Abstract Approximately 1 per 1,000–1,500 pregnanciesis complicated by maternal malignancies. Metastatic in-volvement of the products of conception is a rare event.There have been 62 cases of placental and/or fetal meta-static involvement originating from maternal cancer re-ported since 1866. Only 14 cases of lung cancer associat-ed with pregnancy have been documented. We report onan additional case involving the products of conception,and the management of lung cancer in pregnancy is dis-cussed based on an extensive review of the literature.The case of a 29-year-old woman presenting during the31st week of gestation with metastatic non small-celllung cancer to the placenta, liver and bone is described.The mother was delivered by caesarean section of a heal-thy baby girl during her 32nd week of gestation. Themother’s postpartum course was complicated by dissem-inated pulmonary and bony metastases and malignant

pericardial and pleural effusions causing the patient’sdeath within 1 month after lung cancer was diagnosed.Malignancies spreading to the products of conception aremelanoma (32%), leukemia and lymphomas (15%),breast cancer (13%), lung cancer (11%), sarcoma (8%),gastric cancer (3%) and gynecologic cancers (3%), re-flecting malignancies with a high incidence in women ofreproductive age. All lung cancers were diagnosed withwidely disseminated, inoperable neoplastic disease, in-cluding distant metastases in 46%. The mean age was35.1 years (range, 30–45 years) and 60% of patients hada history of tobacco use. The mean survival was 7.5months (range: 1–42 months). Placenta involvement waspresent in 7 out of 15 cases. Fetal involvement was re-ported in only one case. Because there is no evidence ofa direct adverse effect of pregnancy on the course oflung cancer, we recommend delivery at a time whenenough fetal maturity can be assumed and the subse-quent treatment of the mother.

Keywords Lung cancer · Cancer and pregnancy · Products of conception · Placenta

Introduction

Cancer complicates approximately 1 per 1,000–1,500pregnancies and accounts for one-third of maternaldeaths during pregnancy [1, 2]. One in every 118 inva-sive carcinomas in women may be diagnosed duringpregnancy [3]. The cancers most frequently detected inpregnancy are obviously those with a peak incidenceduring the reproductive years, particularly breast, cervi-cal, melanoma, ovarian and thyroid cancers, as well asleukemia and lymphoma [2, 4]. However, as more wom-en delay childbearing to their fourth and fifth decades oflife, other cancers whose incidence increases with age,may occur that are related to pregnancy, e.g. colon andlung [5, 6, 7, 25, 26]. A major concern is the possibilitythat malignancy may affect the fetus. Data on metastaticinvolvement of the products of conception are sparse

C. Jackisch (✉)Department of Obstetrics and Gynecology, University Hospital Marburg, Pilgrimstein 3, 35037 Marburg,Germanye-mail: jackisch@med.uni-marburg.deTel.: +49-6421-28-64390Fax: +49-6421-28-68969

F. LouwenDepartment of Obstetrics and Gynecology, University of Frankfurt/Main, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany

A. SchwenkhagenAltonaer Strasse 59, 20357 Hamburg, Germany

B. KarbowskiDepartment of Obstetrics and Gynecology, St. Johannes Hospital,Johannesstrasse 9–17, 44137 Dortmund, Germany

K.W. SchmidInstitute of Pathology, University of Essen, Hufelandstrasse 54,45147 Essen, Germany

H.P.G. SchneiderZMBE, von Esmarch-Strasse 56, 48129 Münster, Germany

W. HolzgreveDepartment of Obstetrics and Gynecology, University of Basel,Schanzenstrasse 46, 4031 Basel, Switzerland

Arch Gynecol Obstet (2003) 268:69–77DOI 10.1007/s00404-002-0356-x

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

Christian Jackisch · Frank LouwenAnneliese Schwenkhagen · Brigitta KarbowskiKurt Werner Schmid · Hermann P. G. SchneiderWolfgang Holzgreve

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

since histologic examination of the placenta is not rou-tinely performed. Valid data on the possibility of fetal in-volvement are missing due to the fact that most of thechildren were not followed up. We present a case of ma-ternal non small-cell lung cancer (anaplastic large cellcarcinoma) metastatic to liver, bone, and placenta withno evidence of fetal involvement and a review of the lit-erature of the 62 cases of metastasis of maternal malig-nancy to the products of conception reported since thefirst publication [8] in 1866.

Case report

A 29-year-old white, gravida I, non-smoker was admitted at the31st week of gestation to the obstetric service for further evalua-tion. The past medical history was unremarkable and she had beenwell until 2 weeks prior to admission when fever (max. 38.5°C)and right hip and wrist pain were noted.

Physical examination on admission revealed a pregnant wom-an who appeared chronically ill. Neither abdominal or pelvicmasses nor lymphadenopathy were diagnosed. Colposcopy of thecervix including cytologic smear was unremarkable. Laboratoryevaluations for sexually transmitted diseases, hepatitis, tuberculo-sis, and HIV were negative. Microbiological and cytologic find-ings from needle aspirates of the right hip and wrist joint werenegative for specific disease. A shielded chest X-ray showed amass located next to the aortic arch (Fig. 1). Magnetic resonanceimage of the thorax revealed a single solid mass (6×5 cm) in theupper posterior mediastinum without enlarged lymph nodes(Fig. 2). Computer tomographic-guided fine needle aspiration ofthis mass revealed an epithelioid cancer. Bone marrow aspirationshowed no evidence of malignancy.

On ultrasound scan, the fetus was developing well withoutpathologic findings. After one course of respiratory distress syn-drome prophylaxis, amniocentesis was performed resulting in alecithin/sphingomyelin ratio of 2:1. Following this result, on thetenth day of hospitalisation the patient delivered by caesarean sec-tion a 2400 g female infant with Apgar scores of 8, 9 and 9 at 1, 5and 10 min, respectively. The infant’s clinical course was uncom-plicated and she was discharged at 22 days of age. Evaluation forevidence of malignancy, including chest X-ray and tumour mark-

ers, on the child was unrevealing. The child is alive at the age of15 months and well at the time of this publication and receivesregular paediatric follow up, as well as determination of carcino-embryonic antigen and chest roentgenograms at 3 month intervals.

At the time of delivery, an intraoperative exploration of the pa-tient’s abdomen was grossly normal, including liver, spleen, bow-el, ovary and lymph nodes. Peritoneal washings were negative formalignant cells. After delivery, scans of the brain, neck, thyroidgland, liver and spleen; mammogram; upper and lower intestinos-copy were performed and were within normal limits. Bronchosco-py, including washings and biopsy, were also negative for malig-nancy. The bone scan, however, revealed multiple areas of in-creased uptake in the skull, pelvis, right hip and proximal femursuspicious for metastases. A follow-up chest X-ray showed rapidlocal progression of the tumour. On the sixth post-partum day, athoracotomy showed an unresectable tumour, which was fixed tothe aortic arch. Furthermore, frozen section showed evidence ofdisseminating metastatic spread to both lungs and malignant peri-cardial effusion (200 ml).

The patient’s postoperative course was complicated by patholog-ic fracture of the right hip requiring surgical stabilisation on theninth day after thoracotomy and the development of a new left pleu-ra effusion, which required thoracentesis of 1200 ml. Subsequently,the patient developed progressive pericardial effusion and died ofleft heart failure 34 days after lung cancer had been diagnosed.

Pathologic findings

Postmortem examination

A 6×6×6 cm relatively circumscribed greyish bronchial tumourwas found in the upper lobe of the left lung (Fig. 3), infiltratingthe aortic arch macroscopically. The tumour extended to the peri-cardium, left hilar and peribronchial lymph nodes and both lungs(disseminated metastatic foci up to 0.5 cm in diameter), includingbilateral lymphangiosis carcinomatosa. Osteolytic bone metastasesof the vertebral column and right femur were present, as well asdiffuse metastatic infiltration of the liver. No tumour was foundwithin the reproductive organs. Due to these findings, the tumourwas staged as pT4, pN1, pM1 lung cancer. The cause of death wasleft heart failure caused by haemorrhagic pericardial tamponade.

70

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

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

Histology

Both the primary tumour and its metastases showed a large-cellanaplastic carcinoma of the lung with focal necrosis. Numerousmitoses were noted (Fig. 4). Immunohistochemically, the primarytumour was positive with antibodies against cytokeratins (Kl-1),carcinoembryonic antigen (CEA), epithelial membrane antigen(EMA), as well as the tumour-associated glycoprotein 72 (TAG-72) [9]. No staining with antibodies against vimentin, desmin,smooth muscle actin, α-HCG, β-HCG, α-1-antitrypsin, α-fetopro-tein, placental-like alkaline phosphatase (PLAP), factor-VIII-relat-ed antigen, a melanoma-specific antibody (HMB 45) or S-100 pro-tein could be detected. Discrete focal immunoreactivity for chro-mogranin B, secretogranin II and neuron-specific enolase (NSE),indicating a neuroendocrine differentiation, was found. However,chromogranin A and synaptophysin were negative. The labellingindex (LI) using the cell proliferation marker MIB-1 antibody was>50%. Estrogen and progesterone receptors were negative, im-munohistochemically.

Placenta

The placenta weighed 400 g and measured 17×20×4.5 cm withparacentral insertion of the umbilical cord. Macroscopically, theplacenta contained multiple 0.3 cm grey-yellow coloured foci lo-cated mainly in the intervillous space. Most tumour foci showed

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

Discussion

Cancer diagnosed in association with pregnancy poses adifficult challenge to the patient and her family, the fetusand the medical team caring for both in a interdisciplin-ary approach. Lung cancer is not a common pregnancy-associated neoplasm ranking far beyond cervical cancer,breast cancer, haematopoietic neoplasms and malignantmelanoma [3, 10]. The data on the incidence and mortal-ity statistics demonstrate that lung cancer, once a raredisease, is the leading cause of cancer death amongwomen in industrialised countries with an estimate of79,200 new cases in the United States for 2002 [11].Nevertheless, the rate of smoking among women is stillincreasing.

Among women of reproductive age, 29% smoke. Ofthese women who become pregnant, between 19% and30% continue to smoke [12]. Lung cancer ranks secondas a cause of cancer death in women of reproductive agein 1999 [11]. Epidemiological and toxicological studiessupport the conclusion that smoking is the major causeof lung cancer [11, 12]. However, in males, 84% of lungcancer can be attributed to smoking, while in women thisfigure is less than half [13]. The incidence of lung canceramong nonsmoking women is approximately 6–8 out of100,000 [14]. Besides the increasing incidence in lungcancer and cervical cancer, several complications inpregnancy, such as bleeding, premature rupture of mem-branes, preterm delivery, placenta praevia, abruptio pla-centa and low birth weight can be related to tobacco use[12, 15].The biological behaviour of lung cancer, howev-er, does not seem to be altered by pregnancy [16]. Carci-nomas of the lung are a heterogeneous group of malig-nancies. Lung carcinomas are divided into small-celllung cancer (SCLC) and non-small-cell lung cancer(NSCLC), such as epidermoid or squamous cell carcino-

71

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

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

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

ma, adenocarcinoma and large cell carcinoma. Non-small-cell lung cancer constitutes 70–80% of all lungcancers [17]. Small-cell lung cancer is the most sensitiveto chemotherapy and radiotherapy. Although initiallyhighly responsive to standard treatments, recurrence isfrequent and the 5 year survival is about 5–10% [18]. Innon-small-cell cancer, surgical resection is the therapy ofchoice for stages I and II disease. In more locally ad-vanced disease, a combination of chemotherapy, surgery,and radiotherapy is often considered. Stage IV disease isonly partially responsive to current therapeutic modali-ties. More than 70% of non small-cell lung cancer pa-tients are diagnosed with advanced disease resulting in a5-year survival of less than 5% [19]. Chemotherapy inpregnancy for lung cancer has been reported in only onecase [14].

To identify previous reports on lung cancer associatedwith pregnancy, we performed a computerised literaturesearch using Medline (National Library of Medicine;Bethesda, Md., USA). “Pregnancy”, “lung cancer” and“lung neoplasm” were used as search terms, either aloneor in combination. Only publications with proper data ondiagnosis, course of the pregnancy, fetal outcome andcourse of the disease, as well as pathologic examinationof the placenta, were taken under consideration for thispublication.

Thus, only 14 cases of lung cancer associated withpregnancy have been reported in the literature since 1953(Table 1). Patient characteristics show a mean age of35.1 years (range: 30–45 years), a positive history ofsmoking in 60%. Small-cell lung cancer was diagnosedin five out of 14 cases (36%) and non-small-cell lungcancer in nine out of 14 cases (64%). At presentation,visceral metastases were present in 46.1%. Definitivetreatment was postponed to the postpartum period in allbut two cases in which surgical resection was performedat the 28th week of gestation and chemotherapy was ad-ministered at 26th week of gestation [14, 23]. The meansurvival where reported is 7.7 months (range: 1–42months), excluding one long-term survivor [28]. Placen-ta involvement was present in seven out of 14 cases(50.0%), as defined by the presence of tumour cell detec-tion within the intervillous space. In addition, discreteinfiltration of chorionic villi is described in the case pre-sented. Metastatic involvement to the scalp of the fetus,diagnosed at 2 months after delivery was reported in on-ly a single case [101].

The spread of maternal neoplasms to the products ofconception is a very rare event but a review of the litera-ture based on the latest survey presented in 1989 re-vealed ten cases to which the recent case could be added[27] (Table 2). Metastatic transmission to the products ofconception is most frequently seen in malignant melano-ma (32%), leukemia and lymphoma (15%), lung cancer(11%), breast cancer (13%), sarcoma (8%), gynecologiccancer (3%), and gastric cancer (3%) and other primarytumours (15%), as reported in case reports. Transplacen-tal graft of maternal neoplastic tumour cells to the fetusis exceptionally rare. There are three well-documented

72

Tab

le1

Pre

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7]19

5339

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Yes

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unkn

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No

4 m

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Jone

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3]19

6939

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yea

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28 w

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n

Rea

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[81]

1981

37 y

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Posi

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NSC

LC

larg

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35 w

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No

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2 m

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[89]

1984

35 y

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Star

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1985

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30 y

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a36

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1985

34 y

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Posi

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NC

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squ

amou

s ce

ll ca

rcin

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28 w

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Aft

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regn

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No

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42 m

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Suda

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]19

8633

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1989

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35 w

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ancy

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1989

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73

Table 2 Metastatic involve-ment of the products of conception by maternal malignancy. n.a. not assessed

Author Ref. Year Maternal malignancy Involvement Involvement of the placenta of the fetus

Friedreich [8] 1866 Hepatic carcinoma n.a. +Berghinz [29] 1900 Lymphosarcoma n.a. +Walz [30] 1906 Myxosarcoma + n.a.Markus [31] 1910 Ovarian melanosarcoma + -Senge [32] 1912 Gastric cancer + n.a.Priesel [33] 1926 Hodgkin’s disease + +Weber [34] 1930 Malignant melanoma + +Gray [35] 1939 Adrenal cancer + -Gottron [36] 1940 Malignant melanoma n.a. +Holland [37] 1949 Malignant melanoma + +Bender [38] 1950 Ethmoid cancer + -

1950 Gastric cancer + -Dargeon [39] 1950 Malignant melanoma n.a. +Cross [40] 1951 Breast cancer + -Barr [20] 1953 Lung cancer + -Byrd [41] 1954 Malignant melanoma + -Rynolds [42] 1955 Malignant melanoma + -Biermann [43] 1956 Lymphocytic leukemia + -Cramblett [44] 1958 Lymphocytic leukemia n.a. +Horner [45] 1960 Ovarian cancer + -Freedman [46] 1960 Malignant melanoma + -Hesketh [21] 1962 Lung cancer + -Aronsson [47] 1963 Malignant melanoma n.a. +Cavell [48] 1963 Malignant melanoma n.a. +Diamandopoulos [49] 1963 Myelocytic leukemia + -

1963 Monocytic leukemia + -Rigby [50] 1964 Myelogenous leukemia + n.a.Rosemond [51] 1964 Breast cancer + -Pisarski [52] 1964 Breast cancer + -Bernard [53] 1964 Lymphoblastic leukaemia n.a. n.a.Brodsky [54] 1965 Malignant melanoma + n.a.Rewell [55] 1966 Breast cancer + -Benirschke [56] 1967 Breast cancer + -Jones [22] 1969 Lung cancer + -Metler [57] 1970 Breast cancer + -Hill [58] 1970 Sarcoma (lung) + n.a.Stephenson [59] 1971 Malignant melanoma + -Rothmann [60] 1973 Rectal cancer + -Gillis [C61] 1975 Malignant melanoma + -Angate [62] 1975 Breast cancer + -Holcomb [63] 1975 Malignant melanoma + -Smythe [64] 1976 Undifferentiated cancer + n.a.

1976 Pancreatic cancer + -1976 Malignant melanoma + -

Sokol [65] 1976 Malignant melanoma + -Frick [66] 1977 Angioblastic sarcoma + -Russel [67] 1977 Malignant melanoma + -Read [24] 1979 Lung cancer + -Looi [68] 1979 Malignant melanoma + -Cailliez [69] 1980 Cervical cancer + -Greenberg [70] 1982 Ewing’s cancer + -Orr [71] 1982 Head & neck cancer + -Sedgely [72] 1985 Angiosarcoma breast + n.a.Suda [6] 1986 Lung cancer + -Moller [C73] 1986 Malignant melanoma + -Dildey [27] 1989 Lung cancer + -Anderson [74] 1989 Malignant melanoma + -Delerive [28] 1989 Lung cancer + -Tsujimura [75] 1993 Non Hodgkin’s lymphoma + n.a.Pollack [76] 1993 Medulloblastoma + -

[77] 1993 Non Hodgkin’s lymphoma + -Current case 1994 Lung cancer + -Harpold [101] 2001 Lung cancer n.a. +

cases of villous invasion and fetal metastasis in malig-nant melanoma, causing the death of the infant within10–48 months [34, 37, 54], and four cases with invasionof the villus are documented without spread to the fetus[59, 65, 67, 68]. In malignant melanomas, the capabilityof congenital development and metastasis within the fe-tus has also been described precluding maternal origin[78, 79]. In sarcomas [30, 31, 80], gastric cancer [32],adrenal carcinoma [35], breast cancer [52], cervical can-cer [69], and head and neck cancer [71], villous invasionwithout fetal involvement has also been documented.

Metastatic transmission to the fetus arising from cho-riocarcinoma has been reported recently [81]. The abilityto metastasise to the placenta or umbilical cord is docu-mented in congenital neuroblastoma without transmis-sion to the mother [82, 83, 84]. There was one case ofplacenta involvement with nevus cells apparently trans-ferred from a fetus with a giant pigmented nevus report-ed [85]. The synchronous occurrence of immature terato-mas in both the mother and fetus during pregnancy, eachof independent origin, was also reported recently [86].Most neoplasms involving the products of conceptionare known for their tendency to metastasise haemat-ogenously at an early stage. Lymphatic dissemination isusually less important but might be relevant in cervicalcancer associated with pregnancy [69]. Histological ex-amination of placenta generally shows malignant cellswithin the intervillous space, which is felt to be a com-ponent of the maternal vascular system. A true invasionof the placenta tissue (villous invasion) is, however, avery rare event [87]. Many investigators consider an in-vasion of the villus to be representative evidence of fetalinvolvement [2, 60, 87, 88]. Distribution of primary ma-lignancies among the 12 reported cases of fetal involve-ment indicate malignant melanoma (58.4%), leukemiaand lymphoma (33.3%), and hepatic carcinoma (8.3%)[27]. However, these findings illustrate the potential riskof maternal neoplastic cells to pass over into the fetusand form metastases from the primary maternal malig-nancy.

The various factors causing the metastatic involve-ment of placenta or fetus have been discussed elsewhere[2, 60, 87, 88]. Maternal circulation in the placentadrains into the intervillous space into which the villi pro-ject lined by fetal trophoblast, composed of an outer lay-er of syncytiotrophoblast and the inner cytotrophoblastlayer of Langhans [87, 89] (Fig. 6). Rothman et al. pos-tulated that maternal cancer spreads through the placentaand to the fetal membranes and the fetus via the arterialcirculation. Indeed, all cases of placental metastases his-tologically examined have, therefore, demonstrated tu-mour sequestration in the intervillous spaces [60]. Ma-ternal and fetal circulation are separated by trophoblast,the villus connective tissue and the capillary wall [89].The function of the placenta includes metabolic and ex-change processes by diffusion and active transport mech-anisms. Some authors suggest that the trophoblast mayserve as a physical barrier rejecting foreign maternal an-tigens expressed by the tumour [87, 90, 91]. In a case of

acute lymphatic leukaemia, morphological features ofthe placenta showed evidence of abnormalities that havenot been described previously, such as phagocytosis ofnucleated cells in the villous syncytiotrophoblast and de-struction of tumour cells within the villous trophoblast[92]. Electronmicroscopy revealed that the phagocytisedcells were almost certainly of maternal origin and verypossibly tumour cells. In addition, the use of in situ hy-bridisation in the case of fetal involvement caused bymaternal lung cancer supports these findings [101]. Itwas shown that those phagocytised neoplastic cells un-derwent enzymatic digestion and thus lost their metastat-ic capacity [92]. Phagocytosis of maternal cells by thesyncytiotrophoblast in order to provide metabolites forembryonic and trophoblastic development is commonduring the implantation phase [93]. As pregnancy pro-gresses, active phagocytosis of maternal cells by the vil-lous syncytiotrophoblast has not been documented so far.The detection of nucleated cells within the syncytiotro-phoblast in acute lymphatic leukemia at the 34th week ofgestation demonstrates the ability of the trophoblast tophagocytise cells even in late pregnancy [92].These find-ings may underline the barrier function of the tropho-

74

Fig. 6 Uterine insertion of the human placenta. AV anchoring vil-li; CCC cytotrophoblast cell column; CL villous cytotrophoblast,Langhans’ layer; CTS cytotrophoblast shell; DC cells of the mater-nal decidua basalis; IAC intra-arterial trophoblast cell in the wallsand lumen of the maternal spiral artery; ICT interstitial cytotro-phoblast at the insertion of the basal plate; IVS intervillous space;Sb syncytiotrophoblast bud; SEm syncytiotrophoblast emboluscarried by the venous blood returning from the placenta to the ma-ternal circulation; SpA maternal uteroplacental spiral artery; TGCtrophoblast multinucleate giant cell; UVL uterine vein lumen; VSTsyncytiotrophoblast of the chorionic villous tissue (Reprinted from[89] with permission)

blast as an important factor preventing the invasion ofneoplastic cells.

It is of particular interest that ten out of 14 reportedpregnancy-associated lung cancers were caused by smallcell (neuroendocrine) or large cell anaplastic carcinomas.As in the current case, immunohistochemical studies in-dicate that a high proportion of these large cell anaplasticcarcinomas present a distinct neuroendocrine differentia-tion [94, 95, 96]. There is some evidence that these tu-mours respond to therapeutic modalities such as chemo-therapy, as do small cell anaplastic (neuroendocrine) car-cinomas, resulting in the same median survival [97, 98].Thus, it may be speculated that lung cancer of neuroen-docrine differentiation may be more likely associatedwith pregnancy.

In all cases of pregnancy-associated cancers, the pla-centa should be submitted for histological examination.The presence of placental metastasis of any kind necessi-tates close observation of the infant for evidence ofmetastatic disease. If current smoking patterns continue,the association of pregnancy and lung cancer can be ex-pected to rise. There is no evidence that pregnancy altersthe neoplastic process, although pregnant patients pres-ent 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 symptomatologysuspicious for cancer, almost hidden by symptoms andphysiologic changes of normal pregnancies to avoid aninitial delay in the onset of diagnosis, staging and thera-py resulting in avoidable alterations of both the maternaland fetal prognosis. As reported recently, the AmericanCancer Society (ACS) does not recommend screeningfor early lung cancer detection in asymptomatic individ-uals at risk for lung cancer. The current status of testingfor lung cancer is more complicated today due to theemergence of considerably more powerful imaging withthe use of low-dose helical computed tomography [102].If this technology is effective at identifying early, re-spectable lung cancer, the public health impact could besubstantial.

References

1. Jacobs JH, Stringer CA (1990) Diagnosis and management ofcancer during pregnancy. Sem Perinatol 14:79–87

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