- Email: [email protected]
Subcutaneous metastasis of a GIST tumour unresponsive to Imatinib
Journal of Plastic, Reconstructive & Aesthetic Surgery (2011) 64, e250ee251
CORRESPONDENCE AND COMMUNICATION Subcutaneous metastasis of a GIST tumour unresponsive to Imatinib Gastrointestinal Stromal Tumours (GIST) are rare intestinal tumours of mesenchymal origin. They arise in the muscularis of the intestinal tract. Metastatic spread is most commonly intra-abdominal, affecting the liver and peritoneum. Extra-abdominal spread is unusual and metastases to subcutaneous tissues are extremely rare.1 We describe a case of recurrent metastatic oesophageal GIST with a subcutaneous deposit resistant to Imatinib therapy, despite a clinical response in the primary site and liver metastases.
Case report A 61-year old lady was referred to us by the general surgical team in July 2010, with a large fungating tumour overlying the right deltoid. In 2006 she had been diagnosed with GIST involving the lower 2/3rds of the oesophagus. Initial treatment comprised neoadjuvent therapy with Imatinib and a 2-stage oesophagectomy. Histology confirmed a highrisk tumour with circumferential margin involvement. Within months of the primary surgery she had developed local recurrence at the anastamotic site and two liver metastases. She remained on Imatinib and under regular surveillance. In 2009 the patient fell onto her right shoulder and developed swelling and redness that persisted until her next oncology review. A diagnosis of resolving haematoma secondary to trauma was made, but an ultrasound scan was arranged to confirm this. The scan showed a 2.4 cm 3.6 cm 1.6 cm subcutaneous mass suspicious of a GIST metastasis. A subsequent PET scan confirmed the presence of the subcutaneous metastasis with stable local and regional disease. By 2010 the subcutaneous mass had significantly increased in size. Clinical examination revealed a large fungating tumour to the right deltoid region (Figure. 1) measuring 12 cm diameter and 8 cm wide. It had well defined edges and involved the skin and subcutaneous tissues. The skin displayed haemorrhagic changes and central ulceration. No lymphadenopathy was evident.
An urgent CT scan confirmed the subcutaneous deposit had increased to 13 cm 11 cm 7.5 cm. Multiple areas of necrosis and invasion into deltoid were observed. The humerus and scapula were not involved. No new enlarged mediastinal or hilar lymph nodes were identified. The gastrooesophageal anastamosis and lung nodule remained unchanged. The liver lesions had marginally decreased in size. The tumour was excised under general anaesthetic using electrocautery. A 3 cm peripheral margin was taken and a cuff of deltoid proximally to ensure completeness of excision (Figure. 2). The defect was resurfaced using split thickness skin graft from the right thigh (Figure. 3). Histology confirmed complete excision of a spindle cell tumour with monomorphic cellularlity and abundant mitoses, consistent with a GIST metastatic tumour. Immunohistochemical studies were confirmed as KIT (CD117) and CD34 positive, CK AE1/AE3 negative and SMA negative. The patient was reviewed three months postoperatively and was completely healed with no evidence of recurrence.
Discussion GIST is the most common mesenchymal tumour of the bowel with an estimated incidence of 6.5e14.5 per million. It most often occurs in patients over the age of fifty. Stomach and small bowel are predominant sites, but colon, rectum and oesophagus may be involved. Almost all have a mutation in the tyrosine kinase receptor gene (KIT) or platelet derived growth factor alpha (PDGFA). Metastases are usually seen in the liver, as in this case, as well as the abdominal cavity. Extra-abdominal metastases are less common and sites include lung, bone, skin and soft tissue.2 There are very few published cases of cutaneous or subcutaneous metastases from GIST. The first by Shabahang (2002)3 documented a patient with multiple metastases from a gastric GIST that included liver, spleen, jaw, thigh and groin lesions. Miettinen et al. (2005)4 reviewed 1765 cases of gastric GIST and found that just five had either soft tissue or skin metastases. A further study from by this group (2006) of 906 small intestinal GIST tumours showed no cutaneous metastases.5 A case of subcutaneous metastasis was reported by Anagnostoulis et al. (2007) 6 This followed an ulcerating gastric GIST and the patient died shortly after excision of both lesions.
1748-6815/$ - see front matter ª 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjps.2011.03.038
Correspondence and communication
Figure 1
e251
Figure 3
Pre-operative view.
Post operative view.
Funding sources There are no sponsors or outside sources of funding for this article.
Ethical approval No ethical approval was sought for this article. Consent for publication was obtained from the patient.
References Figure 2
Intra-operative post resection view.
Most recently, Wang et al. (2009) published a series of 5 cases.1 The sites involved were scalp (n Z 2) cheek (n Z 1) abdomen (n Z 2). The average size was just 2 cm. Histologically, two were spindle cell (as in this case) and three were mixed epithelioid and spindle cell. All were confirmed to have CD117 reactivity as in this case. KIT genotyping was performed in 4 cases and each displayed mutations. The use of Imatinib following surgical resection has revolutionalised patient survival. Imatinib is a small molecule that binds competitively to the ATP binding sites of target tyrosine kinases and thereby inhibits their activity. This inhibition halts growth of the GIST cell line containing KIT gene mutation. Prior to the use of Imatinib median survival was nine months and now is closer to five years.7 This case shows that the management of subcutaneous and cutaneous metastases in GIST remains surgical. Given that these tumours are usually KIT positive it is surprising that Imatinib is not more effective in their management. We encourage early detection and surgical excision of these tumours.
Conflict of interest statement There are no conflicts of interest that influence the composition of this article.
1. Wang WL, Hornick JL, Mallipeddi R, et al. Cutaneous and subcutaneous metastases of gastrointestinal stromal tumors: a series of 5 cases with molecular analysis. Am J Dermatopathol 2009;32:297e300. 2. Rubin BP, Heinrich MC, Corless CL. Gastrointestinal stromal tumour. Lancet 2007;369:1731e41. 3. Shabahang M, Livingstone AS. Cutaneous metastases from a gastrointestinal stromal tumor of the stomach: review of literature. Dig Surg 2002;19:64e5. 4. Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol 2005;29:52e68. 5. Miettinen M, Makhlouf H, Sobin LH, et al. Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical and molecular genetic study of 906 cases before Imatinib with long term follow-up. Am J Surg Pathol 2006;30:477e89. 6. Anagnostoulis S, Mimidis K, Papadopoulos V, et al. Subcutaneous metastasis from a gastrointestinal stromal tumor of the stomach: a case report. J BUON 2007;12:549e52. 7. Reynoso D, Trent J. Neoadjuvant and adjuvant Imatinib treatment in gastrointestinal stromal tumor: current status and recent developments. Curr Opin Oncol 2010;22:330e5.
A.P. Jones K. Allison Department of Plastic and Reconstructive Surgery, James Cook University Hospital, Middlesbrough, England, UK E-mail address: [email protected]
CORRESPONDENCE AND COMMUNICATION Subcutaneous metastasis of a GIST tumour unresponsive to Imatinib Gastrointestinal Stromal Tumours (GIST) are rare intestinal tumours of mesenchymal origin. They arise in the muscularis of the intestinal tract. Metastatic spread is most commonly intra-abdominal, affecting the liver and peritoneum. Extra-abdominal spread is unusual and metastases to subcutaneous tissues are extremely rare.1 We describe a case of recurrent metastatic oesophageal GIST with a subcutaneous deposit resistant to Imatinib therapy, despite a clinical response in the primary site and liver metastases.
Case report A 61-year old lady was referred to us by the general surgical team in July 2010, with a large fungating tumour overlying the right deltoid. In 2006 she had been diagnosed with GIST involving the lower 2/3rds of the oesophagus. Initial treatment comprised neoadjuvent therapy with Imatinib and a 2-stage oesophagectomy. Histology confirmed a highrisk tumour with circumferential margin involvement. Within months of the primary surgery she had developed local recurrence at the anastamotic site and two liver metastases. She remained on Imatinib and under regular surveillance. In 2009 the patient fell onto her right shoulder and developed swelling and redness that persisted until her next oncology review. A diagnosis of resolving haematoma secondary to trauma was made, but an ultrasound scan was arranged to confirm this. The scan showed a 2.4 cm 3.6 cm 1.6 cm subcutaneous mass suspicious of a GIST metastasis. A subsequent PET scan confirmed the presence of the subcutaneous metastasis with stable local and regional disease. By 2010 the subcutaneous mass had significantly increased in size. Clinical examination revealed a large fungating tumour to the right deltoid region (Figure. 1) measuring 12 cm diameter and 8 cm wide. It had well defined edges and involved the skin and subcutaneous tissues. The skin displayed haemorrhagic changes and central ulceration. No lymphadenopathy was evident.
An urgent CT scan confirmed the subcutaneous deposit had increased to 13 cm 11 cm 7.5 cm. Multiple areas of necrosis and invasion into deltoid were observed. The humerus and scapula were not involved. No new enlarged mediastinal or hilar lymph nodes were identified. The gastrooesophageal anastamosis and lung nodule remained unchanged. The liver lesions had marginally decreased in size. The tumour was excised under general anaesthetic using electrocautery. A 3 cm peripheral margin was taken and a cuff of deltoid proximally to ensure completeness of excision (Figure. 2). The defect was resurfaced using split thickness skin graft from the right thigh (Figure. 3). Histology confirmed complete excision of a spindle cell tumour with monomorphic cellularlity and abundant mitoses, consistent with a GIST metastatic tumour. Immunohistochemical studies were confirmed as KIT (CD117) and CD34 positive, CK AE1/AE3 negative and SMA negative. The patient was reviewed three months postoperatively and was completely healed with no evidence of recurrence.
Discussion GIST is the most common mesenchymal tumour of the bowel with an estimated incidence of 6.5e14.5 per million. It most often occurs in patients over the age of fifty. Stomach and small bowel are predominant sites, but colon, rectum and oesophagus may be involved. Almost all have a mutation in the tyrosine kinase receptor gene (KIT) or platelet derived growth factor alpha (PDGFA). Metastases are usually seen in the liver, as in this case, as well as the abdominal cavity. Extra-abdominal metastases are less common and sites include lung, bone, skin and soft tissue.2 There are very few published cases of cutaneous or subcutaneous metastases from GIST. The first by Shabahang (2002)3 documented a patient with multiple metastases from a gastric GIST that included liver, spleen, jaw, thigh and groin lesions. Miettinen et al. (2005)4 reviewed 1765 cases of gastric GIST and found that just five had either soft tissue or skin metastases. A further study from by this group (2006) of 906 small intestinal GIST tumours showed no cutaneous metastases.5 A case of subcutaneous metastasis was reported by Anagnostoulis et al. (2007) 6 This followed an ulcerating gastric GIST and the patient died shortly after excision of both lesions.
1748-6815/$ - see front matter ª 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjps.2011.03.038
Correspondence and communication
Figure 1
e251
Figure 3
Pre-operative view.
Post operative view.
Funding sources There are no sponsors or outside sources of funding for this article.
Ethical approval No ethical approval was sought for this article. Consent for publication was obtained from the patient.
References Figure 2
Intra-operative post resection view.
Most recently, Wang et al. (2009) published a series of 5 cases.1 The sites involved were scalp (n Z 2) cheek (n Z 1) abdomen (n Z 2). The average size was just 2 cm. Histologically, two were spindle cell (as in this case) and three were mixed epithelioid and spindle cell. All were confirmed to have CD117 reactivity as in this case. KIT genotyping was performed in 4 cases and each displayed mutations. The use of Imatinib following surgical resection has revolutionalised patient survival. Imatinib is a small molecule that binds competitively to the ATP binding sites of target tyrosine kinases and thereby inhibits their activity. This inhibition halts growth of the GIST cell line containing KIT gene mutation. Prior to the use of Imatinib median survival was nine months and now is closer to five years.7 This case shows that the management of subcutaneous and cutaneous metastases in GIST remains surgical. Given that these tumours are usually KIT positive it is surprising that Imatinib is not more effective in their management. We encourage early detection and surgical excision of these tumours.
Conflict of interest statement There are no conflicts of interest that influence the composition of this article.
1. Wang WL, Hornick JL, Mallipeddi R, et al. Cutaneous and subcutaneous metastases of gastrointestinal stromal tumors: a series of 5 cases with molecular analysis. Am J Dermatopathol 2009;32:297e300. 2. Rubin BP, Heinrich MC, Corless CL. Gastrointestinal stromal tumour. Lancet 2007;369:1731e41. 3. Shabahang M, Livingstone AS. Cutaneous metastases from a gastrointestinal stromal tumor of the stomach: review of literature. Dig Surg 2002;19:64e5. 4. Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol 2005;29:52e68. 5. Miettinen M, Makhlouf H, Sobin LH, et al. Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical and molecular genetic study of 906 cases before Imatinib with long term follow-up. Am J Surg Pathol 2006;30:477e89. 6. Anagnostoulis S, Mimidis K, Papadopoulos V, et al. Subcutaneous metastasis from a gastrointestinal stromal tumor of the stomach: a case report. J BUON 2007;12:549e52. 7. Reynoso D, Trent J. Neoadjuvant and adjuvant Imatinib treatment in gastrointestinal stromal tumor: current status and recent developments. Curr Opin Oncol 2010;22:330e5.
A.P. Jones K. Allison Department of Plastic and Reconstructive Surgery, James Cook University Hospital, Middlesbrough, England, UK E-mail address: [email protected]