Organizing pneumonia (OP), which was previously called bronchiolitis obliterans organising pneumonia, is a well-known clinicopathological entity (1–3) that is associated with non-specific clinical manifestations. Lange initially described OP in 1901 (2) and Epler et al (4) published the largest case series of OP in 1985. OP is considered a rare disease with an incidence of 1.96/100,000 (3); however, incidence has reportedly been increasing since the 1980s (2).

OP may be characterized as primary or secondary OP based on etiology. Primary OP is referred to as cryptogenic organizing pneumonia (COP) (1), has no known cause and is classified as an idiopathic interstitial pneumonia. Secondary OP is associated with various factors, including pathological infection (especially by Mycoplasma pneumoniae, Chlamydia pneumoniae and various types of virus (5), connective tissue diseases, malignancies, administration of various agents, chemotherapy, radiotherapy, organ transplantation (3), the inhalation of harmful gases (1,2) and certain occupations or environments (6). As OP may be idiopathic or associated with a known underlying disease, delayed diagnosis or mis diagnosis is likely to occur (7).

The characteristic clinical features of OP are typically non-specific and include constitutional symptoms with flu-like illness. Common clinical manifestations of OP include cough, dyspnea, fever and weight loss (2,7). Hemoptysis has rarely been reported as the primary presenting symptom of OP (2). The present case report details a Chinese case of COP with hemoptysis as the primary and unique clinical manifestation.

A literature review was carried out and a total of 23 studies published between 1995 and 2015 were included. A total of 119 COP cases were compared and analyzed for clinical manifestations, imaging manifestations, treatment and prognosis. The results of the review indicated that diagnosis of COP with lung cancer was challenging and COP was sometimes treated excessively, for example surgery was performed when steroids would have been sufficient, however the majority of patients with COP had a relatively good prognosis.

A 61-year-old Chinese male patient was presented with bloody sputum at Beijing Tiantan Hospital, Beijing, China, in August 2015. The chest X-ray revealed an abnormal shadow. The patient had no other chronic diseases such as hypertension or diabetes and no history of alcohol abuse or smoking. The results of human immunodeficiency virus and hepatitis B virus testing were negative.

Laboratory tests detected a white blood cell count of 4.92×10⁹/l (normal range, 4.0–10.0×10⁹/l), neutrophil percentage of 58.8% (normal range, 51.0–75.0%), lymphocyte percentage of 31.7% (normal range, 20–40%), monocyte percentage of 8.1% (normal range, 3.0–8.0%), eosinophil percentage of 1.0% (normal range, 0.5–5.0%), basophils percentage of 0.4% (normal range, 0–1.0%), red blood cell count of 4.88×10¹²/l (normal range, 4.0–5.5×10¹²/l), hemoglobin concentration of 145 g/l (normal range, 120–160 g/l), platelet count of 184×10⁹/l (normal range, 100–300) ×10⁹/l) and C-reactive protein level of 0.04 mg/dl (normal range, 0.0–0.6 mg/dl). Hepatic and renal functions and glucose and lipid levels in blood circulation were within normal ranges. Carbohydrate antigen 125, cytokeratin-19 fragment, neuron-specific enolase, squamous cell carcinoma associated antigen, carcino embryonic antigen and pro-gastrin-releasing peptide levels were within normal ranges.

Chest enhanced computed tomography scanning revealed a 3.0×1.1×2.0 cm irregular mass with rough edges and inhomogenous density in the apical region of the right upper lobe (Fig. 1). Pleural pull signs were visible around the mass. The lung demonstrated limitations of pulmonary emphysema. No marked swelling was observed in the lymph nodes in the mediastinal area and bilateral hilum of the lung. There was no effusion in the bilateral thorax and pericardium. Positron emission tomography-computed tomography scan with fluorin-18 fluorodeoxyglucose further revealed a high radioactivity uptake of this agent at the mass and a maximum standardized uptake value of 14.1 was recorded (Fig. 1). The mass appeared lobulated with surrounding burrs, and pleural pull signs were observed in the surrounding area. Primary malignant tumor was suspected from the imaging results.

Bronchoscopy revealed a normal tracheal mucosa and lumen. Pulmonary function tests presented normal volume and ventilatory function. Electrocardiogram examination returned normal results.

A surgical procedure was performed for the diagnosis and treatment of the mass. A partial resection including the mass was performed prior to frozen section examination. The lesion tissue and surrounding normal tissue were removed and kept dry. Tissue blocks were placed on a cold stage for embedding with Richard-Allan Neg 50 frozen section embedding medium (Thermo Fisher Scientific Inc., Waltham, MA, USA). Following quick-freezing (−25-30°C) for 2 min and samples were sliced into sections 3–5 µm thick. Sections were then attached to slides and fixed with fixing fluid composed of 95 ml 95% ethanol and 5 ml glacial acetic acid (Sinopharm Chemical Reagent Co., Ltd., Shanghai, China) for 1–2 min at room temperature. Hematoxylin-eosin (Baso diagnostics Inc., Zhuhai, China) staining was then performed at room temperature for 8–12 min. Examination of frozen sections revealed infiltration by numerous inflammatory cells with fibrous tissue hyperplasia; however, no apparent malignant tumor was identified. Wedge resection of the upper lobe of the right lung was successfully implemented via thoracoscope surgery. On the day following surgery, bedside chest X-ray examination was performed, which confirmed that the mass was completely removed. Electrocardiogram monitoring and blood routine examination results were within normal ranges. Atomization inhalation treatment with ipratropium bromide solution (500 µg; Shanghai Boehringer Ingerhan Pharmaceutical Co., Ltd, Shanghai, China) was administered 3 times per day for three days following surgery, Cefminox sodium (2 g, Qilu Pharmaceutical Co., Ltd, Jinan, China) was infused intravenously twice 1 day following surgery to prevent postoperative infection and Flurbiprofen axetil (100 mg, Beijing Ted Pharmaceutical Co., Ltd, Beijing, China) was infused intravenously twice per day two days following surgery for postoperative analgesia.

Pathological examinations revealed typical characteristics of OP. The alveoli and alveolar ducts were filled with plugs of granulation tissue, which were composed of fibroblasts. Furthermore, chronic inflammatory cell infiltration and a few scattered mononuclear macrophages were detected in tissue sections (Fig. 2).

The symptom of hemoptysis disappeared following the surgical resection and the patient recovered well. As no other lesions were detected in the lung, corticosteroid administration was not considered and follow-up observation was recommended for the patient. Informed consent was obtained from the patient prior to inclusion in the present report.

COP is a rare disease that occurs in both men and women with reports increasing in frequency (26). The illness is not known to be associated with smoking (2). The diagnosis of OP requires a multidisciplinary approach combining clinical and radiological expertise, with histopathological evidence when a lung biopsy has been performed (26). Sometimes, OP may simulate lung cancer (18) or coexist with lung cancer (26). As such, it may be difficult but necessary to make differential diagnosis between OP and lung carcinoma.

OP and lung cancer typically exhibit similar clinical manifestations. Clinical manifestations of OP are non-specific. The typical presentation is of a subacute or chronic clinical course with fever, cough, weight loss and dyspnea, and less commonly with chest pain and hemoptysis (2), whereas lung cancer is typically characterized by chest pain and hemoptysis. For central-type lung cancer, clinical manifestations typically include irritating cough, dyspnoea, asthma, recurrent pneumonia, hemoptysis, and nerve compression symptoms (28). For peripheral lung cancer, chest pain, dyspnoea and pleural effusion are common clinical symptoms (28).

It is difficult to distinguish lung cancer and OP from imaging, as they are diseases characterized by abnormal pulmonary shadows (5,6). Lung cancer typically shows irregular nodules or masses with an obscure boundary (3). Lobulation, spiculation, pleural invasion and lymph node metastases are also common clinical manifestations (28). OP may also present in the form of solid, mixed density, or, more rarely, ground-glass nodules. Typical radiological evidence of OP includes the presence of opacity, or consolidations with ground-glass appearance and lesions may migrate, with bilateral and peripheral distribution (29). Ground-glass opacity surrounding the OP lesion is a common sign, which typically indicates interstitial fibrosis and chronic inflammatory cell infiltration with a patchy area of polypoid granulation tissue (3). The most specific indicators of OP were peri lobular abnormalities, reverse halo sign, radial bands of consolidation containing an air bronchogram, and evolution and migration of the lesions over time (5,26), whereas tumor lesions are stationary. Furthermore, lymph node enlargement and pleural fluid are rarely observed in OP, but are often reported in lung carcinoma.

The pathologic OP pattern typically occurs in patients with lung cancer (18). OP is characterized by granulation tissue plugs within the lumens of small airways extending into the alveolar ducts and airways (2,3,7). Inflammatory debris fill the alveoli and spread to the alveolar ducts and terminal bronchioles, with characteristic endoluminal buds of granulation tissue known as Masson bodies (26). The clusters of granulation tissue, which are composed of fibroblasts and myofibroblasts, form as a result of non-specific tissue repair (23).

OP may accompany lung cancer as a result of the direct influence of a tumor on the surrounding lung parenchyma, or as a consequence of bronchial obstruction (5). Furthermore, anticancer treatment, including chemotherapy and radiotherapy, has been demonstrated to induce OP (5).

At present, the more common treatment methods are systemic corticosteroids therapy and surgical therapy. In 2013, an official statement from the American Thoracic Society/European Respiratory Society (30) recommended the following monitoring strategy of COP: Short-term observation to confirm treatment response and long-term observation to ensure that the response is preserved. Therefore, long-term follow-up observation is often necessary.

COP is not responsive to antibiotic therapy (7). Treatment with systemic corticosteroids typically achieves rapid improvement in symptoms and has a >65% cure rate, without significant sequelae (2,23). The most effective therapy is long-term administration of corticosteroids at high doses that are gradually increased during a treatment period of 6–12 months (29). However, when the corticosteroids are withdrawn or the dosage is decreased, COP may reoccur (7). In addition, prolonged treatment with corticosteroids is often associated with complications, including osteoporosis and trigger infection in diverse organs and systems, for example inhaling glucocorticoids may cause oral candidiasis infection, so patients are advised to use mouthwash after using inhaled glucocorticoids in order to avoid the occurrence of adverse reactions (7). Conversely, some patients may improve without treatment and spontaneous regressions have been observed (3,5). Treatment regimens with corticosteroids are not completely defined at present (23).

Lung biopsy or a pulmonary resection is often required to enable a definitive diagnosis (26). Transbronchial lung biopsy and percutaneous lung biopsy are frequently used techniques, but sampling limitation from the two techniques may lead to misdiagnosis as small biopsy tissues may not represent the intrinsic lesion (25). A full resection of the lesions and histopathological examination of the larger organization are typically necessary (31). Furthermore, thoracoscopy has become a common surgical method (32). In view of OP's benign nature and the efficacy of steroid therapy, unnecessary pulmonary resection should be avoided (3).

In conclusion, the present report detailed a case of COP with hemoptysis as the primary clinical manifestation, which resembled and was mistaken for lung cancer. The patient recovered well following wedge resection of the upper lobe of the right lung via thoracoscope. The present case demonstrated that it is difficult to make differential diagnosis between OP and pulmonary carcinoma, and pulmonary carcinoma should be excluded prior to the diagnosis of OP.

OP is a non-specific inflammatory process caused by various injuries of either definite or idiopathic etiology. Its clinical symptoms and imaging manifestations were varied without specific characteristics, and it may be confused with other lung diseases, especially pulmonary tumor. Occupying lesions and other types of lesions should be excluded prior to the diagnosis of OP. It is difficult to distinguish OP and lung cancer from clinical symptoms and imaging findings alone, and definite diagnosis typically requires pathological examination results.

Treatment with systemic corticosteroids is often effective; however, it typically requires a lengthy treatment period and is accompanied by adverse side effects. Available treatments at present have yet to achieve desirable therapeutic efficacy.

Considering the possibility that OP may coexist with lung carcinoma, small sample biopsy may not necessarily distinguish between the diseases, and large sample pathological examination may be required. Surgery is an adequate treatment, but may be excessive. At present, the thoracoscope is the most commonly used method.

Improvement of diagnostic techniques is required, and further research should be conducted to identify more effective therapeutic methods, in order to reduce or avoid trauma to patients from unnecessary surgeries.