Relationship between the in vitro colony growth of human tumors and cytologic diagnosis.

The cytologic examinations and cloning efficiencies of 47 human tumor specimens (19 ovarian carcinomas, 6 sarcomas, 5 lung carcinomas, and 17 miscellaneous tumors) were compared to evaluate the predictability of clonogenecity by cytologic diagnosis. Cytologic examination preceding clonogenic assay identified the 50% to 60% of all specimens that failed to yield in vitro chemotherapy sensitivity by this assay, with a false-negative rate of 10%. The frequency of cytologically identifiable tumor cells in the plating suspension was independent of the histologic type of tumor (ovarian carcinoma or others) and the nature of the specimen (solid tumor or malignant effusion). Nearly 66% of all specimens were cytologically negative. The in vitro sensitivity can be assessed in approximately 75% of cytologically positive specimens. Cytologic evaluation preceding soft-agar clonogenic assay of human tumors can reduce cost and effort by predicting colony-producing specimens.

Problems in the diagnosis of small cell carcinoma of the lungs by fiberoptic bronchoscopy.

Fiberoptic bronchoscopy (FOB) with the aid of endoscopic biopsies and brush cytology is recognized as a valuable approach in the diagnosis of lung cancer. However, histologic classification of lung cancer based on tiny specimens obtained from FOB can be difficult. Correct identification of small cell carcinoma of the lung is especially important because its recognition usually precludes surgery. In a review of 770 patients who underwent FOB biopsies at The Mount Sinai Hospital, New York, in individuals with proven lung cancer 150 instances of small cell carcinoma were encountered. In four of these instances subsequent surgery, such as scalene node biopsy, mediastinoscopy, or thoracotomy, was performed because clinically and radiologically the tumors did not behave as small cell carcinomas. Pathologic examination of larger tissue samples from these neoplasms provided the following final diagnoses: bronchial carcinoid, adenocarcinoma, squamous cell carcinoma, and small cell carcinomas-combined type. Analysis of the FOB biopsies and brush cytology usually permit diagnosis of small cell carcinoma of the lung. However, in instances where the biologic behavior of a tumor casts doubt on the diagnosis of small cell carcinoma, further studies should be performed, including radionuclide scans, and bone marrow and other biopsies before denying the patient a chance of surgical cure.

The place of fine needle biopsy in the diagnosis of nodules of the thyroid.

Fine needle aspiration cytology with an accuracy rate of 90.2 per cent confirmed by surgical specimens was found to be a useful adjunct in the diagnosis of tumors of the thyroid but did not replace large needle core biopsy. Both methods offered information complementary to each other, and our data indicated that, when possible, they should be used together. Although both false-positive and false-negative results were reported with fine needle cytology aspiration biopsy, it was the false-negative reports which limited its use as a definitive diagnostic tool. Fine needle aspiration biopsy, however, did constitute a safe and useful method of increasing diagnostic ability in the evaluation of thyroid nodules.

Pulmonary tumorlets in cases of "tuberculoma" of the lung with malignant cells in brush biopsy.

Two cases of pulmonary nodules associated with Mycobacterium intracellulare infection were initially interpreted as carcinomas of the lung after brush cytology specimens were reported to contain malignant epithelial cells. In both instances, the cells observed in the cytology specimens exhibited marked cytologic atypia. These cells were identical to those present in tumorlets adjacent to the granulomatous lesion. Tumorlets may thus represent a source of false-positive cytologic findings or constitute a type of microscopic neoplasms of the lung.

The cytologic basis for classification of lung tumors.

Nuclear changes in cells of bronchial biopsies and surgical specimens were studied in relation to nuclear structures of cells at various mitotic phases. Cell structures comparable to early and late G1 and G2 phases were correlated with histologic types of lung tumors according to the 1981 WHO classification. The evolved cellular classification added another parameter for diagnosis of histologic alterations and for interpretation of cellular changes in cytologic specimens. Benign histological alterations contained cells in either early or late G1 phase. Well-differentiated adenocarcinomas, bronchiolo-alveolar cell carcinomas, and carcinoid tumors had cells with structure of the late G1 phase. These were distinguished from benign cells with similar structures by their increased nuclear size, their increased amount of nuclear chromatin, hyperchromasia, and increased nuclear cytoplasmic ratio. Well-differentiated acinar adenocarcinomas, papillary adenocarcinomas, clear cell carcinomas, and large cell carcinomas had cribriform nuclear structures with prominent nucleoli related to early G2 phase. Squamous cell carcinomas, poorly differentiated adenocarcinomas, giant cell carcinomas, and solid carcinomas with mucus formation had usually prominent nucleoli with nuclear structures of the late G2 phase. Small cell carcinomas were the only malignant tumors of the lung that had cells with the malignant cribriform nuclear structure of the early G2 phase without a nucleolus. Cellular markers of malignant neoplasms had also the nuclear structure of early G2 without a nucleolus but differed from small cell carcinoma by their differentiated state with presence of cilia. The cytologic diagnosis of 506 malignant tumors of 1031 cases examined resulted in a sensitivity of 86.6%. The correct diagnosis of 244 of 247 cases without tumor resulted in a diagnostic specificity of 98.8%.

Metastatic nonfunctioning parathyroid carcinoma: ultrastructural evidence of secretory granules and response to chemotherapy.

A 69-year-old woman was admitted to the hospital because of recurrent cervical nodules, a large anterior mediastinal mass, and malignant left pleural effusion. Light and electron microscopy of the resected cervical nodules and cytology of the pleural fluid showed findings consistent with parathyroid carcinoma. There was no evidence of hyperparathyroidism on clinical evaluation, multiple serum calcium and phosphorus determinations, skeletal survey, intravenous pyelogram, or radioimmunoassay of intact and carboxy-terminal parathyroid hormones in the serum. Electron microscopy revealed secretory granules in the cytoplasma of malignant cells. A dramatic and complete resolution of the mediastinal mass and pleural effusion occurred after 18 months of chemotherapy with "MACC" (methotrexate, adriamycin, cyclophosphamide and CCNU).

Carcinoma of the prostate: lymph node aspiration for staging.

Percutaneous fine-needle aspiration biopsy of suspect nodes was used for histologic staging in 33 patients with clinically localized carcinoma of the prostate after an abnormal or suspicious lymphogram. A total of 66 nodes was biopsied, and positive cytology for metastatic carcinoma was obtained from 29 nodes in 20 patients indicating the presence of stage D disease. Thus, staging lymphadenectomy and radical treatment by radiation or surgery were avoided.

Flexible fiberoptic bronchoscopy in the diagnosis of pulmonary complication of lymphoma.

Patients with known lymphoma frequently present with pulmonary abnormalities that require prompt diagnosis. The usual chest radiograph and bacteriologic studies often fail to be of diagnostic value. Since February 1973, we have performed flexible fiberoptic bronchoscopies on 76 patients with Hodgkin and non-Hodgkin lymphoma who presented with pulmonary abnormalities. Biopsy specimens revealed lymphoma in 21 of these 76 patients, pneumocystic carinii infection in six, aspergillus infection in three, and cryptococcus, herpes simplex, and squamous cell carcinoma, respectively, in the remaining three. In all, specific diagnosis was obtained in 33 patients (43%). One death from bleeding occurred in a patient with marked thrombocytopenia and respiratory failure. Flexible bronchoscopy is recommended as a valuable, relatively risk-free procedure in the diagnosis of the pulmonary manifestations, or complications, of lymphoma.

Post-lymphangiography fine needle aspiration lymph node biopsy in staging carcinoma of the prostate: preliminary report.

Five cases of clinical stage B carcinoma of the prostate are reported. Bipedal lymphangiography showed unequivocal involvement of the pelvic nodes in 3 patients and was equivocal in the other 2. Percutaneous transabdominal fine needle aspiration biopsy of abnormal or suspicious iliac nodes was performed and a positive cytolocal diagnosis of metastasis was obtained in all 5 patients. Therefore, staging lymphadenectomy and an extensive radical operation were avoided. Percutaneous fine needle biopsy is a reliable, easy and safe technique that should be used in staging prostatic carcinoma whenever there is evidence of metastatic nodal involvement by lymphangiography.

Flexible bronchoscopy in nonvisualized carcinoma of the lung.

Of 1,000 consecutive patients undergoing fiberoptic bronchoscopy, 331 eventually were proven to have primary lung cancer. Of the 331 carcinomas, 253 were beyond the visual range of the flexible bronchoscope. However, under fluoroscopic guidance, the diagnosis of carcinoma was established in 194 (76.7%) of these nonvisualized tumors. Cytologic analysis of brush specimens was more often positive for malignancy than specimens obtained by forceps biopsy. An expert cytologist and experienced bronchoscopy team are esential for a high percentage of reliable positive diagnoses in bronchogenic carcinoma.