William W. Johnston

The malignant pleural effusion: a review of cytopathologic diagnoses of 584 specimens from 472 consecutive patients

This study reports the cytopathologic diagnoses rendered on all malignant pleural effusions received and processed over a period of 14 years. Specimens of fluid from various body sites (25,464) were examined. Of these, 5888 (23%) were specimens of pleural effusions. Five hundred eighty‐four specimens (9.9% of total pleural fluid specimens) taken from 472 patients were diagnosed as containing cancer cells. Of the malignant pleural effusions, 75.7% were classified as carcinomatous in type. Adenocarcinomas comprised 47.4% of the 584 specimens. The groups of large cell undifferentiated carcinoma and lymphoma/leukemia approximated one another in being the second most common cancer groups (14.3% and 15.0%, respectively). For both males and females, the frequency of organ site or primary tumor type was lung (35.6%), lymphoma/leukemia (15.9%), breast (14.8%), female genital tract (8.1%), and gastrointestinal tract (5.9%). Among male patients, the order of frequency was lung (49.1%), lymphoma/leukemia (21.1%), gastrointestinal tract (7.0%), genitourinary tract (6.0%), and malignant melanoma (1.4%). In female patients, the order of frequency was breast (37.4%), female genital tract (usually ovary) (20.3%), lung (15.0%), lymphoma/leukemia (8.0%), and gastrointestinal tract (4.3%). In 48 patients (10.2%) the primary site of neoplasm was never determined. In 90.5% of patients a cytopathologic diagnosis conclusive for cancer was obtained on the first specimen of fluid. There were no false positive diagnoses.

Prognostic significance of peritoneal cytology in patients with endometrial cancer and preliminary data concerning therapy with intraperitoneal radiopharmaceuticals

One hundred sixty-seven patients with clinical State I carcinoma of the endometrium were treated primarily by operation consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, selective pelvic and para-aortic lymphadenectomy, and cytologic testing of peritoneal washings. Twenty-six (15.5%) of the 167 patients had malignant cells identified on cytologic examinations of peritoneal washings. Recurrence developed in 10 of these 26 (34.0%) compared to 14/141 (9.9%) patients with negative cytologic testing. Of the 26 patients, 13 (50%) had disease outside of the uterus at operation and seven have died of disease (54%). Thirteen patients had malignant cells in the peritoneal washings but no disease outside of the uterus and six (46%) of these have died of disseminated intra-abdominal carcinomatosis. On the basis of the poor outcome of those patients who had malignant cells in the peritoneal washings in the 167 patients studied, a plan of treating such patients with intraperitoneal radioactive chromic phosphate suspension (P-32) was instituted. Twenty-three subsequent patients with clinical Stage I carcinoma of the endometrium were found to have malignant cells in the peritoneal fluid. All 23 received intra-abdominal P-32 suspension instillation after operation. There have been three recurrences with two patients dying of disease. All of the three recurrences appeared at sites distant from the abdominal cavity. Peritoneal cytologic examination appears to be an important factor in the prognosis of endometrial cancer and, when the washings are positive for malignant cells, intraperitoneal chronic phosphate therapy appears to be efficacious.

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.

Transthoracic fine needle aspiration biopsy : Sensitivity in relation to guidance technique and lesion size and location

OBJECTIVE To obtain site- and size-specific data on transthoracic fine needle aspiration (TFNA) and determine the sensitivity in relation to guidance technique and lesion size and location. STUDY DESIGN Data on 112 patients undergoing TFNA between 1992 and 1993 were analyzed for accuracy rates, stratified according to lesion size and location within the lung. The series included 13 benign lesions, 53 metastatic neoplasms and 46 primary carcinomas. RESULTS Overall sensitivity was 90%, with 92% specificity. There was a clear relationship between nodule size and sensitivity of TFNA, with a sensitivity of 60% for lesions < 1 cm but 93% sensitivity for nodules > or = 2 cm in diameter. Similarly, lesion location affected sensitivity. Sensitivity was 100% for peripherally located nodules but was as low as 82% for nodules in the centrobasal portion of the lung. Sensitivity was higher for fluoroscopy (97%) than computed tomography (80%). CONCLUSION The guidance technique as well as lesion location and size affect diagnostic accuracy.

Intraperitoneal chromic phosphate P 32 suspension therapy of malignant peritoneal cytology in endometrial carcinoma

Malignant peritoneal cytology in patients with endometrial carcinoma is a poor prognostic feature, identifying patients at high risk for early intra-abdominal recurrence. Between 1977 and January, 1983, 65 women with endometrial carcinoma who had malignant peritoneal cytology were treated with adjuvant intraperitoneal radioactive chromic phosphate P 32 suspension. Fifty-three patients (80%) were clinical Stage I, nine (14%) were Stage II, and three (7%) were clinical Stage III. Life-table estimates of disease-free survival were 89% for clinical Stage I patients and 94% for surgical Stage I patients beyond 24 months. One patient developed an intraperitoneal recurrence, four had simultaneous intraperitoneal and extraperitoneal recurrences, and six developed recurrences outside of the peritoneal cavity. Few significant acute complications occurred after therapy with radioactive chromic phosphate P 32 suspension. Chronic intestinal morbidity that required surgical correction was encountered in five of 17 patients (29%) who received adjuvant pelvic radiation, compared to none of the 48 patients (0%) who received only radioactive chromic phosphate P 32 suspension (p less than 0.001). Intraperitoneal instillation of radioactive chromic phosphate P 32 suspension is effective therapy for patients with malignant peritoneal cytology from endometrial carcinoma. Caution should be exercised when radioactive chromic phosphate P 32 suspension and external radiation therapy are combined.

Endoscopic brush cytology of the upper urinary tract. Evaluation of its efficacy and potential limitations in diagnosis.

OBJECTIVE To evaluate the efficacy of endoscopic brush cytology in diagnosing transitional cell carcinoma of the upper urinary tract. STUDY DESIGN Sixty-three endoscopic brush cytology specimens from 48 patients were compared with corresponding cytologic specimens obtained by irrigation and catheterization as well as histologic specimens. RESULTS Twenty patients (25 brushes) had histologically documented transitional cell carcinoma (TCC) or carcinoma in situ (CIS) of either the ureter or renal pelvis. Among these, 8 (32%) of the brush samples were reported as positive for TCC, 10 (40%) atypical or suspicious, and 7 (28%) negative. The seven negative cases were ultimately shown to be low grade (I-II/IV) TCC. Combining atypical and positive diagnoses, the calculated sensitivity for diagnosis of TCC by this technique was 72%. The irrigations or catheterized urines from these same patients yielded lower sensitivity, 48%, and detected only higher grade lesions. Ten patients were proven histologically to have nonneoplastic disease (hydroureter, obstruction, inflammation). Sixteen of the 17 brush specimens from these patients were negative, resulting in a specificity of 94%. In the remaining 18 patients (21 brushes) there were 17 negatives and 4 atypicals. Concomitant cytology supported the brush diagnosis in all but one sample. CONCLUSION Brush cytology is a specific and more sensitive sampling method than irrigation or catheterized urine in detecting TCC of the upper urinary tract. Brush cytology does not appear to be successful in diagnosing dysplasia or CIS. As with urinary cytology in general, the technique is less effective in diagnosing low grade (I and II) lesions.

Fine-needle aspiration biopsy of the mediastinum

Fine-needle aspiration is a useful technique to identify neoplasms of many sites, such as breast, thyroid, and lung. Thirty-two mediastinum aspirates from 29 patients were reviewed. Five aspirates yielded insufficient material. Five aspirates were of benign lesions. Four aspirates were suggestive of but not diagnostic of malignancy. Eighteen aspirates contained malignant cells; in 13 of these, a definite cell type was identified, which usually was metastatic lung carcinoma; in five instances, the cell type could not be unequivocally identified. Complications were minimal, two instances of pneumothorax (6.3 percent) and two of hemoptysis (6.3 percent). No deaths or hemorrhage occurred. In 16 of the 29 patients (55 percent), thoracotomy was avoided because of fine-needle aspiration biopsy. It is concluded that fine-needle aspiration biopsy of the mediastinum is a safe, useful diagnostic tool. This procedure may obviate the need for thoracotomy in persons with inoperable cancer, thus lowering medical costs and length of hospital stay.

The significance of peritoneal cytology in patients with carcinoma of the cervix

Between 1972 and 1977, 141 patients with benign gynecologic disease and 149 patients with carcinoma of the cervix were evaluated with peritoneal fluid cytology at time of celiotomy. There was no positive cytology (malignant cells) in the benign disease group. The overall incidence of positive peritoneal cytology in the cervical group was 8.1%. Positive peritoneal cytology was found four times more frequently in adenocarcinoma and adenosquamous carcinomas than squamous carcinomas. The incidence in patients undergoing surgery for recurrent or persistent carcinoma after radiation therapy was 22.6% compared to 4.5% in those treated primarily with definitive surgery. The prognoses do not seem to be influenced by peritoneal cytology status when other poor prognostic factors were considered.

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.

Cytologic diagnosis of lung cancer. Principles and problems.

This diagnostic seminar discusses the current status of the principles and problems of cytology as it is applied to the diagnosis of lung cancer. This discussion is divided into four major parts. Part I presents a discussion of cytopreparatory techniques and cytology of the lung in the absence of cancer. The cytology of benign proliferations which may mimic cancer is emphasized. The role of cytology in the diagnosis of pulmonary infectious organisms is noted. Part II discusses lung cancer as manifested in specimens of sputum, bronchial washings, and bronchial brushings. Part III presents some data on the validity of cytology with respect to role of specimen number and type in lung cancer diagnosis and cell typing in lung cancer. The continued usefulness and importance of multiple specimens of sputum for lung cancer diagnosis are documented. Part IV presents a brief synopsis of fine needle aspiration biopsy of lung cancer.