To adequately diagnosis soft tissue myelolipoma one must confirm absence of hematologic abnormalities and presence of lesion within soft tissue rather than bone marrow or adrenal

INTRODUCTION

Soft tissue ganglion cysts, Baker’s cysts, and bursae are relatively common. Other cystic lesions are relatively uncommon with simple or unicameral bone cysts representing only 3% of biopsied primary bone tumors, aneurysmal bone cysts representing 2% of primary bone tumors, and telangiectatic osteosarcomas representing only 2% of all osteosarcomas. The wide spectrum of clinical behavior exhibited by these cystic lesions often requires tissue confirmation of the radiographic diagnosis to insure proper management. As these lesions frequently result in acellular aspirates, definitive diagnosis is often impossible cytologically but the finding of an acellular or hypocellular aspirate may be helpful in confirming the radiographic impression of a benign cystic lesion.

Synovial cysts

Clinical features

Synovial cysts most frequently develop around the knee (Baker’s cysts) but are also known to occur in the shoulder, hip, elbow, hand, and ankle. Most present as a mass near a joint and may or may not be painful. Slow enlargement in size is common and may lead to impairment of joint function.

INTRODUCTION

Neoplasms showing lipomatous differentiation comprise the numerically largest family of neoplasms in man. They can occur at almost all body sites and display a wide age spectrum ranging from infancy to late adult life. Benign lipomas are most frequent in patients between 40 and 60 years of age while liposarcomas most often come to clinical attention in patients over 50 years of age.

Neoplasms showing true lipomatous differentiation express S-100 protein. Additionally, benign lipomatous neoplasms display a variety of translocations, rearrangements, and other genetic alterations which include translocations involving 12q13–15, 8q11–13, 11q13, and 10q22. Lipomas of usual type show deletions of 13q, while spindle cell and pleomorphic lipomas show loss of 16q13.

Of diagnostic importance is the CHOP gene rearrangement characteristic of myxoid and round cell liposarcomas and amplification of the MDM2 gene in well differentiated liposarcomas and atypical lipomatous neoplasms. This gene amplification helps distinguish these neoplasms from benign lipomas.

LIPOMA

Clinical features

Lipomas occur as both solitary and multiple lesions. Most are removed for cosmetic purposes. Lipomas are rare before 20 years of age but gradually increase in frequency with a maximum prevalence in patients 40 to 60 years old. The frequency of lipomas does not vary with race. Men appear to be more frequently affected.

Lipomas may occur as either superficial or deep neoplasms and, in both locations, are usually asymptomatic slowly growing masses. Pain is rarely apparent in ordinary lipomas, but angiolipomas are often painful. Imaging studies are helpful in identifying a lesion as fatty in nature but are of less aid in separating benign from malignant neoplasms. Magnetic resonance imaging studies of both benign and malignant lipomatous neoplasms demonstrate high signal intensity on T1-weighted images.

INTRODUCTION

This category of neoplasms represents a diverse group of morphologically similar but biologically heterogenous soft tissue and bone neoplasms characterized by an epithelioid or polygonal cell morphology. Numerically, this is the least common group of neoplasms with only granular cell tumor and synovial sarcoma occurring with significant frequency. Synovial sarcoma represents approximately 5–10% of all soft tissue sarcomas and granular cell tumor is a relatively common benign neoplasm.

The characteristic or predominate cell type in each of these neoplasms has an ovoid or polygonal shape in smear preparations. In most of these neoplasms, a similar shape is demonstrable in H&E stained histologic sections yielding a superficial resemblance of these cells to epithelial cells. In the case of synovial sarcoma, the polygonal or ovoid shape seen cytologically appears to be a result of smearing artifact and a more spindle shape characterizes synovial sarcomas histologically. Some members of this cytomorphologic category demonstrate an accepted direction of differentiation such as granular cell tumor which shows neural differentiation and Langerhans cell histiocytosis which demonstrates histiocytic differentiation. Other lesions such as synovial sarcoma, epithelioid sarcoma, and extrarenal rhabdoid tumor represent sarcomas of uncertain type and lack a definitive direction of differentiation. Despite lack of a clear direction of differentiation for some of these neoplasms, characteristic immunohistochemical and molecular profiles exist for synovial sarcoma, clear cell sarcoma of soft parts, Langerhans cell histiocytosis, granular cell tumors, and extrarenal rhabdoid tumors.

INTRODUCTION

A large number of lesions arising within bone and soft tissues may display a myxoid background. In most neoplasms, this is an uncommon phenomenon and is often only focal in distribution. However, a number of lesions consistently show a myxoid background dominating the histologic and cytologic appearance of the specimen. Myxoid change is a relatively infrequent occurrence in schwannomas and synovial sarcomas but, as the names imply, is a characteristic morphologic feature of myxomas, myxoid liposarcomas, myxoid chondrosarcomas, and examples of myxofibrosarcoma and fibromyxosarcoma. The presence of a prominent myxoid stroma frequently indicates a relatively slow growing neoplasm and has been inversely correlated with frequency of metastatic disease.

The nature of the myxoid material varies among lesions. In some cases, the myxoid phenomenon is degenerative as seen in ganglion cysts, while in other instances, the myxoid material appears to be a secretory product such as chondroitin sulphate in myxoid chondrosarcomas.

Morphologically, the myxoid matrix in these lesions is generally not helpful in their specific diagnosis. Vascular pattern, cell distribution, and degree of nuclear atypia are features allowing accurate diagnosis of these lesions. Molecular diagnostic features such as the presence of the t(12;16)(q13;p11) translocation in myxoliposarcomas, the t(9;22)(q22;q21) translocation in extraskeletal myxoid chondrosarcomas, and the t(7;16)(q33;p11) translocation in low grade fibromyxoid sarcomas are helpful diagnostic features.

INTRODUCTION

Patient age has a significant impact on the diagnosis of musculoskeletal lesions. Many musculoskeletal lesions have characteristic ages of presentation. Thus, patient age can narrow the differential diagnosis in the evaluation of musculoskeletal tumors. Spindle cell lesions of the pediatric age group can be divided into those of similar appearance and behavior as adult lesions and those which occur only in infants and children or possess special morphologic features in the pediatric age group. These latter pediatric entities may possess morphologic features that do not reflect behavior when adult criteria are used for evaluation. In some of these processes, growth rate and morphologic appearance may suggest an aggressive neoplasm but in fact when occurring in the pediatric age group follow an indolent course. Hence, spindle cell lesions of adults and children will be discussed separately in this monograph.

Fibromatosis colli

Clinical features

Fibromatosis colli is a well recognized clinical pathologic entity occurring at a precise anatomic site (sternocleidomastoid muscle) and in a specific age group (infancy and childhood). Most cases present within the first few weeks after birth and are associated with muscular torticollis or wry-neck. Pathologically, it is similar to other forms of infantile fibromatosis but because of its unique clinical features is recognized as a separate entity. The lesion is relatively uncommon occurring in only 0.4% of live births. It is important to remember that the clinical finding of torticollis is not identical to the clinical pathologic diagnosis of fibromatosis colli. In fact, a majority of patients clinically presenting with torticollis will have entities other than fibromatosis colli.

INTRODUCTION

Vascular neoplasms demonstrate a wide range of morphologies and behaviors ranging from benign hemangiomas to aggressive, rapidly fatal angiosarcomas. Vascular proliferations may be congenital or non-congenital with fundamentally different etiologies, clinical presentations, and therapeutic implications. Some lesions are congenital malformations and not neoplastic. Other congenital lesions are clinically inapparent at birth but become significant in young adulthood. A number of hemangiomas and hemangioendotheliomas regress as the patient ages. Whether these lesions are truly neoplastic or not is debated. A number of growth factors appear to be important in angiogenesis. Among these are vascular endothelial growth factors A and B (VEGF A and B) and fibroblast growth factor (FGF). Prostaglandin E2, interleukin-8, and platelet derived growth factor also appear to play roles in angiogenesis.

HEMANGIOMA

Clinical features

Hemangiomas are one of the most common soft tissue tumors representing between 7 and 10% of all benign mesenchymal lesions. These neoplasms most commonly come to clinical attention during infancy and childhood when there is a predilection for their formation in the head and neck region. In adults, hemangiomas take the form of capillary or cavernous lesions and are more common in women. They may fluctuate in size during pregnancy and menarche suggesting the importance of estrogen and progesterone in their growth. While hemangiomas may persistently grow, they do not undergo malignant transformation. However, extremely well differentiated cutaneous angiosarcomas and angiosarcomas of the breast exist which are neoplasms fully capable of metastasis but typically morphologically difficult to distinguish from benign hemangiomas.

INTRODUCTION

Cartilaginous neoplasms of bone and soft tissues are relatively common. Osteochondromas and chondromas are the first and second most common benign neoplasms of bone. Chondrosarcomas are the second most common primary sarcoma of bone following osteosarcoma. Cartilage forming neoplasms display a wide range of morphologies and clinical behaviors ranging from totally benign osteochondromas and chondromas to very aggressive grade III chondrosarcomas. While osteochondromas and chondromas are benign neoplasms, both have the potential for malignant degeneration. These two neoplasms also occur as inherited multifocal forms represented by Ollier’s disease, Maffucci syndrome, and osteochondromatosis.

Cartilaginous neoplasms are associated with some of the most difficult differential diagnoses in musculoskeletal pathology. The separation of enchondroma from grade I chrondrosarcoma can be exceedingly difficult requiring integration of clinical, radiographic, and histopathologic data.

CHONDROMA AND ITS VARIATIONS

Clinical features

Chondromas represent benign proliferations of cartilage which account for 10% of all benign bone tumors and may vary considerably in appearance depending on patient age, site of origin, and whether or not a syndrome is present. Chondromas are subdivided into enchondromas, periosteal, or parosteal chondromas, and extraskeletal chondromas. Enchondromas are, by far, the most common.

INTRODUCTION

Spindle cell lesions are numerically the largest category of mesenchymal proliferations occurring in adults and are also the most diagnostically challenging. These lesions vary from benign reactive reparative processes to high grade malignancies including synovial sarcoma, malignant peripheral nerve sheath tumors and some forms of angiosarcoma. These lesions are associated with a significant incidence of both false positive and false negative diagnoses by both cytologic analysis and histologic interpretation of small core biopsies. Unfortunately, ancillary techniques, especially immunohistochemistry are often of little diagnostic aid in separating benign or low grade spindle cell proliferations from fully malignant spindle cell sarcomas. While some spindle cell neoplasms have characteristic age and sites of presentation, these features are of only modest help diagnostically and, in a significant percentage of cases, the cytologic diagnosis will be that of a spindle cell neoplasm followed by a recommendation for surgical biopsy. Cytomorphologic features such as high cellularity, loss of cell cohesion, and nuclear atypia support but do not unequivocally establish the diagnosis of malignancy. Some predominately spindle cell sarcomas can be definitively diagnosed by fine needle aspiration, especially when cell block material is utilized for ancillary studies. Synovial sarcoma, some benign and malignant nerve sheath tumors, and angiosarcomas may have sufficiently characteristic cytomorphology and immunohistochemical or molecular diagnostic profiles to allow definitive diagnosis based on aspirated material. Other lesions including fibrosarcomas, fibromatoses, and smooth muscle neoplasms are associated with insufficiently characteristic morphology to allow definitive diagnosis in the majority of cases.

INTRODUCTION

Small round cell malignancies represent a diagnostic category of primitive neoplasms occurring predominately in infants and children. These neoplasms show limited degrees of differentiation towards mature tissues. While many occur in mesenchymal organs, small round cell tumors are recognized in the kidney (Wilms’tumor), adrenal glands (neuroblastoma), and the brain (medulloblastoma). While the majority of small round cell malignancies arising in the mesenchymal tissues occur in children, small round cell malignancies do occur in adults where they are represented by a variety of lymphomas and small cell carcinomas. Small cell carcinomas frequently have varying degrees of neuroendocrine differentiation and occur at a variety of sites including the lung, bladder, and prostate. Small cell carcinomas may metastasize to bone and soft tissue.

Traditionally, small round cell malignancies have been a source of significant diagnostic challenges as separation on a purely morphologic basis is difficult. While many small round cell malignancies show varying degrees of differentiation towards mature tissues (rosettes in neuroblastomas, tubules in Wilms’ tumors, and cross striations in rhabdomyosarcomas), the majority of cells disclose only a primitive cell morphology. Although electron microscopy is diagnostically useful, immunohistochemistry has enhanced the separation of these lesions into meaningful therapeutic categories. Hence, rhabdomyosarcomas frequently demonstrate immunohistochemical positivity for muscle markers including desmin, caldesmin, muscle actins and myogenin, leukemias and lymphomas demonstrate hematopoietic differentiation markers, and primitive neuroectodermal tumors may express neural markers in at least a fraction of the cells. More recently, molecular diagnostics has demonstrated a number of clinically useful translocations greatly improving our accuracy in the diagnosis of these neoplasms.

INTRODUCTION TO THE DIAGNOSIS OF MUSCULOSKELETAL LESIONS

Fine needle aspiration and core biopsy are used at some oncology centers as the initial technique to obtain a tissue diagnosis for mass lesions occurring within the musculoskeletal system. A majority of such lesions are in actuality metastatic deposits from a primary malignancy arising elsewhere. Metastatic neoplasms usually present little difficulty in diagnosis. Primary lesions of the musculoskeletal system are a significantly greater diagnostic challenge and many authorities in histopathology of bone and soft tissue tumors have recommended against the use of small biopsy techniques for the diagnosis of these lesions. The resistance to the use of small volume specimens, especially fine needle aspiration (FNA), results from a combination of factors including the relative rarity of these lesions, the potential for radical deforming surgery and the young age of the patients in which many of these lesions occur. Musculoskeletal sarcomas account for less than 1% of all malignant neoplasms. The infrequency of these tumors results in limited experience with their morphologic appearances among surgical pathologists and cytopathologists except for those practicing at orthopedic oncology centers. Contributing to this reduction in the utilization of small biopsy procedures is the relatively high percentage of benign proliferations (pseudosarcomas) closely resembling true sarcomas. An additional issue which has slowed the implementation of FNA for the investigation of musculoskeletal neoplasms is concern that the technique may not procure sufficient sample to obtain reliable results with a variety of ancillary techniques including immunohistochemistry and molecular diagnostics.

INTRODUCTION

Neoplastic and non-neoplastic bone forming lesions are found within both the soft tissues (especially muscles and joints) and bones. Aspiration biopsy of heavily ossified lesions generally results in extremely hypocellular or acellular aspirates and in these cases, small core biopsy may also be unsuccessful.

Heterotopic bone may be found as a metaplastic product in both neoplastic and non-neoplastic lesions. Aspiration samples of heterotopic ossification usually yield hypocellular smears or at most reactive fibroblasts scattered in a bloody background. Morphologically dissimilar but potentially etiologically related are aspirates of dystrophic calcification. Both lesions can reach massive size and are frequently found in periarticular areas particularly around the hip. Other lesions with non-neoplastic ectopic ossification include myositis ossificans and fibrodysplasia ossificans progressive.

MYOSITIS OSSIFICANS

Clinical features

Myositis ossificans is a benign bone forming proliferation of a reactive or reparative nature. It most commonly occurs in striated muscle but similar lesions are reported to occur in the subcutaneous tissues and tendons. Myositis ossificans is related to nodular and proliferative fasciitis but differs morphologically in that bone formation occurs with various degrees of maturation. Some authors subdivide myositis ossificans into traumatic and non-traumatic forms but this appears to have little if any clinical value. Many examples follow a traumatic incident and are often associated with pain and tenderness. Over a period of 2 to 3 weeks, the soft tissue swelling becomes increasingly localized and mass-like. With further time, the lesion becomes rock hard as true ossification develops. The masses average between 3 and 6 cm in greatest dimension.