Bone & Soft Tissue Pathology
Case 4 -
Bizarre Parosteal Osteochondromatous Proliferation (Nora's lesion) of a Long Bone
Gene P. Siegal
University of Alabama
Virtual Slides as well as Still Images are displayed below.
For the fastest viewing of virtual slides, click:
under each thumbnail image below. You must have Aperio ImageScope installed on your PC.
Or, click on slide thumbnail images to view each slide
If you do not already have Aperio ImageScope, Windows users with administrator privileges may download and install a free version in order to view USCAP Virtual Slides. Click the icon on the right to get your free copy: ||
in a Web-based slide viewer, which is somewhat slower.
If you have any difficulties viewing these slides, email or call George Clay at +1.724.449.1137.
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
Case 4 - Slide 2
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
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
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.
Bizarre parosteal osteochondromatous proliferation (Nora's lesion) of a long bone
- 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 .
- Golouh R, Zidar A: Subungual Osteogenic Malignant Melanoma: A Case Report. Intl J Surg Pathol. 4:249-253,1997.
- Helliwell TR, O'Connor MA, Ritchie DA, Feldberg L, Stilwell JH, Jane MJ: Bizarre parosteal osteochondromatous proliferation with cortical invasion. Skeletal Radiol. 30:282-285, 2001.
- Kiyozuka Y, Miyazaki H, Yoshizawa K, Senzaki H, Yamamoto D, Inoue K, Okubo Y, Kusumoto K and Tsubura A. An autopsy case of malignant mesothelioma with osseous and cartilaginous differentiation: Bone morphogenic protein-2 in mesothelial cells and its tumor. Digest Dis Sci. 44: 1626-1631, 1999.
- Kraft D, Hailer NP. Nora's lesion at the second metacarpal bone of a twelve-year-old female. Z Orthop Ihre Grenzgeb. 144:228-231, 2006.
- Mackie GC:Bizarre parosteal osteochondromatous proliferation detected by Tl-201 scintigraphy. Clin Nucl Med. 28:591-593, 2003.
- Meneses MF, Unni KK, Swee RG:Bizarre parosteal osteochondromatous proliferation of bone (Nora's lesion). Am J Surg Pathol. 17:691-697, 1993.
- Milchgrub S, Ghandur-Mnaymneh L, Dorfman HD, Albores-Saavedra J:Synovial sarcoma with extensive osteoid and bone formation. Am J Surg Pathol. 17:357-363, 1993.
- Nance KV, Renner JB,Brashear HR, Siegal GP:Massive florid reactive periostitis. Pediat Radiol. 20,186-189, 1990.
- Nilsson M, Domanski HA, Mertens F, Mandahl N: Molecular cytogenetic characterization of recurrent translocation breakpoints in bizarre parosteal osteochondromatous proliferation (Nora's lesion). Hum Pathol. 35:1063-1069, 2004.
- Nora FE, Dahlin DC , Beabout JW: Bizarre parosteal osteochondromatous proliferation of the hands and feet. Am J Surg Pathol. 7:245-250, 1983.
- Rungsipipat A, Yamaguchi R, Naganobu K, Iwamoto K, Uchida K, Tateyama S, Kurogi T, Katayama N. A bone tumour resembling bizarre parosteal osteochondromatous proliferation in a wallaby. Aust Vet J. 76:561-564, 1998.
- Sundaram M, Wang L, Rotman M, Howard R, Saboeiro AP: Florid reactive periostitis and bizarre parosteal osteochondromatous proliferation: pre-biopsy imaging evolution, treatment and outcome. Skeletal Radiol. 30:192-198, 2001.
- Torreggiani WC, Munk PL, Al-Ismail K, O'Connell JX, Nicolaou S, Lee MJ, Masri BA: MR imaging features of bizarre parosteal osteochondromatous proliferation of bone (Nora's lesion). Eur J Radiol. 40:224-231.2001.
- Zambrano E, Nose V, Perez-Atayde AR, Gebhardt M, Hresko MT, Kleinman P, Richkind KE, Kozakewich HP: Distinct chromosomal rearrangements in subungual (Dupuytren) exostosis and bizarre parosteal osteochondromatous proliferation (Nora lesion). Am J Surg Pathol. 28:1033-1039, 2004.