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ABSTRACT: The objective of this study was to evaluate the impact of a weekly tumor board conference on the management of patients with gynecologic malignancies.
The medical records of consecutive patients referred to a multidisciplinary gynecologic oncology tumor board were reviewed. Patient demographics were abstracted from medical records and tumor board minutes. An evaluation was made whether the pathological or radiological findings were changed by the tumor board consultants. If a discrepancy existed, it was determined whether the change impacted clinical management.
From January 2004 to December 2006, 741 patients presented at the tumor board were evaluable. Seventy-one percent of the patients were presented for pathology review and 29% for radiology review. The most common diagnoses were ovarian cancer (29%), endometrial cancer (26%), and cervical cancer (12%). Of the 526 pathology reviews, 27% had a change in diagnosis; this discrepancy altered clinical management 74% of the time (20% of all reviews). Of the 215 radiology presentations, 89% were reviewed to confirm recurrent or persistent disease; malignant disease was confirmed 74% of the time. Review of imaging studies resulted in a new diagnosis or upstaging 10% of the time.
A multidisciplinary tumor board allows a wide range of gynecologic diagnoses and clinical scenarios to be discussed. Careful review of pathology results in a change in the clinical management of 20% of patients presented at the tumor board. The majority of radiology reviews are presented to confirm persistent or recurrent cancer before recommending further therapy.
International Journal of Gynecological Cancer 11/2010; 20(8):1321-5. · 1.65 Impact Factor
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ABSTRACT: Uterine endometrioid adenocarcinoma is the most common invasive tumor of the female genital tract in the United States. Tumor invading into myometrium frequently induces juxtatumoral stromal changes resulting in a desmoplastic reaction or host inflammatory response. However, the relationship between stromal reactions and tumor progression in these tumors has not been well established. We thus examined a total of 103 consecutive cases of invasive uterine endometrioid adenocarcinoma in an attempt to determine if an association exists between the stromal reactions and other well-defined histologic and clinical prognostic factors. We found that the presence of a desmoplastic reaction was associated with a higher International Federation of Gynecology and Obstetrics (FIGO) grade (P<0.01) and lymphovascular invasion (LVI) (P<0.05), and advanced FIGO stage (stage IB vs. IC, P<0.01; stage I vs. II/III/IV, P<0.05). The intensity of the inflammatory lymphocytic response (none/mild vs. moderate/severe) was inversely associated with advanced tumor stage (P<0.05), but not associated with tumor grade or LVI. Our findings revealed that a strong lymphocytic stromal response was predominantly found in the uterine endometrioid adenocarcinomas with early clinical stages. In contrast, a juxtatumoral desmoplastic reaction was more frequently identified in moderately to poorly differentiated tumors with LVI and advanced clinical stages. Multivariate analysis showed that a desmoplastic reaction, LVI, and advanced FIGO stage were significantly associated with unfavorable outcome. The presence of a desmoplastic reaction in the stroma should prompt the pathologist to search for other histologically unfavorable prognostic indicators such as cervical involvement and nodal metastasis. This is even more important in those cases where no staging procedure was performed and in cases where the tumor was an incidental finding.
International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 09/2010; 29(6):562-7. · 2.07 Impact Factor
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ABSTRACT: Evaluation of anal intraepithelial neoplasia (AIN) is subjective. Previous studies have shown p16 and Ki-67 expressions to correlate with AIN grade. Biomarkers like p16 and Ki-67 may improve interobserver agreement. The objectives were (1) to determine the extent of interobserver agreement in evaluating AIN on routine hematoxylin and eosin (H&E) sections and (2) to test whether p16 and/or Ki-67 staining improve interobserver diagnostic agreement.
Seventy-seven anal specimens were retrieved. Sections were stained with monoclonal antibodies against p16 and Ki-67. Blind to the original diagnoses, 4 pathologists assessed H&E alone, p16 alone, Ki-67 alone, and all 3 simultaneously. Diagnoses were normal/reactive, AIN I/HPV, AIN II, and AIN III. Agreement was calculated using kappa and S statistics.
Pathologists were board certified and had 2 to 25 years (mean = 13.6 years) of experience. Fair agreement was observed using H&E diagnosis alone (kappa = 0.38, S = 0.56). The p16 diagnostic evaluation demonstrated the highest agreement (kappa = 0.57, S = 0.73). Interobserver agreement for Ki-67 alone and for H&E/p16/Ki-67 combined were comparable to that of H&E alone (kappa = 0.4, S = 0.54 and kappa = 0.44, S = 0.62, respectively). When the pathologists' diagnoses for all diagnostic evaluations were compared with consensus diagnoses, the lowest average magnitude of disagreement was seen with Ki-67 alone, followed by p16 alone, H&E/p16/Ki-67 combined, and H&E alone.
Interobserver agreement for diagnosis of AIN was fair when based solely on H&E preparation. p16 alone improved interobserver agreement and demonstrated superior agreement when compared with H&E, Ki-67, and H&E/p16/Ki-67 combined.
Journal of Lower Genital Tract Disease 07/2009; 13(3):145-53. · 1.07 Impact Factor
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ABSTRACT: This study aimed at evaluating the expression of tyrosine kinase receptors c-kit, (platelet-derived growth factor receptor-alpha (PDGFR-alpha), and PDGFR-beta in ovarian granulosa cell tumors (GCTs).
Primary ovarian GCT specimens were obtained for immunohistochemical staining.The expressions of c-kit, PDGFR-alpha, and PDGFR-beta were analyzed and scored by a semiquantitative (SQ) method. Normal ovarian tissue from the same patients' specimens served as internal controls.
A total of 21 specimens were available for evaluation. C-kit was expressed in only 2 samples, whereas both PDGFR-alpha and PDGFR-beta stained positive in 100% of tumors. PDGFR targets demonstrated strong positive expression in intensity and amount of tissue stained. Normal ovarian tissue demonstrated complete absence of staining for all 3 antibodies evaluated.
The data demonstrated significant expression of PDGFR targets of imatinib mesylate in GCTs, whereas normal ovarian tissues had a complete absence of staining.This expression profile provides the rationale to investigate the role of imatinib mesylate in PDGFR-positive GCTs.
Reproductive sciences (Thousand Oaks, Calif.) 06/2008; 15(7):673-7. · 2.31 Impact Factor
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ABSTRACT: To estimate the frequency of mismatch repair deficiencies associated with hereditary nonpolyposis colorectal cancer, or Lynch syndrome, in women less than age 50 with endometrial cancer.
Consecutive patients less than age 50 diagnosed with endometrial adenocarcinoma were identified. Available pathologic specimens were freshly sliced, and protein expression for MLH1, MSH2, MSH6, and PMS2 was evaluated by immunohistochemistry. Slides were scored on a semiquantitative method with complete absence of any of the four proteins suggesting a deficiency. All results were confirmed by microsatellite instability testing.
Sixty-one pathology specimens were analyzed. Twenty-one (34%) of the tumors had absence of staining of at least one of the four mismatch repair proteins determined by immunohistochemistry and confirmed by microsatellite instability testing. Obese patients were less likely than nonobese patients to have a mismatch repair deficiency (21% versus 59%, respectively). Non-obese patients had a relative risk for a mismatch repair deficiency of 5.5 (95% confidence interval 1.6-19.1; P=.01).
Many women diagnosed with endometrial cancer before age 50 will have a mismatch repair deficiency discovered by immunohistochemistry and microsatellite instability testing. A number of young women diagnosed with endometrial cancer will require further genetic testing for mismatch repair mutations.
III.
Obstetrics and Gynecology 06/2008; 111(5):1161-6. · 4.73 Impact Factor
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ABSTRACT: Umbilical endometriosis is rare and can be a challenging diagnosis in the absence of classic signs and symptoms.
A case of severe, primary, spontaneous umbilical endometriosis with foci of plasma cell endometritis and diffuse stromal lymphovascular presence occurred.
Despite a lengthy differential, endometriosis must be considered in the evaluation of an umbilical mass. The presence of plasma cell endometritis and stromal lymphovascular elements in the absence of pelvic endometriosis lends evidence to the theory of lymphovascular transport as an etiology of extrapelvic endometriosis.
The Journal of reproductive medicine 02/2008; 53(1):49-51. · 0.87 Impact Factor
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ABSTRACT: Clear cell adenocarcinoma (CCA) of the vagina is traditionally treated with radical surgical resection with tailored postoperative radiation when indicated. Due to a bimodal distribution, women of reproductive age are frequently affected and could benefit from radical trachelectomy to preserve fertility.
A 22 year old female was diagnosed with clinical stage I vaginal clear cell adenocarcinoma in the left fornix abutting the cervix. The patient desired future fertility; therefore, she underwent radical abdominal trachelectomy and upper vaginectomy. Twenty-eight months after initial surgery, she has no evidence of recurrence with regular menstrual cycles.
For patients with CCA of the upper vagina, where removal of the cervix is necessary, a radical trachelectomy with upper vaginectomy should be considered to conserve fertility.
Gynecologic Oncology 06/2007; 105(3):820-2. · 3.89 Impact Factor
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ABSTRACT: In this report, we present the case of a 32-year-old woman with Wegener's granulomatosis of the uterine cervix, review the literature, and discuss the differential diagnosis.
International Journal of Gynecological Pathology 02/2007; 26(1):95-8. · 1.45 Impact Factor
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ABSTRACT: A pilot study to determine genomic microarray differences in patients with normal cervical tissue and cervical intraepithelial neoplasia (CIN) 3.
After institutional review board approval, patients referred to the University of Alabama at Birmingham Colposcopy Clinic for a loop electrosurgical excisional procedure were identified. Tissue biopsies of both normal tissue and CIN 3 from fresh loop electrosurgical excisional procedure specimens were obtained and sent to pathology for histological confirmation. Procurement of these 2 types of tissue from the same patient controls for different types of human papillomavirus infection, smoking and nutritional status, age, immunocompetency, and other microenvironment factors (i.e., the patient serves as their own control). Standard RNA extraction techniques (Qiagen, Inc., Valencia, CA) were used to prepare the tissue specimens for microarray analysis with the Affymetrix GeneChip U133A expression array (Affymetrix, Inc., Santa Clara, CA). Paired samples were eligible for microarray analysis only when both normal tissue and CIN 3 were confirmed by pathology. The data were then subsequently subjected to a log-like transformation and analyzed with a t test. For this study, p<.001 was determined to be statistically significant.
Twenty-one pairs of both normal and CIN tissues were obtained and underwent histological evaluation followed by RNA extraction. Within the normal group, 86% were confirmed as true normals and 14% as CIN. Within the CIN group, 28.5% were found to have CIN 2, 62% were found to have CIN 3, and 9.5% had no evidence of CIN. Mean RNA content of normal samples was 2.0 microg, whereas the mean RNA content of CIN samples was significantly higher at 7.4 microg (p=006). Ultimately, 5 pairs of normal and neoplastic tissues were subjected to microarray analysis. Using a cutoff of p<.001, 24 candidate genes were identified from more than 18,000 genes. In the CIN 3 group, 14 genes were overexpressed and 10 genes were underexpressed. Of the 14 overexpressed genes, 9 were noted to have identities listed in the National Center for Biotechnology Information public domain. Five (56%) of these 9 genes were directly related to immunity-related pathways, and 3 (33%) of the 9 genes were found to be involved in cell cycle function/control. One overexpressed gene was identified as p53.
The presence of CIN is marked by increased transcriptional activity, evident by an almost 4-fold increase in mean RNA content obtained from our CIN samples versus normal cervical tissue. Furthermore, a number of statistically significant overexpressed genes of interest related to immune function/response and cell cycle control were identified in our pilot microarray study. This data have the ability to direct future research endeavors in cervical neoplasia. Future endeavors include the use of laser capture microdissection to evaluate genomic changes strictly at the epithelial level and, as such, exclude stromal response contributions.
Journal of Lower Genital Tract Disease 02/2007; 11(1):25-8. · 1.07 Impact Factor
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ABSTRACT: Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease (GTD) that is generally resistant to conventional chemotherapeutic treatment. Patients with localized disease are usually managed with hysterectomy.
A 29-year-old female presented with vaginal bleeding and an elevated serum human chorionic gonadotropin (HCG). After initial observation, the patient experienced continued vaginal bleeding and a persistently elevated HCG. Therefore, she underwent a dilation and curettage and final pathology revealed PSTT. Since the patient desired future fertility, the patient received combination chemotherapy with etoposide, methotrexate, actinomycin-D followed by etoposide and cisplatin (EMA-EP). The patient had a complete response to chemotherapy and subsequently delivered a term infant 2 years after completion of therapy.
PSTT is thought to be a chemoresistant disease and the preferred method of treatment is hysterectomy or local uterine resection. However, combination chemotherapy is a reasonable option in a properly counseled patient who strongly desires future fertility.
Gynecologic Oncology 01/2007; 103(3):1141-3. · 3.89 Impact Factor
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ABSTRACT: This study was undertaken to determine whether asymptomatic bacterial vaginosis (BV) is associated with an increased risk of endometrial microbial colonization or plasma cell endometritis in nonpregnant women.
In this observational cohort study conducted between August 1995 and August 2001, microbial cultures (n = 769) and histopathology (n = 482) were performed on endometrial specimens obtained from women with a recent preterm or term delivery (83 +/- 16 days). Endometritis was defined as the presence of plasma cells. BV was defined using Amsel and Nugent criteria.
The study population was 71% black, 29% white, 69% single, and 31% had 12 years or more of education. Endometrial cultures were positive for at least 1 microorganism in 83% (n = 637/769) of the women and plasma cell endometritis was present in 39% (n = 190/482). BV was present in 26% (n = 191/722) by Amsel and 38% (n = 289/769) by Nugent criteria. Women with Nugent-BV (RR [relative risk] = 1.12, 95% CI 1.05-1.19) but not Amsel-BV (RR = 1.06, 95% CI 1.00-1.13) were significantly more likely to have a positive endometrial culture. A consistent and significant association was observed between BV (by Amsel or Nugent criteria) and an increased frequency of endometrial colonization with BV-associated microorganisms grouped and defined in various ways (RR ranged from 1.96-4.22). No association between BV and plasma cell endometritis was observed.
Asymptomatic BV is associated with a modest increased likelihood of endometrial microbial colonization and colonization by BV-associated bacteria but is not associated with plasma cell endometritis in nonpregnant women.
American journal of obstetrics and gynecology 01/2007; 195(6):1611-6. · 3.28 Impact Factor
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ABSTRACT: Although uterine anomalies are uncommon, gynecologists must be aware of the anatomical challenges that may be encountered from these anomalies. Cervical cancer in the context of a mullerian lateral fusion defect is rare.
A case of a unilateral IB1 squamous cell carcinoma of the cervix in the setting of a complete uterovaginal septum and cervix duplex is described.
Uterine anomalies compound diagnostic difficulty of routine pathology. Thorough examination and evaluation are crucial for timely diagnosis and treatment. Genital tract duplication, although rare, should always be considered.
Gynecologic Oncology 11/2006; 103(1):346-8. · 3.89 Impact Factor
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ABSTRACT: Inflammatory pseudotumor is a rare benign cause of lymphadenopathy previously reported in several anatomic locations that can simulate malignant neoplasm.
A postmenopausal woman presented with abdominal pain, generalized malaise, leukocytosis, and intermittent fevers up to 102 degrees F. A 5-day course of antibiotics was given with persistence of symptoms. Computed tomography of the abdomen and pelvis demonstrated an ill-defined, retroperitoneal soft-tissue density, and lymphadenopathy. She underwent an exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, and unilateral pelvic and paraaortic lymphadenotomy. Histologic examination revealed inflammatory pseudotumor of the lymph nodes, with immunohistochemical studies demonstrating actin-positive myofibroblastic cells. Four months after surgery, the patient remains asymptomatic without evidence of disease.
Inflammatory pseudotumor of the pelvic lymph nodes is a rare entity and should be included in the differential diagnosis of patients with persistent fever and lymphadenopathy.
Obstetrics and Gynecology 10/2006; 108(3 Pt 2):779-82. · 4.73 Impact Factor
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ABSTRACT: Basosquamous cell carcinoma (BSC) of the vulva is a rare entity with interesting prognostic and therapeutic implications. Currently, there is no definitive treatment due to its low incidence.
A case of recurrent BSC of the vulva treated with unilateral radical vulvectomy and unilateral lymph node dissection is reported.
BSC is a rare disorder of the vulva. The metastatic potential of this tumor is not fully understood, but likely is intermediate between squamous cell carcinoma and basal cell carcinoma. Local recurrence is common and close follow-up is warranted.
Gynecologic Oncology 09/2006; 102(2):400-2. · 3.89 Impact Factor
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Archives of pathology & laboratory medicine 02/2006; 130(1):e5-7. · 2.58 Impact Factor
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ABSTRACT: Although mature cystic teratoma is the most common tumor of the ovary, squamous cell carcinoma arising from a mature teratoma is a rare event. Prognosis depends on clinical stage, grade, and recently described mode of tumor infiltration.
This case involves a 52-year-old woman with stage II squamous cell carcinoma arising in a mature cystic teratoma of the left ovary. Final pathology demonstrated poorly differentiated squamous cell carcinoma with gamma mode of tumor infiltration. The patient completed adjuvant chemotherapy and subsequently died of progressive disease.
Squamous cell carcinoma arising from a benign cystic teratoma is a rare event. Studies have shown stage, grade, and mode of infiltration to be predictors of recurrence and prognosis. This case supports the growing evidence linking the mode of tumor infiltration with overall prognosis of survival.
Gynecologic Oncology 08/2005; 98(1):155-7. · 3.89 Impact Factor
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ABSTRACT: Positron emission tomography (PET) is commonly used to detect occult or recurrent malignancy, including tumors of the female genital tract. Recently, there have been reports of PET scans used in patients with Gestational Trophoblastic Disease (GTD).
A 22-year-old female presented with vaginal bleeding and elevated beta-hCG 7 months after a spontaneous vaginal delivery of a healthy infant. She had a history of molar pregnancy and persistent GTD requiring multi-agent chemotherapy. Metastatic evaluation with computed tomography and magnetic resonance imaging showed no evidence of GTD. A positron emission tomography/computed tomography (PET/CT) scan revealed a focus of metabolic activity in the left pelvis. The patient underwent an exploratory laparotomy that revealed metastatic choriocarcinoma in the left broad ligament.
PET/CT may be useful in the evaluation of occult choriocarcinoma when conventional imaging fails to identify metastatic disease.
Gynecologic Oncology 06/2005; 97(2):713-5. · 3.89 Impact Factor
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ABSTRACT: Alveolar rhabdomyosarcoma is an uncommon malignant soft tissue tumor rarely found in the genital tract. This tumor is associated with a poor prognosis, especially in the adult population. Equally as rare are non-puerperal uterine inversions secondary to sarcomas.
A 21-year-old obese woman was initially evaluated with excessive vaginal bleeding. On exam, a large pedunculated mass protruding from the cervix was seen and biopsy of this mass revealed an alveolar rhabdomyosarcoma. The patient was treated with adjuvant chemotherapy consisting of VAC (Vincristine, Actinomycin, and Cyclophosphamide) for a presumed cervical rhabdomyosarcoma. After five cycles of chemotherapy the patient underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy, at which time a complete uterine inversion was noted with the tumor located at the fundus of the uterus. Final pathology showed alveolar rhabdomyosarcoma of the uterus. The patient then received additional postoperative VAC regimen for a total of 10 treatments and remains in good health with no evidence of disease 20 months from diagnosis.
This case report describes the only reported case of uterine inversion secondary to alveolar rhabdomyosarcoma of the uterus and discusses current therapeutic options for adults.
Gynecologic Oncology 04/2005; 96(3):850-3. · 3.89 Impact Factor
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Michael G Conner
Advances in experimental medicine and biology 02/2005; 563:10-20. · 1.09 Impact Factor
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ABSTRACT: Metastatic cancer to the vulva is a rare diagnosis and is estimated to account for 5-8% of all vulvar cancers.
A 57-year-old postmenopausal woman was referred for the evaluation of a new vulvar mass. CT scan of the pelvis demonstrated a 4 x 6 cm lobular mass of the left labia. An outpatient excisional biopsy revealed a poorly differentiated large cell carcinoma with prominent necrosis and focal perineural invasion consistent with a bronchogenic carcinoma. A subsequent PET scan of the chest revealed a large primary lung carcinoma confirmed by CT-guided biopsy that was identical to the vulvar tumor.
This case represents the only literature described primary lung carcinoma presenting as a vulvar metastasis.
Gynecologic Oncology 10/2004; 94(3):829-31. · 3.89 Impact Factor
