Vulvar keratinizing squamous cell carcinoma in a 26-year-old woman.

A 26-year-old Hispanic woman complaining of "itching" and "herpetic lesions" on the vulva for 9 months was seen at a university hospital. On physical examination, multiple vulvar masses were noted. Biopsies taken from these lesions showed invasive keratinizing squamous cell carcinoma. The vulvectomy specimen revealed 4 tumor masses, the largest located on the mons pubis. Although the incidence of vulvar intraepithelial neoplasia has increased in recent years, only very few cases of invasive carcinoma have been reported in young women. The tumors that occur at a younger age characteristically have basaloid or warty histology, in contrast to those occurring in older women, which usually are well-differentiated keratinizing carcinomas. We believe this is an unusual case of vulvar squamous cell carcinoma. In addition to our patient's young age, her tumor had a histologic profile usually found in lesions of an elderly woman. The tumor was negative for human papillomavirus by polymerase chain reaction analysis and was positive for p53 by immunohistochemistry.

Primary papillary serous carcinoma of the peritoneum: CT-pathologic correlation.

We present the CT findings of three cases of primary papillary serous carcinoma of the peritoneum. All patients presented with massive ascites. CT of the abdomen and pelvis showed omental caking in all patients. The parietal peritoneum of the pelvis showed diffuse enhancement with nodular thickening in all patients. No calcification was noted in the omental and parietal peritoneal masses, although psammoma bodies were present microscopically in one case. The ovaries were normal in size but showed a fine enhancing surface nodularity similar to the pelvic peritoneum. The CT findings of primary papillary serous carcinoma of the peritoneum are nonspecific, but this diagnosis should be considered when peritoneal carcinomatosis is seen on CT with normal-sized ovaries in the absence of other primary malignant neoplasms.

VEGF, flt-1, and KDR/flk-1 as prognostic indicators in endometrial carcinoma.

OBJECTIVE: Tumor angiogenesis is a highly regulated process under the influence of the host microenvironment and mediators. Studies of breast cancer and, more recently, ovarian and cervical cancer, demonstrate that neovascularization correlates with the likelihood of metastasis and recurrence. Vascular endothelial growth factor (VEGF), an important regulator of tumor angiogenesis in the endometrium, flt-1, and KDR/flk-1 are good markers of vascular proliferation. Being that angiogenesis is a precursor to the development of progressive disease, we hypothesize that quantifying VEGF, flt-1, and KDR/flk-1 expression in uterine malignancies is a superior predictor of metastatic potential and survival than is FIGO grade of tumor, depth of invasion, and histology. METHODS: The histologic slides of 47 patients with uterine malignancies (35 adenocarcinomas, 6 papillary serous, and 6 carcinosarcomas) were reviewed. The paraffin blocks from the primary tumor were obtained. Immunohistochemistry staining was performed for VEGF, flt-1, and KDR/flk-1. Microvessel density, used to analyze VEGF and receptor concentrations, was determined by two independent investigators, who were blinded to the patients clinical status. The impact of VEGF, flt-1, and KDR/flk-1 as well as stage, grade, depth of invasion, and nodal status on the incidence of metastases, recurrence, and survival was determined using logistic regression analysis and product limit life system survival analysis, respectively. RESULTS: Results indicated that when evaluating all three histologic types, only stage and grade of tumor were found to impact upon the incidence of recurrence and survival. When patients with carcinosarcoma and papillary serous adenocarcinoma were excluded from the analysis, once again only stage and grade of tumor were significant prognostic indicators of recurrence and survival. Only grade of tumor and depth of uterine invasion were significant predictors of a tumor's metastatic potential. VEGF, flt-1, and KDR/flk-1 proved to be of little significance in predicting metastases, recurrence, and survival. Patients with advanced disease in all three histologic subtypes often had low VEGF and receptor positivity. CONCLUSIONS: In this study, VEGF, flt-1, and KDR/flk-1 receptor concentrations did not correlate with the incidence of metastases, recurrence, and survival.

Neural-network-assisted analysis and microscopic rescreening in presumed negative cervical cytologic smears. A comparison.

OBJECTIVE: To compare cytologists' detection of abnormalities when using neural network-assisted (NNA) review, as employed by the PAPNET Testing System and to compare the effectiveness of this mode of review to that of unassisted, conventional rescreening of cervical smears initially diagnosed as negative. STUDY DESIGN: The study was undertaken as part of a multicenter clinical trial involving over 10,000 smears from 10 investigation sites (9 academic institutions and 1 private laboratory). Using a subset of "negative" control smears from three university laboratories, the false negative detection yields of NNA review (performed using the PAPNET System) and conventional microscopic rescreening (performed as part of routine quality control practice) were compared. The false negative detection yield was defined as the percentage of rescreened negatives reclassified as abnormal. RESULTS: The results demonstrate that using NNA review, the detection yield of false negative smears, as a proportion of negative smears reexamined, is statistically significantly greater than that obtained using conventional quality control rescreening. The false negative yield generated using NNA analysis was 6.2% (142/2293) versus 0.6% (82/13761) for conventional rescreening. A statistically significant improvement in identification of abnormality is observed for NNA review as opposed to unassisted rescreening despite constraining the comparison in the following ways: (1) comparing the yields of rescreening of negative smears obtained from the same time intervals for both methods, (2) comparing the yields of rescreening of negative smears obtained from the years after the Clinical Laboratory Improvement Act (1990 and 1991) for both methods, and (3) disregarding the identification of atypical squamous cells of undetermined significance/atypical glandular cells of undetermined significance cases and comparing only the identification of squamous intraepithelial lesions using the two methods. CONCLUSION: Using neural network-assisted review, cytologists uncovered a significantly higher proportion of previously undetected cervical abnormalities per smear reexamined than they did using unassisted, conventional rescreening.

Cytologic changes in cervical smears associated with prolonged use of depot-medroxyprogesterone acetate.

BACKGROUND: Hormonal effects have always played a significant role in gynecologic cytology. In atrophic and postpartum smears, interpretation may be complicated by large numbers of parabasal cells with high nuclear cytoplasmic ratios and hyperchromatic nuclei that mimic precancerous lesions (squamous intraepithelial lesions, SILs). The authors have observed atrophic and postpartumlike changes in patients receiving depot-medroxyprogesterone acetate for prolonged periods. These alterations may lead to diagnostic uncertainty or falsely suggest the presence of SIL. METHODS: To evaluate the effect of chronic hormone use, smears from 29 depot-medroxyprogesterone acetate users (average age, 35.9 years) who had been amenorrheic for 5-72 months (average, 22.6 months) were identified. This group was matched with 25 nonusers (average age, 31.9 years). Maturation values (MVs) were calculated for both groups and cellular findings were evaluated. RESULTS: The user group had a significantly lower MV (38.45 vs. 64.60, P < 0.001). Among users, 6 of 29 smears (21%) were abnormal. One low grade SIL was biopsy-confirmed, but two high grade SILs and three smears of ASCUS had a negative Papanicolaou (Pap) smear and/or biopsy follow-up. Among nonusers, 4 of 25 smears (16%) were abnormal. Two patients with high grade SIL smears had positive biopsy or Pap smear follow-up, one with an ASCUS smear had a negative Pap smear follow-up, and one with a low grade SIL was lost to follow-up. CONCLUSIONS: The immature cellular pattern seen in smears from long term depot-medroxyprogesterone acetate users led to difficulty in determining the diagnosis in some cases. ASCUS cases among users were associated with high nuclear cytoplasmic ratios and hyperchromasia in parabasal metaplasialike cells. Biopsies in these cases showed epithelial atrophy, which was often associated with acute inflammation. In view of the fact that long term depot-medroxyprogesterone acetate administration may induce changes that mimic high grade SIL in a population already at high risk for SIL, there may be problematic cases in which diagnostic uncertainty is inevitable.

Significant reduction in the rate of false-negative cervical smears with neural network-based technology (PAPNET Testing System).

False-negative cervical Pap smears may lead to disability or death from carcinoma of the uterine cervix. New computer technology has led to the development of an interactive, neural network-based vision instrument to increase the accuracy of cervical smear screening. The instrument belongs to a new class of medical devices designed to provide computer-aided diagnosis (CADx). To test the instrument's performance, 487 archival negative smears (index smears) from 228 women with biopsy-documented high-grade precancerous lesions or invasive cervical carcinoma (index women) were retrieved from the files of 10 participating laboratories that were using federally mandated quality assurance procedures. Samples of sequential negative smears (total 9,666) were retrieved as controls. The instrument was used to identify evidence of missed cytological abnormalities, including atypical squamous or glandular cells of undetermined significance (ASCUS, AGUS), low-grade or high-grade squamous intraepithelial lesions (LSIL, HSIL) and carcinoma. Using the instrument, 98 false-negative index smears were identified in 72 of the 228 index women (31.6%, 95% confidence interval [CI]: 25% to 38%). Disregarding the debatable categories of ASCUS or AGUS, there were 44 women whose false-negative smears disclosed squamous intraepithelial lesions (SIL) or carcinoma (19.3%; 95% CI: 14.2% to 24.4%). Unexpectedly, SILs were also identified in 127 of 9,666 control negative smears (1.3%; 95% CI: 1.1% to 1.5%). Compared with historical performance data from several participating laboratories, the instrument increased the detection rate of SILs in control smears by 25% and increased the yield of quality control rescreening 5.1 times (P < 0.0001). These data provide evidence that conventional screening and quality control rescreening of cervical smears fail to identify a substantial number of abnormalities. A significant improvement in performance of screening of cervical smears could be achieved with the use of the instrument described in this report.

Gastric stromal tumor with peritoneal nodules in pregnancy: tumor spread or rare variant of diffuse leiomyomatosis.

Gastric tumors discovered during pregnancy are rare. A cystic gastric stromal tumor with adjacent peritoneal nodules and associated with ascites was encountered in a 32-year-old pregnant patient. On initial clinical evaluation the mass was thought to originate from the uterine adnexa. The tumor itself was composed of uniform spindle cells with minimal mitotic activity. Immunohistochemical and ultrastructural studies were consistent with a gastrointestinal stromal tumor (GIST). Small nodules on the gastric serosa and adjacent omentum resembled those of leiomyomatosis peritonealis disseminata but were confined to the upper abdomen and on further study lacked evidence of smooth muscle differentiation. Although many of these nodules were not resected, a CT scans 3 and 9 months later failed to detect them. This case of GIST in pregnancy is apparently unique and distinct from leiomyomatosis peritonealis disseminata and rare forms of intestinal leiomyomatosis.

Cytology of suture granulomas in post-hysterectomy vaginal smears.

In histologic sections, foreign body giant cells are often associated with a granulomatous reaction to embedded suture material. However, this finding is unusual in exfoliative cytology samples. We describe the cytologic findings associated with suture granulomas in nine vaginal smears obtained from four women, ages 53 to 72. The patients had undergone hysterectomy for endometrial adenocarcinoma (three patients) and cervical carcinoma in situ (one patient). Smears taken 6 to 34 mo after surgery showed a moderate to severe acute inflammatory reaction, foreign body giant cells, and polarizable suture material. A vaginal cuff biopsy from one patient confirmed the diagnosis. Although multinucleated giant cells in postmenopausal vaginal smears are usually a non-specific finding, phagocytosed refractile material observed post hysterectomy may reflect a chronic tissue reaction to suture material. The presence of an acute inflammatory reaction, foreign body type giant cells, and the appropriate past surgical history, should prompt the pathologist to rapidly screen the slide under polarized light to evaluate the possibility of suture granulomas.

[Placenta accreta during the first trimester of pregnancy. A case report]. / Placenta increta en el primer trimestre de embarazo. Presentación de un caso.

Placenta accreta is defined as the abnormal adherence of the placenta, totally or in part, to the underlying uterine surface. It is uncommon to find this abnormality of the attachment of the placenta in the first half or pregnancy. Only 10 cases have been reported. We present a case of placenta accreta in the first trimester in a patient with three previous curettages as a risk factor, diagnosed during curettage for a fourth missed abortion that required total abdominal hysterectomy. This case follows the pattern of those previously reported.

Minimally invasive Paget's disease of the vulva with extensive lymph node metastases.

Optimal treatment for intraepithelial and invasive Paget's disease of the vulva has been previously evaluated. The treatment of disease with minimal invasion (< or = 1 mm) represents an even greater dilemma. We report a case of Paget's disease of the vulva with 1-mm depth of invasion presenting with extensive inguinofemoral lymph node metastases documented by fine-needle aspiration biopsy.

Hyperbaric oxygen as a prophylaxis for radiation-induced delayed enteropathy.

This trial was accomplished in C3H mice to determine whether hyperbaric oxygen (HBO) could be administered to prevent delayed radiation enteropathy. Fifty mice randomized into two equal groups received 30 Gy abdominopelvic irradiation in 10 fractions. The study group received a course of 30 HBO treatments beginning 7 weeks after the radiation exposure. The control group received only housing and nutritional support after irradiation. A third group of three animals had no radiation or HBO. All animals were sacrificed 7 months after radiation. Animals were inspected grossly for signs of enteropathy. In addition, a special stretch apparatus was used to quantify narrowing and rigidity of ileum just proximal to the ileocecal junction. Those animals who received HBO had fewer gross signs of enteropathy and had less narrowing and less rigidity in their harvested bowel segments. These differences were highly statistically significant. Treatment with HBO drastically reduces signs of radiation enteropathy. Further study including clinical trials are recommended.

Deoxyribonucleic acid ploidy and S-phase fraction are not significant prognostic factors for patients with cervical cancer.

OBJECTIVE: Our purpose was to determine the usefulness of deoxyribonucleic acid ploidy and S-phase fraction as prognostic factors in patients with cervical cancer. STUDY DESIGN: Paraffin-embedded tumor specimens were obtained from 123 patients with cervical cancer (mean age 51 years, range 21 to 87 years). The mean follow-up period was 6.4 years. Deoxyribonucleic acid ploidy and S-phase fraction were determined by flow cytometry. RESULTS: A total of 119 patients were evaluable for deoxyribonucleic acid ploidy and 92 were evaluable for S-phase fraction. The overall rate of deoxyribonucleic acid aneuploidy was 60%, and the median S-phase fraction was 12.5%. Neither factor was significantly related to stage of disease. In univariate survival analyses patients with deoxyribonucleic acid aneuploid tumors had slightly better early survival than did patients with deoxyribonucleic acid diploid tumors (median survivals 2.7 and 1.4 years, respectively, p = 0.08 [Wilcoxon]), but the overall survival was not significantly different, p = 0.37 (log-rank). In multivariate analyses deoxyribonucleic acid ploidy was not a significant predictor of survival. S-phase fraction was not statistically significant in either analysis. CONCLUSION: Deoxyribonucleic acid ploidy and S-phase fraction are not useful prognostic factors for patients with cervical cancer.

Cytologic atypia associated with microglandular hyperplasia.

Although it has long been known that microglandular hyperplasia (MGH) may be associated with cytologic atypia in cervical smears, the cytomorphology of MGH has not been described in great detail. To clarify its cytomorphology, Pap smears obtained from biopsy proven cases of MGH over a 3-yr period were reviewed. Of 122 smears containing endocervical cells, 34 (28%) showed striking glandular abnormalities. In two cases, adenocarcinoma and adenocarcinoma in situ were falsely suggested and a high grade squamous intraepithelial lesion (HGSIL-CIN III) was not confirmed in a conization specimen which showed only low grade SIL and MGH. Review of six cytologic diagnoses of HGSIL (CIN III) unconfirmed on biopsy suggested overcalls related to MGH related atypia in five. Cytologic features of MGH, therefore, may occasionally result in erroneous interpretations of HGSIL as well as glandular neoplasia. Although these changes may be striking, comparison with glandular atypia not associated with MGH shows that they are not entirely specific.

Fine-needle aspiration cytology of mammary adenomyoepithelioma: report of a case with intranuclear cytoplasmic inclusions.

Adenomyoepithelioma of the breast is an uncommon lesion which may recur and rarely metastasizes. We report the fine-needle aspiration (FNA) findings in one case of mammary adenomyoepithelioma in which this tumor's unusual cytomorphology led to a cytologic diagnosis of malignancy, possible metastatic to the breast. Large, atypical, polygonal cells, some with intranuclear cytoplasmic inclusions, were most worrisome cytologically, but corresponded in the biopsied specimen to cells immunohistochemically documented to be of myoepithelial origin. Nests of epithelium and myoepithelial cells sometimes embedded in fibrous, stromal fragments were suggestive of an infiltrating pattern. Recognition of such unusual features in breast FNA is most important since definitive therapy may follow an FNA diagnosis of carcinoma in some clinical settings. In cases with unusual morphology, surgical biopsy should be recommended to clarify the nature of the lesion.

Papilloma of Bartholin's gland duct cyst: first report of a case.

A 50-year-old woman underwent excision of a vaginal cyst. Its distal end lay in the submucosal tissue of the posterior lateral aspect of the vulvar vestibule near the orifice of Bartholin's gland. The caudal wall of the cyst contained a papilloma with an epithelial lining which consisted of columnar and stratified polygonal cells resembling squamous and transitional epithelium. The histochemical attributes of the papillary epithelium were homologous to those of Bartholin's gland. Immunohistochemical studies supported glandular and squamous differentiation. Evolution from a dysontogenetic remnant of Müllerian origin cannot be excluded with certainty, but location and histopathology were consistent with origin from Bartholin's gland duct. The presence of mucin and the absence of a smooth muscle investment exclude derivation from Gartner's duct. Cysts of Bartholin's gland are common, but solid benign tumors are rare. We have been unable to find a report of a papilloma of either vulva or vagina with features similar to those in our patient.