GYNECOLOGIC
ONCOLOGY
44,
28-32
(1992)
Pathologic Evaluation of Gynecologic Specimens Obtained with the Cavitron Ultrasonic Surgical Aspirator (CUSA) AGNES Y. Wu, M.D.,*)’ Departments
of *Pathology
MARK E. SHERMAN,M.D.,* and tGynecology,
NEIL B. ROSENSHEIN,
The Johns Hopkins University School Baltimore, Maryland 21205-2182
M.D.,? of Medicine
AND YENER S. EROZAN, and The Johns
Hopkins
M.D.*”
Hospital,
Received February 15, 1991
Eighty consecutivegynecologic specimensobtained with the Cavitron Ultrasonic Surgical Aspirator (CUSA) were evaluated pathologically. Fifty specimenswere obtained during intraabdominal tumor debulking and thirty resulted from ablation of lower genital tract lesions.In 98% of intraabdominalspecimens and in 93%of patientswith a history of lowergenital tract lesions, the CUSA material permitted an accurate diagnosis.Although artifacts related to cellularthermal injury were ubiquitous,nearly all caseswere interpretable with a combination of cytologic (smear,Cytospin, Millipore filter) and histologic(cell block) prep arations. Squamousintraepithelial lesions(SILs) of the lower genital tract were better preservedin cell block preparations, whereasintraabdominaladenocarcinomas werereadily diagnosed by both cytologic and histologictechniques.Accurate grading of SILs and exclusionof invasion were difficult in somecell blocks due to the fragmented and superficial nature of the samples. Cytologic preparationsof lower genital tract lesionsoften consistedof thick uninterpretablefragmentsand degeneratedsingle cellsthat contributed little to the evaluation of SILs. We conclude that examinationof CUSA specimensconfirmed the surgical removal of pathologictissuein 96%of cases,but an exact diagnosis of SILS wasnot possiblein all cases. Q1992 Aradmk PESS, I~C. INTRODUCTION Ultrasonic Surgical Aspiration is a technique of precise tissue removal by rapid mechanical movement. The Cavitron Ultrasonic Surgical Aspirator (CUSA) combines tissue fragmentation, irrigation, and aspiration in one instrument. The CUSA selectively fragments tissue with high water content and spares collagen-rich tissues, such as blood vessels and nerves, resulting in decreased blood ’ Current address; Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111. * To whom reprint requests should be addressed at 406 Pathology Building, The Johns Hopkins Hospital, 600 N. Wolfe St., Baltimore, MD 21205-2182. 28
0090~825&S/92 $1.50 Copyright 0 1992 by Academic Press, Inc. All rights of reproduction in any form reserved.
loss and intraoperative complications. The CUSA has been successfully employed in ophthalmic [l], neurologic [2,3], urologic [4-61, and other surgical subspecialties [7,8]. Recent reports [9-141 also suggest that the CUSA may be useful in debulking intraabdominal metastases of ovarian tumors and in other gynecologic procedures. In 1988, the Department of Gynecology at our institution began utilizing the CUSA for intraabdominal tumor debulking and removal of intraepithelial lesions of the vulva and vagina. The purpose of this study was to determine the suitability of these tissues for pathologic examination and to evaluate the contribution of cytologic preparations and tissue cell blocks to the final diagnosis. MATERIALS
AND METHODS
Gynecologic specimens procured with the CUSA from 80 cgnsecutive patients between October 1988 and December 1989 were evaluated in the Cytopathology Laboratory of The Johns Hopkins Hospital. Twenty-seven specimens were from the vulva, three from the vagina, and fifty from intraabdominal tumors. Specimens were received fresh and processed immediately or stored at 4°C before preparation. Each specimen was centrifuged at 1OOOg for 10 min and the supernatant was discarded. The cell pellets were used to prepare an air-dried smear stained with the Diff-Quik stain (a Romanowsky stain) and a smear fixed in 95% ethanol stained with the Papanicolaou stain. On the basis of cell counts, the pellets were resuspended in appropriate volumes of balanced electrolyte solution and prepared as two Cytospins and one Millipore filter. Large tissue fragments and cell buttons resulting from centrifugation were fixed in ethanolformalin and embedded in paraffin. A minimum of six levels were cut from the cell block, and alternate sections were stained with hematoxylin and eosin. Generally, the
PATHOLOGY
OF GYNECOLOGIC
29
CUSA SPECIMENS
entire specimen was processed for microscopic examination. All specimens were assessed for adequacy, the degree of cellular preservation, and the diagnostic yield. The Number of cases diagnosis rendered on the specimen obtained with the CUSA was compared with the diagnosis and morphologic 28 appearance of previous or concurrent histopathologic 9 specimens in 71 patients. In 8 patients with a clinical 3 diagnosis of condyloma acuminata of the vulva and in 1 3 with a diagnosis of multiple inclusion cysts of the vulva, 2 2 a surgical pathology specimen was not available for com1 parison. True positives for intraabdominal specimens was 1 defined as the presence of malignant cells in patients with 1 confirmed tumor and for lower genital tract lesions as the confirmation of a diagnosis of squamous intraepithelial 24 1 lesion (SIL).
TABLE 1 Diagnosesof Patientson the Basisof Clinical Findings or ExcisionalTissueBiopsy
Intraabdominal Ovarian carcinoma Cervical squamous carcinoma Endometrial carcinoma Uterine leiomyosarcoma Adenocarcinoma of the fallopian tube Pseudomyxoma peritonei Colon cancer Pancreatic cancer Liposarcoma Vulva Intraepithelial lesion” Multiple inclusion cysts Melanoma Squamous cell carcinoma Vagina Intraepithelial lesion”
a Squamous dysplasia and/or condyloma acuminatum.
1 1 3
RESULTS The initial diagnoses of the 80 cases based on prior or concurrent surgical pathology specimens or the clinical findings are displayed in Table 1. The CUSA specimens permitted a definitive diagnosis
FIG. 1. CUSA aspirates from an ovarian carcinoma. (A) Cell block of omental tissue displaying adenocarcinoma preparation showing typical three-dimensional tissue fragments of malignant glandular cells ( x 380).
(x 150). (B) Cytologic
WU ET AL.
FIG. 2. CUSA aspirates from the vulva. (A) Cell block preparation demonstrating fragments in the cytologic smear. Cellular details are difficult to recognize (x450).
in 49 of 50 (98%) intraabdominal cases. In all 35 patients with adenocarcinoma, the CUSA material was diagnostic. The tumor fragments and cells were well preserved (Figs. 1A and 1B). Thirty-one cases contained adequate diagnostic material in both the cytologic and the histologic preparations. In 3 cases, diagnostic material was present only in the cytologic preparation and in 1 specimen, only the cell block was diagnostic. In nine patients with cervical squamous carcinoma, the CUSA was used to perform an adjuvant lymph node dissection. The lumph nodes were removed by a standard lymphadenectomy and then the CUSA was used to remove residual tissue. In one patient with histologically confirmed lymph node metastases, the corresponding CUSA material in both preparations also contained tumor cells. In the remaining eight cases, the CUSA material was free of tumor cells and the concurrent surgical specimens did not demonstrate node involvement. Intraabdominal metastases removed by ultrasonic surgical aspirate from three uterine leiomyosarcomas were confirmed in the CUSA aspirates. The sarcomatous nature of the lesions was better appreciated in the cell blocks than in the smears, cytospins, or filters. Two cases of pseudomyxoma peritonii were readily diagnosed on the basis of the presence of abundant mucin and fragments
a squamous intraepithelial
lesion (X 120). (B) Tissue
of bland-appearing columnar epithelium. Cytopathologic preparations and cell blocks were of equal diagnostic value. In one patient with a recurrent mixed mullerian tumor, the concurrent excisional biopsy revealed liposarcoma, but the CUSA material was insufficient for cell block preparation and the filter contained a few atypical cells that were not diagnostic. The CUSA permitted an accurate diagnosis in 28 of 30 (93%) patients with lower genital tract lesions. The diagnosis in 23 of 27 (90%) patients with vulvar lesions and 2 of 3 (67%) with vaginal lesions was compatible with the clinical impression of condyloma acuminata, or a prior histologic diagnosis of a squamous intraepithelial lesion. Two specimens obtained from the lower genital tract were nondiagnostic. Both specimens, prepared by Millipore filter only, were inadequate due to insufficient cellularity. In one, the concurrent surgical specimen demonstrated a Clark’s level 2 melanoma of the vulva, whereas the other showed a vulvar intraepithelial neoplasia 3 (severe dysplasia) histologically. Three cases, including two from the vulva and one from the vagina, showed fragments of unremarkable squamous epithelium. One patient proved to have multiple vulvar inclusion cysts. In another with a history of squamous cell carcinoma of the vulva, the corresponding biopsy was also negative. The vaginal lesion,
PATHOLOGY
OF GYNECOLOGIC
FIG. 3. Cell block preparation displaying classic architectural and cytologic features of a vulvar condyloma ( x 60).
CUSA SPECIMENS
31
Our findings suggest that the nature and anatomic location of the lesion and the method of preparation may influence the diagnostic yield. In this study, specimens obtained from two patients with SILs and one with a mixed mullerian tumor were insufficient for diagnosis. The use of both cytologic and histologic preparations improved the diagnostic sensitivity in the detection of intraabdominal spread of adenocarcinema. In contrast, cell blocks were far more useful for diagnosing mesenchymal tumors and SILs. The cell block sections often displayed architectural patterns that simulated those of surgical biopsies. Examination of CUSA specimens could theoretically complement diagnostic biopsies and routine cytologic preparations by permitting microscopic examination of entire lesions. In contrast, laser and cryosurgery destroy abnormal tissues, precluding pathologic examination. In this study, the presence of a lesion was confirmed using the CUSA in nearly all cases; however, exact interpretation of cell blocks was often impaired because the tissue fragments were small, superficial, and lacked underlying stroma. Consequently, grading of SILs and exclusion of microinvasive squamous carcinoma was sometimes difficult. The cytologic preparations (smears, Millipore filters, and Cytospins) contributed little to the assessment of lower genital tract lesions. Several studies [lo-141 have demonstrated that the
previously diagnosed as low-grade SIL, was extremely small and appeared to have been entirely removed during the initial biopsy. In 19 of 20 (954 o ) sq uamous epithelial lesions prepared as cell blocks and cytologic specimens, the cell morphology was superior in cell block preparations (Figs. 2A and 2B). The cytologic preparations consisted mainly of small tissue fragments that were too thick and too poorly preserved to permit definitive interpretation. In contrast, cell blocks often demonstrated architectural features useful in the recognition of condyloma acuminatum (Fig. 3). In cases of squamous dysplasia, grading of the lesion and exclusion of microinvasion were sometimes hampered due to poor orientation, fragmentation, and the superficial nature of the specimen. Artifact, presumed to be related to thermal injury, was an invariable finding in all specimens and rendered part of the material uninterpretable (Fig. 4). Despite the presence of debris and poorly preserved cells and tissue fragments, a pathologic diagnosis was possible in nearly all cases based on at least one of the preparations. DISCUSSION This study demonstrates that an accurate pathologic diagnosis is possible in over 90% of gynecologic specimens obtained with the Cavitron Ultrasonic Surgical Aspirator.
FIG. 4. Cautery artifact with tissue debris typically found in most specimens (X 120).
32
WU ET AL.
CUSA has wide application in gynecologic surgery. Deppe et al. [lo] found that the CUSA permitted removal of ovarian metatases involving the diaphragm, intestine, and liver that would have been untreatable by routine techniques. These authors also achieved optimal cytoreduction in 5 of 6 patients with pelvic and/or paraaortic lymph node metastases, although 2 patients suffered small lacerations of the inferior vena cava [ll]. Vanderburgh and Nahhas [12] successfully employed the CUSA to treat necrotic vulvovaginal ulcers following intracavitory radiation therapy and Rose and Piver [13] used the CUSA to debulk vaginal metastases in patients with Stage III endometrial carcinoma. In a study of 10 patients undergoing debulking of intraabdominal malignancy, Adelson et al. [14] concluded that the CUSA halved the operating time and permitted avoidance of bowel resection in 9 patients. Excellent surgical results have also been reported in vascular organs including the brain, liver, and spleen [2,3,7,8]. Studies performed on animals have suggested that postoperative healing following treatment with the CUSA proceeds normally and that damage to surrounding tissue is minimal [2,6]. It remains to be demonstrated whether the use of the CUSA will reduce the incidence of postoperative complications such as the formation of adhesions and bowel obstruction. Studies have demonstrated that a proportion of cells harvested by the CUSA are intact and viable. Nahhas [15] identified ovarian carcinoma cells in the mist produced by the CUSA and suggested that the possible health hazards posed to operating room personnel using the CUSA deserve further study. Others have shown that ovarian carcinoma, medulloblastoma, and lung carcinoma cells harvested by the CUSA are viable and can be successfully grown in culture [16-181. These findings have led to three observations: pelvic tissue left in situ following treatment with the CUSA is probably uninjured [16], the CUSA may be used to harvest tumor tissue for in vitro studies [17], and spillage of CUSA irrigation fluid may pose a risk to patients. In our experience, hazards posed to operating room personnel by contaminated mists can be greatly minimized by using recently upgraded instruments at optimal irrigation and aspiration settings. We conclude that the CUSA specimens obtained in intraabdominal tumor debulking are nearly always sufficient to confirm the presence of malignancy. Grading squamous intraepithelial lesions and excluding invasion in lower gential tract lesions, however, may be difficult. Cytopathologic preparations are of little use in assessing squamous abnormalities, but may be of value in the diagnosis of intraabdominal tumors.
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