Skeletal Radiol (2992) 21:546 549
Skeletal Radiology
Case report 761 Sabrina V.-M. Patrone, M.D. 1, Charles S. Resnik, M.D. 1, Seena C. Aisner, M.D. 2, and Jeremy W.R. Young, M.D. 1 Departments of i Diagnostic Radiology and 2 Pathology, University of Maryland Medical System, Baltimore, Maryland, USA
Radiological studies
Fig. 1. An anteroposterior radiograph shows no abnormalities in the left clavicle
9 1992 International Skeletal Society
Fig. 2A-C. Three contiguous axial sections through the medial aspects of the clavicles
shows permeative bone destruction on the left compared with the normal right side
S.V.-M. Patrone et al. : Case report 761
Clinical information
A 19-year-old woman noted pain in her left shoulder 2-3 months prior to presentation. She was treated conservatively and the pain improved. Subsequently, she developed severe pain over the left clavicle with associated Correspondence to: Charles S. Resnik, M.D., Department of Radiology, University of Maryland Medical System, 22 South Greene Street, Baltimore, MD 21201, USA
547
swelling. Initially, the pain was intermittent and exacerbated by direct contact, but over a 2-week period it became constant. On physical examination, no swelling was evident. Tenderness to palpation was noted along the left clavicle. No supraclavicular or axillary adenopathy was noted. All initial laboratory values were normal including the white blood cell count and hematocrit. Plain radiographs of
the left clavicle showed no abnormality (Fig. 1). Computed tomography (CT) revealed permeative bone destruction within the medial portion of the left clavicle (Fig. 2). A radionuclide bone scan demonstrated increased tracer activity corresponding to the site of bone destruction noted on CT with no other areas of abnormality. A biopsy of the medial aspect of the left clavicle was performed.
548
Diagnosis: Acute lymphocytic leukemia The radiologic differential diagnosis includes primarily osteomyelitis, Ewing's tumor and lymphoma. Osteosarcoma and metastatic disease would be less likely. Tissue curettings removed from the left clavicle revealed a monomorphic population of round cells consistent with a malignant lymphoid process (Fig. 3). Special stains for periodic acid-Schiff (PAS) were negative. Electron microscopic examination revealed cells with a single large nucleus containing a few organelles, mostly mitochondria. Glycogen and intercellular bridges were absent. These findings together with the light microscopic fndings were compatible with lymphocytic lymphoma or lymphocytic leukemia. Subsequent iliac bone marrow aspirate revealed marrow replaced by a diffuse monomorphic population of lymphoid elements, confirming the diagnosis of acute lymphocytic leukemia (ALL).
Discussion Leukemia, the most common cancer in children, is a generalized myeloproliferative disease. It has a male predominance and a peak age incidence of 2-5 years and presents with a combination of clinical features including fever, pallor, listlessness, hemorrhagic tendencies, hepatosplenomegaly, and lymphadenopathy [10, 12, 15]. In some instances, arthritis may be the presenting feature of childhood leukemia [4, 11]. Approximately 20%-40% of children will have bone pain in addition to their other symptoms [5, 7, 9, 10, 12]. Bone pain may be present in as many as 50% of affected adults [14]. Lymphocytic leukemia occurs less commonly than myelogenous leukemia from the ages of 15 39 years. Radiographically evident bone abnormalities in children with leukemia include generalized osteoporosis (24%-100%), periosteal reaction (2%-50%), metaphyseal radiolucent bands (8%-93%), osteolytic lesions (3%-90%), and osteosclerosis (0%9%) [1, 2, 6, 10, 12-15]. The wide variation in the reported incidence of
S.V.-M. Patrone et al. : Case report 761
Pathological study
Fig. 3. Tissue curettings show a monomorphic population of lymphoid elements. Note the uniformdark nuclei. H&E, x 1000
these findings relates to the varied definitions by different authors. In one study of 1471 patients with ALL, Hughes and Kay found an incidence o f " m a j o r " bone lesions (lytic lesions distinct from mere rarefaction) of 3.2% [6], while Thomas et al. reported that 90% of children had osteolytic lesions (described as usually less than 5 mm in size) [14]. Simmons et al. described the most characteristic radiographic feature in establishing leukemic involvement of the skeleton as punctate areas of radiolucency producing a permeating appearance, commonly seen in the metaphyses of long bones and less frequently in flat bones [13]. Regardless of the true incidence of these abnormalities, they are usually discovered after the diagnosis of leukemia has been established clinically. Fewer than 10 cases presenting only with bone pain and a destructive bone lesion have been reported previously [2, 3, 7, 10, 13]. The current case points out that ALL should be considered in the differential diagnosis of a painful lytic bone lesion even in the absence of systemic signs or symptoms. In the few similar cases described in the literature, a diagnosis of osteomyelitis
was most often entertained [2, 3, 7, 10, 13]. Infection of bone commonly leads to radiographically evident osseous destruction, but early plain film evidence of permeation may be lacking. In this situation, if nonspecific bone pain is a presenting complaint, radionuclide bone scan, computed tomography, or even magnetic resonance imaging may offer the initial evidence of an osseous abnormality. A similar presentation might occur with malignant processes, particularly Ewing's tumor in a child or young adult. The correlation of bone pain with radiographic bone lesions has not been well established. In a study of 137patients with ALL, Rajantie et al. reported that the presence of pain significantly correlated with the presence of abnormalities of the long bones [9]. Thomas et al. found that cortical or periosteal lesions occurred three times more frequently in patients with severe bone pain, but ""osteolytic" lesions were only "somewhat more common" in this group [14]. Silverman observed no significant correlation between the sites of pain and the sites of roentgen lesions, with less than half of lesions being painful and 17 out of 103 patients
S.V.-M. Patrone et al. : Case report 761 having pain w i t h o u t lesions [52]. This is m o r e evidence that the initial clinical picture o f patients with A L L m a y be confusing. The prognosis o f patients with A L L does n o t seem to be affected by the presence o f demonstrable b o n y involvement. N u m e r o u s authors have f o u n d no significant correlation between the degree o f b o n e pain or the extent o f radiological bone disease a n d the survival or length o f remission [1, 5, 8, 9, 14]. In fact, Rajantie et al. reported that the d u r a t i o n o f remission and survival times were greater in patients with long b o n e changes t h a n in those w i t h o u t them [9]. Nevertheless, as in the current case, the discovery o f a b o n e lesion on an imaging study obtained because o f b o n e pain m a y be the initial step in establishing a diagnosis o f A L L . O r t h o p e d i c surgeons and radiologists should be aware o f the possibility o f this rare presentation without systemic signs or s y m p t o m s . In s u m m a r y , this case represents an u n u s u a l presentation o f A L L d e m o n s t r a t i n g a solitary painful osteolytic lesion with no initial systemic or hematological manifestations. Fewer than 10 such cases have been reported previously. A l t h o u g h there is wide variation in the reported inci-
549 dence o f radiographically evident bone abnormalities (generalized osteoporosis, periosteal reaction, metaphyseal radiolucent bands, osteolytic lesions, and osteosclerosis) in children with leukemia, this diagnosis must be included with osteomyelitis and Ewing's t u m o r as possible explanations for localized bone pain.
References 1. Aur RJA, Westbrook HW, Riggs W JR (1972) Childhood acute lymphocytic leukemia: initial radiological bone involvement and prognosis. Am J Dis Child 124:653 2. Benz G, Brandeis W, Willich E (1976) Radiologic aspects of leukaemia in childhood. An analysis of 89 children. Pediatr Radiol 4:201 3. Bos GD, Simon MA, Spiegel PG, Moohr JW (1978) Childhood leukemia presenting as a diaphyseal radiolucency. Clin Orthop 135 : 66 4. Fing CW, Windmiller J, Sartain D (1972) Arthritis as presenting feature of childhood leukemia. Arthritis Rheum 15:347 5. Hann IM, Gupta S, Palmer MK, Morris-Jones PH (1979) The prognostic significance of radiological and symptomatic bone involvement in childhood acute lymphoblastic leukaemia. Med Pediatr Oncol 6 : 51 6. Hughes RG, Kay HEM (1982) Major bone lesions in acute lymphoblastic leukaemia. Med Pediatr Oncol 10:67
7. Jonsson OG, Sartain P, Ducore JM, Buchanan GR (1990) Bone pain as an initial symptom of childhood acute lymphoblastic leukemia: association with nearly normal hematolgoic indexes. J Pediatr 117:233 8. Pastore G, Miniero R, Montezemolo LC di, Felicioni V, Fiandino G, Grazia G, Morgando MP, Trada M, Madon E (1981) The prognostic value of bone involvement in childhood acute lymphoblastic leukaemia. Haematologica 66: 750 9. Rajantie J, Jaaskelainen J, Perkkio M, Siimes MA (1985) Prognostic significance of primary bone changes in children with acute lymphoblastic leukemia. Pediatr Radiol 15:242 10. Rogalsky RJ, Black GB, Reed MH (1986) Orthopaedic manifestions of leukemia in children. J Bone Joint Surg [Am] 68 : 494 11. Saulsbury FT, Sabio H (1985) Acute leukemia presenting as arthritis in children. Clin Pediatr 24:625 12. Silverman FN (1948) The skeletal lesions in leukemia: clinical and roentgenographic observations in 103 infants and children, with a review of the literature. Am J Roentgenol 59:819 13. Simmons CR, Harle TS, Singleton EB (1968) The osseous manifestations of leukemia in children. Radiol Clin North Am 6:115 14. Thomas LB, Forkner CE, Fret E, Besse BE Jr, Stabenau JR (1961) The skeletal lesions of acute leukemia. Cancer 14:608 15. Wilson J (1959) The bone lesions of childhood leukemia. Radiology 72:672
Skeletal Radiology
Case report 761 Sabrina V.-M. Patrone, M.D. 1, Charles S. Resnik, M.D. 1, Seena C. Aisner, M.D. 2, and Jeremy W.R. Young, M.D. 1 Departments of i Diagnostic Radiology and 2 Pathology, University of Maryland Medical System, Baltimore, Maryland, USA
Radiological studies
Fig. 1. An anteroposterior radiograph shows no abnormalities in the left clavicle
9 1992 International Skeletal Society
Fig. 2A-C. Three contiguous axial sections through the medial aspects of the clavicles
shows permeative bone destruction on the left compared with the normal right side
S.V.-M. Patrone et al. : Case report 761
Clinical information
A 19-year-old woman noted pain in her left shoulder 2-3 months prior to presentation. She was treated conservatively and the pain improved. Subsequently, she developed severe pain over the left clavicle with associated Correspondence to: Charles S. Resnik, M.D., Department of Radiology, University of Maryland Medical System, 22 South Greene Street, Baltimore, MD 21201, USA
547
swelling. Initially, the pain was intermittent and exacerbated by direct contact, but over a 2-week period it became constant. On physical examination, no swelling was evident. Tenderness to palpation was noted along the left clavicle. No supraclavicular or axillary adenopathy was noted. All initial laboratory values were normal including the white blood cell count and hematocrit. Plain radiographs of
the left clavicle showed no abnormality (Fig. 1). Computed tomography (CT) revealed permeative bone destruction within the medial portion of the left clavicle (Fig. 2). A radionuclide bone scan demonstrated increased tracer activity corresponding to the site of bone destruction noted on CT with no other areas of abnormality. A biopsy of the medial aspect of the left clavicle was performed.
548
Diagnosis: Acute lymphocytic leukemia The radiologic differential diagnosis includes primarily osteomyelitis, Ewing's tumor and lymphoma. Osteosarcoma and metastatic disease would be less likely. Tissue curettings removed from the left clavicle revealed a monomorphic population of round cells consistent with a malignant lymphoid process (Fig. 3). Special stains for periodic acid-Schiff (PAS) were negative. Electron microscopic examination revealed cells with a single large nucleus containing a few organelles, mostly mitochondria. Glycogen and intercellular bridges were absent. These findings together with the light microscopic fndings were compatible with lymphocytic lymphoma or lymphocytic leukemia. Subsequent iliac bone marrow aspirate revealed marrow replaced by a diffuse monomorphic population of lymphoid elements, confirming the diagnosis of acute lymphocytic leukemia (ALL).
Discussion Leukemia, the most common cancer in children, is a generalized myeloproliferative disease. It has a male predominance and a peak age incidence of 2-5 years and presents with a combination of clinical features including fever, pallor, listlessness, hemorrhagic tendencies, hepatosplenomegaly, and lymphadenopathy [10, 12, 15]. In some instances, arthritis may be the presenting feature of childhood leukemia [4, 11]. Approximately 20%-40% of children will have bone pain in addition to their other symptoms [5, 7, 9, 10, 12]. Bone pain may be present in as many as 50% of affected adults [14]. Lymphocytic leukemia occurs less commonly than myelogenous leukemia from the ages of 15 39 years. Radiographically evident bone abnormalities in children with leukemia include generalized osteoporosis (24%-100%), periosteal reaction (2%-50%), metaphyseal radiolucent bands (8%-93%), osteolytic lesions (3%-90%), and osteosclerosis (0%9%) [1, 2, 6, 10, 12-15]. The wide variation in the reported incidence of
S.V.-M. Patrone et al. : Case report 761
Pathological study
Fig. 3. Tissue curettings show a monomorphic population of lymphoid elements. Note the uniformdark nuclei. H&E, x 1000
these findings relates to the varied definitions by different authors. In one study of 1471 patients with ALL, Hughes and Kay found an incidence o f " m a j o r " bone lesions (lytic lesions distinct from mere rarefaction) of 3.2% [6], while Thomas et al. reported that 90% of children had osteolytic lesions (described as usually less than 5 mm in size) [14]. Simmons et al. described the most characteristic radiographic feature in establishing leukemic involvement of the skeleton as punctate areas of radiolucency producing a permeating appearance, commonly seen in the metaphyses of long bones and less frequently in flat bones [13]. Regardless of the true incidence of these abnormalities, they are usually discovered after the diagnosis of leukemia has been established clinically. Fewer than 10 cases presenting only with bone pain and a destructive bone lesion have been reported previously [2, 3, 7, 10, 13]. The current case points out that ALL should be considered in the differential diagnosis of a painful lytic bone lesion even in the absence of systemic signs or symptoms. In the few similar cases described in the literature, a diagnosis of osteomyelitis
was most often entertained [2, 3, 7, 10, 13]. Infection of bone commonly leads to radiographically evident osseous destruction, but early plain film evidence of permeation may be lacking. In this situation, if nonspecific bone pain is a presenting complaint, radionuclide bone scan, computed tomography, or even magnetic resonance imaging may offer the initial evidence of an osseous abnormality. A similar presentation might occur with malignant processes, particularly Ewing's tumor in a child or young adult. The correlation of bone pain with radiographic bone lesions has not been well established. In a study of 137patients with ALL, Rajantie et al. reported that the presence of pain significantly correlated with the presence of abnormalities of the long bones [9]. Thomas et al. found that cortical or periosteal lesions occurred three times more frequently in patients with severe bone pain, but ""osteolytic" lesions were only "somewhat more common" in this group [14]. Silverman observed no significant correlation between the sites of pain and the sites of roentgen lesions, with less than half of lesions being painful and 17 out of 103 patients
S.V.-M. Patrone et al. : Case report 761 having pain w i t h o u t lesions [52]. This is m o r e evidence that the initial clinical picture o f patients with A L L m a y be confusing. The prognosis o f patients with A L L does n o t seem to be affected by the presence o f demonstrable b o n y involvement. N u m e r o u s authors have f o u n d no significant correlation between the degree o f b o n e pain or the extent o f radiological bone disease a n d the survival or length o f remission [1, 5, 8, 9, 14]. In fact, Rajantie et al. reported that the d u r a t i o n o f remission and survival times were greater in patients with long b o n e changes t h a n in those w i t h o u t them [9]. Nevertheless, as in the current case, the discovery o f a b o n e lesion on an imaging study obtained because o f b o n e pain m a y be the initial step in establishing a diagnosis o f A L L . O r t h o p e d i c surgeons and radiologists should be aware o f the possibility o f this rare presentation without systemic signs or s y m p t o m s . In s u m m a r y , this case represents an u n u s u a l presentation o f A L L d e m o n s t r a t i n g a solitary painful osteolytic lesion with no initial systemic or hematological manifestations. Fewer than 10 such cases have been reported previously. A l t h o u g h there is wide variation in the reported inci-
549 dence o f radiographically evident bone abnormalities (generalized osteoporosis, periosteal reaction, metaphyseal radiolucent bands, osteolytic lesions, and osteosclerosis) in children with leukemia, this diagnosis must be included with osteomyelitis and Ewing's t u m o r as possible explanations for localized bone pain.
References 1. Aur RJA, Westbrook HW, Riggs W JR (1972) Childhood acute lymphocytic leukemia: initial radiological bone involvement and prognosis. Am J Dis Child 124:653 2. Benz G, Brandeis W, Willich E (1976) Radiologic aspects of leukaemia in childhood. An analysis of 89 children. Pediatr Radiol 4:201 3. Bos GD, Simon MA, Spiegel PG, Moohr JW (1978) Childhood leukemia presenting as a diaphyseal radiolucency. Clin Orthop 135 : 66 4. Fing CW, Windmiller J, Sartain D (1972) Arthritis as presenting feature of childhood leukemia. Arthritis Rheum 15:347 5. Hann IM, Gupta S, Palmer MK, Morris-Jones PH (1979) The prognostic significance of radiological and symptomatic bone involvement in childhood acute lymphoblastic leukaemia. Med Pediatr Oncol 6 : 51 6. Hughes RG, Kay HEM (1982) Major bone lesions in acute lymphoblastic leukaemia. Med Pediatr Oncol 10:67
7. Jonsson OG, Sartain P, Ducore JM, Buchanan GR (1990) Bone pain as an initial symptom of childhood acute lymphoblastic leukemia: association with nearly normal hematolgoic indexes. J Pediatr 117:233 8. Pastore G, Miniero R, Montezemolo LC di, Felicioni V, Fiandino G, Grazia G, Morgando MP, Trada M, Madon E (1981) The prognostic value of bone involvement in childhood acute lymphoblastic leukaemia. Haematologica 66: 750 9. Rajantie J, Jaaskelainen J, Perkkio M, Siimes MA (1985) Prognostic significance of primary bone changes in children with acute lymphoblastic leukemia. Pediatr Radiol 15:242 10. Rogalsky RJ, Black GB, Reed MH (1986) Orthopaedic manifestions of leukemia in children. J Bone Joint Surg [Am] 68 : 494 11. Saulsbury FT, Sabio H (1985) Acute leukemia presenting as arthritis in children. Clin Pediatr 24:625 12. Silverman FN (1948) The skeletal lesions in leukemia: clinical and roentgenographic observations in 103 infants and children, with a review of the literature. Am J Roentgenol 59:819 13. Simmons CR, Harle TS, Singleton EB (1968) The osseous manifestations of leukemia in children. Radiol Clin North Am 6:115 14. Thomas LB, Forkner CE, Fret E, Besse BE Jr, Stabenau JR (1961) The skeletal lesions of acute leukemia. Cancer 14:608 15. Wilson J (1959) The bone lesions of childhood leukemia. Radiology 72:672
