Biomedical subjects

Elvio G Silva

Publications and source records attributed to Elvio G Silva.

At least 19 recordsLinked to original sources

PubMed2006

Distribution and viral load of eight oncogenic types of human papillomavirus (HPV) and HPV 16 integration status in cervical intraepithelial neoplasia and carcinoma.

Current human papillomavirus (HPV) DNA testing using pooled probes, although sensitive, lacks specificity in predicting the risk of high-grade cervical intraepithelial neoplasia (CIN 2/3) progression. To evaluate selected HPV genotyping, viral load, and viral integration status as potential predictive markers for CIN progression, we performed HPV genotyping in formalin-fixed, paraffin-embedded cervical tissue with cervical carcinoma (29 cases) and CINs (CIN 1, 27 cases; CIN 2, 28 cases; CIN 3, 33 cases). General HPVs were screened using consensus primers GP5+/GP6+ and PGMY09/11. HPV genotyping and viral load measurement were performed using quantitative real-time PCR for eight oncogenic HPV types (16, 18, 31, 33, 35, 45, 52, and 58). HPV 16 viral integration status was evaluated by measuring HPV 16 E2/E6 ratio. We observed that HPV DNA positivity increased in parallel with the severity of CINs and carcinoma, with 59% positivity in CIN 1, 68% in CIN 2, 76% in CIN 3, and 97% in carcinoma (P trend=0.004). The eight oncogenic HPV types were significantly associated with CIN 2/3 (81%) and carcinoma (93%) (odds ratio (OR), 15.0; 95% confidence interval (CI), 5.67-39.76; P<0.0001) compared with the unknown HPV types (OR, 2.87; 95% CI, 0.89-9.22; P=0.08). HPV 16 was the predominant oncogenic HPV type in CIN 2/3 (51%) and carcinoma (71%) and integrated significantly more frequently in carcinoma than in CIN 2/3 (P=0.004). No significant differences in viral load were observed across the disease categories. Our findings suggest that selected genotyping for the eight oncogenic HPV types might be useful in separating women with a higher risk of CIN progression from those with a minimal risk. We also conclude that the HPV 16 integration status has potential to be a marker for risk assessment of CIN progression.

Adenocarcinoma↗

PubMed2006

Clinical behavior of stage II-IV low-grade serous carcinoma of the ovary.

OBJECTIVE: To analyze the clinical behavior of patients with stage II-IV low-grade serous carcinoma of the ovary seen at our institution who underwent primary surgery followed by platinum-based chemotherapy. METHODS: Patients with stage II-IV low-grade serous carcinoma of the ovary from 1978 to 2003 were identified using existing databases. Clinicopathologic information was obtained from medical records. Progression-free survival and overall survival were estimated by the method of Kaplan and Meier. The log-rank test was used to compare differences between survival curves. Univariable and multivariable analyses were performed using Cox proportional hazards regression. RESULTS: We identified 112 eligible patients. Median age was 43 years.; 90% had stage III disease. Preoperative serum CA 125 was elevated in 86% of patients. The most common sites of extraovarian disease were omentum, fallopian tubes, pelvic peritoneum, and uterus. Response rate to platinum-based chemotherapy in 10 evaluable patients (15% of patients with gross residual disease) was 80%, and 42 patients underwent second-look surgery: microscopically negative findings, 2 (5%); microscopically positive disease, 13 (33%); macroscopically positive disease, 24 (62%); and insufficient information, 3 (7%). Median progression-free survival and overall survival times were 19.5 and 81.8 months. Persistent disease after primary chemotherapy was the only factor associated with shorter overall survival time (hazard ratio 3.46, 95% confidence interval 2.00-5.97, P<.001). CONCLUSION: Metastatic low-grade serous carcinoma of the ovary is characterized by young age at diagnosis and prolonged overall survival. Segregating women with this diagnosis in future clinical trials is warranted.

Adolescent↗

PubMed2006

Ovarian involvement by metastatic colorectal adenocarcinoma: still a diagnostic challenge.

Ovarian involvement by metastatic colorectal adenocarcinoma, although not an uncommon occurrence, remains a diagnostic challenge. The gross and histologic features of such metastases overlap those of primary ovarian epithelial neoplasms such as endometrioid or mucinous adenocarcinoma. The clinical and pathologic features of 86 cases of metastatic colorectal adenocarcinoma involving the ovary were reviewed. Patients ranged in age from 19 to 85 years (median, 51 years); 24% were younger than 40 years. Presenting symptoms included abdominal or pelvic pain (45 cases), rectal bleeding (13 cases), change in bowel habits (20 cases), and vaginal bleeding (5 cases). In 23 cases, an ovarian mass was the first manifestation of the disease. Ovarian involvement was bilateral in 49 cases and unilateral in 33 (including 20 cases in which the only involved ovary measured at least 10 cm in greatest dimension). Involved ovaries ranged from 2 to 24 cm (mean, 10.1 cm), and most featured both solid and cystic areas. Many involved ovaries featured smooth capsules without gross evidence of surface involvement by tumor. In general, the tumors had typical histologic features of metastatic colorectal adenocarcinoma, including a garland pattern and dirty necrosis. In 23 cases, foci with a benign or low malignant potential appearance were seen. Immunohistochemical studies showed that 29 of 29 tumors (100%) were positive for CK20; focal CK7 positivity was seen in 5 of 30 cases (17%). In 9 of the cases, an ovarian primary was diagnosed or favored initially, and 5 of these cases were initially treated as ovarian primaries. Metastatic colorectal adenocarcinoma should be considered in the differential diagnosis of an ovarian mass, even if the mass is large and unilateral or in a young patient, to secure proper treatment of these patients.

Adenocarcinoma↗

PubMed2006

Endometrioid carcinoma simultaneously involving the uterus and the fallopian tube: a clinicopathologic study of 13 cases.

Although the simultaneous presentation of endometrial and ovarian carcinomas of the endometrioid type is well described, little is known about a similar phenomenon involving the endometrium and fallopian tube (FT). We present the clinicopathologic features of 13 such cases seen in the Department of Pathology at The University of Texas M.D. Anderson Cancer Center over an 8 year period (1995 to 2002). FT tumors that could have represented luminal extension of the endometrial carcinoma or that represented an unequivocal metastasis to the FT were excluded. The patients' ages ranged from 34 to 77 years (median 54). The most common symptom was abnormal uterine/vaginal bleeding (11) and all of the patients were considered overweight or obese (mean body mass index was 41). The size of the endometrial carcinomas ranged from 0.3 to 8 cm. According to the FIGO grading of the endometrial endometrioid carcinomas, the cases were distributed as follows: Grade 1 (3) and Grade 2 (10). In 2 cases, there were also small areas of other histologic types, papillary serous carcinoma (1 case), and papillary endometrial carcinoma of intermediate grade (another case). The size of the fallopian tube carcinomas ranged from 0.2 to 17.5 cm. Seven of these tumors were located in the distal/fimbriated end of the FT. There was bilateral involvement in 2 cases. Three of the FT tumors were in situ. The grades of the fallopian tube carcinomas were as follows: Grade 1 (2), Grade 2 (6), and Grade 3 (2). In situ components were seen in all cases. One fallopian tube carcinoma was mixed with serous carcinoma. In 4 cases, there was also an endometrioid carcinoma involving the ovary, all of them with an intact ovarian capsule. Patients were treated as follows: total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) (4), TAH/BSO/chemotherapy (chemo) (4), TAH/BSO/radiation (3), and TAH/BSO/chemo/radiation (2). Follow-up ranging from 6 to 54 months was available in 10 patients: 1 patient died of disease (at 38 mo), 1 patient is alive with disease (at 9 mo), 7 patients have no evidence of disease (6 to 54 mo), and 1 patient died of metastatic endometrial carcinoma (at 9 mo). Simultaneous endometrioid carcinomas of the uterus and FT are unusual and occur primarily in obese perimenopausal women. The tumors are predominantly well or moderately differentiated with dissimilar endometrial and FT grades. The FT carcinoma is usually unilateral and located at the distal end of the tube.

Adult↗

PubMed2006

The recurrence and the overall survival rates of ovarian serous borderline neoplasms with noninvasive implants is time dependent.

Ovarian serous borderline neoplasm with noninvasive implants traditionally have been considered to be nonaggressive tumors associated with an excellent prognosis. However, in our experience, recurrences commonly develop as patients are followed over many years. Eighty cases of advanced-stage ovarian serous borderline tumor with noninvasive implants were identified; the minimum follow-up period for these cases was 5 years or until the death of the patient. The following cases were excluded: patients treated by cystectomy, patients who died of other causes, patients who developed other tumors, and patients who had as the only positive material after resection of the primary borderline neoplasm a tumor detected on a second look or third look operation. Hematoxylin and eosin-stained slides from the original ovarian tumor and the staging biopsies were reviewed in all cases. Slides of the recurrent tumor were available in all cases except for 2 in which the diagnosis was established clinically. The presence or absence of a micropapillary/cribriform pattern and microinvasion in the ovarian tumor was recorded. Follow-up was obtained from the patients' charts. Fischer exact test was used for statistical analysis. The patients' ages ranged from 17 to 67 years (median 36 y). Seventy-three patients were treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy. Seven patients were treated by total abdominal hysterectomy and unilateral salpingo-oophorectomy. The International Federation of Gynecology and Obstetrics stage was as follows: stage II (29 cases), stage III (50 cases), and stage IV (1 case). After surgery, 58 patients were treated with chemotherapy, 7 with radiotherapy, and 1 with hormonal therapy. The follow-up ranged from 5 to 31 years (median 15.7 y). Thirty-five patients (44%) developed recurrences. Only 10% of the patients had a recurrence in less than 5 years, 19% had their recurrences between 5 and 10 years, 10% between 10 and 15 years, and 5% more than 15 years after resection of the primary neoplasm. The only statistically significant feature associated with recurrence was the presence of a micropapillary/cribriform pattern, although this pattern was present in only 26% of the cases that recurred. Of the 35 patients who had a recurrence, 2 were diagnosed clinically, both are alive with progressive disease at 1 and 5 years after the diagnosis of the recurrence; 6 had recurrent serous borderline tumors, all are without evidence of disease with a follow-up ranging from 7 to 18 years after resection of the ovarian borderline tumor (median 14 y); and 27 patients subsequently developed low-grade serous carcinoma, 7 are alive with progressive disease with a follow-up ranging from 10 to 29 years (median 15 y) and 20 died of disease between 3 to 25 years after resection of the ovarian borderline tumor (median 16 y). In summary, the true recurrence rate of ovarian serous borderline tumors with noninvasive implants can only be obtained through a long follow-up. In this group of patients, 77% and 34% of the subsequent tumors developed 5 years and 10 years after diagnosis of the ovarian tumor, respectively. Histologic examination of the recurrent tumor is important in determining further therapy and prognosis for these patients; all patients who recurred with borderline tumor are without evidence of disease, whereas 74% of the patients who recurred with low-grade serous carcinoma died of disease. We propose that patients be followed for a minimum of 10 years to evaluate for recurrences and for 20 years to evaluate for survival.

Adolescent↗

PubMed2006

Association of low-grade endometrioid carcinoma of the uterus and ovary with undifferentiated carcinoma: a new type of dedifferentiated carcinoma?

Low-grade endometrioid carcinomas, either of the endometrium or the ovaries, usually have an excellent prognosis. The association of this type of tumor with undifferentiated carcinoma is rare. In this study, we present the clinicopathologic features of 25 such cases. The age of the patients ranged from 30 to 82 years (median, 51 years). At presentation, the patients had either vaginal bleeding or pelvic pain. The endometrioid carcinoma involved the endometrium in 14 cases, the endometrium and 1 or both ovaries in 9 cases, and the ovaries in 2 cases. Undifferentiated carcinoma associated with low-grade endometrioid carcinoma was found at presentation in 19 grade 1 or 2 endometrioid carcinomas: 15 in the endometrium and 5 in the ovary. In one of these cases, undifferentiated carcinoma was found in the endometrium and the ovary. Undifferentiated carcinoma was found after resection of low-grade endometrioid carcinoma in six cases, involving the retroperitoneum, pelvis, vagina, or liver. The undifferentiated carcinoma was composed exclusively of diffuse sheets and solid nests of epithelial cells in l0 cases. Epithelial cells with isolated foci of keratinization were seen in nine cases and rhabdoid cells in a myxoid background in six cases. Twenty-four patients were treated with total abdominal hysterectomy and with bilateral salpingo-oophorectomy. Twenty-two patients received additional therapy as follows: chemotherapy (), radiotherapy (), and tamoxifen (). Follow-up showed that 15 patients died of disease in 1 to 60 months (median, 6 months), and 5 patients are alive with progressive disease with a follow-up between 6 and 8 months; 1 patient is alive with no evidence of disease at 104 months. In four cases, the diagnosis was made recently, with short follow-ups of 3 and 4 months. Foci of undifferentiated carcinoma may be confused with solid endometrioid adenocarcinoma erroneously leading to the diagnosis of a grade 3 or a significantly less aggressive grade 2 endometrioid carcinoma. The recognition of undifferentiated carcinoma in an otherwise low-grade endometrioid adenocarcinoma is extremely important because it indicates aggressive behavior. In asynchronous cases, being aware of this association can explain the absence of a second primary.

Adult↗

PubMed2005

Subcellular localization of p27kip1 expression predicts poor prognosis in human ovarian cancer.

PURPOSE: The cyclin-dependent kinase inhibitor p27(kip1) regulates cellular progression from G(1) to S phase. Several studies have shown that loss of p27(kip1) protein expression is associated with disease progression in various malignancies. The purpose of this study was to evaluate the subcellular localization of this cyclin-dependent kinase inhibitor in a large cohort of primary ovarian carcinomas and compare the results with clinicopathologic variables and overall survival. EXPERIMENTAL DESIGN: Subcellular localization of p27(kip1) was first assessed by Western blotting in nuclear and cytoplasmic extract from 13 cases of ovarian carcinoma. Subcellular localization of the p27(kip1) protein was evaluated using tissue microarrays containing 421 cases of ovarian carcinoma. RESULTS: The presence of p27(kip1) in the cytoplasm regardless of the nuclear stain correlated strongly with late-stage disease (P < 0.03), extent of cytoreduction (P = 0.03), and shorter disease-specific survival (P < 0.0001). CONCLUSION: Cytoplasmic localization of p27(kip1) predicts poorer prognosis in ovarian carcinoma, particularly in late-stage disease.

Adenocarcinoma↗

PubMed2005

Expression of progesterone receptor is a favorable prognostic marker in ovarian cancer.

OBJECTIVE: Receptors for estrogen (ER), progesterone (PR), or androgen (AR) are predictive and prognostic markers of malignancy of multiple endocrine organs, including endometrial and breast cancer. However, the role of ERs, PRs, or ARs in the carcinogenesis of ovarian cancer, another sex hormone-dependent malignancy, is still controversial despite numerous studies that have attempted to determine their role. The disagreement in the findings may result from the fact that the numbers of tumor samples in studies have been small and that different immunohistochemical methods have been used that can introduce variation in the scoring of the histology. We therefore examined the pattern of expression of ERs, PRs, and ARs in a large number of samples of primary ovarian carcinoma by using a tissue microarray technique. METHODS: We constructed a tissue microarray with 322 samples of primary ovarian carcinoma obtained at surgery performed at The University of Texas M. D. Anderson Cancer Center between 1990 and 2000. Immunohistochemistry studies were performed by using the immunoperoxidase technique against primary antibodies (ER, PR, and AR). RESULTS: ERs, PRs, and ARs were differently expressed in different histotypes of ovarian cancer: ERs were expressed in 77.3% of all cases but more highly expressed in serous and endometrioid types; PRs were expressed in 26.2% of all cases but most highly expressed in the endometrioid type < 64.2%; and ARs were expressed in 43.7% of all cases but were most highly expressed in serous (47.5%) carcinomas. Of particular importance, the expression of PRs, but not ERs or ARs, was associated with better survival (P < 0.0001) in univariate and multivariate analyses. CONCLUSIONS: The PR is an independent marker, with its overexpression associated with a favorable prognosis in women with ovarian cancer.

Adult↗

PubMed2005

A uterine leiomyosarcoma that became positive for HMB45 in the metastasis.

Uterine smooth muscle tumors are usually spindle cell lesions, but a minority is composed of epithelioid cells. Foci of clear cells can be found in these latter tumors. Recently, it has been shown that some of these tumors can be positive for HMB45, and some authors have advocated calling these lesions perivascular epithelioid cell (PEC) tumors or PEComas. The case we describe here clearly shows that the so called PEC is just a smooth muscle cell capable of changing its immunophenotype. The patient involved is a 29-year-old black woman who was found to have an epithelioid leiomyosarcoma of the uterus in November 1995. She was treated with a simple hysterectomy and bilateral salpingo-oophorectomy. A metastatic lesion was found in her liver. She, therefore, also received chemotherapy and was free of disease until October 2002, when a recurrent tumor was detected in her spine. After undergoing resection of the lesion at 2 different times, in 2002 and 2003, the patient was treated with radiotherapy and is currently receiving chemotherapy. On microscopic examination, the tumor in the uterus and liver both proved to be an epithelioid leiomyosarcomas that was diffusely positive for smooth muscle actin. Approximately 15% of the cells had clear cytoplasm, but sections from 2 different blocks were completely negative for HMB45. However, although the tumors resected from the spine in 2002 and 2003 showed features similar to those of the uterine neoplasm, but with a lower percentage of cells positive for smooth muscle actin and more clear cells, several of the clear cells were positive for HMB45. To the best of our knowledge, this is the first case of a uterine smooth muscle cell tumor that became positive for HMB45 when it metastasized.

Actins↗

PubMed2005

Low-grade serous carcinoma of the ovary metastatic to the anterior mediastinum simulating multilocular thymic cysts: a clinicopathologic and immunohistochemical study of 3 cases.

Three cases of serous borderline tumors of the ovary with areas of serous low-grade carcinoma metastatic to the anterior mediastinum simulating multilocular thymic cysts are presented. The patients are women between the ages of 33 and 50 years. The 3 women had a prior history of primary ovarian neoplasms diagnosed over a period ranging from 3 to 20 years; the 3 patients were in stages IIIA, IIIB, and III. Follow-up radiologic examination revealed the presence of an anterior mediastinal tumor. The 3 patients underwent surgical resection of the mediastinal tumor. Grossly, the mediastinal tumors measured from 7 to 9 cm in greatest diameter and were described as cystic with solid areas. Focal areas of hemorrhage were present, but frank necrosis was not identified. Histologically, all the tumors basically showed similar histopathologic features, namely, those described in multilocular thymic cysts, ie, cystic structures lined by either squamous or low cuboidal epithelium, lymphoid hyperplasia, cholesterol cleft granulomas, and remnants of thymic tissue. In addition, within the cystic structures, there was a neoplastic cellular proliferation with papillary architecture, nuclear atypia, and scattered mitotic figures. Immunohistochemical studies for keratin, MOC31, and CA-125 showed positive staining in tumor cells while placental-like alkaline phosphatase was negative. Two patients remain alive and well after follow-up ranging from 6 to 18 months and 1 patient died of tumor 18 years after initial diagnosis.

Adult↗

PubMed2005

Undifferentiated carcinoma of the endometrium.

Undifferentiated carcinoma arising in the endometrium is considered a rare neoplasm with only a few studies published thus far. This limited number of studies is most likely a reflection of the underrecognition of this tumor because of a lack of diagnostic criteria to separate it from endometrial endometrioid adenocarcinoma, FIGO grade 3. In this study, we present the clinicopathologic features of 16 cases of endometrial undifferentiated carcinoma. In addition, we review the clinicopathologic features of 33 cases of endometrial endometrioid adenocarcinoma, FIGO grade 3, and compare them with the undifferentiated cases. The age of the 16 patients with undifferentiated carcinoma of the endometrium ranged from 40 and 69 years (mean, 59 years). Stage was known in 13 patients. Six (46%) patients presented with early stage disease (4 stage I and 2 stage II). Seven (54%) patients presented with advanced stage disease (2 stage III and 5 stage IV). Staging information was not available for 3 patients. Undifferentiated carcinoma was characterized by a proliferation of medium-sized, monotonous, epithelial cells growing in solid sheets with no specific pattern. Glands were not identified. Keratin immunostaining was focally positive in 11 of 12 cases, and EMA was focally positive in all 12 cases. The age of the 33 patients with endometrial endometrioid carcinoma, FIGO grade 3, ranged from 40 to 90 years (mean, 68 years). Twenty-three (70%) patients presented with early stage disease (21 stage I and 2 stage II), and 10 (30%) patients presented with advanced stage disease (8 stage III and 2 stage IV). Focal glandular differentiation was seen in all cases. The solid component was different from the one seen in the undifferentiated carcinomas because well demarcated trabeculae, cords, or groups of cells were identified in all cases. The tumor cells in the solid areas resembled the cells in the glandular component of the tumor. Immunoperoxidase studies for keratin and EMA were positive in 23 of 23 cases. Twelve of the 16 (75%) patients with undifferentiated carcinoma died of disease; 10 (62.5%) of them within 5 years after diagnosis. In contrast, 13 of 33 (39.4%) patients with endometrial endometrioid carcinoma, FIGO grade 3, died of disease. Twelve (36.4%) died within 5 years after diagnosis. In summary, undifferentiated carcinoma of the endometrium appears to be more aggressive than endometrial endometrioid adenocarcinoma, FIGO grade 3. Its proper recognition is important for prognosis and potentially for therapy.

Adenocarcinoma↗

PubMed2005

Differential expression of WT-1 in serous carcinomas in the peritoneum with or without associated serous carcinoma in endometrial polyps.

Although differential WT-1 expression between ovarian and uterine serous carcinoma has been discussed in the literature, there have been no studies of WT-1 expression in serous carcinomas in the peritoneum with or without concurrent serous carcinoma in an endometrial polyp. This study addresses this issue and includes a small series of uterine and ovarian serous carcinomas for comparison. Nine peritoneal serous carcinomas with coexistent serous carcinoma in an endometrial polyp, 10 peritoneal serous carcinomas without serous carcinoma in an endometrial polyp, 9 uterine serous carcinomas, and 12 ovarian serous carcinomas were stained with antibody to WT-1. Ninety-two percent of ovarian serous carcinomas and 80% of peritoneal serous carcinomas without serous carcinoma involving an endometrial polyp expressed WT-1. In contrast, 12% of peritoneal serous carcinomas with serous carcinoma in an endometrial polyp expressed WT-1 with the serous carcinoma in the endometrial polyp staining concordantly. For uterine serous carcinoma without an endometrial polyp, only 11% expressed WT-1. Peritoneal serous carcinomas without coexistent serous carcinoma in an endometrial polyp have a WT-1 expression pattern similar to ovarian serous carcinoma while peritoneal serous carcinomas with coexistent serous carcinoma in an endometrial polyp have a staining pattern similar to uterine serous carcinoma. The difference in WT-1 expression among serous carcinomas suggests a difference in biology based on the site of origin. Additionally, the difference in WT-1 expression between peritoneal serous carcinomas with and without coexistent serous carcinoma in endometrial polyps suggests that peritoneal serous carcinoma may have different pathogenetic pathways.

Cystadenocarcinoma, Serous↗

PubMed2004

Validation of tissue microarray technology in ovarian carcinoma.

High-throughput tissue microarray allows many clinical specimens to be analyzed simultaneously on a single slide. One potential limitation of tissue microarray is the correct representation of each tumor with the small tissue core. Because tumors from different organs have different levels of heterogeneity, it requires a validation study for each one of them. We compared immunostaining of Ki-67, estrogen receptors, and p53 in whole sections of 45 cases of high-grade serous ovarian carcinoma with six core samples from those sections with regard to the number of tissue cores needed to reliably represent a whole section. Staining for Ki-67 was graded high or low by automated image analysis of 10 high-power fields; staining for estrogen receptor and p53 was scored on a 0-to-3 scale. Correlation coefficients for whole-section vs core stains were 0.86 for Ki-67, 0.93 for estrogen receptors, and 0.82 for p53. A total of 54 (6.6%) of the cores were inadequate for scoring. The probability that results from one core would correctly represent all three markers in the whole section was 91%; that for two cores was 96%; and that for three cores was 98%. Our results show that analysis of a single readable core matched the staining pattern of a whole section more than 90% of the time, and analysis of two cores increased that value to more than 95%, demonstrating that ovarian carcinoma tissue microarray is a reliable technique to analyze the expression of markers.

Female↗

PubMed2004

Uterine epithelioid leiomyosarcomas with clear cells: reactivity with HMB-45 and the concept of PEComa.

In this study, we investigated HMB-45 expression in epithelioid uterine leiomyosarcomas with clear cell areas. From 12 epithelioid leiomyosarcomas, we selected 5 that had: 1) clear cell areas and 2) spindle cell areas that were at least focally positive for desmin and caldesmon. The patients' ages ranged from 47 to 82 years (mean 64 years). Presenting symptoms were uterine bleeding (three), abdominal pain (one), and a pelvic mass (one). There was no history of tuberous sclerosis or lymphangioleiomyomatosis. One patient had stage II disease, one stage III, and three stage IV. All were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Two received radiotherapy, and three were also treated with chemotherapy. The tumors ranged in size from 4 x 3 x 3 cm to 10 x 7 x 6 cm; all had significant cellular atypia, areas of coagulative necrosis, and between 10 and 90 mitoses per 10 high power fields. Vascular invasion was seen in three cases. The epithelioid component varied from 50% to 90% in each case; and the percentage of clear cells was < 1% in one case, 5% in one case, and 10% to 80% in three cases. Smooth muscle actin and desmin were positive in all cases. Four cases were positive for HMB-45 only in the clear cell areas. The tumor with < 1% of clear cells was negative for HMB-45. All were negative for S-100 and c-kit. Three patients died of disease at 9, 30, and 32 months; one patient is alive with progressive disease at 6 months, and one patient (stage II disease) is alive with no evidence of disease at 8 months. Unequivocal uterine epithelioid leiomyosarcomas may have clear cells positive for HMB-45. These tumors might belong to the group of lesion designated as PEComas; however, it is advisable to designate them as uterine leiomyosarcomas. In uterine smooth muscle tumors, some epithelioid cells most likely undergo clear cell changes and become positive for HMB-45. It would be advisable to perform this stain in all epithelioid smooth muscle tumors of the uterus.

Adult↗

PubMed2004

Grading ovarian serous carcinoma using a two-tier system.

In this study, we evaluate a two-tier system for grading ovarian serous carcinoma. This system is based primarily on the assessment of nuclear atypia with the mitotic rate used as a secondary feature. The study included 50 cases of low-grade ovarian serous carcinoma and 50 cases of high-grade ovarian serous carcinoma retrieved from the files of the Department of Pathology at the University of Texas M. D. Anderson Cancer Center from a 28-year period. Cases assigned to the low-grade category were characterized by the presence of mild to moderate nuclear atypia. As a secondary feature, they tended to show up to 12 mitoses per 10 high power fields (HPFs), whereas those in the high-grade category had marked nuclear atypia and as a secondary feature more than 12 mitoses per 10 HPFs. For comparison, the tumors were also graded using the Shimizu/Silverberg and the FIGO grading systems. Patients in the low-grade ovarian serous carcinoma group ranged in age from 19 to 75 years (mean 41.7 years) while patients in the high-grade ovarian serous carcinoma group ranged in age from 27 to 76 years (mean 55 years). All of the cases except one were advanced FIGO stage. Using the Shimizu/Silverberg system, the low-grade ovarian serous carcinoma cases were distributed as follows: grade 1, 47 cases; grade 2, 3 cases. Using the FIGO grading system, 35 cases were grade 1 and 15 cases were grade 2. Regarding the high-grade ovarian serous carcinoma group using the Shimizu/Silverberg system, 14 of the cases were grade 2 and 36 cases were grade 3. Using the FIGO grading system, 1 case was grade 1, 38 cases were grade 2, and 11 cases were grade 3. Most of the patients in both groups were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy and also received cisplatinum-based chemotherapy. On follow-up, 37 patients in the low-grade ovarian serous carcinoma group had died of disease at a median 4.2 years after diagnosis compared with 46 patients in the high-grade ovarian serous carcinoma group who died of disease at a median of 1.7 years. Eight patients in the low-grade ovarian serous carcinoma group and 4 patients in the high-grade ovarian serous carcinoma group were alive with disease at median follow-ups of 4.3 and 3.85 years, respectively. Four patients with low-grade serous carcinoma were alive without evidence of disease after a follow-up that ranged from 4.4 to 22.6 years (median 6.85 years), and one died of other causes 14 years after the diagnosis of her ovarian tumor. On multivariate analysis, residual tumor and tumor grade based on the M. D. Anderson two-tier system for grading ovarian serous carcinoma were found to be significant independent prognostic factors (P = 0.003 and 0.04, respectively). Of interest, 60% of the low-grade ovarian serous carcinomas in this study were associated with a serous neoplasm of low malignant potential, whereas this association was present in only 2% of the high-grade ovarian serous carcinomas. This finding could reflect a difference in the pathogenesis of ovarian serous carcinomas of different grades. In summary, there is usually a good correlation between the two-tier grading system herein presented and the Shimizu/Silverberg and the FIGO grading systems. Because this system is based on defined criteria that are easy to follow and because it involves only two diagnostic categories, it should provide better reproducibility in the grading of ovarian serous carcinoma. However, additional studies are required to validate these statements.

Adult↗

PubMed2004

Serous carcinoma of the ovary and peritoneum with metastases to the breast and axillary lymph nodes: a potential pitfall.

Metastasis of ovarian or peritoneal serous carcinoma to the breast and/or axillary lymph nodes is a rare event. Nevertheless, its recognition and distinction from mammary carcinoma are of great clinical importance because the treatment and prognosis differ significantly. Eighteen cases of ovarian or peritoneal serous carcinoma metastatic to the breast and/or axillary LNs from a 14-year period (1990-2003) were retrieved from our files. Clinical information was obtained from the patients' charts. The age of the patients ranged from 21 to 67 years (median, 55 years). The primary tumors included 14 ovarian serous carcinomas (11 high grade and 3 low grade; 2 of the low-grade tumors presented as serous tumors of low malignant potential and recurred as low-grade serous carcinoma) and 4 peritoneal serous carcinomas (3 high grade and 1 low grade). Of the ovarian neoplasms, 1 was stage I and 10 were stage III tumors; the breast and/or axillary lymph node metastases were discovered on average 30 months after presentation (range, 7-135 months). Three of the ovarian serous carcinomas were stage IV tumors; in 1 case, there were axillary lymph node metastases at initial presentation; and in 2 cases, breast and/or axillary lymph node metastases developed at 18 and 102 months. Two of the 4 patients with peritoneal serous carcinoma presented with stage IV disease, having synchronous breast and axillary lymph node metastases; the other 2 patients developed them at 11 and 16 months after presentation. Four patients had multiple breast lesions and 8 patients had a single metastasis. In 4 cases, the breast metastases were initially interpreted as infiltrating ductal carcinoma. The remaining 6 patients had axillary lymph node involvement only. The metastases in 17 of the cases had papillary features, with psammoma bodies present in 4. Immunoperoxidase studies for GCDFP-15 and WT-1 were performed in 4 cases; all 4 were positive for WT-1 and negative for GCDFP-15. Follow-up was available for 17 patients, with 7 patients known to be dead from disease (survival range, 2-31 months) after the development of metastatic disease to the breast or axillary lymph nodes. Ten patients were alive with disease at their last follow-up, which ranged from 1 to 30 months after the breast or axillary LN metastasis developed. Metastases to the breast or axillary lymph nodes from ovarian and/or peritoneal serous carcinomas are uncommon. Most of the patients in whom metastatic disease develops have a known history of advanced stage ovarian or peritoneal carcinoma. Breast and/or axillary LN involvement at initial presentation can occur but is rare. Differentiation between metastatic and primary tumors of the breast is of great importance because treatment and prognosis differ significantly. Clinical history, the presence of papillary architecture, and WT-1 expression are useful in establishing the correct diagnosis.

Adult↗

PubMed2004

Malignant melanoma involving the ovary: a clinicopathologic and immunohistochemical study of 23 cases.

Ovarian malignant melanoma (MM), primary or metastatic, is an extremely rare tumor and in the absence of a previous diagnosis can represent a diagnostic challenge. We present the clinicopathologic and immunohistochemical features of 23 cases seen in our institution over a period of 40 years (1962-2001). The patients' age ranged from 14 to 53 years (mean 35.7 years). Ethnicity was known in 19 patients: 14 white, 4 Hispanic, and 1 black. A previous history of MM was definitively obtained in 14 patients; in these cases, the interval between the primary MM and the ovarian metastasis ranged from 15 to 228 months (mean 77.7 months). The tumor was unilateral in 19 and bilateral in 4 cases. The tumor size ranged from 4.5 to 23 cm (average 10 cm); the melanoma arising in a cystic teratoma was 0.2 mm in thickness. The tumor was grossly pigmented in 8 cases (35%). The architectural pattern was nodular (8 cases), diffuse (6 cases), nodular and diffuse (5 cases), nested (3 cases), and lentiginous arising in a teratoma (1 case). Follicle-like spaces were seen in 8 cases, pseudo-glandular areas in 1 case, pseudo-myxoid areas in 1 case, and cords in 1 case. The tumor cell type was epithelioid in 19 cases, spindled in 2 cases, mixed epithelioid and spindled in 1 case, and small cell in 1 case. Nucleoli were prominent in 18 cases, and nuclear inclusions were present but rare in the majority of cases. Nuclear grooves were seen in 3 cases. Necrosis was extensive in 8 cases, focal in 10 cases, and was absent in 5 cases. In 8 cases, initial diagnoses included sex cord stromal tumor, germ cell tumor, sarcoma, or undifferentiated carcinoma. S-100 was positive in 18 of 19 cases, HMB-45 in 17 of 20 cases, MART-1 in 13 of 15 cases, tyrosinase in 10 of 15 cases, and Mitf in 8 of 14 cases. Inhibin was positive in 3 of 14 cases. Calretinin was focally positive in 1 of 12 cases. Treatment performed in 18 of the cases are as follows: oophorectomy with/without chemotherapy (10); total abdominal hysterectomy with bilateral salpingo-oophorectomy with/without chemotherapy (6); vaginal hysterectomy, bilateral salpingo-oophorectomy, and chemotherapy (1); and total abdominal hysterectomy with salpingo-oophorectomy (1). Follow-up ranging from 2 to 96 months was available in 18 patients. All but one had metastases in other organs, most often in the lungs. Thirteen patients died of disease (range 2-76 months), 3 are alive with disease (6-18 months), and 2 have no evidence of disease at 24 and 96 months; one was the patient with melanoma arising within a teratoma. In conclusion, MM involving the ovary is a rare disease, predominantly seen in women of reproductive age, and is associated with a poor prognosis. The tumor is most often metastatic from another site and is unilateral in most cases. Nodular or diffuse pattern and epithelioid cell type are most frequently seen, and the tumor can be mistaken for germ cell and sex cord stromal tumors. S-100 is the most sensitive marker. MART-1 was positive in the few cases that were negative with HMB-45. Inhibin can be focally positive in some cases.

Adolescent↗

PubMed2004

Serous carcinoma of the ovary, fallopian tube, or peritoneum presenting as lymphadenopathy.

The clinicopathologic features of 35 cases of serous carcinoma of the ovary, fallopian tube, or peritoneum presenting as lymphadenopathy are described. The cases were retrieved from the files of the Department of Pathology at the University of Texas M. D. Anderson Cancer Center from a 20-year period (1982-2002). The following parameters were evaluated: patient age at diagnosis, lymph node involved, primary tumor site, tumor histology, peritoneal disease status, and survival. The patients ranged in age from 30 to 85 years (mean, 59 years). The lymph nodes involved were inguinal, 20 cases; supraclavicular, 11 cases; axillary, 2 cases; cervical, 1 case; and retroperitoneal, 1 case. Primary tumor sites included 20 ovarian, 10 peritoneal, and 2 fallopian tube. In 2 patients, total abdominal hysterectomy/bilateral salpingo-oophorectomy and complete staging showed no additional tumor, and in 1 patient with a previous history of total abdominal hysterectomy/bilateral salpingo-oophorectomy for a benign condition, imaging studies did not identify a primary site. The carcinoma was high grade in 30 cases and low grade in 4 cases. In one case, the diagnosis was made on cytology material and the tumor could not be graded. Peritoneal disease status was known in 33 patients and was as follows: omentum with gross disease, 16 cases; and omentum without gross disease, 17 cases. Follow-up was available in 33 patients and ranged from 4 to 204 months, with a median survival of 36 months for stage III patients and 29 months for stage IV patients. Patients with adenopathy and minimal peritoneal disease (grossly negative omentum) had a median survival of 120 months compared with 24 months for those with bulky peritoneal disease (grossly positive omentum). Serous carcinoma of the ovary, fallopian tube, or peritoneum presenting as a lymph node metastasis is uncommon. In rare cases, a primary site may not be found. The median survival of the patients for stage is not appreciably different from those patients presenting in the usual fashion, suggesting that this atypical presentation does not adversely affect survival. Patients with minimal peritoneal disease and extra-abdominal lymph node metastases survive longer than those with bulky peritoneal disease

Adult↗