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Pediatric core needle biopsy: strengths and limitations in evaluation of masses.

Needle core biopsies (NCB) are widely used in adults but are less often used for the evaluation of pediatric tumors. To determine the diagnostic utility of NCB for pediatric tumors, we performed a retrospective analysis. Fifty NCB of masses from 1992 to 1998, subsequent pathologic specimens, and medical records were reviewed. All patients were less than 21 years of age. Of the NCB 78% (39/50) were diagnostic of a neoplasm, 8% (4/50) were nondiagnostic in cases where a tumor was subsequently diagnosed, and 14% (7/50) revealed inflammatory or reactive lesions, with no subsequent diagnosis of a neoplasm according to medical record review. In cases in which a neoplasm was present, NCB was diagnostic in 91% (39/43). For cases in which there was a previous diagnosis of a tumor, 100% (9/9) of NCB were diagnostic of a recurrence or metastasis. In cases of NCB for primary tumor diagnosis, 88% (30/34) were diagnostic. The most common problems encountered were related to specimen adequacy, such as insufficient tissue, crush artifact, and tumor necrosis. Tumor diagnoses were as follows: primitive neuroectodermal tumor (PNET)/Ewing sarcoma (12), malignant lymphoma/Hodgkin's disease (8), rhabdomyosarcoma (4), germ cell tumor (3), Wilms' tumor (3), neuroblastoma (1), sarcoma, not otherwise specified (4), and other neoplasms (8). There were no complications of the procedure. NCB of pediatric tumors is an effective diagnostic tool and can be used to obtain diagnostic material quickly and safely. NCB was diagnostic in 90% of cases in this series. When NCB provide sufficient material for immunohistochemical, cytogenetic, flow cytometric, and other ancillary studies, the diagnostic efficacy is enhanced. The major limitations in this series were related to sampling problems and specimen adequacy for comprehensive pathologic evaluation.

Adolescent↗

[Minimally invasive surgical procedures of the breast: comparison of different biopsy systems in a breast parenchymal model].

PURPOSE: The purpose of our study was to evaluate various systems for large core biopsy. First to determine the volume of specimen that can be removed with each minimal-invasive method and second to compare their consistency. With respect to the optimum of volume which can be acquired the 12-G system should be optimized by special modifications. METHODS: Examinations were performed on a phantom. We used 8 automatic, one sequential-automatic and 4 halfautomatic highspeed core biopsy systems of 16-, 14- and 12 G as well as the 11G vacuum biopsy. The weight and consistency of the specimen was determined in every case. The 12G system was optimized by enlargement of the biopsy chamber. RESULTS: The 11G vacuum biopsy exhibited best results concerning the weight of the specimen (93.7 +/- 13.5 mg). The results achieved with high speed core biopsy varied with the needle diameter as well as with the technique. Semi- and halfautomatic systems were superior to automatic systems. Best results among highspeed core biopsy systems were achieved with the modified 12G biopsy needle (41.3 +/- 4.4 mg). CONCLUSION: As expected, largest volume of specimen can be removed with vacuum biopsy. High speed core biopsy systems are inferior to vacuum biopsy. Nevertheless, the amount of volume achieved can be increased to 22.4 mg by using 14G needles and to 41.3 mg by using 12G needles. The modified 12-G needle may be considered as an less expensive alternative to 11G vacuum biopsy.

Biopsy↗

Colposcopy and directed biopsy reliability during pregnancy: a cohort study.

The reliability of cytology, colposcopy, and directed biopsy were assessed in pregnancy and compared with that observed in a matched non-pregnant control group in order to evaluate the influence of pregnancy. One hundred and seventeen gravidas in which the final pathology could be ascertained and 234 control patients were examined by the same colposcopist. Concordance between cytology and final diagnosis was complete or within one degree of severity in 55.6% and 77.8% of patients, respectively. Unsatisfactory colposcopy was significantly less frequent in pregnant patients than in controls (12.8% vs. 23.1%, P = 0.023). In pregnant patients, colposcopy provided concordance, overestimation and underestimation of the final diagnosis in 72.6%, 17.6% and 9.8%, respectively. In the same group, the concordance between the histologic findings of directed biopsy and final diagnosis was complete or within one degree of severity in 83.7% and 95.9%, respectively. The reliability of cytology, colposcopy and directed biopsy was not related to pregnancy. These data show that the physiological changes which occur in pregnancy do not significantly alter the reliability of colposcopy and directed biopsy, if the colposcopist is aware of the peculiar difficulties and does not overreact to the accentuated patterns that may occur during pregnancy.

Adolescent↗

Dilating the cervix medically to overcome an unsatisfactory colposcopy: 5 year follow up.

OBJECTIVE: To examine the long term results of placing a hydroscopic sponge in the cervix to expose high lesions and overcome an unsatisfactory colposcopic examination. STUDY DESIGN: Forty-one women presenting with their first abnormal smear but an unsatisfactory colposcopy were offered medical dilation of the cervix with Lamicel. These women had local ablative treatment and were followed for 5 years to establish the risk of recurrent disease after medical dilation. For comparison we measured the risk of recurrence after a cone biopsy performed as primary treatment for women attending a different hospital in the same city. RESULTS: Medical dilation was unacceptable or failed in 16 of the 41 women. It was initially successful at exposing the entire transformation zone and sparing 25 women a cone biopsy. Ten of these presented with recurrent disease requiring a cone biopsy within 5 years. Two cases were lost to follow up leaving 13 out of a total of 38 women who ultimately avoided a cone biopsy. The recurrent disease rate despite local treatment following medical dilation is 43%. The recurrent disease rate in the city following a cone biopsy is 20%. CONCLUSION: Although medical dilation of the cervix may permit lesions in the canal to be visualised, follow up is difficult and the risk of further disease is high. It is not recommended as a routine.

Biocompatible Materials↗

Conservative treatment of cervical intraepithelial neoplasia using a cold-knife section technique.

OBJECTIVE: The purpose of this study was to evaluate a conservative cold-knife section technique for treatment of cervical intraepithelial neoplasia (CIN). This procedure can be adapted to patient age, preservation of childbearing potential and extent of dysplasia. DESIGN: Prospective study. SETTING: Gynecological Oncology Department in French Public Hospital. POPULATION: A total of 460 women treated for CIN between 1985 and 1999 were included. METHODS: A conservative cold-knife cervical section followed by blanket suture reconstruction was used in all cases. MAIN OUTCOME MEASURES: Immediate operative results, recurrence and reproductive function were assessed. RESULTS: The mean length of the cervical specimen was 11.4 mm (range, 4-22 mm). Mean specimen thickness was strongly correlated with age: 10.6 +/- 4.1 mm in women <40 years versus 12.1 in women >40 years; p < 0.001. Complete excision was achieved in 395 cases (85.8%). Post-operative bleeding was observed in 5 cases (1.1%). The mean duration of follow-up was 62 months (range, 12.3-156.5 months). Recurrences developed in 26 patients (6.6%) including CIN 1 in 9 cases, CIN 2 in 9 and CIN 3 in 8. No patient developed carcinoma. The actuarial risk of recurrence was 2.4% (+/- S.D., 0.9) at 24 months and 7.8% (+/-S.D., 1.9) at 60 months. A total of 52 pregnancies were observed in 39 patients. No case of de novo infertility was reported post-operatively. Amenorrhea was noted in 1 patient (0.1%) and dysmenorrhea in 1 patient (0.1%). CONCLUSIONS: This conservative cold-knife section technique is effective for treatment of CIN with low morbidity and little adverse effect on childbearing potential. Exposure of the squamocolumnar junction (SCJ) greatly facilitates follow-up.

Adult↗

Up-regulation of proliferating cell nuclear antigen (PCNA) is closely associated with high-risk human papillomavirus (HPV) and progression of cervical intraepithelial neoplasia (CIN), but does not predict disease outcome in cervical cancer.

OBJECTIVE: Proliferating cell nuclear antigen (PCNA) is essential for DNA replication of mammalian cells and their small DNA tumour viruses. The E7 oncoprotein of high-risk human papillomavirus (HPV) is known to activate PCNA, shown to be up-regulated in CIN and cervical cancer (CC), but still incompletely studied as an intermediate endpoint marker in this disease. MATERIAL AND METHODS: As part of our HPV-PathogenISS study, a series of 150 CCs and 152 CIN lesions were examined using immunohistochemical (IHC) staining for PCNA, and tested for HPV using PCR with three primer sets (MY09/11, GP5+/GP6+, SPF). Follow-up data were available from all SCC patients, and 67 of the CIN lesions had been monitored with serial PCR for HPV after cone treatment. RESULTS: Expression of PCNA increased in parallel with the grade of CIN, with major up-regulation upon transition to CIN3 (OR 21.77; 95%CI 6.59-71.94) (p = 0.0001). Intense PCNA expression was 100% specific indicator of CIN, with 100% PPV, but suffers from low sensitivity (34.8%) and NPV (10.8%). PCNA expression was also significantly associated to HR-HPV with OR 3.02 (95%CI 1.71-5.34) (p = 0.0001), and this association was not confounded by the histological grade (Mantel-Haenszel common OR = 2.03; 95%CI 1.06-3.89) (p = 0.033). Expression of PCNA did not predict clearance/persistence of HR-HPV after treatment of CIN, and it was not a prognostic predictor in CC in univariate or in multivariate analysis. CONCLUSIONS: Up-regulation of PCNA was closely associated with HR-HPV and progressive CIN, most feasibly explained by the abrogation of normal cell cycle control by the E7 ongogene, reverting the p21(Cip1)-mediated inhibition of PCNA. However, the fact that PCNA is also expressed in normal squamous epithelium precludes the use of this marker as a potential screening tool for CC.

Adolescent↗

Cervical adenoid basal tumors comprised of adenoid basal epithelioma associated with various types of invasive carcinoma: clinicopathologic features, human papillomavirus DNA detection, and P16 expression.

Adenoid basal tumors are uncommon cervical lesions that some pathologists consider invasive carcinomas but others consider "epitheliomas" due to their low-grade histological appearance and rarely documented malignant behavior. We report the clinicopathologic features of 10 tumors comprised of both typical low-grade adenoid basal tumors (epitheliomas) intimately associated with invasive carcinomas having infiltrative growth, increased cytological atypia and mitotic activity, and various types of differentiation, including adenoid basal/squamous, pure squamous, adenoid cystic, and small cell neuroendocrine. Tumors were evaluated for the presence of human papillomavirus (HPV) DNA and immunohistochemical p16 expression. The patients in the study group ranged in age from 45 to 81 years (mean, 65 years). Most of the patients presented with abnormal cervicovaginal smears. The initial diagnosis was made on specimens obtained by cervical biopsy, laser electrocautery excision procedure (LEEP), or cone biopsy in 8 patients. Two 2 patients were incidentally diagnosed in hysterectomy specimens. All 10 patients had squamous intraepithelial lesions (9 high-grade, 1 low-grade). In all cases diagnosed in LEEP or cone biopsy specimens, the invasive carcinoma component was present in the excisional specimen and extended to the margins. Seven patients diagnosed on excisional or biopsy specimens who underwent hysterectomy had residual tumor in the cervix, ranging from microscopic foci to deeply invasive. No lymph node metastases were identified in 4 patients who were staged. Seven patients with follow-up were alive without evidence of disease after follow-up intervals of 8 to 84 months (mean, 45 months; median, 29 months). One patient with a component of small cell carcinoma died of other causes without evidence of disease at 18 months. HPV 16 DNA was detected in both the adenoid basal epithelioma and invasive carcinoma components in 9 tumors by in situ hybridization, and HPV 33 was detected by polymerase chain reaction in 1 tumor. All tumors expressed p16 diffusely. Adenoid basal tumors are high-risk HPV-related tumors that can be comprised of both a low-grade adenoid basal tumor, which can be designated as epithelioma, and invasive carcinomas of various types. The invasive component is usually evident in the excisional biopsy specimen, allowing for recognition of a tumor that needs further management.

Aged↗

Cervical neoplasia complicating pregnancy.

This article reviews the key concepts regarding the counseling and management of cervical dysplasia and invasive cervical cancer diagnosed during pregnancy. Emphasis is placed on balancing the maternal and fetal well-being in collaboration with appropriate multidisciplinary teams. Information regarding appropriate diagnosis strategies and the impact of delay in treatment, subsequent prognosis, and treatment algorithms are discussed. Novel fertility-sparing techniques for cervical cancer and their impact on complications of future pregnancies are also discussed.

Algorithms↗

Frozen section evaluation of cervical cold knife cone specimens is accurate in the diagnosis of microinvasive squamous cell carcinoma.

OBJECTIVES: The purpose of this study was to determine the accuracy of frozen section evaluation of cervical cold knife cone (CKC) specimens in the diagnosis of microinvasive squamous cell carcinoma (SCC). METHODS: Using ICD-9 codes for invasive and microinvasive carcinoma of the cervix, a medical record from 1986 to 1998 identified 110 potential study subjects. Society of Gynecologic Oncologists criteria including depth of invasion < or =3 mm and absence of lymph-vascular space involvement were utilized for the diagnosis of microinvasion. Twenty-seven patients met study criteria including a frozen section diagnosis of microinvasive SCC on a cervical CKC specimen at our institution. A pathologist, blinded to patient diagnosis, reevaluated the histologic findings, including grade, depth of invasion, and cell type. RESULTS: Median age of diagnosis was 41 years. Median follow up was 3.6 years. The median time for pathologic review was 28 min (range 15-44 min). Independent retrospective pathologic review of the permanent sections confirmed the diagnosis of microinvasion in 100% (27/27) of patients. No patient experienced a cervical SCC recurrence. At 10 years, disease-specific survival is 100%. CONCLUSIONS: Frozen section is reliable in the evaluation of CKC specimens with microinvasive SCC: this may afford a simplified surgical approach in certain cases. This accuracy should not be assumed to apply to adeno- or adenosquamous carcinoma of the cervix. At our institution which relies heavily on intraoperative pathologic evaluation, utilizing frozen section diagnosis as the basis for definitive surgical approach did not negatively impact disease-free survival.

Adult↗

Human papillomavirus DNA detection and histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in their Pap smears.

OBJECTIVE: To evaluate the association between high-risk human papillomavirus (HPV) DNA detection and histological diagnosis in women referred for atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) at Pap smear. METHODS: In this cross-sectional study, 146 women referred for AGC (124), AGC with high-grade squamous intraepithelial lesion (HSIL) (15), or AIS (7) were tested for HPV DNA using Hybrid Capture II (HC II). All women underwent colposcopic examination, and cervical biopsy was performed for 95 patients. Fifty-one women referred due to AGC with normal colposcopy and normal second Pap smear were scheduled for control visits every 4 months. RESULTS: The overall prevalence of HPV DNA was 38%. HPV DNA was detected in 93% of the women with HSIL associated with AGC and in 71% of women with AIS Pap smear, being significantly higher when compared with the prevalence (29%) in women with AGC alone. Forty-five women (30.8%) had clinically significant histological lesions (CIN 2 or worse). High-risk HPV DNA was detected in only 16% of the women without significant abnormalities in biopsy, in contrast to 96% of those who had CIN 2 or CIN 3 and 75% of women with AIS. Eighty-five percent of women with invasive cervical carcinoma (squamous or adenocarcinoma) tested positive for HPV DNA. HPV DNA detection was significantly associated with histological diagnosis of CIN 2 or worse, with an odds ratio (OR) = 51.8 (95% CI 14.3-199.9). CONCLUSION: HPV DNA detection was strongly associated with the severity of cervical lesion (CIN 2 or worse) in women referred for AGC or AIS in their Pap smear. These data implicate the use of HPV testing in triage of women with AGC Pap smears.

Biopsy↗

Recurrent smear abnormalities where repeat loop treatment is not possible: is hysterectomy the answer?

OBJECTIVE: The objective of this study was to determine the outcome of women who underwent hysterectomy for recurrent cytological abnormalities where repeat loop treatment was considered not to be technically possible because of insufficient remaining cervical tissue. METHODS: Women undergoing a hysterectomy for the above indication at the Northern Gynaecological Cancer Centre over a period of 10 years (1992-2001) were identified from a prospectively collected database. Case notes were then reviewed and women undergoing hysterectomy for other indications were excluded. Relevant demographic and clinical data were then extracted. RESULTS: 33 patients meeting the above criteria were identified. The overall hysterectomy rate for this indication was 0.73%. 20 out of the 33 women had significant pathology on the hysterectomy specimen. 95% of these had high-grade disease with one having a Stage 1A1 squamous carcinoma. None of the patients required more radical treatment than a simple hysterectomy. There were no major complications following the hysterectomy. Positive endocervical margins on the previous loop specimen (P = 0.05) was an important correlating factor predicting the presence of CIN on the hysterectomy specimen. One out of the thirty hysterectomies (3.3%) performed using the vaginal route had incomplete excision compared to one of three (33%) using the abdominal route. Hysterectomy was successful in treating 85.2% of the women; only 4 women subsequently developed vaginal intraepithelial neoplasia. CONCLUSION: Simple hysterectomy appears to be a suitable diagnostic and treatment option for women with recurrent high-grade cytological abnormalities where further loop treatment is technically not possible. Incomplete excision at the endocervical margin on the previous loop specimen was the main factor associated with the presence of cervical intraepithelial neoplasia at hysterectomy.

Adult↗