British Journal of Radiology (2006) 79, 261-263
© 2006 British Institute of Radiology
doi: 10.1259/bjr/64677209
Gastric carcinoma presenting with extensive bone metastases and marrow infiltration causing extradural spinal haemorrhage
S Hussain, MRCP and
S Chui, FRCR
Alexandra Hospital, Woodrow Drive, Redditch B98 7UB, UK
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Abstract
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Gastric carcinoma is the third most common gastrointestinal (GI) malignancy after colon and pancreatic carcinoma. A Japanese study showed that the incidence of bone metastases of gastric cancer was 13.4% among autopsies. It is very rare for the primary presentation of a gastric malignancy to be with bone metastases. This case report is of a 46-year-old female patient, who presented with a thoracic vertebral wedge fracture and was subsequently found to have widespread vertebral metastatic deposits with marrow infiltration. The infiltration and suppression of marrow function was complicated by an acute bleed into the extradural space causing spinal cord compression. This case demonstrates two important features. First, that gastric cancer, although far less common than breast, kidney, thyroid, prostate and bronchial cancer; is a cause of metastases to bone. Second, it highlights the complications of bone metastases, marrow suppression, leukoerythroblastic anaemia, spinal canal haematoma and cord compression. The case is illustrated by axial and sagittal MRI slices.
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Introduction
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Metastases to the bony skeleton from gastric carcinoma are uncommon, with an incidence of 14% in autopsy specimens [1]. It is rare for the primary presentation of a gastric carcinoma to be metastases to the bone [2, 3]. This case is notable for that reason and also because the widespread bone deposits and marrow infiltration were complicated by a leukoerythroblastic anaemia and consumptive coagulopathy, which resulted in haemorrhage into the spinal canal and cord compression.
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Case report
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A 46-year-old woman presented to the medical admissions unit with a 4–5 week history of lower back pain of increasing severity. The pain had become significantly worse over the previous 10 days and, no longer being relieved by non-steroidal analgesia, the patient visited her GP. The GP requested blood tests which showed a normocytic anaemia – haemoglobin 8.9 g dl–1 mean corpuscular volume (MCV) 80.6 fl mean corpuscular haemoglobin (MCH) 27.0 pg; thrombocytopenia with platelet count of 141 x 109 l–1; raised liver function tests with alkaline phosphatase 955 u l–1, alanine aminotransferase (ALT) 66 u l–1, gamma-glutamyl transpeptidase (GGT) 326 u l–1 and raised inflammatory markers with erythrocyte sedimentation rate (ESR) 86 mm h–1. A radiograph of the thoracic spine showed a partial compression fracture of the T10 vertebral body. With these initial investigations completed and the pain uncontrolled by diazepam, the patient was referred to hospital for further investigation and treatment.
Her past medical history was unremarkable. She had been started on diazepam and codeine/paracetamol based analgesics and iron tablets by her GP following his consultation. There was no acute history of trauma to trigger her back pain symptoms. The patient was married with no children and worked as a teacher. She was a non-smoker and only drank alcohol occasionally. She was still having regular periods. Physical examination was unremarkable with no chest, abdominal or central nervous system signs and only features of anaemia were found. Blood tests on admission were similar to those reported by the GP. In addition, haematinics – B12, folate and ferritin – were normal.
Initial management was targeted towards obtaining control of her severe back pain and treating her anaemia with a blood transfusion of three units of packed red cells. Upper gastrointestinal (GI) endoscopy was delayed until her back pain was controlled, but was eventually performed and showed a small amount of fresh blood in the oesophagus, and a thickened gastric mucosa in the pre-pyloric area was found with a small amount of blood oozing from this area. The duodenum was normal. Biopsies of this gastric lesion were taken.
A repeat blood film done after admission showed continuing anaemia and thrombocytopenia and also a raised neutrophil 7.79 x 109 l–1, eosinophil 0.47 x 109 l–1 and basophil 0.12 x 109 l–1 count. The blood film showed a leukoerythroblastic blood picture containing immature granulocytes and some nucleated red blood cells. This picture was highly suggestive of marrow infiltration by tumour. At this point, 1 week after admission, the patient developed a nosebleed, which was very hard to control despite nasal packing. Platelet count was re-checked and was found to show a significant drop to 21 x 109 l–1. Coagulation screen showed elevated prothrombin time 16 s, international normalization rate (INR) 1.4, activated partial thromboplastin time 37 s, and D-Dimer (fibrinogen degradation fragment) 7047 ng ml–1. This coagulation picture was indicative of disseminated intravascular coagulation (DIC). The following day, the on-call doctor was called to urgently review the patient since she had lost the use of her lower limbs. On examination there was paraparesis with reduced tone and areflexia of the lower limbs. Muscle power was determined to be 1/5 in both legs. An urgent MR examination of the lumbar spine was requested.
MR showed two main abnormalities. First, in the cervical, thoracic and lumbar vertebrae there were numerous abnormal vertebrae with marrow replacement in several vertebral bodies with one or two completely infiltrated. Several vertebrae showed bi-concave collapse, particularly D2, D10, D12, L3 and L5. Second, there was a large cylindrical soft tissue mass lying in the spinal cord canal from D11/12 down to the level of L3. The axial scans showed it to be lying posterior in the extradural position behind the dural sac. The dural sac was displaced anteriorly with maximal compression at L2 level. The soft tissue mass was of mixed signal and typical for a haematoma in the extradural space, and was thought to have arisen from a bleed from a lumbar dural vein (Figures 1 and 2
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Figure 1. (a) T1 and (b) T2 weighted MRI axial slices at the level of D12 vertebra show a cylindrical mass in the extradural space displacing the dural sac anteriorly and causing compression. The haematoma is isointense to neural tissue on the axial T1 and shows central hypointensity and peripheral hyperintensity on T2. This pattern is seen in hyperacute to early subacute haematomas (first few days).
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Figure 2. (a) T1 and (b) T2 weighted MRI sagittal slices showing extension of the haematoma from D11/12 disc level down to the body of L3. Widespread metastatic foci are seen in the lumbar and lower thoracic vertebral bodies, appearing as low intensity on the T1 weighted image.
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Histology results from the biopsy taken at endoscopy showed antral type gastric mucosa infiltrated by poorly differentiated adenocarcinoma of diffuse type. Trephine core bone marrow biopsy from the iliac crest showed clumps of non-haemopoietic malignant cells. The marrow architecture was largely replaced by a carcinomatous infiltrate. Special stains showed mucin positivity and positive immunohistology with cytokeratins 7 and 20, EP4 and carcinoembryonic antigen (CEA). Oestrogen and progesterone receptors were negative, as was CA125. These features were entirely consistent with gastric primary site of tumour and against a breast primary.
CT of thorax, abdomen and pelvis was performed for staging of the tumour. CT showed normal lungs with bilateral pleural effusions but no lymphadenopathy. Abdominal CT showed normal liver, spleen, kidneys, adrenals and pancreas. Para-aortic lymphadenopathy was seen with nodes around coeliac axis and superior mesenteric vessels. No pelvic masses or lymphadenopathy were seen.
Following oncology review it was felt that the patient was unlikely to benefit from cytotoxic chemotherapy and prognosis was very poor. Surgical decompression of the haematoma was considered, but felt to be of too great a risk for causing further complications in view of the haematological difficulty in controlling the consumptive coagulopathy. Referral to palliative care was made.
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Discussion
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Gastric carcinoma is the third most common GI malignancy after colon and pancreatic carcinoma. It shows a significant geographic variation with a five times higher incidence in Japan and Finland than in the UK. 95% of gastric carcinomas are adenocarcinomas. A Japanese study showed that the incidence of bone metastases of gastric cancer was 13.4% among autopsies [1]. Bone metastases tend to occur in invasive cancers – Bormann types III and IV. Examination of the histology has shown that more than 80% of bone metastasis from gastric cancer was poorly differentiated adenocarcinoma. Thoracic and lumbar vertebrae are the most frequent sites of bone metastasis [2] although there are reported cases of deposits in calcaneum [4], pelvis [5] and skull base. The prognosis of patients with bone metastases is poor with mean survival times of less than 5 months with the longest survival period in the literature of being 3
years [6].
Leukoerythroblastic anaemia arises when the bone marrow is replaced. Metastases to bone usually occur in areas that contain red marrow. Metastatic deposits destroy and replace bone, partly by their own expansion and partly by stimulating active bone resorption. The presentation on the peripheral blood film is of normocytic, normochromic anaemia with numerous poikilocytes, normoblasts, reticulocytes, immature white cells and thrombocytopaenia. The presence of leukoerythroblastic anaemia is most commonly seen in association with carcinoma of the breast, stomach, prostate and lung [7].
The low haemoglobin in this patient prompted investigation for a cause of bleeding resulting in the discovery of the primary tumour. The additional presence of thrombocytopenia should raise the suspicion for DIC and/or bone marrow involvement by malignant disease and coagulation status and a blood film should be examined. DIC is rare and can have a varied presentation with severe bleeding and thrombosis in large and small vessels due to activation of the coagulation cascade resulting in a consumption coagulopathy. Although it is reported to be associated with every type of malignancy, the strongest association is with GI adenocarcinomas and leukaemia. Treatment directed at decreasing the risk of spontaneous bleeding should be considered. In this case, the posterior position of the haematoma in the spinal canal suggests that it was not related to the vertebral fractures and more likely to be a spontaneous haemorrhage.
Received for publication January 14, 2005.
Revision received April 26, 2005.
Accepted for publication May 12, 2005.
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References
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- Carstens SA, Resnick D. Diffuse sclerotic skeletal metastasis as an initial feature of gastric carcinoma. Arch Intern Med 1980;140:1666–8.[Abstract]
- Bergqvist D, Mattson J. Solitary calcaneal metastases as the first sign of gastric cancer. Ups J Med Sci 1978;83:115–8.[Medline]
- Chung YS, Choi TY, Ha CY, et al. An unusual case of osteoblastic metastasis from gastric carcinoma. Yonsei Med J 2002;43:377–80.[Medline]
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Abstract
Introduction
