Metastatic papillary thyroid carcinoma to lung diagnosed by bronchoalveolar lavage.

The diagnosis of papillary carcinoma of the thyroid metastatic to the lung frequently requires a battery of noninvasive tests. Occasionally, invasive procedures such as open lung biopsy, transthoracic needle biopsy, and transbronchial lung biopsy are employed to confirm the diagnosis. A 31-yr-old woman with papillary thyroid carcinoma treated previously by a near-total thyroidectomy and 131I ablation presented to our clinic with shortness of breath and a clear chest roentgenogram. A post-131I treatment whole body scan revealed widespread 131I pulmonary uptake, and the presence of papillary thyroid cancer was confirmed by bronchoalveolar lavage. We conclude that bronchoalveolar lavage should be considered when tissue confirmation of metastatic papillary carcinoma to the lung is needed. During the evaluation and follow-up of this patient, we were able to determine that metastatic papillary carcinoma to the lung may cause a methacholine bronchoprovocation test to be falsely positive for asthma.

The cough reflex and its relation to gastroesophageal reflux.

Each cough involves a complex reflex arc beginning with the stimulation of sensory nerves that function as cough receptors. There is evidence, primarily clinical, that the sensory limb of the reflex exists in and outside of the lower respiratory tract. Although myelinated, rapidly adapting pulmonary stretch receptors (RARs), also known as irritant receptors, are the most likely type of sensory nerve that stimulates the cough center in the brain, afferent C-fibers and slowly adapting pulmonary stretch receptors (SARs) also may modulate cough. RARS, C-fibers, and SARs have been identified in the distal esophageal mucosa; however, studies have not been performed to determine whether they can participate in the cough reflex. Although gastroesophageal reflux disease can potentially stimulate the afferent limb of the cough reflex by irritating the upper respiratory tract without aspiration and by irritating the lower respiratory tract by micro- or macroaspiration, there is evidence that strongly suggests that reflux commonly provokes cough by stimulating an esophageal-bronchial reflex. Theoretically, the pathways of this reflex may be modeled in a variety of ways, and these are speculated upon in this article. The predominant role of acid in triggering cough by means of this reflex is unclear because of conflicting results from provocative challenge studies. It is interesting to speculate that a distal esophageal-bronchial reflex evolved as an early warning defense so that coughing could be started, just in case the refluxate were to reach the inlet of the lower respiratory tract. That is, thinking teleologically, it is possible that an esophageal-bronchial reflex evolved as one of several mechanisms designed to protect the lungs from aspiration of gastric contents.

The pathology of interstitial lung disease in nylon flock workers.

Flocking is a widely used industrial process in which short lengths of synthetic fibers are applied to backing fabric to produce plush material. In response to an apparent outbreak of interstitial lung disease in flock workers, the Centers for Disease Control hosted a clinical-pathological workshop to identify the defining characteristics of the disease and possible etiologic agents. Six pathologists reviewed 15 biopsies of 15 cases (out of a clinical caseload of 20 patients) and assessed the pattern, extent and degree of pulmonary inflammation, fibrosis, and other changes. A consensus clinical-pathologic diagnosis was reached for each patient and correlated with clinical and radiologic findings. Four of eight open lung biopsies and one of seven closed (transbronchial) lung biopsies demonstrated a characteristic pattern to which the descriptive terminology lymphocytic bronchiolitis and peribronchiolitis with lymphoid hyperplasia was applied. The other biopsies showed nonspecific inflammatory changes, airspace organization, and diffuse alveolar damage. One open lung biopsy demonstrated respiratory bronchiolitis with lymphoid hyperplasia. None of the lung biopsies showed more than mild interstitial fibrosis and no granulomas were identified. The consensus of the workshop was that lymphocytic bronchiolitis and peribronchiolitis with lymphoid hyperplasia was a characteristic and distinctive pattern of injury in the flock workers' lung biopsies. Although the etiology of this disease remains undefined at present, the injury pattern and environmental studies suggest a chronic immunologic response to inhaled material.

Adenocarcinoma and (extragonadal) choriocarcinoma of the gallbladder in a young woman.

This study represents the second case of coexisting adenocarcinoma and choriocarcinoma of the gallbladder reported in the English language medical literature, and the first such case documented by: (1) positive immunostaining of tumor cells for the beta subunit of human chorionic gonadotrophin, and (2) evidence of gonadotrophin secretion in blood and urine. The patient reported herein survived only 1 month following diagnosis, and exemplifies the reportedly lethal behavior of extragonadal choriocarcinoma.

Eosinophilic intracytoplasmic globules in pulmonary adenocarcinomas: a histochemical, immunohistochemical, and ultrastructural study of six cases.

Intracytoplasmic globules have been described in a variety of neoplastic and nonneoplastic conditions, but remain poorly defined. In a review of 100 consecutive cases of lung carcinomas, six cases of mucin-positive adenocarcinoma demonstrated eosinophilic intracytoplasmic globules that ranged in size from less than 1 to 20 mu in diameter. The globules were often located adjacent to areas of tumor necrosis, and occurred either singly or multiply within individual tumor cells. Globules were similar in morphologic appearance to Russell bodies in plasma cells or the eosinophilic globules in hepatocytes of patients with alpha-1-antitrypsin deficiency, but were morphologically distinct from intracytoplasmic mucin vacuoles. The globules were brightly positive with PAS stain with diastase, were brick red with Masson's trichrome stain, and showed variably positive staining with Mallory's phosphotungstic acid-hematoxylin and Ziehl-Nielson stains. Immunoperoxidase staining showed slight staining of some globules with albumin, IgG, IgA, and alpha-1-antitrypsin. Ultrastructurally the globules had a homogeneous density and were often associated with profiles of rough endoplasmic reticulum. We suggest that these globules represent secretory glycoprotein accumulated in the cytoplasm of tumor cells in areas of tumor cell injury.

Pulmonary histopathology in cocaine abusers.

Lung histopathology was reviewed from 52 autopsies with positive toxicologic tests for cocaine from the medical examiners' offices in Dallas and Austin, TX. The median patient age was 34.7 years, and the male to female ratio was 2:1. Twelve individuals primarily used the drug intravenously and six primarily smoked it, but in most patients usage history was not known. The most frequent manner of death was accidental, consisting predominantly of cocaine overdoses. Other frequent manners of death included both natural causes and homicides. Subjects with chest trauma were excluded from the study. Twenty-three age-matched control cases with negative cocaine histories and toxicologic tests also were obtained from medical examiner autopsies. Histopathologic findings in the cocaine abuse group included acute hemorrhage, 58% (P = .05); chronic hemorrhage, 40% (P < .01), interstitial pneumonitis/fibrosis, 38% (P < 0.01); congestion, 88% (P < .01); and intra-alveolar edema, 77% (P < .01). These changes were remarkably consistent regardless of locale or method of use. Our findings demonstrate that pulmonary hemorrhage is more frequent than suggested by clinical hemoptysis and that chronic pulmonary diseases such as interstitial fibrosis may develop in long-term users.

Potential utility of p53 immunopositivity in differentiation of adenocarcinomas from reactive epithelial atypias of the lung.

Reactive atypia of alveolar epithelium occurs in many types of lung injury and may sometimes raise suspicions of adenocarcinoma or bronchioloalveolar carcinoma. To assess whether there is sufficient difference in the frequency of p53 protein immunopositivity in these lesions to provide a practical basis for differentiating malignancy from reactive atypia, we immunostained 110 malignant and inflammatory/fibrotic lung specimens for p53 protein. Paraffin-embedded sections were immunostained with p53 protein antibody (clone BP53-12; BioGenex, San Ramon, CA) and standard capillary gap (Microprobe; Fisher Scientific, Fairlawn, NJ) avidin- biotin complex technique with antigen retrieval solution. Percent of immunopositive cells was semiquantitatively categorized as follows: 0%, less than 1%, 1% to 10%, 10% to 50%, more than 50%. Of reactive atypias, 94% are negative or show p53 immunopositivity in less than 10% of cells. Of p53 positive malignancies, 86% are positive in more than 10% of cells. When p53 immunopositivity occurs in more than 10% of atypical cells, the lesion is usually a malignancy, primarily adenocarcinoma. Most reactive atypias are immunopositive in less than 10% of atypical cells. Important caveats were noted. Rare reactive atypias are p53 immunopositive in greater than 10% of cells. Bronchioloalveolar carcinomas are infrequently p53 immunopositive. Therefore, this approach would be less useful in their differentiation from reactive atypias.

Prognostic significance of histopathologic subtype and stage in small cell lung cancer.

A study of 149 light microscopic tissue slides from 147 patients with recorded initial diagnoses of small cell lung cancer (SCLC) (114 cases) and undifferentiated carcinoma (35 cases) was undertaken to test the reproducibility and prognostic impact of a new histopathologic subclassification of SCLC proposed by the Pathology Panel of the International Association for the Study of Lung Cancer (IASLC). This study was further designed to test the impact of clinical stage, age, sex, and race on survival. The tissue slides were blindly reclassified as SCLC or non-SCLC by a panel of five pathologists with no knowledge of the initial diagnosis. The SCLCs were divided into the three subtypes outlined by the IASLC pathology panel: small (classic or pure), mixed (small cell/large cell), and combined (small cell/squamous carcinoma or small cell/adenocarcinoma). Small cell lung cancer was clinically staged as local, regional, or distant. Consensus diagnosis (defined as agreement by at least three of the five pathologists) was achieved in 144 (96.6%) of the 149 cases. Of these 144 cases, 124 were reclassified as SCLC (115 [92.8%] small, five [4.0%] mixed, and four [3.2%] combined) and 20 were classified as non-SCLC. The median lengths of survival for the small, mixed, and combined subtypes were 225, 1,110, and 203 days, respectively (P = .025). Adequate staging data were available in 123 of the 124 SCLC cases. Of the 123 SCLC cases, 27 (21.9%) were local, 22 (17.9%) were regional, and 74 (60.2%) were distant stage. The median lengths of survival for the local, regional, and distant stages were 428, 251, and 111 days, respectively. This association was highly significant (P = .0001). We conclude that stage is the major determinant of survival in SCLC. Mixed subtypes had significantly longer survival times than the small or combined subtypes (P = .025). Survival times were longer for women than for men, and the survival time difference between men and women was significant (P = .0028). We found no significant differences in survival according to age or race.

Necrotizing tracheobronchitis with progressive airflow obstruction associated with paraneoplastic pemphigus.

Paraneoplastic pemphigus (PNP) is an autoimmune disease associated with leukemia and non-Hodgkin's lymphoma. A patient with stage IVB poorly differentiated lymphocytic lymphoma developed characteristic upper and lower airway involvement with profound mucocutaneous erosion and tracheobronchial epithelial desquamation. Immunofluorescence testing confirmed autoantibody deposition along the basement membrane of bronchial epithelium. Disruption of the cellular adhesion mechanisms, including desmosomes, hemidesmosomes, and possibly the integrin subunits, is presumed to have led to disruption and desquamation of the tracheobronchial epithelial barrier, severe obstruction of the airways and hypoxia, and possibly bacterial superinfection. As far as can be determined, the feature of airflow obstruction occurring in association with PNP has not been described. Physicians should be aware that these complications of PNP may rapidly lead to hypoxic respiratory failure and death.

Transbronchial lung biopsy. Histopathologic and morphometric assessment of diagnostic utility.

The diagnostic utility of transbronchial lung biopsy (TBB) is partly a function of its size. However, objective parameters that reflect biopsy specimen size have not yet been well-defined. We studied clinical records and histopathologic lung tissue slides of 116 patients who underwent diagnostic TBB, aiming to define the possible significance of association between seven parameters and three categories of pathologic diagnoses. Three of the seven parameters were clinical: age, sex, and chest roentgenographic infiltrates (localized vs diffuse). The remaining four parameters were histopathologic and morphometric: total number of tissue fragments, total number of alveoli (per biopsy specimen), total tissue area (alveolated plus nonalveolated), and lung total area (alveolated tissue alone). The three categories of pathologic diagnoses were as follows: infection, tumor, and nonspecific diagnoses. The nonspecific diagnoses included diagnoses of fibrosis and/or chronic inflammation. The alveoli were microscopically counted by one of us (S.D.G.). The number of biopsy fragments, the total tissue area, and the total lung area were measured in square millimeters by a computer-assisted digitizing system using specific (Bio-Quant) software (R and M Biometrics Inc). The significance of the associations between the seven parameters and the three diagnostic categories were assessed by the chi2 test for association. Overall, the following four possible associations were found to be statistically significant: (1) age--a lower percentage of patients with infection was found among patients with increasing age (p less than 0.001); (2) roentgenographic findings--a greater percentage of tumor diagnoses were found in patients with localized infiltrates (p = 0.006); (3) number of biopsy fragments--a greater percentage of patients with diagnoses of infection was identified among patients whose biopsy specimens contained the highest number of tissue fragments (p = 0.04); and (4) number of alveoli--a greater percentage of diagnosis of infection was made in patients whose biopsy specimens contained greater than or equal to 20 alveoli (p = 0.01). Our findings support the notion that the diagnostic utility of TBB is related to its size. However, this relationship between TBB size and diagnostic utility was apparent only for diagnoses of infection and not for diagnoses of tumor. We conclude that TBB specimens containing 20 or more alveoli may (1) be declared to be adequate for diagnosis, (2) in the appropriate clinical setting, they will be most likely to yield a diagnosis of infection, and (3) the number of alveoli does not appear to be associated to the diagnosis of tumor.

Experimental polyacrylamide-induced acute injury in rat lung.

We recently reported the first case of accidental aspiration of polyacrylamide occurring in a 26-year-old man. The patient developed severe airway obstruction and parenchymal lung damage and died. Autopsy revealed numerous polyacrylamide particles in his lungs, as well as extensive bronchiolar and alveolar damage. Gas chromatographic and mass spectrometric assessment of the lung tissue failed to reveal polyacrylamide activity, although assessment of the suspending solvent of the polyacrylamide showed a pattern characteristic of an aliphatic hydrocarbon mixture with a prominent dodecane peak. This experimental study was performed to determine the nature and extent of damage to rat bronchial and alveolar epithelia following endotracheal instillation of polyacrylamide, hydrocarbon mixture (petroleum distillate), dodecane (C12H26), or normal saline. The rat lungs were examined grossly and microscopically 10 min and 24, 72, and 96 h after endotracheal instillation, following inflation and fixation with 10 percent buffered formaldehyde. Gross examination revealed congested, mottled visceral pleural surfaces in the rats treated with polyacrylamide and dodecane. There were no pleural exudates or effusions. Microscopically, vascular engorgement, bronchiolitis, and focal pneumonia were observed. Vascular engorgement was most pronounced at 72 to 96 h in rat lungs treated with polyacrylamide and dodecane and was moderate at 24 h in rats treated with petroleum distillate. Focal organizing pneumonia was marked at 96 h in rats treated with petroleum distillate, at 72 h in those treated with polyacrylamide, and at 24 h in those treated with dodecane. The saline-treated control animals showed no change. Our findings suggest that polyacrylamide, dodecane, and petroleum distillate are strong irritants to the airways. However, a direct obstructive/mechanical effect of the polyacrylamide upon the airway has not been excluded. Airway exposure to polyacrylamide may result in lung injury secondary to the polyacrylamide itself, its suspending agents, or both.

Transbronchial lung biopsy: can specimen quality be predicted at the time of biopsy?

STUDY OBJECTIVES: To determine the bronchoscopist's ability to predict specimen quality at the time of transbronchial biopsy and to determine the influence of biopsy specimen size and alveolar content on diagnostic value. DESIGN: Prospective, blinded, observational analysis. SETTING: Tertiary care academic hospital-based pulmonary practice. PATIENTS: Forty-three adult patients who underwent transbronchial lung biopsy. INTERVENTIONS: Each of 170 biopsy specimens was rated as to likelihood of containing diagnostic tissue, size and ability to float, tissue types present, number of alveoli, and pathologic diagnosis. RESULTS: Fifteen percent of biopsy specimens were small and 40% were large. Seventy-six percent of specimens floated; 61.8% of the 170 biopsy specimens contained abnormal lung tissue; and 14.7% of individual specimens were diagnostic. Fifty-two percent of specimens contained >20 alveoli. Larger biopsy specimens were more likely to contain diagnostic tissue (r=0.29, p=0.001). Cup forceps retrieved smaller pieces of tissue (p=0.007) and were less likely to obtain diagnostic tissue (p=0.06). Physician ratings of specimen quality (mean+/-SD) did not differ between specimens containing normal and abnormal tissue (5.98+/-2.3 vs 5.46+/-5.5; p=0.24) or between specimens containing diagnostic vs nondiagnostic tissue (5.56+/-2.5 vs 6.25+/-2.1; p=0.14). Specimens that floated were no more likely to be diagnostic or abnormal than specimens that sank (p<0.05). Diagnosis when established was made by the first biopsy specimen in 53.3% and the second in 33.3% CONCLUSIONS: Physician estimate of biopsy specimen quality and the float sign are not helpful in predicting that the biopsy specimen contains abnormal or diagnostic tissue. Diagnostic biopsy specimen will likely be obtained if the size of the specimen fills the forceps, 2 to 4 biopsies are performed, and toothed forceps are used.

Flock worker's lung: broadening the spectrum of clinicopathology, narrowing the spectrum of suspected etiologies.

STUDY OBJECTIVES: Workers in the nylon flocking industry recently have been found to be at increased risk of chronic nongranulomatous interstitial lung disease. Although a spectrum of cytologic and histopathologic abnormalities has been observed, nonspecific interstitial pneumonia, lymphoid nodules, and lymphocytic bronchiolitis predominated in the 19 previously reported cases of flock worker's lung. Here we describe five additional patients who appear to expand the histopathologic spectrum and add to the evidence suggesting a causative role for respirable-sized nylon fragments. METHODS: We studied all North American patients (n = 5) found in 1998 to satisfy our previous case definition of flock worker's lung. Two pulmonary pathologists independently reviewed each biopsy specimen. RESULTS: All five patients reported cough and dyspnea. Only one patient had crackles on chest auscultation. High-resolution CT scan, interpreted with attention to subtle ground-glass attenuation, remained a highly sensitive diagnostic test. Pulmonary function tests and plain chest radiograph were less sensitive. One patient's wedge biopsy showed previously described prototypical findings. Two others had transbronchial biopsies showing some of the same features. The fourth patient's wedge biopsy showed desquamative interstitial pneumonia. The fifth patient had bilateral synchronous adenocarcinoma but with radiographic evidence of diffuse interstitial fibrosis. These 5 patients and the 19 patients studied previously were exposed to nylon flock manufactured by a rarely used cutting technology. CONCLUSION: Findings in these five patients appear to broaden the spectrum of the clinicopathology of flock worker's lung and add to the evidence incriminating respirable-sized nylon particulates produced during the manufacture and use of rotary-cut nylon flock.

Effect of erionite on the pleural mesothelium of the Fischer 344 rat.

OBJECTIVE: This study sought to assess the fibrogenic and carcinogenic potential of erionite (a fibrous zeolite) on the pleural mesothelium of the Fischer 344 rat (n = 24). DESIGN: The study was designed to examine rat pleural mesothelial changes by three independent observers at timed intervals, ranging from 1 to 480 days postinoculation using erionite from the Pine Valley, Nevada (USA) area. The mean length and width of the erionite fibers were 2.29 and 0.48 microns, respectively. Only microscopic observations made by majority (2/3) or unanimity (3/3) were accepted for final diagnosis. RESULTS: Pleural and lung tissue were available for examination in 21 of the 24 rats. Fibrosis, chronic inflammation, and foreign body reaction occurred in 6 of 21 rats. Mesothelial hyperplasia and dysplasia occurred in 9 and 3 of the 21 rats, respectively. A single mesothelioma was identified at 434 days in a rat that had gross nodular pleural lesions. CONCLUSIONS: The findings reported herein confirm the strong fibrogenic potential of erionite but are at variance with previous studies reporting much higher yields of mesothelioma. The reasons for the low yield of mesothelioma in this study are not known, but may be related to the study design, the strict criteria used for histopathologic diagnosis, and/or possible differences in erionite physicochemical properties, associated with its geographic distribution, most previous animal studies having used erionite from the Rome, Oregon (USA) area.

Cholesterol embolization to the coronary arteries resulting in acute myocardial infarction: A complication of coronary artery bypass grafting surgery.

Cholesterol emboli dislodged during coronary artery bypass surgery may be released downstream into the native coronary arteries and lead to the development of acute myocardial infarction. An autopsy-proven case of such an event occurring in a 79-year-old woman illustrates this complication of coronary artery bypass surgery. Awareness of this complication by pathologists may facilitate its recognition. Awareness by surgeons, on the other hand, may help to prevent it through decreased intraoperative manipulation of the involved vessels.

Pulmonary coccidioidal pseudomycetoma.

Coccidiomycosis is rarely associated with a pulmonary mycetoma. We report a patient with progressive cavitary coccidiomycosis, whose initial radiographic and clinical appearance simulated a mycetoma. Examination of the surgically resected lung showed necrotizing Coccidioides immitis granulomas with spherules and arthroconidialike structures, but no evidence of a mycetoma. We propose the term pulmonary coccidioidal pseudomycetoma as the best descriptor for this patient's clinical, radiographic, pathologic, and microbiologic presentation.

Successful management of intracardiac extension of tumor thrombus in a patient with advanced nonseminomatous germ cell testicular cancer.

A young patient with testicular germ cell tumor presenting with inferior vena cava thrombus extending into the right heart with free-floating thrombus in the right ventricle and a simultaneous epidural spinal cord compression is presented. Due to the perceived high risk of embolization and the urgent need to begin systemic chemotherapy, he was managed with tumor thrombectomy utilizing cardiopulmonary bypass and hypothermic circulatory arrest followed shortly thereafter by systemic chemotherapy. There were no perioperative complications, and he is alive and without recurrence 24 months following four cycles of systemic chemotherapy.

Monomorphic teratoma of the ovary: a rare cause of triiodothyronine toxicosis.

A case of low thyroid radioactive iodine uptake (RAIU) thyrotoxicosis due to a large struma ovarii comprising pure thyroid tissue is presented, including a detailed diagnostic evaluation, histopathology, and demonstration of rapid recovery of native thyroid function after surgical excision. In addition, the first comprehensive analysis of thyroglobulin obtained from an ovarian struma is reported.

Carcinoma of the larynx. Changing incidence in women.

Laryngeal carcinoma has classically been considered a disease of men with a history of tobacco and alcohol abuse. Substantial increases in the incidence of laryngeal carcinoma have occurred among both men and women from 1947 through 1984. In men, the incidence has increased from 5.6 to 9.0 per 100,000 population and in women, from 0.5 to 1.5 per 100,000 population. We recently encountered three consecutive cases of laryngeal carcinoma in women at the Ben Taub General Hospital, Houston, Tex, diagnosed and treated over a 3-month period. Each woman had a long history of cigarette smoking, and two also had a history of alcohol abuse. These consecutive presentations of laryngeal carcinomas in women prompted us to examine our Cancer Registry Files from 1959 through 1973 and 1974 through 1988. Over these two 15-year periods, the male-to-female ratio declined from 5.6:1 to 4.5:1, reflecting a greater incidence among women.

Modification of the fungi-fluor and the genetic systems fluorescent antibody methods for detection of Pneumocystis carinii in bronchoalveolar lavage specimens.

Four hundred forty-five bronchoalveolar lavage specimens from patients with the human immunodeficiency virus were preserved in Saccomano's fixative and stained for Pneumocystis carinii cysts by a modified method with Fungi-Fluor Solution A (Polysciences, Warrington, Pa) and the Genetic Systems Pneumocystis carinii Immunofluorescence Antibody (Genetic Systems Corp, Seattle, Wash). The majority of patients had been treated for suspected P carinii pneumonia for a few days prior to collection of bronchoalveolar lavage specimens. P carinii cysts were detected in 194 (43.6%) specimens. Both stains identified P carinii in 166 (37.3%) specimens and were negative in 251 (56.4%), yielding a concordance rate of 93.7%. P carinii cysts were detected in 25 (5.6%) specimens by the Genetic Systems stain only, and in 3 (0.7%) specimens by the Fungi-Fluor stain only. The sensitivity for detecting cysts of P carinii was significantly greater with the Genetic Systems stain (P < .01).