Path. Res. Pract. 186, 223-227 (1990)
The Histogenesis of the Microinvasive Basal Cell Carcinoma of the Esophagus
c. A. Rubio and Fu-Shen Liu
Department of Pathology, Cancer Institute, Stockholm, Sweden, Chinese Academy of Medical Sciences Beijing, China
SUMMARY
The spectrum of histological events ranging from basal cell dysplasia to microinvasive basal cell carcinoma was traced in four of 123 resected esophagi from Chinese subjects 7 . Atypical basal cells could be seen in some areas impinging and pushing, and in other areas invading the underlying stroma. The periphery cell layers in some invading clusters retained the characteristics ofthe basal cells with palisaded arrangement. In non-invading areas, the intermediate and superficial cells had normal cell maturation with normal nuclei, a feature which distinguishes basal cell intraepithelial dysplasia from squamous cell intraepithelial dysplasia of the esophagus. Similar histological events have been demonstrated in experimental animals fed with an esophagotropic carcinogen.
Introduction Invasive squamous carcinoma of the esophagus has been histologically divided into various groups by different authors. The WHO classificationS recognizes well, moderately, and poorly differentiated squamous carcinoma. Among undifferentiated carcinomas, some are associated with hormone production. Mandard et al.4, and Troncoso and Ridell 13 also divided invasive squamous carcinoma according to WHO. Troncoso and Riddell 13 recognized a small cell carcinoma which was subdivided into a small cell variant of squamous carcinoma and an oat-cell like tumor (" APUDoma") and a combination of both. Liu and Zhou3 divided invasive squamous carcinoma of the esophagus into three categories: grade I corresponds to well differentiated large cell tumors, grade II shows moderate differentiation, and grade III is composed of small sized, nonkeratinized tumor cells. Among the poorly differentiated squamous cell carcinomas of the esophagus, several authors consider basal cell carcinomas 1,3,12. In this respect, Suzuki and Nagayo12 reported 4.5% basal cell carcinomas among 616 primary esophageal malignant tumors other than squamous cell carcinoma and Lin et al. 2 2.2 % basal epithelial cell © 1990 by Gustav Fischet Verlag, Stuttgart
carcinomatous changes at the margin of 719 resected esophageal specimens for carcinoma. Day 1 describes among the poorly differentiated squamous cell carcinomas of the esophagus one with "basal cell" features which may be apparent in some areas of the tumor. Thus, many authors recognize basal cell carcinoma of the esophagus as an histopathological group. Stinson and Reznik ll stated, however, that a basal cell type carcinoma neither resembled nor behaved like epidermal basal cell carcinomas. According to those authors, basal cell carcinomas do not arise from persisting remnants of the basal layer or the embryonic esophagus and are more appropriately termed undifferentiated carcinomas. Thus, in the literature, there is a discrepancy regarding the identity of the basal cell carcinoma of the esophagus. While reviewing resected esophageal specimens with early esophageal cancer from the Linxian county, and from Beijing, China 7, we found four cases arising in the basal zone of the squamous epithelium of the esophagus. The sequence of histological events in this communication will demonstrate the histogenesis of the basal cell carcinoma of the esophagus, a feature not previously presented in the literature. 0344-0338/90/0186-0223$3.50/0
224 . C. A. Rubio and Liu Fu-shen
Material and Methods
Of the 123 resected esophagi, 76 had microinvasive squamous cell carcinoma7, 4 microinvasive basal cell carcinomas, Slow grade squamous cell dysplasias7 and the remaining 38 high-grade squamous cell dysplasias 7• Thus,
the four cases of microinvasive basal cell carcinoma herein reported were found among 80 resected esophagi with microinvasive carcinoma (i.e. 5.3%). The series of histological events found in the four cases with basal cell carcinoma are illustrated in Figs. 1-6. Adjacent to those four tumors, the basal aspect of the squamous esophageal epithelium was seen populated by atypical small cells with anisokaryosis and anisochromatosis. The intermediate and superficial cell layers, however, showed normal cell maturation with normal nuclei (d. Fig. 1-4). The atypical basal cells were also seen pushing the underlying stroma (d. Fig. 1-3). The invasive carcinoma was found to originate at the basal aspect of the dysplastic epithelium (Fig. 4). The outermost tumor cells in some tumor nests retained the histological characteristics of basal cells with obvious cell palisading (Figs. 5 and 6). One of the four microinvasive basal cell carcinomas of the esophagus herein reported invaded the muscularis mucosae and the remaining three the submucosa. In all four cases, the series of histologic events described and illustrated above were present.
Fig. 1. Basal cell hyperplasia (dysplasia?) of the human esophagus. Note normal squamous epithelium on suprabasal layers
Fig. 2. Basal cell dysplasia of the human esophagus. Suprabasal layers show normal intermediate and superficial squamous cells
A total of 123 resected esophagi having either non-invasive neoplastic lesions and/or early esophagus cancer were reviewed. The patients had been operated at the Cancer Institute, Linxian, Henan Province (86 patients) or at the Cancer Institute, Chinese Academy of Medical Sciences, Beijing (37 patients). The sections were made lengthwise throughout the esophagus and were divided into blocks measuring about 4xO.5 em. The classification of the non-invasive squamous neoplastic lesions as well as of the microinvasive carcinomas in 119 of the 123 cases has been presented elsewhere? The remaining - not previously reported - four cases having microinvasive basal cell carcinoma of the esophagus are described and illustrated below.
Results
I'
(H&E 250x).
(H&E 250x).
Basal Cell Carcinoma of the Esophagus . 225 .... Fig. 3. Questionable invasion of the stroma by atypical basal cells. Human esophagus. Note normal suprabasal squamous intermediate cells (H&E 250x).
Fig. 5. Microinvasive basal cell carcinoma. Human esophagus. Note basal cell palisading at arrows and duets from the esophageal glands proper (at arrowheads) (H&E lOOx).
.... Fig. 4. Detail showing atypical basal cells in an area with questionable invasion. Basal cell palisading at arrows. Note normal suprabasal intermediate cells (H&E 400x).
226 . C. A. Rubio and Liu Fu-shen
Fig. 6. Invading epithelial clusters showing palisading arrangement of the basal tumor cells at arrows (H&E 250x).
Discussion Several authors have separated "basal cell carcinoma" as a special histologic type of squamous carcinoma of the esophagus1,3. Suzuki and Nagayo12 considered "basal cell carcinomas" of the esophagus as a separate group (from squamous cell carcinomas in that organ). So, there is much discussion regarding the histogenesis of these tumors. In fact, histologic evidence for their basal origin has never, as yet, been demonstrated. In the present communication, we traced the series of histological steps preceding invasive basal cell carcinoma of the esophagus. Atypical basal cells could be seen in some areas impinging and pushing, and in other areas invading the underlying stroma. The tumor
Fig.7a-b. Two areas with basal cell dysplasia in the mouse ~ esophagus after treatment with diethylnitrosamine. Note basal cell dysplasia with normal squamous epithelium in the suprabasal layer. In addition, a basal cell carcinoma in Fig. 7a (top left, H&E 250x) and in Fig. (H&E lOOx).
Basal Cell Carcinoma of the Esophagus' 227
cells in some invading clusters retained the characteristics of the basal cells with a palisaded arrangement. The histological characteristics of adjacent intraepithelial alterations in the four cases presented a contrast with the histological appearance of squamous cell dysplasia of the esophagus7. In fact, in the squamous cell dysplasias of the esophagus, cells with atypical nuclei occupy the entire epithelial thickness while in basal cell dysplasia, the nuclei of intermediate and/or superficial cell layers have a normal morphologic appearance. Moreover, in clusters with invasive squamous cell carcinoma, the outermost located tumor cells appear flat and parallel to the surrounding stroma7 while in basal cell carcinoma, the outermost tumor cells often adopt a palisaded pattern. In conclusion, the occurrence of palisading tumor cells in invading clusters together with basal cell dysplasia in the adjacent squamous epithelium should strongly raise the suspicion of an epithelial carcinoma of basal cell origin. At this point, it should be mentioned that similar histological changes can be observed antedating basal cell carcinomas of the esophagus in mice 9,11. Those series of events have been found, serendipitously, after treating mice 9 (Figs. 7 a and b) or rats 11 with diethylnitrosamine, a potent esophagotropic carcinogen. Acknowledgement This study was supported by grants from the Chinese Academy of Medical Sciences.
References 1 Day DW (1986) Biopsy Pathology of the Oesophagus, Stomach and Duodenum. Chapman and Hall Medical, London, p53
2 Lin X, Wu X, Che B, Wu Y (1986) Significance of residual tumor at the esophageal stump after resection for carcinoma. Sem Surg Oncol 2: 257-262 3 Liu FS and Zhou CN (1984) Pathology of carcinoma of the esophagus. In: Huang GJ and K'ai WY (Eds.) Carcinoma of the Esophagus and Gastric Cardia, pp 78-116. Springer-Verlag, Berlin 4 Mandard AM, Marnay J, Gignoux M, Segol P, Blanc L, Ollivier JM, Borel Band Mandard JC (1984) Cancer of the esophagus and associated lesions: Detailed pathologc study of 100 esophagectomy specimens, Hum Pathol15: 660-669. 5 Oota Kand Sobin LH (1977) Histological Typing of Gastric and Oesophageal Tumors. World Health Organization, Geneva 6 Pozharisski KM (1973) Tumours of the oesophagus. In: Turnsov VS (Ed.) Pathology of Tumors in Laboratory Animals. Vol. 1, Tumours of the Rat, pp 87-94. IARC Scientific Publications 5 7 Rubio CA, Liu FS and Zhao HZ (1989) Histological classification of intraepithelial neoplasias and microinvasive squamous carcinoma of the esophagus. Am J Surgic Pathol13: 685-690 8 Rubio CA, Auer GU, Kato Y and Liu FS (1988) DNA profiles in dysplasia and carcinoma of the human esophagus. Anal Quant Cytol HistollO: 207-210 9 Rubio CA (1985) Experimental models. In: DeMeester TR and Levin B (Eds.) Cancer of the Esophagus, pp 21-42. Grune & Stratton, New York 10 Sato E, Mukada T and Sasano N (1982) Dysplasia as related to oesophageal carcinoma in Japan. In: CJ Pfeiffer (Ed.) Cancer of the Esophagus, vol. 1, pp 126-140. CRC Press, Florida 11 Stinson SF and Reznik G (1982) Comparative pathology of experimental esophageal carcinoma. In: CJ Pfeiffer (Ed.) Cancer of the Esophagus, vol. II, pp 140-164. CRC Press, Florida 12 Suzuki Hand Nagayo T (1980) Primary tumors of the esophagus other than squamous cell carcinoma - Histologic classification and statistics in the surgical and autopsied materials in Japan. Int Adv Surg Oncol3: 73-109 13 Troncoso Pand Riddell RH (1985) Pathology. In: DeMeester TR and Levin B (Eds.) Cancer of the Esophagus, pp 89-118. Grune & Stratton, New York
Received February 21, 1989 . Accepted in revised form August 31, 1989
Key words: Esophagus - Microinvasive basal cell carcinoma - Squamous carcinoma Dr. C. A. Rubio, Department of Pathology, Karolinska Institute, S-104 01 Stockholm, Sweden
The Histogenesis of the Microinvasive Basal Cell Carcinoma of the Esophagus
c. A. Rubio and Fu-Shen Liu
Department of Pathology, Cancer Institute, Stockholm, Sweden, Chinese Academy of Medical Sciences Beijing, China
SUMMARY
The spectrum of histological events ranging from basal cell dysplasia to microinvasive basal cell carcinoma was traced in four of 123 resected esophagi from Chinese subjects 7 . Atypical basal cells could be seen in some areas impinging and pushing, and in other areas invading the underlying stroma. The periphery cell layers in some invading clusters retained the characteristics ofthe basal cells with palisaded arrangement. In non-invading areas, the intermediate and superficial cells had normal cell maturation with normal nuclei, a feature which distinguishes basal cell intraepithelial dysplasia from squamous cell intraepithelial dysplasia of the esophagus. Similar histological events have been demonstrated in experimental animals fed with an esophagotropic carcinogen.
Introduction Invasive squamous carcinoma of the esophagus has been histologically divided into various groups by different authors. The WHO classificationS recognizes well, moderately, and poorly differentiated squamous carcinoma. Among undifferentiated carcinomas, some are associated with hormone production. Mandard et al.4, and Troncoso and Ridell 13 also divided invasive squamous carcinoma according to WHO. Troncoso and Riddell 13 recognized a small cell carcinoma which was subdivided into a small cell variant of squamous carcinoma and an oat-cell like tumor (" APUDoma") and a combination of both. Liu and Zhou3 divided invasive squamous carcinoma of the esophagus into three categories: grade I corresponds to well differentiated large cell tumors, grade II shows moderate differentiation, and grade III is composed of small sized, nonkeratinized tumor cells. Among the poorly differentiated squamous cell carcinomas of the esophagus, several authors consider basal cell carcinomas 1,3,12. In this respect, Suzuki and Nagayo12 reported 4.5% basal cell carcinomas among 616 primary esophageal malignant tumors other than squamous cell carcinoma and Lin et al. 2 2.2 % basal epithelial cell © 1990 by Gustav Fischet Verlag, Stuttgart
carcinomatous changes at the margin of 719 resected esophageal specimens for carcinoma. Day 1 describes among the poorly differentiated squamous cell carcinomas of the esophagus one with "basal cell" features which may be apparent in some areas of the tumor. Thus, many authors recognize basal cell carcinoma of the esophagus as an histopathological group. Stinson and Reznik ll stated, however, that a basal cell type carcinoma neither resembled nor behaved like epidermal basal cell carcinomas. According to those authors, basal cell carcinomas do not arise from persisting remnants of the basal layer or the embryonic esophagus and are more appropriately termed undifferentiated carcinomas. Thus, in the literature, there is a discrepancy regarding the identity of the basal cell carcinoma of the esophagus. While reviewing resected esophageal specimens with early esophageal cancer from the Linxian county, and from Beijing, China 7, we found four cases arising in the basal zone of the squamous epithelium of the esophagus. The sequence of histological events in this communication will demonstrate the histogenesis of the basal cell carcinoma of the esophagus, a feature not previously presented in the literature. 0344-0338/90/0186-0223$3.50/0
224 . C. A. Rubio and Liu Fu-shen
Material and Methods
Of the 123 resected esophagi, 76 had microinvasive squamous cell carcinoma7, 4 microinvasive basal cell carcinomas, Slow grade squamous cell dysplasias7 and the remaining 38 high-grade squamous cell dysplasias 7• Thus,
the four cases of microinvasive basal cell carcinoma herein reported were found among 80 resected esophagi with microinvasive carcinoma (i.e. 5.3%). The series of histological events found in the four cases with basal cell carcinoma are illustrated in Figs. 1-6. Adjacent to those four tumors, the basal aspect of the squamous esophageal epithelium was seen populated by atypical small cells with anisokaryosis and anisochromatosis. The intermediate and superficial cell layers, however, showed normal cell maturation with normal nuclei (d. Fig. 1-4). The atypical basal cells were also seen pushing the underlying stroma (d. Fig. 1-3). The invasive carcinoma was found to originate at the basal aspect of the dysplastic epithelium (Fig. 4). The outermost tumor cells in some tumor nests retained the histological characteristics of basal cells with obvious cell palisading (Figs. 5 and 6). One of the four microinvasive basal cell carcinomas of the esophagus herein reported invaded the muscularis mucosae and the remaining three the submucosa. In all four cases, the series of histologic events described and illustrated above were present.
Fig. 1. Basal cell hyperplasia (dysplasia?) of the human esophagus. Note normal squamous epithelium on suprabasal layers
Fig. 2. Basal cell dysplasia of the human esophagus. Suprabasal layers show normal intermediate and superficial squamous cells
A total of 123 resected esophagi having either non-invasive neoplastic lesions and/or early esophagus cancer were reviewed. The patients had been operated at the Cancer Institute, Linxian, Henan Province (86 patients) or at the Cancer Institute, Chinese Academy of Medical Sciences, Beijing (37 patients). The sections were made lengthwise throughout the esophagus and were divided into blocks measuring about 4xO.5 em. The classification of the non-invasive squamous neoplastic lesions as well as of the microinvasive carcinomas in 119 of the 123 cases has been presented elsewhere? The remaining - not previously reported - four cases having microinvasive basal cell carcinoma of the esophagus are described and illustrated below.
Results
I'
(H&E 250x).
(H&E 250x).
Basal Cell Carcinoma of the Esophagus . 225 .... Fig. 3. Questionable invasion of the stroma by atypical basal cells. Human esophagus. Note normal suprabasal squamous intermediate cells (H&E 250x).
Fig. 5. Microinvasive basal cell carcinoma. Human esophagus. Note basal cell palisading at arrows and duets from the esophageal glands proper (at arrowheads) (H&E lOOx).
.... Fig. 4. Detail showing atypical basal cells in an area with questionable invasion. Basal cell palisading at arrows. Note normal suprabasal intermediate cells (H&E 400x).
226 . C. A. Rubio and Liu Fu-shen
Fig. 6. Invading epithelial clusters showing palisading arrangement of the basal tumor cells at arrows (H&E 250x).
Discussion Several authors have separated "basal cell carcinoma" as a special histologic type of squamous carcinoma of the esophagus1,3. Suzuki and Nagayo12 considered "basal cell carcinomas" of the esophagus as a separate group (from squamous cell carcinomas in that organ). So, there is much discussion regarding the histogenesis of these tumors. In fact, histologic evidence for their basal origin has never, as yet, been demonstrated. In the present communication, we traced the series of histological steps preceding invasive basal cell carcinoma of the esophagus. Atypical basal cells could be seen in some areas impinging and pushing, and in other areas invading the underlying stroma. The tumor
Fig.7a-b. Two areas with basal cell dysplasia in the mouse ~ esophagus after treatment with diethylnitrosamine. Note basal cell dysplasia with normal squamous epithelium in the suprabasal layer. In addition, a basal cell carcinoma in Fig. 7a (top left, H&E 250x) and in Fig. (H&E lOOx).
Basal Cell Carcinoma of the Esophagus' 227
cells in some invading clusters retained the characteristics of the basal cells with a palisaded arrangement. The histological characteristics of adjacent intraepithelial alterations in the four cases presented a contrast with the histological appearance of squamous cell dysplasia of the esophagus7. In fact, in the squamous cell dysplasias of the esophagus, cells with atypical nuclei occupy the entire epithelial thickness while in basal cell dysplasia, the nuclei of intermediate and/or superficial cell layers have a normal morphologic appearance. Moreover, in clusters with invasive squamous cell carcinoma, the outermost located tumor cells appear flat and parallel to the surrounding stroma7 while in basal cell carcinoma, the outermost tumor cells often adopt a palisaded pattern. In conclusion, the occurrence of palisading tumor cells in invading clusters together with basal cell dysplasia in the adjacent squamous epithelium should strongly raise the suspicion of an epithelial carcinoma of basal cell origin. At this point, it should be mentioned that similar histological changes can be observed antedating basal cell carcinomas of the esophagus in mice 9,11. Those series of events have been found, serendipitously, after treating mice 9 (Figs. 7 a and b) or rats 11 with diethylnitrosamine, a potent esophagotropic carcinogen. Acknowledgement This study was supported by grants from the Chinese Academy of Medical Sciences.
References 1 Day DW (1986) Biopsy Pathology of the Oesophagus, Stomach and Duodenum. Chapman and Hall Medical, London, p53
2 Lin X, Wu X, Che B, Wu Y (1986) Significance of residual tumor at the esophageal stump after resection for carcinoma. Sem Surg Oncol 2: 257-262 3 Liu FS and Zhou CN (1984) Pathology of carcinoma of the esophagus. In: Huang GJ and K'ai WY (Eds.) Carcinoma of the Esophagus and Gastric Cardia, pp 78-116. Springer-Verlag, Berlin 4 Mandard AM, Marnay J, Gignoux M, Segol P, Blanc L, Ollivier JM, Borel Band Mandard JC (1984) Cancer of the esophagus and associated lesions: Detailed pathologc study of 100 esophagectomy specimens, Hum Pathol15: 660-669. 5 Oota Kand Sobin LH (1977) Histological Typing of Gastric and Oesophageal Tumors. World Health Organization, Geneva 6 Pozharisski KM (1973) Tumours of the oesophagus. In: Turnsov VS (Ed.) Pathology of Tumors in Laboratory Animals. Vol. 1, Tumours of the Rat, pp 87-94. IARC Scientific Publications 5 7 Rubio CA, Liu FS and Zhao HZ (1989) Histological classification of intraepithelial neoplasias and microinvasive squamous carcinoma of the esophagus. Am J Surgic Pathol13: 685-690 8 Rubio CA, Auer GU, Kato Y and Liu FS (1988) DNA profiles in dysplasia and carcinoma of the human esophagus. Anal Quant Cytol HistollO: 207-210 9 Rubio CA (1985) Experimental models. In: DeMeester TR and Levin B (Eds.) Cancer of the Esophagus, pp 21-42. Grune & Stratton, New York 10 Sato E, Mukada T and Sasano N (1982) Dysplasia as related to oesophageal carcinoma in Japan. In: CJ Pfeiffer (Ed.) Cancer of the Esophagus, vol. 1, pp 126-140. CRC Press, Florida 11 Stinson SF and Reznik G (1982) Comparative pathology of experimental esophageal carcinoma. In: CJ Pfeiffer (Ed.) Cancer of the Esophagus, vol. II, pp 140-164. CRC Press, Florida 12 Suzuki Hand Nagayo T (1980) Primary tumors of the esophagus other than squamous cell carcinoma - Histologic classification and statistics in the surgical and autopsied materials in Japan. Int Adv Surg Oncol3: 73-109 13 Troncoso Pand Riddell RH (1985) Pathology. In: DeMeester TR and Levin B (Eds.) Cancer of the Esophagus, pp 89-118. Grune & Stratton, New York
Received February 21, 1989 . Accepted in revised form August 31, 1989
Key words: Esophagus - Microinvasive basal cell carcinoma - Squamous carcinoma Dr. C. A. Rubio, Department of Pathology, Karolinska Institute, S-104 01 Stockholm, Sweden
