The case report is presented of a patient with longstanding cryptogenic fibrosing alveolitis who developed a high grade B cell non-Hodgkin’s lymphoma in an area of fibrosis.
- cryptogenic fibrosing alveolitis
- non-Hodgkin’s lymphoma
- bronchus associated lymphoid tissue (BALT)
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Carcinoma of the lung and pulmonary fibrosis may be associated,1-3 particularly in cryptogenic fibrosing alveolitis (CFA)1 2 and scar tissue.3However, there have been no reports of intrathoracic non-Hodgkin’s lymphoma originating in such tissue. We report the development of a high grade B cell non-Hodgkin’s lymphoma in an area of fibrosis in a case of longstanding CFA.
A 76 year old woman was admitted to hospital with a two week history of being confined to bed by lethargy, shortness of breath, and abdominal pain. Her appetite was poor and she had lost 8 kg in weight over the previous three months.
Three years previously she had presented with increasing dyspnoea. On examination she had finger clubbing and bilateral basal crackles. Thin section high resolution computed tomographic (CT) scanning of the lungs showed bilateral basal reticular shadowing consistent with fibrosing alveolitis, and transbronchial biopsy specimens showed interstitial fibrosis. She had smoked 20 cigarettes a day for 40 years until three years previously. Her pulmonary function tests showed a mixed restrictive and obstructive ventilatory defect with an FEV1/FVC ratio of 70%, a total lung capacity of 75%, and transfer factor approximately 50% of predicted. She made a good symptomatic response to steroid therapy and had remained well for two years.
Examination on admission revealed a low grade pyrexia of 37.2°C, bilateral inspiratory crackles at the lung bases, and some mild epigastric tenderness. There was no palpable lymphadenopathy. Investigations on admission revealed an anaemia of 9.8 g/dl with anisocytosis, polychromasia, and poikilocytosis. Her total white cell count was raised at 33.8 × 109/l with a neutrophilia of 31.7 × 109/l and normal lymphocyte count. Her ESR was 123 mm/hour. Chest radiography demonstrated bilateral basal reticulonodular shadowing consistent with CFA but the shadowing at the left base had increased. Ultrasound scanning of the abdomen was normal. A CT scan of the chest demonstrated a mass associated with collapse of the anterolateral segment of the left lower lobe.
Unfortunately the patient’s condition deteriorated rapidly after admission and she died 10 days later. Post mortem examination revealed a wedge shaped tumour measuring 7.0 cm in maximum diameter at the base of the left lower lobe. The remainder of this lobe was congested. There was also marked bilateral enlargement of the hilar lymph nodes and nodes within the angle of the bifurcation of the trachea. This was greater on the left side with the largest node measuring 4.0 cm in diameter and being situated behind the left main bronchus. Histological examination confirmed bilateral fibrosis consistent with cryptogenic fibrosing alveolitis and demonstrated that the tumour in the left lower lobe was a high grade non-Hodgkin’s lymphoma with mediastinal lymph node involvement. The infiltrate showed features of a diffuse large lymphoid cell non-Hodgkin’s lymphoma (a grade II lymphoma). The tumour cells stained positive for CD20 and CD79a, indicating their B cell lineage. This was therefore a high grade B cell lymphoma with no evidence of a low grade BALT (bronchus associated lymphoid tissue) lymphoma. There was no evidence of lymphoma elsewhere at necropsy.
It is recognised that patients with CFA have an increased relative risk of developing lung cancer, even allowing for other factors such as smoking.1 Previously it has been noted that there is an increased incidence of malignant lung tumours, particularly adenocarcinomas and bronchiolar-alveolar carcinomas, in fibrotic scars in the lung.2 3 Although intrathoracic involvement in non-Hodgkin’s lymphoma is common (occurring in about 10–25% of cases),4 5 it has not been described arising in an area of CFA.
The most common intrathoracic manifestations of non-Hodgkin’s lymphoma are mediastinal, hilar and paratracheal lymphadenopathy, although pleural effusions and lone pulmonary manifestations may occur.4 5 The latter may consist of single or multiple nodules, pneumonic areas, or peribronchial infiltration.4The prognosis for those with single or multiple pulmonary nodules and pleural effusion is generally poor,4-6 all cases being associated with extrathoracic manifestations of lymphoma in one study.4 The prognosis is more favourable in patients who have lymphadenopathy in the absence of other signs of intrathoracic involvement. In this case the lymphoma in the lung parenchyma was associated with mediastinal lymph node involvement without signs of extrathoracic disease and was therefore a primary lymphoma of the lung.
The commonest form of primary lung lymphoma arises from bronchus associated lymphoid tissue (BALT).7 It is a low grade B cell lymphoma, similar histologically to MALTomas of the gastrointestinal tract. However, unlike the mucosal associated lymphoid tissue (MALT) in the gut, BALT is found in only a minority of humans, although it is more prevalent in other species.8 Its role in normal immune regulation in the lung is not fully understood, but it is known that certain conditions, including smoking,9 can induce the presence of BALT. The effect of CFA on the presence or absence of BALT is, however, unknown.
In this case the lymphoma was high grade and it was of B cell origin. BALTomas have been found to undergo transformation to high grade lymphomas in a small number of cases7 where there is histological evidence of low grade BALT tumour in addition to the high grade lymphoma. However, in this case there was no histological evidence of BALT derived tumour. Isolated high grade B cell tumours are also described as are primary T cell lymphomas, although rare, and high grade unclassifiable tumours accounted for 3.2% of lymphomas in one study.7 It is therefore possible that in this case the lymphoma was a BALToma that had undergone transformation to a high grade lymphoma or a primary high grade B cell lymphoma.
Histologically, CFA is characterised by an inflammatory infiltrate in which lymphocytes may predominate and lymphoid aggregates occur. Subsequently there is fibrosis and disruption of normal pulmonary architecture. Other conditions which cause a chronic stimulation of the lymphoid system such as Hashimoto’s thyroiditis10 and gluten enteropathy11 have an increased incidence of lymphoma. It is therefore possible that, in recruiting lymphocytes into the affected area and by causing chronic lymphocytic stimulation, the disease process of CFA creates an environment which predisposes to the development of lymphoma. This may be a direct effect of lymphocyte recruitment or may be mediated by the induction and subsequent malignant transformation of bronchus associated lymphoid tissue.
We thank Dr D Donald, consultant pathologist, and Dr A Lamont, consultant oncologist, for their help in the preparation of this report.