Howard D. Dorfman

Vascular tumors of bone.

Abstract Primary tumors of bone of vascular origin are rare. Consequently, knowledge of their clinical and pathologic features is still scanty. A morass of misleading terminology, particularly in connection with the malignant vascular tumors, has added to the difficulties. This paper is a review of our current knowledge of these lesions based on a series of 42 personally studied cases. It presents a classification of the vascular tumors of bone and its converings and attempts to sort out in an orderly way the confusing array of terms applied to the malignant bone tumors of blood vessel origin.

Florid reactive periostitis of the tubular bones of the hands and feet. A benign lesion which may simulate osteosarcoma.

Twelve patients with florid reactive periostitis of the small bones of the hands and feet are presented. Clinically, the lesion usually presents as a swelling of the affected part, sometimes accompanied by pain, tenderness, and redness. Histologically, the lesion may be mistaken for benign and malignant neoplasms such as osteosarcoma or parosteal osteosarcoma or osteochondromas. The features that distinguish reactive periostitis from the several diagnostic possibilities are presented. It is important for the clinician and the pathologist to recognize the existence of florid reactive periostitis in the hands and feet and to treat accordingly. Local excision appears to be adequate treatment; follow-up indicates little risk for local recurrence.

Epithelioid hemangioendothelioma of bone. A clinicopathologic, ultrastructural, and immunohistochemical study.

In a review of 29 cases of solitary and multicentric hemangioendo the lialsarcomas of bone, 14 were found to have histologic features of epithelioid hemangioendotheliomas. These were characterized by the presence of epithelioid or “histiocytoid” endothelial cells that were either round or spindle-shaped. Intracytoplasmic vacuolization was noted, and some showed nesting of cells, mimicking metastatic adenocarcinoma. The presence of a myxoid matrix suggested the diagnosis of chondrosarcoma in some cases. Some of the tumors strongly resembled the lesions formerly designated as intravascular bronchioloalveolar tumor, angioglomoid tumor of bone, or malignant myxoid angioblastoma of bone. Factor VIIIrelated antigen was detected in five of the six cases examined, and ultrastructural study in five cases confirmed the endothelial nature of the tumor cells; Weibel-Palade bodies were present in three cases. There were 11 men and three women, and the tumors were seen predominantly in patients who were under 30 years of age (10 cases). Four cases involved solitary tumors, and nine were multicentric in bone. The multicentric tumors had a predilection for the bones of one lower extremity (five cases). The total series had a protracted clinical course, and the multicentric tumors appeared to follow a less aggressive course.

Tophaceous pseudogout (tumoral calcium pyrophosphate dihydrate crystal deposition disease)

Most cases of calcium deposition seen radiologically in soft tissues are caused by calcium hydroxyapatite and occur either as a complication of trauma with associated necrosis (eg, fat necrosis), generalized connective tissue diseases (eg, scleroderma), metabolic disturbances (eg, hyperparathyroidism, familial hyperphosphatemia), sarcoidosis, myeloma, or metastases. Hydroxyapatite deposits are seen at many soft tissue sites, including joint capsules, ligaments, blood vessels, dermis, etc. On the other hand, deposits of calcium pyrophosphate are seen typically in the meniscus, articular cartilage, ligamentum flavum, and intervertebral disc. They usually are punctate or linear in distribution within the meniscus or parallel to the subchondral bone end plate. We report seven cases of massive focal calcium pyrophosphate dihydrate (CPPD) crystal deposition disease (tophaceous pseudogout) that occurred in atypical locations for CPPD. The ages of the patients ranged from 31 to 86 years (average, 60.7 years). One patient was male and six were female. The temporomandibular joint was involved in three patients and the metatarsophalangeal joint of the great toe was involved in two patients. The hip joint and cervical spine were involved in one patient each. A mass or swelling with or without pain was a common symptom. None of the patients in our series had clinical or radiographic evidence of CPPD crystal deposition disease in any other joints. Roentgenograms showed calcified lesions with a granular or fluffy pattern. Histologically, the lesions showed small or large deposits of intensely basophilic calcified material containing needle shaped and rhomboid crystals with weakly positive birefringence characteristic of CPPD. Foreign body granulomatous reaction to the CPPD deposition was constantly found. Chondroid metaplasia around and in the areas of CPPD deposition was observed commonly. Some of the chondroid areas showed cellular atypia in chondrocytes suggestive of a malignant cartilage tumor. It is important to recognize this rare form of CPPD crystal deposition disease and to identify the CPPD crystals in the calcified deposits, thus avoiding the misdiagnosis of benign or malignant cartilaginous lesions.

Chondromyxoid fibroma of bone: Thirty-six cases with clinicopathologic correlation

A series of 36 cases of chondromyxoid fibroma (CMF) of bone, a rare benign tumor that may be confused with chondrosarcoma, is presented to aid in correctly identifying and diagnosing these neoplasms. In this series, CMFs were found in patients of all age groups, with no predominance between sexes. Long bone tumors were more common in young patients, while small and flat bone lesions were more common in older patients. Radiographically, long, flat, and small bone lesions were well-defined and benign-appearing. Tumors in the vertebrae had a more aggressive appearance, with marked bone destruction. The histologic picture was of a pseudolobulated tumor with myxoid and chondroid regions. Tumor cells were at times bizarre, pleomorphic, and binucleate, but rarely contained mitoses. Curettage with or without bone grafting and en bloc resection were the most common modes of treatment. The majority of recurrences were seen in patients treated by curettage alone. Radiation therapy was associated with the development of sarcoma in one case. No cases of malignant transformation were found in this series, but unusually aggressive recurrences were noted in CMFs involving a phalanx, the cervical vertebra, and the sacrum.

Morphologic diversity of long bone adamantinoma. The concept of differentiated (regressing) adamantinoma and its relationship to osteofibrous dysplasia

A review of the clinical, radiologic, and histologic features of 25 cases of long bone adamantinoma is presented. To answer some questions concerning the nature of these tumors, relevant tissue markers were analyzed in seven cases using immunohistochemical assays. This study confirmed the epithelial nature of long bone adamantinomas irrespective of their wide‐ranging morphologic patterns that can mimic tumors of various origin. On the basis of distinct radiologic, histologic, and immunohistochemical patterns, a new type of adamantinoma termed “differentiated adamantinoma” could be distinguished from the classic long bone adamantinomas. The diagnostic features characteristic of the differentiated adamantinoma include: patient age (first two decades), intracortical location of the entire lesion, uniform predominance of an osteofibrous dysplasia‐like pattern, and scattered positivity of epithelial elements for cytokeratin. We postulate that the predominance of an osteofibrous dysplasia‐like pattern in differentiated adamantinoma is the result of a secondary reparative process overgrowing matured and regressing tumor tissue. It is possible that this process may lead to the total elimination of recognizable tumor cells from the lesion. Therefore, osteofibrous dysplasia (ossifying fibroma) of long bones, which has a similar anatomic location, age distribution, and radiologic appearance as differentiated adamantinoma, may, in some cases, represent the evolution of an underlying adamantinoma. Our analysis suggests that long bone adamantinoma could be another member of the unique family of tumors that may regress spontaneously.

Correlation between clinicopathological features and karyotype in 100 cartilaginous and chordoid tumours. A report from the Chromosomes and Morphology (CHAMP) Collaborative Study Group

The evaluation of chondroid lesions requires full integration of clinical, radiographic, and pathological data; tumour typing is often a challenge for the diagnostic pathologist. Although a variety of chromosomal abnormalities have been documented in chondroid lesions, the potential usefulness of cytogenetic analysis remains unclear. This study has critically reviewed and analysed 117 karyotyped samples from 100 patients with cartilaginous and chordoid tumours. Cases were selected based on successful chromosomal analysis and adequacy of clinical, radiographic, and pathological information. To ensure objective evaluation, the cytogenetic results were correlated in a double‐blind setting with consensus diagnoses independently determined on each case, after complete review of the histological, radiographic, and clinical findings. Karyotypic aberrations were identified in 41/92 cartilaginous tumours (5/11 osteochondromas, 2/3 chondromyxoid fibromas, 0/4 chondroblastomas, 11/29 chondromas, 0/3 chondroid tumours of undetermined malignant potential, 22/40 chondrosarcomas and 1/2 miscellaneous cartilaginous lesions) and 5/8 chordomas. Complex karyotypic changes were a feature of malignant tumours (chondrosarcoma and chordoma) and of chondrosarcoma among cartilaginous tumours, where they correlated with high tumour grade. Among primary well‐differentiated cartilaginous lesions of bone, the finding of an abnormal karyotype was consistently associated with a grade 1 chondrosarcoma diagnosis. Among karyotypically abnormal cartilaginous tumours, loss of distal 8q was associated with osteochondroma, +5 with synovial chondroma/chondromatosis and parosteal or soft tissue chondroma, alterations of chromosome arm 6q with chondromyxoid fibroma, +7 with bone chondrosarcoma, and 17p1 alterations with grade 3 chondrosarcoma. Alterations involving 12q13 characterized synovial chondroma/chondromatosis in the chondroma group and myxoid chondrosarcoma of bone in the chondrosarcoma group. In conclusion, cytogenetic abnormalities in chondroid lesions are common and are not randomly distributed. They are associated with malignancy/tumour grade as well as with specific diagnoses in many cases, and can therefore be of potential value for tumour typing. Copyright

Nerve fibers in osteoid osteoma.

Osteoid osteomas stained with the Bielschowsky axon stain, demonstrated nerve fibers within the matrix of the nidus in sixteen of eighteen lesions studied. These fibers were associated with blood vessels and were found in greatest abundance adjacent to arterioles. Routine hematoxylin and eosin stains failed to reveal these fibers. Similar but less prominent findings were evident in two of the three osteoblastomas studied. The pain of these lesions may be mediated by the autonomic nervous system via these nerve fibers. It is postulated that tue neural elements demonstrated are sensitive to changes in vascular pressure.

Malignant fibrous histiocytoma of bone: A study of 35 cases

Thirty-five cases of primary malignant fibrous histiocytoma of bone are reported. Twenty of these cases were collected from a retrospective analysis of other malignant bone tumors. The age range was from 11 to 69 years; the average age was 34 years. The tumor occurred most commonly in the distal femur and proximal tibia. The distinguishing histologic feature was a storiform arrangement of spindle cells. The differential diagnosis included fibrosarcoma, osteogenic sarcoma, malignant giant cell tumor, malignant lymphoma, and metastatic carcinoma. Follow-up of at least three years was available in 21 cases. Of these, nine patients were alive and free of metastases three and one-half to 12 years after treatment. Two were alive with solitary metastases at three years, and 10 patients died between three months and three years after treatment. In four cases the lesions were multicentric at the time of diagnosis and in four cases were associated with bone infarction. This tumor must be recognized as an important complication of bone infarction and should be suspected when a patient with a known history of bone infarction develops a change in symptoms. Because the prognosis of this tumor is significantly better than that in those tumors with which it had been previously grouped, and in view of its association with bone infarction, it deserves to be maintained as a distinct clinicopathologic entity. Amputation is the treatment of choice.

Electron microscopy in the diagnosis of malignant schwannoma

Fifteen malignant schwannomas were examined by light and electron microscopy. Five tumors arose in patients with neurofibromatosis and five were contiguous with a peripheral nerve (Group I). Five tumors met neither of these generally accepted diagnostic criteria but were light microscopically seen as compatible with malignant schwannoma when examined under light microscope (Group II). In the better differentiated areas of Group I lesions, long, overlapping, tightly packed cytoplasmic processes were parallel to homogeneous flocculent material, occasionally assuming a linear appearance suggesting basal lamina. In Group II, similar cytoplasmic processes were present but the extracellular material was less extensive and had a less obvious relationship to the plasma membrane. In neither group were fine intracytoplasmic filaments prominent. Malignant schwann cells are seldom as ultrastructurally differentiated as their benign counterparts. Nevertheless, within the context of well‐studied light microscopy and the sampling error inherent in ultrastructural examination, electron microscopy can support the diagnosis of malignant schwannoma.