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Pulmonary Primitive Neuroectodermal Tumor Associated with Digital Clubbing – a Case Report

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Pulmonary Primitive Neuroectodermal Tumor Associated with Digital Clubbing – a Case Report 190 Pulmonary Primitive Neuroectodermal Tumor Associated with Digital Clubbing – A Case Report Sheng-Han Tsai, Han-Yu Chang Digital clubbing, one of the syndromes of hypertrophic osteoarthropathy, is associated with many types of medical illness, including infectious, inflammatory disease, cyanotic heart disease and neoplasm. Classically, digital clubbing has been thought to be associated with lung cancer. The incidence of clubbing fingers in lung cancer is about 10-29%, and it is more associated with non-small cell lung cancer than small cell lung cancer. We present a rare case of pulmonary primitive neuroectodermal tumor with clubbing fingers. A 56-year-old man had suffered from progressive dyspnea on exertion, accompanied with cough, abdominal fullness and body weight loss of 10 kg in the most recent 5 months. On examination, obvious digital clubbing was found in both hands. Imaging study demonstrated a huge left lung tumor. Sonography-guided biopsy was performed and the pathology report suggested primitive neuroectodermal tumor. The patient received chemotherapy with doxorubicin, decarbazine and ifosfamide, and began gradually feeling less dyspneic after chemotherapy. (Thorac Med 2010; 25: 190-196) Key words: nail, lung tumor, hypertrophic osteoarthropathy Introduction especially lung carcinoma [3-4]. The incidence of clubbing fingers in lung cancer is about 10- Digital clubbing is the thickening of the soft 29%, and it is more commonly associated with tissue beneath the proximal nail plate which re- non-small cell lung cancer than small cell lung sults in sponginess and thickening of the distal cancer [5]. Primitive neuroectodermal tumor digit [1]. Clubbing fingers can be an isolated (PNET) is a malignant tumor of neural crest finding or occur as part of the syndrome of hy- origin and arises outside the central nervous pertrophic osteoarthropathy (HOA), which also system. PNET very rarely manifests as primary includes arthralgia and periostitis [2]. Aside lung tumor. Our search of the literature revealed from the rare primary form of HOA, pachyder- that clubbing fingers had never been mentioned moperiostosis, secondary HOA is associated in a patient with pulmonary PNET. Herein, with extrapulmonary or pulmonary disorders, we report the case of a huge pulmonary PNET Division of Chest Medicine, Department of Internal Medicine, National Cheng-Kung University Medical College and Hospital, Tainan, Taiwan Address reprint requests to: Dr. Han-Yu Chang, Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, No. 138, Sheng-Li Rd., Tainan, 704, Taiwan Thorac Med 2010. Vol. 25 No. 4 Pulmonary Tumor with Digital Clubbing 191 combined with digital clubbing. Case Report The presented case is that of a 56-year-old male patient without a medical history, although he had a smoking history of about 20 years. About 5 months before admission, he suffered from progressive shortness of breath during exercise. The associated symptoms included cough with some sputum, and abdominal dis- tension, especially after intake or during a peri- od when he felt dyspneic. He also reported poor appetite and body weight loss of 10 kg within the most recent 5 months. Both the dyspnea and abdominal distension could be relieved by rest. He denied orthopnea, paroxysmal nocturnal Fig. 2. Chest radiograph shows a left opaque lesion with a midline dyspnea, chest pain or hemoptysis. The symp- structure shift to the right side toms progressed, and finally, he felt dyspneic even when walking. He visited a local hospital showed decreased breathing sounds and dull and abdominal sonography revealed a left up- percussion in the lower half of the left lung. per abdominal mass. Gastric lymphoma was Obvious digital clubbing of both hands (Figure suspected and he was referred to our hospital. 1) and leg edema were also found. Hemogram On admission, no fever was noted and the showed mild normocytic anemia (Hb = 12.8 respiratory rate was 18 per minute, with no re- mg/dl). Biochemistry data revealed normal liver spiratory distress noted. Physical examination function, renal function and electrolytes. Arte- rial blood gas showed metabolic alkalosis with respiratory compensation. The chest radiogra- phy (Figure 2) showed nearly total opacity of the left hemithorax with mediastinum and heart shifting to the right side. Panendoscopy was performed for abdominal discomfort and re- vealed external compression with posterior wall indentation of the stomach. Chest computed to- mography (CT) scan (Figure 3) showed a huge heterogeneous mass with focal necrosis and pleural effusion in the left thoracic cavity. There was also compression of the mediastinum, liver Fig. 1. Marked clubbing of the fingers of both hands with a shiny and stomach. Mediastinal lymph node metas- appearance tasis was also suspected. The chest CT favored 胸腔醫學：民國99年25卷4期 192 Sheng-Han Tsai, Han-Yu Chang (A) (B) Fig. 3. (A) Chest CT scan shows a tumor in the left lingual and lower lobe with pleural effusion and subcarinal lymphadenopathy. (B) At the lower level, the tumor occupies almost the whole left thoracic cavity with the heart and great vessel deviating to the right side. an intrapulmonary origin of the tumor. We per- after the treatment and the patient felt less dys- formed intermittent thoracentesis for relief of pneic. the dyspnea. The pleural effusion was reddish and the exudate was lymphocyte-predominant Discussion (54%) in character. Malignant pleural effusion was suspected, but no malignant cells could Digital clubbing, the most ancient sign of be found by effusion cytology. The pathology medicine, was first documented by Hippocrates obtained by sonography-guided biopsy showed about 2500 years ago as “water accumulation” diffuse small blue cells with hyperchromatic in a patient with empyema [6]. Alternatively, it nuclei. In the immunohistochemical study, the is also called Hippocratic finger or drumstick tumor cells were positive for CD99 and synap- fingers. Four grades or stages have been de- tophysin, and negative for cytokeratin, LCA, scribed as follows: fluctuation and softening of S-100, CD34 and TTF-1 (Figure 4). The final nail bed; an increase in the normal 160o angle pathologic diagnosis was PNET. between the nail bed and proximal nailfold; the The pulmonary function test demonstrated a development of a clubbing appearance; shiny severe restrictive ventilatory defect. Bone scan nail and periungual skin and longitudinal ridg- revealed a focal hot spot at the left 11th costo- ing of the nail [7]. Researchers have described vertebral junction and bone involvement was several methods for reaching an accurate diag- considered. Because of advanced disease with nosis, such as the profile sign; modified profile a huge tumor and suspicious metastases to the angle; hyponychial angle; and Schamroth sign lymph node and bone, surgical intervention was [8]. Initially, digital clubbing was considered an not indicated. He then underwent chemotherapy obvious physical sign associated with internal with a regimen of doxorubicin, dacarbazine and illness. With the use of radiologic imaging, it ifosfamide. No obvious side effect was noted was discovered that digital clubbing is usually Thorac Med 2010. Vol. 25 No. 4 Pulmonary Tumor with Digital Clubbing 193 (A) (B) Fig. 4. (A) Histological finding shows diffuse small blue cells with areas of tumor necrosis and focal fibrous tissue. (B) Immunohistochemically, the tumor cells show positive staining for CD99 and (C) synaptophysin. (C) accompanied with periosteal proliferation of the and many hypotheses of the pathophysiology tubular bone. The triad of digital clubbing, arth- have been proposed, but no single theory could ralgia, and periostitis comprises HOA. Current- well explain all the disease entities. The most ly, many authors consider that digital clubbing acceptable mechanism has been proposed by and HOA represent different stages of the same Dickinson and Martin [11]. When the normal syndrome [6, 9]. In this case, the clubbing was pulmonary capillary network is disrupted or by- so obvious that at least grade 4 clubbing was passed (such as by chronic lung inflammation, considered. However, the patient did not have carcinoma or intracardiac right-to-left shunt), arthralgia and no evidence of HOA was noted. the megakaryocytes, which escape being nor- Digital clubbing is an ominous sign with mally fragmented in the lung, can enter sys- which we are familiar; however, we appear temic circulation and impact fingertip circula- to know more about it than we really do [10]. tion. These cells release platelet-derived growth There are many reports describing the associa- factor (PDGF), which can promote blood flow, tion between clubbing and numerous diseases, vascular permeability and connective tissue 胸腔醫學：民國99年25卷4期 194 Sheng-Han Tsai, Han-Yu Chang change, subsequently resulting in the clubbing. sary. Clubbing can be the only or the preceding Recently, observation has suggested that vascu- sign of underlying malignant disease, thus we lar endothelial growth factor (VEGF) may be underscore the importance of a detailed physi- more associated with clubbing [12]. However, cal examination which may lead to the correct the exact mechanism is not fully understood. diagnosis. Clubbing fingers also indicate a poor prognostic sign, as the underlying disease has reached an References advanced stage [6]. Some reports have demon- strated improved clubbing after treatment of the 1. Robert S, Thomas M, Linford S, et
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