Cowden syndrome. Managing multiple skeletal metastases of different origin: a case report
© Angoules et al; licensee BioMed Central Ltd. 2008
Received: 16 October 2008
Accepted: 23 October 2008
Published: 23 October 2008
Cowden Syndrome is a rare autosomal dominant multiple hamartomatous condition, characterised by both benign and malignant tumours affecting multiple systems.
We present a 47-year-old female patient with thigh pain that was diagnosed with Cowden syndrome 20 years ago and developed multiple and different skeletal metastases which became resistant to radio-chemotherapy. A percutaneous plate fixation of the distal femur with an intralesional excision and cementoplasty of the metastasis was performed initially. This was combined with a cemented total hip arthroplasty using an Exeter long revision stem and a cementoplasty of the femoral canal for the proximal lesions.
A meticulous approach to her complex metastatic disease resulted in successful palliative prophylactic reconstructive surgery that improved her quality of life, allowing her independent pain free walking for 12 months.
Cowden Syndrome (CS) is a rare autosomal dominant disorder characterised by multiple hamartomas and an increased risk of breast, thyroid and endometrial carcinomas [1, 2] Germline mutations in the tumour suppressor gene PTEN (phosphatase and tensin homolog) chromosome 10q23.2, which codes for a lipid phosphate mediating cell cycle arrest and apoptosis, were first described in Cowden Syndrome In the next years since PTEN had been identified as the major CS susceptibility gene, a number of inherited cancer and developmental syndromes were associated with germline PTEN mutations. It has therefore been proposed that all such syndromes based on molecular defects are classified as PTEN Hamartoma Tumour Syndromes (PHTS)[2, 5]. Irrespective of clinical phenotype however, the discovery of a germline PTEN mutation should trigger cancer risk surveillance. Skeletal metastases of multiple origins are difficult to treat and palliative surgery usually requires a combination of approaches and techniques.
A 47-year-old female Caucasian patient presented with a right sided limp and ipsilateral thigh pain with an established diagnosis of CS according to the International Cowden Syndrome Consortium Operational Criteria1, positive for tumour suppressor phosphatase and tensin homolog gene (PTEN) mutation.
She was first diagnosed with thyroid follicular carcinoma and was treated with a thyroidectomy in 1989. The patient then developed breast cancer in 1991 for which she underwent lumpectomy followed by adjuvant radio-chemotherapy. Due to local recurrence the following year, she was treated with a left mastectomy and a few months later she underwent right nephrectomy for renal carcinoma. In 2003, she was diagnosed with left scapular renal metastatic and during the same year she developed brain metastases that required a right frontal lobe resection followed by whole brain radiotherapy. On presentation, she was known to have pulmonary and multiple bone metastases. Palliative skeletal radiotherapy was completed having exceeded the maximum radiation limits. As a last resort, she was on interferon treatment as well as bisphosphonates for palliation therapy.
Surgical planning and technique
Our patient presented with a long history of metastatic CS resistant to radio-chemotherapy. We elected to proceed to a combined surgical treatment of both the proximal and distal femoral metastases leaving the unaffected mid femur intact. A percutaneous plate fixation of the distal femur with an intralesional excision and cementoplasty of the metastasis was performed initially. This was combined with a cemented total hip arthroplasty using an Exeter long revision stem and a cementoplasty of the femoral canal. Weber et al recommended curettage with cementation and stabilization for metastatic renal cell carcinomas that are refractory to local adjuvants such as radiotherapy. They showed that this can decrease local progression of the disease. The same authors also advised embolization twelve to thirty six hours pre-operatively for renal cell and thyroid carcinomas especially if the procedure is performed without a tourniquet as in our case. Recently Fuchs et al reported no difference in the long-term survival between wide resection and intralessional curettage of renal cell metastases. However the functional morbidity of a widespread resection and reconstruction and its effect on weight-bearing should be considered and weighed against the potential prolongation of survival. Cemented THA with long stem femoral implant and cemented acetabular component are also recommended for metastatic long bone disease. Uncemented implants are contraindicated as the bone is biologically inert following previous or adjuvant radiotherapy and does not therefore allow ingrowth onto the implants. Cardiopulmonary compromise and thromboembolic events can be minimised by venting the femoral canal and lowering cement pressurisation .
In our case, preoperative biopsy or intraoperative frozen section biopsy were deemed unnecessary as the MRI features of the metastatic lesions were vascular and therefore of renal or thyroid origin.
Mirels classification system is a reliable method of predicting the likelihood of a pathological fracture and was used along with the clinical evaluation of the overall functional status of the patient to guide our treatment. We believe that by preserving the femur we have maintained the limb's functional capacity to a significant extent. That would possibly not have been the case if a widespread bone resection or a complex replacement reconstructive procedure had taken place. In addition to, our surgical approach allowed bone cementoplasty enhancement avoiding major resections, excessive blood loss and a high risk of postoperative infection.
This case reports on CS, a rare disease with multiple skeletal metastases of different origin. The treatment included a combination of cemented arthroplasty, cementoplasty and internal fixation that maintained function and improved our patient's quality of life.
Written informed consent was obtained from the patient's husband for publication of this case report and accompanying images in Journal of Medical Case Reports.
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