Aspiration cytology of neoplastic and non-neoplastic ovarian cysts: is it accurate?

To evaluate the role of aspiration cytology in the distinction between neoplastic and non-neoplastic ovarian cysts, we examined the cytology of 81 aspirates from 80 women 14-67 years of age. We then correlated results with subsequent histology or the clinical follow-up. Aspiration were performed during laparoscopy (32 cases) or immediately after surgical removal of the tumors (49 cases). The cysts ranged in size from 1.0 to 43.0 cm. Papanicolaou-stained cytospin preparations of samples were evaluated, and the lesions were classified into non-neoplastic (68 cases), benign neoplasms (four cases), and malignant neoplasms (nine cases). Cytologic impressions were correlated with histologic findings in 74 cases and with the clinical follow-up in the remaining seven. Nine of the 12 (75%) cystadenocarcinomas, including two serous neoplasms of low malignant potential (LMP), were correctly diagnosed as malignant by cytology. There were no false-positive results. On the other hand, of the 26 benign neoplasms (19 cystadenomas and seven mature cystic teratomas), only four teratomas (15%) could be subclassified specifically. The remaining 68 aspirates were classified as non-neoplastic. Seventy-seven percent of all proven non-neoplastic cysts measured < 8.0 cm, whereas 77% of all benign and malignant neoplastic cysts were > 8.0 cm. The overall diagnostic accuracy was improved from 63% to 69% when cyst size was taken into consideration. In malignant cysts the diagnostic sensitivity was 75%, specificity 100%, and overall accuracy 96%. We arrived at the following conclusions: Aspiration cytology is an accurate predictor of malignancy in ovarian cystic lesions, but because the sensitivity of the technique is not high enough, one should not rely on aspiration cytology alone; The differential diagnosis between cystadenocarcinomas and tumors of low malignant potential cannot be made by cytology; Although it is difficult to distinguish between benign neoplasms and non-neoplastic benign cysts, diagnostic accuracy will improve when the size of the lesion is considered; Aspiration cytology can provide particularly useful information in young women with functional cysts of the ovary to avoid an unnecessary operation; Acellular cyst fluids should not be considered nondiagnostic because they represent benign cysts in the majority of cases; false-negative results of fine-needle aspiration of cystic ovarian lesions is usually due to low cellularity of the sample and secondary degenerative changes; negative fine-needle aspiration results should be followed clinically.

Fine-needle aspiration cytology of the ovary.

FNA cytology has been shown to be highly accurate in diagnosing malignant tumors. In gynecology, an overall accuracy of 94.5% in the differentiation between benign and malignant tumors has been reported. Despite many controversial views regarding its safety, aspiration cytology has been accepted as an innocuous procedure that can be accomplished with minimal discomfort or complications and, in association with laparoscopy, assist in the management of ovarian cysts and masses. Although FNA cannot be considered the first-hand diagnostic procedure for ovarian cancer in postmenopausal patients, it may be extremely helpful in young women, even during pregnancy, to safely differentiate functional and other benign ovarian cysts from malignant ones. In postmenopausal women, especially those in the high risk group for surgical procedures and those undergoing a "second look" intervention following radiation or chemotherapy, aspiration cytology may provide sufficient information to warrant abandoning unnecessary surgery. During laparotomy for suspected unilateral disease, FNA may provide sufficient data about the opposite ovary to allow that organ to remain in place, thus preserving its function in a young patient. The pathologist must be familiar with the cytology of normal pelvic structures and the diagnostic criteria used to differentiate benign from malignant lesions, as well as potential diagnostic pitfalls, such as interpretation based on very few cells or the absence of appropriate clinical information. Although proper classification of ovarian masses can be achieved through FNA, the pathologist should be aware of its limitations, such as difficulties in differentiating adenomas from non-neoplastic cysts, and tumors of low malignant potential from well-differentiated carcinomas. Descriptive histologic terminology should be applied, and terms such as "suspicious" or "atypical" avoided. The aspirated material may not only be used for the diagnosis and classification of ovarian neoplasms, it may also be used for DNA analysis, detection of estrogen receptors and other prognostic markers, thus providing information regarding biologic behavior of the tumors. Finally, it is hoped that aspiration of ovarian lesions routinely detected by sonography, in elderly women or those with a strong family history of ovarian cancer, will allow the physician to accomplish detection of early ovarian cancer.

Growth characteristics of nonmalignant cells in the ATP cell viability assay.

Over the last 5 years, the ATP cell viability assay (ATP-CVA) has been used to study the in vitro response of cell lines and fresh gynecologic human tumors to a variety of antineoplastic agents including chemotherapeutic agents, hormones and biological response modifiers. This assay measures light production as intracellular ATP interacts with the luciferin-luciferase complex. Quantitation of the light produced has been shown to directly correspond with the number of viable cells. A past criticism is that in the ATP-CVA, when applied to fresh tumor tissue, normal cells (fibroblasts, macrophages and lymphocytes) also produce ATP, and if present in sufficient numbers, could lead to errors in chemosensitivity testing results. This study was designed to evaluate the growth characteristics of various benign cells found in fresh tumors. The cells were studied under multiple plating conditions to show the relative increase or decrease of fractional ATP measured at different time points. We found that agar/McCoy underlayer and agarose-coated wells do not permit the growth of nonmalignant cells. In the culture conditions of the ATP-CVA, non-malignant cells do not contribute relevant ATP levels when treated samples are compared to controls on day 6. Therefore, results of the ATP-CVA in fresh tumors should not be affected.

Fine-needle aspiration cytology of palpable lesions of the lower female genital tract.

During January 1978 through May 1989, 232 fine-needle aspirations of palpable lesions of the vulva, vagina, inguinal area, and perineum were performed on 209 women. Five samples were considered inadequate for cytologic evaluation. Eighty-seven (38.3%) aspirates were interpreted as malignant, 80 of which were further classified into specific cell types. Most malignant neoplasms represented metastases from other gynecologic organs. Of the 140 (61.7%) nonmalignant aspirates, only 28 (20%) could be categorized into specific pathologic disorders. The false-positive and false-negative rates were 0 and 4.6%, respectively. We conclude that, because of its safety, simplicity, and accuracy, fine-needle aspiration cytology represents a valuable diagnostic tool in the evaluation of palpable lesions of the lower female genital tract. This technique is particularly helpful in the assessment of primary, metastatic, or recurrent malignant neoplasms of this region.

Retrospective c-erbB-2 immunostaining in aspiration cytology of breast cancer.

Fifty fine-needle aspiration cytologies of breast that were diagnosed as carcinomas were retrieved from the files and retrospectively evaluated for the expression of c-erbB-2 oncoprotein using standard immunocytochemical methods. Corresponding histologic sections of all tumors were similarly studied. Seventeen fine-needle aspirates (34%) reacted positively for the presence of c-erbB-2 oncoprotein. All but one (32%) of the corresponding tissue sections were also positive for c-erbB-2 by immunohistochemistry. All positive cases were infiltrative ductal carcinomas with a preponderance of the comedo type. Positive reactions were localized in the cytoplasmic membrane of tumor cells. The staining was either present in all cells throughout a tumor, or it was completely absent. We conclude that immunocytochemistry for c-erbB-2 oncoprotein can be performed on fine-needle aspiration cytology samples that are previously fixed and stained with the Papanicolaou technique. Furthermore, the sensitivity of immunostaining results are comparable to that obtained in histologic sections.

Metastatic medullary thyroid carcinoma in liver diagnosis by aspiration cytology.

A case of metastatic medullary thyroid carcinoma (MTC) to the liver of a patient with multiple endocrine neoplasia (MEN) Type IIb was suggested by percutaneous fine-needle aspiration cytology and confirmed by histology and immunohistochemistry. The cytologic presentation of this unusual thyroid cancer in liver has not been previously reported. We report such a case and discuss its differential diagnosis from other metastatic tumors of the liver.

Cell proliferative activity and mutation of P53 suppressor gene in human gestational trophoblastic disease.

Cell proliferative activity and the overaccumulation of P53 suppressor gene were evaluated in 26 cases of gestational trophoblastic disease and five cases with normal placentae. Formalin-fixed, paraffin-embedded histological sections were used for immunohistochemistry, utilizing the avidin-biotin-peroxidase technique and antibodies to PCNA (proliferative cell nuclear antigen) and to P53 (product of suppressor gene). Positive reactions for PCNA were graded from 1+ to 3+ (1(+)-less than 10% of cells; 2(+)-10-50%; 3(+)-more than 50%). Eight of 10 cases of choriocarcinoma (80%) showed moderate to strong reactivity for PCNA (2+ and 3+). All 9 cases with hydatidiform mole and 6 of 7 cases with partial mole also demonstrated 2+ and 3+ reactions for PCNA. There was minimal or no PCNA staining in the trophoblastic cells of normal placentae. Five of 10 cases with choriocarcinoma (50%) exhibited P53 overaccumulation as did 7 of 9 cases with hydatidiform mole (78%). In hydatidiform moles, P53 staining was limited to the areas of trophoblastic proliferation separate from chorionic villi. None of the partial moles or normal placentae showed P53 overaccumulation. It is concluded that the cell proliferative activity of choriocarcinomas as well as complete and partial hydatidiform moles are comparable. On the other hand, the mutation of P53 suppressor gene, as demonstrated by the overaccumulation of P53 protein, is seen only in true trophoblastic neoplasms, namely, choriocarcinomas and hydatidiform moles.

Cell proliferative activity and mutation of P53 suppressor gene in human gestational trophoblastic disease

Cell proliferative activity and the over accumulation of P53 suppressor gene were evaluated in 26 cases of gestational trophoblastic disease and five cases with normal placentae. Formalin-fixed, paraffin-embedded histological sections were used for immunohistochemistry, utilizing the avidin-biotin-peroxidase technique and antibodies to PCNA (proliferative cell nuclear antigen) and to P53 (product of suppressor gene). Positive reactions for PCNA were graded from 1+ to 3+ (1+ - less than 10 percent of cells; 2+ - 10 - 50 percent; 3+ - more than 50 percent). Eight of 10 cases of choriocaricinoma (80 percent) showed moderate to strong reactivity for PCNA (2+ and 3+). All 9 cases with hydatidiform mole and 6 of 7 cases with partial mole also demonstrated 2+ and 3+ reactions for PCNA. There was minimal or no PCNA straining in the trophoblastic cells of normal placentae. Five of 10 cases with choriocarcinoma (50 percent) exhibited P53 overaccumulation as did 7 of 9 cases with hydatidiform mole (78 percent). In hydatidiform moles, P53 staining was limited to the areas of trophoblastic proliferation separate from chorionic villi. None of the partial moles or normal placentae showed P53 overaccumlation. It is concluded that the cell proliferative activity of choriocarcinomas as well as complete and partial hydatidiform moles are comparable. On the other hand, the mutation of P53 suppressor gene, as demonstrated by the overaccumulation of P53 protein, is seen only in true trophoblastic neoplasms, namely choriocarcinomas and hydatidiform moles (AU)

Cell proiferative actitiy and mutation of P53 suppressor gene in human gestational trophoblastic disease

Cell proliferative activity and the over accumulation of P53 suppressor gene were evaluated in 26 cases of gestational trophoblastic disease and five cases with normal placentae. Formalin-fixed, paraffin-embedded histological sections were used for immunohistochemistry, utilizing the avidin-biotin-peroxidase technique and antibodies to PCNA (proliferative cell nuclear antigen) and to P53 (product of suppressor gene). Positive reactions for PCNA were graded from 1+ to 3+ (1+ - less than 10 per cent of cells; 2+ - 10 - 50 per cent ; 3+ - more than 50 per cent ). Eight of 10 cases of choriocaricinoma (80 per cent ) showed moderate to strong reactivity for PCNA (2+ and 3+). All 9 cases with hydatidiform mole and 6 of 7 cases with partial mole also demonstrated 2+ and 3+ reactions for PCNA. There was minimal or no PCNA straining in the trophoblastic cells of normal placentae. Five of 10 cases with choriocarcinoma (50 per cent ) exhibited P53 overaccumulattion as did 7 of 9 cases with hydatidiform mole (78 per cent ). In hydatidiform moles, P53 staining was limited to the areas of trophoblastic proliferation separate from chorionic villi. None of the partial moles or normal placentae showed P53 overaccumlation. It is concluded that the cell proliferative activity of choriocarcinomas as well as complete and partial hydatidiform moles are comparable. On the other hand, the mutation of P53 suppressor gene, as demonstrated by the overaccumulation of P53 protein, is seen only in true trophoblastic neoplasms, namely choriocarcinomas and hydatidiform moles.

The role of DNA index as a prognostic factor in early cervical carcinoma.

The value of DNA index as a prognostic factor in early cervical cancers was investigated. A total of 124 patients who underwent radical hysterectomy for stages IB-IA cervical cancers from 1/1982 to 12/1985 were included. Paraffin blocks were available in only 98 patients for the analysis. After dewaxing, rehydrating, and enzyme disaggregation, cells were subjected to dual parameter flow cytometry. Tumor DNA index was calculated and the results were correlated with 5-year survival, stage, grade, tumor size, nodal metastasis, surgical margins, and lymphovascular invasion. There were 1% hypoploid, 7.3% diploid, 72.9% aneuploid, 16.7% tetraploid, and 2.1% hyperploid. At the end of 5 years, there were 69 alive and 27 dead patients with mean DNA indices of 1.50 +/- 0.3 and 1.70 +/- 0.3, respectively. t Test analysis revealed that mean DNA index of deceased patients was significantly higher than that of alive ones (P = 0.008). Survival analysis demonstrated the prognostic significance of DNA index 1.70 (P = 0.017). Median survival of patients with DNA index of 1.70 or greater was 36 months in contrast to 73.5 months for those with DNA index less than 1.70. Multivariate analysis subsequently confirmed DNA index of 1.70 as an independent prognostic indicator with a hazard ratio of 2.05.

Evidence of tumor heterogeneity in cervical cancers and lymph node metastases as determined by flow cytometry.

BACKGROUND: The incidence and significance of tumor heterogeneity in primary tumors and metastatic lymph nodes were investigated in Stage IB-IIA cervical cancers. METHODS: Paraffin-embedded tissues from 96 radical hysterectomy specimens were dewaxed, disaggregated, and subjected to dual parameter flow cytometry. Three-dimensional histograms were generated to delineate different tumor populations. A DNA index difference of at least +/- 0.15 was used to define tumor heterogeneity. RESULTS: Mean DNA index difference of various tumor populations was 0.29 +/- 0.13. Among 69 patients with normal lymph nodes, there were 12 patients (incidence, 17.4%) with tumor heterogeneity in the primary tumors. Of 27 patients with metastatic lymph nodes, 5 (incidence, 18.5%) had evidence of tumor heterogeneity in the primary tumor, and 18 of 47 (incidence, 38.3%) had tumor heterogeneity in metastatic lymph nodes. When using DNA index to determine clonal origin of metastatic lymph nodes, as many as 60% of the metastases could not be traced to the primary tumor. Tumor heterogeneity was associated with a 40% reduction in median survival time. However, because of the small number of patients with tumor heterogeneity, statistical analyses did not show prognostic significance. CONCLUSIONS: Tumor heterogeneity appeared to be a common characteristic of early cervical carcinoma. Additional study is needed to fully evaluate its prognostic value.

The prognostic significance of surgical staging for carcinoma of the endometrium.

This study is based on a retrospective review of 156 patients with endometrial carcinoma from 1978 through 1984 who underwent primary surgical evaluation. All cases were retrospectively restaged using the newly adopted FIGO surgical staging. The preoperative FIGO clinical stage distribution for this study was as follows: 121 (77.6%) Stage I, 22 (14.1%) Stage II, 5 (3.2%) Stage III, 2 (1.3%) Stage IV, and 6 (3.8%) unstaged patients. Most patients had TAH-BSO with a collection of peritoneal washings and retroperitoneal lymph node sampling. Surgical staging revealed 122 (78.2%) Stage I, 9 (5.8%) Stage II, 12 (7.7%) Stage III, and 13 (8.3%) Stage IV patients. Surgery upstaged 12.4% of clinical Stage I. In clinical stage II, 59.0% were downstaged while 27.3% were upstaged. For clinical Stage III, 60.6% were upstaged, but no downstaging occurred. No change in stage occurred for clinical Stage IV patients. Ninety-seven surgically staged patients received no adjuvant therapy. The remaining 59 patients had adjunctive treatment which consisted of radiotherapy (59.3%), hormonal therapy (25.4%), chemotherapy (5.1%), or combined modality treatment (10.2%). All patients were followed until death or a minimum of 5 years (60-139 months; median, 82 months) with the exception of 13 patients who were lost to follow-up (2-58 months; median, 34 months). Five-year survival by clinical staging was as follows: 86.2% for Stage I, 85.9% for Stage II, and 0% for Stage III and IV. Five-year survival by surgical staging was 90.6% for Stage I, 85.7% for Stage II, 58.3% for Stage III, and 0% for Stage IV. The 13 patients who were lost to follow-up were censored in all survival analyses at the time of last contact. Stepwise regression analysis using a parametric proportional hazards model identified surgical stage as the most significant prognostic factor (P = 0.02). Univariate analysis showed that patients with surgical Stage IC had significantly worse prognosis (75.0%, 5 years) than those in surgical Stage IA (93.8% 5 YS) or IB (95.4% 5 years). In summary, this study demonstrates that surgical staging as recommended by FIGO is indicated to accurately determine the initial extent of disease in endometrial carcinoma. In addition, surgical staging is the strongest predictor of survival. Deep myometrial invasion appears to be a significant independent prognostic factor within surgical Stage I. The role of adjunctive radiotherapy in Stage I disease awaits the results from an ongoing multi-institutional, prospectively randomized trial.

Histopathologic predictors of the behavior of surgically treated stage IB squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study.

Disagreement persists about the superiority of Reagan and Ng's method over that of Broders' for the histologic grading of squamous carcinoma of the cervix. Uncertainty about the predictive value and reproducibility of any of the grading methods prompted a comparison of factors previously suggested as indicating the biologic behavior for cervical squamous carcinoma. One hundred ninety-five women, who were enrolled in a Gynecologic Oncology Group treatment protocol of Stage IB squamous carcinoma of the cervix and underwent radical hysterectomy with pelvic and paraaortic node sampling, formed the study population. The tumors were graded first by participating institutional pathologists, with submitted slides subjected to an independent review by two pathologists (R.J.Z. and S.W.). The histologic parameters examined included the presence and amount of keratinization, nuclear pleomorphism, mitotic rate, gestalt grading, pattern of invasion at the stromal interface, and inflammatory cell infiltrate. The depth of invasion and presence or absence of vascular invasion also were assessed. The probability of pelvic lymph node metastasis and the progression-free interval were determined for each parameter. Surprisingly, none of the grading methods was effective in predicting nodal spread or progression-free interval. However, an increasing depth of invasion strongly correlated with nodal spread and a diminished progression-free interval (P less than 0.0001). Vascular invasion was less effective in these predictions (0.05 less than P less than 0.10). Both measurements were reasonable reproducible. It was concluded that histologic grading of surgically treated cervical carcinoma is not useful but that the depth of invasion and vascular invasion are important predictors of behavior that should be reported routinely.

The value of fine-needle aspiration cytology in the diagnosis of inflammatory pancreatic masses.

In order to determine the accuracy of fine-needle aspiration cytology (FNAC) in the diagnosis of inflammatory pancreatic masses (pseudocyst and abscess), we reviewed 91 FNAC specimens performed during 1985-1989 at the University of Miami/Jackson Memorial Medical Center. All specimens were collected under computed tomographic guidance. A sensitivity of 100% and a specificity of 98% were recorded in the diagnosis of inflammatory pancreatic masses. The sensitivity and specificity of the method in the diagnosis of malignant neoplasms were 79.5% and 100%, respectively. We conclude that fine-needle aspiration cytology of pancreas is not only an important diagnostic tool in patients with pancreatic cancer, but can also be used to diagnose inflammatory masses of the pancreas. In fact, aspiration of such masses may not only be diagnostic, but also therapeutic in some patients.

Central nervous system expression of a monoclonal paraprotein in a chronic lymphocytic leukemia patient.

An unusual complication of chronic lymphocytic leukemia (CLL) is reported. The patient, a 79-year-old man, had a long standing history of CLL, that had been complicated by the development of a Guillain-Barré-like syndrome and a peripheral biclonal gammopathy. The biclonal immunoglobulins identified in the serum were IgM lambda and IgG lambda. The patient's condition progressed and he eventually developed ophthalmologic complications. Cerebrospinal fluid (CSF) obtained during evaluation of his visual dysfunction contained numerous small, mature lymphocytes consistent with the presence of CLL cells in the central nervous system (CNS); immunoperoxidase staining of these cells revealed a monoclonal population. Protein electrophoretic evaluation of the patient's CSF showed a single monoclonal band and immunofixation electrophoresis of the CSF revealed that the immunoglobulin present was IgG lambda. No evidence for the monoclonal IgM paraprotein identified in serum could be appreciated in the CSF by immunofixation. Taken together, these findings strongly implied that there was CNS involvement by the leukemia and this process caused the patient's neurologic symptoms. Furthermore, this study demonstrates that chronic lymphocytic leukemia should also be considered as one of the hematopoietic malignancies associated with monoclonal gammopathies involving the CNS.

Vulvar Paget's disease. Is immunocytochemistry helpful in assessing the surgical margins?

From January 1977 to December 1988, 19 patients with biopsy-proven Paget's disease of the vulva underwent simple or radical vulvectomy at the University of Miami/Jackson Memorial Medical Center. All vulvectomy specimens were evaluated immunocytochemically for the expression of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA) and low-molecular-weight keratins 8 and 18 (LMK), both in areas containing neoplastic cells and in histologically negative surgical margins. Neoplastic Paget's cells stained positively for CEA in all cases; they were positive for EMA and LMK in 18 and 17 cases, respectively. In all eight cases with underlying in situ or invasive carcinomas, CEA, EMA and LMK were localized in the underlying tumors as well. None of the histologically proven negative margins reacted for CEA, EMA or LMK on immunocytochemistry. CEA appears to be a valuable immunocytochemical marker for extramammary Paget's disease; EMA and LMK are also expressed by the majority of such cases. None of these markers, however, is of added value in identifying Paget's cells in surgical margins if those margins appear negative on routine hematoxylin-and-eosin staining.

Special report. Immunocytochemistry in diagnostic cytology: a 12-year perspective.

In recent years immunocytochemistry has become an important addition to diagnostic cytology. Its routine application in cytology, however, has not yet reached the practical levels it has achieved in diagnostic histopathology. This review examines the values and limitations of immunocytochemistry in diagnostic cytology and addresses some of the most common technical and analytical factors that can affect the outcome of the procedure.

Carcinomatous meningitis from transitional cell carcinoma of the bladder: case report.

In the past decade, there has been an increasing awareness of central nervous system metastases as a frequent complication of some malignancies, particularly in lung, breast and hematologic cancers. However, the central nervous system remains an uncommon location for metastases from certain primary tumors including those from the genitourinary system. We report on a patient with transitional cell carcinoma of the bladder who was treated with combination chemotherapy, and during the course of his disease developed carcinomatous meningitis. We anticipate this unusual complication of bladder transitional cell carcinoma will be seen more frequently, especially in the light of available data from effective chemotherapeutic regimens. We report this patient to alert physicians to this complication and to consider using prophylactic measures in responding patients as is the case in other malignancies.

Cresyl violet: a rapid, simple, easily interpretable stain for detecting Pneumocystis carinii in sputum.

Over a three-month period at the pathology laboratory of Jackson Memorial Hospital, 110 sputum samples from 62 hospitalized patients with suspected AIDS were examined for Pneumocystis carinii. Sputum specimens were either expectorated spontaneously (most patients) or expectorated after the inhalation of small amounts of nebulized normal saline. Each sputum sample was cytocentrifuged onto two slides. One slide was stained with Gomori methenamine-silver (GMS) and the other with cresyl violet (CV). Among the 62 study patients, 18 were proven to have no histologic evidence of P carinii pneumonia. Of the remaining 44 patients, P carinii organisms were found by GMS stain in 14 (32%) and by CV stain in 18 (41%). Among those with a positive CV stain, the diagnosis was made on the first sputum specimen in 14 patients and on the second specimen in the remaining four patients. CV stain is at least as sensitive as GMS in detecting P carinii cysts in the sputum of AIDS patients with P carinii pneumonia, and its diagnostic sensitivity may exceed 40% under field conditions. Further, CV stain is much simpler to prepare than GMS and much simpler to interpret than Giemsa. It could be easily adapted for general use to expedite the diagnosis and treatment of P carinii pneumonia.