Tumour-induced osteomalacia (also known as oncogenic osteomalacia) is an uncommon condition. The fibroblast growth factor 23 (FGF-23), a polypeptide secreted by mesenchymal tumours, causes phosphaturia, which in turn results in defective mineralisation. In addition, FGF-23 causes suppression of the enzyme 1α-hydroxylase located in the proximal convoluted tubules of kidneys and responsible for final activation of vitamin D (from 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D).1 Once the tumour causing the osteomalacia is found, its excision usually results in complete remission of the bone disorder.2 Herein we report on a patient who presented to us with the features of oncogenic osteomalacia.

A 32-year-old woman born of non-consanguineous parents complained of gradually increasing proximal muscle weakness of both lower limbs over 1 year in February 2012. She also had pain in both hips while walking, which restricted her daily activities. She had no history of any chronic gastro-intestinal illness, and was not taking medication which might affect bone metabolism. Nor was there a family history of any similar illness. Clinical examination revealed severe proximal muscle weakness in both lower limbs. Active movements like external rotation and abduction at the both hips were painful. Otherwise the examination was unremarkable.

Biochemical evaluation revealed hypophosphataemia with phosphaturia (Table). Radiology of the hips showed bilateral femoral neck pseudofractures (Fig 1). These abnormalities favoured a diagnosis of hypophosphataemic osteomalacia. Further workup yielded a high FGF-23 level and computed tomography of the paranasal sinuses showed a soft tissue tumour in the left ethmoidal sinus (Fig 2).

The patient was treated with phosphate supplements and underwent complete excision of the left ethmoidal sinus mass. Histopathological examination confirmed the diagnosis of a phosphaturic mesenchymal tumour. The patient remained stable after surgery. Two months later she was asymptomatic, by which time her muscle weakness had resolved markedly. Respective serial serum phosphate concentrations were 0.90, 1.00, and 1.35 mmol/L at 1, 2 and 4 weeks after surgery. After surgery, her plasma FGF-23 levels were undetectable.

Phosphaturic mesenchymal tumours are rare mesenchymal tumours and mostly comprised of a single histological entity with mixed connective tissue (designated PMT-MCT). Such tumours can occur in the soft tissue or bone.3 Most PMT-MCTs are histologically and clinically benign with rare instances of malignancy. Microscopically, PMT-MCTs are variable in appearance, usually being composed of small, bland round-to-spindle cells embedded in a vascular to myxochondroid matrix with variable amounts of mature adipose tissue (Fig 3). This matrix calcifies in an unusual ‘grungy’ fashion, inciting an osteoclast-rich and fibrohistiocytic response. A very prominent feature of PMT-MCT is its elaborate intrinsic microvasculature. Malignant PMT-MCTs resemble undifferentiated pleomorphic sarcomas or fibrosarcomas.3 After complete excision of the tumour, most patients improve dramatically4 and become symptomatically, biochemically, and radiologically better. Such results should prompt the physicians to search for such treatable and potentially curable causes, whenever they encounter hypophosphataemic osteomalacia.

1. Chokyu I, Ishibashi K, Goto T, Ohata K. Oncogenic osteomalacia associated with mesenchymal tumor in the middle cranial fossa: a case report. J Med Case Rep 2012;6:181. CrossRef

2. Komínek P, Stárek I, Geierová M, Matoušek P, Zeleník K. Phosphaturic mesenchymal tumour of the sinonasal area: case report and review of the literature. Head Neck Oncol 2011;3:16. CrossRef

3. Folpe AL, Fanburg-Smith JC, Billings SD, et al. Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature. Am J Surg Pathol 2004;28:1-30. CrossRef

4. Chong WH, Molinolo AA, Chen CC, Collins MT. Tumor-induced osteomalacia. Endocr Relat Cancer 2011;18:R53-77. CrossRef

An 87-year-old man who previously worked in shipyard with asbestosis was admitted in November 2012 because of fever of unknown origin. He presented with fever on-and-off for 2 months and cough. On physical examination, there was no cervical lymphadenopathy or hepatosplenomegaly and the chest was clear. Complete blood picture, and liver and renal function tests remained unremarkable. Chest X-ray (CXR) and computed tomography (CT) of the thorax yielded calcified pleural plaques, diaphragmatic calcification, diffuse centrilobular nodules, and interstitial septal thickening (Fig 1). Sputum and urine cultures were negative. Further investigations included smears and cultures for acid-fast bacilli and testing for Mycobacterium tuberculosis (MTB) by polymerase chain reaction of sputum, urine, and bronchoalveolar larvage samples, all of which were negative. Searches for aspergillus antigen, cryptococcal antigen, the Weil-Felix test, the Widal test, nasopharyngeal aspirate for influenza and mycoplasma, urine examination for legionella antigen, automminue profiling, and tests for tumour markers, human immunodeficiency virus, and sputum cytology were all non-contributory. The patient’s C-reactive protein was elevated to 3.39 mg/dL (reference range, <0.76 mg/dL). His fever had persisted on-and-off for 2 months despite multiple courses of broad-spectrum antibiotics. Positron emission tomography (PET)–CT yielded pronounced micronodules, especially over both upper lobes (Fig 1) and patchy ground glass opacities over both lower lobes with increased 18-fluorodeoxyglucose (¹⁸FDG) uptake (maximum standardised uptake values of up to 4; Figs 2 and 3). The absence of pulmonary masses, mediastinal or hilar lymphadenopathy or nodular thickening of interlobular septa and any bronchovascular bundle made malignancy or lymphangitis carcinomatosis unlikely. Based on the radiology, the patient was diagnosed to have pulmonary MTB for which anti-MTB treatment was initiated. He developed sudden cardiac arrest 1 day later, and failed resuscitation. Sputum and urine sample culture results available after the patient’s demise grew MTB.

Asbestosis is caused by the inhalation of asbestos which was once used as an electrical and thermal insulator. Asbestos causes fibrosis of the pleura and lung, as well as malignant mesothelioma, and PET-CT is a well-known means of picking up this complication as a linear area of intense ¹⁸FDG uptake surrounding the lungs.1 Fever of unknown origin can be due to infection, malignancy, autoimmune conditions, or drugs. Tuberculosis was one of the most common infectious causes. One of the diagnostic difficulties in our patient was the presence of interstitial lung disease making the interpretation of CXR and CT images challenging. Soussan et al2 has classified the PET appearance of pulmonary MTB into lung and lymphatic patterns and demonstrated improved diagnostic accuracy after taking account of the other specific CT changes such as upper lobe consolidation with cavitations or multiple ill-defined micronodules surrounding a cavity. Findings pertaining to our patient fitted well into previously described lung pattern of increased ¹⁸FDG uptake in MTB. These included predominant lung parenchymal involvement and together with an interval excess of micronodules, especially over the both upper lobes, which led us to make a radiological diagnosis of MTB. The increased in ¹⁸FDG uptake is caused by local accumulation of inflammatory cells.3 Thus, PET-CT is useful in identifying an active pulmonary tuberculoma in the absence of initial microbiological proof. Monitoring the response to anti-MTB treatment can also provide early evidence of drug-resistant MTB.3 4 The earlier performance of PET-CT and institution of anti-MTB treatment may have changed the clinical outcome of our patient.

1. Alavi A, Gupta N, Alberini JL, et al. Positron emission tomography imaging in nonmalignant thoracic disorders. Semin Nucl Med 2002;32:293-321. CrossRef

2. Soussan M, Brillet PY, Mekinian A, et al. Patterns of pulmonary tuberculosis on FDG-PET/CT. Eur J Radiol 2012;81:2872-6. CrossRef

3. Kosterink JG. Positron emission tomography in the diagnosis and treatment management of tuberculosis. Curr Pharm Des 2011;17:2875-80. CrossRef

4. Demura Y, Tsuchida T, Uesaka D, et al. Usefulness of 18F-fluorodeoxyglucose positron emission tomography for diagnosing disease activity and monitoring therapeutic response in patients with pulmonary mycobacteriosis. Eur J Nucl Med Mol Imaging 2009;36:632-9. CrossRef

In July 2012, an extensive eczematous lesion was found incidentally over the external genitalia in a 77-year-old man who was being evaluated for lower limb cellulitis. The affected area had been present for 10 years; it was erythematous, macerated, and itchy. He had consulted countless doctors, but the itchiness was intense and the area of involvement was enlarging despite application of topical creams. On physical examination, the perineum was weepy with excoriation, crusts, and a serous discharge. The erythematous skin was indurated and had a well-defined margin. The penis shaft was swollen with palpable groin lymph nodes (Fig 1). Blood tests showed eosinophilia (1.1 x 10⁹/L) and an elevated erythrocyte sedimentation rate (58 mm/h).

A clinical suspicion of extramammary Paget’s disease (EMPD) was suggested by the dermatologist. Skin biopsy of the right suprapubic region confirmed the diagnosis (Fig 2), while another biopsy of the left groin showed poorly differentiated invasive carcinoma, consistent with invasive EMPD. Urine for cytology, as part of the malignancy screening, showed atypical cells. Computed tomography of the abdomen revealed left ureteric obstruction with enhanced mural thickening of left ureter, of which transitional cell carcinoma could not be excluded. He was referred to a urologist for further assessment. Radiotherapy to the affected skin lesions was given in view of the extensive involvement.

Extramammary Paget’s disease is a rare intraepithelial adenocarcinoma of the skin rich in apocrine glands, first described by Crocker in 1888.1 The disease involves the epidermis, but can potentially metastasise via the lymphatic system.2 Its clinical and histological features are similar to Paget’s disease of the nipple. The penis, scrotum, and vulva are frequently involved in sites. The erythematous area has a sharp margin and scaly surface. Intense itchiness is common and may result in erosion, excoriation, and lichenification.2

Our patient had a typical presentation with longstanding, distressing, and difficult-to-treat, eczema-like perineal lesion with a well-defined border. Delay in diagnosis, up to a decade,3 is notoriously common, because EMPD often mimics benign dermatological diseases such as eczema, contact dermatitis and fungal infection, and even malignant skin conditions like superficial melanoma, basal cell carcinoma, and Bowen’s disease.

A clinical diagnosis should be confirmed by skin biopsy. Immunohistochemistry shows the cells are positive for CEA, CAM 5.2, as well as keratins CK7 and 8. Once EMPD is diagnosed, thorough search for malignancy is mandatory, since up to 37% of patients have associated malignancies, in which case the condition is referred to as secondary EMPD.4 A recent study among Chinese patients showed that 8.3% out of 48 patients with EMPD developed malignancy.3 Location of skin involvement in EMPD predicts the type of cancer; perianal lesions are associated with anal and colorectal cancer, whereas penoscrotal lesions tend to be associated with urogenital malignancies.4 The positivity of Cytokeratin 20 in immunostaining is also highly associated with internal malignancies.5

Treatment is mainly surgical resection with reconstruction. Radiotherapy is an adjunctive therapy or reserved for frail elderly patients.2 Photodynamic therapy and topical imiquimod have been used. Despite these treatments, the local recurrence rate still ranges from 21% to 61%,3 with a median time to recurrence of 2 years.

We would like to thank Dr Shun-chin Ng, Dermatologist, Department of Health, Hong Kong, for his clinical care and manuscript advice. We thank Dr Wing-hung Lau, Department of Pathology, Queen Elizabeth Hospital, for provision of histological diagnosis and picture.

1. Crocker HR. Paget's disease affecting the scrotum and penis. Trans Pathol Soc Lond 1888;40:187-91.

2. Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook's textbook of dermatology. 8th ed. Oxford, UK: Wiley-Blackwell; 2010.

3. Chan JY, Li GK, Chung JH, Chow VL. Extramammary Paget's disease: 20 years of experience in Chinese population. Int J Surg Oncol 2012;2012:416418.

4. Sarmiento JM, Wolff BG, Burgart LJ, Frizelle FA, Ilstrup DM. Paget's disease of the perianal region—an aggressive disease? Dis Colon Rectum 1997;40:1187-94. CrossRef

5. Liegl B, Liegl S, Gogg-Kamerer M, Tessaro B, Horn LC, Moinfar F. Mammary and extramammary Paget's disease: an immunohistochemical study of 83 cases. Histopathology 2007;50:439-47. CrossRef

No abstract available.

No abstract available.