Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

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Volume: Primary Motility Disorders of the Esophagus
Chapter: Diffuse esophageal spasms (Corkscrew esophagus)

Is hyperplasia, not hypertrophy, responsible for the thickened esophagus ?

N. Ectors, K. Geboes, V. Desmet (Leuven)


The primary motility disorders of the esophagus comprise achalasia, diffuse esophageal spasm, nutcracker esophagus and intermediary forms. Except for the latter, these entities are characterized by well defined clinical, radiographic and manometric patterns [1]. In contrast to achalasia, the other entities are not known to have a distinct morphological counterpart and an organic lesion. Review of the literature reveals a « loose » association of diffuse esophageal spasm and esophageal wall thickening. This association ranges however from 0 p. cent to 100 p. cent with a mean of 40 p. cent and a median of 36 p. cent [2-10]. The esophageal wall thickening is due to an increased muscular mass at the level of the muscularis propria, especially the inner layer, and occasionally the muscularis mucosae [7, 11, 12, 13, 14]. Ever since, this morphological change has been described as an « hypertrophy » [2, 5, 11, 12].

The underlying process has however, until recently, never been properly investigated (figure /).


Figure 1. The esophageal wall thickening is mainly due to an increase in muscular mass, which can involve the muscularis mucosae (MM ; as demonstrated on this photograph) as well as the muscularis propria. (E = epithelium; Haematoxylin-eosin X 20).

Hypertrophy and hyperplasia : definitions

The distribution pattern of the esophageal wall thickening, in distal 1/3 or 2/ 3 of the esophagus, from just above or under the aortic arch till proximal of the gastro-esophageal junction [2,4, 5,7, 11, 12, 14, 15, 16] recalls the embryology and anatomy of the esophagus. The proximal part of the esophagus, including the upper esophageal sphincter (5 % of the total length) contains only striated muscle. Roughly, the distal half (50 % to 60 %) including the lower esophageal sphincter is entirely composed of smooth muscle. The remaining 35-45 p. cent consists of a transition zone. The musculature over the whole length of the esophagus is composed of an inner and an outer layer. In contrast to the upper esophageal sphincter which corresponds to a well defined, anatomical structure, the lower esophageal sphincter corresponds rather to a functional and radiological entity with a less well-defined anatomical counterpart.

The innervation of the esophagus is complex. Besides a « global» innervation system (afferent and efferent) for the esophagus including both sphincters, separate innervation systems are known for esophageal striated muscle and smooth muscle.

The non-tumoral mass increase of organic tissue is either due to hypertrophy either to hyperplasia. Both processes originate in response to an increased load, an increased functional demand - - physiological or pathological. Hypertrophy consists of an enlargement of the cells accompanied by an augmented functional capacity while hyperplasia consists of an increase in number of cells by division. The involved process depends on the retained potential of the involved cells to divide.

Striated muscles do not possess this capacity. To our knowledge, the capacity for cell division of smooth muscle of the gastrointestinal tract has never been analyzed. It has however been noted that the muscular mass in the uterus during pregnancy is due to both hyperplasia and hypertrophy. On the analogy, one could suspect that the gastrointestinal musculature can also be subjected to both processes.

Recently, this question has been addressed in diffuse esophageal spasm [17].

Review of the literature

Friesen et al. [17] analyzed by means of transmission electron microscopy surgical biopsies taken via myotomies from 9 proven cases of diffuse esophageal spasm, 8 cases of achalasia and 7 normal controls. Ultrastructural changes were recorded and appeared to be neither pronounced nor consistent. Statistical analysis of the number of muscle cells per unit area allowed them to conclude that the gross thickening of the muscular wall of the esophagus in cases of diffuse esophageal spasm is the result of hyperplasia and not hypertrophy of muscle cells. No change in muscle fiber density or size or presence of bimodality of smooth muscle cells were noted when compared to controls and achalasia.

These findings concerning achalasia cases are confirmed indirectly by those reported by Cassella et al. in 1965 [18].

Smooth muscle biopsies obtained via myotomy from 10 patients with proven achalasia were compared to biopsies from 8 control patients via electron microscopy.

Alterations in cell size were noted. The dilated segment and junctional zone contained as well smooth muscle cells with a transnuclear diameter of less than 3.5 microns as a diameter of more than 8.0 microns in approximately equal proportions (normal transnuclear diameter 4.5-8.0 microns). The distal, narrowed «hypertrophied» segment contains distinctly more smaller cells (transnuclear diameter less than 3.5 microns). The authors concluded that cellular hypertrophy could not explain the esophageal wall thickening. The role of hyperplasia was however not analyzed. An increase in connective tissue was therefore suggested as a possible mechanism.

In another article, also published in 1965, Cassella et al. refer to the electron microscopic appearances of the muscular coat of the distal part of the esophagus in diffuse spasm noted by Byrnes (1963) [20]. He said to have noticed an increased size of the smooth muscle cells together with an increase in connective tissue between the smooth muscle cells. The samples originated from the distal, grossly hypertrophied segment of the esophagus. These findings appear to be in contradiction with the results described by Friesen et al. (1983) [17] and Cassella (1965) [19]. Information concerning methods, controls and figures is however not available.

No reference could be found in the literature concerning the process underlying so-called idiopathic muscular hypertrophy.


Despite many morphological descriptions of the esophagus in diffuse esophageal spasm only brief references have been made to the features of the muscular wall itself. The process involved in the increased muscular mass has only been described recently [17, 19]. Friesen (1965) concludes that hyperplasia is responsible for the thickening of the esophageal wall in diffuse esophageal spasm and achalasia. Cassella (1965) [19] has excluded hypertrophy as a cause of esophageal wall thickening in achalasia, confirming indirectly the conclusions of Friesen.

The limited information available concerning Byrnes' findings in diffuse esophageal spasm contradict these conclusions unless, as in the uterine corpus, the esophageal smooth muscle cells can undergo as well hyperplasia as hypertrophy. Further studies are essential.


1. Vantrappen G, Janssens J,. Hellemans J, et al. (1979) Achalasia, diffuse oesophageal spasm and related motility disorders. Gastroenterology 76 : 450-457.

2. Johnstone AS (1960). Diffuse spasm and diffuse muscular hypertrophy of lower esophagus. Br J Radiol XXXIII (396): 723-735.

3. Craddock DR, Logan A, Walbaum PR (1966) Diffuse esophageal spasm. Thorax 21 : 511-517.

4. Gillies M, Nicks R, Skyring A (1967) Clinical, manometric and pathological studies in diffuse esophageal spasm. Br Med J 2 : 527-530.

5. Westgaard T, Keats TE (1968) Diffuse spasm and muscular hypertrophy. Radiology 90 : 1001-1005.

6. Gonzalez (1973) Diffuse esophageal spams. Am J Roentgenol Ther Nucl Med 117(2): 251-258.

7. Henderson RD, Ho CS, Davidson JW (1974) Primary disordered motor activity of the esophagus (diffuse spasm). Ann Thorac Surg 18(4): 327-336.

8. Flye M, Sealy WC (1975) Diffuse spasm of the esophagus. Ann Thorac Surg 19(6): 677-687.

9. Loebenberg MJ, Lewis JH, Fleisher DE, Jaffe MH, Bertagnolli ME, Cattau EL, Collen MJ, Benjamin SB (1988) Endoscopic ultrasound (EUS) for evaluating esophageal wall thickness (EWT) in esophageal motility disorders (HMD). Gastroenterology 94: 267.

10. Chen YM, Ott DJ, Hewson EG, Richter JE, Wu WC, Gelfand DW, Castell DO (1989) Diffuse esophageal spasm : radiographic and manometric correlation. Radiology 170: 807-810.

11. Nicks R, Gillies M, Skyring A (1968) Diffuse muscular spasm (diffuse muscular hypertrophy of the esophagus). Bull Soc Int Chir 6 : 637-648.

12. Ramsay BH (1967) Esophageal hypertrophy with esophagospasm (curling). Ann Thorac Surg 4(1): 66-70.

13. Enterline H, Thompson J (1984) Pathology of the esophagus. Springer-Verlag New York, Chapter 4, p. 59-62.

14. Demian SDE, Vargas-Cortes F (1978) Idiopathic muscular hypertrophy of the esophagus. Chest 73(1): 28-32.

15. Castell DO (1976) Achalasia and diffuse esophageal spasm. Arch Int Med 136: 571-579.

16. Ferguson TB, Woodbury JD, Roper CL, et al. (1969) Giant muscular hypertrophy of the esophagus. Ann Thorac Surg 8 : 209-216.

17. Friesen DL, Henderson RD, Hanna W (1983) Ultrastructure of the esophageal muscle in achalasia and diffuse esophageal spasm. Am J Clin Pathol 79(3): 319-325.

18. Cassella RR, Ellis FH, Brown AL (1965) Fine structure changes in achalasia of the esophagus. II. Esophageal smooth muscle. Am J Pathol 46: 467-475.

19. Cassella RR, Ellis FH, Brown AL (1965) Diffuse spasm of the lower part of the esophagus. Fine structure of esophageal smooth muscle and nerve. JAMA 191 (5): 107-110.

20. Byrnes CR (1963) Muscular hypertrophy of lower esophagus. Read before the Societe Internationale de Chirurgie, Rome, October 1963.

Publication date: May 1991 OESO©2011