The entity was initially sugested by Horvath în 1919 (1) but the syndrome was described later by Ogilvie in 1947 (2). Usually, the underlying condition is a primitive carcinoma, such as fundic (gastric) carcinoma spreading upwards towards the cardia, but also esophageal squamous cell carcinomas
(3-5) or adenocarcinoma arising in Barrett`s esophagus (6). Differentiation of a small carcinoma from true achalasia may be a difficult task; early neoplasic infiltratration of the sub-mucosal plane may be responsible for inapropiate relaxation of the cardia, long before the settlement of tumoural obstruction.
The aethiological spectrum of the disease has changed; nowadays, pseudoachalasia in no longer exclusively associated with esogastric cancers, emerging new themes of discussion regarding the pathogeny and role of different diagnostic methods.
A 63-years old male patient, with a 6-month medical history of slight retrosternal pain following deglutition and mild disphagia, was reffered to us in january 2008 from another hospital unit, where achalasia of the cardia was documented by barium radiological evaluation and upper endoscopy. Oral intake was not impaired, although a 5 kg weight loss was recorded.
Barium swallow: dilated esophagus and stasis upstream an apparent spastic cardia, also numerous filling defects suggesting the presence of an esophageal neoplastic process (fig. 1).
Upper endoscopy was practiced after a two-day interval of preparation (no oral intake and repeated esophageal lavage) and demonstrated the presence of a non-obstructive fungating (ulcero-vegetant) esophageal cancer located at 33-38 cm from the incisors (fig. 2); the entirely length of the esophagus appeared to be dilated upstream a spastic cardia, but the scope passed through the esophago-gastric junction without difficulty. Biopsies revealed this to be a squamous cell carcinoma.
Thoracic CT scan: middle-third thoracic esophageal cancer, without evidence of mediastinal node enlargement or lung metastases (fig. 3); no liver involvement was demonstrated by abdominal ultrasound.
Obviously, we faced a pseudoachalasia and no functional esophageal tests were performed; the patient was submited to neoadjuvant full-sequence radiation and single-dose chemo-therapy. In april 2008, following radiotherapy, almost all sympthomatic complains were abolished; still, a vigorous achalasic aspect was persistent in radiographic contrast
evaluation, with beaklike narrowing of the distal end (fig. 4).
Thoracic CT scan was repeated: “matted-glass” image overlaping the lower left lung (post-radiotheraphy effect ?); a reduction in parietal thickness was noticed but also the persistence of air-fluid level in a dilated esophagus (fig. 5). Bronchoscopy: no air-pathways involvement. Endoscopic ultrasound revealed a circumferential stenosis located at 35 cm from the incisors, without adventiceal invasion of the aorta and sugested the presence of ganglionar metastasis (108- JESD, TNM T2N1M0).
The pacient was subjected to a subtotal McKeown esofagectomy in july 2008; except from post-radiation adherences to the lower left lung, there were no technical difficulties in mobilizing the thoracic esophagus (fig. 6).
We noticed a marked and consistent thickness of the
thoracic esophagus, during intrathoracic dissection (fig. 7) as well as after its cervical evisceration (fig. 8); a thoracic limphadedectomy was performed.
Longitudinal section of the resected esophageal specimen revealed: a normal morphology of the cardia; esophageal muscular hypertrophy; a non-obstructive pseudo-ulcerous esophageal lession (fig. 9).
Large lymphatic masses atached to the upper lesser
curvature of the stomach were observed during laparatomy, so that lymphadenectomy was practiced en bloc with proximal two-thirds resection of lesser curvature. The stomach was completedly mobilised conserving its right vascular pedicles but it proved to be insufficient in length, so that a right transpleural was prefered for reconstruction followed by cervical end-to-side anastomosis.
Pathological result of lymphadectomy: invasion of lower mediastinal and upper lesser curvature nodes. Concerning the esophageal specimen, most alterations were determined by radiant therapy; neoplastic infiltration of the outer longitudinal muscular layer was observed on a single histological section (fig 10).
The major histological feature was the hypertrophy of the longitudinal muscular layer (fig. 11), otherwise unusual for an esophageal squmaous cell carcinoma.
Pseudoachalazia is a rare entity. The prevalence among patients submitted to manometric exporation for presumed achalasia is 2-4% (7); it is more frequent (9-13%) in elderly patients, for instance those older than 60 years (3,8). A review on 264 cases reported in 1968-2002 (9) reveals that the
underlying cause was: malignant disease ( (53,9% primary and 14,9% secondary), benign lesions (12,6%), sequelae of surgical procedures at the distal esophagus or proximal stomach (11,9%) and, in rare instances (2,6%) an expression of a paraneoplastic process. We consider that surgical sequelae must be excluded; the rationale is that pseudoachalasia-syndrome implies a tumoural, spontaneous pathology.
Beside esophagogastric carcinoma, a large variety of extra/digestive cancers may be resposible for pseudoachalasia, producing cancerous entrapment of the cardia (extralumenal invasion, local metastases); complete reversal of the pathologic motor phenomena is possible following succesfull therapy of the underlying primary (6-11). The underlying cause may be: reticulum cell sarcoma or gastric lymphoma (10, 11), as paraneoplastic process; metastases of ordinary lung carcinoma (12, 13), paraneoplastic process due to pulmonary small cell carcinoma or direct invasion of pleural malignant mesothelioma (6); cardial invasion or metastases produced by
pancreatic carcinoma (7, 13, 14); cholangiocarcinoma (15); breast cancer, as late obstructive esophageal metastases
produced by the lobular infiltrating variety (7, 16, 17) or paraneoplastic effect of breast carcinoma without direct involvement of the esophagogastric junction (6); renal, bladder or
prostatic carcinoma (5, 8, 18), metastases of epidermoid
cervical (19) or vocal cord carcinoma (8).
The pathogenetic mechanisms of malignant pseudoachalasia are still ill-defined but, certainly, they are distinct of benign cardial obstruction. Although uncommon in distal esophageal cancer (20), malignant infiltration of the myenteric plexus may account for failure of cardial relaxation in patients submited to esophagogastrectomy for esophago-gastric cancers (21). The usual histological aspect of malignant pseudoachalasia shows neoplastic cells surrounding the myenteric ganglion cells, otherwise normal in number and morphology (6). Malignant infiltration of inhibitory neurons within the myenteric plexus has a similar functional effect to the neurogenic degeneration (characteristic in idiopathic achalasia) but the onset of sympthomes is rapid and a dilated esophagus is uncommon. Paraneoplastic pseudoachalasia shows no histological alteration of the esophagogastric junction (6); the etiopathogeny of this phenomenon remains unsolved (7).
In spite of an advanced disease, no mechanical obstacle or histological alterations of the myenteric plexus could be demonstrated in our patient; we do not believe that radiant theraphy was responsible for the absence of myenteric
infiltration. The pseudoachalasic behavior of a middle-third thoracic, exophitic cancer (on clinical basis, supported by the radiological aspects, as well as macroscopic and histological hypertrophy of the longitudinal muscular layer) is difficult to explain.
Various benign esophageal tumours or systemic entities with esophageal involvment may be associated to pseudo-achalasia, such as: von Recklinghausen`s neurofibromatosis (22, 23); esophageal leiomyomatosis (24, 25); mesenchymal tumour of the esophagus (26); histiocytosis X (3); amyloidosis (27). The clinical onset of dysphagia is very slow (many years or even decades), usuarlly affecting young patients; unfortunately, in most case cases esophageal sacrifice is necessary.
The difficulty of differentiating achalasia from secondary achalasia produced by early cardial carcinoma (on barium swallow, manometry and endoscopy) is well known (3, 4, 6, 28). In many cases the diagnosis is obtained by CT-scan or endoscopic ultrasound; in rare instances only surgical exploration reveals the underlying cause (7, 9, 26). Malignant pseudoachalazia usually mimics idiopathic disease imperfectly (3, 7); it must be suspected in older patients (age > 50 years), with a recent and short history (less than 6 month) including marked weight loss (28). A positive faecal occult blood test and anaemia may be suggestive for an advanced cancer (4). Due to a slow tumoral growth and progressive impairement of the esophageal motility, benigh pseudoachalasia mimics true achalasia even better then malignant pseudoachalasia.
The main sympthom of squamous cell esophageal
carcinoma is dysphagia. It usually presents late in the natural history of the disease; for many patients (ex: cancers
presenting a infiltrative pattern) the disease is far advanced at the time of diagnosis and the prognosis is very poor. The onset of dysphagia is faster in cancers with ulcerative pattern
(characterised by a predominantly intramural tumour growth). It seems that in some fungating (exophytic) cancers, such as our case, the onset of dysphagia resembles the clinical aspects of primitive achalasia.
Pseudoachalazia is a rare syndrome, with multifarious etiopathogenesis. Its significance is related to the fact that it may be difficult to distinguish from primary achalasia; the outcome and therapeutic course are different.
The syndrome must be kept in mind in the differential diagnosis of any dysphagic patient. Prompt recognition is the key of success, that prevents an inappropiate therapeutic approach and permits appropiate treatment of the underlying disease in due time.
1. HORVATH, W. - Dilatation of the esophagus without anatomical stenosis. Proc. R. Soc. Med., 1919, 12:64.
2. OGILVIE, H. - The early diagnosis of cancer of the esophagus and stomach. Br. Med. J., 1947, 2:405.
3. KAHRILAS, P.J., KISHK, S.M., HELM, J.F., DODDS, W.J., HARIG, J.M., HOGAN, W.J. - Comparison of pseudoachalasia and achalasia. Am. J. Med., 1987, 82:439.
4. ROBERTSON, C.C., GRIFFITH, C.D. M., ATTINSON, M., HARDCASTLE, J.D. - Pseudoachalasia of the cardia: a review. J. Royal Soc. Medicine, 1988, 81:399.
5. MAKKER, H.K., CHISHOLM, R., RATE, A.J., BANCEWITZ, J., BERNSTEIN, A. - Dysphagia due to secondary achalasia as an early manifestation of squamous cell carcinoma. Postgrad. Med. J., 1995, 71:502.
6. LIU, W., FACKER, W., RICE, T.W., RICHTER, J.E., ACHKAR, E., GOLDBLUM, J.R. - The pathogenesis of pseudoachalasia: a clinicopathologic study of 13 cases of a rare entity. Am. J. Surg. Pathol., 2002, 26:784.
7. PORTALE, G., CONSTANTINI, M., ZANINOTTO, G., RUOL, A., GUIRROLI, E., RAMPADO, S., ANCONA, E. - Pseudoachalasia: not only esophago-gastric cancer. Dis. Esophagus, 2007, 20:168.
8. ULLA, J.L., FERNANDEZ-SALGADO, E., ALVAREZ, V., IBANËZ, A., SOTO, S., CARPIO, D., VASQUEZ-SANLUIS, J., LEDO, L., VASQUEZ-ASTRAY, E. - Pseudoachalasia of the cardia secondary to nongastrointestinal neoplasia. Dysphagia, 2008, 23:122.
9. GOCKEL, I., ECKARDT, V.F., SCHMITT, T., JUNGINGER, T. - Pseudoachalasia: a case series and analysis of the literature. Scand. J. Gastroenterol., 2005, 40:378.
10. KLINE, M.M. - Successful tratment of vigourous achalasia
associated with gastric lymphoma. Dig. Dis. Sc., 1980, 25:311.
11. DAVIS, J.A., KANTROWICY, P.A., CHANDLER, H.J., SCHATYKI, R. - Reversible achalasia due to reticulum cell
sarcoma. N. Engl. J. Med., 1975, 293:130.
12. FECZKO, P.J., Halpert, R.D. - Achalasia secondary to nongastro-intestinal malignancies. Gastrointest. Radiol., 1985, 10:273.
13. CAMPOS, C.T., ELLIS, F.H. Jr., LO CICERO, J. 3rd. -Pseudoachalasia. A report of two cases with comments on possible causes and diagnosis. Dis. Esophagus., 1997, 10:220.
14. de BORST, J.M., WAGTMANS, M.J., FOCKENS, P., van LANSCHOTT, J.J., WEST, R., BOECKXSTAENS, G.E.. -Pseudoachalasia caused by pancreatic carcinoma. Eur. J. Gastroenterol. Hepatol., 2003, 15:825.
15. LEUNG, V.K., KAN, P.S., LAI, M.S. - Cholangiocarcinoma presenting as pseudoachalasia and gastroparesis. Hong Kong Med. J., 2003, 9:296.
16. HERRERA, J.L. - Case report: esophageal metastasis from breast cancer presenting as achalasia. Am. J. Med. Sci., 1992, 303:321.
17. NAZARENO, J., TAVES, D., PREIKSAITIS, H.G. - Metastatic breast cancer to the gastrointestinal tract: a case series and review of the literature. World J. Gastroenterol., 2006, 12:6219.
18. MANELA, F.D., QUIGLEY, E.M., PAUSTIAN, F.F., TAYLOR, R.J. - Achalasia of the esophagus on association with renal cell carcinoma. Am. J. Gastroenterol., 1991, 86:1812.
19. BHOLAT, O.S., HALUNCK, R.S. - Pseudoachalasia as a result of metastatic cervical cancer. J.S.L.S., 2001, 5:57.
20. SCHULTZE, K.S., GORESKY, C.A., JABBARI, M., LOUGH, J.O. - Esophageal achalasia asociated with gastric carcinoma: lack of evidence for widespread plexus destruction. Can. Med. Assoc. J., 1975, 112: 857.
21. HELM, J.F., DODDSW, J., HOGAN, W.J., ARNDORFER, R.C. - Carcinoma of the cardia masquerading as idiopathic achalasia. Gastroenterology, 1982, 82:1082A.
22. FOSTER, P.N., STEWART, M., LOWE, J.S. - Achalasia-like disorder of the esophagus in von Recklinghausens neurofibromatosis. Gut, 1987, 28:1522.
23. SICA, G.S., SUJENDRAN, V., WARREN, B., MAYNYARD, N.D. - Neurofibromatosis of the esophagus. Ann. Thorac. Surg., 2006, 81:1138.
24. THOMAS, L.A., BALARATNATNAM, N., RICHARDS, D.G., DUANE, P.D. - Diffuse esophageal leiomyomatosis:
another cause of pseudoachalasia. Dis. Esophagus, 2000, 13:165.
25. RAY, S., SALUJA, S.S., GUPTA, R., CHATTOPADTHYAY, T.K. - Esophageal leiomyomatosis - an unusual cause of pseudoachalasia. Can. J. Gastroenterol., 2008, 22:187.
26. KOTOULAS, C., GALINIS, G., YANNOUPOULOS, P. -Secondary achalasia due to a mesenchymal tumour of the oesophagus. Eur. J. Surg. Oncol., 2000, 26:425.
27. BENJELLOUN, M., PENG, C.L., HÉRITERITIER, F., ROGER, M. - Pseudoachalasia due to amyloidosis treated by botulinum toxin. Rev. Med. Interne, 2007, 28:188. Epub 2006 Dec 5. French.
28. TUCKER, H.J., SNAPE, W.J. Jr, COHEN, S. - Achalasia secondary to carcinoma: manometric and clinical features. Ann. Intern. Med., 1978, 89:315-8.