Discuss the clinical presentation and pathologic findings in a patient with small cell anaplastic carcinoma of the lung. (<250 words)

Small cell anaplastic carcinoma of the lung (also known as "oat cell carcinoma") is one of the four major types of bronchogenic carcinoma. These tumors are highly associated with smoking and are more common in men. The clinical presentation may include cough, dyspnea, or hemoptysis. Spread of the tumor may produce esophageal dysphagia or effusions. Bronchial obstruction may lead to secondary pulmonary infections. A chest x-ray shows a hilar mass or infiltrate since most small cell carcinomas are centrally located. However, these tumors are aggressive, and most have metastasized by the time of diagnosis, with common sites for metastases that include brain, bone, liver, and adrenals. These tumors have the worst prognosis of any lung cancer, and most patients die within a year of diagnosis. Most are not amenable to surgical resection, but radiation and chemotherapy may be helpful in many cases in prolonging survival.

Small cell cancers rarely reach a large size, but infiltrate surrounding tissues. Tumor necrosis may be prominent. Cytologically, the tumor cells are small, with small dark nuclei and scant cytoplasm. They are thought to originate from neuroendocrine-programmed cells of the bronchial epithelium. For this reason, neurosecretory granules may be found in the cytoplasm. Furthermore, paraneoplastic syndromes often occur with oat cell carcinomas. These could include such findings as ADH secretion with a syndrome of inappropriate ADH or ACTH secretion with Cushing's syndrome.

Discuss the possible causes, diagnostic procedures, and pathologic findings in a patient with a solitary peripheral 2-cm lung nodule. (<250 words)

A peripheral lung nodule cannot be ignored, for a peripheral adenocarcinoma is possible. It may occur in a non-smoker, and may be associated with a hypercoagulable state. A solitary metastasis from another primary source such as breast, colon, or prostate could be difficult to distinguish from a primary, because either could be composed of neoplastic cells forming glands. A benign neoplasm at this site, far less common than adenocarcinoma, is a pulmonary hamartoma that is composed of fibrous connective tissue, cartilage, and bronchial mucosa.

Possible infectious causes for a peripheral lung nodule include M. tuberculosis. In a child with hilar adenopathy, such an appearance would suggest primary tuberculosis, while in an adult in which cavitation was present, secondary tuberculosis is suggested. A number of pathogenic fungi can infect lung and present as a peripheral nodule; some are seen in specific geographic distributions: C. immitis in the desert southwest and H. capsulatum in the Mississippi river region. All of these agents produce granulomatous inflammation with caseation, and the organisms can be identified by GMS stain that will show spherules with endospores for Cocci and small, round clusters of fungi for Histo. An acid fast stain could show mycobacteria.

The workup of the nodule could begin with a non-invasive procedure such as a sputum culture. A bronchoalveolar lavage could also be performed and sent for both culture and cytology. Beyond that, a fine needle aspirate or needle biopsy could be performed to get larger tissue samples for diagnosis. If the cellular yield were poor and the mass persisted, then an open lung biopsy or wedge excision could be performed.

Discuss clinical and pathologic findings that are useful in the diagnosis and treatment of a patient with tuberculosis. (<250 words)

(Example 1)

Tuberculosis is usually seen in two stages. The first stage, primary infection, is generally asymptomatic and most infections are are subclinical. A chest radiograph at this time may show a Ghon complex--a combination of a small subpleural granuloma with prominent hilar adenopathy due to caseating granulomas. About 90% of patients remain asymptomatic and the infection resolves with just a few residual calcifications. About 10% of patients go on to the second stage, secondary infection, which is either a reactivation of the original infection or a reinfection. The pattern of pulmonary involvement with secondary tuberculosis is usually that of upper lobe involvement by multiple caseating granulomas, some of which may cavitate. These patients may present with fever, night sweats, weight loss, and cough, possibly with hemoptysis. Patients with diminished health status from underlying diseases such as AIDS, cancer, silicosis, and malnutrition are more likely to have reactivation of infection.If a person is immunocompromised and does not have adequate cell-mediated immunity with a good type IV hypersensitivity response, then there may be a "miliary" pattern of tuberculosis with many small 1 to 3 mm granulomas in lungs and possibly in other organs. Tuberculosis can be diagnosed by examination of sputum for acid fast bacilli and by culture. A chest radiograph is helpful to determine the extent of the disease. Patients must be given adequate therapy in order to eradicate the disease, prevent transmission to others, and reduce the chance for development of resistance.

Discuss clinical and pathologic findings that are useful in the diagnosis and treatment of a patient with tuberculosis. (<250 words)

(Esample 2)

Patients with tuberculosis may come from "at risk" populations such as the homeless, drug abusers, persons who have had contact with other persons with active tuberculosis, or persons from countries in which tuberculosis is common. A helpful screening test for tuberculosis is the PPD skin test read 48-72 hours after intradermal injection of purified protein derivative on the forearm. Past infection with tuberculosis is suggested by >10 mm of induration for persons in the general population, but persons in risk groups may be considered PPD positive with just 5 mm, and in populations where false positive tests are more likely because of previous vaccination or infection with Mycobacteria other than tuberculosis (MOTT), then >15 mm of induration should be used for interpretation. However, false negatives can arise from anergy. Primary tuberculosis, or initial infection, is usually seen in children and consists only of a small peripheral lung granuloma in association with enlarged hilar nodes with caseating granulomas. Most of these cases resolve, but if a patient's immune status is diminished, then there can be development of secondary tuberculosis with upper lobe granulomas and cavitation. Miliary tuberculosis is seen in severely immunocompromised patients. Culture of sputum or bronchoalveolar lavage fluid, or tissue culture from aspirates or biopsies, helps to make the diagnosis and also determine appropriate antibiotic therapy, which may require 6 to 12 months.

Discuss clinical and pathologic findings that are useful in the diagnosis and treatment of a patient with tuberculosis. (<250 words)

(Example 3)

The pathologic appearance of Mycobacterium tuberculosis infection is different in primary, secondary, and milary tuberculosis. The gross appearance of primary tuberculosis with initial infection is a "Ghon complex" with a subpleural mid-lung granuloma combined with markedly enlarged hilar lymph nodes containing caseating granulomas. Patients who have decreased cell-mediated immunity are prone to develop secondary tuberculosis in which the granulomas are mainly in the upper lobes, can be larger, and can cavitate and/or calcify. If the immune status is very poor, then multiple tiny granulomas are seen scattered throughout the lung in "miliary" tuberculosis. Both the gross and radiographic findings of tuberculosis may mimic primary and metastatic lung neoplasms, and fungal granulomas (histoplasmosis, coccidioidomycosis, cryptococcosis) can appear similarly. Microscopically, tuberculosis producing caseating granulomas with central caseous necrosis surrounded by an inflammatory reaction of epithelioid macrophages, Langhans giant cells, lymphocytes, and fibroblasts. An acid fast stain can reveal the slender red rods of the M. tuberculosis bacilli. Mycobacteria other than tuberculosis (MOTT), such as M. kansasii, can sometimes cause a similar disease (though Mycobacterium avium complex is usually a disseminated infection without severe lung involvement). Thus, culture is important to distinguish these organisms and to rule out fungi. Erosion of the granulomas into bronchi can lead to the clinical finding of hemoptysis, and such patients are very infectious to others because tuberculosis is spread by droplet nuclei in aerosols.