Case 4 -

Bizarre Parosteal Osteochondromatous Proliferation (Nora's lesion) of a Long Bone Gene P. Siegal University of Alabama Birmingham, AL

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Case History: A 15 year old young woman first came to attention because of an apparent "regrowth" of an osteochondroma immediately adjacent to the site of a previous lesion removed some 4 years earlier. A diagnosis was made and the patient was not treated beyond a simple re-excision. Now at age 17, she has developed a second recurrence. Case 4 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 4 - Slide 2 Click to view with ImageScope Click to view with a Web-Based Viewer Case 4 - Figure 1 - Radiologic images revealed an abnormal lesion adjacent to the lateral aspect of the distal fibula with some mixed elements including bone and cartilage but without continuity to the fibula marrow. Case 4 - Figure 2 - Radiologic images revealed an abnormal lesion adjacent to the lateral aspect of the distal fibula with some mixed elements including bone and cartilage but without continuity to the fibula marrow. Case 4 - Figure 3 - Representative images of histology. Note the varying proportions of atypical cartilage, bone and spindles fibroblast cell population. Note that some of the bone is "blue". Case 4 - Figure 4 - Representative images of histology. Note the varying proportions of atypical cartilage, bone and spindles fibroblast cell population. Note that some of the bone is "blue". Case 4 - Figure 5 - The intraoperative radiograph demonstrates an expansile mass with lesional contents suggesting both bone and cartilaginous element. Case 4 - Figure 6 - Representative images of original slide. There does appear to be a thin cartilage cap overlying atypical fibroblastic cells and bony spicules. The lesion is very vascular which is better appreciated at higher power. Case 4 - Figure 7 - Representative images of original slide. There does appear to be a thin cartilage cap overlying atypical fibroblastic cells and bony spicules. The lesion is very vascular which is better appreciated at higher power. Case 4 - Figure 8 - Representative radiologic image of recurrence. A surgical defect is noted both in the bone and soft tissues along with a sclerotic proliferation adjacent to the previous site of surgery. Case 4 - Figure 9 - Representative histologic images of the recurrence which are very similar to the previous sections. This time the cartilage is however more hypercellular and the nuclei have increased pleomorphism Case 4 - Figure 10 - Representative histologic images of the recurrence which are very similar to the previous sections. This time the cartilage is however more hypercellular and the nuclei have increased pleomorphism Radiologic Findings: Radiographic images of the first recurrence revealed an abnormal soft tissue lesion adjacent to the lateral aspect of the distal fibula with some mixed elements including bone and cartilage but without continuity to the fibula marrow. The lesion was superficial and well-defined but was noted to produce a pressure effect on the surrounding tendon. Furthermore, it was elliptical in shape with an intermediate signal and appeared extrinsic to the bone. There was a lack of expected high signal on T-2 weighted images. The consulting radiologist felt an organizing hematoma would need to be excluded but a neoplastic proliferation could not be completely eliminated. An intra-operative radiograph from the original surgery was subsequently obtained as was a representative radiograph from the second recurrence. Gross Pathologic Findings: At the time of the first recurrence 3 fragments of bony tissue, the largest measuring 3 X 3 X 1.5 cm were received. This largest piece was said to be covered by an irregularly contoured cartilaginous cap of less than 2 mm in thickness. The other 2 fragments were composed grossly of cancellous bone. Discussion with Differential Diagnoses: A group of closely related tumefactive processes producing bone have been described under the names (massive) florid reactive periostitis, subungual exostosis, fibro-osseous pseudotumor of the digits and bizarre parosteal osteochondromatous proliferation [BPOP]. These lesions tend to favor the fingers and toes and have overlapping histopathologic features. Their relationship to trauma has been speculated upon endlessly without any firm conclusions. It has been argued for some time that these lesions although often difficult to separate histologically can be separated by conventional radiology. This position has recently been strengthened in a large study by Dutch investigators. Nora and associates, utilizing the Mayo Clinic files in the mid 1980s first popularized BPOP. Although it was originally thought to be limited to the bones of the hands and feet, it was subsequently recognized that BPOP could also occur in the skull, gnathic bones and long bones. It has a peak incidence in early adulthood in the second to fourth decades of life but has been described both in young children and the elderly. Neither gender predominates. BPOP has been reported in a wallaby and I have seen a single case in consultation in its paw of a giant breed dog. Clinical history and laboratory studies are usually non-contributory or non-specific. On conventional radiography the lesions in the bones of the hands and feet are seen to be seemingly well marginated masses of heterotopic mineralization or calcification, broadly associated with the bone surface, maintaining an intact cortex, without medullary changes thus separating these relatively easily from osteochondromas. However, in long bones, BPOP may have a more aggressive phenotype radiologically, with cortical destruction. Similarly, early in its progression, Nora's lesion may appear confined to the soft tissue (mini-heterotopic ossification) separate from the juxtaposed bone which when followed over time is seen to develop cortical attachment. Only relatively few MRI studies have been reported in the peer-reviewed literature. The lesion is described as being of low signal intensity on T1 weighted sequences while on T2 weighted and STIR sequences, the lesion is of high signal intensity. Important to the differential diagnoses, the cortex, medullary cavity and adjacent soft tissues are generally described as normal or without significant abnormalities. These lesions have also been detected by Tl-201 scintigraphy. Histologically, as the name suggests, these lesions contain varying proportions of atypical cartilage, bone and spindled fibroblastic cell populations without cytologic atypia often in a vascular background. These spindle cells may fill the intertrabecular spaces raising the possibility of parosteal osteosarcoma. The hypercellular cartilage, in turn, demonstrates varying degrees of calcification and ossification. As with osteoblastoma, the mineralized cartilage has a characteristic basophilic tinctorial quality; i.e. blue bone. Atypical mitoses are not a feature of this lesion although a rare mitotic figure should not dissuade one from the diagnosis. We have recently reviewed the cytogenetic and molecular genetic abnormalities associated with Nora's lesion. The data remains less than complete. However a t(1;17)(q32;q21) balanced translocation has been reported in 1 case, a t(1;17)(q 42;q23) translocation in a second case and a ring chromosome associated with chromosome 12 was identified in a third case. This argues that 1) if non-random unique aberrations exist, these lesions may be closer to neoplasms than reactive processes and 2), these lesions can be separated cytogenetically from t(X;6)balanced translocations known to be associated with subungual exostoses. Although without metastatic capability [1 reported case of a fibrosarcoma arising in the same bone as a BPOP in the world literature], these lesions recur frequently [55% in one Mayo series], as in this case. Approximately one-fifth of cases in the literature recurred more than once. Not surprisingly, this generates a great deal of anxiety among all as the differential diagnoses include not only the benign proliferative lesions alluded to above but low grade surface [parosteal] and soft tissue osteosarcoma. A number of other malignant tumors have also been associated with bizarre cartilage and bone production. Among these are subungual/turret osteogenic malignant melanoma, mesothelioma with osseous and cartilaginous differentiation and synovial sarcoma with extensive osteoid and bone formation. In this case, an osteochondroma was the leading diagnosis. However, in osteochondromas, the characteristic radiographic appearance of the exophytic mass "flowing or sweeping" out of the medullary cavity, in continuity with the cortex, was never appreciated. Typically, a cartilage cap is recognized especially if CT or MR is performed. The cartilage associated with lesion confused both the referring radiologist and pathologist but the lesional bone matrix should have been a tip off and a recurrence in an osteochondroma is exquisitely unusual. The treatment usually proposed is simple excision but knowing its high rate of recurrence would argue that a generous margin should be obtained if it will not compromise function in the patient. Diagnosis: Bizarre parosteal osteochondromatous proliferation (Nora's lesion) of a long bone References: Abramovici L, Steiner GC: Bizarre parosteal osteochondromatous proliferation (Nora's lesion): A retrospective study of 12 cases, 2 arising in long bones. Hum Pathol. 33:1205-10, 2002. Bell WC, Klein MJ, Pitt MJ, Siegal GP: Molecular Pathology of chondroid neoplasms: Part I, Benign lesions. Skeletal Radiol. 35:805-813, 2006. Dhondt E, Oudenhoven L, Khan S, Kroon HM, Hogendoorn PC, Nieborg A, Bloem JL, De Schepper A.Nora's lesion, a distinct radiological entity? Skeletal Radiol. 35:497 502, 2006. Endo M, Hasegawa T, Tashiro T, Yamaguchi U, Morimoto Y, Nakatani F, Shimoda T: Bizarre parosteal osteochondromatous proliferation with a t(1;17) translocation. Virchows Arch. 447:99-102, 2005 . 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