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Double muscularis mucosae in Barrett's esophagus
Double Muscularis Mucosae in Barrett’s Esophagus KAIYO TAKUBO, MD, KOJI SASAJIMA, MD, KIYOHIKO YAMASHITA, MD, YOICHI TANAKA, AND KICHISHIRO FUJITA, MD To clarify the histology and morphogenesis of the double muscularis mucosae in Barrett’s esophagus, eight specimens resected from patients with Barrett’s esophagus were compared histopathologically with 352 specimens resected from patients without Barrett’s esophagus. A double muscularis mucosae was observed in seven (87.5%) of the eight cases with Barrett’s esophagus, but in none of the 352 cases without Barrett’s esophagus. The mucosa in the segment of Barrett’s esophagus consisted of columnar epithelium, a superficial lamina propria, a superficial muscularis mucosae, a deep lamina propria, and a deep muscularis mucosae. The distal end of the superficial muscularis mucosae was connected to the deep muscularis mucosae at the esophagogastric junction, and its proximal end was located in fibrous tissue below the squamocolumnar junction of the mucosal epithelium or the distal edge of the erosive lesion. The deep muscularis mucosae in the portion with Barrett’s esophagus was continuous with the original muscularis mucosae of the proximal esophagus and muscularis mucosae of the stomach. Barrett’s esophagus is considered to be not merely a metaplastic lesion within the epithelium, but a newly developed lesion containing columnar epithelium, lamina propria, and a superficial muscularis mucosae on the lamina propria of the esophageal mucosa. Huht PATHOL 22:1158-1161. Copyright 0 1991 by W.B. Saunders Company
Barrett’s esophagus is an acquired condition in which the lower segment of the esophagus is lined with Morphologic studies have demcolumnar epithelium.’ onstrated that the metaplastic epithelium of Barrett’s esophagus is divided into three types: fundic, cardiac, and specialized columnar epithelia.‘,” Recently, we observed that Barrett’s esophagus has a double muscularis mucosae,4 the presence of which has been described in only one previous case.’ Because we were unable to find any detailed reports of histopathologic observations of the double muscularis mucosae in Barrett’s esophagus, we conducted a systematic microscopic study to elucidate the histopathology and morphogenesis of this tissue in comparison with the histopathologic features of the muscularis mucosae from the lower esophagus of cases without Barrett’s epithelium. MATERIALS From
I978
AND METHODS to 1988,
we examined
specimens from 351 patients
360
resected esophagus
with esophageal
squamous
cell
From the Departments 01. Pathology and Abdominal Surgery. Saitama Cancer Center, Saitsma, Japan; and the First Department of Surgery, Nippon Medical School, Tokyo. Japan. Accepted for publication Januav 15, 199 I. Kq words:columnar-lined esopha~ws, Barrett’s esophagus, doublr muscularis mucosae. Address correspondence and reprint requests to I(aiyo Takubo, MD, Department of Pathologv. Saitama Cancer Center. Komuro 818. Ina-machi, Kitaadachi-gun. S&ma-ken Sti2, .Japan. Copyr-ight 0 199 1 by U’.R. S;~under-s Company 0046~8177/91/221 I-0014$5.00,‘0
1158
MD,
carcinoma, six cases of esophageal adenocarcinoma. and three cases of esophageal ulcer or esophageal stricture. These materials were obtained from the Saitama Cancer Center Hospital and Nippon Medical School Hospital. None of the patients had received radiation therapy or antineoplastic drug therapy preoperatively. The surgical specimens from the 360 cases were cut into 5 mm-thick slices. Microscopic sections from each block were then examined histopathologically. We considered two conditions to be histologic criteria for Barrett’s esophagus: the presence of columnar epithelium proximal to the distal 3 cm of the tubular esophagus and specialized metaplastic columnar epithelium anywhere within the tubular esophagus.” We thus identified eight cases of Barrett’s esophagus: tive were associated with primary adenocarcinoma of the esophagus, one with esophageal epidermoid carcinoma, and two with esophageal ulcer or stricture.
RESULTS Seven of the eight cases (8’7.5%) of Barrett’s esophagus were observed to have a double layer of muscularis mucosae (Fig 1). In the remaining case, an irregularly thickened muscularis mucosae was observed in the mucosa distal to a primary adenocarcinoma of the esophagus. In the 352 cases without Barrett’s esophagus, no double muscularis mucosae was observed, and the muscularis mucosae of the gastric mucosa was continuous with the muscularis mucosae below the esophageal squamous epithelium. In the cases with Barrett’s esophagus, the superficial muscularis mucosae of the metaplastic mucosa lined with columnar epithelium was thinner than the deep muscularis mucosae of the esophagus. The distal end of the superficial muscularis mucosae of the metaplastic mucosa was connected to the deep muscularis mucosae at the esophagogastric junction zone. The proximal end of the superficial muscularis mucosae of the metaplastic mucosa was observed to lie in the fibrous tissue below the squamocolumnarjunction or at the distal edge of the erosive lesion, above the deep muscularis mucosae of the esophagus (Fig 2, left). The proximal end was not connected to the deep muscularis mucosae and exhibited an irregular pattern of smooth muscle fibers (Fig 2, right). In the seven specimens showing a double layer of muscularis mucosae, the deep muscularis mucosae in the specimens from cases with Barrett’s esophagus continued to the original muscularis mucosae of the proximal esophagus and muscularis mucosae of the stomach. The deep lamina propria, lying between the double layers of muscularis mucosae in the cases with Barrett’s esophagus, continued into the original lamina propria
DOUBLE MUSCULARIS
MUCOSAE
IN BARRETT’S
ESOPHAGUS
(Takubo et al)
FIGURE 1. Photomicrograph showing the double muscularis mucosae below the metaplastic mucosa. mm, Superficial muscularis mucosae: MM, deep muscularis mucosae: arrowhead, the duct of the esophageal gland proper: arrows. the terminal portions of the esophageal gland proper. The bottom left panel is a portion of the top panel shown at a higher magnification. Metaplastic columnar epithelium IS observed above the superficial muscularis mucosae, consisting of thin bundles of smooth muscle fibers. The bottom right is another portion of the top panel at a higher magnification. The deep muscularis mucosae is evident. (Hematoxylineosin stain. Magnifications: top, X(8; bottom left and right, x185.)
squamous epithelium of the proxunder the stratified ilnal esophagus and displayed edema and mild inflammatory cell accumulation. The terminal portions of the esophageal glands proper were not observed in the deep lamina propria, but in the area below the deep muscularis muc~osac. All eight rases had specialized columnar epithelium. with goblet cells in the segment with Barrett’s esophagus.
DISCUSSION The occurrence of columnar epithelium lining the lower esophagus has been known for approximately 40 vears ’ and is now a well-recognized entity, known as Barrett’s esophagus. Clinical observation and experimental studies have suggested that this phenomenon might he an acquired metaplastic change.“,7 However, a short segment of Barrett’s esophagus may be very dif-
1159
HUMAN PATHOLOGY
Volume 22, No. 11 (November
1991)
FIGURE 2. Photomicrograph showing the proximal end of the superficial muscularis mucosae (arrow) in fibrous tissue between the epithelium and deep muscularis mucosae (MM) of the esophagus, below the squamocolumnar junction zone. Arrowhead, the terminal portion of the esophageal gland proper. The right panel shows a portion of the left panel at a higher magnification. The proximal end of the superficial muscularis mucosae shows an irregular pattern of smooth muscle fibers (arrowheads) in fibrous tissue. (Hematoxylin-eosin stain. Magnifications left, X37; right, X185.)
ficult to recognize because of the histologic variations in the mucosa of the esophagogastric junction zone” and the lack of clear definition of the junction in the tunica muscularis propria. Therefore, for this study, we used the definitions of Spechler and Goyal” as histologic criteria for Barrett’s esophagus. Many reports have considered the cause of Barrett’s esophagus to be reflux of the gastric contents and subsequent re-epithelialization. It was believed that Barrett’s esophagus developed merely as a result of transformation of the original flat stratified squamous epithelium of the esophagus into a metaplastic columnar epithelium. In the present study, however, we demonstrated that the esophageal segment lined with columnar epithelium contained columnar epithelium, lamina propria on the superficial muscularis mucosae, and a superficial muscularis mucosae. These structures covered the esophageal mucosa, which had lost its original flat stratified squamous epithelium. Most previous histopathologic studies have demonstrated three types of columnar 1160
epithelium in Barrett’s esophagus by observations made on very small biopsy specimens. Surgical pathologists do not often encounter a resected esophagus lined with metaplastic columnar epithelium, except in cases of resected Barrett’s esophagus associated with primary adenocarcinoma. The tiny biopsy specimens available and the invasion by primary adenocarcinoma may prevent detailed microscopic studies of double muscularis mucosae. Histologic variation of the double muscularis mucosae in the esophagus has never been described in histology textbooks.” In this study, the double muscularis mucosae was observed only in the specimens from patients with Barrett’s epithelium, suggesting that the double muscularis mucosae has a very close relationship with this condition. The deep muscularis mucosae in the cases with Barrett’s esophagus continued into the original muscularis mucosae below the stratified squamous epithelium of the esophagus and muscularis mucosae of the stomach, and the superficial muscularis mucosae was
DOUBLE MUSCULARIS
MUCOSAE
IN BARRETT’S
alhays located below the metaplastic columnar epithehum. These findings suggest that the deep muscularis mucosae is the original muscularis mucosae of the esophagus, whereas the superficial muscularis mucosae is aSnewly formed musculaiis mucosae with metaplastic columnar epithelium. The original lamina propria of the esophagus, located toward the proximal end of the superficial muscularis mucosae, continues into the area between the double muscularis mucosae, which has no terminal p~)rtions of the esophageal glands proper. Thus, the area between the two layers of muscularis mucosae was considered to represent not the submucosa of the newllv developed mucosa but rather the lamina propria of the original esophageal mucosa. It is not clear which develops earlier, the metaplastic columnar epithelium of Barrett’s esophagus or the stromal tissue, which consists of the superficial lamina propria and muscularis mucosae. Howkver, the possibility must now be considered that Barrett’s esophagus is not a metaplastic lesion within the epithelium, but a newly developed lesion that consists of metaplastic columnar epithelium, lamina propria, and superficial muscularis nlucosae that overlie the esophageal tnucosa, which has lost its original stratified squamous epithelium. Our present findings suggest that the stromal tissue is of considerable importance in metaplasia of the colum-
ESOPHAGUS
(Takubo et al)
nar epithelium in the esophageal mucosa. similar to a previous observation in an experimental study of the gastrointestinal tract.“’ REFERENCES I. Barrett NR: Chronic peptic ulcer 01 thr ocsophqqus and “oesophagitis.” Kr J Surg 3X: 17.5-l 82. 1050 2. Paul1 A. ‘I.&r JS. Dalton MD, et al: The histologic spertrum 01 Barlett’x esotthamts. N Enel I Med 295:476-480. I!876
4. Tduho K. Ido I’: Primaq adrnoc arcinoma 01 thr ewphagub. (;lmn No Rinsho X3:771-775. 1087 5. liat~> H, IiLuka T. Watanabe H. et al: Double ;tdenoc.tr-~inonl;l in Barrett’s esophagus. .Jpn J Clin Oncc)l I 1:523-530. IO81 ii. Brrmna~- CC;. I.ynch VP, Ellis FH, .Jr: Kurrrtt‘$ ex)phagw (;cmgenital or acquired? An experimental study 01 rsophageal muc-osal reE!eneration in the dog..I Sut-germ I970~ VI 68:209-216, ” 7. Hamilton SR. Yardley JH: Regeneration of~a~iiac tyl)e mwosa a~1 acquisition of Barrett murosa after esophagog:;lstrost~)tll~. (Lstl-cwnterolo~~ 72:66%675, 1977 X. Takuho K. Squamous metaplasia with rt’serv~ cell h\pet-plasia 111thz esophagogastric junction Lone. 4cta Path(vI Jpn 31 349-351). I!IHl 9. Fujita H, FujitaT: ‘Textbook of Histolop, Part :! ‘fclkw).,Jap,m, Igaku-Sh<;in, 1984.pp 10% I 12 10. Sakagami Y. Inaguma Y. Sakakura T, vt ‘11 Intestilre-like t-emodeling of adult mouse glandular stomach I)? implanting of fetal intestinal mesen~hymc. (:ancer Res ‘ll:58455X4!1. 1!tX1
1161
Barrett’s esophagus is an acquired condition in which the lower segment of the esophagus is lined with Morphologic studies have demcolumnar epithelium.’ onstrated that the metaplastic epithelium of Barrett’s esophagus is divided into three types: fundic, cardiac, and specialized columnar epithelia.‘,” Recently, we observed that Barrett’s esophagus has a double muscularis mucosae,4 the presence of which has been described in only one previous case.’ Because we were unable to find any detailed reports of histopathologic observations of the double muscularis mucosae in Barrett’s esophagus, we conducted a systematic microscopic study to elucidate the histopathology and morphogenesis of this tissue in comparison with the histopathologic features of the muscularis mucosae from the lower esophagus of cases without Barrett’s epithelium. MATERIALS From
I978
AND METHODS to 1988,
we examined
specimens from 351 patients
360
resected esophagus
with esophageal
squamous
cell
From the Departments 01. Pathology and Abdominal Surgery. Saitama Cancer Center, Saitsma, Japan; and the First Department of Surgery, Nippon Medical School, Tokyo. Japan. Accepted for publication Januav 15, 199 I. Kq words:columnar-lined esopha~ws, Barrett’s esophagus, doublr muscularis mucosae. Address correspondence and reprint requests to I(aiyo Takubo, MD, Department of Pathologv. Saitama Cancer Center. Komuro 818. Ina-machi, Kitaadachi-gun. S&ma-ken Sti2, .Japan. Copyr-ight 0 199 1 by U’.R. S;~under-s Company 0046~8177/91/221 I-0014$5.00,‘0
1158
MD,
carcinoma, six cases of esophageal adenocarcinoma. and three cases of esophageal ulcer or esophageal stricture. These materials were obtained from the Saitama Cancer Center Hospital and Nippon Medical School Hospital. None of the patients had received radiation therapy or antineoplastic drug therapy preoperatively. The surgical specimens from the 360 cases were cut into 5 mm-thick slices. Microscopic sections from each block were then examined histopathologically. We considered two conditions to be histologic criteria for Barrett’s esophagus: the presence of columnar epithelium proximal to the distal 3 cm of the tubular esophagus and specialized metaplastic columnar epithelium anywhere within the tubular esophagus.” We thus identified eight cases of Barrett’s esophagus: tive were associated with primary adenocarcinoma of the esophagus, one with esophageal epidermoid carcinoma, and two with esophageal ulcer or stricture.
RESULTS Seven of the eight cases (8’7.5%) of Barrett’s esophagus were observed to have a double layer of muscularis mucosae (Fig 1). In the remaining case, an irregularly thickened muscularis mucosae was observed in the mucosa distal to a primary adenocarcinoma of the esophagus. In the 352 cases without Barrett’s esophagus, no double muscularis mucosae was observed, and the muscularis mucosae of the gastric mucosa was continuous with the muscularis mucosae below the esophageal squamous epithelium. In the cases with Barrett’s esophagus, the superficial muscularis mucosae of the metaplastic mucosa lined with columnar epithelium was thinner than the deep muscularis mucosae of the esophagus. The distal end of the superficial muscularis mucosae of the metaplastic mucosa was connected to the deep muscularis mucosae at the esophagogastric junction zone. The proximal end of the superficial muscularis mucosae of the metaplastic mucosa was observed to lie in the fibrous tissue below the squamocolumnarjunction or at the distal edge of the erosive lesion, above the deep muscularis mucosae of the esophagus (Fig 2, left). The proximal end was not connected to the deep muscularis mucosae and exhibited an irregular pattern of smooth muscle fibers (Fig 2, right). In the seven specimens showing a double layer of muscularis mucosae, the deep muscularis mucosae in the specimens from cases with Barrett’s esophagus continued to the original muscularis mucosae of the proximal esophagus and muscularis mucosae of the stomach. The deep lamina propria, lying between the double layers of muscularis mucosae in the cases with Barrett’s esophagus, continued into the original lamina propria
DOUBLE MUSCULARIS
MUCOSAE
IN BARRETT’S
ESOPHAGUS
(Takubo et al)
FIGURE 1. Photomicrograph showing the double muscularis mucosae below the metaplastic mucosa. mm, Superficial muscularis mucosae: MM, deep muscularis mucosae: arrowhead, the duct of the esophageal gland proper: arrows. the terminal portions of the esophageal gland proper. The bottom left panel is a portion of the top panel shown at a higher magnification. Metaplastic columnar epithelium IS observed above the superficial muscularis mucosae, consisting of thin bundles of smooth muscle fibers. The bottom right is another portion of the top panel at a higher magnification. The deep muscularis mucosae is evident. (Hematoxylineosin stain. Magnifications: top, X(8; bottom left and right, x185.)
squamous epithelium of the proxunder the stratified ilnal esophagus and displayed edema and mild inflammatory cell accumulation. The terminal portions of the esophageal glands proper were not observed in the deep lamina propria, but in the area below the deep muscularis muc~osac. All eight rases had specialized columnar epithelium. with goblet cells in the segment with Barrett’s esophagus.
DISCUSSION The occurrence of columnar epithelium lining the lower esophagus has been known for approximately 40 vears ’ and is now a well-recognized entity, known as Barrett’s esophagus. Clinical observation and experimental studies have suggested that this phenomenon might he an acquired metaplastic change.“,7 However, a short segment of Barrett’s esophagus may be very dif-
1159
HUMAN PATHOLOGY
Volume 22, No. 11 (November
1991)
FIGURE 2. Photomicrograph showing the proximal end of the superficial muscularis mucosae (arrow) in fibrous tissue between the epithelium and deep muscularis mucosae (MM) of the esophagus, below the squamocolumnar junction zone. Arrowhead, the terminal portion of the esophageal gland proper. The right panel shows a portion of the left panel at a higher magnification. The proximal end of the superficial muscularis mucosae shows an irregular pattern of smooth muscle fibers (arrowheads) in fibrous tissue. (Hematoxylin-eosin stain. Magnifications left, X37; right, X185.)
ficult to recognize because of the histologic variations in the mucosa of the esophagogastric junction zone” and the lack of clear definition of the junction in the tunica muscularis propria. Therefore, for this study, we used the definitions of Spechler and Goyal” as histologic criteria for Barrett’s esophagus. Many reports have considered the cause of Barrett’s esophagus to be reflux of the gastric contents and subsequent re-epithelialization. It was believed that Barrett’s esophagus developed merely as a result of transformation of the original flat stratified squamous epithelium of the esophagus into a metaplastic columnar epithelium. In the present study, however, we demonstrated that the esophageal segment lined with columnar epithelium contained columnar epithelium, lamina propria on the superficial muscularis mucosae, and a superficial muscularis mucosae. These structures covered the esophageal mucosa, which had lost its original flat stratified squamous epithelium. Most previous histopathologic studies have demonstrated three types of columnar 1160
epithelium in Barrett’s esophagus by observations made on very small biopsy specimens. Surgical pathologists do not often encounter a resected esophagus lined with metaplastic columnar epithelium, except in cases of resected Barrett’s esophagus associated with primary adenocarcinoma. The tiny biopsy specimens available and the invasion by primary adenocarcinoma may prevent detailed microscopic studies of double muscularis mucosae. Histologic variation of the double muscularis mucosae in the esophagus has never been described in histology textbooks.” In this study, the double muscularis mucosae was observed only in the specimens from patients with Barrett’s epithelium, suggesting that the double muscularis mucosae has a very close relationship with this condition. The deep muscularis mucosae in the cases with Barrett’s esophagus continued into the original muscularis mucosae below the stratified squamous epithelium of the esophagus and muscularis mucosae of the stomach, and the superficial muscularis mucosae was
DOUBLE MUSCULARIS
MUCOSAE
IN BARRETT’S
alhays located below the metaplastic columnar epithehum. These findings suggest that the deep muscularis mucosae is the original muscularis mucosae of the esophagus, whereas the superficial muscularis mucosae is aSnewly formed musculaiis mucosae with metaplastic columnar epithelium. The original lamina propria of the esophagus, located toward the proximal end of the superficial muscularis mucosae, continues into the area between the double muscularis mucosae, which has no terminal p~)rtions of the esophageal glands proper. Thus, the area between the two layers of muscularis mucosae was considered to represent not the submucosa of the newllv developed mucosa but rather the lamina propria of the original esophageal mucosa. It is not clear which develops earlier, the metaplastic columnar epithelium of Barrett’s esophagus or the stromal tissue, which consists of the superficial lamina propria and muscularis mucosae. Howkver, the possibility must now be considered that Barrett’s esophagus is not a metaplastic lesion within the epithelium, but a newly developed lesion that consists of metaplastic columnar epithelium, lamina propria, and superficial muscularis nlucosae that overlie the esophageal tnucosa, which has lost its original stratified squamous epithelium. Our present findings suggest that the stromal tissue is of considerable importance in metaplasia of the colum-
ESOPHAGUS
(Takubo et al)
nar epithelium in the esophageal mucosa. similar to a previous observation in an experimental study of the gastrointestinal tract.“’ REFERENCES I. Barrett NR: Chronic peptic ulcer 01 thr ocsophqqus and “oesophagitis.” Kr J Surg 3X: 17.5-l 82. 1050 2. Paul1 A. ‘I.&r JS. Dalton MD, et al: The histologic spertrum 01 Barlett’x esotthamts. N Enel I Med 295:476-480. I!876
4. Tduho K. Ido I’: Primaq adrnoc arcinoma 01 thr ewphagub. (;lmn No Rinsho X3:771-775. 1087 5. liat~> H, IiLuka T. Watanabe H. et al: Double ;tdenoc.tr-~inonl;l in Barrett’s esophagus. .Jpn J Clin Oncc)l I 1:523-530. IO81 ii. Brrmna~- CC;. I.ynch VP, Ellis FH, .Jr: Kurrrtt‘$ ex)phagw (;cmgenital or acquired? An experimental study 01 rsophageal muc-osal reE!eneration in the dog..I Sut-germ I970~ VI 68:209-216, ” 7. Hamilton SR. Yardley JH: Regeneration of~a~iiac tyl)e mwosa a~1 acquisition of Barrett murosa after esophagog:;lstrost~)tll~. (Lstl-cwnterolo~~ 72:66%675, 1977 X. Takuho K. Squamous metaplasia with rt’serv~ cell h\pet-plasia 111thz esophagogastric junction Lone. 4cta Path(vI Jpn 31 349-351). I!IHl 9. Fujita H, FujitaT: ‘Textbook of Histolop, Part :! ‘fclkw).,Jap,m, Igaku-Sh<;in, 1984.pp 10% I 12 10. Sakagami Y. Inaguma Y. Sakakura T, vt ‘11 Intestilre-like t-emodeling of adult mouse glandular stomach I)? implanting of fetal intestinal mesen~hymc. (:ancer Res ‘ll:58455X4!1. 1!tX1
1161