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Biomedical subjects

Y S Fu

Publications and source records attributed to Y S Fu.

At least 73 records · Page 4Linked to original sources

Ovarian metastases are rare in stage I adenocarcinoma of the cervix.

Over a 32-year period at the University of California, Los Angeles Medical Center, all cases of adenocarcinoma and adenosquamous carcinoma of the uterine cervix were reviewed to determine the incidence of ovarian metastases in stage I disease. One of 25 patients (4.0%) who underwent an exploratory laparotomy and radical hysterectomy had a microscopic ovarian metastasis. A literature review identified nine additional patients who had ovarian metastases and stage I adenocarcinoma of the cervix. Including our series, the overall reported rate of ovarian metastases is 1.8%. All ten patients had at least one of the following additional characteristics: They were postmenopausal, they had adnexal pathology, or they had positive pelvic lymph nodes. Thus, ovarian preservation is warranted in premenopausal patients who do not have ovarian pathology or evidence of other metastatic disease at surgery. Bilateral oophorectomy may be performed if frozen-section examination of enlarged or suspicious nodes documents metastases. If the ovaries are left in the pelvis at the completion of the surgical procedure and microscopic spread to other pelvic tissues is documented, pelvic irradiation can be administered.

Adenocarcinoma↗

Squamous cell carcinoma of the uterine cervix--a review with emphasis on prognostic factors and unusual variants.

Although the incidence of squamous cell carcinoma of the cervix has declined in recent years, it remains the most common type of cervical cancer in our society. In this review, the salient pathologic features of squamous cell carcinoma are discussed. Early invasive, International Federation of Gynecology and Obstetrics (FIGO) stage la carcinoma has been a source of controversy in diagnosis and therapy for many years. Specific requirements must be met in order to make this diagnosis. Most importantly, the cervical conization specimen must be handled properly, so that the features of tumor dimensions, vascular involvement, and completeness of excision can be correctly evaluated. Important diagnostic and prognostic pathologic findings of early invasive carcinoma are discussed. The risk of lymph node metastasis in lesions with depths of invasion up to 3 mm is less than 1%. This risk increases significantly with deeper levels of invasion. In the area of frankly invasive squamous cell carcinoma of the cervix, certain pathologic features have been shown to be clinically relevant. These include the extent of local disease, cell type, and the presence of vascular or lymphatic invasion. Regarding cell type, it is critical to distinguish between poorly differentiated small cell squamous carcinoma and small cell undifferentiated carcinoma, as the prognosis for these tumors may differ. Finally, several rare but pathologically distinct variants of squamous cell carcinoma of the cervix are reviewed, with emphasis on differential histologic features. As they often have different natural histories than typical squamous cell carcinoma, correct diagnosis of these lesions is vital.

Carcinoma, Papillary↗

Human papillomaviruses and the pathogenesis of cervical neoplasia. A study by in situ hybridization.

In a previous topographic study of cervical conization specimens, condylomatous changes were commonly present in direct contact with intraepithelial neoplasia and were always located distal (ectocervical side) to the neoplasia. Viral DNA was detected by in situ hybridization using 35S-labeled nick translated DNA probes in 50 of 70 cases (71%) which had adequate lesions: HPV-16 in 30, HPV-18 in ten, HPV-31 in six, and multiple types in four cases. HPV-6/11 was detected only once, in a multiple infection. As a rule, a positive cervix contained a single virus type, and the same virus type was found in condylomatous and neoplastic areas. The results suggest that the neoplastic process is initiated in the area of condyloma toward the endocervix and, once established, extends proximally toward the cervical canal. Capsid antigen was detected in 19 cases, indicating that a proportion of the high-grade lesions is potentially infectious.

Adult↗

Discrimination of benign versus malignant mixed tumors of the salivary gland using digital image analysis.

Seven benign and four malignant mixed tumors of the salivary gland, biopsied using fine-needle aspiration, were analyzed using digital image analysis. Mean nuclear form factor, perimeter, and area were significantly increased in malignant cases. Better separation between diagnostic categories, however, was achieved by utilizing the coefficient of variation (CV) within a case rather than mean value. Form factor CV alone divided cases into nonoverlapping diagnostic categories. This quantitative analog of "pleomorphism" provided a useful marker for malignancy in mixed tumors.

Adenoma, Pleomorphic↗

Vulvovaginal melanoma: report of seven cases and literature review.

Five cases of primary vaginal melanoma were treated at UCLA Medical Center between 1976 and 1986. Two additional cases of melanoma arising at the junction of the vulva and vagina are presented. One of seven (13%) patients is alive, with a median time to recurrence of 7 months, and median survival of 31 months. Four of five vaginal melanomas were located in the distal vagina, and all were advanced at diagnosis (greater than 3 mm depth). Mean size was 3 cm. Initial therapy was local excision in four patients and radical surgery in three. All patients had suboptimal surgical margins: two vaginal primaries had positive margins after local excision, both recurred vaginally within 5 months. Two patients had margins less than 1 mm, one died of distant metastases, the other is alive with disease 30 months after radical distal vaginectomy and hemivulvectomy with post-op pelvic radiotherapy. Three patients had melanoma in situ at the surgical margins, and each had pelvic recurrences between 6 and 26 months. Five of seven cases developed local recurrence as the initial site of treatment failure. All five vaginal cases ultimately developed distant disease, but only two patients had distant disease without local-regional recurrence. Chemotherapy and immunotherapy enabled disease stabilization in three patients. The vulvovaginal junction at the introitus is a high risk site for vaginal and vulvar melanoma. Intraoperative management requires assessment of lateral and deep spread of invasive and in situ melanoma.

Adult↗

Practical approach to cervical human papillomavirus-related intraepithelial lesions.

Members of the Editorial Board who have been active in the study of female genital HPV-related lesions have responded to a series of questions related to the histopathologic diagnosis of such lesions in the uterine cervix, the performance of auxiliary studies, therapeutic choices, and the correlation of cytologic and tissue diagnoses.

Cervix Uteri↗

Rhodamine-123 as a new laser dye: in vivo study of dye effects on murine metabolism, histology and ultrastructure.

Rhodamine-123 (Rh-123) is a mitochondrial-specific dye that has recently proven to be an effective fluorochrome for photo-dynamic therapy of squamous carcinoma cells and melanomas with the Argon laser. Complete eradication of heterotransplanted human tumors in nude mice was possible if tumors were first "sensitized" to Rh-123 and then treated with the Argon laser. Prior to initiation of human testing of this technique, the toxicity and pathological changes in BALB/c mice were tested by an escalating dose schedule after systemic injection of Rh-123. Animals' body weight, blood chemistry, enzymes and organ evaluation for histology, and ultrastructural changes were analyzed for 3 weeks after injection with Rh-123. The results of this study demonstrate that Rh-123 has significant systemic toxicity in BALB/c mice injected at doses of 10 micrograms/g of body weight and above, manifested by chronic weight loss and elevation of muscle enzymes with death of the animals injected at doses higher than 50 micrograms/g of body weight. At doses of 1 micrograms/g of Rh-123, no local or systemic toxicity was observed even after a 3-week follow-up, suggesting that safe and effective tumor sensitization might be possible in humans at this concentration. The high effectiveness of this new technique of photodynamic therapy and the low toxicity of this dye in this preclinical model system suggests that Rh-123 and the Argon laser may represent a powerful new method for treatment of superficial malignancies.

Animals↗

DNA ploidy analysis of cervical condyloma and intraepithelial neoplasia in specimens obtained by punch biopsy.

This study analyzed the feasibility of, and the strategy for, DNA ploidy analysis of cervical condyloma and intraepithelial neoplasia by a computerized digital imaging system. Paraffin-embedded tissue provided satisfactory single-cell preparations for DNA ploidy analysis after enzyme digestion and additional procedures. Negative endocervical curettings and normal squamous mucosa were used as internal diploid controls. With suitable controls, 21 (81%) of the 26 aneuploid lesions were identified as such in the single-cell preparations. The remaining five lesions (not recognized as aneuploid in the single-cell preparations) had ploidy levels between 2.08n and 2.30n and required DNA measurements on 12-microns sections. Criteria for these DNA measurements were defined: specimens intended for DNA ploidy analysis should contain abnormal epithelium of at least 3 mm to 4 mm in greatest dimension and should be accompanied by diploid controls, such as endocervical curettings or normal ectocervical squamous mucosa. With a combination of single-cell preparations and 12-microns tissue sections, it was possible to accurately determine the DNA ploidy patterns of the cervical lesion specimens obtained by punch biopsies. Available evidence suggests that ploidy analysis can provide useful diagnostic and prognostic information.

Biopsy↗

Keratin and involucrin immunohistochemistry of nasopharyngeal carcinoma.

Forty nasopharyngeal carcinomas (NPC) were studied by immunohistochemistry using an antibody to involucrin and the following three keratin antibodies: (1) an antibody to low molecular weight keratin reactive with nonsquamous epithelium, (2) a high molecular weight keratin antibody reactive with suprabasal squamous epithelium, and (3) a keratin antibody reactive with full thickness stratified epithelium. In its pattern of reactivity, the last antibody overlaps the low and high molecular weight keratin antibodies and is used as a broad spectrum keratin antibody. By World Health Organization (WHO) classification, the cases in this article included eight keratinizing squamous cell carcinomas, eight nonkeratinizing carcinomas, 20 undifferentiated carcinomas, and four adenocarcinomas. The antibody to broad spectrum keratin had an overall sensitivity of 87.5% and was positive in all eight keratinizing squamous cell carcinomas, seven nonkeratinizing carcinomas (87.5%), 18 undifferentiated carcinomas (90%), and two adenocarcinomas (50%). Low molecular weight keratin antibody stained one additional NPC, which was negative when broad spectrum keratin antibody was used. Involucrin and high molecular weight keratin antibodies demonstrated near parallel staining in all histologic classes; there was marked localization to areas of squamous differentiation. While involucrin is a marker for foci of greater squamous differentiation, broad spectrum keratin antibody may aid in the diagnosis of all histologic subtypes of NPC.

Adenocarcinoma↗

Resistance of mouse nasopharynx to induction of neoplasia by herpes simplex virus.

In previous studies, carcinoma of the uterine cervix of the mouse was induced by repeated vaginal exposure to inactivated herpes simplex viruses, type 1 or 2. To determine if the mouse nasopharynx is also susceptible to the carcinogenic effects of these viruses, animals were inoculated intranasally with suspensions of formaldehyde-inactivated herpes simplex viruses, type 1 or 2, or control material, four to five times a week. After exposure periods of 12, 20, and 32 weeks, groups of animals were killed randomly and the nasopharynx, along with the larynx, trachea, bronchi, and lungs, were examined histologically. No preinvasive or invasive lesions were detected. These data suggest that the nasopharynx and cervix of the mouse differ in susceptibility to induction of carcinogenesis by inactivated herpes simplex viruses.

Animals↗

Nonsalivary sinonasal adenocarcinoma.

Thirteen cases of primary non-salivary gland adenocarcinoma of the nasal cavity and paranasal sinuses were studied at UCLA over 20 years. All pathologic specimens were reviewed and those tumors that were histologically distinct from the more common salivary gland-derived tumors were included in the study. Three classifications were identified: well, moderately, and poorly differentiated adenocarcinoma. A distinct variant of sinonasal adenocarcinoma was the intestinal type. The clinical behavior of the latter resembled the well or moderately differentiated types, with behavior mainly predicted by the extent of the disease. These groups have prognostic significance, with the poorly differentiated group having the most virulent course. Nine of 13 tumors occurred in the ethmoid sinuses and all were aggressive locally. Only one case had distant metastases (nodal neck disease in a terminal case). Of five long-term survivors (median five-year follow-up), all had extensive surgical resections and three had full-course radiotherapy. The single most important factor in the treatment of these lesions is adequacy of surgical margins. Four of six patients with confirmed negative margins were cured despite extensive tumors. Three survivors had the cribriform plate taken and one required a combined intracranial/extracranial approach for tumor resection. There were no survivors in four patients treated with primary irradiation.

Adenocarcinoma↗

Squamous papillary neoplasia of the adult upper aerodigestive tract.

Selected papillary squamous tumors of the upper aerodigestive tract (UADT) mucosa in adult patients do not have well-defined histologic criteria and the clinical behavior is poorly understood. To better characterize this spectrum of neoplasms, UADT papillary neoplasms were evaluated by routine histology, determination of cellular DNA content using Feulgen-stained tissue sections, and the typing of human papillomavirus (HPV) by in situ hybridization. Solitary papillomas were studied in two patients; there was no recurrence in either case, both had normal DNA content, and one was typed as HPV-6 while the other was typed as HPV-11. Seven adult patients with recurrent papillomatosis and at least one biopsy with dysplasia/atypia were identified (mean age at diagnosis, 13.3 years; mean age at last contact, 42.7 years). Six of seven patients had abnormal DNA cellular content in foci of epithelial atypia. In all biopsies evaluated, the papillomas of the seven patients were consistently typed as either HPV-6 or HPV-11. Six patients with malignant papillary neoplasms also had abnormal DNA cellular content, but none revealed evidence of HPV type 6, 11, 16, or 18 by in situ hybridization of tissue sections. In many of the recurrent papillomas, the degree of epithelial atypia encountered was pronounced and was commonly misdiagnosed as carcinoma in situ or papillary carcinoma. The aneuploid DNA content of these foci of atypia reflected the abnormal cellular appearance and partially explained the overdiagnosis of malignancy. However, none of the seven patients were treated for malignant disease and none progressed to invasive carcinoma, with an average follow-up period of almost 30 years. We conclude that histologic and cytologic atypia in HPV-containing papillomatosis may be appreciable. The aneuploid DNA content may represent premalignant conditions and the patient may be at an increased risk for the subsequent development of squamous cancer. However, none of the seven patients with recurrent papillomatosis developed any evidence of malignancy. In addition, none of the patients with papillary carcinomas had previous recurrent papillomatosis.

Adult↗

Correlative study of human papillomavirus DNA, histopathology and morphometry in cervical condyloma and intraepithelial neoplasia.

This study includes 28 intraepithelial squamous lesions of the cervix associated with human papillomavirus (HPV) DNA sequences detected by the Southern blot technique. Objective analyses of the histologic features by morphometric parameters and mitotic index have demonstrated that lesions of HPV types 6 and 11 can be distinguished from types 16, 18, and 33 by stepwise discriminant functions. The latter lesions have higher mitotic and cellularity indexes and greater nuclear atypia than the former, supporting a greater degree of epithelial proliferation and abnormality seen in association with HPV types 16/18/33.

Biopsy↗

Detection of human papillomavirus in normal and dysplastic tissue by the polymerase chain reaction.

Detection of human papilloma virus (HPV) types 16 and 18 in formalin-fixed, paraffin-embedded tissue by a new in vitro DNA amplification method, the polymerase chain reaction, was compared with detection with genomic DNA probes using in situ hybridization. The polymerase chain reaction replicates exponentially HPV DNA sequences present in a single 5- to 10-micron paraffin-embedded tissue section. The amplified sequences are detected with a DNA hybridization probe in a dot blot assay. The HPV polymerase chain reaction was able to detect on the average less than one HPV genome/cell as determined by tests of paraffin sections of cell pellets with known HPV genomic content. Cervical sections from 21 patients with HPV types 16, 18, or 31 as determined by in situ DNA hybridization were analyzed by the polymerase chain reaction. No disagreements between the two methods were detected. The sections comprising normal and dysplastic epithelium were further analyzed by the HPV polymerase chain reaction. The presence of virus correlated with the presence of dysplasia in the sections, though 3 of 10 normal sections contained HPV, and 1 of 21 sections with dysplasia lacked HPV 16 or 18. The polymerase chain reaction can specifically detect HPV 16 or 18 with high sensitivity from paraffin-embedded tissues.

Autoradiography↗

Peritoneal cytology of ovarian cancer patients receiving intraperitoneal therapy: quantitation of malignant cells and response.

An analysis was performed of malignant and host cells found in peritoneal fluids obtained during intraperitoneal chemotherapy and immunotherapy in patients with ovarian cancer. The concentration of malignant cells and the surgically documented response to the intraperitoneal treatment were correlated. Twenty-three patients were treated with intraperitoneal cisplatin or alpha-2 interferon (rIFN-alpha 2) after persistent carcinoma was documented at second-look laparotomy. Six patients (26%) had a complete response to therapy, and all of these patients had a malignant cell concentration of less than 10(2)cells/cm2/dL. No responses were seen in patients whose initial malignant cell concentration was greater than 10(3)cells/cm2/dL. Among patients treated with intraperitoneal alpha-interferon, five of 11 whose initial concentration of malignant cells was less than 10(2) cells/cm2/dL responded to therapy, whereas none of the patients whose malignant cell concentration was 10(2) cells/cm2/dL or greater responded. In patients treated with intraperitoneal cisplatin, the initial concentration of malignant cells associated with any surgically documented response was less than 10(3)cells/cm2/dL. A host mesothelial reaction was prominent after intraperitoneal alpha-interferon, but not observed in women treated with intraperitoneal cis-platin. The fluctuating pattern of peritoneal white blood cells documented during therapy did not correlate with response. THe evaluation of peritoneal cytology specimens during intraperitoneal chemotherapy should include a quantitative assessment of malignant cells and reactive mesothelial cells in order to reflect more accurately the histologically documented findings. Initial quantitative cytology appears to correlate with the likelihood of a surgically documented response to intraperitoneal therapy.

Aged↗