Table of Contents  
Year : 2015  |  Volume : 8  |  Issue : 6  |  Page : 826-829  

Systemic sclerosis complicated with malignant pleural effusion with high serum CA-125 tumor marker

Department of Chest Medicine, Burdwan Medical College and Hospital, Burdwan, West Bengal, India

Date of Web Publication19-Nov-2015

Correspondence Address:
Rupam Kumar Ta
120, Vivekananada Road, Chotonilpur, P.O.-Sripally, Burdwan - 713 103, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0975-2870.169934

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The malignant pleural effusion in systemic sclerosis (SSc) is an uncommon condition than its common manifestation like interstitial lung fibrosis, pulmonary hypertension, and lung malignancy. We reported here a case of malignant pleural effusion in a 40-year-old female suffering from SSc with high serum tumor marker "cancer antigen-125 (CA-125)". Computed tomogram guided fine needle aspiration cytology from the lung nodule revealed adenocarcinoma lung. The frequency or reasons of an elevated level of a serum or pleural fluid CA-125 in this case are unclear. Excepting ovarian and lung malignancy, increased CA-125 level in serum, and pleural fluid is also detectable in nonmalignant conditions including SSc as a part of serositis. We emphasized here the malignant potential of SSc and the need for long-term follow-up to detect underlying malignancy. High CA-125 level might be interpreted cautiously.

Keywords: Lung cancer, pleural effusion, systemic sclerosis

How to cite this article:
Banerjee SN, Ta RK, Roy A, Barman P. Systemic sclerosis complicated with malignant pleural effusion with high serum CA-125 tumor marker. Med J DY Patil Univ 2015;8:826-9

How to cite this URL:
Banerjee SN, Ta RK, Roy A, Barman P. Systemic sclerosis complicated with malignant pleural effusion with high serum CA-125 tumor marker. Med J DY Patil Univ [serial online] 2015 [cited 2020 Dec 1];8:826-9. Available from:

  Introduction Top

Systemic sclerosis (SSc) is a chronic, often progressive, multisystem and autoimmune disease involving connective tissue, characterized by fibrosis of the skin and visceral organs (lungs, esophagus, kidney and heart) due to exuberant matrix collagen deposition. The interstitial fibrosis of lung parenchyma and pulmonary arterial hypertension are the usual manifestation in both the diffuse and limited form of SSc. [1] In addition, malignancy of lung and other organs like breast, esophagus, liver, even of skin, were noted in SSc. [2] Lung cancer is the most frequent type of cancer seen in SSc, followed by breast cancer. [2] The relative risk of lung malignancy in patients with SSc could be up to 16.5 times that of normal persons. [2] On the contrary, pleural effusion is uncommon in SSc. [3] Till date, magnitude of malignant pleural effusion developing in SSc complicated with lung cancer is not exactly known. The malignant pleural effusion develops in primary lung cancer nearly up to 40% of the cases especially with adenocarcinoma lung. [4] But unlike high prevalence of lung cancer, prevalence of SSc among the general population is less. [2],[5] Tumor marker "cancer antigen-125" (CA-125) level in serum and pleural fluid often raise in both various malignancies like ovarian carcinoma, adenocarcinoma lung and also in nonmalignant diseases like connective tissue diseases like systemic lupus erythematosus (SLE) and SSc as a part of serositis. [6] We are reporting here a case of malignant pleural effusion in a 40-year-old nonsmoker female suffering from progressive SSc for last 20 years with raised serum CA-125.

  Case Report Top

A 40-year-old nonsmoker female presented to us with complaints of worsened dry cough and progressive dyspnea for last 2 months. An intermittent dull aching lower abdominal discomfort was present for last 1-month without any swelling. She had no expectoration, chest pain, wheeze, hemoptysis, palpitation, pedal edema, fever. She disclosed irregular menstruation for 5 months. She was a diagnosed case of progressive SSc since last 20 years with positive anti-nuclear antibody (ANA) and anti-topoisomerase I (Scl-70) antibody titer. She developed interstitial lung disease with an advanced usual interstitial pneumonia (UIP) pattern detected from high resolution computed tomogram (HRCT) thorax since 2010. She was on irregular medication for control of SSc symptoms. On examination, her hands, feet, and facial appearances were typical of SSc. Thickening with tightening of facial and palmar skin suggestive of SSc was present [Figure 1]. Her general survey was unremarkable except for hurried respiratory rate of 42/min with working of accessory respiratory muscles. Fingertip oxygen saturation could not be measured due to fingertip sclerosis. Respiratory system examination revealed shifting of the trachea to the left side. Physical finding in right hemithorax was suggestive of moderate pleural effusion, and a vesicular breath sound was present in upper areas of the right side. In left side velcro rales interspersed with rhonchi were noted. Her heart sound was normal in intensity. Other systems were within normal limit clinically. Her routine blood biochemistry was normal except for low hemoglobin of 9 g/deciliter of blood and normocytic normochromic anemia. Obliviously she had high titer of ANA and scl-70 antibody since last 20 years. Her blood tests for glycemia, renal and liver function tests were normal. Chest X-ray showed right sided moderate pleural effusion and HRCT thorax showed reticular opacities [Figure 2] and septal thickening in the left lung with the basal predominance suggesting interstitial pattern of lung involvement. Ultrasonography (USG) guided pleural fluid analysis showed lymphocytic exudative, low adenosine deaminase, hemorrhagic pleural effusion with presence of malignant cells. USG guided pleural biopsy was done showing metastatic pleural involvement by an adenocarcinoma. Assay of serum CA-125 and carcinoma embryonic antigen (CEA) were done, and the result revealed their high value, 156.9 U/mL and 5.87 ng/mL, respectively. Both these tumor markers were also raised in pleural fluid. Serum CA-19.9 < 2.00 U/mL was normal. The assay of these tumor markers was planned to search for the primary site of malignancy toward ovary because of associated irregular menstruation and lower abdominal discomfort on admission in the absence of hemoptysis and chest pain. HRCT thorax showed bilateral interstitial lung disease of advanced UIP pattern with right-sided pleural effusion and few enhancing pulmonary nodules in the right lung as well as few nodules in the pleura [Figure 3] and [Figure 4]. CT guided fine needle aspiration cytology from the right lung nodules showed lung malignancy of adenocarcinoma variety. USG abdomen was normal including both normal looking ovaries. Recent electrocardiogram and echocardiography were of normal study. Fiberoptic bronchoscopy showed no endobronchial lesion. Broncho alveolar lavage, brush biopsy, and postbronchoscopy sputum revealed no malignant cells. Left and the right bronchial lavage study showed inflammatory cells, alveolar macrophages and groups of degenerating bronchial columnar cells seen but negative for tuberculosis by smear and culture. So, a diagnosis of adenocarcinoma of the lung with metastatic malignant pleural effusion was made in the presence of interstitial fibrosis lung (UIP). She was put on intercoastal chest drain to remove pleural fluid for relief of worsening dyspnea. Pleurodesis was done successfully to prevent reaccumulation of pleural fluid. She was checked up by our institutional oncology department where early palliative care support was suggested. The patient discharged on request thereafter.
Figure 1: Morphological appearance of the polystyrene sulfonate case showing (a) fi sh mouth appearance, thick, tight, glistening of skin, (b) the hand showing thick, tight skin, sclerosis of fi nger, digital pitting, and (c) thick rough tight skin of upper part of the trunk

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Figure 2: (a) Chest X-ray showing moderate pleural effusion and (b) high resolution computed tomogram thorax showing interstitial fibrosis of both lungs with pleural effusion (right side)

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Figure 3: High resolution computed tomogram thorax showing interstitial fibrosis with some lung nodules

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Figure 4: High resolution computed tomogram thorax showing usual interstitial pneumonia pattern interstitial fibrosis

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  Discussion Top

Systemic sclerosis or scleroderma is a connective tissue disorder, characterized by fibrosis, vasculties, chronic inflammation of the skin and visceral organs like the lungs, the kidneys, gastro-intestinal tract and skeletal muscles heart. [1] It causes interstitial fibrosis of lungs leading to restrictive pattern of pulmonary function and also development of pulmonary hypertension. Less commonly cystic lesions and pleural effusion can occur. But an overall increased risk of malignancy in patients with SSc was noted in the medical literature. [2] The most frequent malignancy in patients with SSc is lung cancer followed by breast cancer. [2] Other less common malignancies are esophageal, non-Hodgkin's lymphoma, liver, colon, bladder and also nonmelanoma skin cancer and mesothelioma. [7],[8],[9],[10] However, case reports on malignant involvement of pleural in SSc are very rare till date despite searching medical literature. The relative risk of lung malignancy in patients with SSc has been placed at up to 16.5 times that of normal persons. [2] Among its clinical subtypes (diffuse, limited, and overlap) of SSc, diffuse SSc have the highest relative risk of malignancy. [8] The overall risk of malignancy is significantly more in men than in women. [10] Bronchioloalveolar carcinoma, which is a type of adenocarcinoma, is the most common histological type associated with SSc [11] followed by squamous cell carcinoma, oat cell carcinoma, anaplastic carcinoma, and mesothelioma. [12] Our patient was female and had diffuse variety (SSc) and developed adenocarcinoma lung. Most of the lung cancers associated with interstitial pneumonia usually develop in heavy smokers and are located in the peripheral lung field. Yang et al. [13] reviewed that there was significant nonsmoker predominance in patients with SSc developing lung cancer compared with other connective tissue diseases. Our patient had lung interstitial lung fibrosis, but the lung nodules were centrally located than periphery and she was nonsmoker. As such pleural effusion is rare in SSc. [3] Thompson and Pope [3] using standard chest radiographs, noted pleural effusion in only 7% of patients with SSc. They had small no of cases and not clarified the proportion malignancy in their study. [3] The pathogenesis of pleural effusion in SSc was unknown, but might be related to complications [3] like vasculitis of the pleura, concomitant heart failure and infection that were absent in our patient. The characteristics of the pleural fluid also have not been well defined, although one study noted a high level of CA-125 in pleural fluid and serum in one SSc case. [14] High level of CA-125 in pleural fluid and serum was also detected in our case. Assay of tumor marker (CA-125 titer 156.9 U/mL) was done to search for primary tumor toward ovary on higher probability of ovarian malignancy at this age and in absence of hemoptysis, chest pain and any obvious mass lesion in the chest X-ray. CA-125 is well known to increase in various malignancies and also as a part of serositis of connective tissue diseases like SLE and SSc. [14] Serum CEA value often raise in adenocarcinoma lung. Le Thi et al. [15] concluded in a study that raised serum CA-125 titer higher than 1000 U/mL was always due to the presence of cancer. Markedly raised serum and fluid CA-125 titers have also been reported in benign conditions [16] and indicate its production from benign proliferating mesothelial cells. Increased serum CA-125 levels were detected in 52% of patients with hepatic diseases, in 100% of patients with nongynecological peritoneal carcinomatosis, and in 87% of patients with pleural effusion. [17] Our patient had serum CA-125 value of 156.9 U/mL, which was not very high. So, it was unclear whether high serum CA-125 in our case was because of malignancy or accompanying pleural effusion or combined effect. So, CA-125 did not play any diagnostic role and might be an incidental finding. It is also unclear whether malignant pleural effusion developed in our case as a stage based extension of primary lung cancer or synchronous pleural malignancy. Tumor nodules in the lung were centrally located rather than peripheral nodules. We could not perform immunohistochemistry on our patient for financial constrain because of exhausting initial screening test for suspecting ovarian malignancy. The exact mechanisms linking SSc and malignancy are not well understood. Few studies have shown the occurrence of lung cancer in the presence of pulmonary fibrosis. The occurrence of different types of cancer with SSc suggest different underlying mechanisms, including altered immune response, organ fibrosis, common genetic and environmental links, disease-dependent factors. [2],[5],[18],[19] . Our patient had interstitial fibrosis that might induce to develop adenocarcinoma lung. It is to remember that malignant pleural effusion often develops in lung adenocarcinoma and patients with SSc are at high risk of lung adenocarcinoma, which indicates the fact that malignant pleural effusion is very rare in patients with SSc is uncertain. The average duration to develop of lung cancer is usually in the follow-up period of 5-9 years from the diagnosis of SSc. [20] Our patients developed lung cancer 20 years after the diagnosis of SSc.

  Conclusion Top

Malignant pleural effusion may develop in SSc in nonsmoker female in the background of interstitial lung fibrosis. High serum CA-125 might be nonspecific and to be offered judiciously as a screening tool. Regular follow-up and vigilance is needed to identify the developing cancer in SSc patients to provide comprehensive health care and better quality of life.

  Acknowledgment Top

General support from our departmental staffs for technical and material support and help and acknowledgments of financial and material support.

  References Top

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Thompson AE, Pope JE. A study of the frequency of pericardial and pleural effusions in scleroderma. Br J Rheumatol 1998;37:1320-3.  Back to cited text no. 3
Johnston WW. The malignant pleural effusion. A review of cytopathologic diagnoses of 584 specimens from 472 consecutive patients. Cancer 1985;56:905-9.  Back to cited text no. 4
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Janmcja AK, Tendon S, Gupta KB, Marwah N. Lung malignancy in PSS. Indian J Tuberc 1998;45:161-3.  Back to cited text no. 12
Yang Y, Fujita J, Tokuda M, Bandoh S, Ishida T. Lung cancer associated with several connective tissue diseases: With a review of literature. Rheumatol Int 2001;21:106-11.  Back to cited text no. 13
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Le Thi Huong Du, Mohattane H, Piette JC, Bogdan A, Auzeby A, Touitou Y, et al. Specificity of CA 125 tumor marker. A study of 328 cases of internal medicine. Presse Med 1988;17:2287-91.  Back to cited text no. 15
Daoud E, Bodor G. CA-125 concentrations in malignant and nonmalignant disease. Clin Chem 1991;37:1968-74.  Back to cited text no. 16
Topalak O, Saygili U, Soyturk M, Karaca N, Batur Y, Uslu T, et al. Serum, pleural effusion, and ascites CA-125 levels in ovarian cancer and nonovarian benign and malignant diseases: A comparative study. Gynecol Oncol 2002;85:108-13.  Back to cited text no. 17
Marasini B, Conciato L, Belloli L, Massarotti M. Systemic sclerosis and cancer. Int J Immunopathol Pharmacol 2009;22:573-8.  Back to cited text no. 18
Takeda S. Systemic sclerosis (scleroderma) and malignancy. Nihon Rinsho Meneki Gakkai Kaishi 2004;27:389-96.  Back to cited text no. 19
Bouros D, Hatzakis K, Labrakis H, Zeibecoglou K. Association of malignancy with diseases causing interstitial pulmonary changes. Chest 2002;121:1278-89.  Back to cited text no. 20


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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