ELSEVIER Lung Cancer 15 (1996) 125-130

Case reports

Alpha-fetoprotein-producing adenocarcinoma of the lung

Ichiro Yoshinoa, Itsuro Hayashib, Tokujiro Yano”, Eiji Takai”, Kazuki Mizutani”, Yukito Ichinose”T*

“Department of Chest Surgery, National Kyushu Cancer Center, 3-t-l Notame, Minami-ku, Fukuoka 815, Japan

bDepartment of Pathology, National Kyushu Cancer Center, 3-l-l Notame, Minami-ku, Fukuoka 815, Japan

Received 11 September 1995; accepted 15 February 1996

Abstract

We herein present a case of metachronous primary lung cancers, the first of which was adenosquamous cell carcinoma and the second of which was poorly differentiated adenocar- cinema. At the time the second lung cancer was detected 5 years after being operated on for the first cancer, a high level of serum alpha-fetoprotein (AFP) was noticed, but no elevation of other tumor markers was observed. In addition, no liver metastases, chronic liver diseases or other systemic abnormalities were seen either. The serum AFP level was 696 rig/ml, and the profile of lectin affinity showed a tumor-derived pattern. Two weeks after the operation, the serum AFP level decreased to a normal level. An immunohistochemical analysis confirmed that the exact origin of AFP was the tumor tissue. A specimen taken from the first lung cancer was not stained by the same procedures, which thus indicated this case to be a double primary lung cancer.

Keywords: Alpha-fetoprotein; Non-small cell lung cancer; Tumor indicator; Immunohisto- chemistry

* Corresponding author. Tel.: + 81 92 5413231; fax: + 81 92 5514585.

0169-5002/96/$15.00 0 1996 Elsevier Science Ireland Ltd. All rights reserved PZI SOl69-5002(96)00577-6

126 I. Yoshino et al. /Lung Cancer 15 (1996) 125-130

1. Introduction

Alpha-fetoprotein (AFP) was first detected in the serum of a patient with a primary liver tumor in 1965 [l], and has since been used for a tumor indicator for either primary liver tumors [2,3], or yolk sac tumors [4]. However, AFP has been much less frequently found in other histological types of malignancies [5]. In lung cancer, the elevation of AFP is also rarely accompanied, especially in advanced diseases [6,7], and the phenomenon sometimes suggests tumor involvement of the liver since hepatocytes surrounding metastatic tumor cells can produce AFP [8,9]. We herein report a case of an early lung cancer-producing AFP, and also summarize the findings of previously reported similar cases.

2. Case report

A 54-year-old man had previously undergone a left upper lobectomy of the lung with a combined resection of the chest wall in September 1988 for adenosquamous cell carcinoma of the lung at another hospital. The pathological stage was deter- mined to be p-T3, NO, MO. A high level of serum carcinoembryonic antigen (CEA) (45.5 rig/ml) had decreased to a normal level after a surgical resection of the tumor. Thereafter, the patient was followed-up at the outpatient clinic of Department of Chest Surgery, National Kyushu Cancer Center, Fukuoka, Japan. In July 1993, a chest X-ray revealed a nodular lesion in the right apex of the lung. After analyzing the serum tumor indicators, AFP was found to increase to 696 rig/ml (a normal value is less than 20 rig/ml), while the CEA, squamous cell carcinoma antigen (SCC), siaryl Louis-X @LX), neuron specific enolase (NSE) or human chorionic gonadotropin (HCG) all showed normal levels. In the physical examination, no abnormal findings were observed (no mass in the testis). A blood chemistry analysis showed normal values for liver function. The patient was thus admitted for further analysis. In a lectin chromatography analysis of the serum AFP, percent binding with concanavalin A (Con A) was 81% while a lentil lectin affinity profile showed that the high affinity fraction was dominant (76%). These findings indicated a primary hepatic tumor pattern [lO,ll]. The computed tomography (CT) revealed a tumor of approximately 2 cm in diameter in the S2 region of the right lung (Fig. 1). There were no swollen lymph nodes in bilateral hilum or mediastinum, mediastinal mass or hepatic lesions in the CT. Ultrasonography could not detect any space-oc- cupying lesions in the liver. A bone scan test was normal. Fiberoptic bronchoscopy revealed no abnormal findings in the proximal bronchial trees, and several diagnos- tic interventions under fluoroscopy such as a transbronchial lung biopsy, brushing cytology or washing cytology all proved to be unsuccessful. The pulmonary lesion was, however, suspected to have originated from the second primary lung cancer because of the difference in the positive biomarkers among the metachronous tumors (CEA vs. AFP), the long interval between the occurrence of the tumors

I. Yoshino et al. 1 Lung Cancer 1.5 (1996) 125- 130 127

(approximately 5 years) and the different sites of the tumors (different lungs). In August 1993, the patient underwent a right upper lobectomy and regional lymph node dissection. Immunoperoxidase staining using anti-AFP monoclonal antibody [12] was performed on both the resected specimen as well as the stored specimen of the first lung cancer. The second tumor, which was pathologically diagnosed to be poorly differentiated adenocarcinoma (Fig. 2A), was positively stained by this procedure (Fig. 2B) whereas the first lung cancer, which had been diagnosed as adenosquamous cell carcinoma was negative (data not shown). All of the dissected lymph nodes were microscopically negative for metastasis. The pathological stage was determined to be Stage I (Tl, NO, MO). The serum level of AFP gradually decreased and was 51 rig/ml on the 14th postoperative day, and less than 10 rig/ml on the 21st postoperative day (normal, < 20 rig/ml). Based on these findings, the second tumor was determined to be a second primary lung cancer producing AFP. At 24 months after the second surgery, the patient is alive without recurrence.

3. Discussion

AFP is one of the oncofetal proteins and has been generally accepted as the most reliable tumor indicator for primary liver tumors and yolk sac tumors [2,3]. However, certain gastrointestinal tumors [5] such as gastric, rectal and pancreatic carcinoma as well as lung cancer [6,12- 161 also secrete AFP, although its incidence is rare. When an elevation of the serum AFP level is encountered in a patient with

Fig. 1. Computed tomography of the chest reveals a nodular lesion measuring approximately 2 cm in diameter at the apex of the right lung.

128 I. Yoshino et al. /Lung Cancer 15 (1996) 125-130

Fig. 2. (A) Poorly differentiated adenocarcinoma from the second lung cancer consisting of a sheet of atypical cells (hematoxylin and eosin; magnification: x ZOO). (B) An immunohistochemical analysis of the second tumor. Substrates binding anti-AFP monoclonal antibody were raised by peroxidase in the cytoplasm of certain tumor cells (magnification: x 400).

possibly primary lung cancer, liver metastasis would first be suspected. Walop et al. [7] reported that about 2% (three of 119 tested) of primary lung cancer patients were AFP-positive. However, they also stated that the three AFP-positive patients died within 6 months after the analysis, which thus suggested the possibility of liver metastases. Since hepatocytes surrounding metastatic tumor cells have also been reported to produce AFP [8,9], the true rate of AFP-producing tumors among primary lung cancer remains unknown. Based on the findings of our survey, up to 1995, only nine cases of AFP producing primary lung cancer without liver metas- tases have been reported in detail worldwide, and the majority of these cases cited were adenocarcinoma (six out of nine). Tissue AFP was confirmed in six cases by immunohistochemical staining, while one case showed negative findings in a similar analysis. AFP is divided into hepatic tumor type, germ cell tumor type, and non-tumor type based on its characteristic of affinity to lectin [IO, 111. The Con A-affinity of AFP was a hepatic tumor-type in two of four cases tested. In our case, it was confirmed that adenocarcinoma tissue of the resected lung was the source of AFP by an immunohistochemical analysis although the lectin binding profile showed a hepatic tumor type. The level of serum AFP in the present case was relatively lower than that of the cases cited in Table 1, except for case 5, in which the smaller size of the tumor may have influenced the outcome.

Table

1

Cas

es o

f lu

ng c

ance

r pr

oduc

ing

AFP

with

out

liver

met

asta

ses

Cas

e R

epor

ted

by

Year

Se

x Ag

e H

isto

logy

” AF

P El

evat

ion

of o

ther

tu

mor

in

dica

tors

1 C

orlin

an

d To

mpk

ins

[9]

2 Ya

suna

mi

et a

l. [1

3]

3 M

iyak

e et

al.

[14]

4

Yosh

imot

o et

al.

[12]

S

Saka

et a

l. [lS

] 6

Ishi

kura

et

al.

[6]

I Is

hiku

ra

et a

l. [6

] 8

Ishi

kura

et

al.

[6]

9 O

kuna

ka

et a

l. [1

6]

10

This

stud

y

1972

M

19

81

M

1987

M

19

87

F 19

88

M

1990

M

19

90

M

1990

M

19

92

M

1996

M

66

Anap

last

ic 61

Ad

eno

13

Aden

o 61

La

rge

13

Aden

o 40

Ad

eno

5s

Aden

o 69

Ad

eno

49

Larg

e 54

Ad

eno

Seru

m (

rig/m

l) Co

nA-b

indi

ng

(“XI)

Tiss

ue

10 0

00

160

000

1039

19

700 289

3090

21

23

SOS0

93

00

696

18.7

%

Maj

ority

b

52.1

%

80.7

%

+ CE

A +

HC

G

+ C

EA,

HC

G

+ + - + CE

A

81%

+

“Sm

all,

smal

l ce

ll ca

rcin

oma;

Ad

eno,

ad

enoc

arcin

oma;

La

rge,

la

rge

cell

carc

inom

a.

bAna

lyzed

by

im

mun

oblo

tting

.

130 I. Yoshino et al. / Lung Cancer 15 (1996) 125-130

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