Multiple Osteolytic Lesions of Bone Kathleen Cantwell, MD, Harry C. Press, Jr., MD, and Javan E. Anderson, MD Washington, DC
Clinical History An 82-year-old black male was admitted for bilateral lower leg pain with occasional swelling. Initially, the patient had presented following minor trauma. A fracture of the right radius through a "punched-out" bone lesion was diagnosed as a pathologic fracture.
Radiographic Findings Radiographs of both lower extremities (Figure 1) demonstrated multiple lytic defects throughout both tibias and fibulas. The defects were sharply but irregularly marginated with scant matrices (Figure 2). The endosteal margins were scalloped, and the cortical margins were slightly expansile and disrupted at several points. No significant periosteal reaction was noted. Soft tissue extension was absent.
Requests for reprints should be addressed to Dr. Harry C. Press, Jr., Department of Radiology, Howard University Hospital, 2041 Georgia Avenue NW, Washington, DC 20060. 286
Figure 1. Radiograph of right leg with multiple osteolytic lesions which were bilaterally symmetrical.
Figure 2. Close-up of lesions demonstrating expansile lesion scalloping the endosteum.
JOURNAL OF THE NATIONAL MEDICAL
ASSOCIATION, VOL. 70, NO. 4, 1978
What Is Your Diagnosis? 1. 2. 3. 4. 5.
Metastatic disease Multiple myeloma Brown tumors Reticulum cell sarcoma Multiple enchondromatosis
Metastatic Disease
Multiple Myeloma
Brown Tumors
By far the most common malignant tumor of bone, bony metastases are estimated to have from 27 to 70 percent incidence in cases of malignancy, depending upon the diligence of sampling technique. The mechanism of lytic defects from metastatic foci is felt to be caused by pressure upon bone from expanding tumor mass, as well as influence from substances elaborated by tumor cells. The locations most common for skeletal metastases are the axial skeleton. Although foci can occur distal to the elbows and knees, such occurrences are unusual. Bilateral and symmetrical involvement is also unusual. The usual sources of osteolytic metastases are kidney, thyroid, lung, and gastrointestinal tract. Squamous cell metastases from cervix, oral cavity, and larynx also yield lytic lesions. And, although carcinoma of the breast causes both lytic and blastic effects, its lytic component is more characteristically dominant.' Routes of metastasis involve the blood stream, either venous or arterial. The role of the lymphatics is still not well understood. Embolization of tumor tissue to the bone marrow sets up a focus for growth which crowds out normal marrow.2 The bony lesions in the presenting patient are located in an atypical area for metastatic disease. They are bilateral and are almost symmetrical, which is unusual for metastatic disease. The cortical margins are not destroyed. Although metastatic disease is a possibility, it is not of prime consideration.
Multiple myeloma, a tumor of hematopoietic derivation, is the most common primary neoplasm of bone, comprising 55 percent of primary bone tumors. Developing multicentrically, it is comprised of plasma cells of varying degrees of differentiation. Although "solitary" myeloma is seen, it usually develops into generalized disease after latent periods of five to ten years. There is a slight male predominence. Age occurrence is after the fifth decade, reaching a peak in the seventh decade. Clinically, patients present with bone pain and pathological fractures. Commonly, patients exhibit anemia. Hypercalcemia is seen in approximately 20-50 percent, and Bence-Jones proteinurea in over 50 percent. Radiographically, the ribs, skull, vertebrae, and pelvis are the earliest areas of involvement, although all bones may eventually become involved. Lesions appear punched-out and may reach 5 cm in diameter. No sclerotic margins are associated and the areas are expansile. Generalized osteoporosis is seen. Myeloma patients usually succumb to renal disease from tubular blockage by myeloma proteins, or secondary amyloidosis.3 The bone lesions in this patient conform to the criteria of myeloma lesions. The diagnosis should be high on our list of differentials.
Under the influence of excess parathyroid hormone, osteoclastic and osteocytic resorption of bone occurs with replacement by fibrous tissue. The cysts arising from such fibrous tissue overgrowth undergo hemorrhage giving cut pathologic sections the characteristic brown appearance for which this lesion was named. Brown tumors are present in the third to fifth decades of life. They can occur with primary hyperparathyroidism caused by glandular hyperplasia, parathyroid adenoma, parathyroid carcinoma, or from nonparathyroid tumor production of parathyroid hormone (PTH). Secondary causes include chronic hypercalcemia usually secondary to renal glomerular disease, though brown tumors are less common in the secondary form. Radiographically, highly trabeculated, expanding focal bone lesions occur which are highly destructive. The most common sites of involvement are mandible, pelvis, ribs, and femora although lesions can occur in any part of the skeleton. True giant cell tumors also occur under the influence of excess PTH production. Skeletal metastases of parathyroid carcinoma also occur.
Following parathyroidectomy, brown tumors often sclerose, persisting for many years.4 The trabeculations seen within the lesions are suggestive of brown tumors. Radiographically, the lesions conform to the description of brown tumors, and should be included in our differential diagnosis.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 70, NO. 4, 1978
287
Reticulum Cell Sarcoma
Multiple Enchondromatosis
Known as malignant lymphoma of bone, this tumor is rarely composed solely of recticulum cells, but of a combination of recticulum cells, lymphoblasts, and lymphocytes. In addition, lymphocytic and Hodgkin lymphomas can present as primary lesions of bone. Malignant lymphoma of bone encompasses this entire group of primary bone involvements which are morphologically like their soft-tissue counterparts. In the skeleton, for this tumor to be considered primary, there must be no evidence of lymphomatous disease elsewhere. While occurring at any age, the peak incidence is in the fifth to sixth decades of life. Comprising almost 7 percent of malignant tumors of bone, only 3.4 percent are primary to bone. Roentgenographically, lesions of malignant lymphoma of bone are extensive, affecting 25-50 percent of the skeleton. The destruction is marked, appearing mottled and patchy. The bone cortex is extensively destroyed with ill-defined interface between diseased and normal bone. Soft-tissue extension is frequently seen, sometimes containing calcifications.3 The lesions seen in this patient were sharply marginated without soft-tissue extension or calcifications. The diagnosis of reticulum cell sarcoma is unlikely.
Originally described by Oilier in 1900, multiple enchondromatosis is actually a dyschondroplasia, as opposed to solitary enchondromas which are neoplastic. Characteristically, rounded masses of uncalcified cartilage are seen in metaphyseal and diaphyseal areas of long bones which are almost invariably shortened. This developmental anomaly is nonfamilial. Rounded masses or columnar streaks of decreased density are the typical radiographic appearance. Confined to the metaphyses and diaphyses, bony septae give a striated appearance. Associated dwarfing or clublike deformity is common in the metaphysis secondary to abnormal remodeling. This entity tends to be unilateral, but can be bilateral and extensive. Tubular bones of the hands and feet are often involved.5 The patient demonstrated no regions of shortened extremities. His lesions were neither streaked nor septated. These bony lesions are not consistent with Ollier disease.
Discussion Clinical investigation revealed elevation of serum levels of calcium and parathyroid hormone. The patient underwent surgical neck exploration and a parathyroid adenoma was removed. Following surgery, serum calcium levels remained elevated. The patient continued to complain of bone pain and the bone lesions progressed in size and number. Protein electrophoresis revealed elevation of the beta chain of globulins. Open biopsy of the right tibia proved multiple myeloma. Classically multiple myeloma presents as multiple osteolytic lesions, the destruction being caused by proliferation of plasma cells throughout the bone marrow. The red marrowcontaining flat bones are affected first. Late in the course of the disease, all bones may become affected. These lesions appear punched out and sharply delineated, as contrasted to the less discrete lesions of metastatic disease or the permeative, moth-eaten 288
appearance of malignant lymphoma of bone. Bone cortex is expanded and thinned in myeloma as compared to its more extensive destruction in metastatic disease.5 Brown tumors give a similar roentgenographic appearance to myeloma, and both cause the elevation of serum calcium level. Alkaline phosphatase is much more likely to be elevated in hyperparathyroidism than in myeloma. Inorganic phosphate elevation does not occur in myeloma unless renal disease ensues, but is usually elevated in hyperparathyroidism.' Initial presentation of a pathologic fracture of the radius in this patient implied advanced disease, since lesions of the distal extremities do not appear early. Bone survey revealed extensive involvement of the skeleton. There was absence of Bence-Jones proteinurea as well as elevation of both alkaline phosphatase and parathyroid hormone levels, consistent with parathyroid dis-
ease. Following parathyroidectomy, however, serum calcium levels should have returned to normal levels, and bony lesions should have regressed. Progression of bone disease radiographically warranted open biopsy. The differentiation of bone lesions of myeloma and brown tumors of hyperparathyroidism cannot be made on a single film as seen in Figure 1. This made this diagnosis very difficult and prompted this presentation. Literature Cited 1. Spjut HJ, Dorfman HD, Fechner RE: Atlas of Tumor Pathology, Tumors of Bone and Cartilage. Washington, DC: Armed Forces Institute of Pathology, 1971, pp 367-378 2. Jaffe HL: Tumors and Tumerous Conditions of the Bones and Joints. Philadelphia, Lea & Febiger, 1958, pp 589-591 3. Dahlin DC: Bone Tumors, ed 2. Springfield, Ill, Charles C. Thomas, 1967, pp 116-124, 36, 376 4. Greenfield GB: Radiology of Bone Disease, ed 2. Philadelphia, JB Lippincott, 1975, pp 26-38 5. Edeiken J, Hodes PJ: Roentgen diagnosis of diseases of bone, Golden's Diagnostic Radiology ed 2. Baltimore. Williams and Wilkins, 1973, pp 110-123, 1026-1039
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 70, NO. 4, 1978
Clinical History An 82-year-old black male was admitted for bilateral lower leg pain with occasional swelling. Initially, the patient had presented following minor trauma. A fracture of the right radius through a "punched-out" bone lesion was diagnosed as a pathologic fracture.
Radiographic Findings Radiographs of both lower extremities (Figure 1) demonstrated multiple lytic defects throughout both tibias and fibulas. The defects were sharply but irregularly marginated with scant matrices (Figure 2). The endosteal margins were scalloped, and the cortical margins were slightly expansile and disrupted at several points. No significant periosteal reaction was noted. Soft tissue extension was absent.
Requests for reprints should be addressed to Dr. Harry C. Press, Jr., Department of Radiology, Howard University Hospital, 2041 Georgia Avenue NW, Washington, DC 20060. 286
Figure 1. Radiograph of right leg with multiple osteolytic lesions which were bilaterally symmetrical.
Figure 2. Close-up of lesions demonstrating expansile lesion scalloping the endosteum.
JOURNAL OF THE NATIONAL MEDICAL
ASSOCIATION, VOL. 70, NO. 4, 1978
What Is Your Diagnosis? 1. 2. 3. 4. 5.
Metastatic disease Multiple myeloma Brown tumors Reticulum cell sarcoma Multiple enchondromatosis
Metastatic Disease
Multiple Myeloma
Brown Tumors
By far the most common malignant tumor of bone, bony metastases are estimated to have from 27 to 70 percent incidence in cases of malignancy, depending upon the diligence of sampling technique. The mechanism of lytic defects from metastatic foci is felt to be caused by pressure upon bone from expanding tumor mass, as well as influence from substances elaborated by tumor cells. The locations most common for skeletal metastases are the axial skeleton. Although foci can occur distal to the elbows and knees, such occurrences are unusual. Bilateral and symmetrical involvement is also unusual. The usual sources of osteolytic metastases are kidney, thyroid, lung, and gastrointestinal tract. Squamous cell metastases from cervix, oral cavity, and larynx also yield lytic lesions. And, although carcinoma of the breast causes both lytic and blastic effects, its lytic component is more characteristically dominant.' Routes of metastasis involve the blood stream, either venous or arterial. The role of the lymphatics is still not well understood. Embolization of tumor tissue to the bone marrow sets up a focus for growth which crowds out normal marrow.2 The bony lesions in the presenting patient are located in an atypical area for metastatic disease. They are bilateral and are almost symmetrical, which is unusual for metastatic disease. The cortical margins are not destroyed. Although metastatic disease is a possibility, it is not of prime consideration.
Multiple myeloma, a tumor of hematopoietic derivation, is the most common primary neoplasm of bone, comprising 55 percent of primary bone tumors. Developing multicentrically, it is comprised of plasma cells of varying degrees of differentiation. Although "solitary" myeloma is seen, it usually develops into generalized disease after latent periods of five to ten years. There is a slight male predominence. Age occurrence is after the fifth decade, reaching a peak in the seventh decade. Clinically, patients present with bone pain and pathological fractures. Commonly, patients exhibit anemia. Hypercalcemia is seen in approximately 20-50 percent, and Bence-Jones proteinurea in over 50 percent. Radiographically, the ribs, skull, vertebrae, and pelvis are the earliest areas of involvement, although all bones may eventually become involved. Lesions appear punched-out and may reach 5 cm in diameter. No sclerotic margins are associated and the areas are expansile. Generalized osteoporosis is seen. Myeloma patients usually succumb to renal disease from tubular blockage by myeloma proteins, or secondary amyloidosis.3 The bone lesions in this patient conform to the criteria of myeloma lesions. The diagnosis should be high on our list of differentials.
Under the influence of excess parathyroid hormone, osteoclastic and osteocytic resorption of bone occurs with replacement by fibrous tissue. The cysts arising from such fibrous tissue overgrowth undergo hemorrhage giving cut pathologic sections the characteristic brown appearance for which this lesion was named. Brown tumors are present in the third to fifth decades of life. They can occur with primary hyperparathyroidism caused by glandular hyperplasia, parathyroid adenoma, parathyroid carcinoma, or from nonparathyroid tumor production of parathyroid hormone (PTH). Secondary causes include chronic hypercalcemia usually secondary to renal glomerular disease, though brown tumors are less common in the secondary form. Radiographically, highly trabeculated, expanding focal bone lesions occur which are highly destructive. The most common sites of involvement are mandible, pelvis, ribs, and femora although lesions can occur in any part of the skeleton. True giant cell tumors also occur under the influence of excess PTH production. Skeletal metastases of parathyroid carcinoma also occur.
Following parathyroidectomy, brown tumors often sclerose, persisting for many years.4 The trabeculations seen within the lesions are suggestive of brown tumors. Radiographically, the lesions conform to the description of brown tumors, and should be included in our differential diagnosis.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 70, NO. 4, 1978
287
Reticulum Cell Sarcoma
Multiple Enchondromatosis
Known as malignant lymphoma of bone, this tumor is rarely composed solely of recticulum cells, but of a combination of recticulum cells, lymphoblasts, and lymphocytes. In addition, lymphocytic and Hodgkin lymphomas can present as primary lesions of bone. Malignant lymphoma of bone encompasses this entire group of primary bone involvements which are morphologically like their soft-tissue counterparts. In the skeleton, for this tumor to be considered primary, there must be no evidence of lymphomatous disease elsewhere. While occurring at any age, the peak incidence is in the fifth to sixth decades of life. Comprising almost 7 percent of malignant tumors of bone, only 3.4 percent are primary to bone. Roentgenographically, lesions of malignant lymphoma of bone are extensive, affecting 25-50 percent of the skeleton. The destruction is marked, appearing mottled and patchy. The bone cortex is extensively destroyed with ill-defined interface between diseased and normal bone. Soft-tissue extension is frequently seen, sometimes containing calcifications.3 The lesions seen in this patient were sharply marginated without soft-tissue extension or calcifications. The diagnosis of reticulum cell sarcoma is unlikely.
Originally described by Oilier in 1900, multiple enchondromatosis is actually a dyschondroplasia, as opposed to solitary enchondromas which are neoplastic. Characteristically, rounded masses of uncalcified cartilage are seen in metaphyseal and diaphyseal areas of long bones which are almost invariably shortened. This developmental anomaly is nonfamilial. Rounded masses or columnar streaks of decreased density are the typical radiographic appearance. Confined to the metaphyses and diaphyses, bony septae give a striated appearance. Associated dwarfing or clublike deformity is common in the metaphysis secondary to abnormal remodeling. This entity tends to be unilateral, but can be bilateral and extensive. Tubular bones of the hands and feet are often involved.5 The patient demonstrated no regions of shortened extremities. His lesions were neither streaked nor septated. These bony lesions are not consistent with Ollier disease.
Discussion Clinical investigation revealed elevation of serum levels of calcium and parathyroid hormone. The patient underwent surgical neck exploration and a parathyroid adenoma was removed. Following surgery, serum calcium levels remained elevated. The patient continued to complain of bone pain and the bone lesions progressed in size and number. Protein electrophoresis revealed elevation of the beta chain of globulins. Open biopsy of the right tibia proved multiple myeloma. Classically multiple myeloma presents as multiple osteolytic lesions, the destruction being caused by proliferation of plasma cells throughout the bone marrow. The red marrowcontaining flat bones are affected first. Late in the course of the disease, all bones may become affected. These lesions appear punched out and sharply delineated, as contrasted to the less discrete lesions of metastatic disease or the permeative, moth-eaten 288
appearance of malignant lymphoma of bone. Bone cortex is expanded and thinned in myeloma as compared to its more extensive destruction in metastatic disease.5 Brown tumors give a similar roentgenographic appearance to myeloma, and both cause the elevation of serum calcium level. Alkaline phosphatase is much more likely to be elevated in hyperparathyroidism than in myeloma. Inorganic phosphate elevation does not occur in myeloma unless renal disease ensues, but is usually elevated in hyperparathyroidism.' Initial presentation of a pathologic fracture of the radius in this patient implied advanced disease, since lesions of the distal extremities do not appear early. Bone survey revealed extensive involvement of the skeleton. There was absence of Bence-Jones proteinurea as well as elevation of both alkaline phosphatase and parathyroid hormone levels, consistent with parathyroid dis-
ease. Following parathyroidectomy, however, serum calcium levels should have returned to normal levels, and bony lesions should have regressed. Progression of bone disease radiographically warranted open biopsy. The differentiation of bone lesions of myeloma and brown tumors of hyperparathyroidism cannot be made on a single film as seen in Figure 1. This made this diagnosis very difficult and prompted this presentation. Literature Cited 1. Spjut HJ, Dorfman HD, Fechner RE: Atlas of Tumor Pathology, Tumors of Bone and Cartilage. Washington, DC: Armed Forces Institute of Pathology, 1971, pp 367-378 2. Jaffe HL: Tumors and Tumerous Conditions of the Bones and Joints. Philadelphia, Lea & Febiger, 1958, pp 589-591 3. Dahlin DC: Bone Tumors, ed 2. Springfield, Ill, Charles C. Thomas, 1967, pp 116-124, 36, 376 4. Greenfield GB: Radiology of Bone Disease, ed 2. Philadelphia, JB Lippincott, 1975, pp 26-38 5. Edeiken J, Hodes PJ: Roentgen diagnosis of diseases of bone, Golden's Diagnostic Radiology ed 2. Baltimore. Williams and Wilkins, 1973, pp 110-123, 1026-1039
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 70, NO. 4, 1978
![[Pancreatic panniculitis with multiple osteolytic lesions].](/assets/img/hold.png)
