Squamous Cell Carcinoma Of Vagina Research Articles

Descriptive epidemiology of vaginal cancer incidence and survival by race, ethnicity, and age in the United States

Vaginal cancer is a rare malignancy. It has many of the same risk factors as cervical cancer, including a strong association with persistent human papillomavirus infection. Descriptive studies of the epidemiology of vaginal cancer are scarce in the literature. The 1998 through 2003 incidence data from 39 population-based cancer registries were used, covering up to 83% of the US population. The 1996 through 2003 data from 17 cancer registries were used for survival analysis. Incidence rates, disease stage, and 5-year relative survival rates were calculated by race, ethnicity, and age group. Data analysis focused mainly on squamous cell carcinoma (SCC). Incidence rates for all vaginal cancers combined were 0.18 per 100,000 female population for in situ cases and 0.69 for invasive cases. The median age of invasive cases was older than that of in situ cases (aged 68 years vs 58 years). SCC was the most common histologic type (71% of in situ cases and 66% of invasive cases). Compared with the rate for white women, the age-adjusted incidence rate of invasive SCC was 72% higher (P < .05) among black women, whereas the rate among Asian/Pacific Islander (API) women was 34% lower (P < .05). Hispanic women had a 38% higher rate than non-Hispanic women (P < .05) of invasive SCC. The rates for in situ SCC peaked at age 70 years and then declined, whereas the rates of invasive SCC increased continuously with advancing age. Black, API, and Hispanic women as well as older women were more likely to be diagnosed with late-stage disease, and these groups had lower 5-year relative survival rates than their white, non-Hispanic, and younger counterparts. Incidence rates of vaginal SCC varied significantly by race, ethnicity, and age group. Black, API, and Hispanic women as well as older women had a high proportion of late-stage disease and a low 5-year survival rate.

Risk factors for invasive squamous cell carcinoma of the vulva and vagina—Population‐based case–control study in Denmark

The etiology of vulvar and vaginal squamous cell carcinoma (VV-SCC) has received little attention. A total of 182 women with invasive VV-SCC (116 with VV-SCC(vulva), 66 with VV-SCC(vagina)), 164 uterine corpus cancer controls and 518 population controls were interviewed in a population-based case-control study in Denmark, and 87 (48%) of the VV-SCC cases had tissue samples examined for human papillomavirus (HPV) DNA using the GP5+/6+ PCR-EIA assay and subsequent reverse line blotting for HPV typing. Logistic regression-derived odds ratios with 95% confidence intervals served as relative risks. Cervical cancer-associated high-risk HPVs (hrHPVs) were detectable in most (89%) examined cases of VV-SCC(vagina) and in half (50%) of cases of VV-SCC(vulva) (p < 0.001). In site-specific multivariate logistic regression analyses, statistically significant risk factors for both VV-SCC(vulva) and VV-SCC(vagina) included measures of hrHPV exposure (anogenital warts for VV-SCC(vulva); cervical neoplasia and poor genital hygiene for VV-SCC(vagina)), tobacco smoking and alcohol consumption. Furthermore, socioeconomic variables (marital status and years at school) were associated with risk of VV-SCC(vulva). Comparing hrHPV-positive and hrHPV-negative VV-SCCs in polytomous logistic regression analysis revealed that tobacco smoking and cervical neoplasia were significant risk factors only for hrHPV-positive VV-SCCs. Our study shows that VV-SCC(vulva) and VV-SCC(vagina) share measures of prior hrHPV exposure, tobacco smoking and alcohol consumption as statistically significant risk factors. HPV vaccination programs aimed at reducing the burden of cervical cancers are likely to also provide considerable protection against VV-SCCs.

Exclusive radiotherapy for primary squamous cell carcinoma of the vagina

Purpose To retrospectively analyze results of external beam therapy (EBT) with brachytherapy (BT) for primary vaginal squamous cell carcinoma (PVSCC). Materials and methods From 1970 to 2001, 91 patients were included. FIGO stages were: I (29%), II (38%), III (29%) and IVa (4%). EBT delivered a median total dose of 50 Gy to the pelvis. BT was performed with a customized intra-vaginal applicator and in 36% of applications combined endocavitary and interstitial BT. ICRU Report 38 parameters were reported. Results The 5-year cause specific survival (CSS) rates were: 83% for stage I, 76% for stage II, 52% for stage III, and 2 of the 4 stage IVa patients died 9 and 36 months after treatment. The 5-year pelvis control rates were: 79% for stage I and II and 62% for stage III. Recurrences as a first event were local only in 68% of cases, nodal only in 10%, metastatic only in 13% and combined in 9%. In multivariate analysis: stage (I and II versus II and IV), response to EBT (evaluated at BT), and the number of BT applications were statistically significant for CSS. Grade 2–3 toxicities were as follows (Franco-Italian Glossary): rectum ( n = 3), sigmoid colon and small bowel ( n = 8), bladder ( n = 5), ureter ( n = 4) and vagina ( n = 13). Anterior location of the tumor increased bladder toxicity ( p = 0.01) and total reference air kerma was higher in patients who experienced grade 2–3 urinary or digestive toxicity ( p = 0.03). Conclusion EBT with BT is an effective treatment for patients with stage I–II PVSCC. The incidence and severity of late toxicity were relatively low. Recent advances in the treatment of cervix carcinoma emphasize the need for concomitant radio-chemotherapy in stages III–IV and the use of MRI for treatment planning.

A rare case of primary invasive carcinoma of vagina associated with irreducible third degree uterovaginal prolapse

Primary carcinoma of vagina accounts for less than 2% of all gynecological malignancies. We report a rare case of primary invasive carcinoma of vagina with a third degree uterovaginal prolapse which is even rarer. Mrs X a 60-year-old postmenopausal P5 L4 lady reported to us with complaints of something coming out per vaginum for the past 10 years along with blood stained discharge and difficulty in micturition for the last 4 months. On examination there was third degree cervical descent with a grade three cystocoele and rectocoele. A 4 x 5 cm ulcer was present on middle third of right lateral vaginal wall with marked edema and induration of surrounding tissue. The prolapse was irreducible; was reduced under intravenous sedation with difficulty. On per vaginam examination uterus was normal in size there was no adnexal mass right paracolpium was involved up to lateral pelvic wall and left paracolpium was free. Rectal mucosa was free on per rectal examination (FIGO Stage III). Cervical smear was normal. Biopsy of the ulcer revealed invasive keratinising squamous cell carcinoma of vagina. Chest X-ray was normal. (excerpt)

Stage I squamous cell carcinoma of vagina complicating pregnancy: Successful conservative treatment

Background. Vaginal squamous cell carcinoma in pregnancy is very rare situation. Case. The patient was a 33-year-old woman, presenting with a complaint of vaginal brownish discharge at a 23 weeks of gestation. On pelvic examination at that time, a 2 by 2 cm mass on posterior vaginal fornix was seen. Biopsy of the lesion demonstrated a nonkeratinizing type invasive squamous cell carcinoma. She desired to continue the pregnancy and postpone the treatment until after delivery. On 23 weeks of gestation, we performed wide local excision, confirming T1 stage. On 33 weeks of gestation, a pelvic lymphadenectomy was carried out at the time of cesarean section to secure lymph node status pathologically. Further, she began intracavitary brachytherapy via vaginal cylinder in an adjuvant setting. She is 36 months from her initial surgery and remains disease free. Conclusion. Treatment could be individualized for primary stage I vaginal squamous cell carcinoma complicating pregnancy.

A case with multiple gynecological malignancies

A patient with cervical non-Hodgkin lymphoma was treated with chemotherapy. Fourteen months after the diagnosis of the lymphoma, an endometrial adenocarcinoma was detected as a secondary malignant tumor. The patient was treated with surgery followed by radiotherapy. Approximately 7 years after the diagnosis of endometrial cancer, vaginal invasive squamous cell carcinoma was diagnosed as the third primary malignancy, and a second-line palliative radiotherapy was applied. Seven months after the last radiotherapy, postradiational sarcoma in the vagina was diagnosed. Congenital and acquired immune system disorders, viral oncogenes, and various human leukocyte antigen (HLA) types were investigated. Total blood count and lymphocyte subset analysis were performed, and CD4+ lymphopenia was detected. Serologic tests were carried out for human immunodeficiency virus, hepatitis B virus, human papillomavirus, Epstein-Barr virus, and herpes simplex virus infection. Epstein-Barr virus viral capsid antigen IgG was found positive. Low-risk human papillomavirus panel was detected by Hybrid Capture method in the cervical smear. The HLA investigation revealed HLA-A2, HLA-A3, HLA-B57, HLA-B35, HLA-B4, HLA-B6, HLA-DR3, HLA-DR1, HLA-DR51, HLA-DR52, HLA-DQ6(1), and HLA-DQ7(3). The patient died because of the disease.

A case with multiple gynecological malignancies

A patient with cervical non-Hodgkin lymphoma was treated with chemotherapy. Fourteen months after the diagnosis of the lymphoma, an endometrial adenocarcinoma was detected as a secondary malignant tumor. The patient was treated with surgery followed by radiotherapy. Approximately 7 years after the diagnosis of endometrial cancer, vaginal invasive squamous cell carcinoma was diagnosed as the third primary malignancy, and a second-line palliative radiotherapy was applied. Seven months after the last radiotherapy, postradiational sarcoma in the vagina was diagnosed. Congenital and acquired immune system disorders, viral oncogenes, and various human leukocyte antigen (HLA) types were investigated. Total blood count and lymphocyte subset analysis were performed, and CD4+ lymphopenia was detected. Serologic tests were carried out for human immunodeficiency virus, hepatitis B virus, human papillomavirus, Epstein–Barr virus, and herpes simplex virus infection. Epstein–Barr virus viral capsid antigen IgG was found positive. Low-risk human papillomavirus panel was detected by Hybrid Capture method in the cervical smear. The HLA investigation revealed HLA-A2, HLA-A3, HLA-B57, HLA-B35, HLA-B4, HLA-B6, HLA-DR3, HLA-DR1, HLA-DR51, HLA-DR52, HLA-DQ6(1), and HLA-DQ7(3). The patient died because of the disease.

Periurethral masses: etiology and diagnosis in a large series of women.

To describe the differential diagnosis of periurethral masses in a consecutive series extracted from a single tertiary urogynecologic practice database. A patient database of a private urology and urogynecology practice with 1,950 women was searched for patients who were found to have a periurethral mass during the accrual dates of 1994 to 2002, and these records were reviewed for diagnostic testing and results. All women provided a history, completed a questionnaire, and underwent physical examination, voiding diary, cystoscopy, and videourodynamic testing; selected patients then underwent additional imaging. Seventy-nine (4%) patients aged 41.2 +/- 14 years were identified. Of these, 72 (91%) had been referred for evaluation of persistent irritative lower urinary tract symptoms or incontinence. Seven patients (9%) had been referred specifically because of a periurethral mass. Sixty-six patients (84%; 95% confidence interval [CI] 73%, 91%) had urethral diverticula, of which 4 (6%; 95% CI 2%, 14.8%) contained malignancies. Six patients (7%; 95% CI 3%, 15%) had vaginal cysts histologically identified as fibromuscular tissue, 4 (5%; 95% CI 1%, 12%) had leiomyomata, and 2 (2.5%; 95% CI 0.03%, 8.8%) had ectopic ureteroceles. Two patients had vaginal squamous cell carcinomas (2.5%; 95% CI 0.03%, 8.8%), and 1 had an infected granuloma. Masses were palpable in 42 patients (53.8%; 95% CI 42%, 64%) and in 37 patients either were encountered at surgery (n = 5) or were urethral diverticula diagnosed by voiding cystourethrogram (n = 32). Periurethral masses were encountered in less than 4% of our patient sample. Most masses were urethral diverticula; however, the differential diagnosis included leiomyoma, vaginal cysts, and malignancy. Masses were generally either palpable or seen at imaging studies performed during evaluation of lower urinary tract symptoms.

A recurrent gain of chromosome arm 3q in primary squamous carcinoma of the vagina

Primary carcinomas of the vagina are rare tumors, accounting for 2%–3% of all gynecologic malignancies. Only a few karyotypes based on chromosome banding techniques have been reported. We have, therefore, used comparative genomic hybridization to establish a pattern of genomic imbalances in vaginal squamous cell carcinomas. Analysis of 16 formalin-fixed and paraffin-embedded tumors revealed that 70% of vaginal carcinomas carry relative copy number increases that map to chromosome arm 3q. Other recurring gains were observed on chromosome arms 5p and 19p. Chromosomal losses were infrequent. Most tumors were aneuploid, as measured by image cytometry on Feulgen-stained tissue sections. The cytogenetic data were related to the presence of human papillomavirus genomes, expression of laminin-5 as a marker for invasiveness, and expression levels of markers for proliferative activity and mutated TP53. All relevant clinical data were recorded. The results suggest that vaginal carcinomas are defined by a specific distribution of chromosomal aneuploidies and that the pattern of genomic imbalances is strikingly similar to that observed in squamous cell carcinomas of the uterine cervix. Age at diagnosis ( P = 0.031), tumor size ( P = 0.025), and increased laminin-5 expression ( P = 0.006) have a significant influence on the survival time.

The Role of Surgery in Invasive Squamous Carcinoma of the Vagina

Abstract Objective. The aim of this study was to define the role of surgery in managing patients with a primary squamous vaginal cancer. Methods. A retrospective review was conducted of patients with primary invasive vaginal cancer managed at one institution over a 25-year period. The results were compared with those of all major publications of the past 20 years. Results. A total of 84 patients were reviewed. Forty-five (66%) were of squamous origin. The median follow-up was 45 months (range: 0.6–268). The patients were primarily treated by surgery in 67% and by radiotherapy alone in 33% of cases. The 5- and 10-year overall survival was, respectively, 74 and 58%. For stage I the figures were 91 and 70%. These survival rates compared favorably with those of published series of cases managed by radiotherapy alone. Univariate analysis showed that age ( P = 0.004), size ( P = 0.009), site ( P = 0.016), lymph node status ( P = 0.022), FIGO stage ( P = 0.027), and treatment ( P = 0.003) were relevant prognostic factors. Multiple regression analysis, however, revealed that only age ( P = 0.009) and size ( P = 0.037) were independent prognostic variables. Conclusions. Stage I and II squamous vaginal cancer patients have good outcomes in terms of survival and local tumor control if they are managed by initial surgery followed by selective radiotherapy.

Rapid Progression of Primary Vaginal Squamous Cell Carcinoma in a Young HIV-Infected Woman

Background. The association of human immunodeficiency virus (HIV) infection with rapid progression of cervical and anal squamous cell carcinoma has been clearly established by several studies. Human papilloma virus (HPV) infection of the anogenital tract is believed to be the causative agent of cervical, anal, vaginal, and vulvar squamous cell carcinoma. While a myriad of reports exist in the literature pertaining to the rapid progression of cervical and anal carcinoma in HIV-infected patients, no association of HIV infection and vaginal carcinoma has been reported. We present an unusual case of a young woman infected with HIV who was diagnosed with advanced vaginal carcinoma and succumbed to her disease shortly thereafter despite aggressive treatment.Case. A 40-year-old woman with a 2-year history of HIV infection presented with Stage IVA squamous cell carcinoma of the vagina and a large vesicovaginal fistula from the tumor eroding through the posterior bladder wall. Computed tomography (CT) of the abdomen and pelvis revealed a large tumor replacing the vagina with mild hydronephrosis and diffuse pelvic and inguinal lymphadenopathy. She underwent urinary diversion with a transverse colon conduit followed by pelvic radiation with weekly cisplatin chemosensitization. A repeat CT scan of the abdomen and pelvis upon completion of her treatment revealed progression of disease with multiple liver metastases and gastrohepatic ligament adenopathy. She subsequently died of advanced metastatic vaginal carcinoma 2 months after completion of treatment.Conclusion. Due to the rarity of primary vaginal carcinoma, the clinical behavior of this neoplasm in the HIV-infected patient is poorly understood. Our case indicates that, although vaginal carcinoma is a disease of the elderly, young women infected with HIV and HPV are predisposed not only to develop cervical or anal carcinoma but also may be at increased risk for vaginal carcinoma with more aggressive and less responsive disease. Furthermore, although vaginal carcinoma is usually a slow-growing neoplasm, this case illustrates the aggressive behavior of such a tumor when associated with HIV infection.

Primary Vaginal Squamous Cell Carcinoma Presenting as a Cystic Pelvic Mass

A 57-year-old woman presented with urinary retention, diarrhea, rectal bleeding, a cystic pelvic mass with thick irregular borders posterior to the vagina displacing the cervix and the bladder, and an intact vaginal mucosa. The patient underwent exploratory laparotomy on the assumption that she had an ovarian neoplasm. The mass originated from the posterior vaginal wall and was consistent with primary squamous cell carcinoma. The patient was treated with surgical cytoreduction followed by external radiation therapy and weekly cisplatin with good response. One year following treatment the patient remains without evidence of disease. Primary vaginal squamous cell carcinoma arising from the posterior vaginal wall can present as a cystic pelvic mass resembling an ovarian neoplasm. Cytoreductive surgery followed by chemoradiation might be of value in some patients with primary vaginal carcinoma.

P53Mutations and Presence of HPV DNA Do Not Correlate with Radiosensitivity of Gynecological Cancer Cell Lines

Objective.The correlation betweenp53tumor suppressor gene mutations and the presence of high-risk human papillomavirus (HPV) DNA with thein vitroradiosensitivity of gynecological malignancies was studied in 26 cell lines derived from gynecological cancers of 23 patients.Methods.Comparison of the intrinsic radiosensitivity was performed with mean inactivation dose (D̄) determined with the 96-well plate clonogenic assay.p53mutations were investigated with polymerase chain reaction and single-strand conformation polymorphism (PCR–SSCP) analysis and direct DNA sequencing, and the presence of HPV DNA was studied with PCR using HPV consensus primers.Results. p53mutations were found in 6 of 10 vulvar squamous cell carcinoma (SCC) lines. Nine vulvar and 1 vaginal SCC cell lines were HPV DNA negative and 1 vulvar cell line was HPV 16 positive. All 4 cervical SCC lines were HPV positive and possessed the wild-typep53.Three cell lines expressed HPV 16 and 1 HPV 68. Among 10 endometrial cancer cell lines, 2 cell lines with mutantp53and 1 HPV 16 positive cell line were found. No correlation could be demonstrated between inactivation of thep53gene and radiosensitivityin vitro;the cell lines were evaluated as one group or according to their anatomical origin or histology.Conclusion.Our results indicate that inactivation of thep53gene through mutation or binding with HPV DNA does not increase the resistance of gynecological malignancies to ionizing radiationin vitro.

A transplacental carcinogenicity bioassay in CD-1 mice with zidovudine.

In oral carcinogenicity bioassays, zidovudine (ZDV) induced vaginal epithelial cell tumors in mice given 30 or 40 mg/kg/day and rats given 300 mg/kg/day. To determine if lifetime exposure to ZDV, beginning perinatally, would alter this pattern of carcinogenicity, two groups of 60 pregnant CD-1 mice were given 20 or 40 mg/kg/day of ZDV in 0.5% methyl cellulose from Gestation Day 10 through Lactation Day 21. At weaning, 2 pups per sex from each of 35 litters in each group were assigned to the study and given 20 or 40 mg/kg/day of ZDV in the drinking water until 17-35 days of age, followed by daily gavage for 24 months. Two additional groups of 60 pregnant CD-1 mice each were given 40 mg/kg/day of ZDV daily from Gestation Day 10 through Lactation Day 21; in one, ZDV treatment was halted at weaning and in the other, treatment was stopped 90 days after weaning. Two other groups of 60 pregnant CD-1 mice were left untreated (environmental control) or were given 0.5% methyl cellulose beginning on Gestation Day 10 (vehicle control). Vehicle control progeny received plain drinking water for 17-35 days postweaning and then 0.5% methyl cellulose daily by gavage for 24 months. ZDV treatment did not affect survival or body weight in either sex. In females given 20 or 40 mg/kg/day of ZDV for 24 months there was mild macrocytic anemia. Similar, non-dose-related changes were seen in males in these groups. ZDV-related tumor findings were limited to the vagina, where there were 2 and 11 vaginal squamous cell carcinomas in mice given 20 or 40 mg/kg/day of ZDV daily, respectively. This incidence was not remarkably different from that seen in previously reported bioassays. It was concluded that lifetime oral treatment of mice with ZDV, beginning perinatally, did not alter the previously reported pattern of carcinogenicity and that under the conditions tested ZDV was not a transplacental carcinogen.

A Transplacental Carcinogenicity Bioassay in CD-1 Mice with Zidovudine

In oral carcinogenicity bioassays, zidovudine (ZDV) induced vaginal epithelial cell tumors in mice given 30 or 40 mg/kg/day and rats given 300 mg/kg/day. To determine if lifetime exposure to ZDV, beginning perinatally, would alter this pattern of carcinogenicity, two groups of 60 pregnant CD-1 mice were given 20 or 40 mg/kg/day of ZDV in 0.5% methyl cellulose from Gestation Day 10 through Lactation Day 21. At weaning, 2 pups per sex from each of 35 litters in each group were assigned to the study and given 20 or 40 mg/kg/day of ZDV in the drinking water until 17-35 days of age, followed by daily gavage for 24 months. Two additional groups of 60 pregnant CD-1 mice each were given 40 mg/kg/day of ZDV daily from Gestation Day 10 through Lactation Day 21; in one, ZDV treatment was halted at weaning and in the other, treatment was stopped 90 days after weaning. Two other groups of 60 pregnant CD-1 mice were left untreated (environmental control) or were given 0.5% methyl cellulose beginning on Gestation Day 10 (vehicle control). Vehicle control progeny received plain drinking water for 17-35 days postweaning and then 0.5% methyl cellulose daily by gavage for 24 months. ZDV treatment did not affect survival or body weight in either sex. In females given 20 or 40 mg/kg/day of ZDV for 24 months there was mild macrocytic anemia. Similar, non-dose-related changes were seen in males in these groups. ZDV-related tumor findings were limited to the vagina, where there were 2 and 11 vaginal squamous cell carcinomas in mice given 20 or 40 mg/kg/day of ZDV daily, respectively. This incidence was not remarkably different from that seen in previously reported bioassays. It was concluded that lifetime oral treatment of mice with ZDV, beginning perinatally, did not alter the previously reported pattern of carcinogenicity and that under the conditions tested ZDV was not a transplacental carcinogen.

Nonclinical Toxicology Studies with Zidovudine: Genetic Toxicity Tests and Carcinogenicity Bioassays in Mice and Rats

Zidovudine (ZDV), an antiviral drug active in the treatment of acquired immunodeficiency syndrome (recommended human dose, 100 mg every 4 hr while awake), was evaluated for mutagenic and carcinogenic potential in a battery of short-termin vitroandin vivoassays and in lifetime studies in mice and rats. In L5178Y mouse lymphoma cells (tk+/−locus), a weak positive result was obtained only at the highest concentrations tested (4000 to 5000 μg/ml) in the absence of metabolic activation. In the presence of metabolic activation, the drug was weakly mutagenic at concentrations of 1000 μg/ml and higher. Following 24 hr treatment in the absence of metabolic activation, ZDV was moderately mutagenic at concentrations up to 600 μg/ml; dose-related structural chromosomal alterations were seen at concentrations of 3 μg/ml and higher in cultured human lymphocytes. Such effects were not noted at the two lowest concentrations tested, 0.3 and 1 μg/ml, and BALB/c-3T3 cells were transformed at concentrations of 0.5 μg/ml and higher. No effects were seen in the AmesSalmonellaplate incorporation and preincubation modification assays (possibly due to bacteriocidal activity of ZDV at low concentrations) at concentrations ranging from 0.01 to 10 μg/plate or in a single-dose intravenous bone marrow cytogenetic assay in CD rats. In multidose micronucleus studies, increases in micronucleated erythrocytes were seen in mice at doses of 100 to 1000 mg/kg/day. Similar results were seen in rats and mice after 4 or 7 days of dosing at 500 mg/kg/day. In carcinogenicity bioassays, adjusted doses of 20, 30, or 40 mg/kg/day and 80, 220, and 300 mg/kg/day were given to CD-1 mice and CD rats, respectively, for up to 22 months in mice and 24 months in rats. ZDV caused a macrocytic, normochromic anemia in both species. No evidence of carcinogenicity was seen in male mice or rats. In female mice, five malignant and two benign vaginal epithelial neoplasms occurred in animals given 40 mg/kg/day. A single benign vaginal epithelial tumor was seen in a mouse given 30 mg/kg/day. In rats, two malignant vaginal epithelial neoplasms were seen in animals given 300 mg/kg/day. In a 7-day study in mice, ZDV was shown to be devoid of estrogenic activity. In an oral pharmacokinetics study, the AUC was 17 and 140 μg/ml·hr in female mice and rats given 40 or 300 mg/kg of ZDV, respectively. In contrast, the average steady-state concentration in humans at the recommended daily dose is 0.62 μg/ml. Twenty-four hour urine concentrations were 1245 and 4417 μg/ml in female mice and rats given 40 or 300 mg/kg of ZDV, respectively. These values were approximately 26- and 136-fold higher than the human urine concentration at the recommended daily dose. In a one- to three-day study with intravenously administered sodium fluoroscein in rats and mice, retrograde flow of urine into the vagina was demonstrated. In a subsequent lifetime carcinogenicity bioassay in mice in which ZDV was given intravaginally at concentrations of 5 or 20 mg ZDV/ml in saline, 13 vaginal squamous cell carcinomas were seen at the highest concentration tested. It was concluded that the vaginal tumors seen in the oral carcinogenicity studies were the result of chronic local exposure of the vaginal epithelium to high urine concentrations of ZDV.

121 The relative efficacy of HDR and LDR interstitial brachytherapy in squamous cell carcinoma of vagina

121 The relative efficacy of HDR and LDR interstitial brachytherapy in squamous cell carcinoma of vagina

545 Second malignancies (SM) in esophageal cancer (EC) after combined modality treatment: Implications for follow-up and chemoprevention

From 5/85 to 12/92, 101 consecutive patients (median age: 61 yrs), with locally advanced EC received a combined chemoradiotherapy treatment, Sixty-one pts were treated with FU + CDDP × 4 cycles and concurrent RT (50 Gy) and 40 pts with 2 courses of the same regimen plus concurrent RT (30 Gy) followed by surgery. Overall survival (OS) at 6 yrs was 22%. In 14 pts EC developed after a previous neoplasm and they were excluded from the analysis. In the remaining 87 pts with primary EC (OS 23% with a median follow up of 77 mos) a total of 12 pts (median age 67 yrs, range 49–79) developed a SM after a median of 27.5 mos (range 7–83) from the diagnosis of EC: 4 epidermoid head and neck cancers, 3 gastric adenocarcinomas (1 early gastric cancer), 1 distal esophageal adenocarcinoma, 2 non small cell lung cancers, 1 colon adenocarcinoma, and 1 vaginal squamous cell carcinoma. Actuarial cumulative risk for SM at 2, 4, and 6 yrs is 6%, 17%, and 23% respectively. Total incidence rate was 6% with an age-adjusted incidence of SM 3 times higher than that of primary cancer in the general population. The high incidence of SM in long-term survivors with EC strongly supports a prolonged follow-up oriented to the early detection of SM. This population with high rate of SM should represent an optimal model to assess the role of chemoprevention.

Vaginal Squamous Cell Carcinoma with Sarcomatoid Spindle Cell Features

A vaginal squamous cell carcinoma with prominent sarcomatoid spindle cell features found in a 25-year-old female is presented. The exclusively spindle-shaped growth pattern of the neoplastic cells in the initial biopsy led to the diagnostic impression of a sarcoma. This in turn has resulted in an attempt at completely resecting the tumor. The 5.2 × 3.5-cm resected lesion, however, blended peripherally with a poorly differentiated squamous cell carcinoma. Moreover, the sarcomatoid component reacted with vimentin and cytokeratin, and tonofilaments and desmosomes were seen by electron microscopy. This apparently unique case indicates the need for obtaining representative tissue samples for providing an appropriate diagnosis prior to definitive therapy for vaginal squamous cell carcinoma. The primary treatment for large stage I squamous cell lesions of the vagina is radiotherapy, whereas an equally large sarcoma is best treated by wide local excision alone.

Primary vaginal tuberculosis after vaginal carcinoma

A case of primary vaginal tuberculosis is reported. A 62-year-old woman presented with a slightly eroded, granular vaginal lesion 10 months after radiation therapy for Stage II vaginal squamous cell carcinoma. She had previously undergone a total abdominal hysterectomy and left salpingo-oophorectomy at age 37 for abnormal uterine bleeding. This presentation of genital tract tuberculosis is unusual because of the location of the primary lesion, the age at presentation, the occurrence after radiation therapy, and the possible means of infection. We emphasize the need to maintain a high index of suspicion and to biopsy any suspicious vaginal lesions.