International Journal of Surgical Pathology http://ijs.sagepub.com/
Gestational Lung Adenocarcinoma: Case Report Mihai Ceausu, Sorin Hostiuc, Maria Sajin, Gheorghe Roman, Ovidiu Nicodin and Dan Dermengiu INT J SURG PATHOL published online 25 April 2014 DOI: 10.1177/1066896914531816 The online version of this article can be found at: http://ijs.sagepub.com/content/early/2014/04/17/1066896914531816
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IJSXXX10.1177/1066896914531816International Journal of Surgical PathologyCeauşu et al
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Gestational Lung Adenocarcinoma: Case Report
International Journal of Surgical Pathology 1–4 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1066896914531816 ijs.sagepub.com
Mihai Ceauşu, PhD1, Sorin Hostiuc, PhD2, Maria Sajin, PhD3, Gheorghe Roman, MD4, Ovidiu Nicodin, PhD5, and Dan Dermengiu, PhD6
Abstract Gestational cancer is a dramatic situation, with a deep impact on the patient and family, with an overall incidence of 1 per 100 pregnancies. Lung cancers are extremely rare during pregnancy but have become more frequent in past years, as the mean age of pregnancy has increased. The purpose of this case report is to present a gestational lung adenocarcinoma, with metastasis in the liver and ovaries, diagnosed in the third trimester, with a fatal outcome in days after birth through cesarean section. Keywords gestational lung adenocarcinoma, lung cancer in pregnancy, ovarian metastasis, estrogen receptors, progesterone receptors Gestational cancer occurs in about 1 per 1000 pregnancies1 and represents about 0.07% to 0.1% of all malignant tumors.1 Lung cancers are extremely rare during pregnancy,2 but as the mean age of pregnancy and the number of lung cancer cases in women in general increase—currently ranking second as a cause of cancer death in women with reproductive age3—the number of gestational lung cancers is expected to increase, and, subsequently, Obstetrics and Gynecology (OG) physicians should be made aware of this possibility. The purpose of this case report is to present a gestational lung cancer, diagnosed in the third trimester, with a fatal outcome in days after birth through cesarean section.
Case Presentation A 34-year-old woman without a significant personal history (including smoking), who was 30 weeks pregnant, came to the local emergency hospital for chest pain that started about 1 month before, aggravated in the past 4 days. At admission, she described pain in the right lower limb, fatigability, and productive cough. Laboratory investigation identified a small anemia, an acute inflammatory reaction with increased granulocyte count, positive C-reactive protein (CRP), and hepatic cytolysis. She was transferred to a regional emergency hospital where, at admission, presented only a mild dyspnea. Thoracic computed tomography identified disseminated micronodular and nodular densifications disseminated in the lungs, with floccular peribronchovascular densification extending toward lobar ramifications, subsequent narrowing of the lobar and segmental branches of the right superior lobe
Figure 1. Cut section of the lung showing a multiple nodular infiltrative malignant tumor, with foci of necrosis and hemorrhage and subpleural invasion (gross). 1
Department of Pathology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania 2 Department of Forensic Pathology, National Institute of Legal Medicine, Bucharest, Romania 3 Department of Pathology, Bucharest University Emergency Hospital, Bucharest, Romania 4 Department of Forensic Pathology, National Institute of Legal Medicine, Bucharest, Romania 5 Central Clinical Emergency Military Hospital, Department of Obstetrics and Gynecology, Bucharest, Romania 6 Department of Forensic Pathology, National Institute of Legal Medicine, Bucharest, Romania Corresponding Author: Sorin Hostiuc, Assistant Professor, Department of Forensic Pathology, National Institute of Legal Medicine, Soseaua Vitan Barzesti 9, 042122, Sector 4 Bucuresti, Romania. Emails:
[email protected],
[email protected]
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Figure 2. Microscopic appearance of the pulmonary tumor. Upper left: moderate to poor differentiated adenocarcinoma with little glandular structure (hematoxylin and eosin [HE], 100×). Upper right: CK7 staining intense positive in tumor cells (immunohistochemistry [IHC], 100×). Lower left: TTF1 positive in frequent tumor cell nuclei (IHC, 200×). Lower right: Ki-67 staining about 20% to 25% of tumor cell nuclei (IHC, 200×).
and right inferior lobe, a complete narrowing of the medium lobar bronchus, and secondary atelectasis. The right perihilar densification extended in the Barety lodge and the tracheobronchial space. Also identified were multiple enlarged lymph nodes, including para-aortic and a small right pleural and pericardial effusion. In the superior part of the liver (segments IV and VIII) were multiple hypodense areas, confirmed ultrasonographically. The bronchoscopy showed congestive bronchial edema and no proliferative areas. Cytology identified atypical cells, with nuclei at least 4 times larger than erythrocytes, arranged either separately or in a papillary fashion; some cells had an eccentric nucleus through the accumulation of mucus. Four days after admission an emergency cesarean section was performed under general anesthesia. The child
survived, weighing 1750 g at birth with no metastasis; placenta was also normal. During surgery was suggested the diagnosis of metastatic lung cancer aggravated by pregnancy-related immunosuppression. The patient died after 4 days, in cardiac arrest (asystole), irresponsive to cardiopulmonary resuscitation measures.
Autopsy Findings In lungs were identified numerous nodules of varying sizes, bilateral, gray-white, of increased consistency, imprecisely defined, with tendency to confluence (Figure 1). Similar nodules were identified in the liver. The initial cause of death was considered metastatic lung cancer with a rapid evolution during pregnancy.
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desmoplastic reaction. Lymphatic emboli were present. IHC revealed strong diffuse positivity of CK7, focal moderate positivity of TTF1, and Ki-67 staining approximately 10% to 15% of tumor cell nuclei (Figure 2). ER stained positive about 20% to 25% of the tumor cell nuclei, and PgR stained positive about 15% to 20% of the tumor cell nuclei (Figure 3). In liver, we found an adenocarcinomatosis neoplastic infiltrate with desmoplastic reaction and wide areas of necrosis and hemorrhage. CK7 and TTF1 were positive in tumor cells. The findings were consistent with a metastasis from a pulmonary adenocarcinoma (Figure 4). In the ovaries, we found cortical micrometastases of adenocarcinoma with small foci of necrosis and hemorrhage. CK7 and TTF1 were positive in tumor cells. The uterus was tumor free, with numerous vascular thrombosis and decidual transformation of the endometrial stroma, numerous clots with residual chorionic villi in necrobiosis, and fibrinoid deposits. The kidneys were also tumor free, with wide areas of acute cortical tubular necrosis. The myocardium showed vascular congestion and hypoxic lesions.
Discussion
Figure 3. Microscopic appearance of the pulmonary tumor. Up: Estrogen receptors, staining positive in about 20% to 25% of tumor cell nuclei (200×). Down: Progesterone receptors, staining positive in about 15% to 20% of tumor cell nuclei (200×).
Histology and Immunohistochemistry Histology examination was performed on 5-µm sections stained with standard hematoxylin/eosin and van Gieson. Immunohistochemical analysis was done through the indirect tristadial avidin-biotin complex method of Hsu et al,4 modified by Bussolati and Gugliotta.5 The antibodies (all Novocastra) used for immunohistochemistry (IHC) were as follows: CK7 (clone OV-TL, 1:100), TTF1 (clone NCLTTF1, 1:100), Ki-67 (clone MM1, RTU), ER (clone 6F11, 1:40), and PgR (clone 16, 1:100).
Results In lungs was found a moderately differentiated acinar adenocarcinoma, with trabecular areas and peribronchial and pleural invasion. The tumor showed variable areas of suppurative necrosis and hemorrhage, with moderate
Lung cancer associated with pregnancy is extremely rare. A review done by Jackisch in 2003 identified 14 cases from 1957 to 20012; Boussios et al, after only 10 years, identified a total number of 60 cases.6 The number of adenocarcinomas is smaller, even if this is the most frequent lung cancer in younger women.7 Except for 2 cases, all lung cancers identified during pregnancy were metastatic,6 as was the situation with our patient. Most authors agree that pregnancy does not increase the aggressiveness of lung cancer,2,8,9 but a contribution to the fulminant course of the disease by pregnancy-related immunosuppression, hormonal changes, or perfusion cannot be excluded with certainty.6 Estrogen receptors are abundantly expressed in lung tissue (both normal and atypical), suggesting a possible involvement in pathogenesis.10 Kawai et al found that ER-α expression and the absence of ER-β expression are associated with a poorer prognosis amongst non–small cell lung cancer patients.11 In our case, both estrogen and progesterone receptors were found in tumor cell nuclei, explaining, at least partially, the rapid course and unfavorable prognosis of the disease.
Conclusion Gestational lung cancer, even if extremely rare, is increasing in frequency, especially as the mean age of pregnancy increases. Physicians should be aware of this problem and, in the presence of respiratory symptoms—especially if the future mother is older than 30 and a smoker—should include this pathology in the differential diagnosis.
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Figure 4. Hepatic metastasis. Upper left: Cut section with multiple nodules with various shapes and sizes in parenchyma of the liver (gross). Upper right: neoplastic infiltration of adenocarcinoma (HE, 100×). Lower left: CK7 staining in glandular tumor cells (IHC, 100×). Lower right: TTF1 staining in tumor cell nuclei (IHC, 200×).
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Pavlidis NA. Coexistence of pregnancy and malignancy. Oncologist. 2002;7:279-287. 2. Jackisch C, Louwen F, Schwenkhagen A, et al. Lung cancer during pregnancy involving the products of conception and a review of the literature. Arch Gynecol Obstet. 2003;268:69-77. 3. Jemal A, Thomas A, Murray T, Thun M. Cancer statistics, 2002. CA Cancer J Clin. 2002;52:23-47. 4. Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981;29:577-580.
5. Bussolati G, Gugliotta P. Nonspecific staining of mast cells by avidin-biotin-peroxidase complexes (ABC). J Histochem Cytochem. 1983;31:1419-1421. 6. Boussios S, Han SN, Fruscio R, et al. Lung cancer in pregnancy: report of nine cases from an international collaborative study. Lung Cancer. 2013;82:499-505. 7. Radzikowska E, Głaz P, Roszkowski K. Lung cancer in women: age, smoking, histology, performance status, stage, initial treatment and survival. Population-based study of 20 561 cases. Ann Oncol. 2002;13:1087-1093. 8. Pawelec D, Madey B. [Adenocarcinoma of the lung with metastasis in a 39-year-old pregnant woman]. Pneumonologia polska. 1976;44:283-283. 9. Reiter AA, Carpenter RJ, Dudrick SJ, Hinkley CM. Pregnancy associated with advanced adenocarcinoma of the lung. Int J Gynaecol Obstet. 1985;23:75-78. 10. Mollerup S, Jorgensen K, Berge G, Haugen A. Expression of estrogen receptors alpha and beta in human lung tissue and cell lines. Lung Cancer. 2002;37:153-159. 11. Kawai H, Ishii A, Washiya K, et al. Estrogen receptor α and β are prognostic factors in non–small cell lung cancer. Clin Cancer Res. 2005;11:5084-5089.
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