Paraneoplastic atypical scleromyxedema with advanced gastric cancer

Abstract

Scleromyxedema is a rare, chronic and progressive disorder of unknown origin characterized by a generalized papular eruption and sclerodermoid induration, with histopathologic features of mucin deposition and fibroblast proliferation.1Rongioletti F. Merlo G. Cinotti E. et al.Scleromyxedema: a multicenter study of characteristics, comorbidities, course, and therapy in 30 patients.J Am Acad Dermatol. 2013; 69: 66-72Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar The disease is usually associated with a monoclonal gammopathy.1Rongioletti F. Merlo G. Cinotti E. et al.Scleromyxedema: a multicenter study of characteristics, comorbidities, course, and therapy in 30 patients.J Am Acad Dermatol. 2013; 69: 66-72Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar, 2Nofal A. Amer H. Alakad R. et al.Lichen myxedematosus: diagnostic criteria, classification, and severity grading.Int J Dermatol. 2017; 56: 284-290Crossref PubMed Scopus (17) Google Scholar However, only a few cases associated with neoplasms have been reported.1Rongioletti F. Merlo G. Cinotti E. et al.Scleromyxedema: a multicenter study of characteristics, comorbidities, course, and therapy in 30 patients.J Am Acad Dermatol. 2013; 69: 66-72Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar, 3Rongioletti F. Rebora A. Updated classification of papular mucinosis, lichen myxedematosus, and scleromyxedema.J Am Acad Dermatol. 2001; 44: 273-281Abstract Full Text Full Text PDF PubMed Scopus (353) Google Scholar We report a case of paraneoplastic scleromyxedema with advanced gastric cancer. A 58-year-old woman presented with a several months' history of an erythematous swelling on the neck. The edema started on the posterior side of the neck and later progressed to the face, upper back, and both hands. A few weeks before she visited our department, the patient had exhibited an asymptomatic 4 × 3.5-cm–sized mass with an ulcer by esophagogastroduodenoscopy during a general medical examination with the Korean National Cancer Screening Program. Adenocarcinoma of the esophagogastric junction and regional metastatic lymph node were confirmed and her stage was determined to be advanced. Before the operation, she consulted with our department because of a progressive swelling of the skin. On physical examination, marked thickening of the skin with prominent folds over the posterior neck was observed (Fig 1, A). Erythematous indurative plaques were seen on the forehead with numerous small papules. Erythematous swelling of the eyelids and fingers were also observed. An incisional skin biopsy from the posterior neck was done to rule out scleredema. Pathologic examination showed myxoid degeneration in the upper dermis, increased fibroblasts, and thickened collagen in the dermis (Fig 2). These microscopic features were characteristic of scleromyxedema. The patient had multiple papules in a widespread pattern involving the forehead and fingers and did not have diabetes mellitus or any acute infection before the skin eruption. The combined clinical presentation and microscopic examination of skin tissue strongly suggested the presence of scleromyxedema. A full endocrine work-up, including serum thyroid-stimulating hormone, free thyroxine, adrenocorticotropic hormone, and 24-h cortisol urine test, were within normal limits. Autoantibody screening produced negative results. In addition, protein electrophoresis with immunofixation in blood was negative for a monoclonal component. The patient underwent subtotal gastrectomy and adjuvant chemotherapy for treatment of adenocarcinoma. One month after surgery, the swelling on the neck partially improved and flat balloon-like wrinkles remained. Following 3-month cycles of chemotherapy with tegafur, gimeracil, and oteracil potassium, the skin lesion ameliorated (Fig 1, B). Scleromyxedema is characterized by an extensively symmetrical eruption of small, waxy papules, which progress to sclerosis and induration of the skin, usually on the face, neck, upper trunk, arms, and thighs. In 2001, Rongioletti and Rebora3Rongioletti F. Rebora A. Updated classification of papular mucinosis, lichen myxedematosus, and scleromyxedema.J Am Acad Dermatol. 2001; 44: 273-281Abstract Full Text Full Text PDF PubMed Scopus (353) Google Scholar defined scleromyxedema, also known as generalized lichen myxedematosus using the following criteria: (1) generalized papular and sclerodermoid eruption; (2) mucin deposition, fibroblast proliferation, and fibrosis; (3) monoclonal gammopathy; and (4) the absence of thyroid disease. According to this classification, a case that shows typical clinical and histopathologic features without monoclonal gammopathy belongs to an atypical form of scleromyxedema. Most patients with scleromyxedema have a monoclonal gammopathy, and other systemic manifestations are common. Disease presentation might involve gastrointestinal (eg, esophageal aperistalsis), musculoskeletal (eg, arthritis or myositis), cardiovascular (eg, ischemic heart disease or cardiomyopathy), pulmonary (eg, obstructive or restrictive lung diseases), neurologic (eg, peripheral neuropathy), or ophthalmologic (eg, macular edema) problems.1Rongioletti F. Merlo G. Cinotti E. et al.Scleromyxedema: a multicenter study of characteristics, comorbidities, course, and therapy in 30 patients.J Am Acad Dermatol. 2013; 69: 66-72Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar However, the association between malignancy and scleromyxedema has rarely been described. Among the rare cases, multiple myeloma is the most commonly associated malignancy with scleromyxedema, followed by lymphoma and solid tumors.4Krebs A. Muller A. [Lichen myxedematosus and multiple myeloma type IgG/kappa].Hautarzt. 1980; 31: 649-653PubMed Google Scholar, 5Gimenez Garcia R. Garcia S.G. Suarez Vilela D. Moro Sanchez M.J. Scleromyxedema associated with non-Hodgkin lymphoma.Int J Dermatol. 1989; 28: 670-671Crossref PubMed Scopus (15) Google Scholar, 6Alberts A.S. Schulz E.J. Falkson G. Simson I.W. Coccia-Portugal M.A. Normalization of skin appearance in a patient with scleromyxoedema after intensive chemotherapy for Hodgkin's disease.Dermatologica. 1989; 178: 221-224Crossref PubMed Scopus (14) Google Scholar To our knowledge, there is only 1 case reported showing an association of gastric cancer with scleromyxedema7Farmer E.R. Hambrick Jr., G.W. Shulman L.E. Papular mucinosis. A clinicopathologic study of four patients.Arch Dermatol. 1982; 118: 9-13Crossref PubMed Scopus (71) Google Scholar; In this case report, a 44-year-old man with progressive thickening of the skin of his face, trunk, and extremities was found to have poorly differentiated metastatic carcinoma involving omentum 9 years after his skin eruption. The affected areas gradually increased, and he died 1 month after the detection of cancer. Thus, the causal relationship between skin eruption and cancer was not obvious. Gastric cancers might be associated with a variety of paraneoplastic disorders. Several paraneoplastic dermatoses, including acanthosis nigricans, florid cutaneous papillomatosis, and tripe palms, were reported to be associated with gastric cancer. Tumor production of transforming growth factor α and epidermal growth factor is the proposed mechanisms for these disorders. Successful treatment of the underlying malignancy might result in improvement and occasionally resolution of the condition.8Yang Y.H. Zhang R.Z. Kang D.H. Zhu W.Y. Three paraneoplastic signs in the same patient with gastric adenocarcinoma.Dermatol Online J. 2013; 19: 18966PubMed Google Scholar In our case, the patient's eruption improved after the removal of the tumor; thus, we propose the plausible attribution of paraneoplastic syndrome of gastric cancer. The pathogenesis of scleromyxedema with cancer is unknown. The correlation of serum paraprotein with the natural course of the disease is still debated. Also it has been suggested that a nonparaprotein circulating factor or altered immune regulation is involved in the course of the scleromyxedema.2Nofal A. Amer H. Alakad R. et al.Lichen myxedematosus: diagnostic criteria, classification, and severity grading.Int J Dermatol. 2017; 56: 284-290Crossref PubMed Scopus (17) Google Scholar, 9Lo P.Y. Tzung T.Y. Lichen myxedematosus in a patient with hepatocellular carcinoma.Br J Dermatol. 2000; 143: 452-453Crossref PubMed Scopus (15) Google Scholar Thus, it is likely that immune dysregulation associated with a malignant proliferation of cells could result in the pathogenesis of scleromyxedema. Given the limited data regarding its course and prognosis due to its rare incidence, no standardized treatment of scleromyxedema exists. As a result, the therapeutic response varies greatly among patients. Systemic therapies, including high-dose dexamethasone, intravenous immunoglobulins, low- or high-dose melphalan, photopheresis, thalidomide, and autologous stem cell transplant, have been used.1Rongioletti F. Merlo G. Cinotti E. et al.Scleromyxedema: a multicenter study of characteristics, comorbidities, course, and therapy in 30 patients.J Am Acad Dermatol. 2013; 69: 66-72Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar Among patients with coexistent mucinosis and malignancy, treatment is known to be refractory and is highly dependent on the course of malignancy. Most of the treatments used resulted in poor outcomes; the skin lesions remained unchanged or had gotten worse.9Lo P.Y. Tzung T.Y. Lichen myxedematosus in a patient with hepatocellular carcinoma.Br J Dermatol. 2000; 143: 452-453Crossref PubMed Scopus (15) Google Scholar However, several reports have described chemotherapy being given for the treatment of the primary cancer, resulting in the regression of the skin lesions.1Rongioletti F. Merlo G. Cinotti E. et al.Scleromyxedema: a multicenter study of characteristics, comorbidities, course, and therapy in 30 patients.J Am Acad Dermatol. 2013; 69: 66-72Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar, 5Gimenez Garcia R. Garcia S.G. Suarez Vilela D. Moro Sanchez M.J. Scleromyxedema associated with non-Hodgkin lymphoma.Int J Dermatol. 1989; 28: 670-671Crossref PubMed Scopus (15) Google Scholar, 6Alberts A.S. Schulz E.J. Falkson G. Simson I.W. Coccia-Portugal M.A. Normalization of skin appearance in a patient with scleromyxoedema after intensive chemotherapy for Hodgkin's disease.Dermatologica. 1989; 178: 221-224Crossref PubMed Scopus (14) Google Scholar Also, there are 2 cases of scleromyxedema with malignancy that showed remission of skin lesions after surgery.9Lo P.Y. Tzung T.Y. Lichen myxedematosus in a patient with hepatocellular carcinoma.Br J Dermatol. 2000; 143: 452-453Crossref PubMed Scopus (15) Google Scholar, 10Kubba R. McNeil N.I. Rook A. Lichen myxoedematosus, Crohn's disease, and mucinous ovarian carcinoma.Br J Dermatol. 1975; 93: 34-36Crossref Scopus (9) Google Scholar In our case, indurated cutaneous lesions improved spontaneously several weeks after surgery, and papules and swelling regressed during the course of chemotherapy. Thus, progressive improvement without treating the skin problem itself could suggest the paraneoplastic association. In conclusion, clinicians should be aware of the potential associations of scleromyxedema with neoplasms. Paraneoplastic eruptions might have a better prognosis after surgery or chemotherapy.