Case report
A 54-year-old male presented to the outpatient clinic, complaining for severe upper back pain during the last 4 months. The pain was worse at night, causing severe sleep disturbance, and did not respond to ‘over the counter’ painkillers. He was stable (blood pressure 120/75 mmHg, heart rate 85 beats/min, SpO2 99%) and afebrile (36.6˚C). His medical history included heavy smoking, as well as severe anxiety and panic attacks treated with perphenazine/amitriptyline.
Clinical examination was unremarkable except for tenderness at palpation of the upper thoracic spine. There was no neurological deficit. Laboratory findings included: Hemoglobin=12.7 g/dl, normal white blood cell (WBC=5.400) and platelet count (PLT=210 k/µl). Hepatic (SCOT=25 IU/l, SGPT=30 IU/l, gGT=76 IU/l and ALP=95/IU/l) and renal (Cr 1.06 mg/dl, UR=28 mg/dl) functions were normal. C-reactive protein (CRP=0.43 mg/dl) and prostatic specific antigen (PSA=2.96 ng/ml) were within normal range.
CT scan of the thoracic spine revealed a rounded, mostly sclerotic bone lesion, with smooth transitional margins and small inner lucent areas at the T4 vertebral body (Fig. 1). Thus, it was diagnosed by imaging specialists as a benign lesion unrelated to his symptoms.
Three months later, due to persistence of the pain, he underwent a thoracic spine MRI scan, revealing bone marrow edema of part of the T4 vertebral body and presence of paraspinal and epidural soft tissue mass, along with the already known sclerotic lesion (Fig. 2). Since these findings were highly indicative of malignant nature, bone scintigraphy followed which was, surprisingly, normal.
The patient was further investigated with CTs of the thorax and abdomen and a mass infiltrating part of the body and tail of the pancreas indicating pancreatic tumor was revealed. Consequently a C-arm guided biopsy of the T-4 vertebra revealed histology compatible with pancreatic bone metastasis. In particular, histology demonstrated tumor cells in cavities in-between regenerated bone, consistent with a poor differentiated adenocarcinoma with features indicating pancreatic cancer (Fig. 3).
Hence the diagnosis of pancreatic cancer was confirmed and the patient was referred to the Department of Medical Oncology for antineoplastic treatment. It is of note that, up to that point in time, the patient remained in good condition without weight loss or other usual signs and symptoms related to pancreatic cancer.
Discussion
Pancreatic cancer, at early stages, is often difficult to be diagnosed due to the absence of specific signs and symptoms; therefore, at the time of diagnosis most patients present with advanced disease (3).
Cardinal symptoms and signs include pain located at the upper abdomen radiating at the back, malaise, weight loss and/or jaundice. Less often patients present with recurrent thrombophlebitis and in rare cases with mental and/or personality disorders (4). Most symptoms are related to the location of the primary tumor. Pancreatic body or tail malignancies commonly appear with pain and weight loss, while tumors of the pancreatic head usually present with obstructive jaundice (4). However, the present patient did not have any of these usual symptoms, with the thoracic spinal pain being the only one.
Common metastatic sites include the regional lymph nodes, the liver and less commonly the lungs. Osseous metastases are unusual, while spinal metastatic lesions, as initial presentation, are extremely rare (3). The exact prevalence of bone metastases of this tumor remains unclear. Generally, it is quite rare for the disease to spread outside the abdomen, in the absence of liver disease. Hess et al reported on their tumor registry data from 4,399 patients. In the group of pancreatic adenocarcinoma patients, 85% of metastases occurred in the liver, 12% in the lung and 3% in the skeleton (5). Borad et al, in a retrospective study including 323 patients with pancreatic cancer, reported 7 patients (2.2%) with skeletal disease with all of them having spinal involvement (6). Iguchi et al reported 13 patients (7.3%) with secondary bone lesions in a retrospective study of 178 patients (7). In the same study, the authors underline that serum levels of the bone resorption marker 1CTP, as well as IL-6 and VEGF were elevated in most cases, while elevation of serum PTHrP levels was found in 3 out of 13 patients. Hence, the authors suggest periodical measurement of serum 1CTP in addition to bone scintigraphy for earlier diagnosis of metastatic bone disease (7).
Bone metastases are mainly lytic. Purely blastic lesions have rarely been reported (2). Ray et al published a case of a solitary osteblastic bone metastasis, in the absence of other systemic disease, occurring 7 years after surgical resection and adjuvant treatment for a locally advanced pancreatic adenocarcinoma (8). The patient had good performance status, with no clinical evidence of recurrence, until an elevation of the CA 19-9 tumor marker initiated a systemic workup. Therefore, an isolated sclerotic lesion in the right sacral ala was identified on imaging and was biopsied, histologically revealing adenocarcinoma, consistent with the primary tumor.
Spinal pain as presenting complaint of metastatic pancreatic cancer is rare, with only few cases in the literature reporting painful vertebral metastatic lesions as first clinical manifestation (9). Pneumaticos et al reported a case of cancer of the body of the pancreas presented with severe back pain due to an osteoblastic lesion to third lumbar vertebra (10). The present patient suffered severe back pain and he had had a CT scan of the upper thoracic spine. A sclerotic lesion had been found, which was misdiagnosed as benign, irrelevant to the patient's symptoms.
Although there are many reliable indicators in the radiological evaluation of a potential osteolytic bone tumor (zone of transition, periosteal reaction, cortical destruction), further investigation should be recommended in cases of atypical osteoblastic lesions, due to lack of similar helpful signs in such lesions (with the exception of a pathognomonic sclerotic bone tumor). Certainly, other clinical symptoms should be sought in the presence of such spinal lesions.
Spinal metastases are rare in pancreatic cancer but they can cause significant morbidity such as excruciating pain and neurological dysfunction, even paralysis, due to neural tissue compression (11). Although the overall prognosis of metastatic pancreatic cancer is very poor, early diagnosis and management of spinal metastases is crucial for the patients' quality of life (10).
In conclusion, pancreatic cancer is not usually included in the differential diagnosis of a bone metastasis of unknown origin. Clinicians should increase their awareness and index of suspicion regarding the types of the disease's presentation and to include pancreatic cancer in the investigation of bone metastases of unknown primary tumor.