Gall bladder carcinoma presenting with spinal metastasis: a rare phenomenon.

Skeletal metastasis as a primary presentation of gall bladder carcinoma is rare. A 50-year-old lady presented with neck pain and weakness in her right upper limb of 3 months duration. Clinical and imaging work-up suggested locally advanced gall bladder carcinoma with metastasis to cervical vertebra and sternum. Only one case till date has been reported where the patient presented with neurological symptoms due to pathological fracture secondary to metastasis from an occult gall bladder carcinoma. Although rare, an occult gall bladder cancer may present with neurological symptoms due to pathological fracture of spine secondary to metastasis. We present a brief review of literature of patients who presented with skeletal metastases in clinically silent gall bladder malignancy. Palliative care issues in advanced gall bladder carcinoma have also been discussed.

INTRODUCTION

Gall bladder carcinoma (GBC) is an aggressive malignancy with poor outcome. Most of the patients have advanced disease at the time of diagnosis and present with abdominal pain, anorexia, weight loss, jaundice, and rarely as gastrointestinal bleeding or intestinal obstruction. Skeletal metastasis as a primary presentation of GBC is rare. We report a 50-year-old lady who presented with neck pain and weakness in her right upper limb of 3 months duration. Clinical and imaging work-up suggested locally advanced GBC with metastasis to cervical vertebra and sternum. Only one case till date has been reported where the patient presented with neurological symptoms due to pathological fracture secondary to metastasis from an occult gall bladder carcinoma. The case is presented here because of its rarity with a discussion on management of such patients.

CASE REPORT

A 50-year-old lady presented to out-patient orthopedic clinic with pain in the neck since 3 months and weakness in her right upper limb of 2 months duration. The general physical examination was normal; she had tenderness over C4 and C5 vertebra with sensory and motor deficit (power 3/5) in right upper limb. A right upper quadrant abdominal lump was also discovered during the examination. The patient was put on a hard cervical collar and analgesics were advised. Orthopedicians planned a magnetic resonance imaging (MRI) scan of cervico-dorsal spine and a bone scan. An ultrasound scan of the abdomen was also done to evaluate the incidentally found abdominal lump.

The MRI scan showed altered marrow signal intensity in right half of C4 vertebra and posterior neural arch with paravertebral soft tissue thickening plugging the right C3/C4 neural foramen and encasing vertebral artery [Figure 1]. The bone scan showed an osteolytic lesion in right side of C4 vertebra with increased uptake over mid cervical vertebra. In addition, there was increased focal uptake on the left side of manubrium sterni. Ultrasound scan of the abdomen revealed a large ill-defined heterogeneous mass lesion in the area of gall bladder, which was infiltrating into adjacent liver; the gall bladder was not separately visible. A diagnosis of metastatic lesion in the sternum and C4 vertebra causing cord compression was made and a general surgeon's opinion was sought for the ultrasound findings.

Figure 1

MRI scan cervicodorsal spine: Altered marrow signal intensity in right half of C4 vertebra with paravertebral soft tissue thickening plugging right C3/C4 neural foramen and encasing vertebral artery (arrow)

The history was reviewed; she complained primarily of neck pain with weakness in her right upper limb of 3 months duration which was increasing progressively from 2 months. As we were biased by the ultrasound findings, some direct questions were asked to which she responded by stating some discomfort in her left upper abdomen from last 7 months and decreased appetite from last 4 months. There were no complaints on the right side of abdomen. She related her symptoms to ‘indigestion’. On re-examination, we found her to be of medium built with average nutrition. The general physical examination was essentially normal. Abdominal examination revealed mildly tender, irregular, and hard lump measuring 5 × 4 cm in her right upper abdomen, which was moving well with respiration with surrounding hepatomegaly. A clinical diagnosis of carcinoma of gall bladder was made and a contrast enhanced computed tomography (CECT) scan of abdomen was advised for staging. The CT scan showed a poorly differentiated heterogeneous mass lesion replacing gall bladder with extension into the segment 4 and 5 of liver [Figure 2]. For histological confirmation, an ultrasound (USG)-guided fine needle aspiration cytology (FNAC) was performed from the mass which showed well-differentiated adenocarcinoma of the gall bladder. The patient and her relatives were explained about the nature, stage and likely poor outcome of the disease. She was offered chemotherapy and local radiotherapy for the painful spinal lesion but she opted for ‘no treatment’, left the hospital, and was subsequently lost to follow-up.

Figure 2

CT scan abdomen: Heterogeneous mass lesion replacing gall bladder with extension into segment 4 and 5 of liver

DISCUSSION

GBC is the commonest cancer of the biliary tract worldwide.[1] The geographical distribution of GBC varies widely, with the Eastern part of the world bearing most of its burden.[12] The clinical glumness regarding GBC is due to its rapid growth, late presentation, lack of effective therapy and, hence, poor outcome. Reported 5-year survival rate for GBC is less than 5% with the median survival of less than 6 months.[2] GBC spreads rapidly and by all possible routes viz. local, hematogenous, lymphatic, neural, and transcelomic. Local spread occur early and is more common than distant spread by metastases.[3] Metastases frequently involve liver (76-86%) and regional lymph nodes (60%).[4] Distant metastasis to virtually all organs is possible[345] and has been reported but distant metastasis to bone is rare.[456] The reason may lie in the rapidly growing nature of this malignancy that causes the demise of the patient early due to local infiltration, leaving little time for the development of bony metastasis.

Although bony metastasis does occur with GBC, it is a late feature and is usually associated with symptoms and signs of advanced local disease. The presentation with bony metastasis without any clinical features of primary gall bladder malignancy is extremely rare. Following an extensive review of the published English literature, we could retrieve only six such cases [Table 1].[345789] Our patient presented with neurological deficit secondary to spinal metastasis. Only one such case has been reported so far.[5]

Table 1

Silent gall bladder cancer with osseous secondaries: Cases reported till date

The management of such patients remains disputed and is challenging. Resection of the primary tumor in such an advanced stage may not only be difficult but is controversial as the long term survival remains poor despite resection.[10] Similarly the outcome following radio-chemotherapy in adjuvant and neoadjuvant setting has been diverse but the overall prognosis remains grim.[10] Although treatment in such advanced malignancy may not be curative but palliative treatment must be considered for relief of symptoms to help such patients live a quality life and let them die peacefully rather than agony from the advanced disease. The palliative issues in advanced GBC include relief of pain, jaundice, ascites, bowel obstruction, and symptomatic metastases. Various options are available for palliation of these symptoms and the strategy should be individualized to each patient with intent of providing maximum relief with minimum adverse effects. Palliative radiotherapy and chemotherapy may even prolong life in select patients with advanced disease.

Our patient presented primarily with bony pain and neurological weakness secondary to metastatic deposit in C4 cervical vertebra. We planned to relieve her of this symptom by combination of oral analgesics, a semi-rigid cervical collar and localized radiotherapy to the painful metastatic deposit. She also had poorly defined abdominal discomfort. We planned to deal with this by using analgesics and supportive therapy for her ‘indigestion’. She was put on cervical color and a combination of Tramadol and Paracetamol was already started by our orthopedic colleagues. We decided to continue the drugs and monitor her for analgesic response. We also offered her adjuvant chemotherapy as she was in a good health but she opted for no treatment. We respected her autonomy and did not compel her to undergo treatment. We propose that patients with GBC should be included in clinical trials so that we may have best management strategies for this intricate disease.

CONCLUSIONS

Although rare, an occult GBC may present with neurological symptoms due to pathological fracture of spine secondary to metastasis. The aim of treatment in such unfortunate patients should be palliative.