Dermatosis as the initial presentation of gastric cancer: two cases

Department of General Surgery, Nanjing Drum Tower Hospital, The Affliated Hospital of Nanjing University Medical School, Nanjing 210008, China

＊These authors contribute equally to this work.

Correspondence to: Gang Chen. Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China. Email: 331812195@qq.com.

Dermatosis as the initial presentation of gastric cancer: two cases

Wei Ge＊, Bu-Wei Teng＊, De-Cai Yu, Gang Chen, Li-Ming Zheng, Yi-Tao Ding

Department of General Surgery, Nanjing Drum Tower Hospital, The Affliated Hospital of Nanjing University Medical School, Nanjing 210008, China

＊These authors contribute equally to this work.

Correspondence to: Gang Chen. Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China. Email: 331812195@qq.com.

Paraneoplastic dermatoses are known to be certain dermatosis related with tumor. The common paraneoplastic dermatoses are acanthosis nigricans, acquired ichthyosis, dermatomyositis, erythroderma, and so on. Here we report two cases of paraneoplastic dermatoses associated with gastric cancer. One case was a 57-year-old man with dermatomyositis and proved to be associated with gastric cancer through stomachoscopy. The other was a 66-year-old man with erythroderma and proved to be associated with gastric cancer through stomachoscopy. Both cases were treated with radical total gastrectomy with lymphadenectomy (D2) and esophagojejunostomy of Roux-en-Y. The skin symptom of both cases had improved a lot but still existed after operation. Paraneoplastic dermatoses can be seen as the early manifestation of visceral carcinomas. As a result, gastric cancers should be excluded in the patients with paraneoplastic dermatoses.

Paraneoplastic dermatoses; erythroderma; dermatomyositis; malignancy; gastric cancer

View this article at:http://dx.doi.org/10.3978/j.issn.1000-9604.2014.10.01

Introduce

Paraneoplastic dermatoses are certain skin conditions associated with tumor, such as acanthosis nigricans, dermatomyositis, erythroderma, ichthyosis and so on. The tumors ichthyosis associated with are mostly adenocarcinoma, especially gastrointestinal tumors, accounting for 90%. The tumors dermatomyositis related to are breast cancer, uterine cancer, ovarian cancer, gastric cancer, lung cancer, malignant lymphoma, liver cancer, prostate cancer, kidney cancer, leukemia, and so on. The tumors associated with erythroderma are T-cell lymphoma, lung cancer, stomach cancer, and so on (1-15). This paper described one case of dermatomyositis and erythroderma accompanying gastric cancer respectively.

Case reports

Case 1

A 57-year-old man was admitted to Rheumatism Immunity Branch of The First Hospital of Nanjing with skin erythema and muscle soreness for half a month on May 4th, 2012. Erythema of the inferior orbital, both sides of the nose, forehead, and neck made a surprise attack on the patient half a month ago. Later, aching pain of double shoulder joints, double upper arm, and double side thigh, and movement disturbance of four limbs gradually appeared. So, he went to The First Hospital of Nanjing for further cure.

Physical examination: red papules were scattered in his frontal part, double eyelid, orbit below, neck, and limbs without skin mucous membrane burst, and superficial lymph node enlargement (Figure 1).

Laboratory examination: blood routine test showed that white blood cell count was 5.8×109/L (normal range, 4×109-10×109/L); the proportion of neutrophile granulocyte was 77% (normal range, 51-75%). Erythrocyte sedimentation rate (ESR): 8 mm/h (normal range, 0-15 mm/h). Rheumatism three items and immune globulin showed a normal level in serum, but complement C4 (153.00 mg/L) was low-grade. The test of autoantibody suggested 1:1,000positive of antinuclear antibody of ANA.

Figure 1 (A) Flake red rash in double upper arm without desquamation; (B) fake red rash in the neck without desquamation.

His manifestation of skin, and the laboratory data fulfilled the criteria for the diagnosis of dermatomyositis. As the patient had the medical history of “gastric ulcer with bleeding”, stomachoscopy was made to show lesion in the preventriculus, which was proved to be poorly differentiated carcinoma by pathological examination. Then the patient was transferred to department of gastrointestinal surgery of our hospital for operation.

Radical gastrectomy was performed with general anesthesia on May 13th2012. Firstly a small part of skin, and muscle was biopsied. Radical total gastrectomy was performed with lymphadenectomy (D2) and esophagojejunostomy of Roux-en-Y. On the second day after the operation, the aching pain of muscle relieved obviously, the erythema also receded a little. The postoperative pathological report showed the poorly differentiated ulcerative adenocarcinoma in the anterior wall of the stomach around the cardia with local neuroendocrine differentiation IB (T2, N0, cM0). The following proteins were expressed in cancer cells: EGFR (–), TS (–), β-tubulin (+++), ERCC1 (–), BRCA1 (–), CerbB2 (–), VEGF (+), COX2 (++), Syn focal (+), CgA (–), P63 (+), Ki67 (30%+). The skin biopsy showed a few of neutrophile granulocytes infltrated into the superfcial layer of dermis and cutaneous appendages. The muscle biopsy showed perivascular neutrophile granulocyte cells infiltrated into muscle bundles with a small amount of muscle fiber degeneration and necrosis. The epidermis and muscle were related with dermatomyositis. After one month, the patient still felt muscle aching pain with skin erythema. He visited Department of Rheumatism Immunity Branch for further examination and be treated with oral prednisone (40 mg QD). In the last six months, the patient’s symptoms improved a lot, but still exist.

Case 2

The patient, a 66-year-old man, was hospitalized in Department of Endocrinology in Drum Tower Hospital due to hypoglycemia on August 17th, 2010. He had a history of type 1 of diabetes mellitus for about forty years with insulin therapy. The hypoglycemia often occurred. Last year the patient complained of red papules on his back without obvious precipitating factors. Gradually the similar red papules spread from the head and neck to the trunk limbs, with severe itching. He was treated as chronic eczema, dermatitis or some other skin diseases with oral antihistamines and dexamethasone. He felt a little relief. However, the symptoms got worse with obvious desquamation and itching four months ago. Furthermore his hair lost gradually.

Physical examination: red papules were scattered in his head, face, trunk and limbs. And the papules partially mixed together with swelling, desquamation, itching and also tenderness (Figure 2). Several lymph nodes (0.5-3 cm) were touched in bilateral armpits, with clear border and evident tenderness.

Laboratory examination: blood routine test showed that eosinophil count was 1.7×109/L, the proportion of eosinophils 13.7% (normal range, 0.5-5%), monocyte count 1.1×109/L, the proportion of monocytes 9.1% (normal range, 3-8%), lymphocyte count 0.5×109/L, the proportion of lymphocyte 4.2% (normal range, 20-40%), hemoglobin 82 g/L (normal range, 131-172 g/L). IgG (18.5 g/L) and IgA (4.52 g/L) showed a high level in serum,but complement C4 (0.16 g/L) was low-grade. Erythrocyte sedimentation rate was 60 mm/h (normal range, 0-15 mm/h). The chest X-ray showed the change of interstitial pneumonia. Color Doppler ultrasound of liver showed enlargement of liver’s volume and splenomegaly. The test of autoantibody suggested 1:100 positive of antinuclear antibody of HEP2/granular pattern of monky’s liver.

Figure 2 Red papules, accompanied by swelling and desquamation, were scattered in his head and face, trunk and limbs.

In consideration of the manifestation of the patient’s body skins and the laboratory data, the endocrinologists asked the dermatologists and the rheumatologists for consultation. Erythroderma was considered according to the medical history, physical examination, laboratory data, and the treatment of antihistamines to control symptoms. Meanwhile, tumor markers were detected to rule out the tumors, which may induce erythroderma. And the levels of carcino-embryonic antigen (CEA) (normal range, 0-10 ng/mL), carbohydrate antigen (CA) 125 (normal range, 0-5 ng/mL), and CA50 (normal range, 0-21 ng/mL) were 15.10 ng/mL, 15.10 ng/mL, and 22.10 U/mL respectively, while alpha fetoprotein (AFP), CA72-4, and CA19-9 were normal. Furthermore, an ulcerative mass was detected in the place of the cardia under endoscopy and barium meal examination, which was confirmed as adenocarcinoma. Position emission tomography-computed tomography (PET-CT) imaging showed that one irregular mass in cardia was of hypermetabolism [standard uptake value (SUV) max 3.2, delay imaging SUVmax 5.9], and multiple small lymph nodes in bilateral armpits were not of hypermetabolism. Then the patient was transferred to Department of Gastrointestinal Surgery for operation.

Radical gastrectomy was performed with general anesthesia on Sep 14th2010. Firstly a small part of skin and muscle was biopsied. Radical total gastrectomy was performed with lymphadenectomy (D2) and esophagojejunostomy of Roux-en-Y. On the frst day after the operation, the pruritus relieved obviously, the erythema also receded a little, and the eosinophilic cell could not be detected. The postoperative pathological report showed the poorly differentiated ulcerative adenocarcinoma in the posterior wall of the stomach around the cardia (diffusing type of the classification of Lauren) (IIB, T3, N1, cM0). The following proteins were expressed in cancer cells: EGFR (+), P53 (70%+), COX2 (++), CerbB2 (+), VEGF (++), Ki67 (40%+), SSTR2 (+), Syn (–), CgA (–), CD56 focal (+). The skin biopsy showed perivascular neutrophile granulocyte cell infiltrate into skin biopsy with a few of leukomonocyte in the dermis. The epidermis was related erythroderma (Figure 3).

Figure 3 Gastric cancer (A): growth of malignant cell in gland of stomach (HE, ×200); skin biopsy (B): perivascular neutrophile granulocyte cell infltrate into skin biopsy with a few of leukomonocytes in the dermis (HE, ×400).

Table 1 Gastric cancer associated with dermatomyositis

After one month, the symptoms of pruritus and desquamation improved a lot, the erythema and the papule also receded. Eosinophil count decreased to 0.2×109/L (2.0%). Unfortunately, the patient felt itching severely again about three months after the operation and he visited Department of Dermatology for further examination. The biopsy of the skin on right upper extremity showed accentuation of squamous epithelium’s keratinization, some eosinophils cells infltrate in the dermis. Then, the patient was given by some symptomatic and supportive therapies. In the last six months, the symptoms of pruritus and desquamation improve a lot, but still exist.

Discussion

Paraneoplastic dermatoses are known to be certain dermatosis related with tumor, and the symptoms were parallel with the course of tumor (16). Research showed that etiology was associated with active factors or hormone secreted by tumor, but the specific pathogenesis is not very clear. The common paraneoplastic dermatoses are acanthosis nigricans, acquired ichthyosis, dermatomyositis, erythroderma, and so on.

Dermatomyositis is a kind of autoimmune disease with dermatitis and myositis, which is individualism or overlap exists with systemic lupus erythematosus (SLE), scleroderma, rheumatoid disease, and so on. The clinical manifestations are dermatitis, myositis, and constitutional symptoms such as high fever and joint pain. The pathogenic factor is related with infection of oxoplas or virus, and tumor is also a factor. At present, the malignancy correlated with dermatomyositis is breast cancer, ovarian cancer, ovarian cancer, gastric cancer, lung cancer, malignant lymphoma, mediastinum cancer, liver cancer, prostate cancer, kidney cancer, leukemia, and so on (1-15). Up to now, seven cases of gastric cancer were reported to be correlated with dermatomyositis (Table 1). Dermatomyositis accompanying malignant tumor is common in people between 40-60 years, and the incidence was 15-50% (22). The biggest risk of dermatomyositis is associated with malignant tumor and the older, the higher opportunity of tumor accompanying (23). Callen reported that tumor incidence was 71% in over 50-year-old patients with dermatomyositis (24). Our patient, a 57-year-old man, appeared erythema of neck and face suddenly and felt muscular soreness later. The laboratory examination showed that creatine kinase and lactate dehydrogenase (LDH) rised. In consideration of the manifestation of the patient’s body skins and the laboratory data, the diagnosis of dermatomyositis was made. The patient had the medical history of “gastric ulcer with bleeding”, so the stomachoscopy examination was made to discover lesion. This case suggests that, for sudden dermatomyositis patient, system checks should be made to eliminate tumor in conjunction with the past history.

Papuloerythroderma, also called exfoliate dermatitis, was firstly reported by Ofuji in 1984 (25). Its, typicalmanifestations are diffuse flushing, papules, infiltration, swelling and desquamation in almost all our body, especially in the face and the creases (the “deck-chair” sign) (26). Besides the skins, it may also invade the mucous, the skin appendages, the lymph node, even and the viscera. The mucosal invasion may usually manifest as conjunctivitis, blear-eye, keratitis, corneal or mouth ulcers, or the mucosal erosion of women’s vagina, urethra or anus. Peripheral eosinophilia, lymphopenia, and elevated serum immunoglobulin (Ig) E levels occur in some cases (27). Erythroderma can be induced by lots of factors, such as psoriasis, eczema, seborrheic dermatitis, pityriasis rubra pilaris, lichen planus or some drugs [aspirin (28) and furosemid (29)]. Furthermore, erythroderma is related with malignant lymphoma (30), especially cutaneus T-celllymphoma (31), leukemi, mycosis (32), fungoides (33) and many other diseases, even the common gallstones, fungous infections of the skins, excessive eosinophilia syndrome, dermatomyositis (34), acquired immune defciency syndrome (35), or hepatitis C virus infection.

Table 2 Visceral tumors associated with papuloerythroderma

There are some reports, which support the opinion that visceral tumors such as esophagus, stomach, colon, gallbladder, lung, kidney, prostate, nasopharynx, or pericardium are closely related with erythroderma (36-38). The reports on papuloerythroderma with visceral tumors were summarized in Table 2. Here we describe a case report, which confirmed this relationship between gastric cancer and erythroderma further. In addition, the patient had interstitial pneumonia simultaneously. Therefore, it was concluded that erythroderma and interstitial pneumonia are both a kind of paraneoplastic syndromes, which is frstly reported. This case with no primary skin disease, appeared red papules under no obvious predisposing causes, got no effect after symptomatic treatment, and proved to be associated with gastric cancer by stomachoscopy. As a result, some elderly patients with no primary skin disease, suffering from erythroderma and getting no curative effect through a variety of active treatment, should be highly suspected to accompany tumor.

Conclusions

Until now, there is not exact mechanism on the relationship between gastric cancer and paraneoplastic dermatoses, which is worth investigating further. Paraneoplastic dermatoses can be seen as the early manifestation of visceral carcinomas. As a result, visceral tumors should be excluded in the patients with paraneoplastic dermatoses. Tumors can be detected early with biomakers, gastrointestinal endoscope, and even PET/CT.

Acknowledgements

Consent: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consents is available for review by the Editor-in-Chief of this journal. We thank the patients for giving us written consent for publishing their details.

Disclosure: The authors declare no confict of interest.

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Cite this article as:Ge W, Teng BW, Yu DC, Chen G, Zheng LM, Ding YT. Dermatosis as the initial presentation of gastric cancer: two cases. Chin J Cancer Res 2014;26(5):632-638. doi: 10.3978/j.issn.1000-9604.2014.10.01

10.3978/j.issn.1000-9604.2014.10.01

Submitted May 18, 2014. Accepted for publication Aug 15, 2014.