Focal positivity of immunohistochemical markers for pulmonary squamous cell carcinoma in primary pulmonary choriocarcinoma: A histopathological study

  • Authors:
    • Susumu Matsukuma
    • Kiyohaya Obara
    • Yoshitaka Utsumi
    • Kosuke Miyai
    • Hiroaki Takeo
    • Yoshiro Oshika
    • Koji Sensaki
  • View Affiliations

  • Published online on: September 28, 2018     https://doi.org/10.3892/ol.2018.9525
  • Pages: 7256-7263
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Abstract

Cytokeratin 5/6 (CK5/6), p63, and p40 are commonly used as immunohistochemical markers for squamous cell carcinoma (SqCC) of the lung. To elucidate their positivity in primary pulmonary choriocarcinoma (PPC), the present study examined 4 PPCs, including 1 surgically removed PPC and 3 postmortem PPCs. All PPCs consisted of nested cytotrophoblastic tumor cells and occasional syncytiotrophoblastic tumor cells although 1 surgically removed PPC was markedly affected by pre‑operative therapy‑associated necrosis and 3 postmortem PPCs coexisted with adenocarcinoma. In 1 surgical case, a pre‑operative biopsy specimen of PPC contained a few polygonal tumor cells, which mimicked SqCC and exhibited focal p40+ features. Nuclear p63+ and p40+ features of cytotrophoblast‑like polygonal tumor cells were focally observed in 3 PPCs (75%) and 2 PPCs (50%), respectively. CK5/6+ trophoblastic tumor cells were focally identified in 1 PPC. Additionally, in 2 other PPCs, CK5/6+ tumor cells were scattered in choriocarcinomatous areas, but possible intermingling of CK5/6+ adenocarcinoma cells could not be ruled out. The results emphasized that PPCs could mimic SqCC morphologically and immunohistochemically, although PPC was an extremely rare neoplasm. Surgical pathologists should be aware of this diagnostic pitfall when encountering a few squamous marker‑positive polygonal tumor cells within hemorrhagic necrotic biopsy specimens from lung tumors.

Introduction

Primary lung cancer is the most frequent cause of cancer-related death worldwide (1,2). Accurate histopathological assessment of lung tumors directly contributes to the establishment of patient management strategies. The 2015 World Health Organization (WHO) classification of lung tumors (3) has recommended that non-small cell carcinoma (NSCC) should be classified into more specific subtypes, even in small specimens, such as squamous cell carcinoma (SqCC) or adenocarcinoma, based on immunohistochemical examination. Accepted immunohistochemical markers for SqCC include cytokeratin 5/6 (CK5/6), p63 and p40, and those for adenocarcinoma include thyroid transcription factor-1 (TTF-1) and Napsin A (1,3). Recently, however, we encountered focal p40 positivity in surgically removed primary pulmonary choriocarcinoma (PPC; unpublished data). PPC is a distinct, primary lung cancer, but is not included in the 2015 WHO classification, possibly due to its extreme rarity. Our review of the English literature yielded only 57 previously reported PPCs (439), which exhibited characteristic dimorphic features composed of cytotrophoblastic and syncytiotrophoblastic tumor cells and had considerable amounts of choriocarcinoma components with or without other carcinoma components. In this study, to elucidate the immunoreactivity profiles of PPCs for SqCC markers, we examined this surgical case of PPC and additional 3 autopsy cases of PPC.

Patients and methods

Patients

We consider that PPC should be discriminated from β-chorionic gonadotropin (β-hCG)-producing large or giant cell carcinoma of the lung (20,26). In this study, we defined PPCs as those with characteristic dimorphic morphology composed of mononuclear cytotrophoblastic tumor cells and multinucleated syncytiotrophoblastic tumor cells showing immunoreactivity for β-hCG focally or multifocally. Cases of β-hCG+ primary pulmonary cancer without such dimorphic morphology were not included. To identify additional autopsy cases of PPC, we reviewed hematoxylin and eosin (H&E)-stained slides of 191 primary lung cancers from 179 patients retrieved from autopsy files (1975–2017, June) of the Department of Pathology, Japan Self-Defense Forces Central Hospital (Tokyo, Japan) and identified 3 PPC cases (1.6%), including a previously published case (24). Therefore, we examined a total of 4 cases of PPC. Biopsies had been performed in 1 surgical case and 1 autopsy case. In all 4 cases, PPC components occupied a considerable amount of the primary lung tumor (>10% of the tumor volume) with or without other histological components. We histologically evaluated or assessed PPC and other components of lung cancer referring to the description of previously reported PPCs (439), published textbook of surgical pathology (40), and the 2015 WHO classification (3). The present study was a retrospective study, which was approved by the Medical Research Ethics Committee of Japan Self-Defense Forces Central Hospital (June 5, 2017; approval no. 29–004).

Methods

For all surgically removed, postmortem, and biopsy specimens, 10–20% buffered formalin-fixed and paraffin-embedded samples were available. Samples were recut, stained with H&E, and immunostained for β-hCG (C6405; Nichirei Biosciences, Inc., Tokyo, Japan), CK5/6 (D5/16 B4; Nichirei Biosciences, Inc.), p63 (4A4; Nichirei Biosciences Inc.) and p40 (BC28; Nichirei Biosciences Inc.). If needed, selected sections were stained with periodic acid-Schiff (PAS) and immunostained for TTF-1 (SPT24; Novocastra, Newcastle, UK), Napsin A (IP64; Novocastra), and epithelial membrane antigen (EMA; E29; Nichirei Biosciences, Inc.). Clinical information was obtained from patient medical charts and/or autopsy request forms.

Results

Clinical details
Case 1 (surgical case)

A 53-year-old man presented with cough and chest pain. Imaging examination revealed a 6-cm left lung tumor. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography revealed FDG uptake in the lung tumor, and the maximum standardized uptake value was 12.02. Serum β-hCG level was not examined. Transbronchial biopsy (TBB) specimens from the lung tumor contained a few SqCC-like polygonal cells focally showing p40 positivity (Fig. 1). They showed no distinct keratinization or intercellular bridges and were diagnosed as NSCC according to the algorithm described in the 2015 WHO classification (3). After chemoradiotherapy (carboplatin and paclitaxel plus 60 Gy), the patient underwent left upper lobectomy, which was diagnosed as a necrotic PPC and associated pulmonary metastasis. Serum β-hCG levels 5 days after the surgery were within the normal range (≤ 0.10 mIU/ml), but were increased (31.23 mIU/ml) 9 months after the surgery with metastases in the brain, right lung, and stomach, despite additional chemotherapy (etoposide, methotrexate, actinomycin and cisplatin). Lung and gastric metastases were histologically confirmed by biopsies. The patient died of disease 15 months from the initial presentation.

Case 2 (autopsy case)

A 70-year-old man was hospitalized for hemoptysis and involuntary movement. Imaging examination demonstrated the presence of a 7-cm right lung tumor and multiple metastatic nodules in the brain, liver, right adrenal gland, and both kidneys. Serum β-hCG levels were not examined. Pathological examination of ultrasound-guided percutaneous lung biopsy specimens provided a possible diagnosis of large cell carcinoma. The patient died of disease 2 months after hospitalization.

Case 3 (autopsy case)

A 77-year-old man was admitted to our hospital for evaluation of bloody sputum and loss of appetite (24). Imaging examination revealed a 5-cm left upper lobe nodule, which had been detected 2 months before at another hospital, and multiple metastatic nodules were observed in both lungs as well as the liver, spleen, and pancreatic body. Serum carcinoembryonic antigen levels were slightly increased (6.8 ng/ml). Serum β-hCG levels were not examined. The patient's condition rapidly deteriorated, and the patient died of respiratory failure due to hemorrhagic pulmonary metastases 6 days after admission.

Case 4 (autopsy case)

A 77-year-old man was hospitalized for a stroke-related fall. Imaging examination demonstrated right hemisphere brain infarction and a 4-cm right lung tumor. Serum levels of syalyl LewisX were slightly increased (50 ng/ml). Serum β-hCG levels were not examined. The patient died of respiratory failure due to lymphangiosis carcinomatosa 4 months after hospitalization.

Pathological findings

The main clinicopathological findings are summarized in Table I. PPCs were located on the left upper and right lower lobes in 2 cases each, and their sizes ranged from 3.5 to 10 cm. In case 1, the surgically removed PPC was necrotic (Fig. 2A), and 90% of the tumor volume was histologically affected by necrosis, possibly due to chemoradiotherapy. Viable tumor cells were scattered (10% of the tumor volume) in the peripheral areas (Fig. 2B), with sheet-like growth features of cytotrophoblast-like tumor cells (Fig. 2C) and occasional syncytiotrophoblast-like multinuclear cells (Fig. 2F). A 1.8-cm metastatic nodule in the lingual segment distant from the main PPC and postoperative biopsy specimens from contralateral lung and gastric metastatic lesions exhibited typical choriocarcinomatous features (Fig. 2I and L). No other carcinomatous components were found. In cases 2–4, primary lung tumors had similar choriocarcinoma components (15–35% of the tumor volume; Fig. 3A) coexisting with adenocarcinoma cells (Fig. 3D and F; 5–30% of the tumor volume) and hemorrhagic necrosis (50–60% of the tumor volume). All of these adenocarcinomatous components focally or multifocally showed papillary or papillotubular growth with nestic proliferation and occasionally contained PAS + lumina. In case 3, dedifferentiated carcinomatous features were also observed (5% of the tumor volume) (24). Polygonal tumor cells in the biopsy specimens from PPCs in cases 1 and 2 were retrospectively consistent with trophoblastic tumor cells (Fig. 1B).

Table I.

Clinicopathological results of primary pulmonary choriocarcinoma.

Table I.

Clinicopathological results of primary pulmonary choriocarcinoma.

Immunohistochemistry of Chor

CaseAge (years)/sexSite of PPCSize (cm)TherapySpecimensHistology (proportion of components)p63p40CK5/6Follow-up
152/MLUL6CRT+L+CTPre-OP biopsyA few polygonal tumor cellsb+d (5%)+d (5%)DOD, 15 months
Main tumorChor 10%, Nec 90%+e (5%)+e (5%)+ (1%)
Post-OP biopsyaChor (metastasis in the right lung)+e (60%)+e (60%)
Post-OP biopsyaChor (metastasis in the stomach)+e (60%)+e (60%)
270/MRLL10NoneAntem biopsyPolygonal tumor cellsb+d (5%)+d (5%)DOD, 2 months
Main tumorChor 35%, Nec 60%, Ad 5%+e (5%)+e (1%)f
377/MLUL5.5NoneMain tumorChor 15%, Nec 50%, Ad 30%, Dediff 5%c+e (1%)gDOD, 2 monthsh
477/MRLL3.5NoneMain tumorChor 30%, Nec 50%, Ad 20%fDOD, 4 months

a Post-operative biopsies from metastases in the right lung and stomach.

b Retrospective, consistent with histological features of choriocarcinoma.

c The detailed histology is shown in a previous article (24).

d Positivity observed in polygonal tumor cells.

e Positivity identified in cytotrophoblast-like tumor cells.

f CK5/6+ tumor cells were focally observed in choriocarcinomatous areas, but possible intermingling of CK5/6+ adenocarcinoma cells could not be ruled out.

g There was no CK5/6 positivity in choriocarcinoma components, adenocarcinoma cells, or undifferentiated carcinoma cells.

h The patient succumbed ~2 months after when the lung tumor had been detected in another hospital (24). Antem, antemortem; Ad, adenocarcinoma; Chor, choriocarcinoma; CK5/6, cytokeratin 5/6; CRT+L+CT, preoperative chemoradiotherapy + lobectomy + postoperative chemotherapy; Dediff, dedifferentiated carcinoma; DOD, died of disease; LUL, left upper lobe; M, male; Nec, necrosis; Post-OP, postoperative; Pre-OP, preoperative; RLL, right lower lobe.

Immunohistochemically, all PPCs and biopsy specimens from PPCs and metastatic lesions showed scattered cytoplasmic β-hCG positivity, mostly in syncytiotrophoblastic tumor cells (Figs. 2C, inset, G, J and M, and 3B). The p63+ and p40+ nuclei of cytotrophoblast-like tumor cells were observed (Fig. 2D and E) in 3 and 2 PPCs, respectively, and occupied 5% and 1–5% of choriocarcinomatous components, respectively. Similarly, p63+ and/or p40+ nuclei accounted for 5–10% of tumor cells within biopsy specimens from PPCs in case 1 (Fig. 1C) and case 2, but diffusely occupied 60% of tumor cells within postoperative biopsy specimens from metastatic lesions in case 1 (Fig. 2K, N and O). Positivity for p63 and p40 was not present in syncytiotrophoblastic tumor cells or concomitant adenocarcinoma cells. In case 1, cytoplasmic CK5/6 positivity was focally found in multinucleated or mononuclear trophoblastic tumor cells (Fig. 2H), accounting for 1% of the tumor cells. Additionally, in cases 2 and 4, CK5/6+ tumor cells were focally found in choriocarcinomatous areas (Fig. 3C). However, in these cases, 30% of concomitant adenocarcinoma cells were positive for CK5/6 (Fig. 3E and G). Therefore, possible intermingling of CK5/6+ adenocarcinoma cells within choriocarcinomatous areas could not be ruled out. CK5/6+ adenocarcinoma cells showed poorly differentiated features, but occasionally had distinctive PAS+ lumina (Fig. 3D, inset and F, inset). These cells were strongly positive for EMA, but negative for TTF-1 (Fig. 3H) and Napsin A. CK5/6+ features were not identified in case 3 or any of the biopsy specimens.

Discussion

Previous studies of p63 and/or p40 expression in PPC have been limited, with reports describing only 3 PPCs (Table II), all of which were concomitant with prominent necrosis and were positive for β-hCG (30,32,37). Two PPCs were positive for p63 (32,37), but their detailed morphology was not determined. The other PPC was negative for p63 (30). One of the 2 p63+ PPCs was negative for p40 (37), but p40 positivity was not examined in the other 2 PPCs. However, in addition to tumors of pulmonary origin, some authors (41,42) have observed focal p63/p40 positivity (<10% of tumor cells) in 38–100% of gestational uterine choriocarcinomas. Shih and Kurman (41) demonstrated the presence of p63+ nuclei in cytotrophoblastic tumor cells. In addition, in the normal placenta, p63+/p40+ features were commonly found in cytotrophoblasts (4143), but not in syncytiotrophoblasts (41,42). These findings strongly supported our current results demonstrating that focal p63+ and p40+ cytotrophoblastic tumor cells were detectable in 75 and 50% of PPCs, respectively, and that no p63+ or p40+ syncytiotrophoblastic tumor cells were found in any PPCs. These findings of p63 and/or p40 positivity in PPCs indicated trophoblastic differentiation rather than true squamous differentiation. p63 gene products include transcriptional activation isoforms and N-terminal transactivation (ΔN) isoforms (4143). Currently available anti-p63 antibodies react with both isoforms, whereas anti-p40 antibodies react with ΔN isoforms only (4143), which may explain the higher incidence of p63 positivity than p40 positivity in PPCs.

Table II.

Clinicopathological results of primary pulmonary choriocarcinoma previously examined immunohistochemical markers for squamous cell carcinoma.

Table II.

Clinicopathological results of primary pulmonary choriocarcinoma previously examined immunohistochemical markers for squamous cell carcinoma.

Immunohistochemistry of Chor
Author, yearReported casesAge (years)/sexSite of PPCSize (cm)TherapyHistology of main tumorp63p40CK5/6OthersFollow-up(Refs.)
Berthod et al, 2010132/FRUL1.5L+CTChor+NecNENEβ-hCG+, CK7+, CK20-, TTF-1-ANED, 1 year(30)
Ibi et al, 2012227/FLUL1.8PR+CTChor+Nec+NENEβ-hCG+, CK+, inhibin α+, TTF-1-ANED, 19 months(32)
Zhu et al, 2016367/MLUL9L+CTChor+Nec+NEβ-hCG+, CK7+, CK20-, TTF-1-aANED, >13 months(37)

a Other immunohistochemical expression including positivity for CAM5.2, GATA3, human placental lactogen, and human leucocyte antigen, and negativity for anaplastic lymphoma kinase, Napsin A, and cluster of differentiation 146. ANED, alive with evidence of disease; Chor, choriocarcinoma; CK, cytokeratin; CK5/6, cytokeratin 5/6; CK7, cytokeratin 7; CK20, cytokeratin 20; F, female; M, male; L+CT, lobectomy + postoperative chemotherapy; LUL, left upper lobe; NE, not examined; Nec, necrosis; PR, partial resection of the lung; RUL, right upper lobe; TTF-1, thyroid transcription factor-1.

The present study also demonstrated the presence of focal CK5/6+ trophoblastic tumor cells in 1 case. In our review of the literature, we could not find any articles describing CK5/6 positivity in normal or neoplastic trophoblasts, although they were positive for pancytokeratin (AE1/AE3), CK7, and CK18 and negative for CK20 (22,24,30,34,37,44). Moreover, in 2 other PPCs, scattered CK5/6+ cells were identified, although they may have been intermingled CK5/6+ adenocarcinoma cells. These findings implied the possible occurrence of CK5/6 positivity in biopsy specimens of PPCs with or without coexisting adenocarcinoma cells, which may also simulate SqCC.

PPCs are extremely rare; in addition to the novel PPCs described in this study, only 60 PPCs have been described in the English literature (439). The incidence of PPC would be less than 0.1% of primary pulmonary cancer. In this study, however, we identified PPCs in 1.6% of the consecutive autopsy cases of lung cancer. This incidence was considered relatively high. Unfortunately, we cannot explain this observation, but we hypothesized that these results may be related to the detailed examination performed using many specimens removed postmortem lung cancers.

From a pathogenetic point of view, PPCs may be somewhat different from conventional choriocarcinoma arising in the uterus of women during gestation, although some PPCs may develop from gestation-related pulmonary trophoblastic embolism (11,31,38). This is supported by the following observations: 26 PPCs (43% of 60 PPCs) were observed in men (79,1416,1821,23,24,29,36,37,39); 15 PPCs (25%) were observed in patients who were at least 60 years old (9,13,14,1720,23,24,26,37,39); 2 PPCs (3%) were observed in infants (4,16); and 8 PPCs (13%) coexisted with otherwise specified primary pulmonary cancer, such as adenocarcinoma (6 PPCs including the present additional 2 PPCs) (14,20,24,36), papillary embryonal carcinoma (1 PPC) (8), or small cell carcinoma (1 PPC) (9), although this ‘papillary embryonal carcinoma’ may have been poorly differentiated adenocarcinoma on the basis of histological features shown in the microphotograph of the article (8,24). These findings suggest that PPCs may infrequently represent trophoblastic differentiation of the pulmonary epithelium, pulmonary otherwise specified neoplasm, or abnormally migrated primordial germ cells in lungs (8,20,24,26,3234). Moreover, in the present study, 2 PPCs coexisted with poorly differentiated adenocarcinoma, which were positive for CK5/6 and EMA, but negative for TTF-1 and Napsin A. We believed that these CK5/6+ tumor cells were adenocarcinoma cells because of occasional presence of PAS+ lumina. Notably, these CK5/6+ and TTF-1-/Napsin A-features were exceptional in primary pulmonary adenocarcinoma (1,3), although CK5/6 positivity of primary pulmonary adenocarcinoma only rarely occurs (45). These features may be associated with unusual trophoblastic differentiation of pulmonary adenocarcinoma cells. Furthermore, in such cases, PPC may be found only in late-stage of lung cancer, and in situ or early phase of PPC would not be identified. Unfortunately, however, we did not investigate this hypothesis in the present study, and additional studies are needed.

PPCs are clinically aggressive tumors; 18 (30%) of 60 patients with PPC died within 3 months from disease onset or hospital admission (410,13,15,17,21,2426,29,36,37). Therefore, accurate diagnosis during the early stage of the disease is important for therapeutic management of patients. However, 16 PPCs (27%) were diagnosed by autopsy (4,5,810,1315,17,19,2325). TBB or percutaneous biopsies have been performed in 25 cases, and the specific diagnosis of PPC was rendered in only 7 (28%) of these cases (11,12,21,2931,35). Importantly, the histopathological diagnosis of PPCs seems to be challenging in small biopsy specimens. This may be because PPCs are frequently associated with massive hemorrhagic necrosis (13,15,17,2227,31,32,37), and it is difficult to obtain sufficient amounts of tumor cells for definitive pathological diagnosis. Furthermore, our results in the present study demonstrated that PPCs could mimic SqCC morphologically and immunohistochemically. Morphological mimicry of SqCC has also been noted in percutaneous biopsy specimens (18) and fine needle aspiration cytology specimens (19,27) of PPCs. Recently, Vallonthaiel et al (46) reported a unique case of pulmonary metastatic choriocarcinoma, which was diagnosed as NSCC favoring SqCC, because of the presence of p40+ polygonal tumor cells in the biopsy specimen. These features closely resembled those of the present case 1. In the biopsy specimens from contralateral lung and gastric metastases in case 1, p40+/p63+ tumor cells were not focal and were diffusely distributed. Based on these findings, we suggest that surgical pathologists should be aware of the possible morphological and immunohistochemical mimics of SqCC in biopsy specimens of PPCs or metastatic choriocarcinomas. Particularly when a few SqCC marker+ polygonal cells are encountered in hemorrhagic necrotic biopsy tissues, this diagnostic pitfall should be considered.

Thus, the present study revealed the presence of p63+ and p40+ cytotrophoblastic tumor cells and the possible occurrence of CK5/6+ tumor cells in PPCs. The current results highlighted the diagnostic pitfall that PPCs can mimic SqCC morphologically and immunohistochemically although PPC is extremely rare.

Acknowledgements

The authors would like to thank Mr. Kenji Okada (Department of Pathology, Japan Self-Defense Forces Central Hospital, Tokyo, Japan) for their technical assistance.

Funding

No funding was received.

Availability of data and materials

All data generated or analyzed during the current study are included in this published article.

Authors' contributions

SM assessed the autopsy files and H&E-stained sections, and identified the additional postmortem primary pulmonary choriocarcinoma (PPC). SM drafted the manuscript. SM, YU, KM and HT participated in the histopathological assessment of PPC, including immunohistochemical features, and the editing of photographs. YU, KO, YO and KS participated in the review of the literature and clinical assessment of the PPC cases. SM, KO, YU, KM, HT, YO and SK conceived and designed the study, participated in the study coordination, and edited the manuscript.

Ethical approval and consent to participate

The present study was performed according to the Declaration of Helsinki. The present study was a retrospective study, which was approved by the Medical Research Ethics Committee of Japan Self-Defense Forces Central Hospital (June 5, 2017; approval no. 29-004).

Patient consent for publication

At the time of autopsy or surgery, written informed consent for the use of postmortem and surgical materials in histopathological studies was obtained from the patients' families or the patients.

Competing interest

The authors declare that they have no conflicts of interest.

Glossary

Abbreviations

Abbreviations:

β-hCG

β-human chorionic gonadotropin

CK5/6

cytokeratin 5/6

CK7

cytokeratin 7

CK18

cytokeratin 18

18F-FDG

18F-fluorodeoxyglucose

EMA

epithelial membrane antigen

H&E

hematoxylin and eosin

NSCC

non-small cell carcinoma

ΔN

N-terminal transactivation

PAS

periodic acid-Schiff

PPC

primary pulmonary choriocarcinoma

SqCC

squamous cell carcinoma

TBB

transbronchial biopsy

TTF-1

thyroid transcription factor-1

WHO

World Health Organization

References

1 

Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, et al: International association for the study of lung cancer/American thoracic society/European respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 6:244–285. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Travis WD, Brambilla E, Burke AP, Marx A and Nicholson AG: WHO classification of tumours of the lung, pleura, thymus and heart. 4th edition. IARC press; Lyon: 2015

4 

Kay S and Reed WG: Chorioepithelioma of the lung in a female infant seven month. Am J Pathol. 29:555–567. 1953.PubMed/NCBI

5 

Acosta-Sison H: Can primary pulmonary chorionepithelioma develop after a term pregnancy? Case report. Am J Obstet Gynecol. 76:894–896. 1958. View Article : Google Scholar : PubMed/NCBI

6 

Chan DP and Pang LS: Late solitary pulmonary chorionepithelioma following hydatidiform mole. A report of three cases. J Obstet Gynaecol Br Commonw. 71:192–197. 1964. View Article : Google Scholar : PubMed/NCBI

7 

Cacciamani J: Case of choriocarcinoma of the lung. Clin Notes Respir Dis. 10:10–11. 1971.PubMed/NCBI

8 

Hayakawa K, Takahashi M, Sasaki K, Kawaoi A, Okano T, Osada H, Otsuka T and Murota Y: Primary choriocarcinoma of the lung: Case report of two male subjects. Acta Pathol Jpn. 27:123–135. 1977.PubMed/NCBI

9 

Hattori M, Imura H, Matsukura S, Yoshimoto Y, Sekita K, Tomomatsu T, Kyogoku M and Kameya T: Multiple-hormone producing lung carcinoma. Cancer. 43:2429–2437. 1979. View Article : Google Scholar : PubMed/NCBI

10 

Patra SB, Giri DD and Patra BS: Giant choriocarcinoma of the lung. Indian J Chest Dis Allied Sci. 25:228–231. 1983.PubMed/NCBI

11 

Tanimura A, Natsuyama H, Kawano M, Tanimura Y, Tanaka T and Kitazono M: Primary choriocarcinoma of the lung. Hum Pathol. 16:1281–1284. 1985. View Article : Google Scholar : PubMed/NCBI

12 

Rhee YK, Kim JH, Kim WH, Ha CY, You KH and Jang DS: Primary choriocarcinoma of the lung. Korean J Intern Med. 2:269–272. 1987. View Article : Google Scholar : PubMed/NCBI

13 

Pushchak MJ and Farhi DC: Primary choriocarcinoma of the lung. Arch Pathol Lab Med. 111:477–479. 1987.PubMed/NCBI

14 

Adachi H, Aki T, Yoshida H, Yumoto T and Wakahara H: Combined choriocarcinoma and adenocarcinoma of the lung. Acta Pathol Jpn. 39:147–152. 1989.PubMed/NCBI

15 

Sullivan LG: Primary choriocarcinoma of the lung in a man. Arch Pathol Lab Med. 113:82–83. 1989.PubMed/NCBI

16 

Otsuka T, Ohshima Y, Sunaga Y and Nagashima K: Primary pulmonary choriocarcinoma in a four month old boy complicated with precocious puberty. Acta Paediatr Jpn. 36:404–407. 1994. View Article : Google Scholar : PubMed/NCBI

17 

Toda S, Inoue Y, Ishino T, Yonemitsu N, Terayama K, Miyabara S and Sugihara H: A rare case of primary pulmonary choriocarcinoma in a male: Immunohistochemical detection for human chorionic gonadotropin, epidermal growth factor (EGF) and EGF-receptor. Endocr J. 42:655–659. 1995. View Article : Google Scholar : PubMed/NCBI

18 

Canver CC and Voytovich MC: Resection of an unsuspected primary pulmonary choriocarcinoma. Ann Thorac Surg. 61:1249–1251. 1996. View Article : Google Scholar : PubMed/NCBI

19 

Ikura Y, Inoue T, Tsukuda H, Yamamoto T, Ueda M and Kobayashi Y: Primary choriocarcinoma and human chorionic gonadotrophin-producing giant cell carcinoma of the lung: Are they independent entities? Histopathology. 36:17–25. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Chen F, Tatsumi A and Numoto S: Combined choriocarcinoma and adenocarcinoma of the lung occurring in a man. Cancer. 91:123–129. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Tsai JR, Chong IW, Hung JY and Tsai KB: Use of urine pregnancy test for rapid diagnosis of primary pulmonary choriocarcinoma in a man. Chest. 121:996–998. 2002. View Article : Google Scholar : PubMed/NCBI

22 

Umemori Y, Hiraki A, Aoe E, Murakami T, Maeda T, Matsuda E and Takeyama H: Primary choriocarcinoma of the lung. Anticancer Res. 24:1905–1910. 2004.PubMed/NCBI

23 

Vaideeswar P, Mehta J and Deshpande J: Primary pulmonary choriocarcinoma-a series of 7 cases. Indian J Pathol Microbiol. 47:494–496. 2004.PubMed/NCBI

24 

Yamamoto S, Tanaka H, Takeo H, Yasuda K and Matsukuma S: Primary pulmonary choriocarcinoma combined with adenocarcinoma. Pathol Int. 56:402–407. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Shintaku M, Hwang MH and Amitani R: Primary choriocarcinoma of the lung manifesting as diffuse alveolar hemorrhage. Arch Pathol Lab Med. 130:540–543. 2006.PubMed/NCBI

26 

Kini U and Babu MK: Primary pulmonary choriocarcinoma: Is it still an enigma? Indian J Chest Dis Allied Sci. 49:219–226. 2007.

27 

Vegh GL, Szigetvári I, Soltesz I, Major K, Batorfi J, Dancso J, Zsirai L and Fulop V: Primary pulmonary choriocarcinoma. A case report. J Reprod Med. 53:369–372. 2008.PubMed/NCBI

28 

Seol HJ, Lee JH, Lee KY, Kim JH, Lee NW and Park HJ: Primary pulmonary choriocarcinoma presenting with a hemothrax. J Thorac Oncol. 4:663–665. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Hadgu A, Tindni A and Panda M: Primary pulmonary choriocarcinoma in a male. BMJ Case Rep. 2010:pii: bcr02201027122010. View Article : Google Scholar

30 

Berthod G, Bouzourene H, Pachinger C and Peters S: Solitary choriocarcinoma in the lung. J Thorac Oncol. 5:574–575. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Maestá I, Leite FV, Michelin OC and Rogatto SR: Primary pulmonary choriocarcinoma after human chorionic gonadotropin normalization following hydatidiform mole: A report of two cases. J Reprod Med. 55:311–316. 2010.PubMed/NCBI

32 

Ibi T, Hirai K, Bessho R, Kawamoto M, Koizumi K and Shimizu K: Choriocarcinoma of the lung: Report of a case. Gen Thorac Cardiovasc Surg. 60:377–380. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Serno J, Zeppernick F, Jäkel J, Schrading S, Maass N, Meinhold-Heerlein I and Bauerschlag DO: Primary pulmonary choriocarcinoma: Case report and review of the literature. Gynecol Obstet Invest. 74:171–176. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Di Crescenzo V, Laperuta P, Napolitano F, Carlomagno C, Garzi A and Vitale M: An unusual case of primary choriocarcinoma of the lung. BMC Surg. 13 Suppl 2:S332013. View Article : Google Scholar : PubMed/NCBI

35 

Perwaiz M, Boujaoude Z, Ranasuriya G, Raja H, Gaspard D and Abouzgheib W: Primary pulmonary choriocarcinoma. A diagnostic dilemma. J Bronchol Intervent Pulmonol. 22:183–185. 2015. View Article : Google Scholar

36 

Takahashi T and Kobayashi R: Choriocarcinoma syndrome after resection of primary pulmonary choriocarcinoma: Report of a case. Surg Case Rep. 2:1222016. View Article : Google Scholar : PubMed/NCBI

37 

Zhu R, Jia C, Yan J, Luo Y and Huo Z: Primary pulmonary choriocarcinoma in a male that was successfully diagnosed and treated: A case report and review of the literature. Medicine (Baltimore). 95:e56932016. View Article : Google Scholar : PubMed/NCBI

38 

Snoj Z, Kocijancic I and Skof E: Primary pulmonary choriocarcinoma. Radiol Oncol. 51:1–7. 2016. View Article : Google Scholar : PubMed/NCBI

39 

Kamata S, Sakurada A, Sato N, Noda M and Okada Y: A case of primary pulmonary choriocarcinoma successfully treated by surgery. Gen Thorac Cardiovasc Surg. 65:361–364. 2017. View Article : Google Scholar : PubMed/NCBI

40 

Goldblum JR, Lamps LW, McKenney JK and Myers JL: Rosai and Ackerman's Surgical Pathology. 11th edition. Elsevier; Philadelphia, PA: 2018

41 

Shih IM and Kurman R: p63 expression is useful in the distinction of epithelioid trophoblastic and placental site trophoblastic tumors by profiling trophoblastic subpopulations. Am J Surg Pathol. 28:1177–1183. 2004. View Article : Google Scholar : PubMed/NCBI

42 

Zhang HJ, Xue WC, Siu MK, Liao XY, Ngan HY and Cheung AN: P63 expression in gestational trophoblastic disease: Correlation with proliferation and apoptotic dynamics. Int J Gynecol Pathol. 28:172–178. 2009. View Article : Google Scholar : PubMed/NCBI

43 

Tacha D, Bremer R, Haas T and Qi W: An immunohistochemical analysis of a newly developed, mouse monoclonal p40 (BC28) antibody in lung, bladder, skin, breast, prostate, and head and neck cancers. Arch Pathol Lab Med. 138:1358–1364. 2014. View Article : Google Scholar : PubMed/NCBI

44 

Dabbs DJ: Diagnostic immunohistochemistry. 2nd edition. Churchill Livingston/Elsevier; Philadelphia, PA: 2006, View Article : Google Scholar

45 

Rekhtman N, Ang DC, Sima CS, Travis WD and Moreira AL: Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens. Mod Pathol. 24:1348–1359. 2011. View Article : Google Scholar : PubMed/NCBI

46 

Vallonthaiel AG, Walia R, Pramanik R, Sharma MC and Jain D: p40 in metastatic pulmonary trophoblastic tumour: Potential diagnostic pitfall on histopathology. Malays J Pathol. 39:175–179. 2017.PubMed/NCBI

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December-2018
Volume 16 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
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Spandidos Publications style
Matsukuma S, Obara K, Utsumi Y, Miyai K, Takeo H, Oshika Y and Sensaki K: Focal positivity of immunohistochemical markers for pulmonary squamous cell carcinoma in primary pulmonary choriocarcinoma: A histopathological study. Oncol Lett 16: 7256-7263, 2018
APA
Matsukuma, S., Obara, K., Utsumi, Y., Miyai, K., Takeo, H., Oshika, Y., & Sensaki, K. (2018). Focal positivity of immunohistochemical markers for pulmonary squamous cell carcinoma in primary pulmonary choriocarcinoma: A histopathological study. Oncology Letters, 16, 7256-7263. https://doi.org/10.3892/ol.2018.9525
MLA
Matsukuma, S., Obara, K., Utsumi, Y., Miyai, K., Takeo, H., Oshika, Y., Sensaki, K."Focal positivity of immunohistochemical markers for pulmonary squamous cell carcinoma in primary pulmonary choriocarcinoma: A histopathological study". Oncology Letters 16.6 (2018): 7256-7263.
Chicago
Matsukuma, S., Obara, K., Utsumi, Y., Miyai, K., Takeo, H., Oshika, Y., Sensaki, K."Focal positivity of immunohistochemical markers for pulmonary squamous cell carcinoma in primary pulmonary choriocarcinoma: A histopathological study". Oncology Letters 16, no. 6 (2018): 7256-7263. https://doi.org/10.3892/ol.2018.9525