Pulmonary Sarcomatoid Carcinoma in a Renal Transplant Recipient N. Basic-Jukic* and P. Kes Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, Zagreb, Croatia
ABSTRACT Sarcomatoid carcinomas (SC) are rare malignancies with concomitant occurrence of both carcinomatous and sarcomatous components. Although it may occur throughout the body, lungs are only very rarely involved. We present the first documented case of pulmonary SC (PSC) in a renal transplant recipient, and discuss clinical presentation, diagnostic procedures, treatment, and outcome.
S
ARCOMATOID CARCINOMAS (SC) are rare malignancies with concomitant occurrence of both carcinomatous and sarcomatous components. Primary SC may affect different organs and tissues, of which lungs are only very rarely involved. PSC is a rare histologic type of nonesmall-cell lung cancer, accounting for 0.1%e0.4% of all lung malignancies [1]. Tumors are frequently symptomatic, locally advanced, and have an high rate of recurrence [2,3]. For the first time, we report a case of SC in a renal transplant recipient and discuss clinical manifestations, treatment, and prognosis. CASE REPORT A 50-year-old man was admitted to our department with a history of coughing and hemoptysis for 10 days. He was afebrile, dyspneic, and tachypneic. He had a 25-year history of cigarette smoking (30 cigarettes per day), and received a renal allograft in 2005 for treatment of end-stage renal disease caused by immunoglobulin A nephropathy. The posttransplant course was uneventful, without acute rejection episodes. However, over the years graft function had gradually declined with biopsy-proven graft glomerulopathy, a glomerular filtration rate of 25 mL/min, and proteinuria of 2.5 g/d. Immunosuppressive therapy included mycophenolate mofetil 500 mg twice daily, tacrolimus (trough level, 4.2 mg/L), and prednisolone 5 mg. On admission, chest radiographs demonstrated lung infiltration in the left upper lobe. CT showed a tumor mass measuring 5 4.2 4 cm attached to pleura which was thickened in the area measuring 3 5 1.3 cm. Mediastinal and paraaortal lymph nodes measured 7 mm. Fiber bronchoscopy revealed almost complete obstruction of bronchi in the involved area. The patient underwent left pulmonectomy with resection of peribronchal and mediastinal lymph nodes. A tumor mass with >50% necrotic parts involving the visceral pleura was found. Histologically, 85% of the tumor was built from atypical, poorly differentiated epithelial cells, whereas in the other part pleomorphic, spindle-shaped cells, some with giant nuclei, were found. Immunohistochemically, the tumor cells were positive for vimentin, 0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2014.12.027
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CK (cytokeratin) AE 1/3 and CK 5/6, and negative for thyroid transcription factor (TTF)-1. His postoperative course was complicated with prolonged severe sepsis caused by Klebsiella pneumoniae ESBL, which was treated with meropenem. Respiratory insufficiency demanded 1 month of support on a respirator. Continuous venovenous hemofiltration was used for renal replacement therapy. After improvement of his overall condition, and 3 months after the original admission, an arteriovenous fistula developed and the patient started with regular hemodialysis sessions. His immunosuppression was gradually decreased. Owing to poor overall condition accompanied with allograft failure and need for renal replacement therapy with hemodialysis, his pulmonologists, oncologists, and nephrologists decided to treat conservatively this patient to avoid further deleterious effects of chemotherapy. Ten months after the diagnosis he is still alive.
DISCUSSION
Renal transplant recipients have increased risk for development of malignant diseases [4]. PSC are rare forms of nonesmall-cell lung cancers with coexistence of a sarcomatous and carcinomatous components [1e3]. This group of malignancies is more common in male smokers [5]. Our patient had a long-term history of heavy smoking. This tumor most commonly affects right upper lobes and grows by invading the bronchial tree and surrounding pulmonary structures [6]. In this case, the tumor mass involved the left upper lobe and affected pleura. The diagnosis may only be established by immunohistochemical staining. The epithelial component is stained with antibodies to cytokeratins, EMA, and carcinoembryonic
*Address correspondence to Nikolina Basic-Jukic, MD, PhD, Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia. E-mail: [email protected] ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 47, 834e835 (2015)
PULMONARY SARCOMATOID CARCINOMA
antigen, whereas the sarcomatoid part exhibits positive staining for vimentin. In our patient, the tumor was positive for vimentin, CK AE 1/3, and CK 5/6, and negative for TTF1, which corresponds with previous reports [7,8]. Treatment options include radical surgery and chemotherapy with doxorubicin and ifosfamide. In a study by Italiano et al [9], 50% of patients with metastatic PSC had an initial response to chemotherapy. In a group of 69 patients from China, the median survival time was 19.1 months, and the 5-year survival rate was 17.4%. Absence of distant metastasis, normal or higher body mass index (18.5 kg/m2), normal hemoglobin, tumor size 4 cm, and complete resection were associated with better overall survival (P < .05). Patients with pleomorphic carcinoma had a much worse prognosis [10]. Owing to poor overall condition, our patient did not undergo chemotherapy. In conclusion, PSC are rare, aggressive malignancies. Limited experience in treatment of PSC exists owing to sporadic cases. Multicenter collaborations are necessary to determine the optimal treatment. This is the first documented case of PSC in a renal transplant recipient. It demonstrates that patients with a history of smoking should be screened regularly for the presence of lung cancer to recognize pathologic conditions in a timely manner. Smoking cessation should be promoted among all renal transplant recipients.
835
REFERENCES [1] Park JS, Lee Y, Han J, Kim HK, Choi YS, Kim J, et al. Clinicopathologic outcomes of curative resection for sarcomatoid carcinoma of the Lung. Oncology 2011;81:206e13. [2] Travis WD. Pathology and Genetics of Tumors of the Lung, Pleura, Thymus and Heart. Lyon, France: IARC; 2004. [3] Franks TJ, Galvin JR. Sarcomatoid carcinoma of the lung: histologic criteria and common lesions in the differential diagnosis. Arch Pathol Lab Med 2010;134:49e54. [4] Penn I, Starzl TE. Immunosuppression and cancer. Transplant Proc 1973;5:943e7. [5] Huang SY, Shen SJ, Li XY. Pulmonary sarcomatoid carcinoma: a clinicopathologic study and prognostic analysis of 51 cases. World J Surg Oncol 2013;11:252. [6] Pelosi G, Sonzogni A, De Pas T, Galetta D, Veronesi G, Spaggiari L, et al. Review article: pulmonary sarcomatoid carcinomas: a practical overview. Int J Surg Pathol 2010;18:103e20. [7] Terada T. Sarcomatoid carcinoma of the lung presenting as a cutaneous metastasis. J Cutan Pathol 2010;37:482e5. [8] Hountis P, Moraitis S, Dedeilias P, Ikonomidis P, Douzinas M. Sarcomatoid lung carcinomas: a case series. Cases J 2009;2:7900. [9] Italiano A, Cortot AB, Illie M, Martel-Planche G, Fabas T, Pop D, et al. EGFR et KRAS status of primary sarcomatoid carcinomas of the lung: implications for anti-EGFR treatment of rare lung malignancy. Int J Cancer 2009;125:2479e82. [10] Lin Y, Yang H, Cai Q, Wang D, Rao H, Lin S, et al. Characteristics and prognostic analysis of 69 patients with pulmonary sarcomatoid carcinoma. Am J Clin Oncol 2014 Jul 25 [Epub ahead of print].
ABSTRACT Sarcomatoid carcinomas (SC) are rare malignancies with concomitant occurrence of both carcinomatous and sarcomatous components. Although it may occur throughout the body, lungs are only very rarely involved. We present the first documented case of pulmonary SC (PSC) in a renal transplant recipient, and discuss clinical presentation, diagnostic procedures, treatment, and outcome.
S
ARCOMATOID CARCINOMAS (SC) are rare malignancies with concomitant occurrence of both carcinomatous and sarcomatous components. Primary SC may affect different organs and tissues, of which lungs are only very rarely involved. PSC is a rare histologic type of nonesmall-cell lung cancer, accounting for 0.1%e0.4% of all lung malignancies [1]. Tumors are frequently symptomatic, locally advanced, and have an high rate of recurrence [2,3]. For the first time, we report a case of SC in a renal transplant recipient and discuss clinical manifestations, treatment, and prognosis. CASE REPORT A 50-year-old man was admitted to our department with a history of coughing and hemoptysis for 10 days. He was afebrile, dyspneic, and tachypneic. He had a 25-year history of cigarette smoking (30 cigarettes per day), and received a renal allograft in 2005 for treatment of end-stage renal disease caused by immunoglobulin A nephropathy. The posttransplant course was uneventful, without acute rejection episodes. However, over the years graft function had gradually declined with biopsy-proven graft glomerulopathy, a glomerular filtration rate of 25 mL/min, and proteinuria of 2.5 g/d. Immunosuppressive therapy included mycophenolate mofetil 500 mg twice daily, tacrolimus (trough level, 4.2 mg/L), and prednisolone 5 mg. On admission, chest radiographs demonstrated lung infiltration in the left upper lobe. CT showed a tumor mass measuring 5 4.2 4 cm attached to pleura which was thickened in the area measuring 3 5 1.3 cm. Mediastinal and paraaortal lymph nodes measured 7 mm. Fiber bronchoscopy revealed almost complete obstruction of bronchi in the involved area. The patient underwent left pulmonectomy with resection of peribronchal and mediastinal lymph nodes. A tumor mass with >50% necrotic parts involving the visceral pleura was found. Histologically, 85% of the tumor was built from atypical, poorly differentiated epithelial cells, whereas in the other part pleomorphic, spindle-shaped cells, some with giant nuclei, were found. Immunohistochemically, the tumor cells were positive for vimentin, 0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2014.12.027
834
CK (cytokeratin) AE 1/3 and CK 5/6, and negative for thyroid transcription factor (TTF)-1. His postoperative course was complicated with prolonged severe sepsis caused by Klebsiella pneumoniae ESBL, which was treated with meropenem. Respiratory insufficiency demanded 1 month of support on a respirator. Continuous venovenous hemofiltration was used for renal replacement therapy. After improvement of his overall condition, and 3 months after the original admission, an arteriovenous fistula developed and the patient started with regular hemodialysis sessions. His immunosuppression was gradually decreased. Owing to poor overall condition accompanied with allograft failure and need for renal replacement therapy with hemodialysis, his pulmonologists, oncologists, and nephrologists decided to treat conservatively this patient to avoid further deleterious effects of chemotherapy. Ten months after the diagnosis he is still alive.
DISCUSSION
Renal transplant recipients have increased risk for development of malignant diseases [4]. PSC are rare forms of nonesmall-cell lung cancers with coexistence of a sarcomatous and carcinomatous components [1e3]. This group of malignancies is more common in male smokers [5]. Our patient had a long-term history of heavy smoking. This tumor most commonly affects right upper lobes and grows by invading the bronchial tree and surrounding pulmonary structures [6]. In this case, the tumor mass involved the left upper lobe and affected pleura. The diagnosis may only be established by immunohistochemical staining. The epithelial component is stained with antibodies to cytokeratins, EMA, and carcinoembryonic
*Address correspondence to Nikolina Basic-Jukic, MD, PhD, Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia. E-mail: [email protected] ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 47, 834e835 (2015)
PULMONARY SARCOMATOID CARCINOMA
antigen, whereas the sarcomatoid part exhibits positive staining for vimentin. In our patient, the tumor was positive for vimentin, CK AE 1/3, and CK 5/6, and negative for TTF1, which corresponds with previous reports [7,8]. Treatment options include radical surgery and chemotherapy with doxorubicin and ifosfamide. In a study by Italiano et al [9], 50% of patients with metastatic PSC had an initial response to chemotherapy. In a group of 69 patients from China, the median survival time was 19.1 months, and the 5-year survival rate was 17.4%. Absence of distant metastasis, normal or higher body mass index (18.5 kg/m2), normal hemoglobin, tumor size 4 cm, and complete resection were associated with better overall survival (P < .05). Patients with pleomorphic carcinoma had a much worse prognosis [10]. Owing to poor overall condition, our patient did not undergo chemotherapy. In conclusion, PSC are rare, aggressive malignancies. Limited experience in treatment of PSC exists owing to sporadic cases. Multicenter collaborations are necessary to determine the optimal treatment. This is the first documented case of PSC in a renal transplant recipient. It demonstrates that patients with a history of smoking should be screened regularly for the presence of lung cancer to recognize pathologic conditions in a timely manner. Smoking cessation should be promoted among all renal transplant recipients.
835
REFERENCES [1] Park JS, Lee Y, Han J, Kim HK, Choi YS, Kim J, et al. Clinicopathologic outcomes of curative resection for sarcomatoid carcinoma of the Lung. Oncology 2011;81:206e13. [2] Travis WD. Pathology and Genetics of Tumors of the Lung, Pleura, Thymus and Heart. Lyon, France: IARC; 2004. [3] Franks TJ, Galvin JR. Sarcomatoid carcinoma of the lung: histologic criteria and common lesions in the differential diagnosis. Arch Pathol Lab Med 2010;134:49e54. [4] Penn I, Starzl TE. Immunosuppression and cancer. Transplant Proc 1973;5:943e7. [5] Huang SY, Shen SJ, Li XY. Pulmonary sarcomatoid carcinoma: a clinicopathologic study and prognostic analysis of 51 cases. World J Surg Oncol 2013;11:252. [6] Pelosi G, Sonzogni A, De Pas T, Galetta D, Veronesi G, Spaggiari L, et al. Review article: pulmonary sarcomatoid carcinomas: a practical overview. Int J Surg Pathol 2010;18:103e20. [7] Terada T. Sarcomatoid carcinoma of the lung presenting as a cutaneous metastasis. J Cutan Pathol 2010;37:482e5. [8] Hountis P, Moraitis S, Dedeilias P, Ikonomidis P, Douzinas M. Sarcomatoid lung carcinomas: a case series. Cases J 2009;2:7900. [9] Italiano A, Cortot AB, Illie M, Martel-Planche G, Fabas T, Pop D, et al. EGFR et KRAS status of primary sarcomatoid carcinomas of the lung: implications for anti-EGFR treatment of rare lung malignancy. Int J Cancer 2009;125:2479e82. [10] Lin Y, Yang H, Cai Q, Wang D, Rao H, Lin S, et al. Characteristics and prognostic analysis of 69 patients with pulmonary sarcomatoid carcinoma. Am J Clin Oncol 2014 Jul 25 [Epub ahead of print].
