Vascular Space Involvement Research Articles

Presurgical Assessment and Therapy of Microinvasive Carcinoma of the Cervix

Retrievable pathological specimens and clinical data on 70 patients with microinvasive carcinoma diagnosed on surgical specimens from cone biopsy or hysterectomy (Stage IA) were reviewed and compared to pertinent findings in the literature with the intent of evaluating diagnostic criteria and defining pathological features that may influence the outcome by therapy. Emphasis was given to the preoperative assessment emphasizing that both an accurate colposcopic evaluation and a detailed pathological analysis may reliably point to a conservative therapeutic approach. Increasing depth of stromal invasion was associated with lesion width as well as with endocervical extension, as measured on colposcopy, microcolpohisteroscopy, and histology. Lymph-vascular space involvement was significantly related to depth of invasion. Two patients of 28 with dissected nodes had node metastases as well as lymph-vascular space involvement. Both developed a pelvic recurrence. One had a > 1- to < or = 3-mm invasion depth, the other a > 3- to < or = 5-mm lesion invasion. While advocating a conservative procedure for Stage IA1, we suggest discrimination with regard to Stage IA2 because we believe that lymph-vascular involvement should be meticulously evaluated. In fact, > 1- to < or = 3-mm lesions without lymph-vascular space involvement can be conservatively treated, while for any other lesion falling within the Stage IA2 category a modified radical histerectomy plus pelvic lymphadenectomy should be recommended.

Nodal immune reactivity in FIGO (International Federation of Gyn-Ob) Stage I endometrial carcinoma: relationship with myometrial invasion.

To evaluate T lymphocyte subsets in pelvic and paraortic lymph nodes, in patients with FIGO stage I endometrial carcinoma at different degrees of myometrial invasion and with lymphovascular space invasion. The aim was to define an eventual modulation of regional immune reactivity useful in the therapeutic approach of the disease. Twenty-two women with FIGO stage I endometroid adenocarcinoma were consecutively recruited and selected for immunological study. All the patients underwent primary surgery characterized by radical hysterectomy (Piver's type III) with bilateral salpingo-oophorectomy and systematic pelvic plus paraaortic lymphadenectomy. Lymphocyte tipization was performed by Beckton Dickinson monoclonal antibodies (CD4, CD8, CD56 and CD16) immunohistochemically in frozen-sections (immune assay on lymph nodes). For statistical evaluations. Student's t test and one way analysis of variance were used. Significantly higher percentages of CD4+ lymphocytes were found in pelvic than in paraaortic lymph nodes; however, by analyzing T lymphocyte content in the different pelvic nodal groups, we also observed significantly higher percentages of CD16+ and CD56+ cells in obturator nodes when compared to iliac stations. A significant increase of CD16+ and CD56+ cell percentages was then defined with respect to myometrial involvement and lymphovascular space invasion, in pelvic nodes. From our results, we could not define any clinical importance of nodal lymphocyte distribution in patients with early stage endometrial carcinoma; however, the observed nodal immune reactivity in presence of myometrial invasion seems interesting, with or without lymph vascular space involvement as possible expression of neoplastic systemic diffusion.

Cervical carcinoma with glandular differentiation: Histological evaluation predicts disease recurrence in clinical stage I or II patients

Pathologists confront questions concerning the clinical implications of the more complex, evolving histopathologic classification in cervical carcinoma with glandular differentiation (CCGD) and the associated precursor intraepithelial lesions. Pseudoneoplastic pitfalls, such as microglandular hyperplasia, constitute the subject of recent reports, but the extent of misinterpretation for CCGD is unknown. To address these issues, we retrospectively reviewed all the histopathologic material for 67 patients treated for early clinical stage (I or II) CCGD. Two patients (3%) had pseudoneoplastic glandular lesions (two microglandular hyperplasias). The remaining 65 CCGDs included 35 pure adenocarcinomas (18 mucinous, six serous, five endometrioid, five clear cell, and one adenoid cystic), 26 adenosquamous carcinomas (17 showed ⩾50% and nine showed >10% but <50% squamous differentiation—all nonkeratinizing; four were predominantly glassy cell type, and the others showed the following adenocarcinoma component differentiation: 11 mucinous, eight serous, and three endometrioid) and four villoglandular papillary adenocarcinomas (all four were mucinous). In situ carcinoma was identified in 54%. The two patients with pseudoneoplastic lesions were disease free (after 96 and 108 months). Twenty-one patients with CCGD had recurrent disease at 4 to 144 months (mean, 45; median, 18) including three local recurrences, 10 with distant metastasis, and eight with both. Thirty-five patients with CCGD were disease free at 12 to 216 months follow-up (mean, 80.6; median, 65). Adenosquamous ( P < .0002, predictive value [PV] = .68) and serous differentiation ( P < .05, PV = .61) were the only histological types associated with disease recurrence. Vascular space invasion ( P < .0002, PV = .7), deeper invasion ( P < .0005), nuclear grade ( P = .002, PV = .51), larger tumors on clinical exam ( P < .01) or pathological evaluation ( P < .01), and presence of pelvic lymph node metastasis at surgery ( P < .05, PV = .7) are additional features associated with recurrent disease. A combination of adenosquamous or serous differentiation and vascular space invasion maximized PV for recurrent disease at a level of .75. Mucinous, endometrioid, or clear cell histological types, architectural grade, or the distinction between clinical stages I and H were not associated with recurrent disease. None of the four patients with villoglandular papillary adenocarcinoma exhibited recurrent disease, but confirmation of this histological subtype's prognostic value was hindered by the small number of cases identified ( P = .16). Adenosquamous and serous differentiation, nuclear grading, pathological evaluation of vascular space and lymph node involvement, and recognition of pseudoneoplastic glandular lesions helped predict recurrent disease in low clinical stage CCGD in this retrospective study.

Tumor Angiogenesis as a Prognostic Factor in Cervical Carcinoma

Angiogenesis, the induction of new capillaries and venules, has been associated with tumor growth. Increased tumor size and new vessel growth may further the opportunity for tumor cells to enter the circulation and potentiate metastatic disease. To investigate if tumor angiogenesis could serve as a prognostic factor in cervical carcinoma, we counted microvessels (capillaries and venules) in 29 patients with squamous cell carcinoma of the cervix. Surgical specimens were stained for endothelial cells specifically with Factor VIII to identify all vessels. The microvessels were counted by light microscopy (per 200× field) in tumor sections with the highest population of microvessels. This was performed by two investigators without knowledge of patient outcome or extent of disease. Microvessel counts in patients with squamous cell carcinoma were significantly different from those of control subjects: 56 ± 28.9 and 16.3 ± 3.3 ( P = 0.013). There was no correlation between microvessel count and node status, parametrial involvement, depth of invasion, or gross disease. Microvessel count was significantly correlated with vascular space involvement ( P = 0.017). Four patients who developed recurrent disease within 1 year had high microvessel counts and yet were node negative and VSI negative at surgery. As shown by Folkman in breast cancer, angiogenesis may also be an independent predictor for recurrent disease in squamous cell carcinoma of the cervix. Microvessel counts could be of prognostic value in patients who do not have other risk factors for disease recurrence.

Long-Term Follow-Up of Stage I Cervical Adenocarcinoma Treated by Radical Surgery

From 1972 to 1988 55 patients underwent radical abdominal hysterectomy, pelvic lymph node dissection for treatment of FIGO Stage I cervical adenocarcinoma. A minimum of 60 months follow-up was available on all surviving patients. A detailed retrospective analysis was conducted to determine the influence of radical surgery on survival and to identify prognostic factors for recurrence. A bilateral salpingo-oophorectomy was included as part of the primary surgery in 52 the patients. Histologic subtypes included endocervical adenocarcinoma (44), papillary carcinoma (5), clear cell carcinoma (3), and adenosquamous carcinoma (3). The 5- and 10-year disease-free survival was 85.5%. The median follow-up of the surviving patients was 78.5 months (range, 60 to 240 months). Eight patients recurred, all but 1 of whom died of disease. Median time to recurrence was 28 months (range, 6 to 47 months). Five patients recurred beyond 24 months. One patient recurred locally, 5 recurred regionally, and 2 developed distant recurrences. Lymph node metastases (P < 0.0001), histologic grade (P < 0.0001), depth of invasion (P = 0.0001), presence of paracervical disease (P = 0.0034), and size of the lesion (P = 0.0059) were shown to be significant determinants of recurrence. Two of the 3 patients with a single involved lymph node recurred. Age, parity, history of oral contraceptive use, histologic subtype, and lymph vascular space involvement were not statistically significant determinants of recurrence. Adjuvant whole pelvic radiotherapy did not influence regional recurrence or survival but may decrease local recurrence. Radical abdominal hysterectomy pelvic lymph node dissection is an appropriate treatment of patients with Stage I cervical adenocarcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Cervical Conization as Definitive Therapy for Early Invasive Squamous Carcinoma of the Cervix

Young women who present with stage Ia carcinoma of the uterine cervix may strongly desire preservation of fertility. There is little published information on the outcome of patients treated for early invasive cervical cancer with cervical conization. Patients were considered eligible for conservative management if they had a squamous lesion invading to a depth less than or equal to 3 mm with no lymphatic or vascular space involvement and negative margins. We identified 14 patients who had been treated by cervical conization alone for early invasive carcinoma of the cervix. Pathologic variables were reviewed for all patients. Patient records were retrospectively reviewed for demographic, pathologic, and follow-up information. The mean depth of invasion was 1.6 mm (range, 0.5-2.8 mm). The mean number of cone sections evaluated was nine (range, 6-13 sections). The median follow-up period following conization was 26.5 months (range, 1-170 months). One patient underwent subsequent hysterectomy and was found to have mild dysplasia. Thirteen patients have retained their uteri and none has developed recurrent invasive or preinvasive lesions. We conclude that cervical conization is an acceptable therapy for selected cases of microinvasive squamous carcinoma of the uterine cervix. Larger studies of this patient group are indicated to confirm the safety of conization as definitive therapy in selected cases of early invasive cervical carcinoma.

Differences in the Morbidity of Radical Hysterectomy between Gynecological Oncologists

A multivariate analysis was performed on 405 patients who underwent radical hysterectomy and pelvic lymphadenectomy by eight surgeons for stage IB cervical carcinoma, to determine the influence of primary surgeon on morbidity. Patient characteristics analyzed (mean/proportion) were age (41 years), quetelet index (25.4), American Society of Anesthesiologists classification of physical status (0.5% >2), previous laparotomies (23%), previous radiation (0.7%), prophylactic antibiotics (95%), prophylactic heparin (67%), tumor size (1.0 cm), histology (68% SCC), grade (68% grades 2 or 3), vascular space involvement (45%), pelvic lymph node metastases (6%), and depth of invasion (6.6 mm). Morbidity characteristics analyzed (mean/proportion) were blood loss (910 ml), operative time (3.0 hr), intra-op complications (5%), post-op infectious (21%) and non-infectious complications (7%), transfusions (35%), post-op hospital stay (9.9 days), time to normal urine residual (9.0 days), and bladder dysfunction at 3 months post-op (21%). Mean tumor size was the only preoperative characteristic that was significantly different among surgeons ( P < 0.001). Of the factors evaluated for morbidity, mean blood loss ( P < 0.0001), operative time ( P < 0.001), and postoperative hospital stay ( P < 0.001) varied among physicians as did the incidence of blood transfusion ( P < 0.0001) and bladder dysfunction at 3 months postoperatively ( P < 0.0001). On multivariate analysis, surgeon was independantly significant for blood loss ( P < 0.0001), operative time ( P < 0.0001), postoperative hospital stay ( P < 0.001), incidence of blood transfusion ( P < 0.0001), and bladder dysfunction at 3 months postoperatively ( P < 0.0001). Despite differences in tumor size, patients appeared similar among the surgeons. Differences in patient morbidity among surgeons do exist and are of significant magnitude. Since the design of surgical trials to assess the therapeutic ratio should include not only measures of efficacy, but also measures of morbidity to be meaningful, intersurgical morbidity between centers/surgeons must continue to be quantified.

Surgery for gynecologic malignancies.

There is almost universal acceptance of the importance of cytoreductive surgery in advanced ovarian cancer. However, recent studies argued against attempts to remove every last vestige of tumor in patients with many large tumor masses in the upper abdomen. Successful secondary cytoreduction at second surgery may improve survival in some selected patients. The change from a clinical to a surgical staging for endometrial neoplasia undoubtedly improved the accuracy of staging, but it remains to be seen if appropriate clinical treatment of high-risk patients improves survival. Large loop excision of the transformation zone has become increasingly popular for treating cervical intraepithelial neoplasia. Lesions with no more than a 3-mm depth of invasion and with no vascular space involvement may be treated by simple hysterectomy. The morbidity and postoperative mortality with treatment of invasive squamous carcinoma of the vulva have been reduced by modifying the extent of vulvar and groin dissection. Recent studies suggested that the femoral nodes should be removed when performing inguinal lymphadenectomy. Laparoscopic pelvic and para-aortic lymphadenectomies and even laparoscopically assisted radical hysterectomies have been reported in patients with gynecologic malignancies. It remains to be seen what place laparoscopy will come to occupy in the armamentarium of the gynecologic oncologist.

Long-term survival with adjuvant whole abdominopelvic irradiation for uterine papillary serous carcinoma.

The optimum management of uterine papillary serous carcinoma (UPSC), a clinically aggressive histologic variant of endometrial adenocarcinoma, is a controversial issue. Ten patients with UPSC were reviewed who received whole abdominopelvic irradiation (WAP) as adjuvant therapy after a staging laparotomy and debulking surgery. Nine patients had clinical Stage I disease; the tumors in eight of them were upstaged based on laparotomy findings. There was greater than a 50% invasion of the myometrium in four of the hysterectomy specimens, and vascular space invasion was noted in seven patients. Peritoneal washings were positive in three of the nine specimens obtained; two others showed atypical cells. Five patients are alive with no evidence of disease at 102-133 months. Four patients are dead, and one patient is alive with disease. All recurrences were observed within 30 months of the initial diagnosis and were more common in the presence of deep myometrial invasion and vascular space involvement. Three of the four patients who died had pleural effusions that did not respond to hormonal and/or chemotherapy. Local irradiation produced long-term control of recurrences in two patients, including one with supraclavicular lymph node metastases who had no evidence of disease 117 months after radiation treatment to the involved nodes. These findings suggest that WAP be considered as an adjuvant therapy in the management of UPSC. The patients with the greatest benefit were those with early disease by surgical staging with or without positive peritoneal cytologic findings. For patients at high risk for pleural effusions and pulmonary metastasis, additional adjuvant therapy, such as innovative chemotherapy or low-dose lung irradiation, needs to be considered.

Effect of CO2 laser conization of the uterine cervix on pathologic interpretation of cervical intraepithelial neoplasia

The CO2 laser has become a valuable tool for the treatment of lower genital tract neoplasia. The records of 52 women who underwent CO2 laser cervical conization were analyzed retrospectively to evaluate the effect of tissue thermal damage on histopathologic interpretation. Lesion evaluability, defined by the ability to diagnose neoplasia accurately in the specimen, was satisfactory in only 26 cases; in the other 26, thermal damage was severe enough to preclude accurate diagnosis. A postoperative diagnosis of cervical intraepithelial neoplasia III was made in 17 instances, and microinvasion was suspected but unverifiable in two of these. Two patients had frankly invasive cancer, but vascular space involvement in one could not be evaluated accurately because of thermal damage. Tissue thermal damage sufficient to interfere with accurate histologic evaluation was noted in the majority of laser conization specimens. The value of a conization is both diagnostic and therapeutic. The potential impact of a diagnosis compromised by thermal damage is serious.

Microinvasive carcinoma of the uterine cervix (International federation of gynecology and obstetrics stage IA)

In 1985 the International Federation of Gynecology and Obstetrics (FIGO) subdivided Stage IA cervical cancer and specified metric criteria to demarcate Stage IA from Stage IB. Early stromal invasion (Stage IA1) denotes the first invasive protrusions of a carcinoma in situ into the stroma. Microcarcinomas (Stage IA2) are small cancers a number of orders of magnitude larger than Stage IA1 lesions and with a maximum depth of invasion of 5 mm and a maximum horizontal spread of 7 mm; larger lesions are classified as Stage IB. This study reviews 486 patients previously classified as having Stage IA disease. This yielded 344 Stage IA1 and 101 Stage IA2 lesions; 41 cancers were reclassified as Stage IB. Three hundred nine, 89, and 38 patients were followed for greater than or equal to 5 years. One (0.3%) patient with Stage IA1 disease re-presented with Stage IIB disease 12 years after conization. Five (5.6%) patients with Stage IA2 lesions developed invasive recurrences; three died. None of the 38 patients reclassified as having a Stage IB lesion, including 16 who were treated conservatively, developed a recurrence. The FIGO classification is not a guideline for treatment. Stage IA1 lesions can be treated conservatively, but treatment in Stage IA2 must be individualized. Risk factors such as vascular space involvement and confluency are of high sensitivity but low specificity.

Virulence of papillary endometrial carcinoma

While uterine papillary serous carcinoma (UPSC) has been well described as a virulent subtype of endometrial adenocarcinoma (AC), with behavior similar to that of papillary serous ovarian carcinoma, the papillary endometrial (PE) variant has not been well characterized. We studied 117 patients with endometrial carcinoma identified by our tumor registry, pathology files, and practice records from March 1981 to February 1989: 76 with AC, 26 with PE, and 15 with UPSC. Age and demographic data were similar for all three groups. All of the AC patients, 84% of PE patients, and 87% of UPSC patients had early-stage disease by clinical exam; however, 10% of AC patients, 23% of PE patients, and 87% of UPSC patients had extrauterine disease at surgery (P < 0.05). Deep myometrial invasion occurred in 29% of AC patients, 36% of PE patients, and 60% of UPSC patients (P < 0.05). Comparative analysis of the PE and UPSC groups revealed more marked nuclear anaplasia (P < 0.05) and more frequent vascular space involvement (nonsignificant) in the UPSC group. At 3 years, 75% of the AC group was alive without disease. In contrast, the median progression-free interval for the PE group was 33 months, and for the UPSC group, 9 months (P < 0.05). These data suggest a transition of increasing virulence corresponding with increasing papillary features, from AC to PE to UPSC. The papillary feature may be a new, significant risk factor in endometrial carcinoma.

Virulence of papillary endometrial carcinoma

While uterine papillary serous carcinoma (UPSC) has been well described as a virulent subtype of endometrial adenocarcinoma (AC), with behavior similar to that of papillary serous ovarian carcinoma, the papillary endometrial (PE) variant has not been well characterized. We studied 117 patients with endometrial carcinoma identified by our tumor registry, pathology files, and practice records from March 1981 to February 1989: 76 with AC, 26 with PE, and 15 with UPSC. Age and demographic data were similar for all three groups. All of the AC patients, 84% of PE patients, and 87% of UPSC patients had early-stage disease by clinical exam; however, 10% of AC patients, 23% of PE patients, and 87% of UPSC patients had extrauterine disease at surgery ( P < 0.05). Deep myometrial invasion occurred in 29% of AC patients, 36% of PE patients, and 60% of UPSC patients ( P < 0.05). Comparative analysis of the PE and UPSC groups revealed more marked nuclear anaplasia ( P < 0.05) and more frequent vascular space involvement (nonsignificant) in the UPSC group. At 3 years, 75% of the AC group was alive without disease. In contrast, the median progression-free interval for the PE group was 33 months, and for the UPSC group, 9 months ( P < 0.05). These data suggest a transition of increasing virulence corresponding with increasing papillary features, from AC to PE to UPSC. The papillary feature may be a new, significant risk factor in endometrial carcinoma.

The problem of stage Ia (FIGO, 1985) carcinoma of the uterine cervix

The FIGO definition of stage Ia (microinvasive) carcinoma of the uterine cervix had been vague and caused continued confusion. In 1985 FIGO revised the definition of stage Ia by including measurements in the definition and it also subdivided stage Ia into stages Ia1 and Ia2. One hundred and eighteen of eight hundred and sixty patients with stage 0 to IIb carcinoma, who retrospectively satisfied the new FIGO definition of stage Ia, were reviewed with respect to depth of invasion, horizontal spread, number of invasive foci, vascular space involvement, pattern of invasion, incidence of lymph node metastasis, and clinical outome. There were three potentially high-risk patients: one with pelvic lymph node metastases, one with parametrial metastasis, and the third with recurrence 23 months after initial treatment. It was pointed out that the border between stages Ia1 and Ia2 is very vague in the 1985 FIGO definition. It was proposed that a lesion with 3-mm or less stromal invasion and without vascular space involvement and confluency be defined as stage Ia1 and be safely treated with Simple means.