Fibrodysplasia ossificans progressiva presenting as ankylosing spondylitis

Letters to the Editor

Figure 2 Histopathology of lung. The circumscribed lesion composed of bland cells showed all four architectural patterns described in pneumocytoma: (a) angiomatous, (b) papillary, (c) solid, (d) sclerotic.

In summary, pneumocytoma is a relatively rare, usually benign, pulmonary neoplasm. Although the imaging findings are relatively characteristic in the appropriate clinical setting, biopsy is needed for definitive diagnosis. Received 22 September 2009; accepted 16 November 2010. doi:10.1111/j.1445-5994.2010.02365.x

F. Thien,1 P. Naidoo,2 C. Weng Ong,1 A. Barling3 and S. Monagle4 Departments of 1Respiratory Medicine, 2Radiology, 3Surgery and 4 Pathology, Eastern Health and Monash University, Box Hill Hospital, Melbourne, Victoria, Australia

References 1 Liebow AA, Hubbell DS. Sclerosing hemangioma (histiocytoma, xanthoma) of the lung. Cancer 1956; 9: 53–75. 2 Fujiyoshi F, Ichinari N, Fukukura Y, Sasaki M, Hiraki Y, Nakajo M. Sclerosing hemangioma of the lung: MR findings and correlation with pathological features. J Comput Assist Tomogr 1998; 22: 1006–8. 3 Fraser RS, Pare JAP, Fraser RG. Synopsis of Diseases of the Chest, 2th edn. Philadelphia: WB Saunders Co.; 1994; 517–8. 4 Kim GY, Kim J, Choi YS, Kim HJ, Ahn G, Han J. Sixteen cases of sclerosing hemangioma of the lung including unusual presentations. J Korean Med Sci 2004; 19: 352–8. 5 Situ DR, Long H, Ma GW, Lin ZC, Yun JP, Rong TH. Diagnosis and therapeutics of 24 cases of pulmonary sclerosing hemangioma. Ai Zheng 2008; 27: 861–5.

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6 Sugio K, Yokoyama H, Kaneko S, Ishida T, Sugimachi K. Sclerosing hemangioma of the lung: radiographic and pathological study. Ann Thorac Surg 1992; 53: 295–300. 7 Miyagawa-Hayashino A, Tazelaar HD, Langel DJ, Colby TV. Pulmonary sclerosing hemangioma with lymph node metastases: report of 4 cases. Arch Pathol Lab Med 2003; 127: 321–5. 8 Wang E, Lin D, Wang Y, Wu G, Yuan X. Immunohistochemical and ultrastructural markers suggest different origins for cuboidal and polygonal cells in pulmonary sclerosing hemangioma. Hum Pathol 2004; 35: 503–8. 9 Leslie K, Wick M. Practical Pulmonary Pathology: A Diagnostic Approach. Philadelphia: Churchill Livingstone; 2005; 702–5. 10 Nam JE, Ryu YH, Cho SH, Lee YJ, Kim HJ, Lee DY et al. Air-trapping zone surrounding sclerosing hemangioma of the lung. J Comput Assist Tomogr 2002; 26: 358–61.

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Fibrodysplasia ossificans progressiva presenting as ankylosing spondylitis We report a case of fibrodysplasia ossificans progressiva (FOP) mimicking ankylosing spondylitis (AS). FOP is characterized by progressive replacement of muscle and connective tissue with bone, history of spontaneous soft tissue swellings beginning in childhood (‘flares’) and microdactyly (short malformed big toes or thumbs).1,2 In 2004, a 24-year-old woman presented with a 2-year history of back pain and stiffness which improved with © 2010 The Authors Internal Medicine Journal © 2010 Royal Australasian College of Physicians

Letters to the Editor

Figure 1 (a) Radiography showing erosion, periarticular sclerosis and irregular cortical margins in sacro-iliac joints and fused facet joints (arrows). (b) Computed tomography (CT) showing heterotopic ossification (arrow) of right anterior neck strap muscles. Heterotopic ossification (arrow) of interspinous ligaments (c) and ligamentum flavum (d) as visualized by 3-D CT reconstruction images.

activity and worsened with rest, with no history of prior diarrhoea or psoriasis. Examination revealed a stooped posture, restricted cervical and lumbar spine movements and a 2 ¥ 2 cm firm mass in the right submandibular fossa. Histopathology of the mass showed proliferative fibrous stroma with no malignant cells and it resolved spontaneously within 2 months. Radiography showed eroded sacro-iliac joints (SIJs) with periarticular sclerosis and irregular cortical margins, fused thoraco-lumbar facet joints and no syndesmophytes (Fig. 1a). C-reactive protein (CRP) was 5 mg/L (reference range (RR), 0–10 mg/L) and HLA-B27 was negative. A provisional diagnosis of ‘undifferentiated spondyloarthritis’ was applied and anti-inflammatory agents and exercises were initiated. She subsequently developed polyarthralgia (shoulders and hips) and her back pain deteriorated. In 2005, she developed a mass in her right axilla without preceding trauma. Magnetic resonance imaging showed © 2010 The Authors Internal Medicine Journal © 2010 Royal Australasian College of Physicians

high T2 signal in the right serratus anterior and intercostal muscles suggestive of myositis. CRP was 8 mg/L and creatine kinase 97 U/L (RR 0–180 U/L). The mass improved within days and hence muscle biopsy was deferred. She was lost to follow up and re-presented in 2009 with increasing back stiffness, polyarthralgia, restricted shoulder and spine movements and a mass on the right side of the neck. Computed tomography of neck and spine showed extensive heterotopic ossification (HO) in the anterior neck strap muscles, interspinous ligaments and ligamentum flavum (Figs 1b, c, d). There was no history of ‘flares’ in her childhood. Hands and feet were normal. A clinical diagnosis of FOP was reached based on the radiographic findings of spontaneously occurring extensive HO. Fibrodysplasia ossificans progressiva can mimic AS with inflammatory back pain, polyarthralgia and SIJ involvement and has been reported twice previously.3,4

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Distinction is straightforward with a history of childhood flares and microdactyly, but is challenging in patients with atypical late-onset disease as illustrated herein.1,2,5 The diagnosis is based on distinctive clinical features and radiographic evidence of spontaneous HO, as invasive diagnostic measures are contraindicated as they can trigger accelerated HO.1,2,5 Cutaneous and occasionally deep tissue HO is seen in patients with progressive osseous heteroplasia,6 a rare genetic disease, distinguished from FOP by lack of microdactyly and ‘flares’. Localized HO can occur in the setting of prolonged mechanical ventilation, after trauma and in patients with brain and spinal cord injury. Increased expression of bone morphogenetic protein type-1 receptor, secondary to mutation of a gene encoding activin receptor 1A has been shown in FOP,1 but targeted therapies are unavailable. ‘Flares’ may be managed with glucocorticoids and anti-inflammatory agents.1 FOP causes cumulative disability and preventive strategies, including avoidance of contact sports, falls, invasive diagnostic procedures and i.m. injections to minimize ‘flares’ are recommended. Received 17 September 2009; accepted 12 January 2010. doi:10.1111/j.1445-5994.2010.02363.x 1

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M. Dugar, V. Limaye, L. G. Cleland1 and M. J. Ahern2 Department of Rheumatology, 1Royal Adelaide Hospital, Adelaide, and 2Repatriation General Hospital, Adelaide, South Australia, Australia

References 1 Kaplan FS, Le Merrer M, Glaser DL, Pignolo RJ, Goldsby RE, Kitterman JA et al. Fibrodysplasia ossificans progressiva. Best Pract Res Clin Rheumatol 2008; 22: 191–205. 2 Bridges AJ, Hsu KC, Singh A, Churchill R, Miles J. Fibrodysplasia (myositis) ossificans progressiva. Semin Arthritis Rheum 1994; 24: 155–64. 3 Elloumi M, Fourati H, Ezeddine M, Baklouti S. Myositis ossificans progressiva mimicking ankylosing spondylitis (a case report). Joint Bone Spine 2006; 73: 570–1. 4 Lu LY, Cheng HH, Chuang JC, Chen JH, Chen C. Myositis ossificans progressiva mimicking ankylosing spondylitis: a case report. Zhonghua Yi Xue Za Zhi (Taipei) 1992; 49: 373–8. 5 Kaplan FS, Xu M, Glaser DL, Collins F, Connor M, Kitterman J et al. Early diagnosis of fibrodysplasia ossificans progressiva. Pediatrics 2008; 121: e1295–300. 6 Adegbite NS, Xu M, Kaplan FS, Shore EM, Pignolo RJ. Diagnostic and mutational spectrum of progressive osseous heteroplasia (POH) and other forms of GNAS-based heterotopic ossification. Am J Med Genet A 2008; 146A: 1788–96.

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General correspondence

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Chemotherapy for hormone-refractory prostate cancer: a physician’s dilemma I read with interest the paper by Sewak et al.1 describing a phase 2 study of paclitaxel and vinlorebine in hormonerefractory metastatic prostate cancer. While the results of TAX 3272 and SWOG 99-163 studies, as outlined by the authors, do represent a significant milestone in the treatment of this disease, there are other considerations which should not be overlooked. The treatment is not unanimously effective. Surely, the taxane combinations do work, but only one-third of patients respond and the survival benefit is small, equating to a median of 2.4 months, when compared with patients treated on mitozantrone. This modest improvement was accompanied by a significant increase in overall toxicity, with up to 45% of patients suffering grade 3 to 4 toxic effects. Patient eligibility is another concern. Over 85% of the patients in both the studies had a Karnofsky performance status greater than 70%, with the median age of approximately 68 years. It is obvious that this reasonably healthy cohort of patients is not representative of most patients with treatment-refractory prostate cancer seen in cancer clinics. A significant portion of prostate cancer patients suffer from cardiovascular, pulmonary and renal comorbidities and hence, careful patient selection may be needed to avoid undue treatment-related toxicity. The economics of cost and benefit also merit some deliberation. Economic models used by the National Institute for Health and Clinical Excellence suggest that docetaxel costs between £28 000 and £33 000 per ‘quality-adjusted life year’ gained.4 A few questions still stay unanswered. Who should receive chemotherapy and when is the optimum time to start? Are symptoms requisite, or should patients start chemotherapy before symptoms become apparent? The optimum duration of chemotherapy is also unclear. While patients in TAX 327 trial were treated with 10 cycles of docetaxel every 3 weeks, this duration of treatment was empirical. Also, when is a ‘chemotherapy holiday’ required? Oncologists face this dilemma every day as they seek to identify patients who will benefit most from this therapy. Despite these concerns, docetaxel has quickly emerged as the standard of care and further trials are ongoing in a bid to improve the progression-free and overall survival of patients with hormone-refractory prostate cancer. The TRAPEZE 2 trial is a four-arm phase 2 study recruiting chemotherapy-naïve patients to receive docetaxel and prednisolone either alone as the control arm, or in © 2010 The Authors Internal Medicine Journal © 2010 Royal Australasian College of Physicians