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 ::  Abstract
  ::  Introduction
  ::  Results
  ::  Discussion
  ::  Conclusion
 ::  References
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  Table of Contents     
Year : 2022  |  Volume : 68  |  Issue : 2  |  Page : 98-99

Esophageal squamous cell cancer in Plummer-Vinson syndrome: Is lichen planus a missing link?

1 Department of Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
2 Department of Dermatology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India

Date of Submission02-May-2021
Date of Decision21-Jun-2021
Date of Acceptance06-Sep-2021
Date of Web Publication11-Apr-2022

Correspondence Address:
P Mohan
Department of Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpgm.jpgm_375_21

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 :: Abstract 

This retrospective study analyzed the occurrence of esophageal squamous cell cancer (ESCC) in a cohort of patients with Plummer-Vinson syndrome (PVS) and mucosal lichen planus (LP). ESCC occurred in 6.2% cases of PVS, more than half of whom had associated oral LP. Mucosal LP and PVS together may increase the predisposition to ESCC.

Keywords: Lichen planus, esophageal cancer, esophageal webs, Plummer–Vinson syndrome

How to cite this article:
Mohan P, Munisamy M, Selvan K S, Hamide A. Esophageal squamous cell cancer in Plummer-Vinson syndrome: Is lichen planus a missing link?. J Postgrad Med 2022;68:98-9

How to cite this URL:
Mohan P, Munisamy M, Selvan K S, Hamide A. Esophageal squamous cell cancer in Plummer-Vinson syndrome: Is lichen planus a missing link?. J Postgrad Med [serial online] 2022 [cited 2023 May 29];68:98-9. Available from:

 :: Introduction Top

Esophageal cancer (EC) has a high case fatality ratio and it ranks sixth among the cancer related-mortality worldwide. The incidence, risk factors, and pathology of EC are highly variable and are based on ethnicity and geographic location.[1],[2] The highest incidence of esophageal squamous cell cancer (ESCC) occurs in the “Asian Oesophageal Cancer Belt” extending from eastern Turkey and northern Iran to east Asian countries, northern China, and India.[3] The most well-established risk factors for ESCC include alcohol, tobacco, exposure to environmental carcinogens, dietary factors, nutritional deficiencies, and chronic irritation of the esophagus.[1]

Plummer-Vinson syndrome (PVS) and mucosal lichen planus (LP) are relatively common in the developing world unlike in the West. Both PVS and LP are reported to be premalignant with the risk of esophageal malignancy being 4 to 16% in PVS[3] and 1.09 to 3.2% in mucosal LP.[4] LP was associated with EC in a Finnish cohort with a standardized incidence ratio of 1.95.[5] Although PVS and LP independently increase the cancer risk, they have never been reported to occur simultaneously to cause ESCC. After taking permission from our institutional ethics committee, this study was conducted to look for such an association in our cohort of PVS who developed ESCC.

 :: Results Top

The esophageal web was diagnosed in 170 patients during the years 2013 to 2020. The location of the webs was either in the cricopharynx or upper esophagus. The triad of dysphagia, esophageal web, and iron deficiency anemia was seen in 146 patients and was classified as PVS. ESCC occurred in nine (6.2%) patients with PVS. Esophageal growth was present along with webs at the time of diagnosis in six patients. Three patients developed ESCC during follow-up for the recurrence of dysphagia after the endoscopic dilation of webs. Patients with ESCC reported a recent change in the characteristics of dysphagia. Their symptom of intermittent difficulty in swallowing solid food, which was prevalent for several months or years started to become persistent and progressed to dysphagia to soft solids as well as liquids. This progressive worsening of symptoms was also rapid and accompanied by loss of appetite and weight. The mean (standard deviation [SD]) age of PVS patients with cancer was 52.2 (14.2) years. There was a female preponderance (male: female = 1:8). Patients who developed ESCC had no history of alcohol consumption or tobacco use. The location of the tumor was in the upper, mid, and lower esophagus in two, three, and four patients, respectively. It was well-differentiated in one and moderately differentiated in eight patients. Six out of these nine patients had mucosal LP, with oral LP observed in four patients, genital LP in one patient, and oral and genital LP in one patient. [Figure 1] shows oral and genital LP in a patient with concomitant cricopharyngeal web and esophageal cancer. Esophageal LP was observed in one out of four patients who underwent esophageal mucosal biopsies.
Figure 1: (a) Oral and (b) genital lichen planus (black arrows) in a patient with (c) concomitant cricopharyngeal web (black arrow) and esophageal cancer (white arrow) in the contrast esophagogram and (d) upper gastrointestinal endoscopy showing intact esophageal web (black arrow), (e) ruptured esophageal web (black arrow) and (f) esophageal cancer (black arrow)

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 :: Discussion Top

Esophageal squamous cell carcinoma has its peak incidence in the sixth or seventh decade and a two to three times higher predilection for men. On the contrary, our cohort of ESCC in PVS were predominantly women in their 50s or much earlier. Although tobacco and alcohol are associated with an increased risk of ESCC worldwide, micronutrient deficiency and dietary carcinogens have also been implicated in carcinogenesis, especially in economically underdeveloped or developing regions of the world.[1]

Iron deficiency continues to be a common public health problem in the developing world. It has been reported to be a predisposing factor for webs and mucosal LP. The gastrointestinal tract is highly susceptible to the effects of iron deficiency due to its rapid cell turnover. Hence, iron deficiency and loss of iron-dependent enzymes affect the epithelial cell kinetics causing impaired cell proliferation and differentiation, which results in the degeneration of mucosa and web formation. The epithelial atrophy together with impaired repair mechanisms makes the mucosa highly susceptible to the effects of carcinogens and co-carcinogens, predisposing to malignant transformation.[6] However, it is still unclear, if iron deficiency is the cause or effect in web or LP as they both negatively affect the nutritional status. ESCC was observed in 6.2% of our PVS cohort and more than half of them had oral LP. All patients had iron deficiency anemia. None of them had exposure to tobacco or alcohol.

Classical oral LP was seen in five of our patients. Human papillomavirus (HPV) infection has been associated with LP and has also been implicated in the pathogenesis of malignant transformation in LP.[7] The evidence for HPV in the causation of ESCC is still unclear. Such an association has been reported in meta-analysis in high prevalence areas.[8] Thus, our observation of the concurrent occurrence of PVS, LP, and ESCC leads to several unanswered questions. Whether a true association between PVS and LP exists, or their concurrent occurrence increases the risk of ESCC, or if HPV infection predisposes to ESCC in these patients needs to be explored.

 :: Conclusion Top

In conclusion, ESCC occurred in 6.2% of PVS, more than half of whom had associated oral LP. Mucosal LP and PVS together may increase the predisposition to ESCC, especially in younger women without conventional risk factors. However, this association needs to be proven in future prospective studies in regions where PVS, LP, and ESCC are highly prevalent.

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Conflicts of interest

There are no conflicts of interest.

 :: References Top

Murphy G, McCormack V, Abedi-Ardekani B, Arnold M, Camargo MC, Dar NA, et al. International cancer seminars: A focus on esophageal squamous cell carcinoma. Ann Oncol 2017;28:2086-93.  Back to cited text no. 1
Gholipour M, Islami F, Roshandel G, Khoshnia M, Badakhshan A, Moradi A, et al. Esophageal cancer in Golestan Province, Iran: A review of genetic susceptibility and environmental risk factors. Middle East J Dig Dis 2016;8:249-66.  Back to cited text no. 2
Goel A, Bakshi SS, Soni N, Chhavi N. Iron deficiency anemia and Plummer-Vinson syndrome: Current insights. J Blood Med 2017;8:175-84.  Back to cited text no. 3
Fitzpatrick SG, Hirsch SA, Gordon SC. The malignant transformation of oral lichen planus and oral lichenoid lesions: A systematic review. J Am Dent Assoc 2014;145:45-56.  Back to cited text no. 4
Halonen P, Jakobsson M, Heikinheimo O, Riska A, Gissler M, Pukkala E. Cancer risk of lichen planus: A cohort study of 13,100 women in Finland. Int J Cancer 2018;142:18-22.  Back to cited text no. 5
Bhattacharya PT, Misra SR. Effects of iron deficiency on the oropharyngeal region: Signs, symptoms, and biological changes. In: Preedy V, Patel VB, editors. Handbook of Famine, Starvation, and Nutrient Deprivation. Springer International Publishing; 2017. p. 1-19.  Back to cited text no. 6
Gorsky M, Epstein JB. Oral lichen planus: Malignant transformation and human papilloma virus: A review of potential clinical implications. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;111:461-4.  Back to cited text no. 7
El-Zimaity H, Di Pilato V, Novella Ringressi M, Brcic I, Rajendra S, Langer R, et al. Risk factors for esophageal cancer: Emphasis on infectious agents. Ann N Y Acad Sci 2018;1434:319-32.  Back to cited text no. 8


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