Paraneoplastic dermatomyositis associated with testicular cancer: a case report and literature review
L. A. Dourmishev, J. M. Popov, and D. Rusinova
- Summary
Dermatomyositis (DM) is frequently associated with neoplastic disorders, mainly carcinomas. However, the association of DM with testicular cancer appears to be very rare. A 37-year-old male was treated for a skin rash on the face and arms with pronounced itching. In December 2005, a testicular swelling and ulceration appeared and a unilateral orchiectomy was performed after a diagnosis of seminoma testis was made. However, the skin rash worsened and symmetric muscle weakness appeared in February 2006. The patient was admitted to the Department of Dermatology, Medical University of Sofia, with characteristic heliotrope erythema, eyelid edema, erythematous plaques on the upper chest, and Gottron's papules on the wrists. Severe muscle weakness was found in the proximal limb muscles. The patient's creatine kinase level was significantly elevated, whereas ASAT and ALAT were within normal ranges. Electromyography and skin biopsy supported a diagnosis of DM. Treatment with moderate corticosteroids and a short course of azathioprine markedly improved the skin lesions and muscle weakness. Even in young patients with DM, the risk of neoplasm is increased. Early recognition of the characteristic skin rash may provide a clue to the diagnosis, and screening for neoplasm may improve the prognosis.
KEY Introduction WORDS
dermatomyositis, seminoma testis
Dermatomyositis (DM) is a disease of unknown etiology characterized by the association of progressive, proximal muscle weakness and pathognomonic or specific cutaneous findings. The first two cases of malignancy-associated DM were reported in 1916 by Stertz (1), who described a patient with gastric carcinoma, and Kankeleit (2), who reported on a female with DM associated with breast carcinoma. Since then, many case reports and
multicenter, retrospective, and case-control studies have been published in the literature focusing on the incidence, type of tumors, possible predictive factors, and prognosis in paraneoplastic DM (3—7). Malignancy was associated with DM in 23% to 43% of patients, highly supporting the paraneoplastic nature of the disease (7). We present a rare case of a patient that developed clinical signs of DM 1 month before being diagnosed with testicular
cancer.
Case report
A 37-year-old male was treated in November 2005 for acute dermatitis because of a skin rash on the face and arms with pronounced itching. One month later, testicular swelling and ulceration appeared, seminoma testis (T N0 Mx) was diagnosed, and a unilateral right orchidectomy was performed in January 2006. A CT of the pelvis revealed no indications of metastasis to the lymph nodes. However, the cutaneous lesions worsened, symmetric muscle weakness of the upper and lower extremities appeared, and the patient was admitted to the Department of Dermatology, Medical University of Sofia.
Figure 1. Periorbital violaceous erythema and V-shaped chest exanthema of a patient with paraneoplastic dermatomyositis associated with seminoma testis.
Clinical examination revealed periorbital edema and violaceous erythema of the eyelids (Fig. 1), erythematous plaques on the upper chest, and Gottron's papules on the wrists (Fig. 2). Severe muscle weakness involving the proximal limb muscles was noted; the patient could not raise his hands above his head. The patient's creatine kinase level was significantly elevated at 1,360 U/l, his ESR was slightly elevated (28 mm/h Westergreen), and his ASAT and ALAT were within normal ranges. Indirect immunofluorescence for ANA on HEp-2 cells and the anti-Jo-1 antibody were negative. Electromyography demonstrated multiple polyphasic low-amplitude potentials with sharp edges and short duration typical of myogenic injury. A skin biopsy from a lesion revealed atrophic epidermis with focal basal degeneration and perivascular lymphoid infiltration in the dermis.
Figure 2. Gottron's papules on the wrist of the same patient.
The patient was initially treated with oral methylprednisolone 60 mg daily with decreasing doses, and a short course of azathioprine 100 mg/ daily, which markedly improved the skin lesions and muscle weakness. The patient has been in complete remission since September 2006 and has been maintained on 8 mg methylprednisolone daily and topical sun protection. At his last visit in May 2009, no clinical or laboratory sings of disease activity were evident.
Discussion
Although the association between DM and cancer is well recognized, only a limited number of reports of DM associated with testicular cancer have been reported.
DM is associated with many different types of malignant tumors, mainly carcinomas rather than sarcomas. Breast (3), colon, and lung carcinomas (6) were reported as the most frequent tumors, and ovarian carcinoma was found much more frequently in white women with DM than would be expected in the general population (9). Lymphomas, Hodgkin disease, myeloma, and thymoma are much rarer (4). The association ofDM with testicular cancer appears to be very rare. Our review of the literature suggests that this is the eleventh case of such an association and only the second case of DM associated with seminoma (9—17) (Table 1). The reason could be the relative rareness of both disorders; nevertheless, in some cases, a strong relationship of testicular cancer and DM was evident, as in our patient.
Seminoma is a tumor considered to be relatively homogenous and developmentally close to the germ cells from which it derived during fetal development (18). As a histologic subtype of germ cell, seminoma tumors usually present in males between 15 and 35
Table 1. Case reports of paraneoplastic dermatomyositis (DM) associated with testicular tumors published in the literature.
Author	Year Case	Malignancy
Fife RS et al. (9)	1984	DM after cancer treatment	Metastatic non-seminomatous germ cell tumor
Barker RA et al. (10)	1987	30-year-old man, DM precedes malignancy	Metastatic non-seminomatous germ cell tumor
Clayton A et al. (11)	1998	28-year-old man, DM 2 months after BEP chemotherapy; 30-year-old man, DM precedes malignancy	Malignant teratoma
Hayami S et al. (12)	1998	24-year-old man, DM precedes malignancy	Malignant teratoma
Ishizawa et al. (13)	1999	24-year-old man, DM precedes malignancy	Intratubular GCT
Di Stasi SM et al. (14)	2000	31-year-old man, DM 3 years after orchiectomy	Nonseminomatous GCT
von Heyden B et al. (15)	2000	46-year-old man, DM precedes malignancy	Seminoma
Yoshinaga A et al. (16)	2005	31-year-old man, DM precedes malignancy	Nonseminomatous testicular cancer
Curiel RV et al. (17)	2005	34-year-old man, DM 3 months after orchiectomy	Nonseminomatous testicular cancer
years old as a painless, homogenous, and enlarging testicular nodule (19). This observation underscores the substantial prevalence of patients with DM and testicular cancer presenting in the third decade of life, which contrasts with the age distribution in other paraneoplastic DM patients (20). Seminoma is confined to the testicles in about 70% of cases and metastasizes to the draining lymph nodes in the retroperitoneum in about 25% of cases (19). Metastatic disease is present in 5% of cases and spreads hematogenously to the lung parenchyma, bone, liver, or brain (21).
The malignancy can precede, occur concurrently with, or follow the appearance of DM (20). Thus the definition of clinical and laboratory markers for
association with malignancy are of great importance for disease prognosis. Several predictive factors, such as the patient's age, male gender, cutaneous necroses, an increased ESR level, and very high or, alternately, normal serum levels of creatine kinase (CK) have been proposed (22—24). Our patient, however, fit only two of these criteria: a highly elevated CK serum level and male gender.
Recently Ishizawa et al. (13) focused on the clinical usefulness of LDH-1 as a marker of germ cell tumor appearance. LDH is frequently found to be elevated in patients with DM and polymyositis. However, an increased serum level of LDH-1 in a patient with DM might raise suspicion of a concomitant malignant germ cell tumor from either
the testis or ovary (13), and may have practical significance.
In conclusion, the risk of neoplasm is increased even in younger patients with DM. Early recognition
References
of the characteristic skin rash may provide a clue to the diagnosis, and screening for neoplasm may improve the prognosis in patients with inflammatory myopathies.
1.	Stertz G. Polymyositis. Berl Klin Wochensdir. 1916;53:489.
2.	Kankeleit H. Über primaire nichteitrige polymyositis. Dtsch Arch Klin Med. 1916;120:335-9.
3.	Barnes BE, Mawr B. Dermatomyositis and malignancy. A review of the literature. Ann Intern Med. 1976;84:68-76.
4.	Tymms KE, Webb J. Dermatomyositis and other connective tissue diseases: a review of 105 cases. J Rheumatol. 1985;12:1140-8.
5.	Chow WH, Gridley G, Mellemkjaer L, McLaughlin JK, Olsen JH, Fraumeni JF Jr. Cancer risk following polymyositis and dermatomyositis: a nationwide cohort study in Denmark. Cancer Causes Control. 1995;6(1):9-13.
6.	Sigurgeirsson B, Lindelöf B, Edhag O, Allander E. Risk of cancer in patients with dermatomyositis or polymyositis: a population-based study. N Engl J Med. 1992;326:363-7.
7.	Dourmishev LA. Dermatomyositis associated with malignancy. 12 case reports. Adv Exp Med Biol. 1999;455:193-9.
8.	Davis MD, Ahmed I. Ovarian malignancy in patients with dermatomyositis and polymyositis: a retrospective analysis of fourteen cases. J Am Acad Dermatol. 1997;37:730-3.
9.	Fife RS, Williams S, Eyanson S. Dermatomyositis associated with treated testicular carcinoma. J Rheumatol. 1984;11(3):397-8.
10.	Barker RA, Currie DC, Horwich A, Spiro SG. Metastatic non-seminomatous germ cell tumour and dermatomyositis. Postgrad Med J. 1990;66(771):59-60.
11.	Clayton AJ, Mead GM. Germ cell cancer and dermatomyositis. Clin Oncol (R Coll Radiol). 1998;10(1):56-8.
12.	Hayami S, Kubota Y, Sasagawa I, Suzuki H, Nakada T, Motoyama T. Dermatomyositis associated with intratubular germ cell tumor and metastatic germ cell cancer. J Urol. 1998;159(6):2096-7.
13.	Ishizawa T, Mitsuhashi Y, Kondo S. Dermatomyositis associated with testicular tumour with elevation of serum lactate dehydrogenase (LDH) isoenzyme-1. Acta Derm Venereol. 1999;79(2):167.
14.	Di Stasi SM, Poggi A, Giannantoni A, Zampa G. Dermatomyositis associated with testicular germ cell cancer. J Urol. 2000;163(1):240.
15.	von Heyden B, Kliesch S, Nashan D. Re: Dermatomyositis associated with testicular germ cell cancer. J Urol. 2000;164(6):2030.
16.	Yoshinaga A, Hayashi T, Ishii N, Ohno R, Watanabe T, Yamada T. Successful cure of dermatomyositis after treatment of nonseminomatous testicular cancer. Int J Urol. 2005;12(6):593-5.
17.	Curiel RV, Brindle KA, Kressel BR, Katz JD. Dysphagia after testicular cancer. Arthritis Rheum. 2005;52(12):3712.
18.	Aschim EL, Haugen TB, Tretli S, Daltveit AK, Grotmol T. Risk factors for testicular cancer-differences between pure non-seminoma and mixed seminoma/non-seminoma? Int J Androl. 2006;29(4):458-67.
19.	Hussey DH. The testicle. In: Cox JD, editor. Moss' radiation oncology: rationale, technique, results. 7th ed. St. Louis: Mosby-Year Book; 1994. p. 559-86.
20.	Dourmishev LA, Dourmishev AL. Paraneoplastic dermatomyositis. In: Dermatomyositis: advances in recognition, understanding and management. Berlin: Springer; 2009. p. 157-60.
21.	Thomas GM, Williams SD. Testis. In: Perez CA, editor. Principles and practice of radiation oncology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 1997. p. 1695-715.
22.	Basset-Seguin N, Roujeau JC, Gherardi R, Guillaume JC, Revuz J, Touraine R. Prognostic factors and predictive signs of malignancy in adult dermatomyositis. A study of 32 cases. Arch Dermatol. 1990;126:633-7.
23.	Gallais V, Crickx B, Belaich S. Facteurs pronostiques et signes predictifs de cancer au cours de la dermatomyosite de l'adulte. Ann Dermatol Venereol. 1996;123:722-6.
24.	Chen YJ, Wu CY, Shen JL. Predicting factors of malignancy in dermatomyositis and polymyositis: a case-control study. Br J Dermatol. 2001;144:825-31.
AUTHORS' Lyubomir A. Dourmishev, MD, PhD, Department of Dermatology, Medical ADDRESSES University, 1 St. Georgi Sofiiski, 1431 Sofia, Bulgaria, Tel.: +359 2 923 0416,
E-mail: l_dourmishev@yahoo. com Janko M. Popov, MD, PhD, same address Darena Rusinova, MD, same address