Intramammary Angiomatoid Fibrous Histiocytoma, a Rare EWSR1 Rearranged Mesenchymal Neoplasm in a Previously Unreported Anatomic Location with Review of the Cleveland Clinic Experience.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor that is most commonly reported to arise in the subcutaneous tissues of the upper extremities in adolescents and young adults. At present, the WHO classifies this neoplasm as a tumor of uncertain differentiation. AFH is most often clinically regarded as a tumor of intermediate risk due to low reported rates of recurrence and only rare occurrences of metastases. Its histomorphological hallmarks are a prominent lymphoid cuff surrounding a spindle cell neoplasm with syncytial-appearing cytoplasm. Several variant morphologies have been described. Genetically, the tumor is characterized by translocations involving the EWSR1 gene in over 90% of cases. A widening range of anatomical locations and morphological variants of AFH has been reported in the literature; however, neither anatomic location nor specific morphologic features have been shown to correlate with clinical/biological behavior. We report a unique case of AFH arising in the parenchyma of the breast. The neoplasm showed the typical histomorphology including a peripheral lymphoid cuff. The lesional cells in this case were found to be immunoreactive with desmin, and a positive EWSR1 result was confirmed by break-apart fluorescence in situ hybridization testing. To our knowledge, this is the first report of AFH arising in the breast parenchyma of a postmenopausal female.

Clinicopathologic analysis of HER-2/neu immunoexpression among various histologic subtypes and grades of osteosarcoma.

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.

Prostate carcinoma metastatic to the cervical lymph nodes: report of two cases and review of the literature.

The cervical lymph nodes are a common site of metastasis for cancers originating in the upper aerodigestive tract. Rarely, cancers originating from sites other than the head and neck can metastasize to the cervical lymph node chain. We report on 2 recent patients with metastatic prostate cancer to the cervical lymph nodes.

The role of fine needle aspiration biopsy in the diagnosis and management of osteosarcoma.

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.

Fine-needle aspiration biopsy of sarcomas and related tumors.

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.

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.

Pathology of skeletal metastases.

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.

The value of fine-needle aspiration biopsy in the differential diagnosis of adult myxoid sarcoma.

BACKGROUND: The usefulness of fine-needle aspiration biopsy (FNAB) for the histologic subtyping of specific sarcomas still is somewhat controversial but is becoming increasingly popular in the U.S. METHODS: To determine the accuracy and usefulness of FNAB in the differential diagnosis of myxoid sarcoma, the authors retrospectively reviewed 18 FNAB specimens (16 primary tumors, 1 local recurrence, and 1 metastasis) in 18 patients. The study sample included myxoid/round cell liposarcoma in six patients, myxofibrosarcoma in six patients, myxoid chondrosarcoma in five patients, and myxoid leiomyosarcoma in one patient. RESULTS: All but one tumor were recognized correctly as malignant. With regard to primary tumors, a specific cytologic diagnosis was rendered in 13 of 16 patients (81%). Problematic areas included the diagnosis of high grade myxofibrosarcoma with minimal amounts of myxoid stroma, myxoid liposarcoma with a predominant round cell component, and the single case of myxoid leiomyosarcoma. CONCLUSIONS: FNAB represents a valuable diagnostic tool for the differential diagnosis of myxoid sarcoma, especially myxofibrosarcoma, low grade myxoid liposarcoma, and myxoid chondrosarcoma. Due to its prognostic and therapeutic significance, the presence of a predominant round cell component in myxoid liposarcoma should be documented adequately. Other sarcomas (e.g., leiomyosarcoma) rarely may exhibit a prominent myxoid stroma and therefore should be considered in the differential diagnosis of adult myxoid sarcoma.

Fibrocartilaginous mesenchymoma of bone: case report and review of the literature.

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.

Fine-needle aspiration biopsy of soft tissue sarcomas. A cytomorphologic analysis with emphasis on histologic subtyping, grading, and therapeutic significance.

Because therapy for sarcoma often incorporates histologic subtype, grade, stage, and anatomic location, establishing a specific histologic subtype often is essential. To evaluate the effectiveness of fine-needle aspiration biopsy (FNAB) in histologic subtyping of soft tissue sarcomas, we retrospectively reviewed 73 consecutive aspirates from 67 patients, none of whom had a previously established sarcoma diagnosis. Sarcoma cases were subgrouped according to predominant cytomorphologic features: pleomorphic cell, 19; small round cell, 18; spindle cell, 18; myxoid, 10; epithelioid/polygonal cell, 7; 1 case of well-differentiated liposarcoma was analyzed separately. Ancillary studies were used for 25 cases. Among adequate specimens, 61 tumors were recognized as sarcoma. A specific and accurate histologic subtype was determined in 34 cases. Ancillary studies were most useful for histologic subtyping of small round cell and spindle cell sarcomas. Myxoid sarcomas were subtyped easily based solely on histomorphologic features. Pleomorphic cell and epithelioid/polygonal cell sarcomas were recognized easily as malignant but difficult to subtype by FNAB. With the exception of small round cell sarcomas, histologic subtyping of a sarcoma usually did not directly influence therapy. With meticulous attention to clinicopathologic features and ancillary techniques, many sarcomas, especially small round cell, spindle cell, and myxoid types, may be subtyped successfully by FNAB, within limitations.

Histologic prognostication in soft tissue sarcomas: grading versus subtyping or both? A comprehensive review of the literature with proposed practical guidelines.

Despite the validation of many histologic grading systems for soft tissue sarcomas, none have been universally accepted. Because of the overall rarity of specific histologic sarcoma subtypes, evaluation of grading systems and their prognostic significance have tended to base the results on sarcomas as a general group, diminishing the value and significance of histologic subtyping. A representative review of the literature regarding histologic grading of soft tissue sarcomas and its relationship to histologic subtype, stage, and prognosis is analyzed and discussed. Histologic grading of many soft tissue sarcomas appears to be a valuable predictor of patient survival, as confirmed by the literature. However, accurate histologic subtyping is essential for accurate histologic grading. Histologic grading in some sarcoma subtypes is probably not applicable and may underestimate biologic behavior. Clinicians and pathologists should be aware of the limitations, prognostic significances, and relationships of histologic subtyping and histologic grading in the therapeutic management and prognostication of soft tissue sarcomas.

Myxofibrosarcoma of soft tissues: cytomorphologic analysis of a series.

Within the English literature, myxofibrosarcoma is a recently described entity. Although the histopathologic features have been reported, the cytomorphologic spectrum of myxofibrosarcoma has been far less documented. The cytologic findings of six fine-needle aspiration biopsy specimens (five primaries, one local recurrence) from six patients are described. The patients' ages ranged from 26-77 yr; there were four women and two men. The aspiration biopsy specimens ranged from slightly to markedly cellular. Although a myxoid granular to filamentous background was observed at least focally in all cases, the volume of the myxoid material was inversely proportional to the cellularity and grade of the tumor. Individual tumor cells were round to spindled, often displaying a wide range of cell shapes and sizes. Nuclei were generally large, pleomorphic, and hyperchromatic, frequently containing prominent nucleoli. Cytoplasm ranged from scant to dense and tapering. Multinucleated tumor giant cells were occasionally observed. In general, low- and intermediate-grade myxofibrosarcomas were more easily recognized in cytologic preparations. In contrast, high-grade myxofibrosarcoma was more difficult to specifically subtype and not easily distinguished from other adult pleomorphic sarcomas.

The role of fine-needle aspiration biopsy in the initial diagnosis of pediatric bone and soft tissue tumors: an institutional experience.

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.

Histogenetic relations between giant cell fibroblastoma and dermatofibrosarcoma protuberans. CD34 staining showing the spectrum and a simulator.

The authors describe three lesions that provide further evidence for a close, possibly histogenetic relation between giant cell fibroblastoma and dermatofibrosarcoma protuberans. The first case involves a dermatofibrosarcoma protuberans that contained a single giant cell fibroblastoma-like focus of multi-nucleate giant cells. A second tumor, a giant cell fibroblastoma, recurred 6 years later as a dermatofibrosarcoma protuberans. In the third lesion, there was a juxtaposition and co-mingling of dermatofibrosarcoma protuberans and giant cell fibroblastoma within the same primary lesion. In all cases, both the giant cell fibroblastoma areas and dermatofibrosarcoma protuberans areas stained positively with CD34. A fourth case, a dermatofibrosarcoma protuberans infiltrated skeletal muscle, creating giant cell fibroblastoma-like giant cell mimics--a result of skeletal muscle degeneration or atrophy with nuclear conglomeration. The latter giant cells failed to express CD34 but did show immunoreactivity with desmin. These findings support the concept that giant cell fibroblastoma and dermatofibrosarcoma protuberans probably represent a histologic spectrum of a single CD34 positive (perhaps, dermal dendrocytic) neoplasm, a conclusion supported by a recently cloned t(7;22) breakpoint demonstrated in both neoplasms.

Fine-needle aspiration biopsy of skeletal versus extraskeletal osteosarcoma.

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.

Epithelioid hemangioendothelioma of bone and soft tissue: a fine-needle aspiration biopsy study with histologic and immunohistochemical confirmation.

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.