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Year : 2015  |  Volume : 60  |  Issue : 4  |  Page : 423
Darier's disease in gastric malignancy: An unusual paraneoplastic phenomenon

Department of Dermatology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India

Date of Web Publication10-Jul-2015

Correspondence Address:
Dr. Anusree Gangopadhyay
3/26, R. K. Chatterjee Road, Joyce Apartment, Near Kasba Old Police Station, Kolkata - 700 042, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.160535

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Darier's disease is an autosomal dominant genodermatosis resulting from ATP2A2 gene mutation. A 62-year-old male presented at our outpatient (OPD) with sudden-onset numerous dirty, warty papules over the head, neck, and back since 2 months. Histopathology of the skin lesions revealed acantholytic dyskeratosis suggestive of Darier's disease. He was referred to the gastroenterology department for some gastrointestinal (GI) symptoms where he was diagnosed with adenocarcinoma of the stomach and was subsequently operated. On his next visit to our department for follow-up, we found a marked diminution of the skin lesions in the absence of any specific treatment. In view of the above finding, we concluded that paraneoplastic dermatosis in the form of Darier's disease occurred in this patient. Paraneoplastic Darier's disease with gastric adenocarcinoma is not yet described in dermatology literature and is hence reported here.

Keywords: Darier′s disease, dyskeratosis, gastric malignancy, paraneoplastic phenomenon

How to cite this article:
Gangopadhyay A, Ghosh A, Biswas S, Singha J, Aggarwal I, Chatterjee G. Darier's disease in gastric malignancy: An unusual paraneoplastic phenomenon. Indian J Dermatol 2015;60:423

How to cite this URL:
Gangopadhyay A, Ghosh A, Biswas S, Singha J, Aggarwal I, Chatterjee G. Darier's disease in gastric malignancy: An unusual paraneoplastic phenomenon. Indian J Dermatol [serial online] 2015 [cited 2022 Aug 18];60:423. Available from:

What is known?
Darier′s disease is an autosomal dominant disorder. It is usually not associated with any underlying malignant condition. Again, gastric malignancy is associated with paraneoplastic skin manifestation like tripe palm.

   Introduction Top

Darier's disease is an autosomal dominant disorder of keratinization affecting the skin, mucosa, and nails that typically manifests in the first and second decade of life. [1] Its association with underlying malignancy is extremely rare. We describe an elderly man with nonmetastatic gastric adenocarcinoma presenting with an acquired variant of Darier's disease presumably of paraneoplastic origin.

   Case Report Top

A 62-year-old Muslim farmer was in otherwise good health until 2 months back when he suddenly started noticing some dark-colored, mildly itchy skin eruption. He also complained of nausea, vomiting, and loss of appetite and a single episode of passage of black, tarry stool.

On examination of his skin, numerous hyperpigmented, warty papules were seen over the face, neck, trunk, and scalp. The lesions were characteristically distributed in seborrheic areas like head-neck area, back, and front of chest [Figure 1]. There was punctate keratoderma of palms and soles with a few palmar pits as well [Figure 2]. The oral mucosa was normal. The nails showed a 'V'-like notch at the free edge of the nail plate without longitudinal streaks. On the basis of these clinical features, our provisional diagnosis was Darier's disease. The complete hemogram was unremarkable except a hemoglobin level of 9 mg/dL. His blood sugar, liver, and renal function tests were within normal limits. Chest X-ray was unremarkable. There was neither a past history of similar lesions nor any family history of the same.
Figure 1: Dirty, warty papules over the back

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Figure 2: Palms showing pits and keratoderma

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Histopathology of the skin lesions revealed suprabasal acantholytic cleft and dyskeratotic cells like corps ronds and grains [Figure 3]a and b]. Corroboration of clinical with histopathology findings suggested a diagnosis of Darier's disease.
Figure 3: Diminution of lesions following tumor resection (a) on back; (b) on chest and palm

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He was referred to the gastroenterology department where after a series of investigations including endoscopic biopsy, he was diagnosed with gastric adenocarcinoma.

On his next follow-up in our outpatient department (OPD) 2 months later, we discovered that the skin lesions had remarkably diminished [Figure 4]a and b]. By that time, the gastric tumor had already been excised by the surgical gastroenterologists. It was then that we retrospectively considered Darier's disease to be a paraneoplastic phenomenon.
Figure 4: Histopathology showing (a) prominent hyperkeratosis and suprabasal acantholytic cleft with villi (H and E, ¡¿100); (b) dyskeratotic cells (H and E, ¡¿400)

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   Discussion Top

Paraneoplastic dermatoses describes those benign skin changes in which there is a direct, often parallel course of a dermatosis with an underlying malignancy. [2] Their presence serves as an important marker of potentially associated neoplasm. Usually, these lesions subside following treatment of the cancer. There are several proposed hypotheses on the pathomechanism of paraneoplastic dermatoses, which highlight the role of various tumor-derived growth factors like transforming growth factor β (TGF-β), fibroblast growth factor, and so on. [3] TGF-β promotes the production of extracellular matrix proteins and inhibits their breakdown. [4] Regarding the pathogenesis of paraneoplastic Darier's disease, it can be speculated that the tumor product interferes with keratinocyte calcium homeostasis leading to disturbances in intracellular trafficking of desmosomal proteins. The autosomal dominant variety is due to mutations in the SERCA2 (sarco/endoplasmic reticulum calcium ATPase type 2), which regulates calcium homoestasis in the endoplasmic reticulum. [5] Our case involves an acquired form of Darier's disease whose diagnosis was supported both clinically and histopathologically. Although there are several variants of Darier's disease, the paraneoplastic variety is extremely rare. There is only a single case report on its association with metastatic papillary carcinoma of thyroid. [6] There are some sporadic reports on the occurrence of squamous cell carcinoma of skin, nail bed, esophagus, mouth, and vagina in patients with pre-existing Darier's disease but paraneoplastic association is very rare. [1] According to the criteria proposed by Helen Ollendorff Curth, a specific dermatosis occurs with a specific neoplasm, and a high percentage of association between two conditions is noted. [7] This does not hold true in our case. The paraneoplastic dermatoses that have been reportedly associated with gastric adenocarcinoma are acanthosis nigricans, tripe palms, and florid cutaneous papillomatoses. [8]

We consider this a paraneoplastic process due to its concurrent onset and almost parallel course with malignant neoplasm, which are also important requisites in the Curth criteria. Moreover, in this case, onset of Darier's disease was late, occurring in the seventh decade of life in contrast to its usual onset in the second decade of life. Also the skin changes resolved with treatment of the underlying cancer. This further served as an eye-opener for the clinical investigators of this case. Its paraneoplastic association with gastric adenocarcinoma is very unusual and not known to be mentioned in any dermatology literature so far and hence reported here.

   References Top

Judge MR, McLean WH, Munro CS. Disorders of Keratinization. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook's Textbook of Dermatology. 8 th ed. Oxford, Blackwell Science; 2010. p. 19.1-121.  Back to cited text no. 1
Varghese SA, Sobhanakumari K, Issac CM, Seena P. A myriad of paraneoplastic dermatoses. Indian J Dermatol Venereol Leprol 2011;77:626.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
Ruifrok AC, McBride WH. Growth factors: Biological and clinical aspects. Int J Radiat Oncol Biol Phys 1999;43:877-81.  Back to cited text no. 3
Yoon SJ, Heo DS, Kang SH, Lee KH, Kim WS, Kim GP, et al. Natural killer cell activity depression in peripheral blood and ascites from gastric cancer patients with high TGF-beta 1 expression. Anticancer Res 1998;18:1591-6.  Back to cited text no. 4
Sakuntabhai A, Ruiz-Perez V, Carter S, Jacobsen N, Burge S, Monk S, et al. Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. Nat Genet 1999;21:271-7.  Back to cited text no. 5
Dortzbach KL, Seykora JT, Werth VP. Darier's disease associated with an underlying neoplasm in combination with a nodular fibroproliferative disease. J Am Acad Dermatol 2003;49(Suppl 5):S237-9.  Back to cited text no. 6
Cox NH, Coulson IH. Systemic Disease and the Skin. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook's Textbook of Dermatology. 8 th ed. Oxford, Blackwell Science; 2010. p. 62.1-106.  Back to cited text no. 7
Singhi MK, Gupta LK, Bansal M, Jain V, Kachhawa D. Florid cutaneous papillomatosis with adenocarcinoma of stomach in a 35 year old male. Indian J Dermatol Venereol Leprol 2005;71:195-6.  Back to cited text no. 8
[PUBMED]  Medknow Journal  

What is new?
Darier′s disease is an unusual paraneoplastic manifestation in gastric malignancy, not reported before.


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

This article has been cited by
1 Sporadic late-onset Darier's disease
Christopher Y Chew, Rebecca AD Nguyen
Australasian Journal of Dermatology. 2020; 61(4)
[Pubmed] | [DOI]


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