Idiopathic Muscular Hypertrophy of the Esophagus*

Transcription

1 Idiopathic Muscular Hypertrophy of the Esophagus* Postmortem Incidental Finding m Six Cases and Review of the Literature Saba D. E. Demian, M.D., 00 and Fernando Vargas-Cortes, M.D.t Six cases of idiopathic muscular hypertrophy of the esophagus were found at autopsy in a relatively short period of time. As has been the experience in previously reported cases, our finding was incidental at the autopsy in all of the cases. In only one of our patients were there relevant symptoms and radiographic changes that could be attributed to the disease. How often pa- tients with muscular hypertrophy of the esophagus have the clinical syndrome of ditluse esophageal spasm remains unclear. It is therefore evident that only by awareness of this entity can studies of esophageal function, x-ray films, and appropriate treatment prevent serious morbidity and occasional mortality from the disease. Idiopathic muscular hypertrophy of the esopha-. gus has long been recognized as a clinical and morphologic entity, distinct from achalasia. Since the early reports, idiopathic muscular hypertrophy of the esophagus has been described under a variety of terms, including "curling" or "corkscrew" e-sophagus, giant muscular hypertrophy of the esophagus, and diffuse esophageal spasm; 1 however, despite several reports in the literature with detailed clinical, radiologic, and manometric data, morbidity and occasional mortality due to this entity are reported in clinically unsuspected cases. In a large series of autopsies of esophageal lesions, reference to this condition is not made. 2 The incidental findings of idiopathic esophageal muscular hypertrophy at autopsy in six patients (one of whom was symptomatic) over a relatively short period of time has prompted us to report our cases. It is our hope that by awareness of this entity, its clinical recognition and proper treatment will result in a decrease in morbidity and mortality from the disease. MATER!ALS AND METHODS, Six cases of idiopathic muscular hypertrophy of the esophagus were recogniud at autopsy between September 1912 and May 197!5 at the Department of Pathology, Unlver- From the Department of Pathology, College of Medicine, University of Florida, Gainesville... Presently Assistant Professor of Pathology, University of Texas Southwestern Medical School, Dallas, tassistant Professor of Pathology. Manuscript received March 28; revision accepted April 29, Reprint requests: Dr. Demian, Pathology Department, UnlverNity of Texas Health Science Center, Dallas DEMIAN, YAR&AS CORTES sity of Florida, Shands Teaching Hospital and the Gainesville ( Fla) Veterans Administration Hospital. These cases were found incidentally during 1,360 autopsies performed at these hospitals. complete review of the clinical data was done, with particular emphasis on gastrointestinal symptoms and endoscopic and radiologic findings, when available. The autopsies were carefully examined, with special attention directed to the gastrointestinal tract. Pathologic studies of the esophagus included complete gross description, with measurements of tissue fixed with a formaldehyde solution ( formalin) and with microscopic analysis of sections from both involved and uninvolved portions. Of the involved segments, three sections from different areas were studied. A section from the uninvolved segment of the esophagus, the esophagogastric junction, the posterior wall of the body of the stomach, the pylorus, the duodenum, and the jejunum were examined. Sections were stained with hematoxylin-eosin, Masson's trichrome stain, Wilder's reticulin stain, and phosphotungstic acid-hematoxylin. Clinical Data REsULTS The range of ages of our patients at the time of death was 58 to 76 years, with a median age of 64 years. ~ lpatients l were men. Five were whi!e, a11d one was black. Of our six patients, only one (case 2) had frank symptoms of the upper gastrointestinal tract. He complained of intermittent dysphagia for four years prior to death. Other complaints included retrosternal pain, vomiting of undigested food, and loss of weight. One other patient (case 3) had no related symptoms, but during his postoperative course after radical oral surgery, he had difficulty and pain dur-

2 ing nasogastric intubations. Prior to death, there were repeated unsuccessful attempts at withdrawal of an indwelling Miller-Abbott tube. Review of the symptoms in the remaining patients was not informative. In none of the patients were the findings from physical examination contributory. Esophagoscopic studies and barium swallows were only performed in the symptomatic patient (case 2). A brief summary of the clinical history from this case follows: CASE2 A 66-year-old black man was first seen in 1968 after a loss in weight of 18 kg ( 40 lb ) over a two-year period. He was found to have pulmonary tuberculosis and was treated with triple-drug antituberculosis therapy. In 1970, the patient complained of intermittent dysphagia, and on esophagoscopic studies, erythema and spasm of the distal esophagus were noted. Chest x-ray Sims showed widening of the mediastinum. An esophagograrn showed dilatation of the esophagus in its upper and middle portions, with narrowing of the distal 10 em down to the esophagogastric junction. Fluoroscopically, the esophagus showed active peristalsis, but at times resembling severe tertiary contractions. The configuration of the esophagus was thought to be minimally suggestive of achalasia. Three years later, the patient was readmitted with worsening of his dysphagia. He was having problems swallowing both hard and soft foods and liquids. The dysphagia occurred at times up to two hours after a meal, but not with every meal. The food was said to "stick in his throat" for several minutes, "work its way down," and then "stick" in an area described as just above his epigastrium; vomiting of undigested food followed. A repeat barium swallow (Fig 1 ) showed a dilated proximal esophagus and a long tapered narrowing of the distal esophagus, interpreted as "most likely benign stricture secondary to previous reflux." On his last admission in September 1974, the patient was extremely emaciated, had increasing respiratory difficulty, and died shortly after admission. FiGURE 1. Barium swallow showing persistent narrowing of esophagus distal to esophagogastric junction and proximal esophageal dilatation ( case 2). Pathologic Data In all cases the esophagus in the affected portion was expanded in a fusiform fashion-and was rigid. Four patients had thickening of the wall in the lower two-thirds of the esophagus, one patient in the middle portion, and one in the entire thoracic esophagus. In none of the patients was there any thickening of the esophagogastric junction. The thickening tapered both proximally and distally for lengths ranging from 1.5 em in most cases to up to 7 em distally in one case (case 5). The thickened muscular wall (Fig 2) measured between 0.6 em and 0.9 em, as compared with an average thickness of 0.25 em in the uninvolved segments. The ratio of circular to longitudinal muscle was 4:1 to 5:1, except in case 6, where the ratio was 3.5:1. The mucosal-submucosal thickness ranged from 0.1 to 0.3 em. In one case (case 5), the layer of circular muscle in the FIGURE 2. Gross hypertrophy of esophageal wall, maiqly circular muscular layer (case 6). IDIOPATHIC MUSCULAR HYPERTROPHY OF ESOPHAGUS 29

3 FIGURE 3. Thick fibrous septum containing large blood vessels ( an'ow) divided muscular fibers of hypertrophied circular muscular layer of esophagus ( case 5) ( Masson's trichrome stain, original magnification X 8.7). thickened segment was divided by radiating thick fibrous bands (Fig 3). The luminal circumference at the thickest part of the involved segments was between 1.5 and 3.2 em. In the uninvolved segments the luminal circumference varied between 2.5 and 6 em in five patients. In one case (case 2), in which there was a grossly dilated segment proximal to the hypertrophy, the luminal circumference was up to 7 em. Two patients (cases 3 and 5) had superficial esophageal mucosal ulcers. In the patient in whom a Miller-Abbott tube was in place (case 3), the gastric lumen contained 1,000 ml of clotted blood; and in the lesser curvature, a superficial rhomboid ulcer measuring 3 X 2 em was found. The rest of the patients showed no mucosal esophageal or gastric changes. The pylorus and intestines were grossly unremarkable in all of the patients. Microscopically, the tunica muscularis mucosa was thick in five patients and of these, was very prominent in three (cases 1, 2, and 4). The wall showed a diffuse hypertrophy of the muscular fibers in the circular layer in all cases and in the longitudinal layer in one case (case 6). In one case (case 5), large fibrous septae intercepting the circular muscular layer were seen. In these fibrous septae, there were medium-sized muscular arteries, veins, and capillaries. The ganglia and nerves of the mesenteric plexus were present and appeared unremarkable in all of the cases. Except 30 DEMIAN, YARGA$-CORTES for superficial esophageal mucosal ulcerations in cases 3 and 5 and an acute gastric ulcer in case 3, there were no other significant abnormalities of the mucosa and submucosa in any of the cases. The pylorus and the small and large intestines showed no microscopic abnormalities in any case. On review of the autopsies, malignant neoplasms were found in three patients; these neoplasms included a small cell undifferentiated carcinoma of the lung with metastases to hilar lymph nodes and a hepatocellular carcinoma with cirrhosis of the liver in one patient (case 5), an adenocarcinoma of undetermined origin with disseminated carcinomatosis (case 6), and a metastatic squamous cell carcinoma in the cervical lymph nodes from a resected primary tumor of the floor of the mouth (case 3). These patients died as a result of complications of their neoplasms. The remaining three patients died with pulmonary disease varying from moderate emphysema to severe diffuse interstitial fibrosis. In the patient with treated pulmonary tuberculosis (case 2), healed granulomatous nodules were present in the lungs but not in the esophagus or other organs. DISCUSSION The incidence of esophageal muscular hypertrophy is not known. Although several cases have been reported in clinical sejies 1 s.s and series of autopsies, 6 7 comprehensive reviews of lesions of the esophagus that were cited by Blank and Michael8 contain no description of this lesion. Likewise, in a recent review of gross and microscopic changes in the esophagus in specimens from 1,000 autopsies, Postlethwait and Musser do not refer to this entity. With our incidental finding of six cases of esophageal muscular hypertrophy within a 30-month period in 1,360 autospies, the question is raised as to the true rarity of this condition. In none of our patients was it clinically suspected, as it has been in other reported cases from autopsies in which some deaths could be related to cachexia secondary to this process. 6 9 Nonfatal esophageal perforation was reported by Johnstone, 10 and death following spontaneous perforation of the esophagus associated with smooth muscular hypertrophy was recently reported by Katz and associates.u Alth'ough esophageal muscular hypertrophy is predominant in the sixth and seventh decades of life/ 12 a few fatal cases have been reported in the early years of life Both sexes have been affected, but this condition seems to be more prevalent in male subjects Although Spencer and Hudson 14 made the comment that the disease had not been seen in a black subject, one of our patients was black.

4 In symptomatic patients the salient symptoms, as classically described by Moersch and Camp 12 and subsequently reemphasized by Ellis et aim and by several others, s- 19 include retrostemal pain and dysphagia of intermittent nature. Other symptoms, such as vomiting, appear less well defined; and loss of weight, leading to emaciation, may occur only late in the course of the disease. Occurrence of the symptoms in relation to anxiety has been repeatedly described, with some patients learning to avoid symptoms by not eating during periods of emotional distress. 18 Pain to the point of colic during instrumentation 12 and a sensation of the esophagoscope "being firmly grasped"2 1 have been described in this disease. Although only one of our patients was symptomatic, it is of interest that another of our patients had difficulty during attempts at nasogastric intubation and had retention of a Miller-Abbott tube. In symptomatic patients, barium swallows and studies of motility have been found to be of most diagnostic value. Delayed esophageal emptying, diffuse irregular spasm, curling or narrowing of the esophagus, and emptying by tertiary contractions have been described in this condition Also, thickening of the wall, readily detected both on fluoroscopic examination and in the x-ray films, was described by Johnstone. 10 Defective peristalsis and increased tertiary contraction with hypermotility hll.ve been noted on cineradiographic studies.1.2o.22 The importance of manometric studies for the diagnosis of this condition has been well documented by several authors Distinctive patterns have permitted an accurate clinical diagnosis, not only of the disease but also of its extent. 1 How often the patients with esophageal muscular hypertrophy have the clinical syndrome of diffuse esophageal spasm remains unclear. 17 According to Ferguson et al, 1 these two processes are different manifestations of the same disease, with the muscular thickening being a secondary response to the severe spasm seen in symptomatic patients. Pathologically, idiopathic muscular hypertrophy has been found to be localized to the esophagus in the majority of the cases reported, yet involvement of the pylorus, duodenum, jejunum, and ileum has been found in cases reported in children. ta-ts As in four of our six patients, most of the occurrences of muscular hypertrophy in the esophagus have been localized to the lower portion. In one of our cases, the involvement was mainly in the middle portion, and in other the entire thoracic esophagus was involved, as seen by others None of our patients had involvement of the cardia. Only an occasional report mentions extension of the process to the upper portion of the stomach 9 or associated hypertrophy of the pylorus. 7 In all of our cases, the esophagus appeared as a rigid tube expanded in fusiform fashion. The muscular hypertrophy tapered both at the proximal and distal ends, for lengths up to 7.0 em in one of our patients. This tapering has been previously noted by others. 6 9 In the majority of the reported cases, the circular muscular layer was responsible for the hypertrophy of the esophageal wall, with the longitudinal layer appearing essentially normal; however, in one of our cases, the longitudinal layer also appeared to be thickened, an observation that is only rarely mentioned in the literature In series referring to the ratio between the two muscular layers, the ratio of circular to longitudinal muscle has been noted to be 3:1 to 4: In our patients the ratio ranged from 3.4:1 to 5:1. Thickening of the tunica muscularis mucosa has been reported in a few cases; however, we noted this layer to be thickened in five of our cases. Therefore, it appears that the process is not confined exclusively to the circular layer but can also involve the longitudinal muscle and the tunica muscularis mucosa of the esophagus. Radiating thick fibrous septae that contained large blood vessels and divided the hypertrophied circular muscular layer into segments were seen in one of the patients in our series. In a review of the reported cases in which detailed pathologic description is available, the presence of thick fibrous septae dividing tl1e muscular wall into lobules has only been noted by Hall. 9 Although mild inflammatory infiltrates with a prominent eosinophilic component and with a tendency to perineural or perivascular distribution have been described, 7,13,16,18,19.22 inflammation or interstitial fibrosis was not present to any significant degree in any of our patients. As opposed to achalasia, dilatation is not a significant feature in this condition; however, a mild dilatation was noted in four of the 14 patients of Ferguson et al 1 and was a prominent finding in one of our cases. In all of our cases, the myenteric plexus was intact. Ganglia and nerves were easily identified and were unremarkable. This has also been the unanimous observation in previously reported series and has been one of the bases for the diherentiation of esophageal muscular hypertrophy from achalasia. 6 Using the electron microscope, Cassella et al 23 have reported differences between the diffuse esophageal spasm and achalasia, interpreting the former as a disorder of the afferent system, secondary to wallerian degeneration of afferent fibers of the vagus nerve. Achalasia is considered as a disorder of the efferent motor side of the peristaltic IDIOPATHIC MUSCULAR HYPERTROPHY OF ESOPHAGUS 31

5 arc. 17 Further clinical differences between these two entities have been recognized, as have been differences in results after their surgical treatment The cause of esophageal muscular hypertrophy remains essentially unknown, and analysis of our cases yielded no further information that could be related to the exact nature of the disease. Results of medical and surgical treatment have been reported by several authors As these appear satisfactory, we hope that awareness of this entity will lead to its clinical recognition and appropriate treatment and to the prevention of the serious morbidity or mortality that may occur due to this disease. ACKNOWLEWMENTS: We are indebted to Forrest L. C l o rm.d., e ~ Assistant Professor of Radiology, University of Floriaa, and Chief, Radiology Service Veterans Administration Hospital, Gainesville, Fla, for b interpretation of the x-ray films and his valuable comments. Also, we thank Mrs. Sandra Wiedegreen, Miss Janet Irwin, and Mrs. Ginger Rohr for their typing of the manuscript and editorial assistance. REFERENCES 1 Ferguson TB, Woodbury JD, Roper CL, et al: Giant muscular hypertrophy of the esophagus. Ann Thorac Surg 8: , Postlethwait RW, Musser A W: Changes in the esophagus in 1,000 autopsy specimens. J Thorac Cardiovasc Surg 68: , Ellis FH Jr, Code CF, Olsen AM: Long esophagomyotomy for diffuse spasm of the esophagus and hypertensive gastroesophageal sphincter. Surgery 48: , Ellis FH Jr, Olsen AM, Schlegel JF, et al: Surgical treatment of esophageal hypermotility disturbances. JAMA 188: , Roth HO, Fleshier B: Diffuse esophageal spasm: Clinical radiological, and manometric observations. Ann Intern Mel 61: , Wood DA: Primary idiopathic muscular hypertrophy of the esophagus with narrowing of the lumen. Arch Pathol 14: , Sloper JC: Idiopathic diffuse muscular hypertrophy of the lower oesophagus. Thorax 9: , Blank E, Michael TD: Muscular hypertrophy of the esophagus: Report of a case with involvement of the entire esophagus. Pediatrics 32: , Hall AJ : A case of diffuse fibromyoma of the oesophagus, causing dysphagia and death. Q J Med 9: , Johnstone AS: Diffuse spasm and diffuse muscle hypertrophy of lower oesophagus. Br J Radio! 33: , Katz SJ, Lieberman A, Hechtman HB : Spontaneous perforation of the esophagus associated with smooth muscle hypertrophy. Am J Surg 127 : , Moersch HJ, Camp JD: Diffuse spasm of the lower part of the esophagus. Ann Otolaryngol43: , Guthrie KJ : Idiopathic muscular hypertrophy of oesophagus, pylorus, duodenum, and jejunum in a young girl. Arch Dis Child 20: , Spencer R, Hudson TL: Idiopathic muscular hypertrophy of the gastrointestinal tract in a child. Pediatr Surg 50:(?78-686, Uhrich GI: Idiopathic muscular hypertrophy of the intestinal tract. Am J Surg 110: , Marston EL, Bradshaw HH: Idiopathic muscular hypertrophy of the esophagus. J Thorac Cardiovasc Surg 38: , Fleshier B: Diffuse esophageal spasm. Gastroenterology 52: , Gillies M, Nicks R, Skyring A: Clinical manometric, and pathological studies in diffuse oesophageal spasm. Br Med J 2: , Ramsay BH : Esophageal hypertrophy with esophagospasm (curling). Ann Thorac Surg 4:66-70, Rider JA, Moeller HC, Puletti EJ: Diffuse esophageal spasm. Am J Gastroenterol44:97-106, Ramsay BH, in discussion, Ferguson TB, et al: Giant muscular hypertrophy of the esophagus. Ann Thorac Surg 8: , Kopald HH, Roth HP, Fleshier B, et al: Vagovagal syncope: Report of a case associated with diffuse esophageal spasm. N Eng! J Med 271: , Cassella RR, Ellis FH Jr, Brown AL Jr: Diffuse spasm of the lower part of the esophagus: Time structure of esophageal smooth muscle and nerve. JAMA 191 : , DEMIAN, VARGAS-CORTES