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1.
Plast Reconstr Surg Glob Open ; 11(3): e4845, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36926385

ABSTRACT

This multicenter, retrospective study compared clinical outcomes and healthcare resource use in patients who underwent dual-plane (DP) or prepectoral (PP) implant-based breast reconstruction (IBR) after mastectomy in the United States. Methods: Medical records were selected for patients at five sites undergoing immediate one-stage direct-to-implant (first hospitalization) or two-stage IBR (first and second hospitalization) using either DP or PP. Inverse probability of treatment weighting was used to adjust for potential confounders. Complications and healthcare resource use were assessed with logistic regression; pain severity was assessed with ordinary least-squares regression. Results: After inverse probability of treatment weighting, data from 255 patients (DP = 130, PP = 125) and 441 breasts (DP = 226, PP = 215) were analyzed. Mean pain severity scores were lower with PP versus DP immediately after IBR for first (P = 0.0002) and second hospitalizations (P = 0.0145), and before discharge for first (P < 0.0001) and second hospitalizations (P = 0.0002). A greater proportion of PP versus DP patients had a shorter hospital length of stay (≤ 23 hours) for first hospitalization (P = 0.0052); proportions were similar for second hospitalization (P = 0.5499). Intravenous narcotics were prescribed less frequently to PP versus DP patients during first (61.1% versus 69.8%, respectively; P = 0.1486) and second (37.5% versus 55.3%, respectively; P = 0.0172) hospitalizations. Complication rates were low in both groups after first hospitalization discharge (DP: 13.6%, PP: 12.5%, P = 0.7225). Conclusion: This retrospective study suggests that the PP technique in IBR may offer benefits related to clinical outcomes and health resource utilization; however, larger studies, including randomized controlled trials, are needed to confirm.

2.
Am J Ophthalmol Case Rep ; 28: 101744, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36393908

ABSTRACT

Purpose: To report a case of an exogenous endophthalmitis caused by the fungal species Glomerella cingulata. Observations: A 71-year-old male presented with an infectious keratitis that evolved into endophthalmitis. Combined cataract extraction and pars plana vitrectomy was performed and the vitreous specimen cultured Glomerella cingulata, a variant of the Colletotrichum gloeosporioides fungal species. Despite early treatment with topical, systemic and intravitreal doses of both voriconazole and amphotericin B, the patient had a poor visual and anatomical outcome. Conclusions and Importance: Glomerella cingulata may rarely cause endophthalmitis with devastating visual outcomes.

3.
Histopathology ; 79(6): 957-965, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34214216

ABSTRACT

AIMS: Most vulvar squamous cell carcinomas are human papillomavirus (HPV)-associated or TP53-mutant. A third category of HPV-independent TP53-wild-type lesions is uncommon and not fully understood. Differentiated exophytic vulvar intraepithelial lesion (DEVIL) has been characterised as a precursor of this latter category. The reproducibility of the diagnosis of DEVIL and its distinction from lesions with overlapping morphology has not been studied. Our aim was to establish the interobserver agreement in the diagnosis of DEVIL and its distinction from neoplastic and reactive conditions of the vulva on haematoxylin and eosin evaluation. METHODS AND RESULTS: A set of 35 slides was evaluated by eight reviewers (two trainees and six practising gynaecological pathologists). The set included DEVIL, condyloma, established vulvar precursors [high-grade squamous intraepithelial lesion (HSIL) and differentiated vulvar intraepithelial neoplasia (dVIN)] with superimposed acanthosis or verruciform growth, lichen simplex chronicus (LSC), and psoriasis. Kappa (κ) values were calculated. Overall, interobserver agreement was moderate (κ = 0.56), improving to substantial (κ = 0.7) when evaluation was performed by practising pathologists. Agreement was strong for the diagnosis of HSIL (κ = 0.88), and substantial for the diagnosis of DEVIL (κ = 0.61), condyloma (κ = 0.79), and LSC (κ = 0.72). Agreement was moderate for the diagnosis of dVIN (κ = 0.59) and psoriasis (κ = 0.53). Perfect agreement (6/6) among practising pathologists was observed in 43% of cases, and majority agreement (5/6 or 4/6) was observed in 48% of cases. CONCLUSIONS: Reproducibility in the diagnosis of verruciform vulvar lesions, including the novel DEVIL, is acceptable overall. Reproducibility is higher for well-known lesions such as HSIL and condyloma than for more challenging diagnoses such as DEVIL, dVIN, and psoriasis. Agreement is higher among practising gynaecological pathologists, suggesting that training and experience improve reproducibility. Our findings support the inclusion of DEVIL as a diagnostic entity in the classification of vulvar squamous lesions.


Subject(s)
Precancerous Conditions/diagnosis , Precancerous Conditions/pathology , Vulvar Diseases/diagnosis , Vulvar Diseases/pathology , Diagnosis, Differential , Female , Humans , Observer Variation
5.
Plast Reconstr Surg ; 144(1S Utilizing a Spectrum of Cohesive Implants in Aesthetic and Reconstructive Breast Surgery): 43S-50S, 2019 07.
Article in English | MEDLINE | ID: mdl-31246760

ABSTRACT

Prepectoral breast reconstruction carries many benefits to patients, including its minimally invasive (muscle-sparing) nature, and its reduction in symptoms such as pain and animation deformity, relative to subpectoral reconstruction. However, without the traditional use of the pectoralis major muscle to mask the upper pole of the implant, and dictate the shape of the upper pole, certain steps must be taken to ensure the optimal aesthetic outcome in prepectoral reconstruction. Surgeons have utilized acellular dermal matrices, fat grafting, and highly cohesive implants to improve outcomes. Among the most important steps is the proper implant selection. To this end, the authors routinely utilize round form-stable gel implants, when performing prepectoral breast reconstruction. These implants offer improved aesthetic outcomes, given their ability to reduce rates of rippling and edge visibility. Furthermore, the characteristics of a soft and naturally shaped breast are achieved despite the lack of muscle coverage. The authors believe that reproducibly successful prepectoral reconstruction is dependent on proper technique. In this article, we present the proper techniques necessary for optimizing outcomes when using these implants in 2-stage prepectoral breast reconstruction.


Subject(s)
Breast Implantation/methods , Breast Implants , Breast Neoplasms/surgery , Mastectomy/adverse effects , Patient Satisfaction , Breast/anatomy & histology , Breast/surgery , Breast Implantation/instrumentation , Elasticity , Esthetics , Female , Humans , Patient Reported Outcome Measures , Patient Selection , Pectoralis Muscles/surgery , United States
6.
Gland Surg ; 8(1): 90-94, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30842933

ABSTRACT

Pre-pectoral reconstruction is steadily becoming more mainstream with recent publications showing equivalent results with traditional sub-pectoral published literature. Multiple authors have demonstrated short-term acceptable rates of infection, expander failure, success in radiated patients, and overall patient satisfaction. Some data has even shown improved outcomes in prepectoral reconstruction when compared to published subpectoral literature. For the past 4 years, our practices have utilized a "piggy-back" method of immediate pre-pectoral expander reconstruction before performing delayed immediate microsurgical free tissue transfers. This method has many advantages and has in many cases become our standard for patients wanting deep inferior epigastric perforator flaps (DIEPs) for definitive reconstruction.

7.
Int J Gynecol Pathol ; 38(3): 230-240, 2019 May.
Article in English | MEDLINE | ID: mdl-29750700

ABSTRACT

A chemotherapy response score (CRS) system was recently described to assess the histopathologic response and prognosis of patients with tubo-ovarian high-grade serous carcinoma (HGSC) receiving neoadjuvant chemotherapy. The current study was performed as an independent assessment of this CRS system. We retrospectively identified advanced stage HGSC patients who received neoadjuvant chemotherapy and underwent interval debulking. If available, a hemotoxylin and eosin slide from the omentum and the adnexa was selected for the study. Slides were independently scored by 13 pathologists using the 3-tiered CRS system. Reviewers then received web-based training and rescored the slides. Overall survival and progression-free survival were estimated using the Kaplan-Meier method and compared using the log-rank test. A total of 68 patients with omental (n=65) and/or adnexal (n=59) slides were included in the study. Interobserver reproducibility was moderate for omentum (κ, 0.48) and poor for adnexa (κ, 0.40), which improved for omentum (κ, 0.62) but not for adnexa (κ, 0.38) after online training. For omental slides, a consensus CRS of 1/2 was associated with a shorter median progression-free survival (10.9 mo; 95% confidence interval, 9-14) than a CRS of 3 (18.9 mo; 95% CI, 18-24; P=0.020). In summary, a 3-tiered CRS system of hemotoxylin and eosin-stained omental deposits can yield prognostic information for HGSC patients receiving neoadjuvant chemotherapy, and web-based training improved reproducibility but did not alter determination of clinical outcomes. The CRS system may allow oncologists to identify potential nonresponders and triage HGSC patients for heightened observation and/or clinical trials.


Subject(s)
Carcinoma/drug therapy , Ovarian Neoplasms/drug therapy , Adnexa Uteri/pathology , Adnexa Uteri/surgery , Aged , Carcinoma/diagnosis , Carcinoma/pathology , Carcinoma/surgery , Cytoreduction Surgical Procedures , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Neoadjuvant Therapy , Observer Variation , Omentum/pathology , Omentum/surgery , Online Systems , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Prognosis , Retrospective Studies , Treatment Outcome
8.
Clin Lab ; 62(9): 1731-1737, 2016 Sep 01.
Article in English | MEDLINE | ID: mdl-28164597

ABSTRACT

BACKGROUND: Keratoconus is an ocular degeneration characterized by the thinning of corneal stroma that may lead to varying degrees of myopia and visual impairment. Genetic factors have been reported in the pathology of keratoconus where Asians have a higher incidence, earlier onset, and undergo earlier corneal grafts compared to Caucasians. The visual system homeobox 1 (VSX1) gene forms part of a paired-like homeodomain transcription factor which is responsible for ocular development. The gene was marked as a candidate in genetic studies of keratoconus in various populations. Single nucleotide polymorphisms (SNPs) in the VSX1 gene have been reported to be associated with keratoconus. The detection of the SNPs involves DNA amplification of the VSX1 gene followed by genomic sequencing. Thus, the objective of this study aims to establish sensitive and accurate screening protocols for the molecular characterization of VSX1 polymorphisms. METHODS: Keratoconic (n = 74) and control subjects (n = 96) were recruited based on clinical diagnostic tests and selection criteria. DNA extracted from the blood samples was used to genotype VSX1 polymorphisms. In-house designed primers and optimization of PCR conditions were carried out to amplify exons 1 and 3 of the VSX1 gene. PCR conditions including percentage GC content, melting temperatures, and differences in melting temperatures of primers were evaluated to produce sensitive and specific DNA amplifications. RESULTS: Genotyping was successfully carried out in 4 exons of the VSX1 gene. Primer annealing temperatures were observed to be crucial in enhancing PCR sensitivity and specificity. Annealing temperatures were carefully evaluated to produce increased specificity, yet not allowing sensitivity to be compromised. In addition, exon 1 of the VSX1 gene was amplified using 2 different sets of primers to produce 2 smaller amplified products with absence of non-specific bands. DNA amplification of exons 1 and 3 consistently showed single band products which were successfully sequenced to yield reproducible data. CONCLUSIONS: The use of in-house designed primers and optimized PCR conditions allowed sensitive and specific DNA amplifications that produced distinct single bands. The in-house designed primers and DNA amplification protocols established in this study provide an addition to the current repertoire of primers for accurate molecular characterization of VSX1 gene polymorphisms in keratoconus research.


Subject(s)
DNA Primers/genetics , Eye Proteins/genetics , Homeodomain Proteins/genetics , Keratoconus/genetics , Nucleic Acid Amplification Techniques/methods , Genes, Homeobox , Genetic Testing , Humans , Malaysia
10.
Mod Pathol ; 21(8): 937-42, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18500258

ABSTRACT

Diffuse p53 immunostaining distinguishes 85% of serous (Type II) from endometrioid (Type I) carcinomas and is an independent marker for poor prognosis. Interobserver reproducibility for the diagnosis of these entities, as well as selection and prediction of p53 immunostaining results, is unknown. Reproducibility of three pathologists regarding: (1) a two (I and II) and (2) three part classification (I, II or indeterminate); (3) recommendation for p53 staining and (4) expectations of p53 staining results were computed with the kappa (k) statistic. All cases were immunostained for p53 and independently scored. A two and three tiered classification scheme achieved high (k=0.71) and moderate (k=0.49) reproducibility. Non-unanimous cases were more likely to be reclassified into an 'indeterminate' category (27 cases, 39% of passes) compared to those with unanimous (82 cases, 14% of passes) classification. Pathologists recommended p53 immunostaining with poor (k=0.28) reproducibility, but staining prediction was made with good concordance (69%, k=0.50). Moreover, p53 staining was more common in diagnostically discordant (46%) compared to concordant (16%) cases. A subset of endometrial cancers do not readily fit within a two-class system and can be culled from cases that (1) do not achieve interobserver concordance and (2) are more likely to be chosen for p53 immunostaining and (3) are more likely to stain positive for p53. Because p53 is an important marker for endometrial adenocarcinoma outcome, and cannot be predicted in advance in indeterminate cases, p53 immunostaining should be employed in cases with observer disagreement in a binary system.


Subject(s)
Biomarkers, Tumor/analysis , Cystadenocarcinoma, Serous/pathology , Endometrial Neoplasms/pathology , Tumor Suppressor Protein p53/analysis , Biopsy , Cystadenocarcinoma, Serous/chemistry , Cystadenocarcinoma, Serous/classification , Decision Making , Endometrial Neoplasms/chemistry , Endometrial Neoplasms/classification , Female , Humans , Hysterectomy , Immunohistochemistry , Observer Variation , Reproducibility of Results
11.
Am J Surg Pathol ; 29(12): 1609-14, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16327433

ABSTRACT

Although established histologic criteria for the diagnosis of endocervical adenocarcinoma in situ (AIS) have been published, some lesions are not readily classified or present with more subtle degrees of epithelial atypia. Lesions confined to the surface mucosa may be particularly challenging, possibly because they represent early disease. Twelve cases of superficial AIS (SAIS) confined to the surface mucosa or crypt openings culled from the in-house and consultation practices were examined histologically, immunostained for MIB-1 and p16, and analyzed (when possible) for HPV nucleic acids by DNA-DNA in situ hybridization (INFORM). The mean age was 26.7 years for SAIS versus 37.0 years for 42 consecutive cases of conventional AIS from the same practice (P < 0.001). Seven and five were biopsies and conization specimens, respectively. Five coexisted with CIN, four arose in endocervical papillae, and two arose in endocervical polyps. Nuclear hyperchromasia was conspicuous in 10 and mitoses were present in all; however, apoptosis was rare or absent in four, and six exhibited only mild nuclear atypia. Mib-1 staining exceeded 40% in 5 of 7 cases tested, and all (8 of 8) were strongly positive for p16(ink4). Five of five were positive for HPV by ISH with an "integrated" dot-like pattern. SAIS is an early variant of AIS that 1) occurs at a younger mean age, 2) exhibits variable atypia, and 3) arises adjacent to morphologically normal columnar epithelium. Diffuse p16 expression and integrated HPV pattern are identical to that seen in more extensive forms of the disease. Superficial AIS should be suspected in endocervical columnar epithelium with segmental nuclear hyperchromasia with mitotic activity, and confirmed by biomarker staining (p16 and Mib-1) if the pathologist is uncertain of the diagnosis.


Subject(s)
Adenocarcinoma/pathology , Biomarkers, Tumor/analysis , Carcinoma in Situ/pathology , Uterine Cervical Neoplasms/pathology , Adenocarcinoma/diagnosis , Adolescent , Adult , Apoptosis , Biopsy , Carcinoma in Situ/diagnosis , Carcinoma in Situ/metabolism , Carcinoma in Situ/virology , Cell Nucleus/pathology , Conization , Cyclin-Dependent Kinase Inhibitor p16/analysis , DNA Probes, HPV , DNA, Neoplasm/metabolism , DNA, Viral/analysis , Female , Humans , Immunohistochemistry , In Situ Hybridization , Ki-67 Antigen/analysis , Mitosis , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Retrospective Studies , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/virology , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Dysplasia/metabolism , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/virology
12.
Clin Cancer Res ; 11(21): 7651-7, 2005 Nov 01.
Article in English | MEDLINE | ID: mdl-16278384

ABSTRACT

PURPOSE: Mucinous adenocarcinoma of the ovary is one of the common histologic types of ovarian cancer. Its pathogenesis is largely unknown. In addition, the differential diagnosis of metastatic mucinous carcinomas to the ovaries, particularly those originating from the appendix, remains challenging. The purpose of this study is to identify molecular biomarkers for mucinous ovarian adenocarcinoma and compare them with those of appendiceal origin. EXPERIMENTAL DESIGN: Genome-wide loss-of-heterozygosity (LOH) analysis was done on DNA isolated from 28 microdissected primary mucinous ovarian carcinomas and five appendiceal adenocarcinomas. Markers from high-loss regions were selected for further analysis on a total of 32 ovarian and 14 appendiceal cancers. RESULTS: High levels of LOH rates (>40%) were detected on chromosome arms 9p, 17p, and 21q in mucinous ovarian carcinoma cases. The frequency of allelic loss was similar between high-grade and low-grade mucinous ovarian carcinoma cases but was significantly higher in ovarian versus appendiceal cases. In addition, LOH rates on five chromosomal loci were statistically different between ovarian and appendiceal carcinomas. CONCLUSION: A high frequency of LOH can be found in mucinous ovarian adenocarcinomas independent of grade. Despite histologic similarities between mucinous ovarian carcinomas and metastatic appendiceal carcinomas, they have distinct LOH profiles, which may be used for distinguishing the two diseases.


Subject(s)
Adenocarcinoma, Mucinous/genetics , Appendiceal Neoplasms/genetics , Appendiceal Neoplasms/pathology , Carcinoma/genetics , Genome , Genotype , Heterozygote , Loss of Heterozygosity , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Adenocarcinoma, Mucinous/pathology , Adult , Aged , Aged, 80 and over , Alleles , Biomarkers, Tumor , Carcinoma/pathology , Female , Genetic Techniques , Genome, Human , Humans , Male , Middle Aged
13.
Tex Heart Inst J ; 32(2): 238-40, 2005.
Article in English | MEDLINE | ID: mdl-16107126

ABSTRACT

Atrial myxoma is the most common benign tumor of the heart. Patients who have atrial myoxmas usually present with cardiac obstruction, arrhythmias, or peripheral embolization. A tumor originating in the left atrium most often embolizes to the cerebrovascular system. Complete myxoma embolization to the peripheral vessels is rare and usually occurs with tragic consequences. We present an unusual case of acute lower extremity ischemia due to the complete embolization of a left atrial myxoma.


Subject(s)
Heart Neoplasms/complications , Ischemia/etiology , Leg/blood supply , Myxoma/complications , Neoplastic Cells, Circulating/pathology , Embolectomy , Female , Heart Atria , Humans , Iliac Artery , Middle Aged
14.
J Low Genit Tract Dis ; 9(3): 154-9, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16044055

ABSTRACT

OBJECTIVE: Human papillomavirus (HPV) risk assignment influences management after a cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL). This study addressed whether type-specific HPV testing predicts risk of biopsy outcome of high-grade cervical intraepithelial neoplasia (CIN 2,3). MATERIALS AND METHODS: A total of 162 ASCUS or LSIL diagnoses with colposcopic follow-up were evaluated and placed in 3 groups: Analysis 1: (high-risk HPVs including types 53 and 66; Analysis 2 (high-risk HPVs excluding types 53 and 66); and Analysis 3 (high-risk HPVs including type 53 and excluding type 66). RESULTS: CIN 2,3 biopsy results followed low-risk HPVs in 0%, 3%, and 0% of scenarios 1, 2, and 3, respectively; 21%, 40%, and 27% of smears were classified as low risk, respectively. Of HPV 53 infections, 13.6% had CIN 2,3 biopsy outcomes. CONCLUSIONS: Type-specific HPV testing accurately classifies a group of HPV-positive LSIL/ASCUS cases at low risk for CIN 2,3 at the first follow-up visit. Classifying HPV 53 as low-risk increases slightly the proportion of HSIL outcomes in the low-risk group, but may not increase cancer risk. HPV 53 merits designation as a high-risk HPV based only [corrected] on the proportion of CIN 2,3 in follow-up biopsy.


Subject(s)
Cervix Uteri/pathology , Papillomaviridae/classification , Papillomavirus Infections/complications , Uterine Cervical Dysplasia/pathology , Uterine Cervical Neoplasms/pathology , Biopsy , Female , Humans , Papillomaviridae/isolation & purification , Predictive Value of Tests , Risk , Risk Assessment , Uterine Cervical Neoplasms/virology , Uterine Cervical Dysplasia/virology
15.
Am J Clin Pathol ; 124(1): 58-61, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15923175

ABSTRACT

We studied the appropriateness of interpreting squamous cells with enlarged, smooth, bland nuclei in perimenopausal women ("PM cells") as atypical squamous cells (ASCs). Papanicolaou smears (Paps) from 100 women (40-55 years old) with a cytologic interpretation of ASC of undetermined significance (ASCUS) and human papillomavirus (HPV) testing or a biopsy within 6 months were reviewed by 2 observers without knowledge of the biopsy diagnosis or HPV results. Cases in which both reviewers agreed that the Paps were diagnosed more properly as "negative for intraepithelial lesion or malignancy" were compared with cases of "true ASCUS," using histologic squamous intraepithelial lesion and/or a positive high-risk HPV test as a positive outcome (abnormal follow-up). Of 100 cases, 28 were reclassified as benign by both observers. In 15 of these, the original ASCUS interpretation was based on cells with bland nuclear enlargement (2-3 times the area of intermediate cell nuclei), smooth nuclear membranes, and fine chromatin. Abnormal follow-up was identified in 1 (7%) of 15 benign cases but in 30 (42%) of 72 true ASCUS cases (P = .023). PM cells are a significant cause of ASC overdiagnosis in women 40 to 55 years old. Cervical Paps with cells no more atypical than these can be interpreted safely as negative for intraepithelial lesion or malignancy.


Subject(s)
Cell Nucleus/ultrastructure , Cervix Uteri/cytology , Cervix Uteri/pathology , Perimenopause , Uterine Cervical Dysplasia/pathology , Adult , Age Factors , Cell Nucleus/pathology , Female , Humans , Middle Aged , Papanicolaou Test , Predictive Value of Tests , Retrospective Studies , Vaginal Smears
16.
J Infect Dis ; 189(8): 1348-54, 2004 Apr 15.
Article in English | MEDLINE | ID: mdl-15073670

ABSTRACT

BACKGROUND: Little is known about the dynamics of human papillomavirus (HPV) during the follow-up of cervical intraepithelial neoplasia (CIN) 2/3 after biopsy. METHODS: A total of 127 women with biopsy-confirmed CIN2/3 were enrolled in a phase 2 double-blinded, randomized, placebo-controlled clinical trial of ZYC101a. Colposcopic, cytologic, and HPV testing were performed over the course of 6 months, before a loop electrical surgical excision procedure was performed at study exit. RESULTS: Of the women tested, 99% were found to be HPV positive at study entry, 50% were found to be HPV type 16 positive at study entry, 22% were found to be positive for multiple HPV types at study entry, and 37% were found to be positive for additional HPV types during follow-up. Of those with a histologic outcome of CIN1 at study exit, 78% were found to be positive for additional HPV types; in 39%, the original type was replaced with a new HPV type. Virus load at study entry did not predict outcome, but pre-study-exit virus load correlated with a histologic outcome of any CIN, and changes in virus load correlated with risk for an outcome of CIN2/3 at study exit. CONCLUSIONS: The type and number of HPVs at study entry, detection of additional viral types, and virus load changes during follow-up influence histologic outcome at study exit. An outcome of CIN1 at study exit is most likely due to additional HPV infections, rather than morphologic reversion of CIN2/3 to CIN1. Knowledge of the dynamics of HPV infection during the biopsy-to-excision period is critical to understanding the natural history of HPV infection, its contribution to disease outcome, and interpretations of drug efficacy.


Subject(s)
Antiviral Agents/therapeutic use , DNA/therapeutic use , Papillomaviridae/growth & development , Papillomavirus Infections/drug therapy , Uterine Cervical Dysplasia/virology , Uterine Cervical Neoplasms/virology , Biopsy , Clinical Trials, Phase II as Topic , DNA, Viral/chemistry , DNA, Viral/genetics , Double-Blind Method , Female , Humans , Nucleic Acid Hybridization , Papillomaviridae/genetics , Papillomaviridae/metabolism , Papillomavirus Infections/pathology , Papillomavirus Infections/virology , Polymerase Chain Reaction , Randomized Controlled Trials as Topic , Treatment Outcome , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/pathology , Viral Load , Uterine Cervical Dysplasia/drug therapy , Uterine Cervical Dysplasia/pathology
17.
Am J Clin Pathol ; 121(1): 87-92, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14750245

ABSTRACT

Cases of atypical glandular cells (AGC) diagnosed on liquid-based preparations were culled from a 3-year period. When available, residual cellular material was analyzed for human papillomavirus (HPV) by polymerase chain reaction and correlated with cytologic and histologic (biopsy) outcome. Of 178,994 cytologic cases, 187 (0.1045%) contained AGC compared with 8,740 (4.8828%) atypical squamous cells (ASC) for an AGC/ASC ratio of 0.021. HPV results and follow-up were available for 108 specimens from 106 patients. Depending on the end-point (histologic/cyto-logic), the sensitivity range of HPV testing for significant cervical disease (high-grade squamous intraepithelial lesion [SIL], adenocarcinoma in situ [ACIS], invasive carcinoma) was 83% with a specificity range of 78% to 82%, a positive predictive value of 57% to 61%, and a negative predictive value of 91% to 95%. Fifteen false-positive results included concurrent ASC or low-grade SIL, ASC on follow-up cytology, and previous ACIS with a negative follow-up cone biopsy result. Noncervical glandular neoplasia (including atypical endometrial hyperplasia) was confirmed in 13 cases (1 recurrent), only 2 of which scored positive for HPV. HPV-positive AGC has a substantially higher positive predictive value for significant disease than ASC (61% vs historic 20%) and merits consideration in the triage of patients with atypical endocervical cells not otherwise specified. However, noncervical or other HPV-negative glandular neoplasia must be considered in all patients with AGC, particularly older patients.


Subject(s)
Papillomaviridae/isolation & purification , Papillomavirus Infections/pathology , Uterine Cervical Dysplasia/pathology , Uterine Cervical Neoplasms/pathology , DNA, Viral/analysis , Female , Follow-Up Studies , Humans , Mass Screening , Papillomaviridae/genetics , Papillomavirus Infections/complications , Polymerase Chain Reaction , Predictive Value of Tests , Single-Blind Method , Uterine Cervical Dysplasia/virology , Uterine Cervical Dysplasia/complications , Uterine Cervical Neoplasms/virology , Vaginal Smears/classification , Vaginal Smears/methods
18.
Am J Surg Pathol ; 27(3): 281-92, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12604884

ABSTRACT

The gross and routine microscopic features of 25 stage I primary mucinous ovarian carcinomas without clinical evidence of recurrence and 25 mucinous carcinomas metastatic to the ovaries were compared. Findings that were frequent in the latter and strongly favored a metastasis were: 1) bilaterality, 2) microscopic surface involvement by epithelial cells (surface implants), and 3) an infiltrative pattern of stromal invasion. Findings that were less frequent but present exclusively or almost exclusively in metastatic carcinomas were: 1) a nodular invasive pattern, 2) ovarian hilar involvement, 3) single cell invasion, 4) signet-ring cells, 5) vascular invasion, and 6) microscopic surface mucin. Findings that were frequent in, and strongly favored, primary ovarian carcinoma were: 1) an "expansile" pattern of invasion and 2) a complex papillary pattern. Findings that were less frequent but also favored a primary tumor were: 1) size >10 cm, 2) a smooth external surface, 3) benign-appearing and borderline-appearing areas, 4) microscopic cystic glands, and 5) necrotic luminal debris. Findings that did not distinguish the tumors were: 1) a cystic gross appearance, 2) gross solid, papillary, necrotic, or hemorrhagic areas, 3) nature of cyst contents (mucinous vs nonmucinous), 4) stromal mucin (pseudomyxoma ovarii), 5) cribriform, villous, or solid growth patterns, 6) focal area resembling typical colonic carcinoma, 7) goblet cells, or 8) tumor grade. Primary and metastatic mucinous ovarian carcinomas can be distinguished from each other in the great majority of cases based solely on their conventional histopathologic findings. Careful gross evaluation is also important with special attention paid to the external surface of the ovarian tumor(s) to detect abnormalities that have the features of surface implants on microscopic evaluation.


Subject(s)
Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/secondary , Gallbladder Neoplasms/pathology , Ovarian Neoplasms/pathology , Ovarian Neoplasms/secondary , Pancreatic Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging
19.
Adv Anat Pathol ; 10(2): 55-68, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12605088

ABSTRACT

Until recently, the histologic diagnosis of obstetrical and gynecologic neoplasia was based principally on morphologic criteria. However, interobserver reproducibility for entities such as squamous intraepithelial, endometrial, and trophoblastic disease varies widely between observers. This inherent variability in interpretation between individuals has led to wide ranges in diagnostic precision between practices, and in many cases, between recognized experts. The advent of immunohistochemistry, and the more recent accelerated discovery of new genes and their functions has resulted in the discovery of cellular proteins or nucleic acids that are differentially expressed in tumors. When applied in conjunction with existing histologic criteria, these "biomarkers" have the potential to enhance diagnostic consistency and reproducibility. The gains expected are to practicing diagnostic pathologists (who will enjoy greater diagnostic consistency) and to academics (for whom biomarkers may uncover new pathways unappreciated by histologic diagnosis alone). However, fundamental to the success in both arenas will be critical analysis of the potential pitfalls in immunohistochemistry, strict validation of new markers as they arrive in the field, and a realistic view of their value in the laboratory management of obstetrical and gynecologic diseases.


Subject(s)
Biomarkers, Tumor/analysis , Genital Neoplasms, Female/chemistry , Genital Neoplasms, Female/pathology , Ki-67 Antigen/analysis , Female , HMGA2 Protein/analysis , Humans , Hydatidiform Mole/chemistry , Hydatidiform Mole/pathology , Immunohistochemistry , PTEN Phosphohydrolase , Phosphoric Monoester Hydrolases/analysis , Pregnancy , Tumor Suppressor Protein p53/analysis , Tumor Suppressor Proteins/analysis , Tumor Virus Infections/pathology , Uterine Cervical Neoplasms/chemistry , Uterine Cervical Neoplasms/pathology , Uterine Neoplasms/chemistry , Uterine Neoplasms/pathology , Vulvar Neoplasms/chemistry , Vulvar Neoplasms/pathology , Vulvar Neoplasms/virology
20.
Int J Gynecol Pathol ; 22(1): 22-4, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12496693

ABSTRACT

Adenocarcinoma in situ (AIS) is the acknowledged precursor to most cases of invasive adenocarcinoma of the cervix. However, diagnostic terminology for lesions that do not fulfill all of the published criteria for AIS has not been standardized. Some have used the terms "glandular dysplasia" or " atypical hyperplasia" for purported antecedents of AIS, whereas others have adopted the term "cervical intraepithelial glandular neoplasia" (CIGN) for the entire spectrum of endocervical atypicality including AIS, with subcategories of "low-grade" and "high-grade" CIGN. In this article the appropriateness of using these terms in diagnostic reports (versus the use of AIS to include some or most of the lesions encompassed by them, with nonspecific terminology for the remainder) is examined in the light of the relevant objective studies bearing on this question. An opinion is offered favoring the latter approach.


Subject(s)
Adenocarcinoma/pathology , Carcinoma in Situ/pathology , Pathology, Clinical/standards , Uterine Cervical Dysplasia/pathology , Uterine Cervical Neoplasms/pathology , Female , Humans , Neoplasm Staging , Reproducibility of Results
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