Aggressive uterine sarcoma with rhabdoid features: diagnosis by peritoneal fluid cytology and absence of INI1 gene mutation.

We report a primary uterine sarcoma with classic histologic, immunohistochemical, and ultrastructural features of a malignant extrarenal rhabdoid tumor (MERT). It arose in a 71-year-old woman who presented with postmenopausal bleeding, ascites, and a right pelvic mass. Malignant cells with rhabdoid morphology were identified by cytologic examination of the peritoneal fluid. Exploratory laparotomy revealed a 10-cm right adnexal mass and disseminated peritoneal tumor. Pathologic study showed diffuse expansion of the endometrial stroma by rhabdoid-like cells with transmural infiltration of the myometrium and extensive involvement of uterine serosa and right ovary by tumor. Neoplastic cells were immunoreactive for vimentin, cytokeratin, and epithelial membrane antigen, and cytoplasmic whorls of intermediate filaments were observed by electron microscopy. Fluorescence in situ hybridization (FISH) studies with chromosome 22-specific probes showed no loss of the INI1 gene, and no coding sequence mutation was identified.

Benign cellular changes in Pap smears. Causes and significance.

OBJECTIVE: We reviewed consecutive cases classified as benign cellular changes (BCC) over a four-month period. STUDY DESIGN: Cases classified as BCC were retrieved from the cytology files. A search was carried out to identify the previous Pap smears and concomitant cervical biopsies. RESULTS: One thousand one hundred three cases (23% of our gynecologic smears) were classified as BCC. Ninety-two patients (8.3%) underwent concurrent cervical biopsies. Specific infections accounted for 8% of BCC cases; reactive changes accounted for 92%. Of the biopsy specimens, 8.3% had no significant pathologic change. The most common biopsy diagnoses were cervicitis (31.5%), immature squamous metaplasia (16.3%) and reserve cell hyperplasia (10.8%). Miscellaneous benign diagnoses accounted for 21.7%. Cervical intraepithelial neoplasia (CIN) 1/human papillomavirus (HPV) was present in 14% of cases. All patients with biopsy diagnoses of CIN 1 had at least two previous abnormal Pap smears. Previous biopsy reports were available for review in 127 (12%) of the 1,103 patients. Of these 127 cases, 53.5% had a previous diagnosis of CIN/HPV; 9.4% had invasive carcinoma. A benign diagnosis was reported in 36.5%. CONCLUSION: The majority of BCC cases are due to reactive and inflammatory processes. In patients with a previous history of CIN, BCC may be of some significance. In patients with no significant prior cervical abnormalities, a Pap smear classified as BCC represents a reactive process.

Financial impact of tertiary care in an academic medical center.

OBJECTIVE: To analyze the financial impact of three complex vascular surgical procedures to both an academic hospital and a department of surgery and to examine the potential impact of decreased reimbursements. SUMMARY BACKGROUND DATA: The cost of providing tertiary care has been implicated as one potential cause of the financial difficulties affecting academic medical centers. METHODS: Patients undergoing revascularization for chronic mesenteric ischemia, elective thoracoabdominal aortic aneurysm repair, and treatment of infected aortic grafts at the University of Florida were compared with those undergoing elective infrarenal aortic reconstruction and carotid endarterectomy. Hospital costs and profit summaries were obtained from the Clinical Resource Management Office. Departmental costs and profit summary were estimated based on the procedural relative value units (RVUs), the average clinical cost per RVU ($33.12), surgeon charges, and the collection rate for the vascular surgery division (30.2%) obtained from the Faculty Group Practice. Surgeon work effort was analyzed using the procedural work RVUs and the estimated total care time. The analyses were performed for all payors and the subset of Medicare patients, and the potential impact of a 15% reduction in hospital and physician reimbursement was analyzed. RESULTS: Net hospital income was positive for all but one of the tertiary care procedures, but net losses were sustained by the hospital for the mesenteric ischemia and infected aortic graft groups among the Medicare patients. In contrast, the estimated reimbursement to the department of surgery for all payors was insufficient to offset the clinical cost of providing the RVUs for all procedures, and the estimated losses were greater for the Medicare patients alone. The surgeon work effort was dramatically higher for the tertiary care procedures, whereas the reimbursement per work effort was lower. A 15% reduction in reimbursement would result in an estimated net loss to the hospital for each of the tertiary care procedures and would exacerbate the estimated losses to the department. CONCLUSIONS: Caring for complex surgical problems is currently profitable to an academic hospital but is associated with marginal losses for a department of surgery. Economic forces resulting from further decreases in hospital and physician reimbursement may limit access to academic medical centers and surgeons for patients with complex surgical problems and may compromise the overall academic mission.

Do qualifiers of ASCUS distinguish between low- and high-risk patients?

OBJECTIVE: To evaluate the qualification of a Pap smear classified as atypical squamous cells of undetermined significance (ASCUS) favor reactive or neoplasia as recommended by the Bethesda System. STUDY DESIGN: The smears from 105 concurrent patients with a cytologic diagnosis of ASCUS not otherwise qualified were reviewed and subclassified as ASCUS favor reactive, low grade squamous intraepithelial lesion (LSIL) or high grade squamous intraepithelial lesion (HSIL) based on the Bethesda System criteria. The cervical biopsy diagnoses were correlated. RESULTS: Of the 105 cases classified as ASCUS, 37 were subclassified as favor reactive, 51 as favor LSIL and 17 as favor HSIL on cytologic review. In the ASCUS favor reactive group, 19 (51%) had reactive changes on biopsy, 17 (46%) had cervical intraepithelial neoplasia (CIN) 1, and 1 (2%) had CIN 3. A total of 48% patients had CIN. In the favor LSIL group, there was CIN 1 in 28 cases (55%), CIN 2 or 3 in 12 (23%) and benign changes in 11 (22%) on biopsy. Seventy-eight percent had CIN. In the 17 cases classified as ASCUS favor HSIL group, all had CIN. CONCLUSION: Of the total 105 cases of ASCUS, 71% had CIN, 29% had reactive changes on follow-up biopsies, and 48% of patients in the ASCUS favor reactive group had CIN. Qualifiers of ASCUS have questionable utility in patient management.

Atypical glandular cells of undetermined significance and other glandular cell abnormalities in a high-risk population.

OBJECTIVES: We set out to determine our rate of atypical glandular cells of undetermined significance (AGUS) classification, to compare our AGUS rate to rates reported by others, and to determine the correlation between AGUS and histological abnormalities in our population. MATERIALS AND METHODS: Reports from all Papanicolaou (Pap) smears and associated histological specimens interpreted by the University of Florida Department of Pathology between 1992 and 1996 were reviewed. RESULTS: A total of 462 (1.2%) of 39,484 Pap smears were classified as epithelial cell abnormality-glandular cell, with 328 (0.83%) AGUS, 102 (0.26%) endometrial cells out of phase or in a postmenopausal woman, and 32 (0.08%) adenocarcinoma. A total of 146 (45%) of the AGUS cases had timely biopsies: 95 (65.1%) had benign findings, 27 (18.5%) had cervical intraepithelial neoplasia, 14 (9.6%) had adenocarcinoma (10 endometrial, 2 endocervical, 2 extrauterine), 9 (6%) had endometrial hyperplasia, and 1 (0.7%) showed endocervical glandular cell dysplasia. CONCLUSIONS: AGUS on Pap is associated with a clinically significant histological abnormality in a moderate percentage of patients. Both squamous and glandular lesions are seen, supporting the need for aggressive evaluation of the cervix, endocervix, and endometrium when AGUS is reported.

Squamous intraepithelial lesions of the cervix in a high-risk population.

OBJECTIVES: We set out to examine our use of the squamous intraepithelial lesion (SIL) category, compare our SIL rate to rates reported by others, and determine the corre-lation between SIL and histologically proven cervical intraepithelial neoplasia (CIN) in our population. MATERIALS AND METHODS: Reports from all Papanicolaou smears and associated histological specimens interpreted by the University of Florida Department of Pathology between 1992 and 1996 were reviewed. RESULTS: Of 39,484 Papanicolaou smears, 2,101 (5.3%) were classified as low-grade squamous intraepithelial lesion (LGSIL) and 1,366 (3.5%) were classified as high-grade (HGSIL). Of the LGSIL cases, 972 (46.3%) underwent timely biopsy: Findings were benign in 29.9%; 41.7% had CIN1,20.9% had CIN2, and 7.5% had CIN3. Of the HGSIL cases, 932 (68.2%) underwent timely biopsy: Findings were benign in 12.3%; 17.1% had CIN1, 26.7% had CIN2, 42.2% had CIN3, and 1.6% showed squamous cell carcinoma. Condusions. Our LGSIL rate is similar to reported rates, but our HGSIL rate of 3.5% is higher. We found good correlation between SIL on Papanicolaou smear and CIN on biopsy (70.1% for LGSIL and 86% for HGSIL).

Cellular immune reactivities in women with silicone breast implants: a preliminary investigation.

BACKGROUND: Surgical implantation of silicone breast prostheses has been conducted and considered safe for over 30 years. Some implant recipients, however, complain of a group of symptoms similar to those observed in connective tissue disorders, rheumatoid arthritis, systemic lupus erythematosus, or polymyositis. To date, immunologic sequelae have not been confirmed and remain controversial. OBJECTIVE: To examine an autoimmune-like basis for the "silicone associated disease" reported by some women with silicone breast prostheses. METHODS: Proliferative responses of peripheral blood mononuclear cells against a panel of control and connective tissue proteins and to compounds common to silicone prostheses were measured in 26 women who received silicone breast implants (with implants in place an average of 166.4 [standard deviation (SD) 58.3] months), and 23 age-matched and sex-matched healthy controls. RESULTS: The frequency and intensity of cellular immune responses against collagen I, collagen III, fibrinogen, and fibronectin were significantly increased in silicone breast implant recipients versus controls. In implant subjects, the highest frequency of immune reactivity was directed against collagen I (11/26, 42%) with collagen III being the most immunostimulatory self-antigen with a mean stimulation index (SI) of 8.2 [95% confidence interval (95% CI) 3.2]. In addition, 10/26 (39%) of the implant recipients responded to more than one of the connective tissue antigens versus 0/23 (0%, P = .0007) healthy controls. Immunologic reactivities to other antigens, including silicone-based compounds, were remarkably similar. CONCLUSIONS: The identification of self-reactivity towards these connective tissue antigens may provide important information for attempts at associating silicone breast implants with disease.

Atypical squamous cells of undetermined significance in a high-risk population.

OBJECTIVES: We set out to develop a benchmark for our use of the term atypical squamous cells of undetermined significance (ASCUS), to compare our ASCUS rate to rates reported by others, and to determine the correlation between ASCUS and histologically-proved cervical intraepithelial neoplasia (CIN) in our population. MATERIALS AND METHODS: All Papanicolaou (Pap) smears and associated cervical biopsies or endocervical curettages interpreted by the University of Florida Department of Pathology between 1992 and 1995 were reviewed. RESULTS: Of 28,494 Pap smears; 17% were classified as "epithelial cell abnormality, squamous," with 7.4% ASCUS, 5.6% low-grade squamous intraepithelial lesion, and 4.0% high-grade squamous intraepithelial lesion. Of the 2,100 ASCUS cases, 753 had timely biopsies; 45.8% were benign, 53.8% showed CIN, and 0.4% showed carcinoma. Of the CIN cases, 39.2% were CIN1, 8.1% were CIN2, and 6.5% were CIN3. CONCLUSIONS: Our 7.4% ASCUS rate is similar to published rates. Our high rate of neoplasia associated with ASCUS (54.2%) and our low ASCUS-squamous intraepithelial lesion ratio (0.77) indicate that we do not overuse the ASCUS classification.

In vitro measurement of silicone bleed from breast implants.

A method to measure gel bleed from intact silicone gel-filled breast implants was developed. This nondestructive technique permits accurate and reproducible serial measurements of silicone bleed from smooth wall breast implants (n=10) under simulated physiologic conditions in vitro. Gel bleed rates from new low bleed gel-filled implants and intact explants (unbarriered, low bleed, double lumen) were determined. These results demonstrate the reliability of this method to quantify silicone gel bleed and may permit a meaningful comparison of bleed rates from implants in the future.

Detection of breast implant rupture with aspiration cytology.

A new method for diagnosis of ruptured silicone gel-filled implants was developed. The method uses a recently described technique for insertion of a catheter into an implant capsule. This allows irrigation with saline and recovery of cells for cytopathologic diagnosis. Cytopathologic diagnosis was both sensitive (94 percent) and specific (95 percent) in the detection of intracellular foreign material accompanying ruptured implants. The intracellular material has been positively identified as silicone. This laboratory study included 42 samples obtained at three time intervals on 5 rabbits, each of which had one "ruptured" and one intact implant for a total of 10 implants.

Complications related to retained breast implant capsules.

Citing evidence that breast implant-related capsules resolve uneventfully, surgeons have elected to leave the capsules in place when implants are removed because capsulectomy adds both morbidity and expense to the procedure. However, recent clinical and histopathologic evidence suggests that uneventful resolution is not always the case, and several potential problems may arise from retained capsules after removal of the implant. Retained implant capsules may result in a spiculated mass suspicious for carcinoma, dense calcifications that obscure neighboring breast tissue on subsequent imaging studies, and cystic masses due to persistent serous effusion, expansile hematoma, or encapsulated silicone filled cysts. Furthermore, retained capsules are a reservoir of implant-related foreign material in the case of silicone gel-filled implants and textured implants promoting tissue ingrowth. To avoid complications from retained capsules, total capsulectomy or postoperative surveillance should be offered to patients.

The synovial structure of breast-implant-associated bursae.

Over 2 million silicone breast prostheses have been implanted since they were introduced in the 1960s. After implantation, a fibrovascular tissue reaction referred to as a "capsule" is observed. Many consider this capsule to be a static structure, an effective barrier to the egress of foreign material. However, reports documenting the presence of silicone within lymph nodes of patients with apparently unruptured implants indicate that silicone may be transported away from the breast-implant capsule. To characterize the cells making up the breast-implant capsule, 183 capsules from 103 ruptured or bleeding implants and 80 intact implants were studied. Gross and light microscopic studies were performed on all, and selected capsules were subjected to ultrastructural study and Fourier-transform infrared spectroscopy. Light microscopic examination of the capsule revealed an organized, layered structure with an associated network of endothelia-lined spaces. The capsules varied in cellularity, depending on the type and integrity of the implant. The superficial cell layer of all capsules had cytoplasmic processes directed toward the surface. These long cytoplasmic processes contained vacuoles ultrastructurally, indicating phagocytic and pinocytotic capability. These cells bore immunological markers of bone marrow derived macrophage-type cells. The extracellular matrix of the surface layer consisted of an amorphous fibrillar protein lacking the ultrastructural periodicity of mature collagen. No cell-to-cell junctions were observed. Deeper capsular layers were characterized by fibroblast-type cells in a collagen matrix. No capsules studied contained basement membrane or basal lamina between the stroma of the capsule and the surface cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Fourier transform infrared microspectroscopy used to identify foreign materials related to breast implants.

Clinically useful methods to identify and document the presence of foreign material in tissues surrounding breast implants are needed. Fourier transform infrared microspectroscopy is an ideal technique for examining tissue for the presence of implantable biomaterials. Because the spectroscopy is microscopically guided, the pathologist is assured that the obtained spectrum is from the region of interest in a tissue section. Scanning electron microscopy yields elemental data but cannot be used to identify compounds. Because each compound has a unique spectrum by Fourier transform infrared microspectroscopy, the spectrum obtained enables identification of the various foreign materials observed by light microscopy in tissues surrounding breast implants. Histopathology from implant capsules demonstrating a silicone gel-filled implant, a saline-filled textured implant, a polyurethane foam-covered gel-filled implant, a Dacron fixation patch, and a paraffin injection granuloma are presented with corresponding Fourier transform infrared microspectroscopy spectra.

Ploidy results in prostatic carcinoma vary with sampling method and with cytometric technique.

To evaluate the effect of sampling method and cytometric method on DNA ploidy results, a comparison study was performed on 20 whole prostate glands removed at prostatectomy. Fresh sampling was by sampling fine-needle aspiration (FNA). Paraffin sampling was by microdissection and re-embedding of 3 to 13 (average 6) 5-mm foci of microscopically proven tumor. Analysis was by flow cytometry and by image cytometry (microscopically guided). In tumor negative cases, flow and image cytometry of the FNA was diploid in each case, and flow cytometry of paraffin-embedded tissue was diploid in 5/6 cases. In tumor positive cases, non-diploid tumor was detected by image cytometry of the FNA in 70%, by flow cytometry of the FNA in 29%, and by flow cytometry of paraffin-extracted nuclei in 21%. The most effective combination was sampling fine-needle aspiration and image analysis.