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Bronchocentric Granulomatosis With Mucus Impaction Due to Bronchogenic Carcinoma An Association With Clinical Relevance.

Bronchocentric granulomatosis (BCG), first described by Liebow in 1973,[1] consists of filling of the lumen of a bronchiole with dense plugs of mucus and cellular debris, necrosis of mucosa, and its replacement by polymorphous inflammation and radially palisaded epithelioid histiocytes. The bronchiole may become surrounded by fibrosis. About one third of cases[2] are associated with asthma and have many eosinophils in addition to lymphocytes and histiocytes. The other two thirds of these cases are unassociated with asthma and have sparse eosinophils. The development of BCG in patients with asthma and pulmonary infection, particularly aspergillosis and tuberculosis, suggests that BCG is a reaction pattern and not a primary disease process.

Bronchocentric granulomatosis can present radiologically as a single mass, as multiple masses, or as a more diffuse disease. In a patient with a pulmonary nodule on chest radiographs, the clinician must rule out a malignant neoplasm. If a biopsy of such a lesion shows BCG, can one assume that BCG is the only process accounting for the radiologic change? We describe 4 patients with primary carcinoma of the lung associated with BCG. Such an occurrence, to our knowledge, has not been documented previously in the literature.


A search of pathology records at the Massachusetts General Hospital from 1986 to 1998 identified 4 patients with lesions of BCG in association with primary pulmonary carcinoma. Hospital records were reviewed for preoperative features of the patients and for postoperative follow-up.

Histologic sections stained with hematoxylin-eosin constituted the principal item of study. Sections of biopsies and of the definitive pulmonary lobectomy were available in all cases. Mucicarmine, Alcian blue, elastic, and trichrome stains were used selectively to help define morphology. Acid-fast, methenamine silver, and Gram stains were applied in a search for the presence of organisms. Immunoperoxidase stains were used in one case to rule out lymphoma.


Case 1

A 74-year-old man developed cough and weight loss due to a lung tumor, which was resected by right upper lobectomy. The carcinoma obstructed a bronchus (Figure 1, A). The tumor was a moderately differentiated squamous cell carcinoma (Figure 1, B). There was bronchiectasis with mucus plugs and granulomatous inflammation distal to the tumor (Figure 1, C). Bronchioles were obstructed by necrotic cells and lipid. Bronchiolar mucosa was destroyed and replaced by histiocytes in the manner of BCG.


Case 2

A 45-year-old man from Brazil experienced the insidious onset of left shoulder pain, which radiated to the left anterior chest wall. Chest radiographs showed a mass that invaded the left posterior third rib (Figure 2). Needle biopsy revealed a large cell carcinoma. One month following 40 Gy of radiotherapy, the mass was removed by left upper lobectomy with chest wall resection. A large cell carcinoma was accompanied by a bronchiolocentric granulomatous process (Figure 3, A) around mucus and necrotic material. Palisading histiocytes rimmed the necrotic material in the former lumen (Figure 3, B). An atypical lymphoid infiltrate in a subcarinal lymph node proved to be reactive hyperplasia by immunopathologic study.


Case 3

A 60-year-old woman with a recent history of pneumonia was found to have a mass in the right upper lobe. She underwent thoracoscopic wedge resection of the tumor. Diagnosis by frozen section was benign. A right upper lobectomy was carried out. Permanent sections showed a poorly differentiated adenocarcinoma. The specimen showed no tumor other than that in the block used for frozen section. However, granulomatous inflammation and granulomas were present around mucin in several foci in this and other blocks of tissue (Figure 4, A). The mucus stained positively with mucicarmine and Alcian blue. Elastic (Figure 4, B) and trichrome stains showed mural sclerosis and fibrosis of blood vessels in scar around the lesions of BCG. No organisms were present on acid-fast, silver, and Gram stains.


Case 4

A 45,year-old woman with intermittent anterior chest pain, a cough producing thick secretions, and a positive skin test for tuberculosis underwent resection of an adenocarcinoma, which in part had a bronchioloalveolar growth pattern and was multifocal. There were accompanying lesions of bronchiectasis, bronchiolar obstruction due to mucinous detritus, peribronchiolar scarring, and BCG. Stains for bacteria, fungi, and mycobacteria were negative. Six years later, a fine-needle aspirate of a cervical vertebra showed malignant cells consistent with metastasis from a primary lung carcinoma.


The study group consisted of 2 men and 2 women, ranging in age from 45 to 74 years (mean 56 years). Each patient presented with a solitary mass on chest radiographs and underwent bronchoscopy, staging mediastinoscopy, and pulmonary lobectomy. Two tumors were in the right lung, and 2 were in the left. The diagnosis of bronchogenic carcinoma was made by bronchoscopic biopsy in one patient, transthoracic needle biopsy in another, video-assisted thoracoscopic wedge resection in a third, and at the time of thoracotomy and lobectomy in the fourth. One tumor was squamous cell carcinoma, 2 were adenocarcinomas, and 1 was large cell carcinoma. None of the patients had asthma.

The histologic features of BCG common to all cases were bronchioles filled with mucus, necrotic debris, lipid, or a combination of these substances, as well as necrosis of bronchiolar mucosa and replacement of the mucosa by palisaded histiocytes. The lesions of BCG were in lung apart from grossly identifiable tumor. All resection margins, blood vessels, lymphatics, and regional lymph nodes were free of tumor. There was no clinical evidence of metastatic disease at the time of lobectomy in any of the patients. A summary of the clinical histories, including follow-up, and the main pathologic findings are provided in the Table

Summary of Clinical Histories, Pathologic Findings, and Follow-up(*)
Case No. Sex/Age, y Pathology

 1 F/45 BCG + BAC, MD
 2 M/45 BCG + LCC, U
 3 M/74 BCG + SCC, MD
 4 F/60 BCG + AC, P

Case No. Stains for
 Organisms [dagger]

 1 N
 2 N
 3 N
 4 N

Case No. Follow-up

 1 10 y; died with intracranial metastases
 2 None; patient reportedly returned to his home
 in Brazil
 3 17 mo; doing well; chest radiograph negative
 4 1 mo; doing well; small pneumothorax on chest

(*) BCG indicates bronchocentric granulomatosis; BAC, bronchioloalveolar cell carcinoma; MD, moderately differentiated; LCC, large cell carcinoma; U, undifferentiated; SCC, squamous cell carcinoma; AC, adenocarcinoma; and N, negative. [daggers] Stains included Gram, silver, and acid-fast.


The association of BCG with benign pulmonary disease has been described in 2 broad groups of patients, namely, those with an accompanying eosinophilia and those without.[3] Bronchocentric granulomatosis with eosinophilia typically occurs in asthmatic patients and may be associated with intrabronchial Aspergillus or rarely with other organisms. In patients without a known allergic diathesis or infectious process, BCG without eosinophilia seems more enigmatic. Common to both groups of patients is the mucus plugging, and the histiocytes are assumed to be an immunologic reaction to the mucus, the organism, or both. Our cases suggest another type of reaction for BCG, namely, a response to necrotic tissue as well as mucus. This necrotic tissue could conceivably contain tumor antigens that are eliciting the reaction, or lipid resulting from tissue breakdown could incite the granulomatous reaction.

Simultaneous granulomatous inflammation and neoplasia, either in different parts of the body or in close topographic relationship, have long been recognized.[4] A common example is the granulomatous reaction to degenerated keratin and lipid in some keratinizing squamous cell carcinomas in the skin, lung, and other organs. Bronchial obstruction due to a carcinoid tumor has resulted in eosinophilic material in bronchioles surrounded by palisading histiocytes, compact granulomas, and the presence of atypical mycobacteria.[5] Fungi and mycobacteria always have to be excluded when evaluating granulomatous destruction of bronchioles, including BCG.[6]

One example of BCG presented as a solitary enlarging lung mass, and transthoracic fine-needle aspiration was interpreted as "suspicious for adenocarcinoma" After lobectomy and negative stains for microorganisms, however, the mass was diagnosed as BCG with cytologic features suggestive of malignancy.[7] Whether or not this patient had or would have developed carcinoma, lobectomy provided definitive treatment. Apart from this study, we know of no other reports of BCG coexisting with bronchogenic carcinoma or suggestions that the BCG may be a reaction to necrotic tissue. Noncaseating granulomas of sarcoidal type can develop in the lung and hilar lymph nodes in association with bronchogenic carcinoma and presumably represent an immune response of the host to the carcinoma.[8-13] Systemic granulomas in sarcoidosis in patients with malignancy might represent a more generalized cell-mediated response to tumor antigen.[13] Bronchocentric granulomatosis in one patient with rheumatoid arthritis was thought to represent a widespread immunologic response and not a distinct entity.[14] In our cases, the histiocytes could be a reaction to inspissated or excessive mucus, lipid material, degenerated tumor tissue, or a combination of the three, with or without mechanical obstruction of a conducting airway by tumor. An immunologic response to tumor antigen would be akin to the sarcoidal reaction seen in other cases of bronchogenic carcinoma.

There are no definitive clinical, radiologic, or immunologic features of BCG.[15] The diagnosis depends on morphology of biopsy specimens or resected lung tissue. The most problematic differential diagnosis is Wegener granulomatosis, [16] where there is also debate about the relationship between necrotic tissue and the granulomatous reaction. Regardless of the pathogenesis, the importance of recognizing the association of bronchogenic carcinoma and BCG is clear. A diagnosis of BCG in a lung biopsy of a solitary mass does not rule out the presence of an accompanying bronchogenic carcinoma.


[1.] Liebow AA. The J. Burns Amberson Lecture: pulmonary angiitis and granulomatosis. Am Rev Respir Dis. 1973;108:1-8.

[2.] Mark EJ. Lung Biopsy Interpretation. Baltimore, Md: Williams & Wilkins; 1984:99-100.

[3.] Koss MN, Robinson RG, Hochholzer L. Bronchocentric granulomatosis. Hum Pathol. 1981;12:632-638.

[4.] Symmers W St C. Localized tuberculoid granulomas associated with carcinoma: their relationship to sarcoidosis. Am J Pathol. 1951;27:493-515.

[5.] Case records of the Massachusetts General Hospital: case 23-1989. N Engl J Med. 1989;320:1540-1550.

[6.] Myers JL, Katzenstein AA. Granulomatous infection mimicking bronchocentric granulomatosis. Am J Surg Pathol. 1986;10:317-322.

[7.] Mourad WA, Vallieres E, Power RF, Hirji M. Fine-needle aspiration cytology of bronchocentric granulomatosis: a potential diagnostic pitfall. Diagn Cytopathol. 1996;14:263-267.

[8.] Case records of the Massachusetts General Hospital: case 7-1982. N Engl J Med. 1982;306:412-420.

[9.] Ellman P, Harson A. The coexistence of bronchial carcinoma and sarcoidosis. Br J Tuberc. 1958;52:218-222.

[10.] Goodbody RA, Taylor AJ. Sarcoidosis and bronchial carcinoma. Tubercle. 1957;38:419-421.

[11.] Lynch JP III, Flint A, Miller DM, Fantone JC. Noncaseating pulmonary granulomas associated with small cell carcinoma of the lung. Am J Med. 1985;78: 691-696.

[12.] Schoenfeld Y, Avidor E, Eldar M, Vidne B, Levery M, Pinkhas J. Squamous cell carcinoma associated with sarcoidosis in the lung. Oncology. 1978;35:112 113.

[13.] Reich JM, Mullooly JP, Johnson RE. Linkage analysis of malignancy-associated sarcoidosis. Chest. 1995;107:605-613.

[14.] Hellems SO, Kanner RE, Rensetti AD Jr. Bronchocentric granulomatosis associated with rheumatoid arthritis. Chest. 1983;83:831-832.

[15.] Clee MD, Lamb D, Urbaniak SJ, Clark RA. Progressive bronchocentric granulomatosis: case report. Thorax. 1982;37:947-949.

[16.] Mark EJ, Matsubara O, Tan-Liu NS, Fienberg R. The pulmonary biopsy in the early diagnosis of Wegener's (pathergic) granulomatosis: a study based on 35 open lung biopsies. Hum Pathol. 1988;19:1065-1071.

Accepted for publication January 24, 2000.

From the Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass.

Reprints: Eugene J. Mark, MD, Department of Pathology, Massachusetts General Hospital, 32 Fruit St, Boston, MA 02114.
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Author:Houser, Stuart L.; Mark, Eugene J.
Publication:Archives of Pathology & Laboratory Medicine
Date:Aug 1, 2000
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