Franz M. Enzinger

Malignant fibrous histiocytoma. An Analysis of 200 Cases

The clinicopathologic findings in 200 cases of malignant fibrous histiocytoma (MFH) with follow‐up information are presented. This tumor occurred principally as a mass on an extremity (lower extremity 49%, upper extremity 19%) or in the abdominal cavity or retroperitoneum (16%) of adults (peak incidence 61–70 years of age). It typically involved deep fascia (19%) or skeletal muscle (59%) and only rarely was confined to the subcutis without fascial involvement (7%). The MFH had variable morphologic features and frequently showed transitions from areas having a highly ordered storiform pattern to less differentiated areas having a pleomorphic appearance. The rate of local recurrence of the tumor was 44%, and of metastasis, 42%. Metastasis was most frequently to the lung (82%) and lymph nodes (32%). Factors that influenced the rate of metastasis included depth, size, and inflammatory component of the tumor. Tumors that were small, superficially located, or had a prominent inflammatory component metastasized less frequently than larger, more deeply located tumors. In our experience the MFH is the most common soft tissue sarcoma of late adult life, and many tumors previously diagnosed as pleomorphic variants of liposarcoma, fibrosarcoma, or rhabdomyosarcoma are probably examples of MFH. Although the histogenesis of this neoplasm remains controversial, we feel it is best regarded as a primitive and pleomorphic sarcoma showing partial fibroblastic and histiocytic differentiation, as reflected by collagen production and occasional phagocytosis.

Epithelioid hemangioendothelioma a vascular tumor often mistaken for a carcinoma

Epithelioid hemangioendothelioma is a unique tumor of adult life which is characterized by an “epithelioid” or “histiocytoid” endothelial cell. Forty‐one cases of this rare tumor have been recognized at the Armed Forces Institute of Pathology. They may occur in either superficial or deep soft tissue, and in 26 cases appeared to arise from a vessel, usually a medium‐sized or large vein. They are composed of rounded or slightly spindled eosinophilic endothelial cells with rounded nuclei and prominent cytoplasmic vacuolization. The latter feature probably represents primitive lumen formation by a single cell. The cells grow in small nests or cords and only focally line well‐formed vascular channels. The pattern of solid growth and the epithelioid appearance of the endothelium frequently leads to the mistaken diagnosis of metastatic carcinoma. The tumor can be distinguished from a carcinoma by the lack of pleomorphism and mitotic activity in most instances and by the presence of focal vascular channels. Ultrastructural study in four cases confirmed the endothelial nature of the tumor in demonstrating cells surrounded by basal lamina, dotted with surface pinocytotic vesicles, and occassionally containing Weibel‐Palade bodies. Follow‐up information in 31 cases indicated that 20 patients were alive and well following therapy; three developed local recurrences and six metastases. It is suggested the term epithelioid hemangioendothelioma be used to designate these biologically “borderline” neoplasms. The significance of the epithelioid endothelial cell is not entirely clear. Since it may be observed in both benign and malignant vascular lesions, its presence alone does not define a clinicopathologic entity.

Hemangiopericytoma: An analysis of 106 cases*

A series of 106 cases of hemangiopericytoma was analyzed. The neoplasms occurred principally in adults (median age, 45 years), were deep seated, and were most common in the thigh (27 cases) and the pelvic retroperitoneum (26 cases). A painless mass was the first symptom in 96 of the patients. The median size of the excised tumors was 6.5 cm. Surgical removal of the tumor was often complicated by hemorrhage because of marked dilatation of the vascular bed in the vicinity of the neoplasm, probably as the result of rapid exchange of blood from the arterial to the venous circulation within the tumor. Microscopically, benign and malignant forms could be distinguished. The latter were characterized by increased cellularity, prominent mitotic activity, and foci of necrosis or hemorrhage. Follow-up information was obtained in 93 cases. Seventy-one of the 93 patients were living (two with recurrence and four with metastasis), and 22 had died (13 as the result of recurrence or metastasis in more than two-thirds of the related causes). Recurrence preceded metastasis in more than two-thirds of the patients with evidence of metastasis. The 10 year survival rate was 70 per cent. The morphologic differences from other mesenchymal tumors showing a hemangiopericytoma-like vascular pattern are discussed, and the close resemblance of hemangiopericytoma to richly vascular forms of fibrous histiocytomas and synovial sarcoma is emphasized. Congenital or infantile hemangiopericytoma is described as a separate entity having a distinctive microscopic pattern and behavior.

Epithelioid sarcoma. A sarcoma simulating a granuloma or a carcinoma

This article reviews the pathologic features and the behavior of 62 cases of a peculiar form of sarcoma that has repeatedly been confused with a chronic inflammatory processa necrotizing granulomaand a squamous cell carcinoma. The tumor occurs chiefly in young adults (median age 23 years) and most commonly affects the soft tissues of the handthe forearmand the pretibial region. It tends to grow in a nodular or multinodular manner along fascial structures and tendonsoften with central necrosis of the tumor nodules and ulceration of the overlying skin. Most of the tumors grow slowlyand many of our cases had been present for months or years prior to surgery. Microscopicallythe tumor consists of irregular nodular masses of largedeeply acidophilic polygonal cells merging with spindle cellsfrequently associated with large amounts of hyalinized collagen. Follow‐up information on 54 patients (87%) revealed slowrelentless clinical course with frequent recurrence (85%) and late metastasis (30%). Cure may be achieved by wide local excision at early stage of disease.

Epithelioid sarcoma: diagnosis, prognostic indicators, and treatment

A retrospective review of 241 cases of epithelioid sarcoma reaffirmed the propensity of this tumor to occur in the distal extremities of young adults. The tumor was generally firm and nontender, and involved the dermis, subcutis or deeper soft tissues, particularly fascial planes, aponeuroses, and tendon sheaths. Follow-up data, available in 202 cases (84%), showed a 77% recurrence and a 45% metastatic rate. The most common initial sites of metastasis were lymph nodes (48%) and lungs (25%). A more aggressive course was associated with a proximal or axial tumor location, increased size and depth, hemorrhage, mitotic figures, necrosis, or the presence of vascular invasion. More favorable behavior was observed when the tumor arose in younger individuals, in distal extremities, or in females between the ages of 10 and 49. (The last observation calls for further work with steroid receptors.) Radical excision or amputation still appears to be the initial treatment of choice, though adjunctive high-dose radiotherapy to the excision site may prove to be of additional value.

Extraskeletal neoplasm resembling Ewing's sarcoma

This article reviews the pathologic features and the behavior of 39 small, round, or oval cell sarcomas occurring in the soft tissues and considered histologically indistinguishable from Ewings sarcoma of bone. The tumors affected chiefly young adults (median age 20 years) and most commonly involved the soft tissues of the lower extremity and the paravertebral region. Microscopically, they consisted of solidly packed small, round, or ovoid cells of great uniformity, arranged in sheets or lobules separated by strands of fibrous connective tissue. The nucleus of the tumor cells contained finely divided chromatin, a distinct nuclear membrane, and frequently a minute nucleolus. The scanty ill‐defined cytoplasm contained varying amounts of glycogen. Sometimes the histologic picture was dominated by a “peritheliomatous” pattern, or by large areas of necrosis or hemorrhage. Followup data ranging from 1 month to 14 years were available in 35 of the 39 cases (93%). Of these, 13 were alive and 22 had died. In the majority of the fatal cases, the clinical course was rapid; metastatic lesions developed within a few months after the primary tumor was excised. The lungs and the skeleton were the two most common sites of metastasis. Cure may be achieved by wide local excision of the tumor at an early stage of the disease, combined with radiation therapy and chemotherapy.

Inflammatory fibrosarcoma of the mesentery and retroperitoneum: A tumor closely simulating inflammatory pseudotumor

We report 38 cases of inflammatory fibrosarcoma occurring in 23 females and 15 males, 2 months to 74 years of age (median, 8.5 years; mean, 15 years) with symptoms of abdominal pain (17 cases), anemia (21 cases), fever (14 cases), mass (16 cases), and gastrointestinal obstruction (7 cases). Primary tumor sites included mesentery and retroperitoneum (31 cases), omentum (two cases), mediastinum (two cases), liver (one case), diaphragm (one case), and abdominal wall (one case). Sizes ranged from 2.4 cm to 20 cm (mean, 9.6 cm). Follow-up data in 27 cases revealed local recurrences in 10 patients, with multiple local recurrences in three and histologically proven distant metastases to lung (two cases) and brain (one case). Five patients died from their disease (median, 20 months). All tumors, including metastases, consisted of fibroblasts, myofibroblasts, and plasma cells, with variable degrees of fibrosis and calcification. Immunostains indicate myofibroblastic differentiation; 18 of 20 (90%) stained for actin, 15 of 18 (83%) for vimentin, and 10 of 13 (77%) for keratin (primarily in a submesothelial location). Ultrastructural studies also disclosed myofibroblastic features. The locally aggressive, recurrent nature of these neoplasms, as well as the occurrence of metastases and tumor deaths, indicate that they are potentially malignant neoplasms that we believe are better classified as inflammatory fibrosarcomas, not as cellular inflammatory pseudotumors.

Extraskeletal myxoid chondrosarcoma: An analysis of 34 cases

Abstract Myxoid chondrosarcoma arising from extraskeletal soft tissues is a comparatively rare neoplasm characterized by ill defined nodular masses composed of cords and strands of small acidophilic cells separated by abundant mucoid stroma. Cartilaginous origin of the cells is suggested by their close resemblance to developing chondroblasts, the staining reactions of the mucoid ground substance indicating the presence of large amounts of sulfated mucopolysaccharides, and the electron microscopic findings. All 34 tumors of this series occurred in the extremities; 24 involved muscle tissue or were intimately attached to tendons or ligaments. Their size ranged from 1.5 to 23 cm. The ages of the patients ranged from 13 to 89 years, with a mean of 49 years. Recognition of this tumor and clear distinction from chondrosarcoma of bone are of particular importance because of the difference in behavior. Of the 31 patients with follow-up information, 11 had died—four of metastatic neoplasms and seven of unrelated intercurrent disease. Twenty were alive, but during the follow-up period four of the living patients developed recurrences; one, metastasis; and two, recurrence and metastasis. It is remarkable that all three living patients with metastasis were still alive 10, 12, and 20 years after the initial surgery.

Malignant melanoma of soft parts. A reassessment of clear cell sarcoma.

A retrospective study of 141 cases of clear cell sarcoma of tendons and aponeuroses revealed that the tumor occurred predominantly in young patients between 15 and 35 years of age, was slightly more common in female than in male patients, and originated chiefly from tendons, aponeuroses, and fascial structures of the extremities with a predilection for the feet and knees. The tumor presented as an insidiously growing mass causing pain or tenderness in slightly more than half of the patients. The preoperative duration of symptoms varied greatly, and in 29 cases the time interval between discovery of the tumor and operation exceeded 5 years. Microscopically, the tumors valried little in appearance and were composed of short fascicles of fusiform cells with a clear to granular eosinophilic cytoplasm, vesicular nuclci with prominent nucleoli, and occasional multinucleated giant cells. Melanin was demonstrated in 72% of the 92 tumors in which the Fontana or Warthin-Starry preparation for melanin was performed. S-100 Protein, a neuroectodermal marker, was positive in 13 of 19 cases. Follow-up information was available in 115 patients. Thirty-four(29.6%) were alive and well with no evidence of recurrence. Twenty-four (20.9%) patients were alive with one or two recurrences, three (2.6%) were alive following pulmonary lobectomy for metastatic sarcoma, and one was alive with metastasis in the thoracic spine. Fifty-three of the 115 Patients with follow-up information had died, 50 from metastatic tumor and three from miscellaneous causes. The prevailing sites of metastasis were the lung and the regional lymph nodes. The exact histogenesis remains obseure, but the presence of intracellular melanin in two-thirds of the cases supports origin from migrated neural crest cells with the capacity for producing melanin. For this reason the term, malignant melanoma of soft parts, seems preferable over the purely descriptive term of clear cell sarcoma.

Postradiation soft tissue sarcomas: An analysis of 53 cases

The clinicopathologic features of 53 cases of postradiation soft tissue sarcoma (PRS) were correlated with the physical characteristics of the administered radiation. All but three patients received radiation for malignant processes. Of the secondary sarcomas, malignant fibrous histiocytoma (MFH) accounted for 36 cases (68%), followed by seven extraskeletal osteosarcomas (13%), six fibrosarcomas (11%), two malignant Schwannomas (4%), one extraskeletal chondrosarcoma, and one angiosarcoma. The sex incidence, age of the patient at time of diagnosis, and location of the PRS correlated only with the clinical characteristics of the initial treated condition. The latency period (mean 10 years) showed an indefinite relationship to patient survival but no definite relationship to the patients age at the time of the initial radiation. There was no difference between patients treated with megavoltage radiation (39 patients) and with orthovoltage radiation (seven patients) in the type of sarcoma, location, or survival, although the orthovoltage group received a lower mean radiation dose (3880 rads) than the megavoltage group (4446 rads). Megavoltage radiation, however, produced deeper tissue radiation changes and was associated with a shorter latency period. Most PRS were poorly differentiated, produced abundant collagen, and had a dismal prognosis.