Subchondral Metastasis

Abstract

Subchondral metastasis is a rare occurrence and poses a diagnostic dilemma as initial films may show a lytic lesion in the subchondral region often misinterpreted as being benign.. We present five cases of subchondral metastasis as well as a review of the literature. In our cases, we present subchondral metastasis in the elbow, shoulder, and hip joints. All patients had pain over the affected joint and most presented with a lytic lesion in the subchondral bone. Three patients have died since presentation and two are doing well at last follow up visit. Subchondral metastasis is a rare entity, but it should be included in the differential of a lytic lesion in the subchondral bone.

INTRODUCTION

The entity of subchondral metastasis is a subset of yellow marrow metastasis. In some joints, there is an area of yellow marrow immediately adjacent to the cartilagenous articular surface. T2-weighted MRI images of a normal shoulder joint show this region as an area of increased signal from its increased adipose content (Figure 1). Involvement of this area by contiguous spread of bone tumors as well as spread of leukemia and lymphoma has been reported^1,2, but reports of direct involvement specifically of the subchondral marrow with tumor metastasis are exceedingly rare. The predominance of reports in this area deal with disease involving the synovium, patella or adjacent red marrow tumors. These lesions pose a diagnostic dilemma as patients may have no other symptoms of malignancy and initial films may be negative. Furthermore, these lesions may show as a well-circumscribed lytic area and may be misinterpreted as being benign. We present five cases of subchondral metastasis.

Figure 1.

T2-weighted image of a normal 19-year old shoulder illustrating increased signal in the subchondral region.

MATERIALS AND METHODS

Review of our records yielded five cases of subchondral metastasis. The patient's ages ranged from 50 to 85 with four men and one woman. The primaries were non-small-cell lung carcinoma, papillary thyroid carcinoma, squamous skin carcinoma and renal cell carcinoma. Plain films, CT and MRI scans as well as the medical records were reviewed.

Case Number	Age	Primary	Presentation
1	66	Lung	Right shoulder pain and swelling
2	79	Squamous skin	Right elbow pain and swelling
3	50	Papillary thyroid	Right hip pain
4	85	Renal cell	Right arm and hip pain
5	55	Lung	Right arm and shoulder pain

Case 1 - F.B.

A 66-year-old man with a long history of smoking and alcoholism presented to an outside clinic with a seven month history of right shoulder pain and swelling. The pain had progressed to a constant dull ache, radiating to the neck and down the right arm. The patient had a long history of COPD, as well as a lung mass on chest film a year earlier. This mass was biopsied and histologic exam revealed granulomatous disease. Plain films of the shoulder demonstrated a 2.5 cm lytic area in the humeral head. A technetium-99m methylene diphosphonate (Tc-99m-MDP) bone scan demonstrated high uptake in the proximal right humerus without other areas of abnormal uptake. Flexible sigmoidoscopy, prostate specific antigen, barium enema, and upper gastrointestinal series films were within normal limits.

The patient was referred to our institution a month later with persistent shoulder pain and worsening swelling. Plain films demonstrated a large lytic lesion in the humeral head with associated collapse (Figure 2). Chest films and chest CT showed a spiculated soft tissue density in the right upper lobe as well as a smaller nodule in the left lower lobe. MR images of the right shoulder demonstrated a 4.5cm mass in the proximal humerus with isointense signal on T1 weighted images and hyperintense signal on T2 weighted images. The mass had a scalloped appearance and was associated with a moderate joint effusion. An open biopsy of the mass demonstrated atypical glandular structures consistent with poorly differentiated adenocarcinoma. The patient was treated with radiation therapy to the right shoulder, but he died 6 months later from widespread metastasis.

Figure 2.

Case 1 - A 66-year-old man presents with a seven-month history of right shoulder pain and swelling. A plain film of the shoulder demonstrates a subchondral lytic lesion in the humeral head with pathologic fracture.

Case 2 - D.C.

A 79-year-old man presented to the oncology service with right elbow pain and swelling for six weeks. His history is significant for recurrent squamous as well as basal cell cancers on the face and trunk, as well as transitional cell carcinoma of the bladder. He had undergone many resections for the skin tumors, as well as a cystoprostatectomy for his transitional cell carcinoma. Metastatic workups were negative after each resection. The patient developed a subcutaneous nodule on the abdomen which was biopsy proven as metastatic squamous carcinoma.

At initial presentation at the Oncology service, the patient was treated with Indocin for presumed osteoarthritis or pseudogout. Subsequent plain films of the elbow demonstrated a lytic subchondral lesion in the distal right humerus, involving the trochlea and capitulum (Figure 3). A Tc-99m-MDP bone scan showed increased uptake in the right elbow as well as the left sixth rib. The masses were presumed to be metastatic nodules. The patient received 3000cGy of radiation therapy to the right distal humerus, with a modest decrease in size of the lytic area. The area continued to be painful and the swelling increased in the next two months. The patient elected to pursue medical management rather that surgical resection, and has been managed with pain medications and nine courses of infusional pamidronate. The patient was doing well 15 months after the initial discovery of metastasis to the right elbow.

Figure 3.

Case 2 - A 79-year-old man presented with a three-month history of pain and swelling in the right elbow. Plain films demonstrate a subchondral lucency involving the medial and lateral epicondyles.

Case 3 - R.V.

A 50-year-old woman with no previous history of malignancy presented with a 2-year history of right hip pain that had worsened over the last 3 months. Plain films and a CT scan of the right hip demonstrated a geographic lucency in the right femoral head (Figures 4 and 5). Because of the subchondral location of the lesion, a giant-cell tumor was considered the most likely diagnosis, and a femoral head and neck resection followed by total hip arthroplasty was performed. Histologic examination of the specimen revealed a metastatic papillary thyroid carcinoma. The patient was treated with total thyroidectomy and 150mCi of iodine-131. A subsequent I-131 imaging study showed increased uptake in the proximal right femur without other evidence of metastasis. The proximal right femur then treated with 5000 cGy of external beam radiation over 5 weeks. After a five year asymptomatic period, the patient presented with new left hip pain. An I-131 scan showed diffuse uptake in the right and left femurs as well as focal intensities in the proximal and distal right femur and right lung base. The patient was treated with 329 mCi of I-131 at that time. Another I-131 scan taken a year later showed persistent uptake in the proximal right femur and the patient was treated with an additional 300 mCi of I-131. The patient was managed with pain medications until her eventual death from disseminated metastasis two years later, a total of seven years after initial presentation of her subchondral hip metastasis.

Figures 4 & 5.

Case 3 - A 50-year-old woman with no previous history of malignancy presented with a 2-year history of right hip pain. Plain films demonstrate a geographic, well-marginated lesion involving the subchondral region of the femoral head and lateral portion of the femoral neck. A CT scan of the right hip demonstrates cortical destruction laterally and sclerosis medially. A giant- cell tumor was considered the most likely diagnosis.

Figure 4.

Figure 5.

Case 4 - G.D.

A 65-year-old man presented to the urologic oncology service with a three month history of right arm and hip pain. His history is significant for stage III renal cell cancer with a radical nephrectomy five years earlier. One year later, the patient developed pulmonary metastasis and was treated with chemotherapy. He subsequently developed neck pain which radiated down both arms. Plain films showed a lucent area in the body of C6, and the patient underwent 3600 cGy of local radiation therapy followed by corpectomy, tumor debulking, and spinal canal stabilization. The patient presented with the right hip and arm pain 18 months later.

Plain films taken at the presentation to the oncology service of the demonstrated a pathologic fracture in the midshaft of the right humerus as well as a lytic area in the anterolateral aspect of the femoral head and neck (Figure 6). MR images of the pelvis demonstrated an area of low T1 signal and high T2 signal in the proximal right femur consistent with subchondral metastasis. The patient underwent embolization of the femoral mass followed by hemiarthroplasty of the right hip. Histologic analysis revealed a metastatic clear cell adenocarcinoma. The patient has since undergone a tumor resection of the right humeral mass and was doing well at last follow-up, seven years after initial presentation.

Figure 6.

Case 4 - A 65-year-old man presented with a three month history right hip pain. Plain films of the right hip demonstrate a lytic area in the anterolateral distal femoral head and the proximal femoral neck.

Case 5- J.L.

A 55-year-old man with a 60-pack-year smoking history, but no diagnosis of malignancy, presented with a 2-month history of right arm, shoulder and hip pain, and hemoptysis. A chest radiograph revealed an extensive right superior sulcus tumor with rib destruction. A CT scan of the chest showed invasion of the right axilla, but no evidence of mediastinal or hilar disease. Fine needle aspirate of the chest lesion showed a poorly differentiated non-small-cell carcinoma. A metastatic workup included a Tc-99m-MDP bone scan negative for metastasis. Plain films and CT scans of the right hip showed no abnormalities.

The lung tumor was staged as T3N0M0, and the patient began radiation therapy in preparation for surgical resection. Over a period of four weeks, however, the pain in the right hip increased. On physical examination, there was pain, weakness and limited range of motion in the right hip. Other joints were unremarkable. A repeat plain film of the right revealed a lytic lesion in the right femoral head. A scalp lesion was biopsied, demonstrating a non-small-cell metastasis.

Radiation therapy was continued to the lung mass as well as to the right hip. Approximately three weeks later, the patient was discovered to have diffuse abdominal metastases. Plain films of the right femur now demonstrated a pathologic fracture. In spite of a short course of chemotherapy, the patient's clinical condition deteriorated, and he died three weeks later.

DISCUSSION

Metastasis is a common occurrence in many cancer patients. There are two general theories of the mechanisms of metastasis. One deals with mechanical factors³ and the other is termed the "seed and soil" theory⁴. The mechanical theory suggests the vascular architecture of certain organs is conducive to implantation and growth of metastatic cells from hematogenous spread. Organs with transitions from large to small vessels or a prominent small vessel bed are areas where metastatic cells would become trapped by mechanical factors. Even so, studies suggest a discrepancy between the vascular patterns and frequency of metastasis of certain organs⁵. As cancer cells circulate, they encounter numerous antigens in the endothelium of different organs. The seed and soil theory implies that certain cancers preferentially interact with some of these antigens, thus increasing the probability of metastasis to a particular site. Once attached, cancer cells must extravasate and proceed to grow in the target organ. It is the interaction of these two theories which explains the discrepancy between vascular anatomy and preferential metastatic sites

Bone metastasis is a common event in many tumors such as breast, prostate, lung, thyroid, and kidney⁵. Metastasis to bone preferentially involves the red marrow and bones rich in red marrow^5,6, and consequently, metastases generally arise proximal to the elbows and the knees. Red marrow possesses a prominent vascularity with many sudden transitions from large to small vessels, a large sinusoidal vessel bed and a porous endothelium made for the entrance of hematopoietic cells into the blood stream^5,7,8. Red marrow also is postulated to have a different antigen composition of its endothelium from that of other locations of bone, although this is currently under evaluation. Cancer cells show a preferential adherence to certain red marrow endothelial antigens⁸. This increases the probability that circulating cancer cells will become entrapped in this area and establish a metastatic focus. Yellow marrow, on the other hand, is predominantly fatty tissue with sparse vascularity. The prominent sinusoidal vessels of red marrow are replaced by capillaries and venules with a continuous endothelial lining⁶. The paucity of blood vessels suggests that growth of tumor would be difficult in this area. Also, it has been suggested that the endothelial antigen composition of yellow marrow differs from that of red marrow. Metastasis may occur in mixed red and yellow marrow, but the involvement of purely yellow marrow is distinctly rare⁸. Numerous animal models have been created to evaluate the pathogenesis of metastatic tumors to bone⁹.

The patients involved in this study possessed identifiable primary tumors. Three of the patients had no previous history of malignancy, while the other two patients had a history of previous cancer resection. Three patients had biopsy proven metastasis, while one patient elected conservative care due to his advanced age and another died shortly after presentation. All patients presented with pain in the area of metastasis, that being the hip, shoulder or elbow. All patients eventually showed a lytic lesion on plain film at the site of metastasis, with a well-circumscribed border also being a common presentation. Bone scan was done on two patients, with one showing increased radionucleotide uptake and the other showing no identifiable uptake in the area of metastasis. CT examination showed a lucent area in the areas of metastasis, and MR images demonstrated an area of low signal intensity on T1 imaging and high signal on T2 imaging. Three patients died from disseminated metastasis, one at seven years, another at six months and the other at three weeks since presentation. Two patients have remained stable following radiation therapy and pain management.

In a review of the literature, 10 cases of involvement of subchondral bone of metastatic tumor were found. The ages ranged from 29 to 77 with an average age of 58. The cases include: melanoma metastatic to the distal femur^10,11, rhabdomyosarcoma metastatic to distal femur¹², renal cell metastatic to proximal humerus¹³, bronchogenic carcinoma metastatic to distal femur^14,15,16 bronchogenic carcinoma metastatic to the proximal humerus¹⁴, breast carcinoma metastatic to distal femur¹⁷ and unknown primary metastatic to proximal femoral head². As in our study, all cases presented with persistent pain and/or swelling in the joint of metastatic disease. Seven of the ten cases had a previous diagnosis of cancer and three patients presented with monoarticular arthropathy as the first manifestation of malignancy^2,13,14. In comparison, our study included three initial presentations of cancer. Nine of ten cases showed a lytic lesion of plain films of the area involved^10,12–18. Five of ten cases showed abnormal areas of uptake on bone scan in the metastatic areas^{2,11,15,16,17}, four cases did not have bone scanning, and one case had a negative bone scan at the time of presentation¹². Our cases demonstrated one positive and one negative bone scan in the area of metastasis. The presence of subchondral metastasis was indicative of a poor prognosis with an average survival of 3.5 months after diagnosis. Two patients were successfully managed with radiation therapy to the area of metastasis^11,13. This is in contrast to our study where two patients were well at last follow-up and three patients died of metastatic disease at seven years, six months and three weeks after presentation.

The presentation of subchondral metastasis is similar to metastasis to other tissue compartments of the joint space. These areas which can cloud the diagnosis of subchondral metastasis include: patellar metastasis^{18,19,20,21,22,23}, synovium^{17,24,25,26,27,28,29,30,31}, acetabulum³², glenoid and scapula^33,34, sternoclavicular joint¹, and calcaneus³⁵. The most common tumor associated with joint space metastasis is bronchogenic carcinoma, followed by breast and gastrointestinal tract malignancies³⁰. The joint most commonly involved is the knee, with case reports of involvement in the hip, shoulder, and elbow³⁰.

Since the most common presentation of subchondral metastasis is a well-circumscribed subchondral lytic lesion on plain film, metastasis can be confused with many benign entities. Osseous involvement may mimic subchondral cysts, periarticular osteopenia or subchondral sclerosis in common arthropathies¹. Involvement may also simulate crystal-induced arthritis²¹, ischemic necrosis¹⁹, infection³⁶, giant-cell tumors and myeloma. Similarly, the synovial thickening often seen with metastasis to subchondral bone may simulate rheumatoid arthritis, villonodular synovitis, calcium pyrophosphate deposition or gout. Subchondral metastasis should be considered whenever a lytic lesion at the end plate of bone fails to respond to standard arthritic therapy.