Peripheral airway cell marker expression in non-small cell lung carcinoma. Association with distinct clinicopathologic features.

Paraffin sections of 247 primary and metastatic non-small cell lung carcinomas, the corresponding non-neoplastic lungs, and 75 other specimens were examined by immunohistochemical procedures using a panel of antibodies against the specific products of peripheral airway cells: the major surfactant-associated protein and 10-kD Clara cell protein. Non-small cell lung carcinoma tumors most frequently positive for either peripheral airway cell marker were adenocarcinomas (41%), especially those with papillolepidic growth pattern (56%), followed by large cell carcinomas (25%), other adenocarcinomas (22%), and squamous cell carcinomas (16%). Immunoreactivity was mainly focal and the expression of the two peripheral airway cell markers was discordant. The incidence of marker expression was similar in metastatic and primary non-small cell lung carcinoma. Other organs and their tumors were negative, with few exceptions. Non-small cell lung carcinomas positive for peripheral airway cell markers were associated with younger age and less-intense smoking, and surfactant-associated protein reactivity was more common in women than in men. Peripheral airway cell markers were independent prognostic factors for survival and delayed development of metastases in patients with less-advanced disease. It is concluded that surfactant-associated protein and 10-kD Clara cell protein are specific markers for non-small cell lung carcinoma and peripheral airway cell differentiation and provide useful tools to study the pathogenesis, biology, and prognosis of non-small cell lung carcinoma.

Metabolic activation of 4-ipomeanol in human lung, primary pulmonary carcinomas, and established human pulmonary carcinoma cell lines.

4-Ipomeanol (IPO) is a pulmonary-specific toxin that is metabolically activated by a cytochrome P450 pathway in lung tissue. In this study, IPO metabolism, as determined by measurement of [14C]IPO covalent binding, was evaluated in a diverse sampling of 18 established, human lung cancer cell lines as well as in normal lung tissue and primary lung carcinoma tissue obtained at the time of thoracotomy from 56 patients with lung cancer. [14C]IPO covalent binding in lung cancer cell lines ranged from 248 to 1,047 pmol of bound [14C]IPO per milligram of protein per 30 minutes (mean +/- SE = 547 +/- 62.2). IPO metabolism in normal lung tissue ranged from 12 to 2,007 pmol of covalently bound [14C]IPO per milligram of protein per 30 minutes (mean +/- SE = 549 +/- 60). In lung cancer tissue, values ranged from 0 to 2.566 pmol of covalently bound [14C]IPO per milligram of protein per 30 minutes (mean +/- SE = 547 +/- 60, P greater than .3). When patients were divided into smokers and current non-smokers (no tobacco products smoked for greater than 6 mo), no effects of cigarette smoking were observed for either normal lung tissue or lung tumor tissue (P greater than .1 in all instances). A wide range of IPO metabolic activity was observed among different histological classifications of lung cancer cell lines and of fresh lung cancer tissues. IPO metabolism was simultaneously compared in normal lung tissue and lung cancer tissue from individual patients, but no positive correlation was observed (r = .10; P greater than .30). The results clearly demonstrate a wide range of IPO metabolism in both normal and lung cancer cells and indicate that a wide diversity of human lung cancers possess the metabolic enzyme system(s) necessary for the bioactivation of IPO to a potentially cytotoxic intermediate. Therefore, the continued exploration for any possible therapeutic potential of IPO in patients with lung cancer appears warranted.

The clinical significance of variant-morphology small-cell carcinoma of the lung.

Past attempts to subclassify small-cell lung cancer (SCCL) histology (oat cell, fusiform, polygonal, intermediate, etc) have not been useful because of interrater variability and a lack of clinical significance. A review of outcome in a previous series suggested that a different histologic subtype, small-cell/large-cell (SC/LC) conferred an inferior response and survival analogous to the relative chemotherapy and radiation resistance seen in the variant-morphology (SC/LC) cultured cell lines. To evaluate the clinical impact of SC/LC we applied the proposed International Association for the study of Lung Cancer (IASLC) histology subclassification that incorporates the SC/LC category for patients with extensive-disease SCCL entering Eastern Cooperative Oncology Group (ECOG) protocol 1582. All cases were reviewed for eligibility by one pathologist, and all possible SC/LC (variant) plus 10% of all cases were reviewed together with a second pathologist; 577 of the 628 patients who entered were eligible, of whom 550 had histologic material submitted for review and are considered for this analysis. Initial review disclosed 24 cases with SC/LC (4.4%) and 526 with "classic" histology. The second review showed 100% agreement for classic form, but only 11 SC/LC cases with concordance between the reviewing pathologists. Eight of 24 (33%) cases from first review and three of 11 (27%) with concordance on second review achieved complete response (CR) compared with 101 of 526 (19%) for "classic" SCCL (P = .11 and .45, respectively, for the first and second review groups).(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized comparison of standard chemotherapy versus alternating chemotherapy and maintenance versus no maintenance therapy for extensive-stage small-cell lung cancer: a phase III study of the Eastern Cooperative Oncology Group.

The present randomized, prospective study was designed to assess whether alternating induction cyclophosphamide, doxorubicin, vincristine-altretamine (hexamethylmelamine), etoposide, and methotrexate (CAV-HEM) chemotherapy is better than standard chemotherapy (CAV) in improving response, survival, and remission time in 577 evaluable patients having extensive-disease small-cell lung cancer (SCLC). In addition, the study was designed to assess the impact of maintenance chemotherapy following a complete response (CR) on the time to progression and survival. The response rates (CR plus partial response [PR]) for CAV-HEM and CAV were 64% and 61%, respectively, but 23% of the patients on CAV-HEM achieved a CR compared with 16% for CAV alone (P = .03). Among complete responders, the continuation of therapy significantly increased the remission time for patients on CAV, while maintenance therapy for patients on CAV-HEM had no significant impact on remission time. However, the increased remission had little effect on survival. Patients on CAV maintenance therapy survived marginally longer than those patients on no maintenance therapy, whereas patients who received CAV-HEM and no maintenance therapy survived longer than those on maintenance therapy. CAV-HEM was associated with significantly higher severity of complications (ie, mainly myelosuppression) than CAV (P = .01). Maintenance chemotherapy was associated with significantly more complications than no maintenance therapy. Patients on CAV-HEM lived significantly longer than those on CAV alone (45.9 weeks v 42.7 weeks; P = .002). Ten percent of patients treated on CAV-HEM survived at least 2 years, compared with 4% on CAV alone. In our study involving patients with extensive-disease SCLC, the alternating induction chemotherapy significantly increased the CR rates and had a small impact on long-term survival compared with the results achieved with standard induction chemotherapy. Moreover, when the alternating induction chemotherapy was used, long-term maintenance chemotherapy was not needed.

Pulmonary carcinoid tumors: CT assessment.

Computed tomography assessment of 634 surgically proven solitary pulmonary nodules included 12 pulmonary carcinoid tumors. Five were central (involving or directly abutting the bronchial tree), and seven were peripheral (surrounded by parenchyma). Three central and one peripheral lesion had CT numbers indicative of focal calcifications, frequently in the periphery of the nodule. Nodule size ranged from 1.2 to 3 cm. Nine nodules were smooth and round, two were irregular and lobulated, and in one the entire peripheral contour was difficult to assess because of postobstructive atelectasis secondary to tumor occlusion of the bronchus. The calculated average CT number ranged from 80.5 to 179 HU.

v-Ha-ras oncogene insertion: a model for tumor progression of human small cell lung cancer.

Small cell lung cancer (SCLC) manifests a range of phenotypes in culture that may be important in understanding its relationship to non-SCLCs and to tumor progression events in patients. Most SCLC-derived cell lines, termed "classic" SCLC lines, have properties similar to SCLC tumors in patients, including high expression of neuroendocrine markers and low c-myc oncogene expression. A significant number of SCLC lines characterized as "biochemical or morphologic variant" SCLC lines have decreased levels of endocrine differentiation markers associated with increased proliferative indices, amplification of the c-myc oncogene, and growth patterns and biochemical markers more typical of non-SCLCs. To delineate further the relationships between these phenotypes and the molecular events involved, we have inserted the v-Ha-ras gene in SCLC cell lines with (biochemical variant) and without (classic) an amplified c-myc gene. These two SCLC subtypes had markedly different phenotypic responses to similar levels of expression of v-Ha-ras RNA. No biochemical or morphologic changes were observed in classic SCLC cells. In contrast, in biochemical variant SCLC cells, v-Ha-ras expression induced features typical of large cell undifferentiated lung carcinoma, including adherent monolayer growth patterns, increased cloning efficiency, increased levels of non-SCLC cell markers, ultrastructural characteristics and an acquired resistance to polyamine depletion typical of large cell carcinoma, but not SCLC, in vitro. Expression of v-Ha-ras in biochemical variant SCLC cells directly demonstrates that important transitions can occur between phenotypes of human lung cancer cells and that these may play a critical role in tumor progression events in patients. The findings provide a model system to study molecular events involved in tumor progression steps within a series of related tumor types.

Profiles of prostaglandin biosynthesis in normal lung and tumor tissue from lung cancer patients.

prostaglandin (PG) biosynthetic profiles from endogenous arachidonic acid were determined by capillary gas chromatography-mass spectrometry in matched fresh normal lung (NL) and lung cancer (LC) tissue fragments obtained from 42 individual LC patients at the time of diagnostic thoracotomy. The histological diagnoses represented were squamous cell carcinoma (N = 20), adenocarcinoma (N = 7), small cell carcinoma (N = 4), mixed cell carcinoma (N = 2), bronchioloalveolar cell carcinoma (N = 2), large cell undifferentiated carcinoma (N = 3), bronchial carcinoid (N = 1), and metastatic tumors (N = 3). When PG biosynthesis was determined in NL tissue separately, low mean levels of PGE2 and PGF2 alpha (less than 2 pmol/mg protein/15 min), intermediate levels of PGD2 and 6-keto-PGF1 alpha (6KPGF1 alpha) (2-7 pmol/mg protein/15 min), and high levels of thromboxane B2 (TXB2) (greater than 7 pmol/mg protein/15 min) were observed. There was no particular correlation with cigarette smoking history and PG biosynthesis in NL. When PG production in LC tissue was evaluated separately, high levels of PGE2, PGF2 alpha, and 6KPGF1 alpha as well as TXB2 and low levels of PGD2 were noted. In addition, LC tissue from cigarette smokers demonstrated elevated levels of PGE2, 6KPGF1 alpha, and TXB2 when compared to current nonsmokers with LC (P less than 0.05 in all instances). Simultaneous comparison of PG production in matched LC and NL tissue from individual patients indicated increased biosynthesis of PGE2 and PGF2 alpha and low levels of PGD2 in LC compared to NL tissue (P less than 0.05 in all instances; paired, two-tailed, Student's t test). Individual comparison of PG biosynthesis according to LC histological cell type revealed that PGE2 and PGF2 alpha were consistently elevated in all four common primary LC histological cell types, the only exception being large cell undifferentiated carcinoma. Interestingly, this latter LC histological cell type presented a unique profile with lower levels of PGE2 and PGD2 in LC than in NL tissue (P less than 0.05 in both instances). In addition, the biosynthesis of all 5 PGs studied was consistently higher in primary than metastatic adenocarcinomas of the lung (P less than 0.05 in all instances). No differences were observed in NL and LC tissue for the major LC histological cell types when PGD2, TXB2, or 6KPGF1 alpha biosyntheses were compared. These findings indicate that the profiles of PG biosynthesis in LC and NL tissue from individual patients may differ substantially. These differences may reflect, in part, contributions to the PG biosynthetic profile unique to malignant cells.

Comparison of intrapulmonary, percutaneous intrathoracic, and subcutaneous models for the propagation of human pulmonary and nonpulmonary cancer cell lines in athymic nude mice.

The propagation efficiencies, growth patterns, histological appearances, and roentgenographic demonstration of tumors derived from six continuous human pulmonary tumor cell lines implanted intrathoracically (i.t.) and intrabronchially (i.b.) were compared with the conventional s.c. implantation method at three different tumor cell inocula (N = 184, i.b.; N = 185, i.t.; N = 180, s.c.). A tumor-related mortality of 100% was noted when the six different human lung tumor cell lines, including A549 adenocarcinoma, NCI-H125 adenosquamous carcinoma, NCI-H460 large cell undifferentiated carcinoma, NCI-H69 small cell carcinoma, and NCI-H358 and NCI-H322 bronchioloalveolar cell carcinomas, were implanted i.b. at a 1.0 x 10(6) tumor cell inoculum. A similar (92%) tumor-related mortality was observed when these same lung tumor cell lines were implanted i.t. at a 1.0 x 10(6) tumor cell inoculum (P greater than 0.10), whereas minimal (5%) tumor-related mortality was noted when cells from the six different cell lines were implanted s.c. (P less than 0.001). In addition, a dose-dependent, tumor-related mortality was noted for either i.t. or i.b. implantation when lower (1.0 x 10(5) or 1.0 x 10(4] tumor cell inocula were employed. Histological characteristics and growth patterns of tumors propagated employing the three implantation techniques were closely comparable for all three propagation methods and, in all instances, histological appearances of the tumors were representative of the current tumor cell lines from which they were derived. Approximately 30% of the lung tumors propagated i.t. grew in the chest wall and/or in the lung parenchyma as well as in the pleural space. In contrast, tumors propagated i.b. grew predominantly in the lung parenchyma. When five nonpulmonary human tumor cell lines (including U251 glioblastoma, LOX amelamontic melanoma, HT-29 colon adenocarcinoma, OVCAR 3 ovarian adenocarcinoma, and adriamycin-resistant MCF-7 breast adenocarcinoma) were propagated i.b. or i.t., there was considerable site-specific variability in tumor-related mortality depending on the tumor type. These data demonstrate that both the i.b. and i.t. models should be useful for the in vivo propagation and study of certain human pulmonary and nonpulmonary carcinomas as well as being advantageous for future studies of cancer biology and developmental therapeutics.

Integrated pathology reporting, indexing, and retrieval system using natural language diagnoses.

Pathology computer systems are making increasing use of natural language diagnoses. The Johns Hopkins Medical Institutions integrated pathology reporting system, a commercial product with extensive, locally added enhancements, covers all information management functions within autopsy and surgical pathology divisions and has on-line linkages to clinical laboratory reports and the medical library's Mini-MEDLINE system. All diagnoses are written in natural language, using a word processor and spelling checker. A security system with personal passwords and different levels of access for different staff members allows reports to be signed out with an electronic signature. The system produces financial reports, overdue case reports, and Boolean searches of the database. Our experience with 128,790 consecutively entered pathology reports suggests that the greater precision of natural language diagnoses makes them the most suitable vehicle for follow-up, retrieval, and systems development functions in pathology.

Kasabach-Merritt syndrome: therapeutic considerations.

During the past 15 years we have managed six children with capillary hemangiomas in association with consumptive coagulopathy--the Kasabach-Merritt syndrome. Their ages when first seen ranged from 2 weeks to 4 years with a mean of 19 months. In three of the patients, the hemangiomas remained small for many months and then suddenly enlarged and hemorrhagic diatheses appeared. The duration of the thrombocytopenia ranged from 5 to 20 months, a time span that in some of the patients was influenced by the type of treatment used. Each patient received a variety of therapies including the following: medications to control the coagulopathy; mechanical, cytolytic, and pharmacologic treatment to eradicate the lesion; and blood product support with platelets and cryoprecipitate for severe bleeding. A prompt elevation of the platelet count occurred in three of the patients after the lesion was biopsied. Subtotal resection of the lesion resulted in an immediate increase of the platelet count in one patient. A transient increase in platelet counts and fibrinogen levels was observed in another patient following several embolizations of a portion of the hemangioma. Other modes of therapy were difficult to evaluate, especially because the same therapy applied at different times in the same patient effected a different type of response. Eventually, all of the patients experienced resolution of their lesions and, with this, concomitant reversal of the coagulopathy.

Anaplastic sarcoma arising in a mature metachronous bilateral Wilms' tumor after irradiation and chemotherapy. Spontaneous versus induced malignant change.

A 1-year-old male infant developed a classic Wilms' tumor of the left kidney. Treatment consisted of a left nephrectomy, chemotherapy, and irradiation to the left flank and associated abdomen. Two years later, a mass in the right kidney was discovered; open renal biopsy demonstrated a mature Wilms' tumor consisting entirely of rhabdomyomatous elements in the biopsy specimen. The patient was given a second course of chemotherapy and 2000 rad to the right flank. Over the next 8 years, the mass continued to grow without evidence of metastatic spread. Renal function deteriorated secondary to compression of the surrounding normal renal parenchyma by the enlarging tumor; creatinine clearance from the solitary kidney decreased from 120 ml/min to 40 ml/min during the 12 months prior to removal of the lesion. Via a nephron-sparing procedure, the 3400 g tumor measuring 19 cm X 16 cm X 9 cm was enucleated from the right kidney without compromise to the remaining normal tissue. Pathologic examination of the surgical specimen revealed a mature Wilms' tumor with a malignant anaplastic sarcoma arising in the central portion. Postoperatively, the patient received a third course of chemotherapy with no irradiation to the tumor bed. Currently, he is disease-free with normal renal function more than 20 years after diagnosis of the metachronous bilateral Wilms' tumor. This is the first reported case of an anaplastic sarcoma arising within a Wilms' tumor; this individual also is the longest surviving patient with metachronous Wilms' tumor. The various possibilities regarding the development of the anaplastic sarcoma within the Wilms' tumor of the right kidney are discussed, including the possible role of chemotherapy and irradiation in the development of a second malignancy.

The role of surgery in the management of selected patients with small-cell carcinoma of the lung.

This study was designed to evaluate the efficacy of surgical resection of the primary tumor and lymph nodes in patients with localized small-cell carcinoma who had responded to induction chemotherapy. The study was performed in 37 patients who received two cycles of chemotherapy consisting of cyclophosphamide, doxorubicin, and etoposide. Those patients who achieved a complete or partial (greater than 50%) response were evaluated for thoracotomy and the primary tumor and regional lymph nodes excised when feasible. Postoperatively, the patients received prophylactic cranial irradiation and were maintained on the same chemotherapy for an average of 11 months. Twelve patients were resected and found to have residual small-cell carcinoma in the operative specimen (ten) or no residual disease (two). Seven of these patients (58%) are alive without evidence of disease (median follow-up, 24 months). Seven other patients who were resected proved to have either residual foci or small-cell carcinoma mixed with adenocarcinoma or large-cell carcinoma (four) or only focal areas of adenocarcinoma, large-cell carcinoma, or squamous-cell carcinoma with no evidence of residual small-cell carcinoma. Five of these patients (71%) are alive without evidence of disease (median follow-up, 36 months). Two of the 16 patients who were not resected but treated with chemotherapy and radiation are alive at 15 and 31 months without evidence of disease, the other 14 are dead of disease.

What is new in epithelioid hemangioendothelioma of the liver?

An unusual hepatic vascular neoplasm has been delineated in recent years. It has characteristic morphologic features consisting of multiple nodules with relatively acellular centers which may be focally calcified. More peripherally there is a cellular zone containing elongated or plump tumor cells embedded in a fibromyxoid stroma. At the outer edge of the nodules, and particularly in vessels, the tumor cells may assume an epithelioid appearance. The tumor cells exhibit focally positive staining for Factor VIII related antigen and Weibel Palade bodies may be seen on electron microscopy. The tumor is malignant, but may have an indolent course over many years. It may be associated with hepatic cirrhosis and pulmonary osteoarthropathy. Other organs, particularly the lung and soft tissues are frequently involved.

Profiling of prostaglandin biosynthesis in biopsy fragments of human lung carcinomas and normal human lung by capillary gas chromatography-negative ion chemical ionization mass spectrometry.

Methods for the profiling of prostaglandin F2 alpha (PGF2 alpha), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6KPGF1 alpha) biosynthesis in tissue samples of clinical origin by capillary gas chromatography-negative ion chemical ionization mass spectrometry (CGC-NICIMS) are detailed. Aliquots (25 microliter 1) of incubates (1 ml volume) of human lung carcinoma and normal human lung tissue fragments (total protein content = 0.2 to 2.0 mg) were derivatized for vapor phase analysis in the presence of 0.75 to 1.60 ng of tetradeuterated analogs of PGE2, PGF2 alpha and 6KPGF1 alpha without prior extraction and/or chromatography. The derivatized analytes and internal standards were detected by simultaneous monitoring of ions at six different masses characteristic for each of the derivatized prostanoids. The inter-sample and intra-sample coefficients of variation for the assay method were typically less than 12%. The analysis of biological samples was completed with less than 2.5% of each derivatized sample per injection. The samples were of adequate purity for the identification and quantitation of each of the eicosanoids. The methods described in this report are highly selective and highly sensitive with detection limits of 0.1 to 0.2 picograms per injection. The analytical procedures provide the basis for comparisons of the qualitative and quantitative profiles of prostaglandin biosynthesis and should be adaptable for use in a variety of biological and clinical studies.

Frozen section detection of lymph node metastases in prostatic carcinoma: accuracy in grossly uninvolved pelvic lymphadenectomy specimens.

We reviewed our frozen section experience with 310 pelvic lymphadenectomy specimens during the last 5 years. A total of 40 patients (12.9 per cent) had positive lymph nodes on permanent section. In 6 of these patients the lymph nodes were involved grossly and in 34 there were only microscopic metastases. Intraoperative assessment of lymph node involvement classified correctly 299 patients (96.5 per cent of the total number). Whereas previous studies have demonstrated a failure on frozen section to detect all but a few microscopic metastases, we were able by frozen section to identify metastases in 23 of 34 patients (67.6 per cent) with grossly uninvolved lymph nodes. Of the positive frozen sections 16 were in patients with unilateral metastases only, and in 13 of these cases frozen section identified the only positive node present. The average diameter of the metastases found on frozen section was 2.4 mm. In 11 of the 34 patients frozen section did not disclose any of the metastases present on permanent sections (average 1.4 mm.) (false negative rate 3.5 per cent of all patients, 27.5 per cent of those with positive nodes and 32.3 per cent of those with microscopic involvement of lymph nodes only). Ten patients had unilateral metastases and 1 had bilateral involvement. The ability to identify the majority of microscopic metastases, given their adverse effect on prognosis, supports the usefulness of routine frozen section on grossly uninvolved pelvic lymph nodes as a staging procedure before radical prostatectomy.

Ultrasonography of prostatic carcinoma employing amplitude-enveloped (AM) and frequency-demodulated (FM) imaging: in vivo, in vitro, and pathologic correlation.

Thirty patients with biopsy proven carcinoma of the prostate were examined with transrectal (TR) (5-MHz linear array transducer) and transabdominal (TA) (3-MHz sector scanner) ultrasonography prior to prostatectomy. All patients had clinical stage A (n = 5) or B (n = 25) disease. Following retropubic radical prostatectomy, in vitro waterbath studies of the resected specimens were performed obtaining both conventional amplitude-enveloped (AM) images and frequency-demodulated (FM) images. The ability of each imaging modality (TR, TA, AM, FM) to detect the cancerous lesion was determined, and in all cases correlation with pathology was obtained. Transabdominal suprapubic ultrasonography did not prove helpful in detecting early carcinoma. Longitudinally oriented linear array transrectal ultrasonography was positive in nearly two thirds of the patients. Insignificantly lower positive correlation with pathologic findings was obtained from in vitro AM images; the lesions were often better visualized on transverse than on longitudinal images. The highest correlation with pathology was obtained from the in vitro frequency-demodulated images.

Prognosis of untreated stage A1 prostatic carcinoma: a study of 94 cases with extended followup.

Previously we showed that in cases of stage A prostatic cancer, if the tumor involved 5 per cent or less of the tissue and was not high grade (stage A1), only 2 per cent of the tumors progressed at 4 years. The current study investigated a larger group of 94 men with stage A1 disease and extended followup. While 26 men (mean age 75 years) died of other causes less than 4 years after diagnosis, of the 50 men who remained at risk 8 years or longer from the time of diagnosis 8 (16 per cent) had progression of disease. The intervals from diagnosis to progression ranged from 3.5 to 8 years, with 6 of the 8 patients dying of the cancer. Neither volume nor grade predicted progression, since of the 8 tumors that progressed 4 involved less than 1 per cent of the tissue and 6 were low grade. Based on these findings we conclude that stage A1 tumors progress at longer intervals from diagnosis and at lower frequency than stage A2 tumors. However, patients with stage A1 disease are not entirely free of risk of progression, and because 16 per cent of the men in this study who were at risk 8 years or longer experienced progression this factor must be recognized in the management of young men with stage A1 tumors.

Sputum cytopathology: use and potential in monitoring the workplace environment by screening for biological effects of exposure.

Sputum cytopathologic monitoring detects squamous cell lung cancers at an extremely early stage (x-ray negative). It holds further potential for preventing disease by detecting epithelial alterations which reflect environmental hazards. The addition of sputum cytology screening to screening by chest x-ray film does not significantly reduce mortality from all types of lung cancer, but preliminary analysis of Johns Hopkins Lung Project data suggests that mortality from squamous cell carcinoma is reduced. Quantitative automated cytopathology systems and biochemical/immunological cell markers enhance understanding of these precursors and offer great promise for increasing capacity, accuracy, and usefulness in cytopathology screening of workers. Cytological specimens collected over years of screening workers considered at risk may be important to eventually understanding development and prevention of major occupational diseases.

Disseminated calcitonin-poor medullary thyroid carcinoma in a patient with calcitonin-rich primary tumor.

A multiple endocrine neoplasia type Ia patient who initially had a calcitonin-rich medullary thyroid carcinoma followed an indolent clinical course for 7 years after surgical resection. Sudden rapid dissemination of tumor led to death 2 years later. At autopsy, calcitonin immunostaining of tumor was diffusely negative, with slight positivity in less than 5% of cells. The loss of a marker of differentiation in association with the marked change in the clinical course suggests the development within the well-differentiated tumor of a poorly differentiated, biologically aggressive population of tumor cells.

The echogenic focus in prostatic sonograms, with xeroradiographic and histopathologic correlation.

The sonograms of 42 patients scanned before and after radical prostatectomy were reviewed, giving specific attention to echogenic foci. All patients had clinical stage A or B adenocarcinoma of the prostate. Comparison of the scans with xeroradiographic and histopathologic studies showed all echogenic foci, with or without acoustic shadowing, to represent prostatic calcifications. Calcifications were located in the central portion of the gland exclusively, either immediately adjacent to the urethra or at the margins of the "internal gland", separate from the peripheral location of small tumors. With carcinomatous spread toward the urethra, calculi were found surrounded by tumor. This was considered a result of secondary involvement rather than dystrophic tumor calcification. Prostatic calcifications seem unrelated to the development of adenocarcinoma but must be recognized to prevent erroneous interpretation.