected extrauterine presentations, and appropriate use of immunohistochemical and molecular biomarkers. These tools are essential in distinguishing gestational choriocarcinoma from nongestational mimics of germ cell or somatic origin, which have profound therapeutic and prognostic implications.

Context.—: Human epidermal growth factor receptor 2 (HER2)-low breast carcinoma is a clinical entity that has targeted therapy.

Objectives.—: To evaluate the effect of antibody clone/sample size on HER2 status and reinterpret archived HER2-stained slides following current guidelines.

Design.—: We collected 86 estrogen-receptor+/HER2- breast carcinoma core needle biopsy (CNB) samples with archived slides stained with HER2 (HercepTest) and for Oncotype DX (ODX) assay. These slides were scored by 3 pathologists (consensus score) and then compared to the reported scores. The CNB and excisional biopsy (EB) samples were stained with 4B5. We performed a 3-way comparison between CNB-4B5, CNB-HercepTest, and EB-4B5. The mRNA values were abstracted from the ODX report. The mRNA values were compared with the EB-4B5 scores (semiquantitative [H-score] and categorical [zero, 1+, and 2+] system), the consensus score of CNB-HercepTest, and then with the consensus scores of CNB-4B5.

Results.—: Upon rescoring the archived CNB-HercepTest slides, 45.3% were discordant; 12 of 19 (63.2%) reported as 1+ were HER2-zero. The discordance rate between CNB-4B5 and EB-4B5 was 24.4%; between CNB-4B5 and CNB-HercepTest, 59.3%; and between CNB-HercepTest and EB-4B5, 62.8%. The mRNA values correlated with EB-4B5 when using the H-score (P = .003) or the categorical system (zero, 1+, 2+) (P = .008), and with CNB-4B5 (P = .002), but did not correlate with CNB-HercepTest.

Conclusions.—: The discordance of HER2 staining depended on the sample size and antibody clone. Tissue stained with 4B5 (CNB or EB), but not with CNB-HercepTest, correlated with mRNA values.

Context.—: Pathologic evaluation of intestinal biopsies or resection specimens is often part of the diagnostic workup for patients with pseudo-obstruction or other forms of severe intestinal dysmotility. Some of these patients have one of several types of primary intestinal myopathy, but the pathologic features that identify and/or distinguish these conditions have been incompletely defined and need to be readdressed in the context of newly recognized genetic etiologies.

Objective.—: To convey a practical approach to surgical pathology diagnosis of primary intestinal myopathy based on a comprehensive review of pathology findings in patients with primary intestinal myopathy, including data collected from patients with intestinal myopathy-related pathogenic gene variants.

Data sources.—: A review of the literature as well as cases from multiple institutions that were examined by the author.

Conclusions.—: Microscopic alterations indicative of primary intestinal myopathy must be distinguished from nonspecific findings associated with chronic distension, surgical procurement, or preanalytic tissue processing. Most histopathologically recognizable forms of primary intestinal myopathy can be grouped as either structural alterations of the muscularis propria or degenerative leiomyopathies. Some histopathologic findings correlate with specific types of primary intestinal myopathy, but biopsies or resections from many patients with pathogenic variants in genes that encode smooth muscle contractile proteins show no diagnostic alterations. In some situations, an invasive procedure to obtain tissue for histopathologic evaluation has limited utility and molecular genetic testing may be a superior initial diagnostic approach.

Context.—: Complexity of ordering and transfusing blood is particularly evident in the pediatric population. Simplification, clarification, and standardization of blood orders can decrease complexity and improve patient safety.

Objective.—: To improve patient safety by optimizing electronic ordering of blood components in pediatrics through a collaborative process improvement initiative.

Design.—: A multidisciplinary working group, formed as part of a value stream analysis to improve transfusion safety at Children's Healthcare of Atlanta (Atlanta, Georgia), focused on decreasing variability and providing clarity when ordering, preparing, and transfusing blood using the electronic health record. Through benchmarking with other pediatric institutions and a collaborative design process with multiple local stakeholders, an extensive redesign in the existing orders and order sets occurred. Metrics were collected to determine if a change was an improvement.

Results.—: Nurse and laboratory informaticists, a pathology informaticist, and a transfusion medicine specialist built the new orders based on the design. The new orders focused on the following changes: standardization, introduction of logic, naming conventions, clarifying definitions, adding calculations, improving transparency of history and laboratory data, removing aliquots, clarifying communication, and implementing additional modules to inform the provider of necessary information about the patient. Metrics included a decrease in the number of orders changed within an hour, decreased calls from the blood bank to the provider to clarify the order, and an absence of overtransfusions and transfusion-related serious safety events for a year following implementation.

Conclusions.—: This collaborative initiative, using standard process improvement tools, resulted in standardized blood orders improving transfusion safety.

Context.—: Following the validation of a multicolor flow cytometry (MFC) assay for measurable residual disease (MRD) in acute myeloid leukemia (AML), this study examines its clinical applicability.

Objective.—: To evaluate the practicality and performance of MFC-based MRD detection in AML.

Design.—: Prospectively assessed AML MRD MFC in unselected AML patients achieving morphologic remission with follow-up studies, molecular genetics, and survival data.

Results.—: Among 379 patient bone marrow samples in this cohort, an interpretable result was obtained in 359 (95%). A total of 57 of the 359 cases (16%) were positive for MRD, and the most frequently observed immunophenotype was CD34+CD117+ myeloid (n = 46; 81%), followed by CD34-/CD117+ myeloid (n = 8; 14%) and monocytic (n = 3; 5%). Of 57 MRD+ cases, 6 (11%) had no leukemia-associated immunophenotypes available, and 16 of 51 (31%) with leukemia-associated immunophenotype for comparison exhibited significant immunophenotypic drift/switch, highlighting the importance of the "deviation from normal" approach. The remaining 302 cases were MRD negative; among these, 21 (7%) displayed a preleukemic immunophenotype that was associated with persistent clonal hematopoiesis in 18 patients (86%). A positive MFC result was strongly associated with subsequent follow-up positive MRD (41 of 45 [91%] versus 14 of 240 [6%], P < .01), morphologic relapse (42 of 55 [76%] versus 48 of 301 [16%], P < .01), an inferior overall survival (12.5 months versus not reached, P < .01), and leukemia-free survival (6.5 months versus not reached, P < .01). Among MRD-negative patients, a preleukemic phenotype was associated with a shorter overall survival (P = .03), but not leukemia-free survival (P = .16).

Conclusions.—: Our study provides data-driven technical insights for laboratories considering MFC AML MRD implementation and offers strong evidence supporting the utility of MRD assessment by MFC in patients with AML undergoing various stages of treatment and surveillance.

Context.—: Autoimmune atrophic gastritis (AIAG) is a chronic, immune-mediated inflammation restricted to the gastric body. Despite well-defined histologic features, the pathologic progression is still not fully understood.

Objective.—: To evaluate the pathologic progression of AIAG.

Design.—: AIAG cases with at least 2 follow-up biopsies were reviewed. Clinical data, including anemia and autoimmune antibody status, were collected. Gastric samples were analyzed to assess inflammation, atrophy, enterochromaffin-like cell hyperplasia, and the development of neuroendocrine tumors (NETs) or carcinoma.

Results.—: The cohort included 180 cases from 32 patients (21 females, 11 males), with an average follow-up of 6.8 years and 5.7 biopsies per patient. Inflammation, atrophy, and intestinal metaplasia remained stable in 59.4% (19 of 32), 78.1% (25 of 32), and 50% (16 of 32) of follow-up biopsies, respectively. Six patients had NETs in the AIAG index cases, with 5 experiencing recurrence after endoscopic excision. During follow-up, 6 additional patients developed NETs, half of whom had recurrence following endoscopic excision. The NETs were well differentiated with a Ki-67 index less than 3%. Two patients were initially diagnosed with adenocarcinoma in the background of AIAG, and 2 more developed adenocarcinoma during follow-up. No significant changes were observed in the antrum during follow-up, which consistently showed minimal to mild inflammation and reactive gastropathy.

Conclusions.—: Long-term follow-up indicates that AIAG is linked to the pathologic progression of NETs and gastric adenocarcinoma. The NETs arising in the background of AIAG are well differentiated and show no evidence of metastasis. These findings may provide guidance on optimal endoscopic surveillance intervals for patients with AIAG.

Context.—: Although pathology at McGill's teaching hospitals famously began with William Osler, he left Montreal before the medical school had established a pathology department.

Objective.—: To explore the early history of academic pathology and its leadership at McGill, with a primary focus on the second department head, Horst Oertel.

Design.—: Available primary and secondary historical resources were reviewed.

Results.—: John George Adami, the first professor of pathology, recruited Oertel in 1914, and Oertel became acting department head when Adami enlisted. At the end of World War I, Adami did not return, and Oertel was appointed department head. In the early 1920s, using Rockefeller Foundation and other philanthropic funding, Oertel oversaw the establishment of a new McGill Pathological Institute; unfortunately, he based the institute upon an autopsy-centric 19th-century German model, even though surgical pathology and clinical pathology were beginning to blossom elsewhere in North America. As a result, McGill missed an opportunity to lead in these arenas. This paper dissects Oertel's fascinating but tumultuous professional career at McGill, including his battles with renowned neurosurgeon/neuropathologist Wilder Penfield, medical museum/congenital heart disease specialist Maude Abbott, and McGill's Dean of Medicine Charles Martin, who expected the newly created institute to raise the faculty's research profile by promoting collaborative clinical research. Oertel was a legendary educator who wove history, philosophy, and humanities into his pathology lectures.

Conclusions.—: Oertel's legacy at McGill was mixed. Although he was considered strong academically, more forward-looking and collaborative leadership could have positioned McGill near the forefront of North American pathology.