Elizabeth D. Euscher

Thyroid transcription factor-1 expression in endometrial and endocervical adenocarcinomas.

Thyroid transcription factor-1 (TTF-1) is widely used in the diagnosis of lung and thyroid carcinomas. Although there have been reports of TTF-1 immunoreactivity in tumors other than those originating in the lung or thyroid, endocervical and endometrial adenocarcinomas have not been studied in large numbers. Our study provides data regarding the incidence and distribution of TTF-1 expression in these tumors. Twenty-eight endocervical (9 well, 12 moderately, and 7 poorly differentiated), 32 endometrioid endometrial adenocarcinomas (11 grade I, 8 grade II, and 13 grade III), and 13 uterine serous carcinomas were retrieved and stained with TTF-1. None of the tumors had a neuroendocrine component. The hematoxylin and eosin and anti-TTF-1 antibody stained sections were reviewed, and the presence and distribution of TTF-1 nuclear positivity was recorded. A semiquantitative grading system used to evaluate the distribution of TTF-1 staining (0=negative, 1+=<5%, 2+=5% to 25%, 3+=26% to 50%, 4+=51% to 75%, and 5+=>75%). TTF-1 expression was seen in 1 of 28 (4%) of the endocervical adenocarcinomas and this was 4+ in distribution. The positive endocervical carcinoma was poorly differentiated. TTF-1 expression was present in 6 of 32 (19%) of the endometrioid adenocarcinomas (1 grade I, 2 grade II, and 3 grade III) and varied from 1+ to 4+ in distribution. Only 2 of 32 (6%) of the endometrioid adenocarcinomas stained diffusely (4+). There was no apparent correlation between the degree of differentiation and TTF-1 positivity in the adenocarcinomas. Three of 13 (23%) serous carcinomas were also positive (1 case 5+ and 2 cases 1+). Although TTF-1 is generally considered to be a relatively specific marker for lung and thyroid neoplasms, the occasional expression of endometrial and endocervical carcinomas should be kept in mind when evaluating neoplasms of uncertain origin. It should also be taken into consideration in the evaluation of adenocarcinomas involving the lung in patients with a history of a gynecologic malignancy.

Laparoscopic extraperitoneal para-aortic lymphadenectomy in locally advanced cervical cancer 1

Failure to detect metastasis to para‐aortic nodes in patients with locally advanced cervical cancer leads to suboptimal treatment. No previous studies have prospectively compared positron emission tomography (PET)/computed tomography (CT) with laparoscopic extraperitoneal staging in the evaluation of para‐aortic lymph nodes.BACKGROUND Failure to detect metastasis to para-aortic nodes in patients with locally advanced cervical cancer leads to suboptimal treatment. No previous studies have prospectively compared positron emission tomography (PET)/computed tomography (CT) with laparoscopic extraperitoneal staging in the evaluation of para-aortic lymph nodes. METHODS Sixty-five patients were enrolled; 60 were available for analysis. Patients with stage IB2-IVA cervical cancer without evidence of para-aortic lymphadenopathy on preoperative CT or magnetic resonance imaging (MRI) were prospectively enrolled. All patients underwent preoperative PET/CT. Laparoscopic extraperitoneal lymphadenectomy was performed from the common iliac vessels to the left renal vein. RESULTS The median age at diagnosis was 48 years (range, 23-84). The median operative time was 140 minutes (range, 89-252). The median blood loss was 22.5 mL (range, 5-150). The median length of hospital stay was 1 day (range, 0-4). The median number of lymph nodes retrieved was 11 (range, 1-39). Fourteen (23%) patients had histopathologically positive para-aortic nodes. Of the 26 patients with negative pelvic and para-aortic nodes on PET/CT, 3 (12%) had histopathologically positive para-aortic nodes. Of the 27 patients with positive pelvic but negative para-aortic nodes on PET/CT, 6 (22%) had histopathologically positive para-aortic nodes. The sensitivity and specificity of PET/CT in detecting positive para-aortic nodes when nodes were negative on CT or MRI were 36% and 96%, respectively. Eleven (18.3%) patients had a treatment modification based on surgical findings. CONCLUSIONS Laparoscopic extraperitoneal para-aortic lymphadenectomy is safe and feasible. Surgical staging of patients with locally advanced cervical cancer should be considered before planned radiation and chemotherapy.

Thyroid transcription factor-1 expression in ovarian epithelial neoplasms

Thyroid transcription factor-1 (TTF-1) protein expression is widely used in the diagnosis of lung and thyroid carcinomas. Although there have been reports of TTF-1 immunoreactivity in tumors other than those originating in the lung or the thyroid, the expression of this marker has been studied in only a limited number of ovarian neoplasms. Our study examines the incidence of TTF-1 expression in a variety of ovarian epithelial neoplasms. Tissue microarrays of 138 ovarian serous carcinomas, 65 endometrioid adenocarcinomas, 35 mucinous adenocarcinomas, 30 mucinous neoplasms of low malignant potential, and 10 clear cell carcinomas were stained with anti-TTF1-antibody. In addition, whole tissue sections of 19 serous carcinomas, 5 endometrioid adenocarcinomas, 7 mucinous adenocarcinomas, and 3 clear cell carcinomas were stained. In the tissue microarrays, TTF-1 nuclear expression was demonstrated in 2 of 65 (3%) of the endometrioid adenocarcinomas; no nuclear immunoreactivity was identified in the remaining ovarian neoplasms. In the whole tissue sections, TTF-1 nuclear staining was present in 7 of 19 (37%) serous carcinomas, 1 of 5 (20%) endometrioid adenocarcinomas, and 1 of 3 (33%) clear cell carcinomas. In most of the positive cases, staining was focal, but in one endometrioid adenocarcinoma in the tissue microarray and in one serous and one clear cell carcinoma in the whole tissue sections, there was diffuse positivity. Overall, there was nuclear staining in 0.7% of tumors in the tissue microarray and 26% in the whole tissue sections. Although TTF-1 nuclear expression is generally considered to be a relatively specific marker for lung and thyroid neoplasms, the occasional immunoreactivity of ovarian carcinomas should be considered in the evaluation of neoplasms of unknown primary origin. It should also be taken into consideration when evaluating adenocarcinomas involving the lung in patients with a history of a gynecologic malignancy.

Laparoscopic extraperitoneal para-aortic lymphadenectomy in locally advanced cervical cancer: a prospective correlation of surgical findings with positron emission tomography/computed tomography findings.

Failure to detect metastasis to para‐aortic nodes in patients with locally advanced cervical cancer leads to suboptimal treatment. No previous studies have prospectively compared positron emission tomography (PET)/computed tomography (CT) with laparoscopic extraperitoneal staging in the evaluation of para‐aortic lymph nodes.BACKGROUND Failure to detect metastasis to para-aortic nodes in patients with locally advanced cervical cancer leads to suboptimal treatment. No previous studies have prospectively compared positron emission tomography (PET)/computed tomography (CT) with laparoscopic extraperitoneal staging in the evaluation of para-aortic lymph nodes. METHODS Sixty-five patients were enrolled; 60 were available for analysis. Patients with stage IB2-IVA cervical cancer without evidence of para-aortic lymphadenopathy on preoperative CT or magnetic resonance imaging (MRI) were prospectively enrolled. All patients underwent preoperative PET/CT. Laparoscopic extraperitoneal lymphadenectomy was performed from the common iliac vessels to the left renal vein. RESULTS The median age at diagnosis was 48 years (range, 23-84). The median operative time was 140 minutes (range, 89-252). The median blood loss was 22.5 mL (range, 5-150). The median length of hospital stay was 1 day (range, 0-4). The median number of lymph nodes retrieved was 11 (range, 1-39). Fourteen (23%) patients had histopathologically positive para-aortic nodes. Of the 26 patients with negative pelvic and para-aortic nodes on PET/CT, 3 (12%) had histopathologically positive para-aortic nodes. Of the 27 patients with positive pelvic but negative para-aortic nodes on PET/CT, 6 (22%) had histopathologically positive para-aortic nodes. The sensitivity and specificity of PET/CT in detecting positive para-aortic nodes when nodes were negative on CT or MRI were 36% and 96%, respectively. Eleven (18.3%) patients had a treatment modification based on surgical findings. CONCLUSIONS Laparoscopic extraperitoneal para-aortic lymphadenectomy is safe and feasible. Surgical staging of patients with locally advanced cervical cancer should be considered before planned radiation and chemotherapy.

Lymphatic mapping and sentinel lymph node detection in women with vaginal cancer

OBJECTIVE To determine the patterns of lymphatic drainage from primary vaginal cancers utilizing lymphoscintigraphy and to determine if this clinical information would affect treatment planning. METHODS For women with newly diagnosed vaginal cancer, pretreatment lymphatic mapping and sentinel lymph node identification were performed using lymphoscintigraphy. In patients who underwent surgery, sentinel lymph nodes were identified intraoperatively using radiocolloid and patent blue dye. The impact of pretreatment lymphoscintigraphy findings on radiation planning in women who received radiation as initial treatment was noted. RESULTS Fourteen women were enrolled during the study period. At least 1 sentinel lymph node was identified on pretreatment lymphoscintigraphy in 11 patients (79%). The median number of sentinel nodes found per patient was 2, and bilateral sentinel nodes were found in 6 (55%) of the 11 patients with sentinel nodes identified. Among these 11 patients, 5 (45%) had sentinel nodes identified in the groin only, 4 (36%) had sentinel nodes identified in the pelvis only, and 2 (18%) had sentinel nodes identified in both the groin and the pelvis. No relationship was observed between sentinel lymph node location and primary tumor histologic subtype or location. Three (33%) of the 9 women treated initially with radiation therapy had their radiation field altered as a result of the lymphoscintigraphy findings. CONCLUSION In women with vaginal cancer, lymphatic drainage from the primary lesion does not always follow the lymphatic channels that would have been predicted anatomically. The addition of lymphoscintigraphy to the pretreatment evaluation for women with vaginal cancer may significantly improve comprehensive treatment planning.

Uterine tumors with neuroectodermal differentiation: A series of 17 cases and review of the literature

Uterine tumors with neuroectodermal differentiation, frequently referred to as primitive neuroectodermal tumors (PNETs), are uncommon. The clinicopathologic features of 17 such cases reviewed at the M.D. Anderson Cancer Center (MDACC) are presented along with a review of the literature. All of the pathology material was reviewed at MDACC, and in all cases, immunohistochemistry contributed to the diagnosis. In 12 cases, in situ hybridization techniques were used to determine whether a rearrangement of the EWSR1 gene, required for a diagnosis of peripheral PNET, was present. Clinical information was obtained from a patient chart review. Ages ranged from 31 to 81 years (median 58). Clinical presentations included vaginal bleeding (9), back pain (1), presumed fibroids (2), pelvic mass (1), incidental finding at hysterectomy (1), and unknown (3). Twelve patients had surgery or imaging to determine stage: I (2), II (0), III (6), and IV (4). Five patients had biopsy only. Ten tumors had only neuroectodermal components. In 7 tumors, the neuroectodermal component was admixed with an additional component including unclassified sarcoma (2 cases), rhabdomyosarcoma, endometrioid carcinoma, adenosarcoma and malignant mixed Mullerian tumor (2 cases). Follow-up, available for 13 patients, ranged from 2 to 41 months with 7 patients dead of disease 2 to 26 months after diagnosis. Six patients are alive with no evidence of disease after follow-up ranging from 6 to 41 months. Four patients were lost to follow-up. Results for the most commonly used immunohistochemistry studies include cytokeratin, 13/15 tumors negative (2 focally positive); synaptophysin, 15/16 tumors positive; neurofilament, 10/11 tumors positive; and CD99, 7/9 tumors positive (2 tumors had nonspecific cytoplasmic staining). None of the 12 tumors tested had a detectable rearrangement in the EWSR1 gene. Uterine tumors with neuroectodermal differentiation, similar to more common endometrial malignancies, tend to occur in postmenopausal women and frequently present with vaginal bleeding. An immunohistochemistry panel including cytokeratin, neurofilament, synaptophysin, and CD99 can highlight neuroectodermal differentiation and identify tumors for which molecular testing should be considered. Tumors without a rearrangement of the EWSR1 gene should be descriptively characterized as uterine tumors with neuroectodermal differentiation or alternatively central type PNETs rather than PNET, not otherwise specified to avoid confusion with peripheral PNET.

Ultrastaging improves detection of metastases in sentinel lymph nodes of uterine cervix squamous cell carcinoma.

The technique of sentinel lymph node (SLN) detection is increasingly being applied in patients with uterine cervix carcinoma. This study presents the pathologic findings of SLNs in 48 such patients. The institutional pathology files were searched for all patients with a diagnosis of cervical squamous cell carcinoma who had SLNs reported. Patient age, follow-up, tumor size, presence/absence of lymphatic invasion, number and status of SLNs and non-SLNs, location of SLNs, and size of metastases in SLNs were recorded. All SLNs were sectioned in 2-mm slices perpendicular to the long axis and submitted entirely for microscopic examination. For all SLNs negative on the initial hematoxylin and eosin (H&E) stained slides, an ultrastaging protocol was performed consisting of 5 sets of slides at 40-μm intervals (1 H&E slide+2 unstained slides), representing an additional 5 intervals. Lymph nodes negative by the additional H&E intervals had immunohistochemistry for cytokeratin performed on 1 unstained slide. Forty-eight patients ranging from 25 to 62 years of age had a total of 208 SLNs removed. Fifteen (31%) patients had positive SLNs with 1 to 5 positive SLNs per case. The metastasis size ranged from a single cell to 27 mm. Twelve patients had metastasis detected by routine processing in 23 SLNs, whereas ultrastaging detected metastases in 3 SLNs of 3 additional patients. In 2 patients with metastasis detected by ultrastaging, the metastasis was detected by wide H&E intervals (level 2 for 1 patient; level 3 for 1 patient); in 1 patient, the metastasis was detected only by immunohistochemistry and consisted of a single cell. Of the 15 patients with positive SLNs, 3 patients had a total of 6 positive non-SLNs. All of the patients with a positive SLN are currently living. Thirty-three (69%) patients had negative SLNs. Of these, 1 patient had a single positive non-SLN for a false negative rate of 6.25%. Negative SLN predicts negative non-SLN. For most patients with a positive SLN, the SLN will be the only metastasis detected; a minority of patients with a positive SLN may have a positive non-SLN.

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

Cyclic sciatica from extrapelvic endometriosis affecting the sciatic nerve. Case report

Sciatic (catamenial) radiculopathy, waxing and waning with the menstrual cycle, is an uncommon condition typically caused by pelvic endometriosis affecting the lumbosacral plexus or proximal sciatic nerve. The authors describe a woman with catamenial sciatica caused by endometriosis affecting the sciatic nerve trunk in the upper thigh. Symptomatic with leg pain for 5 years, this patient developed gluteal atrophy and sensory loss and decreased strength in the L-5 dermatomyotome, a distribution confirmed by electromyography. Magnetic resonance imaging suggested thickening of the sciatic nerve at and distal to the sciatic notch. At operation the nerve showed extrinsic and intrinsic abnormality, proven to be endometriosis. Her symptoms improved, and she began gonadotropin-releasing hormone agonist therapy for further suppression. This very unusual case shows that endometriosis can affect the sciatic nerve over a range of territory inside and outside the pelvis, and that surgery must be appropriately directed to avoid negative exploration. Surgical decompression achieves good relief of symptoms, and medical therapy also allows sustained suppression of this disease.

A phase II trial of paclitaxel and carboplatin in women with advanced or recurrent uterine carcinosarcoma

Background Systemic therapy for advanced uterine carcinosarcoma (CS) has been disappointing. The most widely studied regimen is ifosfamide and cisplatinum. Moderate success has been documented using paclitaxel in ovarian CS. The purpose of this study was to evaluate carboplatin/paclitaxel in advanced and recurrent uterine CS. Methods A single-arm, prospective, phase II trial opened in October 2001. Primary end points were time to progression (TTP) and response rate (RR). Quality-of-life data were obtained. Patients treated adjuvantly received 6 cycles of carboplatin/paclitaxel every 21 days. Patients with disease at study entry were treated until response, progression, or toxicity. Results Of 23 patients enrolled, 9 received adjuvant treatment, 13 had documented disease, 1 was inevaluable. Eight of 13 patients with measurable disease had a complete or partial response (62% RR). Overall, median TTP was 9.5 months. In the adjuvant group, median TTP was 15 months. With measurable disease, median TTP was 7.9 months. Median overall survival was 21.1 months. There was no difference in survival between patients with or without measurable disease. For patients having prior radiation, median TTP with recurrence in the radiated field was 13.3 months, and 14.5 months if outside the field (P = 0.71). Two patients (9%) had treatment-limiting toxicity. Quality-of-life scores improved from baseline over time. Conclusions Carboplatin and paclitaxel have improved tolerability and RR (62%) compared with previous reports of ifosfamide/cisplatin or ifosfamide/paclitaxel in treating uterine CS. This regimen seems promising and should be considered in combined therapies with targeted agents.