Archives of pathology & laboratory medicine最新文献

Context.—: Many drugs can induce liver injury; however, vaccine-induced liver injury is a rare phenomenon. SARS-CoV-2 messenger RNA (mRNA) vaccines are now widely administered, and clinical evidence of liver injury has been reported.

Objective.—: To characterize the histologic features of SARS-CoV-2 mRNA vaccine-associated liver injury.

Design.—: Thirteen liver biopsies from 12 patients with elevated liver enzymes clinically favored to be secondary to SARS-CoV-2 mRNA vaccine were identified between 2021 and 2022. Demographics, clinical information, and histologic features of liver biopsies were reviewed.

Results.—: All patients (median age, 58 years; M:F = 4:8) received at least 1 dose of SARS-CoV-2 mRNA vaccines (7 Pfizer and 5 Moderna). Four patients had a history of liver disease. Nine patients developed symptoms between 1 day and 2 months after receiving the vaccine dose. Viral serologies were negative. Drug-induced liver injury was thought to be less likely clinically in the 3 patients who had started new medications. Autoimmune antibodies were detected in 9 patients. Moderate to severe active hepatitis was the dominant histologic pattern of injury (9 of 13 biopsies; 69%). Resolving hepatitis, cholestatic hepatitic injury, and bile duct injury were identified in 1 biopsy each. All patients recovered spontaneously or with steroid therapy except one patient who developed autoimmune hepatitis.

Conclusions.—: Moderate to severe active hepatitis is commonly observed in SARS-CoV-2 mRNA vaccine-associated liver injury, and female patients may be more susceptible to injury. Liver injury resolves spontaneously or with steroid treatment. In rare cases, these vaccines may trigger an underlying immune condition.

Context.—: Gastrointestinal manifestations of Kaposi sarcoma are rare but may cause morbidity. Lower gastrointestinal involvement is particularly rare and lesions may resemble conventional bowel polyps.

Objective.—: To study 15 patients who presented with lower gastrointestinal tract Kaposi sarcoma with polypoid architecture.

Design.—: The surgical pathology files of the departments of pathology at multiple institutions were searched for cases of Kaposi sarcoma forming polyps in the lower gastrointestinal tract (jejunum, colon, rectum); 15 cases with such features were identified. Clinicopathologic information was extracted from the medical record and documented by reviewing individual hematoxylin-eosin stained slides.

Results.—: The patients were 13 men and 2 women aged 26-80 years (median = 44 years). Gastrointestinal tract involvement was multifocal in 11 cases and unifocal in 4. The tumors involved the rectum, recto-sigmoid junction, cecum, ascending colon, transverse colon, and descending colon and presented as polypoid lesions measuring 0.2-2.1 cm. Six patients had upper gastrointestinal tract involvement in addition to lower gastrointestinal lesions. Histologically the tumors were characterized in 6 cases by a dense spindle cell proliferation in the lamina propria; however, the remaining cases showed only a subtle fascicular spindle cell proliferation in the lamina propria that did not form an expansile mass.

Conclusions.—: Biopsies of gastrointestinal polyps showing absence of the common features of hyperplastic or adenomatous polyps, particularly in immunocompromised patients, should be carefully examined for the presence of a stromal spindle cell proliferation. Use of immunohistochemical stains, particularly human herpesvirus-8, can help in establishing the correct diagnosis.

Context.—: Urothelial denudation seen in transurethral biopsy specimens may occasionally indicate the presence of discohesive high-grade urothelial carcinoma (HGUC).

Objective.—: To determine if denuded urothelial cells can be detected in the supernatants of formalin solution collected from the containers of transurethral biopsy/resection specimens after the entire tissue was submitted for histologic examination.

Design.—: We assessed the formalin supernatants by processing for cell block (n = 43) or ThinPrep smear (n = 57).

Results.—: In the cell block cohort, only 2 of 43 cases (5%) (1 pTa HGUC, 1 pT1 HGUC) showed rare urothelial cells. By contrast, in the ThinPrep method, the smear was satisfactory for evaluation in 52 of 57 cases (91%). The cytologic diagnosis of HGUC was made in the smears from 7 of 12 (58%) pTa/pT1 cases and 6 of 9 (67%) pTis cases. Remarkably, HGUC cells were detected in 2 of 5 cases (40%) with histologic diagnosis of urothelial atypia suspicious for but not diagnostic of urothelial carcinoma in situ. Additionally, in 31 cases exhibiting urothelial denudation without definitive cancer on hematoxylin-eosin-stained slides, HGUC cells (2 of 31; 6%), atypical urothelial cells (5 of 31; 16%), or benign-appearing urothelial cells (20 of 31; 65%) were present, and only 4 of 31 (13%) were unsatisfactory.

Conclusions.—: Cytologic examination of ThinPrep smears from the formalin supernatants even following submission of the entire transurethral biopsy/resection specimens for histologic examination is useful for assessing denuded urothelial cells. This technique can particularly be applied to nonneoplastic cases showing extensive urothelial denudation to detect possible malignant cells and/or indeterminate cases to assist to make a more definitive diagnosis.

Context.—: Gross evaluation of post-neoadjuvant chemotherapy breast carcinoma is challenging when the primary tumor is not localized before therapy with a radio-opaque wire/clip, a situation common in resource-constrained settings.

Objective.—: To compare 2 grossing approaches in post-neoadjuvant chemotherapy breast carcinoma specimens to evaluate the sampling adequacy.

Design.—: Fifty breast carcinoma specimens were grossed in a 2-step manner. Tumor bed was identified using clinico-radiologic and gross correlation and 1 slice was selected as most representative (sample I). Subsequently, the entire tumor bed was submitted in grids of multiple slices (sample II). Agreement between methods was assessed using κ values.

Results.—: Sample I prepared an average of 8 blocks per case while sample II prepared 26 blocks. Pathologic complete response (pCR) by both methods was calculated. Sample I documented 23 cases with pCR of which 21 were confirmed by sample II. The 2 cases missed by sample I had less than 5% residual tumor (residual cancer burden class I). Both cases were human epidermal growth factor receptor 2 (HER2)-positive and residual tumor was seen in the slices adjacent to the selected slice. The concordance between the 2 methods was 94% with κ value of 0.915 for sample I, indicating excellent correlation with sample II.

Conclusions.—: The average cost of sample I was 33% of that of sample II and helped calculate the residual cancer burden with similar accuracy. However, in HER2-positive cases, pCR may be overestimated. Hence, we recommend sampling slices adjacent to the selected tumor slice. Further study using this method is essential due to its limited sample size and single-center design before considering implementation in the general population.

Context.—: In this era of health care challenges, efficient resource use is crucial. Patients with inflammatory bowel disease (IBD) may undergo surgery owing to treatment-refractory disease or strictures. Unlike colorectal cancer resections, there are no guidelines for lymph node retrieval in nonmalignant IBD resections.

Objective.—: To assess the usefulness and cost-effectiveness of extensive lymph node examination in nonmalignant IBD resections.

Design.—: A retrospective analysis of 354 cases from 2011 to 2018 was conducted. Resections for suspected malignancy or lesions grossly suggestive of carcinoma were excluded. Patient data, resection type, lymph node count, and follow-up information were collected.

Results.—: Results showed 51% (180) of cases had 12 or more examined lymph nodes. Only 1 case (0.3%) revealed microscopic invasive carcinoma associated with stricture without metastasis to 26 examined lymph nodes. No metastatic disease was found among the 4972 evaluated lymph nodes. Estimated total savings were at least $19 812, with approximately 10.4 minutes saved on microscopic evaluation. During a mean 5.7-year follow-up, no patients developed metastatic disease from an intestinal primary tumor. Among the 20 deceased patients, cause of death was available for 14 patients (70%), of whom 11 (55%) died of nonneoplastic causes and 3 (15%) of nonintestinal malignancies.

Conclusions.—: While lymph node assessment is crucial in IBD-associated colorectal carcinoma, a colorectal cancer protocol-type lymph node search is unnecessary without clinical or gross pathologic suspicion. A conservative approach to lymph node sampling optimizes resources without compromising patient care.

Context.—: Pathology training programs generally prepare graduates well for the workforce, but there may be other aspects to navigating a job that make the transition from being a trainee to a practicing pathologist challenging.

Objective.—: To identify perceived challenges of independent practice for early career pathologists and assess how these impressions evolve throughout their first year.

Design.—: A survey was distributed to 12 anatomic pathology fellows from 4 institutions near the end of their final training year, and 6 months and 1 year after starting their first job. The surveys queried participants' comfort level with signing out cases independently and interacting with colleagues/trainees via Likert attitude scale questions, with free-text segments to elaborate on challenges experienced.

Results.—: The response rate to all 3 surveys was 100%. Confidence and comfort level with different aspects of independent sign-out increased incrementally over time. Main challenges encountered at 6 months included a high case load, signing out cases in areas outside of their subspecialty, time management, balancing teaching while signing out, laboratory issues, and developing relationships with clinicians. At 12 months, main challenges included time management, high case load, understaffing, laboratory issues, and signing out cases in areas outside of their subspecialty.

Conclusions.—: This study identified real-time challenges faced by those adjusting to their first year of independent practice. By gaining a better understanding of the factors that make this transition challenging, we can find tailored ways to support our early career pathologists.

Context.—: Noninvasive self-sampling is a convenient option that may be highly accepted by women for home-based detection, which could increase the screening rate for cervical cancer (CC) and reduce its incidence and mortality.

Objective.—: To compare the distribution of high-risk human papillomavirus (hr-HPV) between the vulva and cervix and to explore the clinical value of vulvar HPV detection in CC screening.

Design.—: The study was nested within a clinical trial on a recombinant HPV 9-valent vaccine for women ages 20 to 45 years. Women with paired vulvar and cervical specimens were included and underwent cytology and HPV detection. The consistency of HPV detection between vulvar and cervical specimens was evaluated using Cohen κ statistics. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to evaluate the diagnostic accuracy of primary CC screening. The primary end points were cervical intraepithelial neoplasia (CIN) grade 2/3 or worse (CIN2+/3+).

Results.—: A total of 7999 women were enrolled, and 83/33 cases were diagnosed as CIN2+/CIN3+. The HPV-positive rate in vulvar specimens (1785 of 7999; 22.32%) was higher than that in cervical specimens (1390 of 7999; 17.38%), and there were no significant differences in the distribution of hr-HPV genotypes between the vulva and cervix in patients with CIN2+/CIN3+. Vulva-based HPV primary screening showed sensitivity, specificity, PPV, and NPV comparable to those for cervix-based HPV primary CC screening in the detection of CIN3+.

Conclusions.—: The distribution of vulvar and cervical HPV was similar in patients with CIN2+/CIN3+. Vulva-based HPV primary CC screening had acceptable diagnostic efficacy and might be used as a modality for primary CC screening.

Context.—: The characteristic molecular signature for both atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma is amplified sequences derived from chromosome 12q13-15, including MDM2 proto-oncogene (MDM2). As the progression of atypical lipomatous tumor/well-differentiated liposarcoma to the more aggressive dedifferentiated liposarcoma has the potential to adversely affect patient outcomes, the extent of the latter component might be important to evaluate.

Objective.—: To investigate the correlation between clinicopathologic characteristics, including tumor size, modified Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade, molecular data, and outcomes in 123 surgically resected MDM2-amplified liposarcomas.

Design.—: Pathology reports and clinical records were reviewed. A log-rank test was used to compare the survival trends, and univariate logistic regression was performed to identify variables associated with adverse events (distant metastasis and/or death), from which the P value was derived to construct a multivariate regression model.

Results.—: In univariate analysis, the largest single dimension of the dedifferentiated component, the percentage of cells with gain of chromosome 12, mitotic count, and the presence of modified FNCLLC grade 3 were associated with adverse events. In multivariate analysis, the largest single dimension of the dedifferentiated component (odds ratio: 1.169; 95% CI: 1.053, 1.299; P = .003), and a higher mitotic count (odds ratio: 1.133; 95% CI: 1.037, 1.237; P = .006) were correlated with adverse events. There was no statistically significant association between current local recurrence status, overall largest tumor dimension, overall tumor volume, MDM2 copy number, or MDM2 to chromosome 12 centromere probe ratio and adverse outcomes.

Conclusions.—: Staging dedifferentiated liposarcoma based on the size of the dedifferentiated component better predicts the outcome.

Context.—: During platelet shortages, many hospitals produce low-dose platelets by splitting a standard platelet unit (>3 × 1011 platelets in the United States) in 2, then providing these low-dose units to patients. While low-dose units were previously found to be effective for prophylactic purposes in patients undergoing chemotherapy in the Prophylactic Platelet Dose (PLADO) trial, their use in actively bleeding patients has not yet been assessed.

Objective.—: To assess the use and safety of low-dose platelets in actively bleeding patients.

Design.—: We performed a retrospective review of cardiac surgery cases receiving platelet units for 18 months at 1 hospital. Two cohorts, those receiving only whole-dose platelets (37 cases) and those receiving only low-dose platelets (38 cases), were compared during the intraoperative and the 24-hour perioperative period. Mean number of platelet transfusions, dose of other blood products, estimated blood loss, bleeding complications in index cases, and all-cause mortality within 30 days of discharge were compared.

Results.—: There was no significant difference in mean number of intraoperative platelet transfusions between the cohorts (1.61 versus 1.53, P = .57). There was no significant increase in the transfusion of other blood products, estimated blood loss, bleeding complications in index cases, or all-cause mortality within 30 days of discharge in the low-dose platelet cohort, apart from a small increase in requirement for fresh frozen plasma in the perioperative period.

Conclusions.—: These results suggest that low-dose platelets are tentatively equivalent to whole-dose platelets in cardiac surgery during shortages, with similar transfusion requirements and clinical outcomes between groups. Future multicenter studies are needed to confirm these findings.

Context.—: The main objectives of the Paris System are to detect high-grade urothelial carcinoma, to standardize morphologic criteria and the cytopathologic report, to reduce the prevalence of the atypia category, and to improve the malignancy risk stratification.

Objective.—: To compare the results and sensitivity of cytologic classification before and after reclassification by the Paris System.

Design.—: Urinary cytology samples from patients with a histologic diagnosis of urothelial carcinoma were reclassified on the basis of the Paris System categories. The diagnoses before reclassification were divided into 5 categories (A, B, C, D, E) and compared with the Paris System (I, II, III, IV, V). Sensitivity was calculated considering cytohistologic agreement in relation to high-grade urothelial carcinoma.

Results.—: A total of 111 urinary cytology samples from patients were analyzed, corresponding to 40 histologic samples; of these, 12 (30%) were high grade and the remaining were low grade. Comparison of the correlated categories showed an increase from 3 (3 of 111; 2.7%) (A) to 31 (31 of 111; 27.9%) (I) in unsatisfactory cases and a decrease from 67 (67 of 111; 60,0%) to 30 (30 of 111; 27.0%) in negative cases, while the atypia category remained unchanged (15 cases [15 of 111; 13.5%]) (C and III). Suspicious cases increased from 5 (5 of 111; 4.5%) (D) to 14 (14 of 111; 12.6%) (IV) and cases of urothelial carcinoma were unchanged (21 cases [21 of 111; 18.9%]) (E and V). Sensitivity was 69% for the previous classification and 90% for the Paris System.

Conclusions.—: The Paris System improved the sensitivity of urinary cytology and the standardization of the unsatisfactory criteria, with an increase of cases in this category and a decrease of cases previously classified as negative among patients with a subsequent histologic diagnosis of urothelial carcinoma.