Answer to CPC #5 (Tuesday, January 21, 2003)

The radiologic studies establish that this is a process that involves the pulmonary parenchyma, the pleural space and the soft tissue of the left chest wall. There is consolidation of the left upper lobe, a left-sided pleural effusion and an ill-defined soft tissue mass involving the left chest wall. Therefore, this process bridges multiple tissue planes in the left thorax. It appears radiographically to be extending from within the pulmonary parenchyma into the pleura and chest wall.

The differential diagnosis for this case revolves around primary pulmonary or chest wall neoplasms, benign processes capable of forming mass lesions, and infectious processes. Among primary pulmonary malignancies, bronchogenic carcinoma and mesothelioma are extremely rare in children, as are primary pulmonary sarcomas. Lymphoma would be more common than any of these possibilities, but is unlikely given the absence of lymphadenopathy on imaging studies. A primary chest wall neoplasm (such as a sarcoma) is not consistent with the radiographic findings of a pulmonary infiltrate adjacent to the chest wall mass. Benign processes capable of forming pulmonary mass lesions include systemic lupus erythematosis, sarcoidosis, rheumatoid arthritis, and Wegener's granulomatosis. None of these lesions commonly extends into the chest wall, or is particularly common in children.

The presence of an elevated white blood cell count and the tenderness of the mass lesion in the chest wall are difficult to reconcile with a malignancy, and are more suggestive of an inflammatory or infectious process. Two main types of infectious processes should be considered in this patient. The presence of a heart murmur, along with poor dentition, suggests that the process might be endocarditis with septic embolization and chest wall abscess. The absence of a significant murmur or other stigmata of endocarditis (such as Janeway lesions) makes this unlikely. Pneumonia with associated empyema and rupture/penetration into the chest wall (also known as empyema necessitans) is the more likely diagnosis. The patient is at high risk for aspiration of anaerobic bacteria given the presence of a cleft palate, along with periodontal disease, which increases the number of bacteria in the patient's oral cavity. Aspirations are typically polymicrobial; agents frequently isolated on culture include anaerobes, Staph aureus, and gram negative rods. Other agents to consider, in addition to bacteria, include Nocardia, Blastomycosis, Mucormycosis and Mycobacterium tuberculosis. Nocardia infection is associated with defects in cell mediated immunity in 50% of patients, including transplant patients and patients with AIDS. Nocardia is typically acquired through the pulmonary route, but disseminates in 1/3 of cases to involve the skin and brain. The presence of a chest wall mass would be most unusual for Nocardia, and the patient does not have a known defect in cell mediated immunity; these two facts make Nocardia infection unlikely. Blastomycosis is typically acquired in the southeastern United States where it is inhaled from the soil. Blastomycosis may involve the lung and cutaneous tissue, but pleural involvement is uncommon. Mucormycosis is typically a rapidly progressive disorder which affects patients with low absolute neutrophil counts (such as patients treated for leukemia) or with uncontrolled diabetes. Tuberculosis is also a consideration; the patient could have a primary pulmonary focus with extension of a cold abscess into the chest wall. The absence of significant lymphadenopathy on chest x-ray argues against this possibility, though the patient's PPD status was unknown at the time of diagnosis.

The most likely agent of infection, based upon the history, is Actinomyces species. These filamentous bacteria are part of the normal flora of 50% of healthy people. Actinomycosis is acquired by breakage of normal mucosal protection. A common means of acquiring pulmonary actinomycosis is by aspiration, for which this patient is at high risk. It is also typical that Actinomycosis will invade from the pulmonary parenchyma through to the chest wall via the pleural space. Actinomycosis infection is often characterized by a lack of respect of tissue planes. Other types of actinomycosis include cervicofacial infections (often associated with periodontal disease), abdominal infections (often associated with bowel perforation) and pelvic infections (often associated with usage of intrauterine devices). These organisms are anaerobic, and often difficult to culture, requiring two to four weeks to grow.

The patient underwent an open biopsy of the tumor mass. Frozen section evaluation revealed a background of histiocytes surrounding microabcesses, which in turn surrounded pink-blue amorphous material (Figure 1). At higher power, the amorphous material has a blue center and a pink rim; this is referred to as the Splendore-Hoeppli phenomena, which occurs when bacteria or filamentous bacteria (blue colored on the H&E stain) are coated by pink antibody protein (Figure 2, Figure 3). This histologic finding correlates with the gross finding of yellow sulfur granules. Based upon these findings, the frozen section evaluation indicates that there is not a malignancy or neoplasm present, but rather an infectious process. Microbiological cultures were suggested.

Figure 1

Figure 2

Figure 3

Special stains revealed that the organisms were positive with the Gram-Weigert stain (Figure 4), and the silver stain (GMS) (Figure 5). They were negative with typical acid fast stains and negative with the modified acid fast (FITE) stain (Figure 6). These findings support the diagnosis of Actinomyces versus the other filamentous bacteria in the differential, Nocardia (Figure 7). However, since not all Nocardia are modified acid fast positive, cultures are still required to definitively identify the organism. This patient's culture did reveal Actinomyces israelii. The patient was treated with penicillin and responded completely to therapy.

Figure 4

Figure 5

Figure 6

Figure 7

In summary, this patient suffered from Actinomyces infection of the lung, with extension into the left chest wall, simulating a neoplastic process. The capacity of Actinomycosis to produce tumor-like masses that simulate neoplasia should always be remembered in patients who present with what appears to be cancer, but for which multiple biopsies do not reveal a neoplastic process.