Arch Gynecol Obstet (2003) 268:6977 DOI 10.

1007/s00404-002-0356-x

R E V I E W A RT I C L E

Christian Jackisch Frank Louwen Anneliese Schwenkhagen Brigitta Karbowski Kurt Werner Schmid Hermann P. G. Schneider Wolfgang Holzgreve

Lung cancer during pregnancy involving the products of conception and a review of the literature
Received: 3 October 2000 / Accepted: 7 May 2002 / Published online: 21 November 2002 Springer-Verlag 2002

Abstract Approximately 1 per 1,0001,500 pregnancies is complicated by maternal malignancies. Metastatic involvement of the products of conception is a rare event. There have been 62 cases of placental and/or fetal metastatic involvement originating from maternal cancer reported since 1866. Only 14 cases of lung cancer associated with pregnancy have been documented. We report on an additional case involving the products of conception, and the management of lung cancer in pregnancy is discussed based on an extensive review of the literature. The case of a 29-year-old woman presenting during the 31st week of gestation with metastatic non small-cell lung cancer to the placenta, liver and bone is described. The mother was delivered by caesarean section of a healthy baby girl during her 32nd week of gestation. The mothers postpartum course was complicated by disseminated pulmonary and bony metastases and malignant
C. Jackisch () Department of Obstetrics and Gynecology, University Hospital Marburg, Pilgrimstein 3, 35037 Marburg, Germany e-mail: jackisch@med.uni-marburg.de Tel.: +49-6421-28-64390 Fax: +49-6421-28-68969 F. Louwen Department of Obstetrics and Gynecology, University of Frankfurt/Main, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany A. Schwenkhagen Altonaer Strasse 59, 20357 Hamburg, Germany B. Karbowski Department of Obstetrics and Gynecology, St. Johannes Hospital, Johannesstrasse 917, 44137 Dortmund, Germany K.W. Schmid Institute of Pathology, University of Essen, Hufelandstrasse 54, 45147 Essen, Germany H.P.G. Schneider ZMBE, von Esmarch-Strasse 56, 48129 Mnster, Germany W. Holzgreve Department of Obstetrics and Gynecology, University of Basel, Schanzenstrasse 46, 4031 Basel, Switzerland

pericardial and pleural effusions causing the patients death within 1 month after lung cancer was diagnosed. Malignancies spreading to the products of conception are melanoma (32%), leukemia and lymphomas (15%), breast cancer (13%), lung cancer (11%), sarcoma (8%), gastric cancer (3%) and gynecologic cancers (3%), reflecting malignancies with a high incidence in women of reproductive age. All lung cancers were diagnosed with widely disseminated, inoperable neoplastic disease, including distant metastases in 46%. The mean age was 35.1 years (range, 3045 years) and 60% of patients had a history of tobacco use. The mean survival was 7.5 months (range: 142 months). Placenta involvement was present in 7 out of 15 cases. Fetal involvement was reported in only one case. Because there is no evidence of a direct adverse effect of pregnancy on the course of lung cancer, we recommend delivery at a time when enough fetal maturity can be assumed and the subsequent treatment of the mother. Keywords Lung cancer Cancer and pregnancy Products of conception Placenta

Introduction
Cancer complicates approximately 1 per 1,0001,500 pregnancies and accounts for one-third of maternal deaths during pregnancy [1, 2]. One in every 118 invasive carcinomas in women may be diagnosed during pregnancy [3]. The cancers most frequently detected in pregnancy are obviously those with a peak incidence during the reproductive years, particularly breast, cervical, melanoma, ovarian and thyroid cancers, as well as leukemia and lymphoma [2, 4]. However, as more women delay childbearing to their fourth and fifth decades of life, other cancers whose incidence increases with age, may occur that are related to pregnancy, e.g. colon and lung [5, 6, 7, 25, 26]. A major concern is the possibility that malignancy may affect the fetus. Data on metastatic involvement of the products of conception are sparse

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since histologic examination of the placenta is not routinely performed. Valid data on the possibility of fetal involvement are missing due to the fact that most of the children were not followed up. We present a case of maternal non small-cell lung cancer (anaplastic large cell carcinoma) metastatic to liver, bone, and placenta with no evidence of fetal involvement and a review of the literature of the 62 cases of metastasis of maternal malignancy to the products of conception reported since the first publication [8] in 1866.

Case report
A 29-year-old white, gravida I, non-smoker was admitted at the 31st week of gestation to the obstetric service for further evaluation. The past medical history was unremarkable and she had been well until 2 weeks prior to admission when fever (max. 38.5C) and right hip and wrist pain were noted. Physical examination on admission revealed a pregnant woman who appeared chronically ill. Neither abdominal or pelvic masses nor lymphadenopathy were diagnosed. Colposcopy of the cervix including cytologic smear was unremarkable. Laboratory evaluations for sexually transmitted diseases, hepatitis, tuberculosis, and HIV were negative. Microbiological and cytologic findings from needle aspirates of the right hip and wrist joint were negative for specific disease. A shielded chest X-ray showed a mass located next to the aortic arch (Fig. 1). Magnetic resonance image of the thorax revealed a single solid mass (65 cm) in the upper posterior mediastinum without enlarged lymph nodes (Fig. 2). Computer tomographic-guided fine needle aspiration of this mass revealed an epithelioid cancer. Bone marrow aspiration showed no evidence of malignancy. On ultrasound scan, the fetus was developing well without pathologic findings. After one course of respiratory distress syndrome prophylaxis, amniocentesis was performed resulting in a lecithin/sphingomyelin ratio of 2:1. Following this result, on the tenth day of hospitalisation the patient delivered by caesarean section a 2400 g female infant with Apgar scores of 8, 9 and 9 at 1, 5 and 10 min, respectively. The infants clinical course was uncomplicated and she was discharged at 22 days of age. Evaluation for evidence of malignancy, including chest X-ray and tumour mark-

Fig. 2 Magnetic resonance image showing the tumour next to the aortic arch

ers, on the child was unrevealing. The child is alive at the age of 15 months and well at the time of this publication and receives regular paediatric follow up, as well as determination of carcinoembryonic antigen and chest roentgenograms at 3 month intervals. At the time of delivery, an intraoperative exploration of the patients abdomen was grossly normal, including liver, spleen, bowel, ovary and lymph nodes. Peritoneal washings were negative for malignant cells. After delivery, scans of the brain, neck, thyroid gland, liver and spleen; mammogram; upper and lower intestinoscopy were performed and were within normal limits. Bronchoscopy, including washings and biopsy, were also negative for malignancy. The bone scan, however, revealed multiple areas of increased uptake in the skull, pelvis, right hip and proximal femur suspicious for metastases. A follow-up chest X-ray showed rapid local progression of the tumour. On the sixth post-partum day, a thoracotomy showed an unresectable tumour, which was fixed to the aortic arch. Furthermore, frozen section showed evidence of disseminating metastatic spread to both lungs and malignant pericardial effusion (200 ml). The patients postoperative course was complicated by pathologic fracture of the right hip requiring surgical stabilisation on the ninth day after thoracotomy and the development of a new left pleura effusion, which required thoracentesis of 1200 ml. Subsequently, the patient developed progressive pericardial effusion and died of left heart failure 34 days after lung cancer had been diagnosed. Pathologic findings Postmortem examination A 666 cm relatively circumscribed greyish bronchial tumour was found in the upper lobe of the left lung (Fig. 3), infiltrating the aortic arch macroscopically. The tumour extended to the pericardium, left hilar and peribronchial lymph nodes and both lungs (disseminated metastatic foci up to 0.5 cm in diameter), including bilateral lymphangiosis carcinomatosa. Osteolytic bone metastases of the vertebral column and right femur were present, as well as diffuse metastatic infiltration of the liver. No tumour was found within the reproductive organs. Due to these findings, the tumour was staged as pT4, pN1, pM1 lung cancer. The cause of death was left heart failure caused by haemorrhagic pericardial tamponade.

Fig. 1 A-P Chest X-ray: Showing the tumour next to the aortic arch

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Fig. 3 Primary lung cancer macroscopically infiltrating the aortic arch. The tumour showed focal haemorrhage and necrosis

Fig. 5 The tumour cells in the intervillous space with discrete infiltration of chorionic villi (Orginal magnification 400)

an additional discrete infiltration of chorionic villi. (Fig. 5). The tumour cells in the placenta had the same morphology and pattern of immunohistochemical staining as in the primary tumour.

Discussion
Cancer diagnosed in association with pregnancy poses a difficult challenge to the patient and her family, the fetus and the medical team caring for both in a interdisciplinary approach. Lung cancer is not a common pregnancyassociated neoplasm ranking far beyond cervical cancer, breast cancer, haematopoietic neoplasms and malignant melanoma [3, 10]. The data on the incidence and mortality statistics demonstrate that lung cancer, once a rare disease, is the leading cause of cancer death among women in industrialised countries with an estimate of 79,200 new cases in the United States for 2002 [11]. Nevertheless, the rate of smoking among women is still increasing. Among women of reproductive age, 29% smoke. Of these women who become pregnant, between 19% and 30% continue to smoke [12]. Lung cancer ranks second as a cause of cancer death in women of reproductive age in 1999 [11]. Epidemiological and toxicological studies support the conclusion that smoking is the major cause of lung cancer [11, 12]. However, in males, 84% of lung cancer can be attributed to smoking, while in women this figure is less than half [13]. The incidence of lung cancer among nonsmoking women is approximately 68 out of 100,000 [14]. Besides the increasing incidence in lung cancer and cervical cancer, several complications in pregnancy, such as bleeding, premature rupture of membranes, preterm delivery, placenta praevia, abruptio placenta and low birth weight can be related to tobacco use [12, 15].The biological behaviour of lung cancer, however, does not seem to be altered by pregnancy [16]. Carcinomas of the lung are a heterogeneous group of malignancies. Lung carcinomas are divided into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), such as epidermoid or squamous cell carcino-

Fig. 4 Photomicrograph depicting a large cell anaplastic tumour with numerous mitosis (Orginal magnification 100)

Histology Both the primary tumour and its metastases showed a large-cell anaplastic carcinoma of the lung with focal necrosis. Numerous mitoses were noted (Fig. 4). Immunohistochemically, the primary tumour was positive with antibodies against cytokeratins (Kl-1), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), as well as the tumour-associated glycoprotein 72 (TAG72) [9]. No staining with antibodies against vimentin, desmin, smooth muscle actin, -HCG, -HCG, -1-antitrypsin, -fetoprotein, placental-like alkaline phosphatase (PLAP), factor-VIII-related antigen, a melanoma-specific antibody (HMB 45) or S-100 protein could be detected. Discrete focal immunoreactivity for chromogranin B, secretogranin II and neuron-specific enolase (NSE), indicating a neuroendocrine differentiation, was found. However, chromogranin A and synaptophysin were negative. The labelling index (LI) using the cell proliferation marker MIB-1 antibody was >50%. Estrogen and progesterone receptors were negative, immunohistochemically. Placenta The placenta weighed 400 g and measured 17204.5 cm with paracentral insertion of the umbilical cord. Macroscopically, the placenta contained multiple 0.3 cm grey-yellow coloured foci located mainly in the intervillous space. Most tumour foci showed

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ma, adenocarcinoma and large cell carcinoma. Nonsmall-cell lung cancer constitutes 7080% of all lung cancers [17]. Small-cell lung cancer is the most sensitive to chemotherapy and radiotherapy. Although initially highly responsive to standard treatments, recurrence is frequent and the 5 year survival is about 510% [18]. In non-small-cell cancer, surgical resection is the therapy of choice for stages I and II disease. In more locally advanced disease, a combination of chemotherapy, surgery, and radiotherapy is often considered. Stage IV disease is only partially responsive to current therapeutic modalities. More than 70% of non small-cell lung cancer patients are diagnosed with advanced disease resulting in a 5-year survival of less than 5% [19]. Chemotherapy in pregnancy for lung cancer has been reported in only one case [14]. To identify previous reports on lung cancer associated with pregnancy, we performed a computerised literature search using Medline (National Library of Medicine; Bethesda, Md., USA). Pregnancy, lung cancer and lung neoplasm were used as search terms, either alone or in combination. Only publications with proper data on diagnosis, course of the pregnancy, fetal outcome and course of the disease, as well as pathologic examination of the placenta, were taken under consideration for this publication. Thus, only 14 cases of lung cancer associated with pregnancy have been reported in the literature since 1953 (Table 1). Patient characteristics show a mean age of 35.1 years (range: 3045 years), a positive history of smoking in 60%. Small-cell lung cancer was diagnosed in five out of 14 cases (36%) and non-small-cell lung cancer in nine out of 14 cases (64%). At presentation, visceral metastases were present in 46.1%. Definitive treatment was postponed to the postpartum period in all but two cases in which surgical resection was performed at the 28th week of gestation and chemotherapy was administered at 26th week of gestation [14, 23]. The mean survival where reported is 7.7 months (range: 142 months), excluding one long-term survivor [28]. Placenta involvement was present in seven out of 14 cases (50.0%), as defined by the presence of tumour cell detection within the intervillous space. In addition, discrete infiltration of chorionic villi is described in the case presented. Metastatic involvement to the scalp of the fetus, diagnosed at 2 months after delivery was reported in only a single case [101]. The spread of maternal neoplasms to the products of conception is a very rare event but a review of the literature based on the latest survey presented in 1989 revealed ten cases to which the recent case could be added [27] (Table 2). Metastatic transmission to the products of conception is most frequently seen in malignant melanoma (32%), leukemia and lymphoma (15%), lung cancer (11%), breast cancer (13%), sarcoma (8%), gynecologic cancer (3%), and gastric cancer (3%) and other primary tumours (15%), as reported in case reports. Transplacental graft of maternal neoplastic tumour cells to the fetus is exceptionally rare. There are three well-documented

4 months 4 months 8 months Unknown 2 months 3 months Unknown 42 months 2 months 4 months 7 months No evidence 1 month No unknown No No No No No No No No No No Yes Invasion of villi No No No No No No No No No No No No No

n. a. n. a. No 32 weeks NSCLC adenocarcinoma Negative 45 years 2001 [101] None

Placenta involvement

Tumor cells in intervillous space

Yes Yes Yes No Yes No No No No No Yes Yes Yes

Gross deposits

Yes Yes Yes No Yes No No No No No Yes No Yes

Table 1 Pregnancy associated with lung cancer. n.a. not assessed; CHT chemotherapy [4 cycles cisplatin+vinorelbine)

22 weeks Unknown 34 weeks 28 weeks 35 weeks 23 weeks 36 weeks 28 weeks 22 weeks 37 weeks 35 weeks 32 weeks 31 weeks

SCLC oat cell carcinoma SCLC oat-cell carcinoma SCLC anaplastic oat-cell carcinoma NSCLC adenocarcinoma NSCLC large cell carcinoma NSCLC adenocarcinoma SCLC oat-cell carcinoma NCSLC squamous cell carcinoma NSCLC large cell carcinoma NSCLC large cell carcinoma NSCLC large cell carcinoma SCLC oat cell carcinoma NSCLC large cell carcinoma

History of smoking

Unknown Unknown 20 years Negative Positive Unknown 30 years Positive Positive 20 years Positive Positive None

39 years

39 years 39 years 37 years 35 years 45 years 34 years 33 years 41 years 44 years 30 years 29 years

1953 1962 1969 1976 1981 1984 1985 1985 1986 1988 1989 1989 1994

[57] [64] [73] [88] [81] [89] [30]

[5] [90] [7] [91]

Suda et al. Brhwiler et al Dildy et al. Delerive et al. Jackisch et al. (current case) Harpold et al.

Barr Hesketh Jones Pawellec D Read et al. Reiter et al. Stark et al.

Jnne et al.

Author

[14]

Ref

2001

Year

31 years

Age

15 years

NSCLC adenocarcinoma

Lung cancer Histology

26 weeks

Week of gestation

CHT in pregnancy No

After pregnancy After pregnancy After pregnancy In pregnancy After pregnancy After pregnancy After pregnancy After pregnancy After pregnancy After pregnancy After pregnancy After pregnancy After pregnancy

Treatment

No

No

Yes 8 weeks 1 month post partum No 12 months

Spread to fetus

Survival

73 Table 2 Metastatic involvement of the products of conception by maternal malignancy. n.a. not assessed Author Friedreich Berghinz Walz Markus Senge Priesel Weber Gray Gottron Holland Bender Dargeon Cross Barr Byrd Rynolds Biermann Cramblett Horner Freedman Hesketh Aronsson Cavell Diamandopoulos Rigby Rosemond Pisarski Bernard Brodsky Rewell Benirschke Jones Metler Hill Stephenson Rothmann Gillis Angate Holcomb Smythe Sokol Frick Russel Read Looi Cailliez Greenberg Orr Sedgely Suda Moller Dildey Anderson Delerive Tsujimura Pollack Current case Harpold Ref. [8] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [20] [41] [42] [43] [44] [45] [46] [21] [47] [48] [49] [50] [51] [52] [53] [54] [55] [56] [22] [57] [58] [59] [60] [C61] [62] [63] [64] [65] [66] [67] [24] [68] [69] [70] [71] [72] [6] [C73] [27] [74] [28] [75] [76] [77] [101] Year 1866 1900 1906 1910 1912 1926 1930 1939 1940 1949 1950 1950 1950 1951 1953 1954 1955 1956 1958 1960 1960 1962 1963 1963 1963 1963 1964 1964 1964 1964 1965 1966 1967 1969 1970 1970 1971 1973 1975 1975 1975 1976 1976 1976 1976 1977 1977 1979 1979 1980 1982 1982 1985 1986 1986 1989 1989 1989 1993 1993 1993 1994 2001 Maternal malignancy Hepatic carcinoma Lymphosarcoma Myxosarcoma Ovarian melanosarcoma Gastric cancer Hodgkins disease Malignant melanoma Adrenal cancer Malignant melanoma Malignant melanoma Ethmoid cancer Gastric cancer Malignant melanoma Breast cancer Lung cancer Malignant melanoma Malignant melanoma Lymphocytic leukemia Lymphocytic leukemia Ovarian cancer Malignant melanoma Lung cancer Malignant melanoma Malignant melanoma Myelocytic leukemia Monocytic leukemia Myelogenous leukemia Breast cancer Breast cancer Lymphoblastic leukaemia Malignant melanoma Breast cancer Breast cancer Lung cancer Breast cancer Sarcoma (lung) Malignant melanoma Rectal cancer Malignant melanoma Breast cancer Malignant melanoma Undifferentiated cancer Pancreatic cancer Malignant melanoma Malignant melanoma Angioblastic sarcoma Malignant melanoma Lung cancer Malignant melanoma Cervical cancer Ewings cancer Head & neck cancer Angiosarcoma breast Lung cancer Malignant melanoma Lung cancer Malignant melanoma Lung cancer Non Hodgkins lymphoma Medulloblastoma Non Hodgkins lymphoma Lung cancer Lung cancer Involvement of the placenta n.a. n.a. + + + + + + n.a. + + + n.a. + + + + + n.a. + + + n.a. n.a. + + + + + n.a. + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + n.a. Involvement of the fetus + + n.a. n.a. + + + + + + + + n.a. n.a. n.a. n.a. n.a. n.a. n.a. +

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cases of villous invasion and fetal metastasis in malignant melanoma, causing the death of the infant within 1048 months [34, 37, 54], and four cases with invasion of the villus are documented without spread to the fetus [59, 65, 67, 68]. In malignant melanomas, the capability of congenital development and metastasis within the fetus has also been described precluding maternal origin [78, 79]. In sarcomas [30, 31, 80], gastric cancer [32], adrenal carcinoma [35], breast cancer [52], cervical cancer [69], and head and neck cancer [71], villous invasion without fetal involvement has also been documented. Metastatic transmission to the fetus arising from choriocarcinoma has been reported recently [81]. The ability to metastasise to the placenta or umbilical cord is documented in congenital neuroblastoma without transmission to the mother [82, 83, 84]. There was one case of placenta involvement with nevus cells apparently transferred from a fetus with a giant pigmented nevus reported [85]. The synchronous occurrence of immature teratomas in both the mother and fetus during pregnancy, each of independent origin, was also reported recently [86]. Most neoplasms involving the products of conception are known for their tendency to metastasise haematogenously at an early stage. Lymphatic dissemination is usually less important but might be relevant in cervical cancer associated with pregnancy [69]. Histological examination of placenta generally shows malignant cells within the intervillous space, which is felt to be a component of the maternal vascular system. A true invasion of the placenta tissue (villous invasion) is, however, a very rare event [87]. Many investigators consider an invasion of the villus to be representative evidence of fetal involvement [2, 60, 87, 88]. Distribution of primary malignancies among the 12 reported cases of fetal involvement indicate malignant melanoma (58.4%), leukemia and lymphoma (33.3%), and hepatic carcinoma (8.3%) [27]. However, these findings illustrate the potential risk of maternal neoplastic cells to pass over into the fetus and form metastases from the primary maternal malignancy. The various factors causing the metastatic involvement of placenta or fetus have been discussed elsewhere [2, 60, 87, 88]. Maternal circulation in the placenta drains into the intervillous space into which the villi project lined by fetal trophoblast, composed of an outer layer of syncytiotrophoblast and the inner cytotrophoblast layer of Langhans [87, 89] (Fig. 6). Rothman et al. postulated that maternal cancer spreads through the placenta and to the fetal membranes and the fetus via the arterial circulation. Indeed, all cases of placental metastases histologically examined have, therefore, demonstrated tumour sequestration in the intervillous spaces [60]. Maternal and fetal circulation are separated by trophoblast, the villus connective tissue and the capillary wall [89]. The function of the placenta includes metabolic and exchange processes by diffusion and active transport mechanisms. Some authors suggest that the trophoblast may serve as a physical barrier rejecting foreign maternal antigens expressed by the tumour [87, 90, 91]. In a case of

Fig. 6 Uterine insertion of the human placenta. AV anchoring villi; CCC cytotrophoblast cell column; CL villous cytotrophoblast, Langhans layer; CTS cytotrophoblast shell; DC cells of the maternal decidua basalis; IAC intra-arterial trophoblast cell in the walls and lumen of the maternal spiral artery; ICT interstitial cytotrophoblast at the insertion of the basal plate; IVS intervillous space; Sb syncytiotrophoblast bud; SEm syncytiotrophoblast embolus carried by the venous blood returning from the placenta to the maternal circulation; SpA maternal uteroplacental spiral artery; TGC trophoblast multinucleate giant cell; UVL uterine vein lumen; VST syncytiotrophoblast of the chorionic villous tissue (Reprinted from [89] with permission)

acute lymphatic leukaemia, morphological features of the placenta showed evidence of abnormalities that have not been described previously, such as phagocytosis of nucleated cells in the villous syncytiotrophoblast and destruction of tumour cells within the villous trophoblast [92]. Electronmicroscopy revealed that the phagocytised cells were almost certainly of maternal origin and very possibly tumour cells. In addition, the use of in situ hybridisation in the case of fetal involvement caused by maternal lung cancer supports these findings [101]. It was shown that those phagocytised neoplastic cells underwent enzymatic digestion and thus lost their metastatic capacity [92]. Phagocytosis of maternal cells by the syncytiotrophoblast in order to provide metabolites for embryonic and trophoblastic development is common during the implantation phase [93]. As pregnancy progresses, active phagocytosis of maternal cells by the villous syncytiotrophoblast has not been documented so far. The detection of nucleated cells within the syncytiotrophoblast in acute lymphatic leukemia at the 34th week of gestation demonstrates the ability of the trophoblast to phagocytise cells even in late pregnancy [92].These findings may underline the barrier function of the tropho-

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blast as an important factor preventing the invasion of neoplastic cells. It is of particular interest that ten out of 14 reported pregnancy-associated lung cancers were caused by small cell (neuroendocrine) or large cell anaplastic carcinomas. As in the current case, immunohistochemical studies indicate that a high proportion of these large cell anaplastic carcinomas present a distinct neuroendocrine differentiation [94, 95, 96]. There is some evidence that these tumours respond to therapeutic modalities such as chemotherapy, as do small cell anaplastic (neuroendocrine) carcinomas, resulting in the same median survival [97, 98]. Thus, it may be speculated that lung cancer of neuroendocrine differentiation may be more likely associated with pregnancy. In all cases of pregnancy-associated cancers, the placenta should be submitted for histological examination. The presence of placental metastasis of any kind necessitates close observation of the infant for evidence of metastatic disease. If current smoking patterns continue, the association of pregnancy and lung cancer can be expected to rise. There is no evidence that pregnancy alters the neoplastic process, although pregnant patients present more often in advanced stage diseases [1, 3, 7, 99, 100, 101]. For all physicians caring for pregnant women, it is an enormous task to uncover the symptomatology suspicious for cancer, almost hidden by symptoms and physiologic changes of normal pregnancies to avoid an initial delay in the onset of diagnosis, staging and therapy resulting in avoidable alterations of both the maternal and fetal prognosis. As reported recently, the American Cancer Society (ACS) does not recommend screening for early lung cancer detection in asymptomatic individuals at risk for lung cancer. The current status of testing for lung cancer is more complicated today due to the emergence of considerably more powerful imaging with the use of low-dose helical computed tomography [102]. If this technology is effective at identifying early, respectable lung cancer, the public health impact could be substantial.

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