Use of immunohistochemistry in fine needle aspiration of thyroid nodules in patients with a history of malignancy. A report of two cases.

BACKGROUND: A history of a nonthyroid malignancy may present a diagnostic dilemma in the assessment of fine needle aspiration (FNA) of thyroid nodules. One reported series, on patients with prior malignancies and a thyroid nodule, indicated that in 17% of patients, the thyroid nodule represented metastatic malignancy, 6% were classified as primary thyroid cancers, and the remainder were benign or inconclusive lesions. The resolution of this problem is essential to patient management. CASES: We report two cases in which patients with a history of renal cell carcinoma presented with a thyroid nodule. The first patient was an 80-year-old female whose Papanicolaou-stained FNA demonstrated clusters of round to polygonal cells with round to ovoid, hyperchromatic nuclei and abundant, wispy cytoplasm. The second patient was a 55-year-old female with clusters and single cells with round to oval, eccentric nuclei and copious, granular, gray cytoplasm noted on Papanicolaou-stained material. In each case, the diagnosis was inconclusive on initial review of Papanicolaou-stained slides, and immunohistochemical staining was ordered to better characterize the lesions. Tumor cells from case 1 were positive for cytokeratin cocktail and vimentin and negative for thyroglobulin, epithelial membrane antigen and calcitonin, suggestive of metastatic renal cell carcinoma. In contrast, the tumor cells from case 2 expressed cytokeratin, thyroglobulin and vimentin, consistent with a primary thyroid neoplasm. In each case, the cytologic diagnoses were confirmed in the resected specimens. CONCLUSION: Immunohistochemistry is a helpful adjunct in the evaluation of thyroid nodules in patients with a past history of malignancy.

Exfoliative cytology of lymphoepitheliomalike carcinoma of the uterine cervix. A report of two cases.

BACKGROUND: Lymphoepitheliomalike carcinomas (LECs) are morphologically similar to undifferentiated nasopharyngeal carcinoma but occur at sites other than the nasopharynx. They rarely occur in the uterine cervix. Sixty-five cases of LEC of the cervix have been published to date, and the pitfalls of histopathologic interpretation have been discussed. This undifferentiated carcinoma with a prominent lymphocytic infiltrate represents a challenge for the pathologist examining a scant cervical biopsy or Pap smear. Distinguishing LEC as a separate entity is important. Despite the fact that the epithelial component is poorly differentiated, this neoplasm is associated with a lower frequency of lymph node metastases, is potentially radiosensitive and has a better prognosis. Although mentioned in passing in several papers, the exfoliative cytology of this cervical neoplasm has not been adequately discussed. We report the cytologic features of LEC in cervical smears obtained from two patients. CASES: The first patient presented with menometrorrhagia and postcoital bleeding. The cervical smear taken at the time of presentation was reported as unsatisfactory for evaluation. ASCUS was diagnosed on a vaginal smear obtained one year earlier. The second patient presented with a complaint of postcoital bleeding. A cervical smear and the cervical biopsy taken at the time of presentation were reported as ASCUS and high grade dysplasia versus carcinoma, respectively. A retrospective review of the cervical smears revealed rare malignant cells occurring singly or in small groups. The tumor cells had a high nuclear/cytoplasmic ratio, irregular nuclear membrane and hyperchromatic nuclei with coarse chromatin and were obscured by heavy inflammation and blood. The background resembled that of a menstrual smear. CONCLUSION: The diagnosis of LEC of the cervix is often made on a loop electrical excision procedure or on a hysterectomy specimen. The presence of heavy inflammation and blood, which can obscure the malignant nature of the cells, presents the cytopathologist with a challenging diagnosis of LEC in cervical smears. In view of the prognostic implications, it is desirable for the pathologist to classify LEC as a distinct entity.

Human cytomegalovirus blocks interferon-gamma stimulated up-regulation of major histocompatibility complex class I expression and the class I antigen processing machinery.

Interferon-gamma stimulates major histocompatibility complex (MHC) class I antigen processing and presentation by inducing the expression of major histocompatibility complex class I heavy chains, beta2-microglobulin, the transporter associated with antigen processing, and components of the proteasome complex. We demonstrate that this effect of interferon-gamma on the major histocompatibility complex class I pathway is inhibited in human cytomegalovirus-infected fibroblasts and endothelial cells. This is the result of a direct human cytomegalovirus/cell interaction leading to a block in interferon-gamma signal transduction beginning at early times after infection and peaking at 72 hr after infection. These observations suggest a novel level of herpesvirus interference with antigen processing: protection of infected cells from the immunoregulatory effects of interferon-gamma. Thus protected, human cytomegalovirus persists and may exacerbate graft rejection or lead to fulminant infection in the immunocompromised transplant recipient.

Exfoliative cytology of atypical polypoid adenomyoma. A case report.

BACKGROUND: An atypical polypoid adenomyoma (APA) is a well-defined entity. It occurs in the endometrium, lower uterine segment and endocervix. It is usually composed of atypical complex glands with squamous metaplasia admixed with myofibromatous stroma. CASE: A 35-year-old female presented with one-year history of irregular menstrual periods. A diagnosis of adenocarcinoma in situ was rendered on her cervicovaginal smear. Pelvic examination revealed an enlarged uterus due to a leiomyoma. Colposcopic examination revealed a 0.6-cm, sessile, polypoid mass at the junction of the endocervix and ectocervix. A cone biopsy of the lesion showed irregular, endometrial-type glands embedded in a prominent myofibromatous stroma. The atypical glandular component of the mass demonstrated varying degrees of architectural complexity, ranging from simple to complex hyperplasia. In tissue sections the lesion was diagnosed as APA of the cervix. The patient underwent a hysterectomy for the leiomyoma. The hysterectomy specimen showed an 8.5-cm leiomyoma. The cervix and uterine corpus revealed no residual APA. CONCLUSION: APA of the cervix should be considered among the differential diagnoses of atypical glandular cells of undetermined significance. The diagnosis of APA cannot be made on cytology; the final diagnosis requires histologic confirmation.

Fine-needle aspiration cytological features of dermoid cyst of the parotid gland: a report of two cases.

We describe the cytological features of dermoid cyst of the parotid gland the value of preoperative diagnosis by fine-needle aspiration (FNA) cytological evaluation. Both patients had painless parotid masses. On physical examination, a freely movable parotid mass was found in each case. CT scan showed a cystic mass in the parotid gland in each patient. FNA in both cases showed anucleated and nucleated squamous epithelium and keratin debris. The clinical features and cytological findings in each case were interpreted as suggestive of a dermoid cyst. Histological examination of surgical specimens confirmed the presence of a dermoid cyst of the parotid gland in each case. FNA is a reliable method for preoperative diagnosis and permits selection of an appropriate form of surgical procedure for dermoid cyst of the parotid gland.

Perforin-positive cytotoxic lymphocytes in pregnancy.

OBJECTIVE: To investigate whether perforin-positive, cytotoxic lymphocytes are present in the first and second trimester as well as at term during normal gestation. STUDY DESIGN: A monoclonal antibody raised against human perforin was used to detect perforin expression in mononuclear cells in first-trimester abortion, second-trimester preterm labor due to cervical incompetence and term placentas obtained after normal delivery. Fresh frozen tissue sections containing first- and second-trimester decidua and placental tissues as well as decidua of maternal and fetal surfaces of term placenta were stained using an immunoperoxidase method. RESULTS: Occasional perforin-positive lymphocytes were present in stroma of chorionic villi of term placenta, while most were found in decidua and coagulated blood in maternal vessels and intervillous spaces. The majority of these lymphocytes were CD3-, CD2+ and CD56+. Quantitative comparison of decidual perforin-positive lymphocytes demonstrated a relative increase in these lymphocytes in decidua of second-trimester and term placentas. CONCLUSION: The presence of perforin-positive cytotoxic lymphocytes in maternal blood and decidua during gestation suggests their roles in pregnancy.

Exfoliative cytology of neuroendocrine small cell carcinoma of the endometrium. A report of two cases.

BACKGROUND: In the female genital tract, neuroendocrine small cell carcinoma can occur in the endometrium as well as the cervix, ovary and vagina. This tumor has a high propensity for systemic spread and a poor prognosis. Small cell carcinoma of the endometrium is cytologically identical to its counterparts in the lung and other sites. Its characteristic appearance in a cervicovaginal smear should raise concern about small cell carcinoma. Other tumors of the uterus should be considered in the differential diagnosis, including adenocarcinoma with neuroendocrine features, small cell nonkeratinizing squamous cell carcinoma, endometrial stromal sarcoma, rhabdomyosarcoma, primitive neuroectodermal tumor, non-Hodgkin's lymphoma and metastatic breast carcinoma. CASES: Case 1 was a 59-year-old, white female, and case 2 was a 47-year-old, white female. Both patients presented with vaginal bleeding. The Papanicolaou smears in both cases had similar, characteristic exfoliative cytology. The tumor cells were small and either single or arranged in groups and files. They had barely visible cytoplasm, darkly staining nuclei with finely stippled chromatin, and inconspicuous nucleoli. The characteristic molding of the nuclei was also present. Immuno-histochemical staining for neuron-specific enolase and synaptophysin was positive in tissue sections. Pancytokeratin, vimentin, muscle-specific actin, desmin, alpha-fetoprotein, S-100, glial fibrillary acid protein, common leukocyte antigen and chromogranin were negative. CONCLUSION: When a uterine small cell carcinoma is suspected in a cervicovaginal smear, the similarity of cervical and endometrial small cell carcinoma requires a differential curettage and immunohistochemical demonstration of neuroendocrine differentiation in order to arrive at the final diagnosis.

Adenocarcinoma of the uterine cervix associated with pregnancy: a retrospective 10-year investigative study.

We conducted chart reviews on 56 women of childbearing age (up to age 40) diagnosed with adenocarcinoma of the cervix. Of these, 16 (30%) were identified as having pregnancy-associated disease. Eleven of the 16 were diagnosed with invasive adenocarcinoma (i.a.) and 5 with adenocarcinoma in situ (AIS). Prior cervicovaginal smears were available on 12 of the 16 women; of these, only one was reported as showing cancer. Mean age at time of diagnosis of AIS and IA in the pregnant women was 33 and 30.3 yr and in the nonpregnant women, 30.6 and 32.8 yr, respectively. We found an absolute increase in the number of cases of adenocarcinoma of the cervix over the past decade in both pregnant and age-matched nonpregnant women of childbearing age (1984-1988: 6, pregnant; 12, nonpregnant; 1989-1994: 10, pregnant; 28, nonpregnant) but no significant difference in the percentages of the disease in pregnant vs. nonpregnant populations (Z = 0.95). We also found an overall increase in the number of diagnosed cases of adenocarcinoma of the cervix (especially in situ) in both study groups over the same time period (1984-1988: 3, AIS; 14, IA; 1989-1994: 15, AIS; 24, IA).

Peritoneal washing in borderline epithelial ovarian tumors in women under 25: the use of cell block preparations.

Serous tumors of low malignant potential are uncommon in women under 30-years-old peritoneal washings play an important role in the diagnosis and prognosis of ovarian neoplasms. Accurate diagnosis of peritoneal washings is important in determining therapeutic regimens and in determining patient prognosis. In peritoneal washings, these tumors can be difficult to distinguish from reactive benign mesothelial cells. The cases of four women with borderline serous ovarian tumors, all of whom were under the age of 25, and had peritoneal washings which were positive for papillary tumors were reviewed.

Ovarian mucinous cystadenoma associated with mural leiomyomatous nodule and massive ovarian edema.

Mural nodules associated with mucinous and serous tumors of the ovary may represent a reactive process, a benign tumor, or a malignant neoplasm. Mural leiomyomatous nodule in mucinous cystadenoma is extremely rare. Two such cases had been described previously. In this case a 43-year-old white female presented with 24-h history of left quadrant pain and a left adenexal cystic mass on ultrasound examination. An exploratory laparotomy revealed a left ovarian mass with torsion on its pedicle. Frozen section of the cystic mass showed a mucinous cystadenoma with mural smooth muscle proliferation. A total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Histologic examination of the mass revealed a mucinous cystadenoma with a mural leiomyomatous nodule and an enlarged ovary with massive stromal edema. This is the first case of a mural leiomyomatous nodule in association with a mucinous cystadenoma in an ovary with massive edema. This case broadens the histologic spectrum in which a mural leiomyomatous nodule may be encountered.

Significant reduction in the rate of false-negative cervical smears with neural network-based technology (PAPNET Testing System).

False-negative cervical Pap smears may lead to disability or death from carcinoma of the uterine cervix. New computer technology has led to the development of an interactive, neural network-based vision instrument to increase the accuracy of cervical smear screening. The instrument belongs to a new class of medical devices designed to provide computer-aided diagnosis (CADx). To test the instrument's performance, 487 archival negative smears (index smears) from 228 women with biopsy-documented high-grade precancerous lesions or invasive cervical carcinoma (index women) were retrieved from the files of 10 participating laboratories that were using federally mandated quality assurance procedures. Samples of sequential negative smears (total 9,666) were retrieved as controls. The instrument was used to identify evidence of missed cytological abnormalities, including atypical squamous or glandular cells of undetermined significance (ASCUS, AGUS), low-grade or high-grade squamous intraepithelial lesions (LSIL, HSIL) and carcinoma. Using the instrument, 98 false-negative index smears were identified in 72 of the 228 index women (31.6%, 95% confidence interval [CI]: 25% to 38%). Disregarding the debatable categories of ASCUS or AGUS, there were 44 women whose false-negative smears disclosed squamous intraepithelial lesions (SIL) or carcinoma (19.3%; 95% CI: 14.2% to 24.4%). Unexpectedly, SILs were also identified in 127 of 9,666 control negative smears (1.3%; 95% CI: 1.1% to 1.5%). Compared with historical performance data from several participating laboratories, the instrument increased the detection rate of SILs in control smears by 25% and increased the yield of quality control rescreening 5.1 times (P < 0.0001). These data provide evidence that conventional screening and quality control rescreening of cervical smears fail to identify a substantial number of abnormalities. A significant improvement in performance of screening of cervical smears could be achieved with the use of the instrument described in this report.

Automated screening for quality control using PAPNET: a study of 638 negative Pap smears.

To determine if the PAPNET screening system can be used for quality control to lower false-negative rates for Pap smears 638 manually screened, "negative" Pap smears were subjected retrospectively to the PAPNET screening system. Twenty-nine of the smears came from 18 patients who subsequently had biopsyproven high-grade squamous intraepithelial lesions (SIL). The remaining 609 negative smears were arbitrarily selected as controls. One hundred twenty-eight (128) of the retrospectively reviewed smears (20%) were selected by PAPNET for microscopic referral because of potential abnormalities. Abnormalities were confirmed on 14 of these smears upon microscopic evaluation. Five of these 14 smears were from smears obtained from four of the 18 women with high-grade SIL. The incidence of manually screened false-negatives detected by PAPNET rescreening was 14/638 or 2.2% for the entire patient population in this study and 5/29 or 17.24% for the targeted patients known to have subsequently developed highgrade lesions. The 2.2% decrease in the false-negative rate in this experiment may be partly artificial as this study group was seeded with false-negative cases at high risk for containing missed abnormalities. The implementation of the PAPNET system for quality control may lower false-negative rates for Pap smears.

Pneumocystis carinii thyroiditis diagnosis by fine needle aspiration cytology: a case report.

BACKGROUND: Extrapulmonary infection or dissemination of Pneumocystis carinii (PC) is rare, but under certain conditions the parasite can spread via the bloodstream or lymphatic vessels. Systemic pneumocystosis most often involves the lymph nodes, stomach, spleen, liver, skin, pancreas, choroid and eye. Isolated lesions containing PC have also been identified in the thyroid. CASE: A 41-year-old homosexual male infected with the human immunodeficiency virus (HIV) developed a PC infection in the thyroid gland. The patient had had thrush and anal herpes since being diagnosed as HIV positive in 1984. In 1992 the patient developed a mass in the area of the right lobe of the thyroid gland. Smears from fine needle aspiration cytology of the thyroid mass revealed epithelioid cells. However, a cell block revealed numerous PC organisms on Gomori methenamine-silver stain; that finding was confirmed by an excisional biopsy. The patient had not previously been diagnosed with PC pneumonia. CONCLUSION: Our case of thyroid involvement with PC expands the clinical spectrum of extrapulmonary pneumocystosis in patients with the acquired immunodeficiency syndrome. We believe that in these patients the incidence of Pneumocystis thyroiditis will continue to rise and be reported.

Comparative cytologic findings of in situ and invasive adenocarcinoma of the uterine cervix.

The cytologic findings in 13 cases of cervical adenocarcinoma in situ (mean age 33.9 yr) were compared with those in 9 cases of cervical invasive adenocarcinoma (mean age 45.7 yr). All diagnoses were confirmed by biopsy. The major differences found were that a necrotic background (66% invasive vs. 0% in situ) and macronucleoli (77% invasive vs. 0% in situ) were more common in invasive cases, whereas associated squamous-cell dysplasia (69% in situ vs. 0% invasive) was more common in in situ cases. Other differences included syncytial tissue fragments with irregular cell borders, frequent cell drop-off, and markedly atypical single columnar cells (or markedly atypical naked nuclei) seen more commonly in invasive cases, whereas monolayer sheets and/or syncytial tissue fragments with smooth borders and rare cell drop-off were more common in in situ cases. Although none of these features is diagnostic individually, in combination they are helpful in distinguishing between in situ and invasive adenocarcinoma. Nine of 13 of the in situ cases showed associated squamous-cell dysplasia. In all nine of these cases, the glandular dysplasia was overlooked or underestimated in severity on original cytologic diagnosis. This suggests that the presence of a squamous lesion may lead to decreased detection of glandular lesions, perhaps because the features of squamous lesions are more well known; thus they are more easily recognized, at the expense of glandular lesions. All invasive adenocarcinomas were identified as carcinoma in the original diagnosis with seven specified as invasive adenocarcinomas.

Black thyroid: a pitfall for aspiration cytology.

Black thyroid discoloration following long-standing use of minocycline has been reported. Morphologic findings of aspiration cytology of these lesions was first reported from The Ohio State University. This abstract describes a second case of black thyroid that was preceded by aspiration cytology. In both cases, thyroidectomies were performed based on "indeterminate" fine-needle aspiration cytology (FNAC). Degenerative changes in follicular epithelial cells in black thyroid causes nuclear hyperchromasia and chromatin clumping, which may be mistaken for neoplasia. Pigment present in follicular epithelial cells and macrophages may be obscured by pigments with similar microscopic appearances, such as hemosiderin. A clinical history of the chronic use of a tetracycline derivative should alert the pathologist to the possibility of black thyroid. Diagnosis may be made by applying special stains on the cell block. The pigment stains with Melanin stain (Fontana) and bleaches with potassium permanganate. In the light of increasing use of FNAC of the thyroid gland and the large number of patients who received tetracycline therapy in the last two decades, it is likely that some practicing cytopathologists may experience this pitfall.

Necrosis of a Hürthle cell tumor of the thyroid following fine needle aspiration. Case report and literature review.

A Hürthle cell tumor of the thyroid gland resected ten days after fine needle aspiration (FNA) showed extensive necrosis accompanied by a small area of hemorrhage. Although no vascular thrombosis was noted in the histologic specimen, it is possible that the necrosis was the result of compromised vascular supply due to the FNA.

Prognostic factors in patients with primary transitional cell carcinoma of the upper urinary tract.

A total of 50 patients with primary transitional cell carcinoma of the upper urinary tract underwent deoxyribonucleic acid ploidy characterization by flow cytometric analysis of paraffin embedded specimens. The primary tumor was diploid in 29 patients (58%) and aneuploid in 21 (42%). Aneuploidy was identified more frequently in grade 3 than in grades 1 and 2 neoplasms (p = 0.001). Additionally, grade 3 neoplasms occurred more often with invasive (stages T2 to T3) compared to superficial (stages TA, TIS and T1) tumors (p = 0.002). However, deoxyribonucleic acid ploidy was not significantly associated with tumor stage. Among the 49 patients treated by a definitive operation the median survival free of disease and median over-all survival were 33.7 and more than 120 months, respectively. Variables examined included deoxyribonucleic acid ploidy, tumor grade, tumor stage, primary tumor site and type of operation. In the univariate analysis deoxyribonucleic acid ploidy was the only significant predictor of survival free of disease (p = 0.04). Aneuploid tumors had a median survival free of disease of 19 versus 59 months for diploid tumors. However, in the multivariate analysis of factors affecting survival free of disease, the type of operation performed was the only significant variable. Patients undergoing nephroureterectomy with en bloc bladder cuff excision had a favorable survival free of disease (p = 0.04). Tumor stage was the only significant factor associated with over-all survival in univariate and multivariate analyses (p = 0.02 and 0.005, respectively). Patients with superficial tumors had a median survival of more than 120 versus 72 months for patients with invasive tumors. The data suggest that deoxyribonucleic acid ploidy may be a useful parameter to identify risk groups and plan the management of patients with primary transitional cell carcinoma of the upper urinary tract.

Cystic thyroid nodules. The dilemma of malignant lesions.

A retrospective study of 221 surgically resected thyroid nodules disclosed that 71 (32%) were cystic and 150 (68%) were solid lesions. Ultrasonography correctly characterized cystic nodules in all but one case. Comparing cystic and solid nodules, there were no differences in patient demographics (mean ages, 47.7 +/- 1.8 SEM vs 45.9 +/- 1.2 years; sex, 78% females both groups), the proportion that were solitary (39% vs 40%), or the nodule size (49% vs 47% greater than or equal to 2 cm in diameter). Of cystic thyroid lesions, 4% were simple cysts, 82% were degenerating benign adenomas or colloid nodules, and 14% were malignant compared with 23% of solid lesions that were malignant. Most cystic lesions (81%) contained bloody fluid. One benign true cyst was filled with thick brown fluid, while clear yellow fluid was repeatedly aspirated from one malignant cystic nodule. Malignant fine-needle aspiration cytology was the best predictor of cancer (100%). Much less predictable were signs of local compression or invasion (43%), a history of head or neck irradiation (33%), cyst recurrence after aspiration (29%), or an increase in the cystic nodule's size (7%). Indeterminate cytology identified malignancy with about half the frequency in cystic lesions as compared with solid nodules (13% vs 27%). The only false-negative fine-needle aspiration cytology occurred in a cystic lesion. In patients with cystic papillary cancers, needle aspirates contained insufficient material for diagnosis in 20% that occurred in no patient with solid papillary carcinoma. The sensitivities and specificities of fine-needle aspiration cytology for solid nodules were 100% and 55%, and for cystic nodules were 88% and 52%. Thus, cystic lesions are as likely as solid thyroid lesions to harbor a malignancy that cannot be predicted from the cyst's clinical characteristics or the patient's demographic data. Although fine-needle biopsy is the best predictor of malignancy in either cystic or solid thyroid lesions, it is slightly less reliable when a thyroid lesion is fluid filled rather than solid. We believe that most cysts not abolished by aspiration should be surgically excised.

Flow cytometric analysis of primary and metastatic bladder cancer.

A total of 22 patients with high grade P2-4N+ transitional cell carcinoma of the bladder underwent flow cytometric analysis of nuclei obtained from paraffin embedded specimens from the primary (bladder) and metastatic (lymph node) sites. Tumor heterogeneity was defined as polyclonal aneuploidy of the primary tumor (not identified in the population studied) or as a difference in the deoxyribonucleic acid index of the primary and metastatic sites of 0.20 or more (8 patients). With these criteria 8 patients (36%) had heterogeneous tumors and 14 (64%) had homogeneous tumors. The median survival of 14 patients with aneuploid and 8 with diploid primary tumors was 17.5 and 8.0 months, respectively (p equals 0.08, Lee-Desu test). When patient survival was compared to the ploidy of the metastatic site, or in patients with diploid primary and metastatic lesions versus deoxyribonucleic acid aneuploidy at either the primary and/or metastatic site, the aneuploid tumors had a longer survival but this difference was not significant (p equals 0.13 and 0.23, respectively). Our study demonstrates the value of flow cytometry to identify primary metastatic tumor heterogeneity. It also suggests that the presence of metastasis may be a more important factor to define the biological potential of transitional cell carcinoma than is deoxyribonucleic acid ploidy.

Is DNA ploidy an independent prognostic indicator in infiltrative node-negative breast adenocarcinoma?

To evaluate DNA content as an independent, long-term prognostic indicator in infiltrative, node-negative adenocarcinoma of the breast, flow cytometric DNA analyses were performed retrospectively in 165 patients. The exclusive use of paraffin-embedded tissue permitted the study of patients for whom 3 to 15 years' follow-up was available. Other investigators have shown a relationship between DNA nuclear content and well-known prognostic indicators of breast carcinoma, such as estrogen receptors, age, menopausal status, and stage of tumor. However, very few of these studies were based on patients with long-term clinical follow-up and investigated the independent prognostic value of DNA nuclear content. The frequency of aneuploidy in the patients in this study was 57%, with DNA indices ranging from 0.73 to 2.59. Survival in patients with localized breast carcinoma with DNA aneuploid tumors was 84.1% at 5 years and 75.5% at 10 years. Those with diploid tumors showed survival of 87.8% at 5 years and 73.4% at 10 years. These data show no independent prognostic value for DNA nuclear content. The relationship between DNA content, tumor histologic type, and age was also investigated. High-grade tumors were more often aneuploid. There was no association between DNA content and age. Of 165 patients, information regarding estrogen receptor status was available in only 77; 45% of those with aneuploid tumors and 35% with diploid tumors were estrogen receptor-negative. This difference was not significant. The authors conclude that simple determination of DNA ploidy fails to indicate prognosis for infiltrative, node-negative breast carcinoma.