Nitrofurantoin

A 73-year-old woman presents to her physician complaining of a nonproductive nagging cough. Her medical history is remarkable for breast cancer treated by mastectomy 25 years prior to hospital admission and left lower extremity melanoma treated by excision 15 years prior to admission. She has a history of type II diabetes, a history of asthma that began around the age of 12 years, hypothyroidism, and a history of childhood acne treated with radiation therapy. She also has a 10 pack-year history of smoking, having stopped 43 years ago. Her surgical history is notable for a tonsillectomy, adenoidectomy, nasal polyps, dilatation and curettage, hysterectomy, and thyroidectomy. At presentation, the patient is receiving levothryoxine, conjugated estrogen, and latanoprost eye drops. She reports multiple allergies to medications, including iodinated contrast, erythromycin, codeine, tetracycline, nitrofurantoin, aspirin, atropine, and bacitracin.

Physicial examination shows a well-nourished woman breathing comfortably on room air. Her pulse is 81 beats/min, respiratory rate is 18 breaths/min, and BP is 112/54 mm Hg. Her neck is supple to palpation without evidence for cervical or supraclavicular lymphadenopathy. Her oropharynx is within normal limits. Her chest is clear to auscultation without evidence for wheezing or crackles. Her cardiac examination is within normal limits.

A chest radiograph (Fig 1) demonstrates a focal, oblong, 4-cm mass in the right middle lobe. Chest CT (Fig 2) shows that this mass is of slight increased attenuation compared to the skeletal muscle. No adenopathy is noted. The patient undergoes bronchoscopy, which demonstrates no evidence for an endobronchial lesion in the central or segmental airways. Whole-body positron emission tomography (PET) is then performed and shows intermediate uptake in the majority of the mass with a small focus of markedly increased 18-fluorodeoxyglucose (FDG) uptake within the center of the lesion (Fig 3). There is intermediate uptake in the right hilum on the PET scan. The patient is subsequently referred for a right middle lobe lobectomy.

[FIGURES 1-3 OMITTED]

What is the diagnosis?

Diagnosis: Mucoid impaction with fungal hyphae and bronchocentric granulomatosis

Gram stain showed scattered WBCs, culture findings were sterile, and there was no evidence of malignancy.

DISCUSSION

Bronchocentric granulomatosis was first described by Liebow in 1973 (1) and describes a rare granulomatous process centered on the bronchi and bronchioles. While the etiology of bronchocentric granulomatosis is uncertain, it has been postulated that it is a hypersensitivity reaction to endobronchial Aspergillus, as Aspergillus species have been cultured from the tissue specimens in a significant percentage of all cases, 75% of cases in one series. (2) The typical histopathologic features of bronchocentric granulomatosis are observed in the distal airways, and classically include replacement of bronchiolar epithelium with granulomatous inflammation and palisading histiocytes, occasionally involving adjacent small pulmonary arteries. The process is destructive, and tissue elastin stains are useful in the demonstration of airway and vessel remnants. Mucoid impaction of larger and more proximal airways often accompanies the granulomatous inflammation centered around the bronchioles, and remnants of fungal hyphae within the mucin may be identified. Bronchocentric granulomatosis is the typical histopathologic correlate of allergic bronchopulmonary aspergillosis in the asthmatic patient, but may be observed in other fungal and mycobacterial infections, and in the nonasthmatic patient as well, where organisms may be difficult to demonstrate histologically.

Clinical presentations are variable, with many patients presenting with acute respiratory symptoms and others with a more prolonged clinical course that can simulate that of lung carcinoma. This process has been reported to occur in both children and adults with an equal gender distribution. Many patients with this process have a history of asthma or allergic bronchopulmonary aspergillosis. However, many patients with bronchocentric granulomatosis also have no history of asthma, and often the tissue specimens from these patients are sterile, raising the suggestion that this is a pathologic process not a separate disease entity. (2,3) Additionally, this histologic pattern has been seen in patients with infectious processes including tuberculosis, histoplasmosis, coccidioidomycosis, blastomycosis, and echinoccoccus, as well as in a child with Epstein-Barr virus. (4) Patients with a variety of systemic noninfectious processes, including rheumatoid arthritis and Wegener granulomatosis, have also been reported to acquire bronchocentric graulomatosis. Cases have also been documented in people who are status post heart-lung and bone marrow transplantation.

Radiographically, bronchocentric granulomatosis presents most classically as either lobar consolidation and/or collapse or with the presence of nodules or masses in the lungs. These lesions rarely cavitate and are usually limited to one side of the thorax. (1-3) Presentation on the chest radiograph is very similar to other cases of mucoid impaction that occur in cases of bronchiectasis as well as in cases of bronchial obstruction. Most commonly, bronchiectasis due to bronchial atresia, allergic bronchopulmonary aspergillosis, or cystic fibrosis will demonstrate oblong elongated tubular homogenous opacities on the chest radiograph that are indicative of mucoid impaction. Bronchial obstruction due to either a primary or secondary neoplasm, an aspirated foreign body, or bronchial stenosis from an inflammatory, neoplastic, or infectious etiology may present with mucoid impaction and/or partial consolidation or atelectasis distal to the primary airway abnormality. The presence of high attenuation within an endobronchial mass on CT, as in this case, has been described with allergic bronchopulmonary aspergillosis (5) and is suggestive of inspissated secretions in the airways and mucus plugging.

This case demonstrates the classic radiographic manifestation of bronchocentric granulomatosis and illustrates how it can manifest in a similar fashion to a neoplastic process. The presence of an oblong homogenous tubular opacity with high attenuation demonstrated on chest CT is indicative of an airways process. In conjunction with a bronchoscopy that excluded an endobronchial lesion centrally, this radiographic presentation is classic for mucoid impaction. FDG-PET imaging of bronchocentric granulomatosis has not been reported in the literature. In this case, there was intermediate activity without avid FDG uptake to suggest the presence of malignancy. Malignancy has been associated with bronchocentric granulomatosis in one case reported in the literature. (6) Although PET has a sensitivity of 95% for detecting malignancy, (7) several malignancies including carcinoid and bronchioloalveolar cell carcinoma are known to often have low FDG uptake. In cases that have a characteristic radiographic presentation of mucoid impaction with a negative bronchoscopy and intermediate FDG metabolism, bronchocentric granulomatosis should be strongly considered in the differential considerations.

REFERENCES

(1) Liebow AA. The J. Burns Amberson Lecture: pulmonary angiitis and granulomatosis. Am Rev Respir Dis 1973; 108: 1-18

(2) Sulavik S. Bronchocentric granulomatosis and allergic bronchopulmonary aspergillosis. Clin Chest Med 1988; 9:609-621

(3) Ward S, Heyneman L, Flint J, et al. Bronchocentric granulomatosis: computed tomographic findings in five patients. Clin Radiol 2000; 55:296-300

(4) Millar JGC, Valacer D, Stavola J, et al. Idiopathic bronchocentric granulomatosis in an adolescent. Pediatr Pulmonal 1997; 23:62-65

(5) Logan PM, Muller NL. High resolution computed tomography and pathologic findings in pulmonary aspergillosis: pictorial essay. Can Assoc Radiol J 1996; 47:444-452

(6) Houser S, Mark E. Bronchocentric granulomatosis with mucus impaction due to bronchogenic carcinoma. Arch Pathol Lab Med 2000; 124:1168-1171

(7) Marom EM, Sarvis S, Herndon JE 2nd, et al. T1 lung cancer: sensitivity of diagnosis with fluorodeoxyglucose PET. Radiology 2002; 223:453-459

Manuscript received April 8, 2004; revision accepted November 9, 2004.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

Correspondence to: Lynne M. Hurwitz, MD, Duke University Medical Center, Box 3808, Durham, NC 27710

* From the Departments of Radiology (Drs. Hurwitz and McAdams) and Pathology (Dr. Sporn), Duke University Medical Center, Durham, NC.

COPYRIGHT 2005 American College of Chest Physicians
COPYRIGHT 2005 Gale Group