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Year : 2014  |  Volume : 17  |  Issue : 3  |  Page : 117-120

A case of prolonged fever with pulmonary nodules-looking beyond neoplasms

1 Department of Medicine, Nil Ratan Sircar Medical College and Hospital, Kolkata, West Bengal, India
2 Department of Pathology, Nil Ratan Sircar Medical College and Hospital, Kolkata, West Bengal, India

Date of Web Publication6-Sep-2014

Correspondence Address:
Bitoti Chattopadhyay
Flat No. 2G, Nature's Nest, 140, P.G.H. Shah Road, Jadavpur, Kolkata 700 032, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1118-8561.140297

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We present an unusual case of a middle aged female without other known co-morbidities presenting clinically with isolated prolonged fever and a radiological evidence of persisting focal lung opacity mimicking neoplasm. She was subsequently diagnosed to have nonspecific interstitial pneumonia on video-assisted thoracoscopic surgery guided lung biopsy. She responded excellently to oral corticosteroids both clinically and radiologically. This case illustrated the need to think beyond infective and neoplastic etiologies in a patient with persistent lung nodule.

Keywords: Fever, idiopathic and non-specific interstitial pneumonia

How to cite this article:
Chattopadhyay B, Chatterjee A, Boler AK, Debnath NB. A case of prolonged fever with pulmonary nodules-looking beyond neoplasms. Sahel Med J 2014;17:117-20

How to cite this URL:
Chattopadhyay B, Chatterjee A, Boler AK, Debnath NB. A case of prolonged fever with pulmonary nodules-looking beyond neoplasms. Sahel Med J [serial online] 2014 [cited 2023 Oct 4];17:117-20. Available from: https://www.smjonline.org/text.asp?2014/17/3/117/140297

  Introduction Top

First described in 1994, non-specific interstitial pneumonia (NSIP) has been recently identified as a distinct form of idiopathic interstitial pneumonia. [1],[2] The most common symptoms of NSIP are dyspnea and cough that develop sub-acutely over weeks to months. Only about one-third of patients have fever in the course of the disease and even fewer develop nodular opacities in the lung. Bilateral patchy infiltrates are major radiological findings. [3],[4],[5] We report an unusual case of NSIP presenting clinically with prolonged fever and focal lung opacity mimicking neoplasm.

  Case report Top

A 48-year-old non-hypertensive, non-diabetic female homemaker presented with low grade, intermittent fever without chill or rigor for 2 months. She had no history of cough, exertional dysp.noea, chest pain, haemoptysis, significant weight loss, anorexia, and tuberculosis or chronic medication. She was a non-smoker and did not keep any pet. She had no history of any known allergic diseases like asthma, allergic rhinitis or atopic dermatitis oreczematous skin lesions or rashes. There was no, joint pain or bleeding manifestations suggestive of a collagen vascular disease or a small vessel vasculitis like Churg Strauss syndrome. She had a persistent nodular opacity involving the right lower lobe in her previous chest radiographs despite repeated courses of broad-spectrum antibiotics.

Physical examination was unremarkable except for the presence of fever (101°F). There was no clubbing and lungs were clear clinically. Initial blood reports showed haemoglobin 8.3 gm/dl, white cell count of 10,200/mm 3 (polymorphs 80%, lymphocytes 12%, monocytes 2%, eosinophils 6%). The erythrocyte sedimentation rate was 100 mm in the 1 st hour. In view of eosinophilia, serum immunoglobulin E level and stool routine examination were done which were normal. Subsequently the eosinophilia resolved with a course of albendazole tablet 400 mg once daily at bedtime for 3 days. Blood culture, urine microscopy and culture, echocardiography and ultrasound examination of whole abdomen were non-contributory. Sputum microscopy for acid fast bacilli, mantoux test and human immunodeficiency virus serology were negative. Connective tissue screen revealed negative antinuclear antibody, positive rheumatoid factor (93.8 IU/ml), negative anti cyclic citrullinated peptide, negative perinuclear anti-neutrophil cytoplasmic antibodies and cytoplasmic anti-neutrophil cytoplasmic antibodies. Chest radiograph showed persistent right lower zone nodular opacity even after parenteral empirical broad spectrum antibiotics [Figure 1]. High-resolution computerised tomography (HRCT) scan of thorax showed multiple nodular opacities involving right middle and lower lobes with mild bronchiectatic changes [Figure 2].
Figure 1: Chest X-ray showing nodule in the lower lobe of the right lung

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Figure 2: High-resolution computerised tomography scan of thorax showing lung nodule in the right lower lobe mimicking neoplasm

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Bronchoscopy did not reveal any endobronchial lesion. Bronchoalveolar lavage showed no malignant cells and mycobacterial and fungal cultures were negative. Pulmonary function tests showed restrictive pattern with forced expiratory volume in 1 second (FEV1)-2.8 L forced vital capacity (FVC)-3.1 L, FEV1/FVC ratio of 91% (approx.) and reduced diffusing capacity for carbon monoxide (54% of predicted). Serum cancer antigen (CA)-125, carcinoembryonic antigen, alpha-foetoprotein, CA-15-3 were within normal limits. Video assisted thoracoscopic biopsy of the lung nodule was done. Histopathological examination showed lung parenchyma with intra-alveolar and intrabronchial accumulation of foamy histiocytes. The interstitium showed fibrocollagenous tissue densely infiltrated by inflammatory cells and lymphoid aggregates with germinal centre. These findings were consistent with cellular phase of NSIP, a variety of interstitial lung disease (ILD) [Figure 3]. Serum KL-6 value was elevated at 1295 U/ml.
Figure 3: Photomicrograph × 400 H and E, stain showing interstitial chronic infiltration of lymphocytes and plasma cells with occasional lymphoid aggregates.
The alveolar spaces are fi lled with alveolar macrophages

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The patient was started on Tab. Prednisolone 40 mg daily for 6 weeks. It subsequently tapered gradually by 5 mg every month along with other supportive care. There was radiological resolution of the lesion at the end of treatment.

  Discussion Top

The classification of interstitial pneumonia has undergone modifications in recent years, [2],[6],[7] with emphasis on pathologic, therapeutic and prognostic differences. Katzenstein and Myers described four histologic forms of idiopathic interstitial pneumonia with (NSIP) as a separate entity, distinct from usual interstitial pneumonia (UIP), desquamative interstitial pneumonia, respiratory bronchiolitis interstitial lung disease and acute interstitial pneumonitis. [2] In contrast to UIP, which is synonymous with cryptogenic fibrosing alveolitis or idiopathic pulmonary fibrosis, NSIP responds better to steroids and carries a better prognosis. [2],[8],[9],[10]

NSIP has been classified into cellular and fibrotic forms. [1] The inflammatory and fibrotic processes present in NSIP are temporally homogeneous histologically, unlike UIP which is characterised by variegated appearance and fibroblastic foci. [2] The chest radiograph is abnormal in about 90% of patients with NSIP. Abnormalities are usually bilateral with a basal predominance. They may be consolidative and patchy, reticulonodular, or mixed. Other described features are reduced lung volume, pleural effusion (5%), hilar nodes (6%) and normality (6%). [11] A number of HRCT features have been described in NSIP, which may occur in isolation or in combination. The most common finding is that of bilateral patchy areas of ground-glass attenuation, which may be symmetric or asymmetric, diffusely distributed in all zones or with a basal predominance. The subpleural region is most commonly affected. Consolidation is seen in some patients almost always in combination with ground-glass opacity. It is bilateral, basal and subpleurally predominant. Honeycombing and thickened bronchovascular bundles have also been described. Hartman et al. [12] described less common HRCT findings, which include poorly defined nodular opacities (centrilobular, subpleural and lower zone predominance), pleural effusion and enlarged hilar/mediastinal lymph nodes.

The diagnosis in our patient was secured from video assisted thoracoscopic biopsy of the lung nodule. It has been emphasised that diagnosing the various entities of interstitial pneumonias requires a wedge of the lung that can only be supplied by thoracoscopy or thoracotomy. Small biopsy specimens such as percutaneous needle and trans-bronchial biopsies cannot provide sufficient tissue. [2]

Cordier et al. [13] reviewed 16 patients of bronchiolitis obliterans organizing pneumonia and distinguished three groups of patients. The first group of patients presented with multiple patchy migratory pulmonary involvement of the pneumonia type whose clinical course was subacute, with cough, fever, weight loss, mild dyspnea, and increased erythrocyte sedimentation rate. Chest X-ray film and computed tomography scan showed multiple alveolar opacities and patients showed remarkable improvement with oral corticosteroids.

The most common symptoms of NSIP are dyspnea and cough that develop sub-acutely over weeks to months. Only about one-third of patients have fever in the course of the disease. However, our patient had prolonged fever as the only complaint. It is not usual for physicians to consider ILD as a diagnosis while starting workup of a patient presenting with prolonged fever. We did not consider ILD as our primary diagnosis to start with. So the patient was worked up as a case of Fever with lung nodule and our primary aim was to rule out a neoplastic pathology. The differential diagnosis were infections like tuberculosis, fungal and other bacterial pneumonias, collagen vascular diseases like systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, primary vasculitis like Wegener's Granulomatosis, Churg-Strauss syndrome, and most importantly primary or metastatic neoplasms of lung causing non-resolving pneumonia. The eosinphilia was likely due to an underlying parasitic infection which is frequent in India. We did not think of ILD as our primary diagnosis even after HRCT due to lack of tell-tale signs like bilateral subpleural ground glass opacities. It is the biopsy that ultimately led to the diagnosis. Our patient emphasises the need for considering such unusual diagnosis in patients presenting with fever and persistent lung nodule. Moreover, such lung nodules may mimic neoplasm and diagnostic differentiation is essential as treatment modalities differ widely. There was marked symptomatic improvement with oral corticosteroids, which is usual in NSIP as compared to other interstitial pneumonias.

  Acknowledgment Top

The authors would like to thank Dr. Anup Sadhu, Consultant Radiologist, Eko Diagnostics at Medical College Campus, College Street, Kolkata, India.

  References Top

1.Katzenstein AL, Fiorelli RF. Nonspecific interstitial pneumonia/fibrosis. Histologic features and clinical significance. Am J Surg Pathol 1994;18:136-47.  Back to cited text no. 1
2.Katzenstein AL, Myers JL. Idiopathic pulmonary fibrosis: Clinical relevance of pathologic classification. Am J Respir Crit Care Med 1998;157:1301-15.  Back to cited text no. 2
3.Nagai S, Kitaichi M, Itoh H, Nishimura K, Izumi T, Colby TV. Idiopathic nonspecific interstitial pneumonia/fibrosis: Comparison with idiopathic pulmonary fibrosis and BOOP. Eur Respir J 1998;12:1010-9.  Back to cited text no. 3
4.Kim TS, Lee KS, Chung MP, Han J, Park JS, Hwang JH, et al. Nonspecific interstitial pneumonia with fibrosis: High-resolution CT and pathologic findings. AJR Am J Roentgenol 1998;171:1645-50.  Back to cited text no. 4
5.Park JS, Lee KS, Kim JS, Park CS, Suh YL, Choi DL, et al. Nonspecific interstitial pneumonia with fibrosis: Radiographic and CT findings in seven patients. Radiology 1995;195:645-8.  Back to cited text no. 5
6.Liebow AA. Definition and classification of interstitial pneumoniasin human pathology. Prog Respir Res 1975;8:1-31.  Back to cited text no. 6
7.Katzenstein AL, Myers JL. Nonspecific interstitial pneumonia and the other idiopathic interstitial pneumonias: Classification and diagnostic criteria. Am J Surg Pathol 2000;24:1-3.  Back to cited text no. 7
8.Ryu JH, Colby TV, Hartman TE. Idiopathic pulmonary fibrosis: Current concepts. Mayo Clin Proc 1998;73:1085-101.  Back to cited text no. 8
9.Bjoraker JA, Ryu JH, Edwin MK, Myers JL, Tazelaar HD, Schroeder DR, et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998;157:199-203.  Back to cited text no. 9
10.Cottin V, Donsbeck AV, Revel D, Loire R, Cordier JF. Nonspecific interstitial pneumonia. Individualization of a clinicopathologic entity in a series of 12 patients. Am J Respir Crit Care Med 1998;158:1286-93.  Back to cited text no. 10
11.King TE Jr. BOOP: An important cause of migratory pulmonary infiltrates? Eur Respir J 1995;8:193-5.  Back to cited text no. 11
12.Hartman TE, Swensen SJ, Hansell DM, Colby TV, Myers JL, Tazelaar HD, et al. Nonspecific interstitial pneumonia: Variable appearance at high-resolution chest CT. Radiology 2000;217:701-5.  Back to cited text no. 12
13.Cordier JF, Loire R, Brune J. Idiopathic bronchiolitis obliterans organizing pneumonia. Definition of characteristic clinical profiles in a series of 16 patients. Chest 1989;96:999-1004.  Back to cited text no. 13


  [Figure 1], [Figure 2], [Figure 3]


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