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There is no shortage of comprehensive review articles on bone and soft tissue pathology, almost always representing a regurgitation of the literature with little to no guidance on personal "best practices," recommended applications of ancillary testing, and alternative points of view. This special issue of Human Pathology uniquely unites evidence-based medicine, where appropriate, with the collective personal experiences of a wide range of accomplished pathologists from varying institutions and backgrounds, addressing problematic areas, updated and sometimes imperfect classification systems, and their personal preferences for cost-effectively incorporating ancillary testing. For the preponderance of general pathologists (and specialists), whether academic or non-academic, non-neoplastic musculoskeletal diseases represent a far higher percentage of their practice than bone and soft tissue neoplasia. One of the most common frozen sections performed at many hospitals throughout the USA is revision arthroplasty, relying on the pathologist to help determine the presence (or absence) of periprosthetic joint infection, largely based on the hematoxylin & eosin (H&E) slide. Not every institution has access to the latest molecular techniques; fortunately, many of the current immunohistochemical antibodies serve as reliable surrogate markers of genetic mutations, allowing for cheaper but accurate diagnoses, when deemed necessary. Furthermore, molecular testing is often not necessary to establish a specific diagnosis, even among neoplasms with known underlying genetic abnormalities. It must be remembered that most bone and soft tissue tumors were recognized and classified correctly, before we uncovered and understood, among a subset, their underlying and unique molecular aberrations. Perhaps not surprisingly, in some cases, more than one molecular pathway may lead to the same histologic tumor subtype. Less commonly, an identical genetic driver/fusion may result in immunophenotypically and biologically distinct neoplasms, sometimes with entirely different clinical behaviors. "Dedifferentiation," a concept recognized among a variety of bone and soft tissue neoplasms, including but not limited to chondrosarcoma, parosteal osteosarcoma, and liposarcoma, needs to be objectively reassessed, particularly for liposarcoma. The following reviews attempt to address the above concepts, re-emphasizing the important role the practicing pathologist continues to (and must) play in the differential diagnoses of neoplastic and non-neoplastic musculoskeletal diseases., Competing Interests: Declaration of competing interest There are no sources of funding for this manuscript, and the author has nothing to disclose or conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Bone and soft tissue tumors (BST) are a highly heterogeneous group largely classified by their line of differentiation, based on their resemblance to their normal counterpart in adult tissue. Yet, rendering a specific diagnosis can be challenging, primarily due to their rarity and overlapping histopathologic features or clinical presentations. Over the past few decades, seemingly histogenetic-specific gene fusions/translocations and amplifications have been discovered, aiding in a more nuanced classification, leading to well-established objective diagnostic criteria and the development of specific surrogate ancillary tests targeting these genetic aberrations (e.g., immunohistochemistry). Ironically, the same research also has revealed that some specific tumor subtypes may be the result of differing and often multiple gene fusions/translocations, but, more interestingly, identical gene fusions may be present in more than one phenotypically and biologically distinct neoplasm, sometimes with entirely different clinical behavior. Prime examples include, EWSR1::ATF1 and, less commonly, EWSR1::CREB1 gene fusions present in both clear cell sarcoma, a malignant high-grade tumor with melanocytic differentiation, and angiomatoid fibrous histiocytoma, a mesenchymal neoplasm of intermediate malignancy with a generally indolent course. Similarly, MDM2 amplification, once deemed to be pathognomonic for atypical lipomatous tumor/well differentiated and dedifferentiated liposarcoma, has been documented in a range of additional distinct tumors, including low grade osteosarcomas (e.g. low grade central and surface parosteal) and high-grade intimal sarcomas, amongst others. Such findings reinforce the importance of careful attention to morphological and clinicoradiological features and correlation with molecular testing before rendering a specific diagnosis. Future classification systems in BST neoplasms cannot be solely based on molecular events and ideally will balance morphologic features with molecular analysis. Herein, we provide a narrative literature review of the more common BST neoplasms with shared genetic events but differing demographics, morphology, immunophenotype, and clinical behavior, re-emphasizing the importance of the hematoxylin and eosin slide and the "eye" of the practicing pathologist., Competing Interests: Declaration of competing interest The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024. Published by Elsevier Inc.)

Osteoid osteomas typically arise in the long bones of extremities. Patients often report pain relieved by NSAIDS, and radiographic findings are often sufficient for diagnosis. However, when involving the hands/feet, these lesions may go unrecognized or misdiagnosed radiographically due to their small size and prominent reactive changes. The clinicopathologic features of this entity involving the hands and feet are not well-described. Our institutional and consultation archives were searched for all cases of pathologically confirmed osteoid osteomas arising in the hands and feet. Clinical data was obtained and recorded. Seventy-one cases (45 males and 26 females, 7 to 64 years; median 23 years) arose in the hands and feet, representing 12% of institutional and 23% of consultation cases. The clinical impression often included neoplastic and inflammatory etiologies. Radiology studies demonstrated a small lytic lesion in all cases (33/33), the majority of which had a tiny focus of central calcification (26/33). Nearly, all cases demonstrated cortical thickening and/or sclerosis and perilesional edema which almost always had an extent two times greater than the size of the nidus. Histologic examination showed circumscribed osteoblastic lesions with formation of variably mineralized woven bone with single layer of osteoblastic rimming. The most common growth pattern of bone was trabecular (n = 34, 48%) followed by combined trabecular and sheet-like (n = 26, 37%) with only 11 (15%) cases presenting with pure sheet-like growth pattern. The majority (n = 57, 80%) showed intra-trabecular vascular stroma. No case showed significant cytology atypia. Follow up was available for 48 cases (1-432 months), and 4 cases recurred. Osteoid osteomas involving the hands and feet follow a similar age and sex distribution as their non-acral counterparts. These lesions often present with a broad differential diagnosis and may initially be confused with chronic osteomyelitis or a reactive process. While the majority of cases have classic morphologic features on histologic exam, a small subset consists solely of sheet-like sclerotic bone. Awareness that this entity may present in the hands and feet will help pathologists, radiologists, and clinicians accurately diagnose these tumors., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

For decades, the diagnosis, treatment, and even pathogenesis of the osteofibrous dysplasia/osteofibrous dysplasia-like adamantinoma/classic adamantinoma spectrum of neoplasms have been controversial. Herein, we discuss and illustrate the radiographic and histologic spectrum, differential diagnoses, unifying chromosomal and molecular abnormalities, and current controversies and treatment recommendations for each entity., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Context.—: Bone and soft tissue tumors are heterogeneous, diagnostically challenging, and often defined by gene fusions., Objective.—: To present our experience using a custom 34-gene targeted sequencing fusion panel., Design.—: Total nucleic acid extracted from formalin-fixed, paraffin-embedded (FFPE) tumor specimens was subjected to open-ended, nested anchored multiplex polymerase chain reaction and enrichment of 34 gene targets, thus enabling detection of known and novel fusion partners., Results.—: During a 12-month period, 147 patients were tested as part of routine clinical care. Tumor percentage ranged from 10% to 100% and turnaround time ranged from 3 to 15 (median, 7.9) days. The most common diagnostic groups were small round blue cell tumors, tumors of uncertain differentiation, fibroblastic/myofibroblastic tumors, and adipocytic tumors. In-frame fusion transcripts were identified in 64 of 142 cases sequenced (45%): in 62 cases, the detection of a disease-defining fusion confirmed the morphologic impression; in 2 cases, a germline TFG-GPR128 polymorphic fusion variant was detected. Several genes in the panel partnered with multiple fusion partners specific for different diagnoses, for example, EWSR1, NR4A3, FUS, NCOA2, and TFE3. Interesting examples are presented to highlight how fusion detection or lack thereof was instrumental in establishing accurate diagnoses. Novel fusion partners were detected for 2 cases of solid aneurysmal bone cysts (PTBP1-USP6, SLC38A2-USP6)., Conclusions.—: Multiplex detection of fusions in total nucleic acid purified from FFPE specimens facilitates diagnosis of bone and soft tissue tumors. This technology is particularly useful for morphologically challenging entities and in the absence of prior knowledge of fusion partners, and has the potential to discover novel fusion partners.

Primary sclerosing epithelioid fibrosarcoma (SEF) of bone is a rare and scarcely reported neoplasm. We document clinicopathological and molecular features of 9 additional cases. Five males and 4 females had a mean age of 39 years (14-71 years). Most tumors affected flat/irregular bones; only 3 cases involved a long bone. By radiology, it has characteristic radiographic features of a predominantly lytic expansile lesion with a sclerotic rim. Referring diagnoses were SEF (n = 2), low-grade osteosarcoma (n = 2), chondrosarcoma (n = 1), and chondromyxoid fibroma (n = 1). Histologically, five cases revealed classical morphology of SEF of soft tissue. Remaining cases were classified as hybrid SEF/low-grade fibromyxoid sarcoma, characterized by spindle or stellate cells, prominent stroma, and giant hyalinized areas. Various morphological deviations such as prominent vasculature (n = 3), osteoid-like material (n = 4), or parallel bone trabeculae (n = 2) were observed. Immunohistochemically, all cases showed diffuse and strong MUC4 expression. SATB2 was observed in 5/8 cases. Using FISH, EWSR1, and FUS rearrangements were detected in 4 cases and 1 case, respectively. EWSR1-CREB3L1 fusion was identified in 1 additional case by next-generation sequencing. Recurrence and metastasis were observed in 1 case and 2 cases, respectively. All but one patient were alive with disease for a mean interval of 31 months. SEF of bone is a relatively indolent sarcoma of adults, most commonly located in the flat/irregular bones. Due to overlapping histological features, it is often misdiagnosed as osteosarcoma or a chondroid tumor. Most SEF of bone exhibit EWSR1 rearrangements, but rare cases may harbor a FUS gene fusion.

The existence of "aggressive" osteoblastoma (OB) or malignant transformation of OB is controversial. Over a few decades, we have encountered a group of "borderline" sclerosing osteoblastic lesions that are difficult to classify, tending toward local recurrence, especially following curettage. A search of the consultative and institutional files from 3 co-authors for atypical OB, malignant transformation of OB, well-differentiated osteosarcoma (OS), and OB-like OS diagnoses revealed 8 similar cases. There were 6 males and 2 females, ages 11 to 55 years (mean, 26 y). Three arose in metatarsals, 2 in the fibula, and 1 each in the humerus, tibia, and femur. Radiologically, most were expansile, lytic to sclerotic, with circumscribed and at least partially sclerotic borders. Pathologically, all displayed a predominant, sclerosing sheet-like neoplastic bone growth pattern, associated with minor components of conventional OB. No solid sheets of osteoblasts or permeation of surrounding bone were identified. Six cases were reviewed by >1 expert orthopedic pathologist, often with divergent opinions. Four were initially diagnosed as OB, 2 as low-grade OS, 1 as high-grade OS, and 1 as atypical sclerosing osteoblastic neoplasm. Clinical follow-up for 7 patients ranged from 12 to 138 months (mean, 71 mo). Four underwent curettage only; 2, curettage and en bloc resection with negative margins; 1, en bloc intralesional resection, and 1 amputation. 5 locally recurred, with 3 "reclassified" as OSs. One local recurrence was considered dedifferentiation. Whether these tumors represent low-grade OSs or aggressive forms of OB remains unclear. We recommend classifying these neoplasms as "atypical sclerosing osteoblastic neoplasm" and performing complete resection with negative margins.

Adamantinoma represents a distinct group of bone tumors showing both mesenchymal and epithelial differentiation most commonly involving the tibial diaphysis. Most adamantinomas contain a fibro-osseous component and an epithelial component consisting of squamous or basaloid cells. Adamantinomas are considered malignant neoplasms requiring en bloc excision that frequently recur locally and can rarely metastasize. Rare adamantinomas show an epithelial component consisting predominantly of monomorphic spindle cells, which, combined with an epithelial immunophenotype, can mimic monophasic synovial sarcoma. Synovial sarcoma is very rare in bone. It is considered a high-grade sarcoma that typically necessitates chemotherapy. However, the relationship between spindle cell adamantinoma and intraosseous synovial sarcoma has not been investigated. The current study was prompted by identification of a presumed spindle cell adamantinoma of the tibia with diffuse keratin expression that harbored a SS18 gene region rearrangement. FISH of eight additional bone tumors initially classified as spindle cell adamantinoma based on clinicoradiopathologic findings revealed one additional case with SS18 rearrangement. Histologically, both intraosseous synovial sarcoma and spindle cell adamantinoma demonstrated uniform fusiform nuclei with scant cytoplasm, short fascicles and low mitotic activity. The adamantinomas, but not the synovial sarcomas, were more likely to show overt epithelial differentiation in the form of pseudoglands or squamous nests. Immunohistochemistry of all cases, irrespective of SS18 status, showed diffuse keratin positivity in the spindle cell component, and less consistent EMA positivity. Clinical follow-up was available in both intraosseous synovial sarcomas, one of which recurred and the other metastasized. Two of the six spindle cell adamantinomas with follow-up metastasized. The above findings highlight the morphologic and immunophenotypic overlap between spindle cell adamantinoma and intraosseous synovial sarcoma of the tibia. Investigation of SS18 status to exclude synovial sarcoma is suggested prior to rendering a diagnosis of spindle cell adamantinoma.

The diagnosis of small round cell tumors always has been extremely difficult, and our current classification systems continue to evolve. Since its initial discovery by Dr James Ewing, the historical context of what is acceptably included under the designation "Ewing sarcoma" has changed. Although Ewing sarcoma and primitive neuroectodermal tumor were both initially described in the early 20th century, these tumors were considered likely distinct entities until the end of that same century, almost 75 years later. With modern immunohistochemistry and more recent advances in molecular techniques, the understanding of Ewing sarcoma and Ewing-like tumors has improved dramatically but also raises new questions and challenges. We now know that this category of tumors is remarkably more heterogenous than initially thought, especially in regards to its cytogenetics and molecular properties, and some of these differences likely have prognostic relevance. Whether we are now expanding the spectrum of Ewing sarcoma or simply recognizing new entities is controversial. Therapeutic approaches to address these new categories and/or entities need further focus and attention. Herein, we provide a comprehensive historical perspective on Ewing sarcoma, Ewing-like tumors (CIC and BCOR-rearranged sarcomas), and related and/or similar small round cell tumors, often included in the differential diagnosis, including mesenchymal chondrosarcoma, desmoplastic small round cell tumor, and small cell osteosarcoma. We also seek to provide updates and insights into the evolving classification and clinical relevance of the Ewing family of tumors.

Clear cell chondrosarcoma is a rare chondrosarcoma variant often involving the long bone epiphyses of young to middle aged adults. We report herein a case involving the left femoral head in a 25-year-old female with a 3-month history of worsening left hip pain. Radiographs revealed a complex, multifocal and lytic lesion centered in the left proximal femoral epiphysis with involvement of the femoral neck. Computed tomography-guided fine needle aspiration biopsy with concomitant core needle biopsy was performed, and a diagnosis of clear cell chondrosarcoma was rendered. Cytologic smears revealed aggregates of matrix material accompanied by a population of mostly uniform spindled to epithelioid and histiocytoid cells, rarely accompanied by osteoclast-type giant cells. The patient underwent surgical resection with -total hip replacement, and subsequent pathologic examination confirmed the initial needle biopsy diagnosis. There has been no evidence of local recurrence or distant metastases with 3-years follow-up. To our knowledge, this is the first reported example of a primary clear cell chondrosarcoma initially evaluated by fine needle aspiration biopsy., (© 2017 Wiley Periodicals, Inc.)

Conventional cytogenetic analysis performed from open biopsy tissue samples may be a useful adjunct for the histologic subtyping of bone and soft tissue sarcomas. However, its diagnostic utility in fine needle aspiration biopsy (FNAB) specimens is unclear. We retrospectively reviewed 24 consecutive FNAB bone and soft tissue sarcoma specimens, procured from 1995 to 2003, in which aspirated material was obtained for cytogenetic analysis. The study sample included eight Ewing sarcomas, six synovial sarcomas, five rhabdomyosarcomas, two myxoid liposarcomas, and one each of myxoid chondrosarcoma, osteosarcoma, and atypical lipoma. Cytogenetic analysis confirmed the t(X;18) in all six synovial sarcomas and the t(11;22) in three Ewing sarcomas. The t(2;13) was strongly suggested in one alveolar rhabdomyosarcoma. For two of these cases (both of which were synovial sarcomas), cytogenetic analysis was necessary for definitive diagnosis. While the positive cytogenetic results were supportive in the remainder, all were initially and accurately subtyped based on cytomorphology and/or immunohistochemistry. Cytogenetic analysis was noncontributory (eg no growth) in 14 sarcoma cases, but excluding the case of atypical lipoma, this did not preclude the rendering of an accurate diagnosis. Cytogenetic analysis can be performed on FNAB specimens from bone and soft tissue sarcomas and may be a useful diagnostic aid in difficult cases. However, when cell block material is available for immunohistochemistry, the majority of such cases are successfully subtyped.

Background: Dedifferentiated chondrosarcoma is a rare, poorly understood and often fatal sarcoma that usually manifests as a high grade, non-cartilage-producing sarcoma juxtaposed against a low grade chondrosarcoma. A correct diagnosis requires recognition of both components. In the absence of complete resection, rendering a specific diagnosis on small biopsy specimens, such as fine needle aspiration biopsy (FNAB), may be extraordinarily difficult., Cases: We retrospectively reviewed 4 cytology samples (3 primary, 1 metastatic) from 3 patients with dedifferentiated chondrosarcoma, initially analyzed by FNAB, emphasizing the potential for sampling error. Two women, aged 78 and 57 years, both of whom had prior histories of carcinoma, presented with lesions involving the right and left femur, respectively. One 27-year-old man with multiple osteochondromatosis developed a dedifferentiated chondrosarcoma of the left pelvis. Two primary cytologic specimens consisted of moderately cellular smears containing a spindled to polygonal, nonspecific, pleomorphic sarcoma unaccompanied by definite matrix material; 1 of these had a concomitant core needle biopsy (CNB), also demonstrating pleomorphic sarcoma. The third primary cytologic specimen revealed low grade chondrosarcoma, but a concomitant CNB showed only a high grade, non-matrix-producing sarcoma. The last patient developed a metastasis to the opposite femur; FNAB revealed a high grade spindle cell sarcoma. In none of the FNAB or CNB specimens were both low and high grade components of dedifferentiated chondrosarcoma recognized. However, the diagnosis was strongly suspected based on the clinical and radiographic findings., Conclusion: Due to sampling error, the diagnosis of dedifferentiated chondrosarcoma may be difficult to establish by cytologic examination alone. Clinical and radiographic correlation is essential for an accurate diagnosis.

The diagnosis of a bone tumor is often an arduous task, even for the most experienced orthopedic pathologist. As a starting point, the classification of bone tumors is based on a histogenetic perspective encompassing the type of matrix produced (or not produced) by the tumor. In general, the surgical pathology report should include data pertinent to the treatment and prognostication of an individual patient, and the report should be delivered to the clinician in a clear, concise fashion. Reporting of most bone tumors is similar and includes such information as the type of surgery done, anatomic site, histological type and grade of the tumor (if applicable), and the adequacy of surgical margins. Special emphasis is needed for those tumors with distinct and well-established prognostic and therapeutic features such as osteosarcoma and Ewing's sarcoma/peripheral neuroectodermal tumor. Our recommendation emphasizes a standardized protocol for these sarcomas, especially in light of evidence that postchemotherapeutic tumor necrosis is of prognostic significance. It is also important to note that radiographic imaging plays a very important, often critical, role in allowing the pathologist the opportunity to reach the best final diagnosis. This is especially true when a malignant interpretation is contemplated and in subtyping lesions. We recommend close collaboration between musculoskeletal radiologists, clinicians, and pathologists when dealing with complicated neoplasms of bone.

Overexpression of the HER-2/neu oncogene appears to have prognostic significance in breast cancer. Recently, some have reported a relationship between increased immunohistochemical expression in osteosarcoma and poor clinical outcome. Despite limited data, a pilot trial of Herceptin, which targets the oncogene product, has been initiated for the therapy of some metastatic osteosarcomas (CCG-P9852). Archival formalin-fixed, paraffin-embedded tissue obtained from 41 patients diagnosed with osteosarcoma was examined immunohistochemically by 2 antibodies against the HER-2/neu oncogene product: CB-11 (monoclonal, 1/100) and Oncor (polyclonal, 1/200). All but one tumor (case of recurrent dedifferentiated parosteal osteosarcoma) represented primary tumor samples; when applicable, only prechemotherapy biopsies were analyzed. The study sample included the full spectrum of histologic subtypes and grades of osteosarcoma (25 conventional high grade; 3 telangiectatic; 1 small cell; 6 parosteal; 1 periosteal; and 5 low-grade intramedullary). A case of metastatic breast cancer with known overexpression of the HER-2/neu oncogene served as the positive control. Complete membranous positivity, considered prognostically significant in breast cancer, was not seen in any of our osteosarcoma cases. At least focal cytoplasmic positivity was documented in 40 (98%) tumors using the CB11 antibody and in 34 (83%) using the Oncor antibody. The intensity of the cytoplasmic staining (0, 1-3+) did not correlate with histologic subtype/grade, response to chemotherapy (<90% versus > or = 90% necrosis), metastasis, or survival. Immunohistochemical overexpression of the HER-2/neu oncogene, defined as complete membranous positivity, is not present in our series of osteosarcomas. Cytoplasmic positivity is observed in most osteosarcomas, irrespective of histologic subtype/grade, and is not associated with response to preoperative chemotherapy or disease progression.

Background: Largely due to a lack of experience, familiarity, and/or confidence, few centers rely on simple fine-needle aspiration biopsy (FNAB) for the diagnosis of sarcomas and related tumors., Methods: The authors have reviewed their own experience in more than 200 cases of FNAB of bone and soft-tissue tumors, as well as cases reported in the literature., Results: FNAB has proven to be accurate and useful in 8 consecutive years of clinical experience. No serious complications have occurred., Conclusions: FNAB is recommended as an integral part of the initial evaluation of amenable orthopaedic tumors, including sarcomas, especially in cases with classic clinical and radiographic findings.

We retrospectively reviewed our experience with fine needle aspiration biopsy (FNAB) in the diagnosis and management of skeletal osteosarcoma. The bi-institutional study sample involved 30 consecutive aspirates from 29 patients (28 primary tumors, 1 pulmonary metastasis, 1 local recurrence). There were 17 children and 12 adults. Two aspirates were unsatisfactory for diagnosis. Of the adequate primary osteosarcoma cases analyzed by FNAB, 24 of 26 were diagnosed as osteosarcoma. All pediatric cases were correctly interpreted as osteosarcoma and treated appropriately. There were 2 incomplete diagnoses. A secondary osteosarcoma arising within an otherwise clinically, radiologically, and histologically typical giant cell tumor (malignant giant cell tumor) was not diagnosed preoperatively on FNAB due to nonrepresentative sampling. Chronologically, the first patient with osteosarcoma analyzed by FNAB was diagnosed simply as "spindle cell neoplasm." No complications resulted from the procedure. With adequate clinical and radiologic correlation, FNAB represents a technically, easily performed, cost-effective, and accurate procedure for establishing the diagnosis of skeletal osteosarcoma. Immediate interpretation of aspirated material allows for therapy planning and oncologic consultation at the initial clinic visit.

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.

Metastatic disease involving the skeleton is an unfortunate and common occurrence in cancer patients. Choosing the best diagnostic approach requires knowledge of the patient's clinical history, the radiologic appearance of the lesion, the differential diagnosis, and the ability of the diagnostic modality to answer the questions that must be addressed. In difficult cases, interaction between the pathologist and clinician before biopsy may make the difference between a rapid procedure serving to definitively diagnose and effectively stage a patient and a costly procedure that provides little or no information.

Fibrocartilaginous mesenchymoma of bone is a rare primary neoplasm. Our literature search produced only 12 previously reported cases. Radiographic and computed tomography (CT) findings have been described, but the magnetic resonance imaging (MRI) appearance has not been reported previously. We report a patient with fibrocartilaginous mesenchymoma of the ilium and describe the imaging findings on conventional radiography, bone scan, CT, and MRI.

The use of fine-needle aspiration biopsy (FNAB) in the initial evaluation of pediatric bone and soft tissue tumors is controversial, especially for those patients being considered for histiogenetic-specific therapeutic protocols, e.g., the Intergroup Rhabdomyosarcoma Study Group, the Pediatric Oncology Group. We retrospectively reviewed 33 consecutive FNAB specimens (28 primary tumors, 5 metastases) from 32 pediatric patients (< or = 19 yr of age), none of whom had a previously established tumor diagnosis. In one patient, FNAB of the primary tumor and a presumed axillary metastasis were obtained concomitantly. The cytomorphologic analysis included osteosarcoma, eight patients; rhabdomyosarcoma, five; neuroblastoma, five; Ewing's sarcoma/primitive neuroectodermal tumor, four; Langerhans' cell histiocytosis, three; and one each synovial sarcoma, undifferentiated sarcoma, infantile myofibromatosis, fibroma, chondroblastoma, chondromyxoid fibroma, and desmoplastic small round-cell tumor. Ancillary studies, e.g., immunocytochemical analysis, were used in 13 cases. Cytogenetic analysis helped to confirm one Ewing's sarcoma [t (11;22) (q24;q12)] and one synovial sarcoma [t(X;18) (p11;q11)]. With adequate FNAB specimens, a histogenetic-specific diagnosis was rendered in 27 (93%) of 29 cases, and all were correctly recognized as either benign or malignant. One case each of Langerhans' cell histiocytosis, chondroblastoma, and infantile myofibromatosis yielded unsatisfactory specimens. Fibroma and desmoplastic small round-cell tumor were initially misclassified as nodular fasciitis and rhabdomyosarcoma, respectively. Of 18 patients clinically eligible for histogenetic-specific therapy protocols, an accurate diagnosis was obtained in 17 patients. With a multidisciplinary approach and judicious use of ancillary studies, FNAB represents a highly accurate and cost-effective technique for the diagnosis of pediatric bone and soft tissue tumors, especially sarcomas, and should be considered as a viable diagnostic technique for pediatric therapeutic protocols.

We retrospectively reviewed two fine-needle aspiration biopsy (FNAB) specimens from two patients with histologically confirmed epithelioid hemangioendothelioma (EH). Both patients were men, ages 79 and 39 years; their primary tumors arose in the soft tissues of the mediastinum and within the proximal tibia, respectively. The former patient had symptoms of superior vena cava syndrome; multicentric intraosseous lesions involved the proximal tibia of the latter patient. All cytologic smears were hypercellular and composed of mostly disassociated single cells and small aggregates of ovoid to polygonal-shaped epithelioid cells. Nuclei were variable, ranging from ovoid and reniform to round and polylobated and surrounded by an abundant amount of dense cytoplasm. Binucleated epithelioid neoplastic cells were frequent. Nuclear pleomorphism ranged from slight to moderate, and small solitary to multiple nucleoli were identified within the majority of tumor cells. Rare neoplastic cells with a single, sharply demarcated intracytoplasmic vacuole and intranuclear cytoplasmic pseudoinclusions were observed in the smears of one tumor. Metachromatic stromal fragments, probably representing hyalinized chondromyxoid stroma, were seen in the other tumor. Neither case was recognized initially on FNAB as EH. Immunohistochemically, sections from the surgical biopsy specimens of both cases showed diffuse and strong immunopositivity for the endothelial marker CD31. Although the cytomorphology of EH appears distinct, clinicoradiologic correlation is essential, and immunohistochemistry may be helpful to avoid misdiagnoses.

Background: Although fine-needle aspiration biopsy (FNAB) of primary skeletal osteosarcoma (OS) has been described adequately, to the authors' knowledge, cytologic descriptions of extraskeletal OS appear limited to only rare case reports., Methods: In an attempt to analyze the utility and accuracy of FNAB in a diagnosis of skeletal versus extraskeletal OS, the authors retrospectively reviewed their 5-year experience. The study sample included 15 skeletal OS specimens (13 primary, 1 local recurrence, and 1 pulmonary metastasis) in 14 patients ages 10-58 years (mean, 27 years; median, 25 years) and 5 extraskeletal OS specimens (3 primary and 2 metastatic) in 4 patients ages 36, 37, 65, and 79 years, respectively. Based on accepted clinical criteria, two patients (a mother with extraskeletal OS and a daughter with skeletal OS) had Li-Fraumeni syndrome., Results: Of the adequate primary skeletal OS cases analyzed by FNAB, 10 of 12 (83%) were diagnosed correctly and subsequently treated according to a disease specific protocol. One case was considered unsatisfactory. One tumor initially was diagnosed as a giant cell tumor and another was referred to nonspecifically as "spindle-cell neoplasm." On histologic examination, the former case demonstrated a high grade fibroblastic OS arising within a giant cell tumor. None of the primary extraskeletal OS cases analyzed by FNAB was recognized as OS. One was diagnosed nonspecifically as "sarcoma" and the other was referred to simply as "atypical mesenchymal cells." A third case was comprised of scant fragments of adipose tissue, fibrous tissue, and cartilage and was considered unsatisfactory. Both examples of metastatic extraskeletal OS were recognized by FNAB., Conclusions: With appropriate clinicoradiologic correlation, skeletal OS generally is easily diagnosed by FNAB. Because of the older age of most patients with extraskeletal OS and the rather nonspecific radiographic findings (e.g., soft tissue mass), extraskeletal OS may not be recognized easily by FNAB and most likely requires incisional biopsy to establish a definitive diagnosis in most cases. Additional larger series will be required before drawing definite conclusions.

Background: Chondrosarcoma of bone is a well recognized, relatively common clinicopathologic entity. Morphologically distinct soft tissue chordoid sarcoma (CS), or extraskeletal myxoid chondrosarcoma, is a relatively rare tumor that has generally been documented in extraosseous soft tissues., Methods: The clinical and pathologic features of two patients with biopsy-proven CS from the pathology files of the Mayo Clinic and St. Thomas's Hospital were evaluated. Routine hematoxylin and eosin-stained slides were reviewed in both cases. Sections from both were examined immunohistochemically using the avidin-biotin-peroxidase technique and employing commercially available antibodies to the following antigens: S-100 protein, cytokeratin (AE1/AE3), epithelial membrane antigen (EMA), CD31, and factor VIII. Appropriate positive and negative controls were utilized throughout these procedures. Cytogenetic analysis was performed on fresh samples obtained from one tumor. Clinical data were obtained from the patients' medical records., Results: The two cases of primary CS of bone arose from the right distal femur and right scapula, respectively, in 2 men ages 48 and 76 years, respectively. Morphologically, the tumors were lobulated, multinodular, and comprised of a uniform population of rounded to slightly spindled cells. Nuclei were hyperchromatic with inconspicuous nucleoli and surrounded by clear, vacuolated to eosinophilic cytoplasm. Neoplastic cells were arranged in anastomosing chords, strands, and, less often, nests and pseudopapillary structures embedded in an abundant, mostly hypovascular, mucinous matrix. Foci of hemorrhage and cystic degeneration were present in both tumors. No well developed hyaline cartilage or neoplastic osteoid was observed. Immunohistochemically, one neoplasm showed focal positivity for S-100 protein but was uniformly negative for cytokeratin (AE1/AE3), factor VIII, and CD31. The other tumor showed no immunopositivity with cytokeratin, EMA, or S-100 protein. Cytogenetic analysis in the latter tumor revealed a nonrandom reciprocal chromosomal translocation, t(9;22)(q22-31;q11-12). Both patients developed local recurrences and widespread distant metastases. Wide surgical excision was the primary mode of therapy. One patient died of tumor., Conclusions: Skeletal CS is an extraordinarily rare neoplasm with a distinct morphology. Although follow-up data were limited to only four examples, including two from the literature, the clinical course appears worse than that for usual chondrosarcoma of bone. Wide surgical resection appears to represent the best mode of therapy. The role of chemotherapy and radiation therapy has not been clearly defined.

Chondroblastoma of bone is a well-characterized entity. When the radiographic features are classic and the lesion is present in typical locations (i.e., epiphysis of a long bone), the diagnosis is often easily established by fine-needle aspiration biopsy and/or surgical curettage. Tumors in unusual locations, in older patients, or when complicated by aneurysmal bone cysts may pose more diagnostic difficulty. We report four examples (three primary and one-recurrent) of chondroblastoma of bone diagnosed by fine-needle aspiration biopsy. All patients were men, ranging from 18 to 28 yr of age. Sites of involvement included the acromion process of the scapula, left humerus, right ischium, and left distal femur. Three of the tumors were diagnosed as chondroblastoma on fine-needle aspiration cytology; the fourth case, involving the scapula, consisted mostly of a large aneurysmal bone cyst and remained unrecognized until surgical curettage was performed. Typical-appearing chondroblasts were present in three of the cases; osteoclast-type giant cells were observed in all four cases. Matrix material consistent with chondroid was also identified in all cases. We believe that in the absence of inflammatory cells, the presence of classic-appearing chondroblasts, even without chondroid matrix, is sufficient for a diagnosis of chondroblastoma of bone.