•
Observations on Radionuclide Imaging in Hypertrophic Pulmonary Osteoarthropathy 1
Nuclear Medicine
Leonard Rosenthall, M.D., and Joel Kirsh, M.D. 99mTc pyrophosphate was employed in the study of patients with hypertrophic pulmonary osteoarthropathy. Several facts emerge when comparing the radionuclide, radiographic and clinical findings . Radionuclide imaging reveals the presence and extent of subperiosteal activity with greater clarity than does radiography. Synovitis associated with the syndrome is readily disclosed, and the regression of the skeletal manifestations following excision of the pulmonary lesion can be documented. INDEX TERMS: Bones, radionucllde studies. Lung neoplasms, radionuclide diagnosis • Neoplasms, metastases Radiology 120:359-362, August 1976
(HPO) is a clinical syndrome consisting of clubbing of fingers and toes, periostitis with bone tenderness, arthritis, and autonomic disorders such as profuse sweating, flushing and blanching. Pathologically, the distal ends of the long bones, metacarpals and metatarsals are principally involved, with edema of the periosteum, round cell infiltration and subperiosteal new bone formation. In severe disease, the ribs, clavicles, scapulae, pelvis and malar bones are included. The synovium, articular capsule and membranes adjacent to the affected joints are often edematous and infiltrated with lymphocytes, plasma cells and a few polymorphonuclear leucocytes. Cartilage degeneration may result from advanced proliferative fibrous tissue at joint margins. Prompt relief of symptoms can occur with resection of the primary lung lesion or intrathoracic vagotomy. Detection of HPOwith bone-seeking radiopharmaceuticals has been reported in the past. The advent of 18F (6, 9) followed by 99mTc-phosphate complexes (5, 7) has disclosed this entity with greater frequency than either 85Sr (1) or 87mSr (2) because of the improved quality of the images. This communication illustrates the various manifestations of HPO elicited by 99mTc-pyrophosphate (99mTcPPi) skeletal imaging.
H
YPERTROPHIC PULMONARY OSTEOARTHROPATHY
.....,
TECHNIQUE
Each patient was given 15-20 mCi 99mTcPPi intravenously and imaged 2-5 hours after delivery with a total body rectilinear scanner and/or a gamma camera. Three hundred thousand counts were accumulated on the gamma camera for all images except the handsand feet. The latter regions were imaged for equal times, but sufficient to collect about 100,000 counts. CASE REPORTS CASE I. J.1. is a 56-year-old man with an adenocarcinoma of the lung. He had a one-month history of cough , shortness of breath, decreased
Fig. 1. CASE I. 99mTcPPi images demonstrating pericortical deposition in the tibiae, ulnae and radii. Focal midfemoral shaft uptakes were due to metastases. Hands show evidence of periarticular concentration about some of the joints secondary to synovitis and bone uptake at the finger tips is probably due to clubbing and hyperemia.
appetite and weight loss. Clubbed fingers developed and his joints were painful, tender, swollen, warm and red. Some relief was obtained with indomethacin. The 99mrcPPi scan showed peri cortical concentration in the tibiae compatible with HPO (Fig 1). No HPO was disclosed in the femora, but there was focal metastatic disease. Both forearms showed the characteristic location of HPO at the distal ends of the ulna and radius . Periarticular uptake of 99mTcPPi was noted about most of the
1 From the Division of Nuclear Medicine, The Montreal General Hospital, Montreal, Quebec. Revised manuscript accepted for publication in January 1976. shan
359
360
LEONARD ROSENTHALL AND JOEL KIRSH
Augusl1976
•
0,'
Fig. 2. CASE II. A. Total body scan prior to surgery July 1972 showing increased pericortical concentration along the femoral and tibial shafts. B. Gamma camera images July 1972 demonstrating periarticular concentration about the knees, in particular the patellae, the proximal and distal interphalangeal joints of the hands and increased concentration in the right ulna and radius. C and D. One year after surgery, August 1973, the peri cortical and periarticular concentration returned to normal. joints and at the distal phalanges of the fingers which were obviously clubbed.
CASE II. M.O. is a 49-year-old woman. Two years prior to admission, she was followed in the Rheumatology Clinic for treatment of a presumptive diagnosis of rheumatoid arthritis. She was maintained on indomethacin therapy which gave some relief of pain. Three months prior to admission, she suffered bouts of fever, severe pain in both ankles and knees, clubbing of the finger tips and pitting edema from the knees to the toes. A chest radiograph revealed a left lower lobe mass which histologically was a poorly differentiated squamous cell carcinoma. A bone scan (Fig 2, A and B) prior to surgery showed characteristic pericortical concentration in the femurs , some linear and patchy con-
centration in the legs, abnormal right forearm, and increased periarticular concentration of the proximal and distal interphalangeal joints of the hands and both knees . The feet and ankles were not imaged. Within 24 hours of surgery there was a very significant amelioration of the pain in the lower extremities and a regression of the edema. One year following surgical removal of the tumor the radionuclide bone scan showed no evidence of HPO in the lower extremities and right forearm . The periarticular concentration in the knees and hands secondary to synovitis returned to normal (Fig 1, C and D). Clinically, she was free of all inflammatory signs and only minimal clubbing of the finger tips persisted. CASE III. A.S. This 63-year-old man with a poorly differentiated epidermoid carcinoma had HPO. Hands were puffy and the fingers were
HYPERTROPHIC PULMONARY OSTEOARTHROPATHY
Vol. 120
361
Nuclear Medicine
Fig. 3. CASE III. A. 99"'TcPPi gammacamera imagesdepictingpericortical concentration in the femora,tibiae, ulnae,radii and some of the proximal phalanges of the hands andmetacarpals. Note the absence of periarticular concentration about the metacarpo-phalangeal joints(compare with Fig. 4). .B. Radiographs of the hands, right ulna, radius, femur, tibia and fibula showing far less subperiosteal activity than the images in Figure 3, A.
clubbed, but there was no joint pain or limitation of movement. A 99 mTcPPi bone survey showed the typical pericortical concentration of HPO in the femora, tibiae, ulnaeanddistal radii (Fig.3). Someof the proximal phalanges clearly exhibited the " parallel track" deposition of HPO with 99"'TcPPi and the metacarpals showed variable involvement. Of interest was the lack of periarticular concentration in the metacarpo-phalangeal jointsof the hands, an area which did not exhibit synovitis clinically. A low, but abnormal concentration of 99"'TcPPi was registeredabout the proximal interphalangeal joints and this could be due to a subclinical synovitis which would surface later on (4). C ASE IV. P.R. A bronchogeniccarcinoma was the etiology of a diffuse HPO of the extremities in this 55-year-old man. Figure 4 is an illustration of the hands depicting generalized periarticular bone concentration of 99"'TcPPi indicative of inflammatory synovitis, increased uptake at thedistalends of the fingers associated with marked clubbing, anddeposition in some of the metacarpals.
DISCUSSION
About 80
%
of lung lesions associated with HPO are
bronchogenic carcinomas; pleural tumors make up 10%, and a miscellaneous group of intrathoracic malignancies account for 5% (3). Chronic suppurative pulmonary inflammatory disease and congenital cyanotic heart disease are non-malignant causes of HPO contributing to the remainder. The incidence of HPO in patients with bronchogenic carcinoma varies in different reports, but it is approximately 10 % . This rather high frequency makes it particularly imperative to distinguish metastatic bone disease and HPO in radionuclide bone images. High quality images will usually depict the peri cortical deposition of HPO as opposed to a central increase in concentration which is associated with metastatic disease. Abnormal concentration of activity peripheral to the knees and el bows is more apt to prompt a diagnosis of HPO than metastatic disease as it is unusual for the latter to be disclosed in those areas. However, h igh quality gamma camera images may show the peri cortical concentration charac-
362
LEONARD ROSENTHALL AND JOEL KIRSH
August 1976
than some soft-tissue swelling about the joints in the radiographs, there was no direct evidence of synovitis, whereas the radionuclide study exhibited an increased periarticular concentration of 99mTcPPi. In conclusion, skeletal imaging with good quality views of the hands and feet employing 99mTc-phosphate complexes (pyrophosphate, diphosphonate) offers a very sensitive method of determining the presence and evaluating the extent of HPO. Subperiosteal bone deposition, synovitis, and regression of these processes with excision of the intrathoracic malignancy are readily exhibited. Fig. 4. CASE IV. Gamma camera images of the hands exhibiting a combination of metacarpal, periarticular and distal phalangeal concentration .
Division of Nuclear Medicine Montreal General Hospital Montreal, Quebec, Canada H3G 1A4
REFERENCES teristic of HPO, even in the phalanges of the hand as illustrated in Figure 3, and avoid confusion. The manifestation of inflammatory synovitis is readily appreciated as a periarticular bone uptake with 99l1Tfcppi. This is also seen in synovit is of other etiologies (4) and metabolic bone disease (9). Radionuclide regression of pericortical uptake of HPO and associated periarticular concentration of synovitis following removal of the primary tumor is demonstrated in CASE II (Fig. 2). Unfortunately, the radionuclide study was obtained one year after the pneumonectomy and the precise time the bone scan returned to normal could not be ascertained . The appearance of the radionuclide bone images correlated well with clinical signs and symptoms. Radionuclide disclosure of HPO is considerably more sensitive than radiography. Very subtle radiographic evidence of subperiosteal bone deposition was seen clearly and with greater extent along the shaft with use of 99mTcPPi. Other
1. Bieler E., Albrecht HJ: Das sZintigraphische Bild der Osteoarthropie hypertrophiante. Nucl Med (Stuttg), 10:196-200. 1971 2. Chaudhuri TK, Chaudhuri TK, Shapiro RL, et al: Positive 87mSr bone scan in a case of hypertrophic pulmonary osteoarthropathy.J Nucl Med 13:120-121 , Jan 1972 3. Coury C: Hippocratic fingers and hypertrophic osteoarthropathy: a study of 350 cases. Br J Dis Chest 54:202-209, Jul 1960 4. Desaulniers M, Fuks A, Hawkins D, et al: Radiotechnet ium polyphosphate joint imaging. J Nucl Med 15:417-423, Jun 1974 5. Donnelly B, Johnson PM: Detection of hypertrophic pulmonary osteoarthropathyby skeletal imaging with 99mrc-labelOO diphosphonate. Radiology 114:389-391, Feb 1975 6. Harmer CL, Burns JE, Sams A, et al: The value of f1uorine-18 for scanning bone tumours . Clin RadioI20:204-212, 1969 7. Kay CJ, Rosenberg MA: Positive 99mTc-polyphosphate bone scan in a case of secondary hypertrophic osteoarthropathy. J Nucl Moo 15:312-313, Apr 1974 8. Rosenthal! L, Kaye M: Technetium-99m-pyrophosphale kinetics and imaging in metabolic bone disease. J Nucl Med 16:33-39, Jan 1975 9. Shirazi PH, Rayudu GVS, Fordham EW: 18F bone scanning: review of indications and results of 1,500 scans. Radiology 112: 361-368, Aug 1974
Observations on Radionuclide Imaging in Hypertrophic Pulmonary Osteoarthropathy 1
Nuclear Medicine
Leonard Rosenthall, M.D., and Joel Kirsh, M.D. 99mTc pyrophosphate was employed in the study of patients with hypertrophic pulmonary osteoarthropathy. Several facts emerge when comparing the radionuclide, radiographic and clinical findings . Radionuclide imaging reveals the presence and extent of subperiosteal activity with greater clarity than does radiography. Synovitis associated with the syndrome is readily disclosed, and the regression of the skeletal manifestations following excision of the pulmonary lesion can be documented. INDEX TERMS: Bones, radionucllde studies. Lung neoplasms, radionuclide diagnosis • Neoplasms, metastases Radiology 120:359-362, August 1976
(HPO) is a clinical syndrome consisting of clubbing of fingers and toes, periostitis with bone tenderness, arthritis, and autonomic disorders such as profuse sweating, flushing and blanching. Pathologically, the distal ends of the long bones, metacarpals and metatarsals are principally involved, with edema of the periosteum, round cell infiltration and subperiosteal new bone formation. In severe disease, the ribs, clavicles, scapulae, pelvis and malar bones are included. The synovium, articular capsule and membranes adjacent to the affected joints are often edematous and infiltrated with lymphocytes, plasma cells and a few polymorphonuclear leucocytes. Cartilage degeneration may result from advanced proliferative fibrous tissue at joint margins. Prompt relief of symptoms can occur with resection of the primary lung lesion or intrathoracic vagotomy. Detection of HPOwith bone-seeking radiopharmaceuticals has been reported in the past. The advent of 18F (6, 9) followed by 99mTc-phosphate complexes (5, 7) has disclosed this entity with greater frequency than either 85Sr (1) or 87mSr (2) because of the improved quality of the images. This communication illustrates the various manifestations of HPO elicited by 99mTc-pyrophosphate (99mTcPPi) skeletal imaging.
H
YPERTROPHIC PULMONARY OSTEOARTHROPATHY
.....,
TECHNIQUE
Each patient was given 15-20 mCi 99mTcPPi intravenously and imaged 2-5 hours after delivery with a total body rectilinear scanner and/or a gamma camera. Three hundred thousand counts were accumulated on the gamma camera for all images except the handsand feet. The latter regions were imaged for equal times, but sufficient to collect about 100,000 counts. CASE REPORTS CASE I. J.1. is a 56-year-old man with an adenocarcinoma of the lung. He had a one-month history of cough , shortness of breath, decreased
Fig. 1. CASE I. 99mTcPPi images demonstrating pericortical deposition in the tibiae, ulnae and radii. Focal midfemoral shaft uptakes were due to metastases. Hands show evidence of periarticular concentration about some of the joints secondary to synovitis and bone uptake at the finger tips is probably due to clubbing and hyperemia.
appetite and weight loss. Clubbed fingers developed and his joints were painful, tender, swollen, warm and red. Some relief was obtained with indomethacin. The 99mrcPPi scan showed peri cortical concentration in the tibiae compatible with HPO (Fig 1). No HPO was disclosed in the femora, but there was focal metastatic disease. Both forearms showed the characteristic location of HPO at the distal ends of the ulna and radius . Periarticular uptake of 99mTcPPi was noted about most of the
1 From the Division of Nuclear Medicine, The Montreal General Hospital, Montreal, Quebec. Revised manuscript accepted for publication in January 1976. shan
359
360
LEONARD ROSENTHALL AND JOEL KIRSH
Augusl1976
•
0,'
Fig. 2. CASE II. A. Total body scan prior to surgery July 1972 showing increased pericortical concentration along the femoral and tibial shafts. B. Gamma camera images July 1972 demonstrating periarticular concentration about the knees, in particular the patellae, the proximal and distal interphalangeal joints of the hands and increased concentration in the right ulna and radius. C and D. One year after surgery, August 1973, the peri cortical and periarticular concentration returned to normal. joints and at the distal phalanges of the fingers which were obviously clubbed.
CASE II. M.O. is a 49-year-old woman. Two years prior to admission, she was followed in the Rheumatology Clinic for treatment of a presumptive diagnosis of rheumatoid arthritis. She was maintained on indomethacin therapy which gave some relief of pain. Three months prior to admission, she suffered bouts of fever, severe pain in both ankles and knees, clubbing of the finger tips and pitting edema from the knees to the toes. A chest radiograph revealed a left lower lobe mass which histologically was a poorly differentiated squamous cell carcinoma. A bone scan (Fig 2, A and B) prior to surgery showed characteristic pericortical concentration in the femurs , some linear and patchy con-
centration in the legs, abnormal right forearm, and increased periarticular concentration of the proximal and distal interphalangeal joints of the hands and both knees . The feet and ankles were not imaged. Within 24 hours of surgery there was a very significant amelioration of the pain in the lower extremities and a regression of the edema. One year following surgical removal of the tumor the radionuclide bone scan showed no evidence of HPO in the lower extremities and right forearm . The periarticular concentration in the knees and hands secondary to synovitis returned to normal (Fig 1, C and D). Clinically, she was free of all inflammatory signs and only minimal clubbing of the finger tips persisted. CASE III. A.S. This 63-year-old man with a poorly differentiated epidermoid carcinoma had HPO. Hands were puffy and the fingers were
HYPERTROPHIC PULMONARY OSTEOARTHROPATHY
Vol. 120
361
Nuclear Medicine
Fig. 3. CASE III. A. 99"'TcPPi gammacamera imagesdepictingpericortical concentration in the femora,tibiae, ulnae,radii and some of the proximal phalanges of the hands andmetacarpals. Note the absence of periarticular concentration about the metacarpo-phalangeal joints(compare with Fig. 4). .B. Radiographs of the hands, right ulna, radius, femur, tibia and fibula showing far less subperiosteal activity than the images in Figure 3, A.
clubbed, but there was no joint pain or limitation of movement. A 99 mTcPPi bone survey showed the typical pericortical concentration of HPO in the femora, tibiae, ulnaeanddistal radii (Fig.3). Someof the proximal phalanges clearly exhibited the " parallel track" deposition of HPO with 99"'TcPPi and the metacarpals showed variable involvement. Of interest was the lack of periarticular concentration in the metacarpo-phalangeal jointsof the hands, an area which did not exhibit synovitis clinically. A low, but abnormal concentration of 99"'TcPPi was registeredabout the proximal interphalangeal joints and this could be due to a subclinical synovitis which would surface later on (4). C ASE IV. P.R. A bronchogeniccarcinoma was the etiology of a diffuse HPO of the extremities in this 55-year-old man. Figure 4 is an illustration of the hands depicting generalized periarticular bone concentration of 99"'TcPPi indicative of inflammatory synovitis, increased uptake at thedistalends of the fingers associated with marked clubbing, anddeposition in some of the metacarpals.
DISCUSSION
About 80
%
of lung lesions associated with HPO are
bronchogenic carcinomas; pleural tumors make up 10%, and a miscellaneous group of intrathoracic malignancies account for 5% (3). Chronic suppurative pulmonary inflammatory disease and congenital cyanotic heart disease are non-malignant causes of HPO contributing to the remainder. The incidence of HPO in patients with bronchogenic carcinoma varies in different reports, but it is approximately 10 % . This rather high frequency makes it particularly imperative to distinguish metastatic bone disease and HPO in radionuclide bone images. High quality images will usually depict the peri cortical deposition of HPO as opposed to a central increase in concentration which is associated with metastatic disease. Abnormal concentration of activity peripheral to the knees and el bows is more apt to prompt a diagnosis of HPO than metastatic disease as it is unusual for the latter to be disclosed in those areas. However, h igh quality gamma camera images may show the peri cortical concentration charac-
362
LEONARD ROSENTHALL AND JOEL KIRSH
August 1976
than some soft-tissue swelling about the joints in the radiographs, there was no direct evidence of synovitis, whereas the radionuclide study exhibited an increased periarticular concentration of 99mTcPPi. In conclusion, skeletal imaging with good quality views of the hands and feet employing 99mTc-phosphate complexes (pyrophosphate, diphosphonate) offers a very sensitive method of determining the presence and evaluating the extent of HPO. Subperiosteal bone deposition, synovitis, and regression of these processes with excision of the intrathoracic malignancy are readily exhibited. Fig. 4. CASE IV. Gamma camera images of the hands exhibiting a combination of metacarpal, periarticular and distal phalangeal concentration .
Division of Nuclear Medicine Montreal General Hospital Montreal, Quebec, Canada H3G 1A4
REFERENCES teristic of HPO, even in the phalanges of the hand as illustrated in Figure 3, and avoid confusion. The manifestation of inflammatory synovitis is readily appreciated as a periarticular bone uptake with 99l1Tfcppi. This is also seen in synovit is of other etiologies (4) and metabolic bone disease (9). Radionuclide regression of pericortical uptake of HPO and associated periarticular concentration of synovitis following removal of the primary tumor is demonstrated in CASE II (Fig. 2). Unfortunately, the radionuclide study was obtained one year after the pneumonectomy and the precise time the bone scan returned to normal could not be ascertained . The appearance of the radionuclide bone images correlated well with clinical signs and symptoms. Radionuclide disclosure of HPO is considerably more sensitive than radiography. Very subtle radiographic evidence of subperiosteal bone deposition was seen clearly and with greater extent along the shaft with use of 99mTcPPi. Other
1. Bieler E., Albrecht HJ: Das sZintigraphische Bild der Osteoarthropie hypertrophiante. Nucl Med (Stuttg), 10:196-200. 1971 2. Chaudhuri TK, Chaudhuri TK, Shapiro RL, et al: Positive 87mSr bone scan in a case of hypertrophic pulmonary osteoarthropathy.J Nucl Med 13:120-121 , Jan 1972 3. Coury C: Hippocratic fingers and hypertrophic osteoarthropathy: a study of 350 cases. Br J Dis Chest 54:202-209, Jul 1960 4. Desaulniers M, Fuks A, Hawkins D, et al: Radiotechnet ium polyphosphate joint imaging. J Nucl Med 15:417-423, Jun 1974 5. Donnelly B, Johnson PM: Detection of hypertrophic pulmonary osteoarthropathyby skeletal imaging with 99mrc-labelOO diphosphonate. Radiology 114:389-391, Feb 1975 6. Harmer CL, Burns JE, Sams A, et al: The value of f1uorine-18 for scanning bone tumours . Clin RadioI20:204-212, 1969 7. Kay CJ, Rosenberg MA: Positive 99mTc-polyphosphate bone scan in a case of secondary hypertrophic osteoarthropathy. J Nucl Moo 15:312-313, Apr 1974 8. Rosenthal! L, Kaye M: Technetium-99m-pyrophosphale kinetics and imaging in metabolic bone disease. J Nucl Med 16:33-39, Jan 1975 9. Shirazi PH, Rayudu GVS, Fordham EW: 18F bone scanning: review of indications and results of 1,500 scans. Radiology 112: 361-368, Aug 1974
