The United States Food and Drug Administration held a public hearing in January 2018 to consider how it should evaluate a self-collection device for cervical cytology. Although no such device has ...been approved for use in the US market, the implications for patients and cytologists could be both sweeping and complex. Herein, the existing literature basis for self-collected Papanicolaou testing is reviewed, and some questions raised by this testing are considered. Questions include: what would be the value to patients; how effective could self-collected Papanicolaou tests be; how might ordering and collection work; what are the unique pre-analytic, analytic, and post-analytic challenges of self-collected Papanicolaou testing; and what effect might self-collection have on cervical cancer rates?
Vaginal adenocarcinoma is the second most common primary cancer of the vagina, yet there has been very little study of most subtypes other than clear cell carcinoma. We reviewed 18 cases of primary ...vaginal endometrioid adenocarcinoma, in our experience the second most common subtype. The patients ranged from 45 to 81 years of age (mean 60). Most presented with vaginal bleeding, and had had a prior hysterectomy. Five had a history of unopposed estrogen therapy but none had a history of intrauterine diethylstilbestrol exposure. The tumors were at the vaginal apex in 10 cases, in the posterior wall in 3, the lateral wall in 3, and the anterior wall in 1. On microscopic examination, each of the tumors had a pure or predominant component of typical endometrioid adenocarcinoma. There was squamous metaplasia in 4 cases, mucinous metaplasia in 4, and prominent nonvillous papillae in 2. The tumors were grade 1 of 3 in 4 cases, grade 2 in 13, and grade 3 in 1. Eleven cases were FIGO stage I, 5 stage II, and 2 stage IV. Vaginal endometriosis was identified in 14 cases, and is important in indicating a primary vaginal tumor, rather than secondary spread from the endometrium. Other subtypes of adenocarcinoma (such as serous when the tumor has a papillary pattern) and atypical forms of endometriosis, including polypoid endometriosis, are the most common other differential diagnostic considerations. The prognosis seems to be good in low-stage patients, with 11 patients alive and well and 2 alive with recurrent disease.
Distinguishing between low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) can be difficult on certain Papanicolaou (Pap) tests, hindering ...interobserver concordance. We investigated the variables influencing the interpretation of LSIL versus HSIL in Pap test slides rejected from the College of American Pathologists PAP education program.
Eleven cytologists, who were unaware of the reference interpretation, examined 21 Pap slides (11 submitted as LSIL and 10 as HSIL) rejected from the PAP education program and recorded the number of LSIL cells, HSIL cells, keratinized dysplastic cells, LSIL clusters with mixed HSIL cells, atypical squamous metaplasia, atypical glandular cells, the presence of inflammation or infectious organisms, and the overall interpretation (LSIL or HSIL). We evaluated the significance of these 11 variables using a nonlinear mixed model analysis.
LSIL had greater concordance (92 of 121 responses; 76.0% concordance) than HSIL (68 of 110 responses; 61.8% concordance; P < 0.001). The only predictors of misclassified cases were the number of atypical squamous metaplastic cells and the number of HSIL cells (P < 0.001). The more of these cells identified, the more likely the reviewers were to classify the slide as HSIL. The reproducibility of the diagnosis was fair (Gwet’s agreement coefficient, 0.33).
Interobserver reproducibility is a challenge for a subset of cases with features intermediate between LSIL and HSIL. Atypical squamous metaplasia and dysplastic nuclei with a nuclear/cytoplasmic ratio greater than one half of the cell volume (HSIL) present on a Pap test influenced the likelihood that a reviewer would interpret the case as HSIL rather than LSIL.
•Some Pap tests show features intermediate between LSIL and HSIL with consequent poor reproducibility.•Review by 11 observers of 21 such slides confirmed poor reproducibility and identified only number of HSIL and ASC-H cells as statistically correlated with correct classification from among 11 variables.
Biopsies traditionally are performed under ultrasound (US), computed tomography (CT), or fluoroscopic guidance. In situations in which lesions are difficult to visualize with US or CT guidance, ...magnetic resonance (MR) imaging often can provide better imaging results. The authors describe a case in which a recurrent calf mass not well visualized under fluoroscopy, CT, or US was identified on MR imaging. In the absence of real-time needle visualization, percutaneous interventions under MR guidance have been limited by prohibitively long imaging times. A novel guidance system providing real-time MR guidance of needle position was used to procure a core biopsy specimen of the lesion.
This report describes the morphological features of a pleomorphic giant cell carcinoma with focal trophoblastic differentiation of the urinary bladder in a male, 12 years post living related donor ...renal transplant. The voided urine cytology demonstrated rare decoy cells admixed with markedly atypical urothelial cell clusters, papillae and giant cells. Cystoprostatectomy demonstrated a nodular mass involving the trigone and right lateral-posterior wall, adjacent to the ureteral orifice. Hematoxylin-eosin stained sections showed two synchronous malignancies: (a) pleomorphic giant cell carcinoma with focal trophoblastic differentiation of the urinary bladder, metastatic to the omentum and (b) prostatic adenocarcinoma, Gleason score 3+4=7, involving the right prostate lobe. Strong diffuse expression of polyomavirus large T antigen was demonstrated in the primary and metastatic pleomorphic giant cell carcinoma, supporting a possible role for polyomavirus (BK) in the oncogenetic pathway. The prostatic adenocarcinoma was negative for polyomavirus large T antigen. Our findings of p63, CK7 and CK903 expression in pleomorphic giant cell carcinoma suggest that the tumor is of urothelial derivation. This is the first report describing the morphological features of urinary bladder pleomorphic giant cell carcinoma with trophoblastic differentiation, positive for polyomavirus large T antigen, arising in the background of BKV reactivation.
Introduction Although it is widely accepted that cytologic alterations secondary to a biliary stent can be difficult to distinguish from adenocarcinoma in pancreatobiliary exfoliative cytology, no ...systematic study has been undertaken to identify the cytologic features that best distinguish these entities. Materials and methods A training set of 29 bile duct brushings (14 with biliary stents, originally classified as atypical or suspicious, with >6 months of benign clinical follow-up; and 15 diagnosed as adenocarcinoma with histologic confirmation) was evaluated for the following: nuclear enlargement, nuclear contour, nuclear overlap, chromatin distribution, nuclear-cytoplasmic ratio, anisonucleosis, macronucleoli, mitoses, acute inflammation, disorganization, necrosis, cell borders, single atypical cells, and 2 distinct cell populations. A distinct validation set of 31 equivocal stented brushings—13 later diagnosed with carcinoma and 18 with ≥6 months of benign follow-up—were similarly evaluated. Cases were categorized as benign or malignant using a scoring algorithm based on statistically significant features. Results Five features achieved statistical significance: atypical single cells ( P = 0.0001), 2 distinct cell populations ( P = 0.0007), and anisonucleosis ( P = 0.0422) favored malignancy; distinct cell borders ( P = 0.0018) and acute inflammation ( P = 0.0035) favored benign. The algorithm correctly classified 12 of 14 benign and 15 of 15 malignant cases in the training set and 16 of 18 benign and 7 of 13 malignant cases in the validation set. Conclusions Most bile duct brushings from patients with biliary stents could be definitively and correctly classified as either benign or malignant using 5 morphologic features: single atypical cells, binary cell population, anisonucleosis, distinct cell borders, and acute inflammation.
The terminology for human papillomavirus(HPV)–associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It ...often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) Project was co-sponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology and included 5 working groups; 3 work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors, and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted on at the consensus meeting. The final, approved recommendations standardize biologically relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail the appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care.
Introduction Urine cytology is often used to screen for polyomavirus in renal transplant patients. There are qualitative cytologic differences between urine from transplant and nontransplant ...patients, particularly the presence of epithelial cell clusters, that can pose diagnostic difficulty. Materials and methods Voided urine cytology specimens from 100 renal transplant patients and 100 nontransplant patients were reviewed for cell clusters. Immunocytochemistry for renal cell carcinoma marker (RCC) and cytokeratin 7 was performed on 10 recent specimens. Clinical data was reviewed with a focus on evidence of graft dysfunction or malignancy. Results Eighteen patients (18%) in the renal transplant group and no nontransplanted patients (0%) exhibited cell clusters with characteristic morphology: 3-dimensional cohesive groups; high nucleus-to-cytoplasm ratio; round, eccentrically placed nuclei with a prominent central nucleolus; and granular or vacuolated cytoplasm. Some had significant nuclear atypia. The groups were RCC–positive in 8 of 10 cases, and cytokeratin 7–positive in 6 of 10 cases, which is consistent with renal tubular epithelial clusters (RTECs). Clinical follow-up revealed that 88% (15 of 17) of those with RTECs developed graft dysfunction in a median of 65 days, compared with 6% (4 of 64) without RTECs (sensitivity 79%, specificity 97%, positive predictive value 88%, negative predictive value 94%). No patient developed a urinary tract malignancy. Conclusions RTECs are relatively common in urine cytology from transplant patients, but are rare in other urine specimens. Recognition is important as they can be mistaken for urothelial carcinoma or adenocarcinoma. There appears to be a strong association with later development of graft dysfunction. These cells are most likely evidence of renal tubular injury secondary to a variety of factors, including rejection.
PDF