Journal of Clinical Oncology, Vol 21, Issue 1
(January), 2003: 166-167
© 2003 American Society for Clinical Oncology
Uncommon Syndromes and Treatment Manifestations of Malignancy
Case 1. Unusual Association of Lupus and Sarcoma
G. Rossi,
M. Lucioni,
L. Sammarchi,
M. Paulli,
G. Beluffi,
A. Martini,
A. Ravelli
Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Università di Pavia, Pavia; and Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Università di Genova, Genova, Italy
A 14-year-old girl was admitted to her local hospital with a 1-month history of intermittent low-grade fever, knee arthritis, and macular erythematous skin rash over the face, trunk, and lower limbs. Laboratory investigations showed increased erythrocyte sedimentation rate (43 mm/h) and C-reactive protein (98 mg/L), decreased serum complement levels (C3 35.8 mg/dL, C4 6.4 mg/dL), positive antinuclear antibodies (1:320, homogeneous pattern) and LE test, mild proteinuria (312 mg/24 hours), and 2+ microhematuria. A diagnosis of systemic lupus erythematosus (SLE) was made and corticosteroid therapy with 1 mg/kg/d prednisone was begun. This was followed by improvement of clinical manifestations and laboratory abnormalities. Prednisone treatment was gradually tapered and discontinued after 4 years. Six months before prednisone withdrawal, she had secondary amenorrhea. Gonadotropin hormones (follicular stimulating and luteinizing hormone) and pelvic ultrasonography were normal, whereas prolactin level was increased to 71 ng/mL (normal < 10 ng/mL). She was placed on estrogenic progestagenic therapy. Two months after prednisone discontinuation, she developed persistent dry cough with worsening exertional dyspnea. Chest x-ray disclosed a diffuse bilateral micronodular parenchymal infiltrate. A lupus exacerbation with lung involvement was suspected, and prednisone therapy at 1 mg/kg/d was restarted. Because respiratory symptoms did not improve and repeated chest x-ray after 3 weeks was unchanged, she was referred to our institute. On admission, she was afebrile and appeared in good general health. Physical examination revealed enlarged bilateral cervical lymph nodes of 0.5 to 1 cm in diameter, localized tumors of the head, and an abdominal wall nodule of 1 x 2 cm in diameter. There was no skin rash, arthritis, or hepatosplenomegaly. Complete blood count, erythrocyte sedimentation rate, C-reactive protein, liver and kidney function tests, and serum complement levels were normal. Antinuclear, anti-DNA and anticardiolipin antibodies, lupus anticoagulant, and rheumatoid factor were negative. Urinalysis revealed no hematuria or proteinuria. Angiotensin converting enzyme, Mantoux test, 24-hour urinary calcium, urinary vanilmandelic acid, serologies for Chlamydia, Legionella, Mycoplasma, and Bartonella were normal or negative. Serum prolactin was markedly increased at 3,967 ng/mL. Chest x-ray (Fig 1 ) and high-resolution computed tomography (CT) pulmonary scan showed diffuse, round, nodular opacities in both lung fields and bilateral hilar lobular opacities, which spared the mediastinum. There were no signs of "ground glass" involvement of the interstitium. Bronchoscopy disclosed a normal respiratory mucosa. Broncho-alveolar wash specimens contained lymphocytes, giant cells, and reactive pneumocytes; no acid-fast bacilli were detected. A CT scan of the abdomen revealed an irregular, solid mass of 15 mm in diameter in the right perirenal region. Magnetic resonance imaging of the cerebrum showed multiple contrast-enhanced expansive lesions of intracranial origin with extrameningeal extension and bony erosions (Fig 2). Surgical excision of the abdominal nodule led to the diagnosis of alveolar soft-part sarcoma. Histologically, the tumor showed a distinct alveolar pattern composed of large round to polygonal cells (Fig 3). Immunohistochemical analysis revealed positivity for CD68, Mib-1, (proliferation marker), and neuron-specific enolase. Electron microscopy disclosed cytoplasmic crystals highly characteristic of alveolar soft-part sarcoma (Fig 4). Chemotherapy with vincristine, ifosfamide, and carboplatin was carried out, but response was disappointing and the patient died after 6 months.
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Fig 1. Chest x-ray showing diffuse, round, nodular opacities in both lung fields and bilateral hilar lobular opacities.
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Fig 2. Magnetic resonance imaging of the cerebrum showing multiple contrast-enhanced expansive lesions of intracranial origin with extrameningeal extension and bony erosions.
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Fig 3. Histologically, the tumor showed a distinct alveolar pattern composed of large round to polygonal cells.
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Fig 4. Electron microscopy disclosed cytoplasmic crystals highly characteristic of alveolar soft-part sarcoma.
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Alveolar soft part sarcoma is a rare soft-tissue neoplasm of uncertain histogenesis that accounts for 5% of pediatric nonrhabdomyosarcoma soft-tissue sarcomas.1 It commonly occurs in the second and third decades of life and usually involves the musculoskeletal fascial planes of lower extremities, thighs, and buttocks. One third of patients develop lung and brain metastases, generally 10 or more years after diagnosis.2,3 Because chemotherapy has been ineffective in controlling disease, complete surgical resection offers the only hope of prolonged survival. The patient on whom we report here developed an autoimmune syndrome consistent with SLE, which was treated elsewhere with prolonged corticosteroid therapy, and was found to have, 4 and a half years later, a disseminated alveolar soft-part sarcoma. Although the association between SLE and sarcoma may have been coincidental, we cannot exclude the possibility that the lupus syndrome may have been an early manifestation of sarcoma. Because both SLE and sarcoma are rare in childhood, a chance association seems unlikely. Furthermore, it is well known that autoimmune phenomena and rheumatic features can occur in patients with malignancies, including soft-tissue sarcoma.4,5 In our patient, a possible link between sarcoma and lupus could have been the hyperprolactinemia. Current evidence indicates that prolactin may play a role in the pathogenesis and clinical expression of SLE, and it has been suggested that hyperprolactinemia may trigger the onset of SLE in susceptible individuals.6 In summary, our observation leads us to postulate that the paraneoplastic nature of the lupus syndrome is a likely explanation of the association between the two diseases in the same patient.
REFERENCES
1. Rao BN: Nonrhabdomyosarcoma soft tissue in children: Prognostic factors influencing survival. Semin Surg Oncol 9:524–531, 1993[Medline]
2. Lieberman PH, Brennan MF, Kimmel M, et al: Alveolar soft-part sarcoma: A clinico-pathologic study of half a century. Cancer 63:1–13, 1989[CrossRef][Medline]
3. Evans HL: Alveolar soft part sarcoma: A study of 13 typical examples and one with a histological atypical component. Cancer 55:912–917, 1985[CrossRef][Medline]
4. Abu-Shakra M, Buskila D, Ehrenfeld M, et al: Cancer and autoimmunity: Autoimmune and rheumatic features in patients with malignancies. Ann Rheum Dis 60:433–441, 2001[Abstract/Free Full Text]
5. Farber JN, Koh HK: Malignant fibrous histiocytoma arising from discoid lupus erythematosus. Arch Dermatol 124:114–116, 1988[Abstract/Free Full Text]
6. Jara LJ, Vera-Lastra O, Miranda JM, et al: Prolactin in human systemic lupus erythematosus. Lupus 10:748–756, 2001[Abstract/Free Full Text]
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