Bone stromal cells in pagetic bone and Paget's sarcoma express RANKL and support human osteoclast formation

Paget's disease is a focal disorder of bone remodelling, in which there is an increase in osteoclast formation. A rare complication of Paget's disease is the development of a sarcoma, most commonly an osteosarcoma. Osteoclast formation occurs in the presence of macrophage-colony stimulating factor and receptor activator for nuclear factor-kappaB ligand (RANKL), and it has been shown that bone stromal cells in Paget's disease can influence osteoclast formation by modulating the expression of RANKL and its decoy receptor, osteoprotegerin (OPG). In this study we show that pagetic bone stromal cells express RANKL and that these cells promote osteoclast formation by a RANKL-dependent mechanism. Osteoclast formation in co-cultures of monocytes and either pagetic bone stromal cells or Paget's sarcoma stromal cells was not only induced by a contact-dependent mechanism but also occurred via the release of a soluble factor. In contrast to bone stromal cells isolated from normal controls, stromal cells isolated from morphologically normal bone in one patient with Paget's disease also stimulated osteoclast formation in this way; this osteoclastogenesis was inhibited by OPG. Our results indicate that Paget's bone stromal cells support osteoclast formation by a RANKL-dependent process which involves not only cell-cell contact but also secretion of soluble RANKL.     

Juxtacortical osteosarcoma. A distinct malignant bone neoplasm

The purpose of this report is the study of a malignant bone tumor of similar histological picture with conventional (intramedullary) osteosarcoma. Contributing factors in the study of juxtacortical osteosarcoma are the clinical, X-ray and histologic pictures. A case of parosteal osteosarcoma in a 28-year-old male is reported. In conjuction with X-ray findings we review the histological characteristics of the tumor through serial sections of the peripheral, central and parosteal parts and the findings are described in detail. In addition to the histological findings, differential diagnosis and prognosis are also discussed. From the general study of the tumor it has been shown that juxtacortical osteogenic sarcoma behaves differently in contrast to classic osteosarcoma, depending on the degree of differentiation of the tumor.     

Hyperplastic callus formation in osteogenesis imperfecta

A case of a child with the hyperplastic callus formation in association with osteogenesis imperfecta is presented. The soft tissue mass arising at the site of femoral fracture was clinically and radiologically suspected to be a hyperplastic callus, although a possibility of osteosarcoma could not be completely excluded. A drill biopsy of the soft tissue mass was performed which showed osteocartilaginous callus. The soft tissue mass disappeared following biopsy. This occurrence is also reported in previously described cases.     

Cartilage-forming tumours of bone and soft tissue and their differential diagnosis

The prevalence of primary malignant bone tumours is estimated to be 1:100,000 within the general population: 17–24% of these are malignant cartilaginous tumours (chondrosarcomas). The incidence of benign bone tumours is largely unknown, due to lack of registration as well as frequent failure to present clinically. Benign cartilaginous tumours of bone include chondroma, osteochondroma, chondroblastoma and chondromyxoid fibroma, whereas among the malignant cartilaginous bone tumours conventional, juxtacortical, mesenchymal, dedifferentiated, and clear cell chondrosarcomas are recognized. The histological distinction between the different entities is based on cell type/differentiation, matrix formation and architecture, combined with radiodiagnostic and clinical data. Extraskeletal cartilaginous lesions are extremely uncommon and include soft tissue chondroma, mesenchymal and extraskeletal myxoid chondrosarcoma. The formation of cartilaginous matrix can be found in many other non-cartilaginous tumours (such as periosteal osteosarcoma and chondroblastic osteosarcoma) and tumour-like lesions (such as fibrous dysplasia, Nora's lesion, primary synovial chondromatosis, dysplasia epiphysealis hemimelica and callus formation) These conditions may lead to an erroneous diagnosis of a primary osseous cartilaginous tumour.     

Periosteal osteosarcoma of the femur with bone marrow involvement: A case report

Periosteal osteosarcoma is an exceedingly rare type of chondroblastic osteosarcoma, showing rather better prognosis, and secondary bone marrow involvement is unusual. A case of a 22 year old male with periosteal osteosarcoma of the right femur with an associated bone marrow lesion is presented. The juxtacortical tumor, 16 ×11 × 9 cm, was located on the bone cortex of the upper diaphysis and extended into the surrounding soft tissues. A minimal bone marrow lesion was present, although the bone cortex was quite intact. Microscopically, the tumor consisted exclusively of atypical chondroblastic cells with a small osteoblastic area. The bone marrow lesion, interestingly, contained both multiple nodules of well-differentiated chondrosarcomatous components and a few demarcated foci of atypical spindle cells producing a fine osteoid matrix. It was reasonable to conclude, therefore, that this tumor was a periosteal osteosarcoma with an unusual secondary bone marrow lesion rather than a conventional (central) chondroblastic osteosarcoma with soft tissue invasion. The patients good prognosis with no tumor recurrence or metastasis during more than 7 years follow-up after surgery supports this conclusion.     

Soft tissue amyloidoma of the extremities: a case report and review of the literature

The deposition of amyloid as a distinct, clinically apparent mass is uncommon, particularly in soft tissues. Among reported sites of soft tissue amyloidomas, the extremities are quite rare. Amyloid tumors can mimic malignant neoplasms both clinically and radiologically. We report a case of AA amyloidoma presenting in the deltoid region with radiological features suggesting sarcoma. Cytomorphology from fine-needle aspiration material, tissue histology, and appearance by magnetic resonance imaging are described. The literature on soft tissue amyloidoma is reviewed.     

Critical reappraisal of primary osseous composite sarcoma (malignant mesenchymoma) – analysis of four cases and literature review

In accordance with recent terminology, it is proposed that malignant mesenchymoma should be renamed ‘composite sarcoma’ and defined as ‘a sarcoma composed of two or more cellular types each of which is sufficiently differentiated to permit clear recognition of its histogenetic type microscopically, immunohistochemically or ultrastructurally; excluding fibrosarcomatous and high‐grade pleomorphic undifferentiated sarcomatous component, dedifferentiated sarcoma and the combination of osteosarcoma and chondrosarcoma which is regarded as a single histogenetic type’. Four cases of primary osseous composite sarcoma (POCS) were identified among 928 primary bone sarcomas. Their age ranged from 10 to 87 years, peak incidence in the second decade with equal sex distribution. Most presented with pain, commonest in the knee, affecting the metaphysis, appearing radiologically as expansile infiltrative osteolytic lesions with cortical erosion, periosteal reaction, variable extent of osteoblastic areas and soft tissue extension. All contained variable amounts of conventional high‐grade osteosarcoma with or without chondrosarcoma component; the other constituents were liposarcoma, rhabdomyosarcoma and leiomyosarcoma. In all cases, Ki67 proliferative index was over 35%, there was no CDK4 and MDM2 amplification. The absence of low‐grade component supported the de novo origin of POCS rather than derivation from divergent dedifferentiation. The two older patients with hitherto undescribed osteoleiomyosarcoma died 2 and 10 months after operation, whereas the two younger with osteorhabdomyosarcoma and osteoliposarcoma enjoyed disease‐free survival at 16 and 6 years after chemotherapy despite the latter showing lung metastasis at presentation. Identification of the different lines of differentiation together with their approximate amounts and histological grades is therefore mandatory for POCS as multi‐agent chemotherapy catered for each sarcoma component might offer hope for long‐term disease‐free survival.     

Paget sarcoma of the cervical vertebrae: An autopsy case report and review of the literature

A 69 year old Japanese woman was hospitalized for emergency treatment of sudden onset of tetraplegia and somnolence. The patient had a long history of occipital pain without definite diagnosis. After admission, the patient progressively developed generalized palsy including respiratory paralysis, and died of bronchopneumonia. Autopsy revealed osteosarcoma of the cervical vertebrae with the features of Paget's disease involving the skull and the cervical vertebrae. Paget sarcoma is rare in Japan, where Paget's disease of the bone is an uncommon condition. A review of the world literature failed to reveal any reports describing Paget sarcoma of the cervical vertebrae. The present report indicates that the development of Paget sarcoma in the upper cervical vertebrae may cause life-threatening neurologic complications.     

Central low-grade osteosarcoma with pagetoid bone formation: a potential diagnostic pitfall.

Central low-grade osteosarcoma is an uncommon form of osteosarcoma, which is often difficult to distinguish from benign bone lesions. We reviewed the radiographic studies, the histologic material and the clinical records of two patients with central low-grade osteosarcoma that closely simulated the histologic appearance of Paget's disease of bone. The patients were two women aged 46 and 53 years. Radiologically, they presented a large ill-defined densely sclerotic lesion involving the proximal tibia. Both lesions only focally presented the conventional histologic appearance of central low-grade osteosarcoma, with a proliferation of fibroblast-like cells embedded in a dense collagenous stroma and irregular anastomosing tumor bone trabeculae. The most striking feature was the presence of extremely thickened irregular plates of bone with an irregular mosaic pattern of cement lines that closely resembled that of Paget's disease of bone. One patient, who had been initially treated for Paget's disease for 7 years, experienced disease progression. At resection of proximal tibia, there was evidence of dedifferentiation to high-grade osteosarcoma. After 2 months, she developed local recurrence that was treated with above-knee amputation, followed by chemotherapy. She died with multiple lung metastases 4 months later. The other patient is alive 9 months after wide tumor resection. These cases further expand the spectrum of central low-grade osteosarcoma, and underscore the diagnostic difficulties in separating central low-grade osteosarcoma from benign bone diseases, which may lead to delay in diagnosis, inadequate treatment, and eventually to dedifferentiation. Recognition of this variant of central low-grade osteosarcoma is based on the aggressive radiologic appearance and on adequate tumor sampling for histologic examination.     

Hepatocellular carcinoma presenting with multiple bone and soft tissue metastases and atypical cytomorphological features—A rare case report

Hepatocellular carcinoma (HCC) with atypical cytomorphological features and presenting with bone and soft tissue metastasis is very rare. We report a 65‐year‐old male patient of HCC who presented with bone and soft tissue metastases and was clinically and radiologically suspected to have a soft tissue sarcoma. The patient presented with severe cervical pain with palpable masses in right scapular, nape of neck, and occiput area of scalp. Radiologically, these were large, bulky soft tissue masses expansile, destructive, and lytic in nature. Cytomorphologic studies revealed HCC with uncommon features of multinucleated osteoclast‐like giant cell and very prominent intracytoplasmic hyaline bodies (IHBs). Cytology, immunohistochemistry on cell block preparation, rising serum α‐fetoprotein (AFP) levels (1121.93–5000 ng/ml), and PIVKA II levels confirmed the diagnosis. The patient has been on follow‐up on sorafinib for 2 months and is doing well. This case emphasizes the need for systematic approach in cases of HCC with atypical clinical presentation and unusual cytomorphology. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Intraosseous Rosai‐Dorfman disease diagnosed by touch imprint cytology evaluation: A case series

Sinus histiocytosis with massive lymphadenopathy, also known as Rosai‐Dorfman disease (RDD) is a rare benign disorder that primarily affects the lymph nodes. Localized lymphadenopathy is the most common clinical manifestation of this disorder. However, RDD has been described in several extra‐nodal sites including the head and neck region, soft tissue, skin, upper respiratory tract, gastro‐intestinal tract and central nervous system (CNS). Involvement of the bone is considered very rare, occurring in less than 10% patients. RDD is one of the histiocytoses and the differential diagnosis includes entities such as Langerhans cell histiocytosis and Erdheim‐Chester disease. In the rare intraosseous variant, the clinical and radiologic differential diagnosis is broader and includes neoplasms such as osteosarcoma and Ewing sarcoma. In this report, we describe three cases of extra‐nodal, intraosseous RDD where touch imprint cytology played a crucial role in diagnosis. Two of the cases initially presented with involvement of the head and neck region and later developed intraosseous disease; while the third patient presented with primary bone involvement. The diagnosis was established by core biopsy with touch imprints of the bone lesions. The cytologic samples showed numerous histiocytes, often with neutrophils within their cytoplasm (emperipolesis) in addition to lymphocytes and plasma cells. The diagnosis of RDD was confirmed with appropriate immunohistochemical stains. Our account of these three cases of intraosseous Rosai‐Dorfman disease highlights the role of cytology in the diagnosis of this rare entity.     

Is fine-needle aspiration biopsy a practical alternative to open biopsy for the primary diagnosis of sarcoma? Experience with 140 patients

We reviewed the clinicopathologic features of 145 consecutive fine-needle aspiration biopsy (FNAB) specimens from 140 patients without a previous diagnosis of sarcoma. Among 138 adequate specimens, 42 bone sarcomas and 80 soft tissue sarcomas were recognized as sarcomas; histologic subtyping was easier in bone than in soft tissue sarcomas and in pediatric than in adult cases. There was no correlation in accuracy of subtyping in low- vs high-grade sarcomas. FNAB was most accurate for subtyping of skeletal osteosarcoma, pediatric small round cell bone/soft tissue sarcomas, synovial sarcoma, skeletal chondrosarcoma, and adult myxoid soft tissue sarcomas. Although almost always recognized as sarcoma, subtyping of adult pleomorphic soft tissue sarcomas generally was not possible but did not influence therapy; all were considered high-grade sarcomas for treatment purposes. There were 4 misinterpretations of subtype in soft tissue sarcomas; none resulted in a change in therapy. Cytogenetic analysis on aspirated material confirmed t(11;22) in 2 Ewing and t(X;18) in 3 synovial sarcomas. No procedure-related complications occurred. Among bone and soft tissue sarcomas, FNAB was sufficient for initiation of definitive therapy in 87% and 83% of patients, respectively. Most FNAB specimens from bone and soft tissue sarcomas are recognized easily as sarcoma, but subtyping seems more accurate in bone sarcomas. Although histologic subtyping of adult soft tissue sarcomas is often impossible, no influence on initial therapy is usually observed. In contrast, subtyping of pediatric sarcomas by FNAB seems highly accurate and is necessary for appropriate therapy.     

L‐type amino acid transporter‐1 and CD98 expression in bone and soft tissue tumors

L‐type amino acid transporter‐1 (LAT1) is expressed in many cancers. We examined LAT1 and CD98 expression immunohistochemically in surgically resected specimens of various bone and soft tissue tumors. Out of 226 cases, 79 (35%) were LAT1⁺ and 95 (42%) were CD98⁺. In bone tumors, LAT1 was highly expressed in osteoblastoma (89%), chondrosarcoma (50%), and osteosarcoma (60%); in soft tissue tumors, LAT1 was highly expressed in rhabdomyosarcoma (80%), synovial sarcoma (63%), Ewing's sarcoma (60%), epithelioid sarcoma (100%) and angiosarcoma (100%). In malignant soft tissue tumors, LAT1 expression was associated with higher histological grade. High CD98 expression was seen in many bone tumors of intermediate and high malignancy. Among soft tissue tumors, CD98 was expressed in tendon sheath giant cell tumor and malignant peripheral nerve sheath tumor (57%), Ewing's sarcoma (50%) and undifferentiated sarcoma (64%). Some of the malignant soft tissue tumors expressed both LAT1 and CD98. This study showed that LAT1 and CD98 was expressed in many malignant and intermediate bone tumors, and some malignant soft tissue tumors.     

Periosteal osteoblastoma: a case report and a review of the literature

Osteoblastomas located on the surface of cortical bone, so-called periosteal (juxtacortical) osteoblastomas, are extremely rare. A 24-year-old man complained of pain and swelling in the left knee. The clinical and radiological investigation showed a tumor located in the posterior portion of the distal shaft of the femur. The radiological differential diagnosis included parosteal osteosarcoma, periosteal chondroma and periostitis ossificans. A frozen section was obtained and histology revealed an osteoblastoma with large epithelioid-appearing osteoblasts consistent with an aggressive osteoblastoma. An en bloc resection of the tumor was performed and the definitive histology of the whole specimen revealed a typical osteoblastoma. The authors draw attention to the fact that periosteal osteoblastoma is a rare tumor that could be mistaken clinically and histologically for other and more common tumors at this location.     

Breast diseases associated with systemic medical disorders

A wide range of systemic disorders may present as breast lesions, in some cases mimicking primary breast carcinoma and other primary breast diseases clinically and radiologically. The distinction between the manifestation of a systemic medical disorder in the breast and primary breast pathology is clinically important as management and follow-up may defer widely. However, apart from diabetes mellitus-associated breast disease, the manifestation of systemic disorders on breast tissue is rare and the general histopathologist is unlikely to encounter this regularly. This review examines the most common benign breast lesions associated with systemic medical disorders and drugs, including the typical clinical and radiological findings, pathogenesis, and macroscopic and microscopic findings. The specific features and immunohistochemical techniques helpful in differentiating benign disease from carcinoma will be discussed and illustrated using examples from our own practice.     

Orthopaedic implant-related sarcoma: a study of twelve cases.

Sarcoma developing in association with a metallic orthopaedic prosthesis or hardware is an uncommon, but well recognized complication. We review 12 cases of sarcomas arising in bone or soft tissue at the site of orthopaedic hardware or a prosthetic joint. Nine patients were male, and three were female. Their ages ranged from 18 to 85 (mean 55) years at the time of diagnosis of the malignancy. Five patients had undergone hip arthroplasty for degenerative joint disease, four had been treated with intramedullary nail placement for fracture, two had staples placed for fixation of osteotomy, and one had hardware placed for fracture fixation followed years later by a hip arthroplasty. The time interval between the placement of hardware and diagnosis of sarcoma was known in 11 cases and ranged from 2.5 to 33 (mean 11) years. The patients presented with pain, swelling, or loosening of hardware and were found to have a destructive bone or soft tissue mass on radiography. Two sarcomas were located primarily in the soft tissue and 10 in bone. Seven patients developed osteosarcoma, four malignant fibrous histiocytoma, and one a malignant peripheral nerve sheath tumor. All sarcomas were high grade. Three patients had metastatic disease at the time of diagnosis. Follow-up was available on eight patients: five patients died of disease 2 months to 8 years (mean 26 months) after diagnosis; two patients died without evidence of disease 7 and 30 months after diagnosis; and one patient is alive and free of disease 8 years after diagnosis. Sarcomas that occur adjacent to orthopaedic prostheses or hardware are of varied types, but are usually osteosarcoma or malignant fibrous histiocytoma. They behave aggressively and frequently metastasize. Clinically, they should be distinguished from non-neoplastic reactions associated with implants, such as infection and a reaction to prosthetic wear debris.     

Malignant fibrous histiocytoma of bone: initial diagnosis by aspiration biopsy cytology

Aspiration biopsy cytology by fine needle is becoming a popular diagnostic procedure for soft-tissue lesions; it also can be used successfully to diagnose some lesions from bone. The value of this procedure for making the initial diagnosis is illustrated by a case in which a malignant fibrous histiocytoma from a skull bone afflicted with Paget's disease was aspirated and interpreted as a sarcoma. This was later confirmed and subclassified by histology and electron microscopy from the tissue.     

Neuron-specific enolase and Leu-7 immunoreactive small round-cell neoplasm. The relationship to Ewing's sarcoma in bone and soft tissue

The authors present an immunohistochemical analysis of tissue from five cases of morphologically distinctive Ewing's sarcoma in bone and soft tissue. The mean age of the five patients was 16.6 years, with a range of 6-28 years. The tumors existed in chest wall, pelvis, and lower extremities. Two siblings with tumor in bone were clinically diagnosed as having Ewing's sarcoma. All cases had immunoreactivity for neuron-specific enolase (NSE), and four cases revealed positive staining for Leu-7. Neuron-specific enolase is highly specific for neurons and neuroendocrine cells. In addition, immunoreactivity for Leu-7, expressing a natural killer activity, has been demonstrated in peripheral nerve fibers and neuroendocrine cells. The authors suggest that NSE and Leu-7 immunoreactive small round-cell neoplasm is probably a primitive neuroectodermal tumor and should be categorized as Ewing's sarcoma in bone and soft tissue.     

Soft tissue osteochondroma: case report and immunohistochemistry for parathyroid hormone-related protein

Surface lesions of bone usually present little diagnostic dilemma because the majority are conventional osteochondromas. Other surface bone lesions include periosteal chondroma, periosteal chondrosarcoma, and parosteal osteosarcoma. Mineralized soft tissue lesions such as myositis ossificans, synovial chondroma, and synovial sarcoma may present in a similar fashion when they occur in a juxtaarticular position. The soft tissue osteochondroma or paraarticular osteochondroma may simulate some of these more aggressive tumors, and its recognition is important to avoid overtreatment. A case of an 11-year-old male with a soft tissue osteochondroma is reported to illustrate the characteristic radiographic and histological features of this rare entity. No prior reports have examined soft tissue osteochondroma for expression of parathyroid hormone related protein, an established cartilage tumor proliferative mitogen.