Cheryl A. Szpak

Use of a monoclonal antibody (B72.3) as a novel immunohistochemical adjunct for the diagnosis of carcinomas in fine needle aspiration biopsy specimens

Monoclonal antibody B72.3 has been shown to be reactive with a high-molecular-weight glycoprotein complex termed TAG(tumor-associated glycoprotein)-72. By the avidin-biotin immunoperoxidase method, fine needle aspirates and corresponding surgically excised tumor tissues from both malignant and benign tissues were analyzed for TAG-72 expression. Staining (range, 1 to 100 per cent of tumor cells) with monoclonal antibody B72.3 was observed in needle aspirates from 18 of 18 adenocarcinomas and adenosquamous carcinomas of the lung, 17 of 21 adenocarcinomas of the breast, and six of six adenocarcinomas of the colon, as well as adenocarcinomas from other body sites. In contrast, small cell carcinomas of the lung, malignant melanomas, lymphomas, and sarcomas did not stain with the antibody. Benign lesions from the breast, lung, pancreas, parotid, and thyroid also failed to stain. In 66 patients, tumor-bearing tissue had also been resected and was available for comparative examination with monoclonal antibody B72.3. In 62 of these 66 patients, the staining patterns in the aspirates were found to be predictive of the patterns of antibody reactivity in the comparable surgically resected tissues. From these studies it is concluded that monoclonal antibody B72.3 defines a tumor-associated antigen that is expressed in neoplastic cells but not in benign cells and is most selectively expressed in adenocarcinomas. This monoclonal antibody may be used as a novel adjunct for the diagnosis of carcinoma in fine needle aspiration biopsy specimens.

Leiomyosarcoma of the uterus: Clinicopathologic study of 21 cases

A detailed clinicopathologic study of 21 patients with uterine leiomyosarcoma was undertaken. The diagnosis of leiomyosarcoma was made for those uterine smooth muscle tumors showing cellular atypia and 5-9 mitoses per 10 high-powered fields (M/10 HPF) and those with 10 or more M/10 HPF. Using these strict pathologic criteria to define leiomyosarcoma, menopausal status, margin type (pushing vs infiltrating), tumor size, grade, location, and the presence of vascular invasion and/or hemorrhage were not associated with prognosis. The 5-year survival rate was 25%. Survival rates were not improved by the use of adjuvant chemotherapy in those patients rendered free of gross disease by initial surgery.

Histologic features associated with hormonal responsiveness of ectopic endometrium

Objective To correlate histologic parameters of endometriosis with hormonal responsiveness. Design Seven hundred sixty-eight unselected endometriotic implants and the corresponding intrauterine endometrium from 196 patients were classified by standard endometrial dating criteria. In addition, other histologic characteristics of endometriotic implants such as the amount of stroma, amount of fibrosis, the presence of surface epithelium, presence of focal hemorrhage, and gland characteristics were also noted. Setting Academic tertiary referral center. Main Outcome Measures Comparison of histologic dating between endometriotic implants and the corresponding endometrium as a function of histologic parameters. Results Implants that were synchronous with the corresponding eutopic endometrium had more stroma than those that were out of phase. The amount of fibrosis was inversely related to hormonal responsiveness. The presence of surface epithelium in implants was also associated with an impaired response (28.0% versus 48.0% in phase). Endometriomas were found to be in phase with the corresponding endometrium less often than other types of implants (21.7% versus 43.3%). Although endometriomas had similar amounts of stroma when compared with other implants, they had significantly more fibrosis (850.2 μ m versus 195.0 μ m). Conclusions These results suggest that the unpredictable response of endometriotic implants to cyclic endogenous hormones and hormonal therapy may be related to the architectural relationships between the cellular elements found in normal endometrium.

Prognostic value of peritoneal washings in patients with malignant mixed müllerian tumors of the uterus

Peritoneal washings from 36 women with all pathologic stages of mixed müllerian tumors of the uterus (27 homologous stroma, nine heterologous stroma) were reviewed in a blinded retrospective fashion for the presence and type of malignant cells collected. Malignant tumor cells were demonstrated in the washings of 16 patients; 13 contained adenocarcinoma only, two contained adenocarcinoma and sarcoma, and one contained sarcoma cells only. Coxs logistic regression analysis showed that cytologic examination of peritoneal washings when combined with pathologic staging provides a statistically significant discriminant of disease-free survival. Patients with a favorable prognosis (pathologic Stage I and peritoneal washings free of malignancy) had sevenfold increased disease-free survival compared with survival of the patients with an unfavorable prognosis (pathologic Stages II, III, or IV or malignant cells present in peritoneal washings). Three of the 18 patients with pathologic Stage I disease manifested malignant tumor cells in the peritoneal washings and all three patients died of disease in less than 1 year. The presence of malignant cells in peritoneal washings in patients with mixed müllerian tumor apparently limited to the uterus suggests a clinical course that is similar to that of those with more advanced disease.

Pigmented Squamous Cell Carcinoma of the Conjunctiva: A Clinicopathologic Ultrastructural Study

The clinical and morphologic features of a pigmented squamous cell carcinoma of the bulbar conjunctiva in a 57-year-old black man are reported. The tumor resembled the more usual epibulbar squamous cell carcinoma but had many melanin containing cells within it. Transmission electron microscopy disclosed melanosomes within squamous epithelium, melanocytes, and macrophages. The only cells within the tumor with morphologic features of a malignant neoplasm were squamous in type. The literature on this rare conjunctival tumor, which has a good prognosis following complete excision, is reviewed. Pigmented squamous cell carcinomas need to be distinguished from the more common nodular melanomas, which have a more ominous outlook.

Tumor-associated antigen TAG-72: Correlation of expression in primary and metastatic breast carcinoma lesions

SummaryVariability of tumor-associated antigens among and within human tumor cell groups presents a potential problem in the development and optimization of immunodiagnostic and therapeutic procedures for cancer. We determined the degree of expression of a tumor-associated antigen in the primary and metastatic lesions of 23 patients with infiltrating ductal carcinoma; this was accomplished using monoclonal antibody B72.3, an IgG1 generated against membrane-enriched fractions of human metastatic breast carcinomas and reactive with a 220,000–400,000 d glycoprotein complex, termed TAG-72, and the avidin-biotin complex immunoperoxidase method on fixed tissue sections. Sixteen of the 23 breast carcinomas (70%) demonstrated MAb B72.3 reactivity (range 5% to 100% of tumor cells staining). Reactivity of lymph node metastases was present in 14 of 21 patients (67%). MAb reactivity in metastases to distant sites, including bone, adrenals, liver, skin and effusions, was present in 10 of 18 patients (56%). In one patient, neither the primary carcinoma nor the metastasis to the lymph node demonstrated reactivity. There was a statistically significant positive correlation between MAb B72.3 reactivity in both primary and lymph node metastases (Kendalls Correlation Coefficient = 0.60, p = 0.0006) and between lymph node and distant metastases (Kendalls Correlation Coefficient = 0.48, p = 0.02) of the same patient. No correlation existed between antibody reactivity seen in the primary and that found in the distant lesions of that patient. These studies thus demonstrate that monoclonal antibody B72.3 can detect expression of a tumor-associated antigen in both primary and metastatic infiltrating ductal carcinoma lesions, and may prove valuable in the understanding of tumor biology of metastases and as a means for diagnosing occult disease.

Phenotypic Heterogeneity of a Tumor-Associated Antigen in Adenocarcinomas of the Colon and Their Metastases as Demonstrated by Monoclonal Antibody B72.3

To determine the potential antigenic heterogeneity which might exist between a primary colon carcinoma lesion and its metastases, we stained the formalin and Zenkers fixed paraffin-embedded tissues from the resection specimens of 12 patients with Dukes Stage C adenocarcinoma of the colon with monoclonal antibody (MAb) B72.3. This MAb previously has been shown to react with a high molecular weight tumor-associated glycoprotein (termed TAG-72), which is selectively expressed in adenocarcinomas versus normal adult tissue. Five to 90% of malignant cells from all primary lesions stained with MAb B72.3 in paraffin-embedded tissue. A significantly diminished percentage of cells stained from the metastases in lymph nodes and distant sites. Pearson correlation coefficients showed that the antigenic expression of the metastasis in the lymph node was a better indicator of the antigenic expression of the metastasis in the distal site than was the primary lesion in the colon. These findings suggest that the effective use of monoclonal antibodies for diagnostic imaging or therapeutic purposes may require the evaluation of the antigenic expression in regional node metastases rather than that of the primary lesion.

The importance of determining karyotype in premenarchal females with gonadal dysgerminoma: two case reports

Gonadal dysgerminomas developed in two girls, aged 12 and 15 years. Both were initially treated with conservative unilateral gonadectomy. Forty-six, XY gonadal dysgenesis was not suspected in either patient due to the normal appearance of the contralateral gonads and internal female genital organs. One died of a second germ cell malignancy which developed in the contralateral ovary 9½ years later. The diagnosis of 46, XY gonadal dysgenesis was established by karyotype in both patients. Although conservative surgical management is desirable for nulliparous women with unilateral dysgerminomas, the presence of 46, XY gonadal dysgenesis should be suspected in all premenarchal girls with ovarian germ cell malignancies. If karyotyping reveals the presence of an Y chromosome, bilateral gonadectomy is indicated because of the risk that another neoplasm may develop in the contralateral ovary.

Vasography: Effect of Various Agents on Vas Deferens Patency

Vasography is a common diagnostic procedure utilized in evaluating the male genital tract for causes of azoospermia, for evaluation of persistent perineal pain and seminal vesiculitis, and recently used in the staging of prostate cancer. In order to evaluate the effects of injectable agents on the healthy vas deferens, 7 groups of 10 rats had the left vas deferens injected by vasopuncture with saline, 4 contrast agents, doxycycline and absolute alcohol. The animals were sacrificed 8 weeks later, and were examined for patency of the vas and inflammatory response. Results revealed that vasopuncture did not produce obstruction. Vasography with water-soluble contrast media does entail a low risk of inflammation in the rat, but produces no obstruction. Intra-vas injection of doxycycline, injected by some for treatment of chronic seminal vesiculitis and perineal pain, is not deleterious in the rat model.

Prognostic Value of Cytologic Examination of Peritoneal Washings in Patients with Endometrial Carcinoma

Peritoneal pelvic washings from 54 women with pathologic stage I endometrial carcinoma were evaluated in a blind retrospective fashion for the concentration of malignant cells present. None of the 42 patients with normal washings developed recurrence after a median disease-free survival of 36 months. Of the 12 patients with adenocarcinoma in the washings, 4 had high concentrations of malignant cells (greater than 1000 cells/100 ml sample), and all 4 died as a consequence of carcinoma within two years. The remaining eight patients had lower concentrations of malignant cells in the washings (less than 1000 cells/100 ml sample), and six of these patients had no evidence of disease after 37 to 64 months. Coxs nonparametric statistical model showed that increasing concentrations of adenocarcinoma cells in washings significantly shortened the time to recurrence of disease. The abundance of malignant cells has prognostic importance in identifying those patients with pathologic stage I disease who may require more aggressive therapy.