Adenocarcinoma Arising in Type 1 Congenital Cystic Adenomatoid Malformation: A Case Report and Review of the Literature
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1 The Korean Journal of Pathology 2008; 42: denocarcinoma rising in Type 1 Congenital Cystic denomatoid Malformation: Case Report and Review of the Literature Jinyoung Yoo Sun Mi Lee Ji Han Jung Myeong Im hn 1 Deog Gon Cho 2 Seok Jin Kang Kyo Young Lee Departments of Pathology, 1 Diagnostic Radiology, and 2 Thoracic Surgery, St. Vincent s Hospital, The Catholic University of Korea, Suwon, Korea Malignancies in congenital cystic adenomatoid malformations (CCMs) of the lung are rare. We report a 41-year-old male patient with a pulmonary cystic lesion suspicious for CCM, unrecognized until the patient was 40 years of age, and which subsequently became more consolidated during the interval between initial presentation and surgery. Microscopic examination of the resected specimen revealed features of type 1 CCM with a mucinous adenocarcinoma, metastatic to the mediastinal lymph nodes. This case illustrates the importance of prompt surgical resection for all suspected CCMs, especially those discovered in adulthood. Received : July 2, 2008 ccepted : September 9, 2008 Corresponding uthor Seok Jin Kang, M.D. Department of Pathology, St. Vincent s Hospital, The Catholic University of Korea, 93 Ji-dong, Paldal-gu, Suwon , Korea Tel: Fax: sjkang@vincent.cuk.ac.kr Key Words : Congenital cystic adenomatoid malformation; denocarcinoma Malignancies in congenital cystic adenomatoid malformations (CCM) are rare with a reported incidence of less than 1%. 1,2 ronchioloalveolar carcinoma (C) arising in type 1 CCM was first described in 1953, and to the best of our knowledge, only 16 cases of CCM with malignant change have been reported since that time in the English literature. 3,4 They usually occur in adults whose CCMs have not been resected in childhood. We report a case of adenocarcinoma in association with a preexisting type 1 CCM, probably aggravated during the time of surgical delay. CSE REPORT 41-year-old man was admitted to the Department of Thoracic Surgery for surgical excision of a suspected CCM in the lung. The lesion had first been detected 17 months earlier, when the patient had been evaluated for a rib fracture following a traffic accident. Computed tomography (CT) at that time showed a cm sized lesion in the medial basal segment of the right lower lobe. It consisted of multiple small air cysts and exhibited mild enhancement, suggesting an infected cystic lung lesion such as an adult CCM (Fig. 1). The patient had been visiting a local clinic for copious sputum production for the previous 2 years, but he was otherwise well. Conservative treatment was implemented for his rib fracture, while surgical excision was advised for the lung lesion. However, the patient was lost to follow-up. Nine months later, he was diagnosed with stomach cancer based on gastroendoscopic biopsy. illroth II subtotal gastrectomy demonstrated a poorly differentiated tubular adenocarcinoma, limited to the mucosa (T1aN0M0) (Fig. 2). The patient recovered well and received oral chemotherapy. However, his carcinoembryonic antigen (CE) level remained elevated. On a follow-up CT scan, the lung lesion showed increased size ( cm) and greater consolidation (Fig. 1). The patient underwent a right lower lobectomy with subsequent dissection of multiple calcified mediastinal lymph nodes. Grossly, the spec- 396
2 denocarcinoma in dult CCM 397 Fig. 1. Coronal reconstruction images of the initial chest CT scans demonstrate air-cysts with internal fluid in the right lower lobe, suggestive of an adult form of CCM with inflammation (). Seventeen months after the initial scan, the lesion was increased in size and virtually replaced by fluid and consolidation (). Fig. 2. Gastric biopsy reveals poorly differentiated tubular adenocarcinoma in the mucosa. imen had a relatively solid area (70%) with poorly preserved hemorrhagic cystic spaces (Fig. 3). Cystic changes were found in the periphery of the lobe. Histologically, the cysts were lined by pseudostratified ciliated columnar cells with underlying fibrous tissue and smooth muscle, but scant cartilage. This was consistent with a type 1 CCM, based on Stocker s classification (Fig. 4). 5 The bulk of the lesion consisted of tall columnar mucosecretory epithelial cells in bronchioloalveolar and solid patterns, with mucin production, consistent with adenocarcinoma, mixed subtype (Fig. 4, C). lthough the transition from bland columnar epithelial cells to atypical cells was indiscernible, Fig. 3. Gross photograph shows a large well-circumscribed lesion, composed of hemorrhagic spaces and tan white solid glistening components. the cysts adjacent to the typical CCM demonstrated adenocarcinoma involvement (Fig. 4D). Tumor cells were positive for thyroid transcription factor-1 (TTF-1) and cytokeratin 7 (CK7), but negative for cytokeratin 20 (CK20). However, patients with gastric adenocarcinoma have a TTF-1 negative, CK7 negative, and CK20 negative immunophenotype (Fig. 5). The mediastinal lymph nodes showed extensive metastasis. The patient was discharged from the hospital after an uneventful post-operative course, and he has been on chemotherapy with no recurrence during one year of follow-up.
3 398 Jinyoung Yoo Sun Mi Lee Ji Han Jung, et al. C D Fig. 4. The cysts are lined by ciliated pseudostratified columnar epithelium with underlying fibrous tissue and smooth muscle, consistent with type1 CCM. Notice the interspersed goblet cells (). The solid area reveals mucinous bronchioloalveolar carcinoma () and adenocarcinoma with mucin production (C). Malignancy (*) is noted adjacent to the CCM cysts (**) (D). TTF-1 CK7 CK20 TTF-1 CK7 CK20 Fig. 5. On immunohistochemical staining, the gastric cancer is TTF-1(-)/CK7(-)/CK20(-) (), while the lung carcinoma is TTF-1(+)/CK7(+)/ CK20(-) ().
4 denocarcinoma in dult CCM 399 DISCUSSION CCM is characterized by anomalous fetal development of the small airways and distal lung parenchyma, which leads to an adenomatoid proliferation of terminal respiratory structures and cyst formation. 6 Most CCMs are diagnosed and managed within the first two years of life. In rare instances, however, such lesions may remain unrecognized until adulthood. lthough frequently complicated by recurrent infection, 3 adult CCMs may be asymptomatic. Hence, they may be detected only incidentally on routine chest radiography or during a study of a non-pulmonary lesion, as in the present case. Our patient had sought medical attention for his copious sputum. However, he had never undergone a radiologic examination until he suffered ribs fractured in a traffic accident. few patients with (or history of) CCMs have developed carcinomas, usually mucinous Cs. 1,7 This has led to the suspicion of the potential for malignant transformation in CCMs. Our case demonstrated mucinous C, invasive carcinoma, and features of a type 1 CCM in the residual cysts. long with these histological features, the sequential progression of imaging abnormalities provides evidence for tumor development in the setting of CCM. Mani et al. 3 documented a type 1 CCM with a full spectrum of precursor (atypical adenomatous hyperplasia) and neoplastic lesions (C and invasive adenocarcinoma), suggesting the predisposition of type 1 CCMs toward malignancy. Lantuejoul et al. 8 recently noted loss of heterozygosity on analysis of microsatellite alterations and direct sequencing polymerase chain reaction for molecular studies in seven cases of type 1 CCM with associated mucinous proliferation. The mucinous cells were found to share the same differentiation profile with the corresponding mucinous C cells, thus justifying their consideration as C precursors. n earlier study of 22 CCMs also revealed gains in chromosomes 2 and 4 in both atypical goblet cell hyperplasia and carcinoma, but not in respiratory-type surface epithelium or surrounding normal lung tissue. This supports the pre-neoplastic status of goblet cell proliferation in CCM. 2 ll 16 cases of type 1 CCM-related malignancies previously reported in the medical literature were Cs, exclusively mucinous type, with or without invasive carcinoma (5 including the present case vs. 12). 1,3,9 Most patients (11/17, 65%) were adults. Of the five children with available follow-up, one died of disease at 15 years of age, and four were free of disease for a period ranging from 18 months to 16 years. Of the six adult patients with available follow-up, one died of disease at 4 years, and five were free of disease for 3 months to 4 years. There are too few such cases to characterize the differences in prognosis between pediatric and adult patients. However, the age at diagnosis ranged from 6 months to 60 years, with a mean age of 25.2 years, which is much younger compared to the mean age of C diagnosis in the general population (59 years). 10 This supports the fact that carcinoma associated with type 1 CCM usually occurs in adults whose CCMs have not been resected in childhood. We reported a case of type 1 CCM that eventually developed metastatic adenocarcinoma during the surgical delay, in order to emphasize the importance of prompt surgical treatment for adult CCMs. These lesions should be resected as soon as possible to prevent malignant change and progression to invasion. REFERENCES 1. MacSweeney F, Papagiannopoulos K, Goldstraw P, Sheppard MN, Corrin, Nicholson G. n assessment of the expanded classification of congenital cystic adenomatoid malformations and their relationship to malignant transformation. m J Surg Pathol 2003; 27: Stacher E, Ullmann R, Halbwedl I, et al. typical goblet cell hyperplasia in congenital cystic adenomatoid malformation as a possible preneoplasia for pulmonary adenocarcinoma in childhood: a genetic analysis. Hum Pathol 2004; 35: Mani H, Shilo K, Galvin JR, Stocker JT, Franks TJ. Spectrum of precursor and invasive neoplastic lesions in type 1 congenital pulmonary airway malformation: case report and review of the literature. Histopathology 2007; 51: Korol E. The correlation of carcinoma and congenital cystic emphysema of the lungs: report of ten cases. Dis Chest 1953; 23: Stocker JT, Madewell JE, Drake RM. Congenital cystic adenomatoid malformation of the lung: classification and morphologic spectrum. Hum Pathol 1977; 8: Morelli L, Piscioli I, Licci S, Donato S, Catalucci, Del Nonno F. Pulmonary congenital cystic adenomatoid malformation, type I, presenting as a single cyst of the middle lobe in an adult: case report. Diagn Pathol 2007; 2: enjamin DR, Cahill JL. ronchioloalveolar carcinoma of the lung and congenital cystic adenomatoid malformation. m J Clin Pathol 1991; 95: Lantuejoul S, Nicholson G, Sartori G, et al. Mucinous cells in type1 pulmonary congenital cystic adenomatoid malformation as mucinous bronchioloalveolar carcinoma precursors. m J Surg Pathol
5 400 Jinyoung Yoo Sun Mi Lee Ji Han Jung, et al. 2007; 31: West D, Nicholson G, Colquhoun I, Pollock J. ronchioloalveolar carcinoma in congenital cystic adenomatoid malformation of lung. nn Thorac Surg 2007; 83: arsky SH, Cameron R, Osann KE, Tomita D, Holmes EC. Rising incidence of bronchioloalveolar carcinoma and its clinicopathologic features. Cancer 1994; 73:
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