Esophageal intramural pseudodiverticulosis: A report of two cases with analysis of similar, less extensive changes in “normal” autopsy esophagi

Esophageal Intramural Pseudodiverticulosis: A Report of Two Cases With Analysis of Similar, Less Extensive Changes in "Normal" Autopsy Esophagi L. JEFFREYMEDEIROS,MD, WILHELMG. DOOS, MD, AND KAROLYBALOGH,MD Esophageal intramural pseudodiverticulosis (EIPD) is an uncommon cause of dysphagia. In this report, we describe two cases we encountered at autopsy. In both cases, the pseudodiverticula represented dilated excretory ducts of submucosal mucous glands. In addition, we retrospectively examined histologic sections of esophagus taken randomly from 100 autopsies, and prospectively studied 20 esophagi in a standardized fashion. Our findings suggest that the early pathologic changes of EIPD are more common than is appreciated in the literature. We found submucosal chronic inflammation surrounding mucous glands in more than 60% o f esophagi at autopsy. Excretory duct dilatation and small pseudodiverticula were also commonly found, their prevalence related to the number of sections of esophagus studied. The finding of chronic inflammation associated with the earliest degrees o f duct dilatation and pseudodiverticula formation suggests that inflammation may play a role in the etiology of this disorder. HUM PATHOL 19:928--931. 9 1988 by W.B. Saunders Company.

Esophageal intramural pseudodiverticulosis (EIPD) is an u n c o m m o n disease; less than 70 cases h a v e b e e n r e p o r t e d , p r i m a r i l y in the radiologic literature.1 EIPD is characterized by the development of multiple, epithelium-lined cysts within the esophageal wall; each cyst connects to the esophageal lum e n via a narrow ostium. 2-5 Patients with EIPD often experience dysphagia. T h e diagnosis is usually first m a d e by esophagography; strictures and/or motility From the Department of Pathology, New England Deaconess Hospital; and the Department of Pathology, Boston Veteran's Administration Hospitals, Boston. Accepted for publication October 29, 1987. Key words: esophagus, pseudodiverticulosis,chronic inflammation, autopsy, "normal." Address correspondence and reprint requests to Karoly Balogh, MD, Department of Pathology, New England Deaconess Hospital, 185 Pilgrim Rd, Boston, MA 02215. 9 1988 by W.B. Saunders Company. 0046-8177/88/1908-001055.00/0

disorders are commonly associated radiologic findings. 6,7 T h e etiology of EIPD is obscure. This disorder was initially described in the G e r m a n a n d Italian literature as cystic esophagitis because i n f l a m m a t i o n was believed to have a causal role. 8 In 1960, Mendl et al 6 "rediscovered" the disorder and likened its develo p m e n t to that of Rokitansky-Aschoff sinuses in the gallbladder. T h e y c o n c l u d e d that the esophageal cysts represented pulsion-type diverticula and coined the term "intramural diverticulosis of the esophagus. ''6 S u b s e q u e n t a u t o p s y studies d e m o n strated that the cysts r e p r e s e n t e d dilated excretory ducts of esophageal mucous glands. 2-5 Thus, the disease was r e n a m e d "esophageal intramural pseudodiverticulosis." We have e n c o u n t e r e d two cases of EIPD. In addition, we have occasionally observed similar, t h o u g h less severe, pathologic changes in the esophagi of individuals who died without dysphagia or clinical evidence of EIPD. T h e r e f o r e , we examined a larger series of "normal" autopsy esophagi to (1) assess the prevalence o f lesions similar to, although less severe than, EIPD in an autopsy population, a n d to (2) determine if the morphologic changes in these lesions might help clarify the etiology of this disease. REPORT OF TWO CASES Case No. 1. A 62-year-old white man sought medical attention at a local hospital for left hip pain, anorexia, and weight loss. His left hip was edematous and tender; biopsy of subcutaneous tissue revealed metastatic undifferentiated carcinoma. Bone scan demonstrated multiple lesions in the ribs, vertebrae, and left ischium. Review of systems also revealed a 2-year history of dysphagia to solid food. A bar-

FIGURE t. The luminal surface of the esophagus of case no. 1. Numerous submucosal nodules [pseudodiverticula], each with a central ostium, are found along the entire length of the esophagus.

928

ESOPHAGEALINTRAMURALPSEUDODIVERTICULOSIS[Medeiros et al)

FIGURE 2. In case no. 2, numerous dilated [up to 1.0 cm] pseudodiverticula are present, confined to the submucosa of the esophagus, and grossly visible [inset]. Chronic inflammation is minimal compared with case no. I. [Hematoxylin-eosin stain; approximate magnification x10.]

ium esophagogram proved a stricture in the u p p e r third of the esophagus. The patient was transferred to New England Deaconess Hospital (Boston) for palliative radiation therapy. Despite radiation treatment, supportive therapy, and esophageal dilatation, which led to resolution of dysphagia and improved oral intake, the patient died 5 days later. Autopsy revealed a 2.0-cm small cell carcinoma surr o u n d i n g the main right lower lobe bronchus and widespread metastases. Bronchopneumonia was the cause of death. CaseNo. 2. An 85-year-old black man with a history of remote myocardial infarct, ventricular ectopy, and congestive heart failure entered the Boston City Hospital Emergency Room complaining o f acute shortness of breath. Chest radiograph demonstrated a right lung infiltrate; the diagnosis of aspiration bronchopneumonia was made and the patient was treated with antibiotics and theophylline. T h e next day, the patient developed refractory supraventricular tachycardia followed by terminal ventricular fibrillation. T h e patient became hypotensive and died. Autopsy revealed cardiomegaly (600 g) and globular dilatation of the cardiac chambers with minimal atherosclerosis. Microscopically, the myocardium was focally replaced by interstitial fibrosis, but discrete areas of recent necrosis were not identified. The etiology of the cardiac changes was obscure. Aspiration bronchopneumonia was the cause of death.

upper one third. In case no. 2, multiple, larger pseudodiverticula, up to 1-cm in diameter, were found confined to the distal one third o f the esophagus (Fig 2). A stricture was not present in the second case. In each case, viewed from the luminal surface (Fig 1), multiple submucosal nodules were seen with central, 0.1-cm ostia. On cut surface, each nodule proved to be a cyst that communicated with the lumen, was confined to the esophageal wall, and was lined by gray-white mucosa. Many o f the cysts in case no. 1 were filled with white, viscous material. Microscopically, in both cases, the cysts were confined to the submucosa and were lined by both cuboidal and stratified squamous epithelium with transitions between the epithelial types (Fig 3). In case no. 1, adjacent mucous glands were prominent and had ectatic ducts which were lined by glandular epithelium that had u n d e r g o n e oncocytic metaplasia (Fig 3). A prominent inflammatory infiltrate composed of lymphocytes, eosinophils, and plasma cells surrounded the cysts and infiltrated the mucous glands. In case no. 2, a scant infiltrate o f lymphocytes and macrophages surrounded the cysts, and mucous glands were not prominent nor were they infiltrated by inflammatory cells. Oncocytic metaplasia of the glandular epithelum was not found (Fig 2).

E s o p h a g e a l Findings

The protocol and histologic slides of consecutive autopsies p e r f o r m e d at New England Deaconess Hospital were reviewed. Each case with randomly taken sections of "normal" esophagus was selected for further study until 100 cases were accrued. For each case, the age, sex, patho-

In case no. 1, multiple, 0.2 to 0.4-cm pseudodiverticula were found along the entire length of the esophagus (Fig 1), associated with the remnants of a fibrous stricture in the

FIGURE 3. Case no. I. A pseudodiverticulum lined by cuboidal and stratified squamous epithelium. To the right of the field, mucous glands exhibit oncocytic metapiasia and chronic inflammation is marked. [Hematoxylin-eosin stain; approximate magnification x400.]

929

MATERIALSAND METHODS

HUMAN PATHOLOGY TABLE 1.

Votume 19, No. 8 (August fl988]

Prevalence of Dilated Ducts, Cysts, a n d Chronic Inflammation in "Normal" Autopsy Esophagi

10-19 No. with dilated ducts Random 1 Standardized 0 No. with cysts Random 0 Standardized 0 No. with chronic inflammation Random 0 Standardized 0

Patient Age (yr) 50-59 60-69

70-79

80-89

90-99

Total No. (%)

7 5

2 1

2 2

0 0

14 (14) I 1 (55)

1 1

2 1

2 0

0 1

0 0

7 (7) 3 (15)

12 1

19 6

15 3

7 1

1 0

67 (67) 13 (65)

20-29

30-39

4049

1 0

0 1

0 1

1 1

0 0

0 0

2 0

2 0

4 2

7 0

logic findings, and the location of the histologic section within the esophagus (when known) were recorded. Following examination of the esophagus, the number of mucous glands and the presence or absence of duct dilatation, cyst formation, and chronic inflammation were noted. Duct dilatation was defined as expansion of the excretory duct lumen to at least twice its normal diameter. Cyst formation was considered to be present if the diameter of the dilated duct was at least 0.1 cm. We also prospectively studied 20 "normal" autopsy esophagi in the following manner. Four histologic sections were taken from each specimen at the gastroesophageal junction and from sites 7-cm, 14-cm, and 21-cm proximal to the gastroesophagealjunction. Three levels of each section were studied. For these cases, the same clinical and pathologic parameters were assessed as for the 100 cases with random esophageal sections.

m o n l y f o u n d in " n o r m a l " esophagi. I n o v e r 60% o f cases, s o m e d e g r e e o f s u b m u c o s a l chronic i n f l a m m a tion associated with ducts o r glands was f o u n d . I n the g r o u p with r a n d o m sections, 14% h a d dilated excretory ducts (Fig 4) a n d 7% h a d d e v e l o p e d cysts. I n the g r o u p o f 20 a u t o p s y e s o p h a g i studied prospectively, 55% e x h i b i t e d dilated e x c r e t o r y d u c t s o f m u c o u s glands a n d 15% h a d cystic changes. T h e r e was no a p p a r e n t r e l a t i o n s h i p b e t w e e n s u b m u c o s a l chronic i n f l a m m a t i o n or d u c t dilatation a n d age. Cysts occ u r r e d only in individuals o l d e r t h a n 40 years. As s h o w n in T a b l e 2, the n u m b e r o f s u b m u c o s a l m u c o u s glands r a n g e d f r o m 0 to six p e r r a n d o m histologic section o f e s o p h a g u s . F o r the 20 e s o p h a g i m o r e systematically studied, we f o u n d b e t w e e n 0 a n d nine s u b m u c o s a l m u c o u s glands p e r case, except for one u n u s u a l e s o p h a g u s with 24 glands. N i n e p e r c e n t o f the r e t r o s p e c t i v e l y s t u d i e d cases a n d a p p r o x i mately h a l f o f the prospectively studied g r o u p h a d at least f o u r glands p e r e s o p h a g u s . G l a n d n u m b e r did not c o r r e l a t e with s e g m e n t o f e s o p h a g u s e x a m i n e d (ie, u p p e r , mid, or lower). T h e n u m b e r o f glands r o u g h l y c o r r e l a t e d with age; in few patients u n d e r 50 years o f a g e was t h e r e m o r e t h a n o n e g l a n d p e r e s o p h a g u s f o u n d . Only patients at least 60 years old h a d e s o p h a g i in which five o r m o r e glands w e r e identified.

RESULTS T w o h u n d r e d ninety-seven consecutive autopsies w e r e reviewed to a c c r u e 100 cases in which histologic sections o f e s o p h a g u s h a d b e e n taken; 42 f r o m the distal third, nine cervical, a n d 49 unspecified. T h e m e d i a n age o f the patients was 66 years, with a r a n g e o f 19 to 92 years. Fifty-six patients were m e n a n d 44 w e r e w o m e n . F o r the 20 prospectively studied cases, the m e d i a n age o f the patients was 67 years (range, 28 to 84 years) a n d t h e sex ratio was a p p r o x i m a t e l y equal. For b o t h g r o u p s , t h e r e was n o correlation bet w e e n the m a j o r pathologic findings a n d the histologic c h a n g e s within the e s o p h a g u s . As illustrated in T a b l e 1, findings similar to those seen in E I P D , a l t h o u g h less extensive, w e r e c o r n -

DISCUSSION T h e pathologic findings in the two cases o f E I P D presently described are in a g r e e m e n t with the obser-

FIGURE 4. Random section of esophagus from an elderly man who died without esophageal symptoms. The excretory duct in the field is dilated and is more than twice its normal diameter. Chronic inflammation is present. [Hematoxylin-eosin stain; approximate magnification x 200.]

930

ESOPHAGEALINTRAMURALPSEUDODIVERTICULOSIS[Medeiros et al] TABLE 2,

Number of Mucous Glands in "Normal" Autopsy Esophagi

No. of Glands

Patient Age (yr) 10-19

20-29

30-39

Random (one histologic section per esophagus) 0 0 0 3 1

2 3 4 5 6 Total

4049

50-59

60-69

70-79

80-89

90-99

Total

5

12

15

12

4

1

1

0

1

3

2

4

5

1

0

0 0 0 0 0 1

0 1 1 0 0 2

1 0 0 0 0 5

0 0 0 0 0 8

2 2 0 1 0 19

6 1 3 0 3 32

1 2 0 0 1 21

2 4 0 0 0 11

0 0 0 0 0 1

52 18 12 10 4 1 4 100 4

Standardized (four histologic sections per esophagus) 0 0 0 1

0

0

2

1

0

0

1

0

0

1

0

0

1

0

0

0

2

2 3 4 5 6 7 8 />9 Total

0 0 0 0 0 0 0 0 0

1 0 0 0 0 0 0 0 1

0 0 t 0 0 0 0 0 3

0 0 1 0 0 0 0 0 1

0 1 0 0 0 0 0 0 1

1 0 0 0 1 2 0 2 9

1 0 0 0 0 0 0 1 3

0 1 0 1 0 0 0 0 2

0 0 0 0 0 0 0 0 0

3 2 2 1 1 2 0 3 20

vations of previous autopsy studies; the cysts corresponded to dilated excretory ducts of submucosal mucous glands. 2-5 Furthermore, the markedly different appearance of each case is of interest. Perhaps these cases represent an early (case no. 1) and late (case no. 2) stage of EIPD. In the early stage, there is extensive chronic inflammation, which may play a role in cyst formation. In this stage, ducts are dilated but cysts are not fully developed. Later, cysts are relatively large and are lined by thinned, atrophic epithelium; chronic inflammation, to a great extent, has subsided. Previous investigators 3,s have suggested that adenosis, either congenital or acquired, must be present before the development of EIPD. In contrast, Umlas and Sakhuja 5 and De la Pava et al 9 have studied "normal" autopsy esophagi and have found up to eight glands per histologic section of esophagus, a number of glands similar to that seen in esophagi involved by EIPD. The findings of the present study support the contention that adenosis (ie, an increased number of glands .per histologic section of esophagus) as not a prerequisite for the development of EIPD. We found between 0 to six glands per single random section of esophagus and between 0 to nine glands per four standardized sections of esophagus, with the exception of one case in which we found 24 mucous glands per four sections; we would consider this patient to have had adenosis. We also found a loose correlation between increasing age and greater numbers of submucosal glands. Mitros 1~ states that cyst formation, of a lesser extent than seen in EIPD, can be found in 17% of esophageal specimens studied at autopsy. Similar findings were reported by De la Pava et al. 9 Our study supports and extends their observations. We found

931

submucosal chronic inflammation surrounding mucous glands in over 60% of cases. On random sections, duct dilatation and cysts were found in 14% and 7%, respectively. In the 20 esophagi more systematically examined, duct dilatation was found in 55% and cyst formation was observed in 15% of cases. These findings suggest that the earliest changes of EIPD are commonly present and that chronic inflammation is present very early in the evolution of this disease.

REFERENCES 1. Santos GH, Baker SR, Frater RWM: Intramural pseudodiverticutosis of the esophagus. J Thorac Cardiovasc Surg 87:120, 1984 2. Boyd RM, Bogoch A, Greig JH, et ah Esophageal intramural pseudodiverticulosis. Radiology 113:267, 1974 3. L u p o v i t c h A, T i p p i n s R: E s o p h a g e a l i n t r a m u r a l pseudodiverticulosis: A disease of adnexal glands. Radiology 113:271, 1974 4. Wightman AJA, Wright EA: Intramural oesophageal diverticulosis: A correlation of radiological and pathological findings. B r J Radiol 47:496, 1974 5. Umlas J, Sakhuja R: T h e pathology of esophageal intramural pseudodiverticulosis. Am J Clin Pathol 65:314, 1976 6. Mendl K, McKay JM, T a n n e r CH: Intramural diverticulosis of the oesophagus and Rokitansky-Aschoff sinuses in the gallbladder. Br J Radiol 33:496, 1960 7. B r u h l m a n n WF, Zollikofer CL, Maranta E, et al: Intramural pseudodiverticulosis of the esophagus: Report of seven cases and literature review. Gastrointestin Radiol 6:199, 1981 8. Piazza M, Dalla Palma P: "Polycystic dystrophy" of the esophagus. Am J Clin Pathol 67:307, 1977 9. De la Pava S, Pickren JW, Adler RH: Ectopic gastric mucosa of the esophagus. A study on histogenesis. NY State J Med 64:1831, 1964 10. Mitros FA: Inflammatory and neoplastic diseases of the esophagus. In Appleman H D (ed). Pathology of the Esophagus, Stomach and Duodenum. New York, Churchill Livingstone, p 26, 1984