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Squamous cell carcinoma arising in a ciliated hepatic foregut cyst: Case report and literature review
ARTICLE IN PRESS
Pathology – Research and Practice 205 (2009) 498–501 www.elsevier.de/prp
TEACHING CASES
Squamous cell carcinoma arising in a ciliated hepatic foregut cyst: Case report and literature review Xiangsheng Zhanga,, Zhen Wangb, Yanjun Dongc a
Department of Pathology, Binzhou Medical College, Shandong 256603, China Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH 44195, USA c Department of Pathology, Binzhou Medical College Affiliated Hospital, Shandong 256603, China b
Received 3 July 2008; received in revised form 11 November 2008; accepted 1 December 2008
Abstract We report a case of squamous cell carcinoma arising in a ciliated hepatic foregut cyst (CHFC) in the left lobe of the liver in a 60-year-old woman. Gross examination revealed an irregular, partially encapsulated, smooth tumor mass with multiple cystic areas, 3–5 mm in size. Microscopically, the lining of the microcysts was composed of ciliated columnar epithelium with scattered goblet cells. Multiple foci of squamous metaplasia of the columnar epithelium were observed, which showed areas with dysplastic changes and other areas with carcinomatous transformation. Our case also showed an inconspicuous or absent smooth muscle layer. This case suggests that CHFC deserves careful clinical follow-up and differential diagnosis to exclude malignant transformation. Total surgical excision of the cyst is recommended. r 2009 Elsevier GmbH. All rights reserved. Keywords: Liver; Foregut cyst; Squamous cell carcinoma
Introduction Hepatic foregut cyst is an extremely rare, benign, most often solitary and unilocular cystic lesion of the liver arising from remnants of the embryonic foregut, first described by Dr. Friedreich in 1857. As the primitive foregut gives origin to the tracheobronchial tree, the esophagus, and the liver, the common developmental origin may account for the specific histologic features of the presence of pseudostratified, ciliated, mucin-secreting, columnar epithelium in hepatic foregut cyst. Therefore, in 1984, Wheeler and Edmondson [7] first used the term ‘‘ciliated hepatic foregut cyst (CHFC)’’ to describe such a lesion sharing the common Corresponding author. Tel.: +86 543 396 0229.
E-mail address: [email protected] (X. Zhang). 0344-0338/$ - see front matter r 2009 Elsevier GmbH. All rights reserved. doi:10.1016/j.prp.2008.12.003
morphologic pattern with both esophageal and bronchial cysts. Since then, 70 other cases of CHFC have been reported [5], and these have always been considered benign in nature. Recently, however, there have been documented three cases of malignant transformation [1,2,6] in these cysts. Here, we present another case of invasive squamous-cell carcinoma arising from a CHFC in a 60-year-old woman, which is also considered another case of the rare histological variant of CHFC, where the smooth muscle layer is inconspicuous or absent [4].
Case report A 60-year-old woman presented with a 1-month history of vague fullness in the right upper quadrant.
ARTICLE IN PRESS X. Zhang et al. / Pathology – Research and Practice 205 (2009) 498–501
Her medical history was unremarkable. Physical examination demonstrated right-upper-quadrant pain on palpation with guarding but no rebound tenderness or peritoneal signs. Serological neoplastic markers (AFP, CA 19–9, and CEA) as well as hepatitis B and C markers were all negative. Abdominal ultrasonography detected a moderately delineated, avascular, hypoechoic mass of 6 cm in diameter with spotted shadow-free strong echoes located in the medial segment (S4) of the left liver. Computed tomographic scan and magnetic resonance imaging (MRI) confirmed that the mass was subcapsularly located in the left liver. The patient was admitted to our hospital for an exploratory laparotomy. At surgery, a large moderately delineated mass was found in the left liver, with the ventral surface of liver and gallbladder adherent to omentum minus and to the serosal surface of lesser curvature of stomach. Mass blunt separation and enucleation from the liver, along with the gallbladder and partial omentum minus resection, were performed. The patient’s postoperative course was uncomplicated, and at the time of writing this report, she had remained well after 6 months of follow-up.
Pathological findings On gross examination, the resected specimen revealed an irregular, smooth tumor mass measuring 7 6 5 cm3. A cut section showed partially encapsulated, gray-white, solid tumor parenchyma with multiple cystic areas, 3–5 mm in size (Fig. 1). The gallbladder was unremarkable. The entire specimen was routinely processed, and the paraffin-embedded sections were stained with hematoxylin–eosin. Immunohistochemistry was performed using monoclonal antibodies to CK5/6, CK8/18, Syn, CgA, NSE, and somatostatin.
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Fig. 2. Cyst shows characteristic pseudostratified ciliated epithelium and surrounding connective tissue. Hematoxylin and eosin staining, 200.
Microscopic examination showed well or moderately well-differentiated, sheet-like growing invasive squamous cell carcinomas with scattered keratinization cells and keratinizing cysts. Multiple microcysts with different sizes were observed, and the cyst was partially lined by single or pseudostratified columnar epithelium (Fig. 2), which was composed of cylindrical cells or ciliated cells with scattered goblet cells. Multiple foci of squamous metaplasia of the columnar epithelium were observed associated with areas of high-grade dysplasia from which a solid bulk of well-differentiated squamous cell carcinoma was noted (Fig. 3). Some areas of subepithelial connective tissue of the microcysts contained a more organized, glandular-like architecture, which was similar to the bronchial mucosal and submucosal gland in appearance. We also observed that the layer of smooth muscle cells in the cyst wall was inconspicuous or absent, and an outer fibrous capsule extended into the carcinoma area. The gallbladder sections showed chronic cholecystitis. Immunohistochemical staining supported the above microscopic findings and showed focal CK5/6 staining with carcinoma and keratinizing cysts cells, while the lining columnar epithelium of the cysts was CK8/18-positive. Syn, CgA, NSE, and somatostatin were all negative.
Discussion
Fig. 1. Surgical resection specimen. Solid tumor mass with multilocular hepatic cysts appearance.
The foregut extends from the oropharynx to the hepatic diverticulum. The oropharynx, esophagus, stomach, duodenum, liver, gallbladder, pancreas, tracheobronchic tree, and lungs develop as a consequence of branching of the foregut [1]. Congenital cysts, giving rise to bronchogenic or esophageal cysts, appear to be caused by evagination from the different portions of the embryologic foregut [6]. CHFC is an extremely rare
ARTICLE IN PRESS 500
X. Zhang et al. / Pathology – Research and Practice 205 (2009) 498–501
Fig. 3. The left picture shows squamous dysplasia with squamous carcinoma below; the middle one shows squamous metaplasia and dysplasia; and the right one shows the characteristic pseudostratified ciliated epithelium. Hematoxylin and eosin staining, 200.
Table 1.
Summary of four cases of squamous cell carcinoma arising from a CHFC in the literature.
Age/sex
Ref. no.
Year
Clinical presentation
Pathological features
Outcome
51/M
[1]
1999
1-month epigastric pain
Died after 2 months
21/M
[5]
2002
6-month vague fullness, mild pain, fever and a weight loss
40/F
[7]
2002
Right upper quadrant pain with back and thoracic pain
60/F
Our patient
2007
1-month vague fullness in the right upper quadrant
Cyst occupying subhepatic space, 12.0 10.0 0.1–0.7 cm Cyst located in segments V and VI of the right liver, 10 cm in the largest diameter Cyst located in segments V of the right liver, 13 9 7 0.3-0.4 cm Tumor mass located in segments IV of the left liver, with multiple cystic areas, 3–5 mm in size
cystic malformation of the liver that probably arises from the remnants of the primordium of the hepatic diverticulum or an independent bud of the nearby enteric foregut in a way similar to that of bronchogenic and esophageal cysts [5]. The majority of patients with CHFC are asymptomatic, and the cyst is usually an incidental finding during abdominal imaging studies, surgical exploration, or at autopsy [3]. It tends to occur more frequently in the medial segment of the left hepatic lobe of middle-aged males. The wall of CHFC is composed of four layers: an inner ciliated pseudostratified columnar epithelium with scattered goblet cells, loose subepithelial connective tissue, several layers of smooth muscle cells, and an outer fibrous capsule [2]. In our case, the solid tumor mass with multilocular hepatic cysts appearance, together with the inconspicuous or absent smooth muscle layer, however, makes our case unique compared with the majority of other reported cases. CHFC have always been considered benign nonneoplastic lesions; however, three cases with malignant
Died after 9 months
Records lost
Alive after 6 months of follow-up
transformation have been documented in the English literature, and the case reported here is another case of squamous cell carcinoma arising from a CHFC, as shown in Table 1. It is considered that squamous carcinoma of CHFC might develop in a context of inflammation like that in biliary cyst. The differential diagnosis of a large hepatic cyst includes simple cyst, hydatid cyst, hepatobiliary cystadenoma, and cystadenocarcinoma. Therefore, detailed imaging investigations and pathologic evaluations were necessary to render the correct diagnosis of this liver lesion and to exclude malignancy. Most studies agree that total surgical excision of the cyst is necessary. In conclusion, we present another case of squamous cell carcinoma arising in a CHFC in the left lobe of the liver in a 60-year-old woman. Our case showed a solid tumor mass with multilocular hepatic cysts appearance and inconspicuous or absent smooth muscle layer. CHFC deserves careful clinical follow-up and differential diagnosis, as malignant transformation is possible. Total surgical excision of the cyst is recommended.
ARTICLE IN PRESS X. Zhang et al. / Pathology – Research and Practice 205 (2009) 498–501
References [1] A.S. de Lajarte-Thirouard, N. Rioux-Leclercq, K. Boudjema, et al., Squamous cell carcinoma arising in a hepatic forgut cyst, Pathol. Res. Pract. 198 (10) (2002) 697–700. [2] A. Furlanetto, A.P. Dei Tos, Squamous cell carcinoma arising in a ciliated hepatic foregut cyst, Virchows Arch. 441 (3) (2002) 296–298. [3] J.D. Jakowski, J.G. Lucas, S. Seth, et al., Ciliated hepatic foregut cyst: a rare but increasingly reported liver cyst, Ann. Diagn. Pathol. 8 (6) (2004) 342–346.
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[4] Y. Sato, S. Kitagawa, Y. Zen, et al., Ciliated hepatic cyst without smooth muscle layer: a variant of ciliated hepatic foregut cyst?, Pathol. Int. 56 (6) (2006) 340–344. [5] D.J. Vick, Z.D. Goodman, M.T. Deavers, et al., Ciliated hepatic foregut cyst: a study of six cases and review of the literature, Am. J. Surg. Pathol. 23 (6) (1999) 671–677. [6] D.J. Vick, Z.D. Goodman, K.G. Ishak, Squamous cell carcinoma arising in a ciliated hepatic foregut cyst, Arch. Pathol. Lab. Med. 123 (11) (1999) 1115–1117. [7] D.A. Wheeler, H.A. Edmondson, Ciliated hepatic foregut cyst, Am. J. Surg. Pathol. 8 (6) (1984) 467–470.
Pathology – Research and Practice 205 (2009) 498–501 www.elsevier.de/prp
TEACHING CASES
Squamous cell carcinoma arising in a ciliated hepatic foregut cyst: Case report and literature review Xiangsheng Zhanga,, Zhen Wangb, Yanjun Dongc a
Department of Pathology, Binzhou Medical College, Shandong 256603, China Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH 44195, USA c Department of Pathology, Binzhou Medical College Affiliated Hospital, Shandong 256603, China b
Received 3 July 2008; received in revised form 11 November 2008; accepted 1 December 2008
Abstract We report a case of squamous cell carcinoma arising in a ciliated hepatic foregut cyst (CHFC) in the left lobe of the liver in a 60-year-old woman. Gross examination revealed an irregular, partially encapsulated, smooth tumor mass with multiple cystic areas, 3–5 mm in size. Microscopically, the lining of the microcysts was composed of ciliated columnar epithelium with scattered goblet cells. Multiple foci of squamous metaplasia of the columnar epithelium were observed, which showed areas with dysplastic changes and other areas with carcinomatous transformation. Our case also showed an inconspicuous or absent smooth muscle layer. This case suggests that CHFC deserves careful clinical follow-up and differential diagnosis to exclude malignant transformation. Total surgical excision of the cyst is recommended. r 2009 Elsevier GmbH. All rights reserved. Keywords: Liver; Foregut cyst; Squamous cell carcinoma
Introduction Hepatic foregut cyst is an extremely rare, benign, most often solitary and unilocular cystic lesion of the liver arising from remnants of the embryonic foregut, first described by Dr. Friedreich in 1857. As the primitive foregut gives origin to the tracheobronchial tree, the esophagus, and the liver, the common developmental origin may account for the specific histologic features of the presence of pseudostratified, ciliated, mucin-secreting, columnar epithelium in hepatic foregut cyst. Therefore, in 1984, Wheeler and Edmondson [7] first used the term ‘‘ciliated hepatic foregut cyst (CHFC)’’ to describe such a lesion sharing the common Corresponding author. Tel.: +86 543 396 0229.
E-mail address: [email protected] (X. Zhang). 0344-0338/$ - see front matter r 2009 Elsevier GmbH. All rights reserved. doi:10.1016/j.prp.2008.12.003
morphologic pattern with both esophageal and bronchial cysts. Since then, 70 other cases of CHFC have been reported [5], and these have always been considered benign in nature. Recently, however, there have been documented three cases of malignant transformation [1,2,6] in these cysts. Here, we present another case of invasive squamous-cell carcinoma arising from a CHFC in a 60-year-old woman, which is also considered another case of the rare histological variant of CHFC, where the smooth muscle layer is inconspicuous or absent [4].
Case report A 60-year-old woman presented with a 1-month history of vague fullness in the right upper quadrant.
ARTICLE IN PRESS X. Zhang et al. / Pathology – Research and Practice 205 (2009) 498–501
Her medical history was unremarkable. Physical examination demonstrated right-upper-quadrant pain on palpation with guarding but no rebound tenderness or peritoneal signs. Serological neoplastic markers (AFP, CA 19–9, and CEA) as well as hepatitis B and C markers were all negative. Abdominal ultrasonography detected a moderately delineated, avascular, hypoechoic mass of 6 cm in diameter with spotted shadow-free strong echoes located in the medial segment (S4) of the left liver. Computed tomographic scan and magnetic resonance imaging (MRI) confirmed that the mass was subcapsularly located in the left liver. The patient was admitted to our hospital for an exploratory laparotomy. At surgery, a large moderately delineated mass was found in the left liver, with the ventral surface of liver and gallbladder adherent to omentum minus and to the serosal surface of lesser curvature of stomach. Mass blunt separation and enucleation from the liver, along with the gallbladder and partial omentum minus resection, were performed. The patient’s postoperative course was uncomplicated, and at the time of writing this report, she had remained well after 6 months of follow-up.
Pathological findings On gross examination, the resected specimen revealed an irregular, smooth tumor mass measuring 7 6 5 cm3. A cut section showed partially encapsulated, gray-white, solid tumor parenchyma with multiple cystic areas, 3–5 mm in size (Fig. 1). The gallbladder was unremarkable. The entire specimen was routinely processed, and the paraffin-embedded sections were stained with hematoxylin–eosin. Immunohistochemistry was performed using monoclonal antibodies to CK5/6, CK8/18, Syn, CgA, NSE, and somatostatin.
499
Fig. 2. Cyst shows characteristic pseudostratified ciliated epithelium and surrounding connective tissue. Hematoxylin and eosin staining, 200.
Microscopic examination showed well or moderately well-differentiated, sheet-like growing invasive squamous cell carcinomas with scattered keratinization cells and keratinizing cysts. Multiple microcysts with different sizes were observed, and the cyst was partially lined by single or pseudostratified columnar epithelium (Fig. 2), which was composed of cylindrical cells or ciliated cells with scattered goblet cells. Multiple foci of squamous metaplasia of the columnar epithelium were observed associated with areas of high-grade dysplasia from which a solid bulk of well-differentiated squamous cell carcinoma was noted (Fig. 3). Some areas of subepithelial connective tissue of the microcysts contained a more organized, glandular-like architecture, which was similar to the bronchial mucosal and submucosal gland in appearance. We also observed that the layer of smooth muscle cells in the cyst wall was inconspicuous or absent, and an outer fibrous capsule extended into the carcinoma area. The gallbladder sections showed chronic cholecystitis. Immunohistochemical staining supported the above microscopic findings and showed focal CK5/6 staining with carcinoma and keratinizing cysts cells, while the lining columnar epithelium of the cysts was CK8/18-positive. Syn, CgA, NSE, and somatostatin were all negative.
Discussion
Fig. 1. Surgical resection specimen. Solid tumor mass with multilocular hepatic cysts appearance.
The foregut extends from the oropharynx to the hepatic diverticulum. The oropharynx, esophagus, stomach, duodenum, liver, gallbladder, pancreas, tracheobronchic tree, and lungs develop as a consequence of branching of the foregut [1]. Congenital cysts, giving rise to bronchogenic or esophageal cysts, appear to be caused by evagination from the different portions of the embryologic foregut [6]. CHFC is an extremely rare
ARTICLE IN PRESS 500
X. Zhang et al. / Pathology – Research and Practice 205 (2009) 498–501
Fig. 3. The left picture shows squamous dysplasia with squamous carcinoma below; the middle one shows squamous metaplasia and dysplasia; and the right one shows the characteristic pseudostratified ciliated epithelium. Hematoxylin and eosin staining, 200.
Table 1.
Summary of four cases of squamous cell carcinoma arising from a CHFC in the literature.
Age/sex
Ref. no.
Year
Clinical presentation
Pathological features
Outcome
51/M
[1]
1999
1-month epigastric pain
Died after 2 months
21/M
[5]
2002
6-month vague fullness, mild pain, fever and a weight loss
40/F
[7]
2002
Right upper quadrant pain with back and thoracic pain
60/F
Our patient
2007
1-month vague fullness in the right upper quadrant
Cyst occupying subhepatic space, 12.0 10.0 0.1–0.7 cm Cyst located in segments V and VI of the right liver, 10 cm in the largest diameter Cyst located in segments V of the right liver, 13 9 7 0.3-0.4 cm Tumor mass located in segments IV of the left liver, with multiple cystic areas, 3–5 mm in size
cystic malformation of the liver that probably arises from the remnants of the primordium of the hepatic diverticulum or an independent bud of the nearby enteric foregut in a way similar to that of bronchogenic and esophageal cysts [5]. The majority of patients with CHFC are asymptomatic, and the cyst is usually an incidental finding during abdominal imaging studies, surgical exploration, or at autopsy [3]. It tends to occur more frequently in the medial segment of the left hepatic lobe of middle-aged males. The wall of CHFC is composed of four layers: an inner ciliated pseudostratified columnar epithelium with scattered goblet cells, loose subepithelial connective tissue, several layers of smooth muscle cells, and an outer fibrous capsule [2]. In our case, the solid tumor mass with multilocular hepatic cysts appearance, together with the inconspicuous or absent smooth muscle layer, however, makes our case unique compared with the majority of other reported cases. CHFC have always been considered benign nonneoplastic lesions; however, three cases with malignant
Died after 9 months
Records lost
Alive after 6 months of follow-up
transformation have been documented in the English literature, and the case reported here is another case of squamous cell carcinoma arising from a CHFC, as shown in Table 1. It is considered that squamous carcinoma of CHFC might develop in a context of inflammation like that in biliary cyst. The differential diagnosis of a large hepatic cyst includes simple cyst, hydatid cyst, hepatobiliary cystadenoma, and cystadenocarcinoma. Therefore, detailed imaging investigations and pathologic evaluations were necessary to render the correct diagnosis of this liver lesion and to exclude malignancy. Most studies agree that total surgical excision of the cyst is necessary. In conclusion, we present another case of squamous cell carcinoma arising in a CHFC in the left lobe of the liver in a 60-year-old woman. Our case showed a solid tumor mass with multilocular hepatic cysts appearance and inconspicuous or absent smooth muscle layer. CHFC deserves careful clinical follow-up and differential diagnosis, as malignant transformation is possible. Total surgical excision of the cyst is recommended.
ARTICLE IN PRESS X. Zhang et al. / Pathology – Research and Practice 205 (2009) 498–501
References [1] A.S. de Lajarte-Thirouard, N. Rioux-Leclercq, K. Boudjema, et al., Squamous cell carcinoma arising in a hepatic forgut cyst, Pathol. Res. Pract. 198 (10) (2002) 697–700. [2] A. Furlanetto, A.P. Dei Tos, Squamous cell carcinoma arising in a ciliated hepatic foregut cyst, Virchows Arch. 441 (3) (2002) 296–298. [3] J.D. Jakowski, J.G. Lucas, S. Seth, et al., Ciliated hepatic foregut cyst: a rare but increasingly reported liver cyst, Ann. Diagn. Pathol. 8 (6) (2004) 342–346.
501
[4] Y. Sato, S. Kitagawa, Y. Zen, et al., Ciliated hepatic cyst without smooth muscle layer: a variant of ciliated hepatic foregut cyst?, Pathol. Int. 56 (6) (2006) 340–344. [5] D.J. Vick, Z.D. Goodman, M.T. Deavers, et al., Ciliated hepatic foregut cyst: a study of six cases and review of the literature, Am. J. Surg. Pathol. 23 (6) (1999) 671–677. [6] D.J. Vick, Z.D. Goodman, K.G. Ishak, Squamous cell carcinoma arising in a ciliated hepatic foregut cyst, Arch. Pathol. Lab. Med. 123 (11) (1999) 1115–1117. [7] D.A. Wheeler, H.A. Edmondson, Ciliated hepatic foregut cyst, Am. J. Surg. Pathol. 8 (6) (1984) 467–470.