Diffuse Infiltrate Focal Infiltrate

Common Common

Cytomegalovirus Gram-negative rods

Pneumocystis carinii Staphylococcus aureus

Drug reaction Aspergillus

Candida

Malignancy

Uncommon Uncommon

Bacteria Cryptococcus

Aspergillus Mucor

Cryptococcus Pneumocystis carinii

Malignancy Legionella pneumophila

plethora of entities involved makes diagnosis and treatment a distinct challenge. Some of the individual microbial agents afflicting HIV-infected patients have already been discussed; this

section will focus only on the general principles of HIV-associated pulmonary disease.

• Despite the emphasis on "opportunistic" infections, it must be remembered that bacterial lower respiratory tract infection caused by the "usual" pathogens is one of the most

serious pulmonary disorders in HIV infection. The implicated organisms include Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Gram-negative

rods. Bacterial pneumonias in HIV-infected patients are more common, more severe, and more often associated with bacteremia than in those without HIV infection.

• Not all pulmonary infiltrates in HIV-infected individuals are infectious in etiology. A host of noninfectious diseases, including Kaposi sarcoma ( Chapter 6 and Chapter 11 ),

pulmonary non-Hodgkin lymphoma ( Chapter 14 ), and primary lung cancer, occur with increased frequency and need to be excluded.

• The CD4+ T cell count can define the risk of infection with specific organisms. As a rule of thumb, bacterial and tubercular infections are more likely at higher CD4+ counts

(>200 cells/mm3 ). Pneumocystis pneumonia usually strikes at CD4+ counts below 200 cells/mm3 , while cytomegalovirus and Mycobacterium avium complex infections are

uncommon until the very late stages of immunosuppression (CD4+ counts <50 cells/mm3 ).

Finally, it is useful to remember that pulmonary disease in HIV-infected patients may result from more than one cause, and even common pathogens may present with atypical

manifestations. Therefore, the diagnostic workup of these patients may be more extensive (and expensive) than would be mandated in an immunocompetent individual.

Lung Transplantation

Indications for transplantation may include almost all nonneoplastic terminal lung diseases, provided that the patient does not have any other serious disease, which would preclude lifelong

immunosuppressive therapy. The most common indications are end-stage emphysema, idiopathic pulmonary fibrosis, cystic fibrosis, and primary pulmonary hypertension. While bilateral

lung and heart-lung transplants are possible, in many cases a single lung transplant is performed, offering sufficient improvement in pulmonary function for each of two recipients from a

single (and all too scarce) donor. When bilateral chronic infection is present (e.g., cystic fibrosis, bronchiectasis), both lungs of the recipient must be replaced to remove the reservoir of

infection.

Morphology.

With improving surgical and organ preservation techniques, postoperative complications (e.g., anastomotic dehiscence, vascular thrombosis, primary graft dysfunction) are happily

becoming rare. The transplanted lung is subject to two major complications: infection and rejection.

Pulmonary infectionsin lung transplant patients are essentially those of any immunocompromised host, discussed earlier. They include bacterial and viral (especially cytomegalovirus)

pneumonias, Pneumocystis carinii pneumonia (PCP), and fungal infections. In the early posttransplant period (the first few weeks), bacterial infections are most common. With

Gancyclovir prophylaxis and matching of donor-recipient CMV status, CMV pneumonia occurs less frequently and is less severe, although some resistant strains are emerging. Most cases

occur in the third to twelfth month after transplant. PCP is rare, since almost all patients receive adequate prophylaxis (usually Bactrim™). Fungal infections are mostly due to Candida and

Aspergillus species, and they involve the bronchial anastamotic site and/or the lung.

Acute rejectionof the lung occurs to some degree in all patients despite routine immunosuppression postoperatively. It often occurs during the early weeks to months after surgery but

may occur years later whenever immunosuppression is decreased. Patients present with fever, dyspnea, cough, and radiologic infiltrates. Since these are similar to the picture of infections,

diagnosis often relies on transbronchial biopsy. The morphologic features of acute rejection are primarily those of inflammatory infiltrates (lymphocytes, plasma cells, and few neutrophils

and eosinophils), either around small vessels, in the submucosa of airways, or both.[112]

Chronic rejectionis a significant problem in at least half of all lung transplant patients by 3 to 5 years. It is manifested by cough, dyspnea, and an irreversible decrease in lung function

tests. The major morphologic correlate of chronic rejection is bronchiolitis obliterans,the partial or complete occlusion of small airways by fibrosis, with or without active inflammation

( Fig. 15-41 ). Bronchiolitis obliterans is patchy and therefore difficult to diagnose via transbronchial biopsy. Bronchiectasis may develop in long-standing cases.

The acute cellular airway rejection (the presumed forerunner of later, fibrous obliteration of these airways) is generally

Figure 15-41Chronic rejection of lung allograft, with total occlusion of bronchiole (bronchiolitis obliterans). Adjacent pulmonary artery branch is normal. (Courtesy of Dr. Thomas

Krausz, Department of Pathology, The University of Chicago, Pritzker School of Medicine, Chicago, IL.)

TABLE 15-10-- Histologic Classification of Malignant Epithelial Lung Tumors

Squamous cell carcinoma

Small cell carcinoma

••Combined small cell carcinoma

Adenocarcinoma

••Acinar; papillary, bronchioloalveolar, solid, mixed subtypes

Large cell carcinoma

••Large cell neuroendocrine carcinoma

Adenosquamous carcinoma

Carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements

Carcinoid tumor

••Typical, atypical

Carcinomas of salivary gland type

Unclassified carcinoma

interesting postulate is that changes in cigarette type (filter tips, lower tar and nicotine) have caused smokers to inhale more deeply and thereby expose more peripheral airways and cells

(with a predilection to adenocarcinoma) to carcinogens.[124] There may be mixtures of histologic patterns, even in the same cancer. Thus, combined types of squamous cell carcinoma and

adenocarcinoma or of small cell and squamous cell carcinoma occur in about 10% of patients. For common clinical use, however, the various histologic types of lung cancer can be

clustered into two groups on the basis of likelihood of metastases and response to available therapies: small cell carcinomas (most often metastatic, high initial response to chemotherapy)

versus non-small cell carcinomas (less often metastatic, less responsive). The strongest relationship to smoking is with squamous cell and small cell carcinoma.

Morphology.

Lung carcinomas arise most often in and about the hilus of the lung. About three fourths of the lesions take their origin from first-order, second-order, and third-order bronchi. A small

number of primary carcinomas of the lung arise in the periphery of the lung substance from the alveolar septal cells or terminal bronchioles. These are predominantly adenocarcinomas,

including those of the bronchioloalveolar type, to be discussed separately.

Squamous cell carcinoma of the lung begins as an area of in situ cytologic dysplasia that, over an unknown interval of time, yields a small area of thickening or piling up of bronchial

mucosa. With progression, this small focus, usually less than 1 cm2 in area, assumes the appearance of an irregular, warty excrescence that elevates or erodes the lining epithelium. The

tumor may then follow a variety of paths. It may continue to fungate into the bronchial lumen to produce an intraluminal mass. It can also rapidly penetrate the wall of the bronchus to

infiltrate along the peribronchial tissue ( Fig. 15-42 ) into the adjacent region of the carina or mediastinum. In other instances, the tumor grows along a broad front to produce a cauliflowerlike

intraparenchymal mass

Figure 15-42Lung carcinoma. The gray-white tumor tissue is seen infiltrating the lung substance. Histologically, this large tumor mass was identified as a squamous cell carcinoma.

Figure 15-43Cytologic diagnosis of lung cancer is often possible. A, A sputum specimen shows an orange-staining, keratinized squamous carcinoma cell with a prominent hyperchromatic

nucleus (arrow). B, A fine-needle aspirate of an enlarged lymph node shows clusters of tumor cells from a small cell carcinoma, with molding and nuclear atypia characteristic of this

tumor (see also Fig. 15-44C ); note the size of the tumor cells compared with normal polymorphonuclear leukocytes in the left lower corner.

Figure 15-44Histologic appearance of lung carcinoma. A, Well-differentiated squamous cell carcinoma showing keratinization. B, Gland-forming adenocarcinoma. C, Small cell

carcinoma with islands of small deeply basophilic cells and areas of necrosis. D, Large cell carcinoma, featuring pleomorphic, anaplastic tumor cells and absence of squamous or glandular

differentiation.

Figure 15-45Bronchioloalveolar carcinoma with characteristic growth along pre-existing alveolar septa, without invasion. (Courtesy of Dr. Jerome B. Taxy, Department of Pathology, The

University of Chicago, Pritzker School of Medicine, Chicago, IL.)

TABLE 15-11-- New International Staging System for Lung Cancer

T1 Tumor <3 cm without pleural or main stem bronchus involvement

T2 Tumor >3 cm or involvement of main stem bronchus 2 cm from carina, visceral pleural involvement, or lobar atelectasis

T3 Tumor with involvement of chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura, pericardium, main stem bronchus 2 cm from carina, or entire lung

atelectasis

T4 Tumor with invasion of mediastinum, heart, great vessels, trachea, esophagus, vertebral body, or carina or with a malignant pleural effusion

N0 No demonstrable metastasis to regional lymph nodes

N1 Ipsilateral hilar or peribronchial nodal involvement

N2 Metastasis to ipsilateral mediastinal or subcarinal lymph nodes

N3 Metastasis to contralateral mediastinal or hilar lymph nodes, ipsilateral or contralateral scalene, or supraclavicular lymph nodes

M0 No (known) distant metastasis

M1 Distant metastasis present

Stage Grouping

Stage Ia T1 N0 M0

Stage Ib T2 N0 M0

Stage IIa T1 N1 M0

Stage IIb T2 N1 M0

T3 N0 M0

Stage IIIa T1–3 N2 M0

T3 N1 M0

Stage IIIb Any T N3 M0

T3 N2 M0

T4 Any N M0

Stage IV Any T Any N M1

Adapted from Mountain C: Revisions in the International System for Staging Lung Cancer. Chest 111:1710, 1997.

TABLE 15-12-- Local Effects of Lung Tumor Spread

Date: 2016-04-22; view: 708