Shinshu M ed J, 64⑵ :79 〜83, 2016

Complete Response of Advanced Invasive Mucinous
Adenocarcinoma of the Lung with Gemcitabine and Pemetrexed
Kentaro M IURA and Ryoichi KONDO
Department of Thoracic Surgery, National Hospital Organization Matsumoto Medical Center

In 2011, mucinous bronchioloalveolar carcinoma was reclassiﬁed as invasive mucinous adenocarcinoma,
mucinous adenocarcinoma in situ, and mucinous minimally invasive adenocarcinoma. A part of the invasive
mucinous adenocarcinoma of the lung diﬀerentiates to gastric mucous cells, and we term this type ofcarcinoma gastric‑like invasive mucinous adenocarcinoma.However,treatment approaches have not yet been
established.
An 84‑year‑old Japanese male visited our hospital because of multiple consolidations and ground‑glass
opacity on his chest computed tomography. Surgical biopsy of the right lung ground‑glass opacity wasperformed,and it was diagnosed as gastric‑like invasive mucinous adenocarcinoma by immunohistochemical
analysis. Treatment with gemcitabine and pemetrexed was quite eﬀective, and the radiologic response wascomplete. We suggest that it is meaningful to determine whether the diagnosis of gastric‑like invasive
mucinous adenocarcinoma is correct because this may indicate a favourable response to the anticancer drug
gemcitabine. Shinshu Med J 64 : 79 ―83, 2016
(Received for publication July 23, 2015;accepted in revised form December 16, 2015)
Key words:ground‑glass opacity, invasive mucinous adenocarcinoma, gemcitabine, pemetrexed
Abbreviations:IMA, invasive mucinous adenocarcinoma ;CT, computed tomography;GGO, ground‑glass opacity;
NSCLC, non‑small cell lung carcinoma

Introduction
In 2011, mucinous bronchioloalveolar carcinoma
was reclassiﬁed as invasive mucinous adenocarcinoma (IMA),mucinous adenocarcinoma in situ,ordeﬁned. We report a case of advanced gastric‑likeIMA, which demonstrated a complete response totreatment with gemcitabine and pemeterexed.
Case presentation

mucinous minimally invasive adenocarcinoma . It

An 84‑year‑old Japanese male visited our hospi-

is said that the response rate of advanced IMA total because of multiple consolidations and ground‑chemotherapy is lower than that of other non‑small

glass opacity(GGO)on his chest computed tomogra-

cell lung carcinomas (NSCLC) . Conversely, anphy (CT). He was a former smoker, and his past

IMA part of the lung appears to diﬀerentiate into

medical histories comprised pancreatic cancer (Fig.

gastric mucous cells ; we term this type of car-1) and adenoma of the colon for which surgicalcinoma gastric‑like IMA.However,its features andresection was done approximately 2 years previous-

approach to therapy have not yet been clearlyly.The largest lesion existed on the left upper lunglobe, which was considered the main tumor, andCorresponding author:Kentaro M iura
Department of Thoracic Surgery, Shinshu University
School of Medicine, 3‑1‑1 Asahi, Matsumoto, Nagano

some consolidations and GGOs were located at thebilateral pulmonary lesion on his chest CT (Fig. 2).

390‑8621, Japan

Bronchoscopic examination was performed ; how-E‑mail:kmiura＠shinshu‑u.ac.jp

ever, it only detected inﬂammatory cells, and theNo. 2, 201679

M iura.Kondo

cancerBile duct cancer

aFig. 1bHistopathological ﬁndings of pancreatic and bile duct cancers.
Pancreatic (a)and bile duct cancers (b) (Hematoxylin and eosin staining) are shown. These weremucus‑producing tumors;however, the malignancy grade was higher in these cancers than in lungcancer.

Fig. 2High‑resolution computed tomography of the lung at the time of initial visit.
There were multiple GGOs and consolidations in the bilateral lungs.The main tumor existed at theleft upper lobe. The lung biopsy was taken for the right upper lobe (S2 segment) via video‑assisted
thoracoscopic surgery (arrowhead).

diagnosis was not correct.To conﬁrm the diagnosis,

ic mucosa, and we diagnosed this as gastric‑likewe performed surgical partial resection of the right

IMA, stage IV (cT4N0M 1a). In genetic screening,lung GGO lesion via video‑assisted thoracoscopic

epidermal growth factor receptor mutations, ana-surgery (Fig. 2).

plastic lymphoma kinase rearrangements, and Kir-

The histopathological ﬁndings revealed the exis-sten rat sarcoma mutations were not recognized.

tence of low‑grade atypical cells ﬁlled with mucin in

The administration of the oral ﬂuoropyrimidine

their cytoplasm along with the surface of alveolaranticancer agent,TS‑1 (50 mg/day,Taiho Pharma-wall,and it demonstrated aerogenous dissemination

ceutical, Tokyo, Japan) was immediately initiated.

by hematoxylin and eosin staining (Fig. 3). An im-However, a chest CT done 3 months after TS‑1

munohistochemical analysis was positive for alcian

administration revealed a progressive course ofblue‑periodic‑acid Schiﬀstain(AB/PAS)and mucin‑6disease,and its eﬀect was not satisfactory(Fig.4a).

(M UC6) and was slightly positive for thyroid tran-In addition, blood tests revealed abnormal hepaticscription factor‑1(TTF‑1)(Fig.3).Although metas-function.Abdominal CT showed dilation of the biletatic lung tumor was considered, it was diagnosed

duct ; he was diagnosed with bile duct cancer by

as primary lung cancer because it revealed aer-endoscopic biopsy(Fig.1),and a stent was placed inogenous dissemination and its malignancy grade

the bile duct.For the treatment of both the lung andwas lower than pancreatic cancer. These facts in-bile duct cancers,we chose gemcitabine (GEM ZAR,

dicated organoid diﬀerentiation to the gastric pylor-Eli Lilly and Company, Indianapolis, USA) and80

Shinshu M ed J Vol. 64

Advanced IMA of the lung with gemcitabine and pemetrexedFig. 3abcdHistopathological ﬁndings of lung cancer.
Hematoxylin and eosin staining revealed the existence of low‑grade atypical cells ﬁlled with mucinin their cytoplasm along with the surface of alveolar wall,and it demonstrated aerogenous dissemination (a). An immunohistochemical analysis was slightly positive for TTF‑1 (b)and positive for AB‑PAS (c)and MUC6 (d).

pemetrexed (Alimta, Eli Lilly and Company, Indianapolis,USA)as the new chemotherapy regimen

Discussion

in expectation of beneﬁcial eﬀects on both IM A and

It is reported that a part of IM A shows organoid

bile duct cancer. The doses for gemcitabine (1,200diﬀerentiation mimicking gastric pyloric mucosa .

mg/m × 0.7 dose on day 1), and pemetrexed (500

It is diagnosed by immunostaining,which is positive

mg/m × 0.7 dose day 1),administered over 28‑day

for gastric surface mucous cell‑type or gastriccycles, were chosen in consideration of his age.

gland mucous cell‑type mucins . This IM A type isFurthermore, he was administered folic acid andsaid to exist in approximately 60% of all IMA. Invitamin B supplements. The radiologic response

this case, AB/PAS and M UC6 stainings were posi-was complete after 10 cycles without side eﬀects.

tive. This concept was advocated ﬁrst by Honda et

Lesions were replaced by cavities (Fig. 4b). In

al but remains relatively unknown. We term thisaddition,as the bile duct cancer had not worsened in

type of IMA as gastric‑like IMA.The treatment fora CT scan, it was considered that this combination

gastric‑like IMA has not been established, andof drugs was eﬀective against bile duct cancer.Theclinical features have not been clearly delineated.Itchemotherapy is ongoing, and he is alive without

may be important to check whether gastric‑likerecurrence of cancer.

IMA or non‑gastric‑like IMA is an accurate term
or not. The clinical features of gastric‑like IMA
have not yet been deﬁned, and its diﬀerences fromNo. 2, 201681

M iura.KondoabFig. 4

The changes before and after treatment with gemcitabine and pemetrexed.
TS‑1 was not eﬀective,and the lesions of GGOs and consolidations had grown compared with thoseat the initial visit (a). After treatment with gemcitabine and pemetrexed, the lesions of GGOs andconsolidations almost completely disappeared, and these lesions were replaced by cavities (b).

other non‑gastric‑like IM As have not been clariﬁed.

not specify whether IMA was gastric‑like or not.

There was a review regarding gemcitabine and

There are no reports about the use of chemotherapy

pemetrexed therapy for advanced NSCLC . Theyin the treatment of gastric‑like IMA. We experi-administered gemcitabine 1,250 mg/m on days 1

enced some cases of advanced gastric‑like IMA inand 8 and pemetrexed 500 mg/m on day 8.Medianwhich pemetrexed and other drugs without gem-

survival was 10.4‑11.6 months,and overall response

citabine were administered ; however, all of themrate was 8.7%‑44.1%. It appears to be rare torevealed a progressive course of the disease. It

demonstrate the complete response that was obser-appears that gemcitabine may be a key drug forved in our case.

gastric‑like IM A.

Alternatively, gemcitabine is often used for carcinomas of the biliary duct and pancreas. It is said

Conclusions

that most of the biliary duct and pancreas car-

The combination of gemcitabine and pemetrexed

cinomas produce ectopic phenotypic expression of

was eﬀective in the treatment of advanced gastric‑gastric mucins . Therefore, because our caselike IMA.Gastric‑like IMA has not yet been recog-

appeared to be a gastric‑like carcinoma, gem-

nized and focused on, and its clinical features andcitabine might be eﬀective.

signiﬁcance have not been clariﬁed. However, weHowever, in this case, the possibility of pemeter-suggest that it is beneﬁcial to examine whether IMA

exed eﬀectiveness should not be ruled out. Yamak-is gastric‑like or not because it may indicate aawa et al.reported two cases of advanced IMA thatfavorable response to gemcitabine. We hope toindicated favorable responses using

investigate more cases of gastric‑like IMA andcisplatin,pemetrexed,and bavacizumab .Some cases of IMA

clarify its clinical and pathological features.

have been reported as having favorable responses
using pemeterexed82; however, these reports doShinshu M ed J Vol. 64

Advanced IMA of the lung with gemcitabine and pemetrexed

COIAcknowledgments

The authors declare that they have no competing

We would like to special by thank Dr.Keiko Ishii

interests.

(Department of Diagnostic Pathology, Okaya
Municipal Hospital, Japan) for assistance with thepathological diagnosis.
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