Lennart Angervall

A multivariate analysis of the prognosis after surgical treatment of malignant soft-tissue tumors.

Ninety‐seven patients who had received their primary and definitive surgical treatment for a soft‐tissue sarcoma during the years 1956–1976 were studied with respect to local recurrence, metastasis, and survival. The aim of the treatment was to eradicate the tumor while preserving good function. The influence of host and tumor properties and different diagnostic and surgical procedures on the prognosis was studied by means of nonparametric multivariate analysis. Ninety‐four percent of the tumors were located in the extremities. Malignant fibrous histiocytoma was the most common histologic type. A four‐grade scale of histologic malignancy was used. Eighty‐eight percent of the tumors were Grade III or IV. In 85% of the patients with an extremity lesion, local extirpation was carried out. The overall local recurrence rate was 21.7% and in 76 patients who underwent an adequate surgical procedure it was 6.6%. The overall five‐year survival rate was 59%. The survival depended on the local control of the primary tumor, which was related to the adequacy of the surgical procedure and to the histologic grade of malignancy. No patient with a Grade I or II tumor died. The five‐year survival rate for patients with Grade III tumors was 68% and for patients with Grade IV tumors 47%.

Clear-cell sarcoma of tendons and aponeuroses

A clinico-pathological, light microscopic and immunohistochemical study of 15 clear-cell sarcomas, with an ultrastructural analysis of 6 of the tumors, is presented. The tumors showed a strong predilection for tendons and aponeuroses of the extremities in predominantly young and middle-aged people. The clinical setting, course and light microscopic appearance agree well with the original description by Enzinger (1965). Nine of the 15 patients developed metastases, most of them including lymph nodes, and 8 of the patients had died at the time of follow-up (median follow-up time 4.8 years). Reducing pigment was demonstrated within the cells of 2 tumors. Ultrastructurally the 6 tumors studied had a uniform appearance with characteristically rounded or oval tumor cells with a single nucleus containing one or two very prominent nucleoli, a light-staining cytoplasm with a moderate amount of organelles and a variable content of glycogen. Polymorphic melanosomes were seen in the cells of one of the tumors. External laminas enclosed groups of tumor cells and invested parts of individual tumor cells. With immunoperoxidase analysis for S-100 protein positive staining was observed in the vast majority of the tumor cells of all 15 clear-cell sarcomas. Metastases appearing in 9 of the 15 cases showed positive staining for S-100 protein. There was a strong staining of the cytoplasm and generally a weak and varying staining of nuclei. The immunohistochemical and electron microscopic findings indicate that clear-cell sarcoma is a homogenous entity among soft tissue sarcomas, of probable neural crest derivation.

Intermuscular and intramuscular lipomas and hibernomas. A clinical, roentgenologic, histologic, and prognostic study of 46 cases.

A series of 9 intermuscular and 34 intramuscular lipomas, and 1 intermuscular and 2 intramuscular hibernomas is presented. One intramuscular lipoma infiltrated not only muscle but also fascia and tendon. The shoulder region and the thigh were the most common sites of the lipomas. Clinically the tumor appeared in most cases as a painless, fairly soft mass. Dysfunction of the engaged muscle was apparent in only 4 patients. A characteristic change in consistency and form was shown in 14 cases: the tumor being soft and flat when the muscle was relaxed, and becoming firm and more spherical when the muscle was contracted. Some tumors, having developed in a closed fascial space, were firm on palpation even when the muscle involved was relaxed. Radiography was performed in 36 patients with lipoma. In 31 of these the tumor was clearly visible because of its radiotranslucency. Streaks of higher density caused by muscle fiber bundles were seen within the tumor area in some cases. Angiography was performed in 14 patients with lipoma. Usually the tumor appeared poor in vessels in relation to surrounding muscle, and in no patient was increased vascularity, abnormal vessel formation, or early venous filling observed. Microangiography of 2 of the lipomas demonstrated their poor vascular supply in relation to the surrounding muscle. Angiography in 2 patients with hibernoma showed that the tumor was highly vascular with irregular vessels and early venous filling, findings usually held as contributory signs of malignancy in the diagnosis of soft tissue tumors. Microangiographic studies of these hibernomas, earlier reported, also demonstrated their high vascularity. A followup study has shown the benign course of intermuscular and intramuscular lipoma and hibernoma.

Uroepithelial tumors of the renal pelvis associated with abuse of phenacetin‐containing analgesics

This is a review of 62 patients with abuse of phenacetin‐containing drugs and uroepithelial tumors of the renal pelvis. Most of the patients had a pre‐existing nephropathy with papillary necrosis as a prominent feature. Fifty‐six per cent of the patients have died, most of them from the tumor disease, but many were uremic at the time of death. Thus, the co‐existing nephropathy contributed to the poor prognosis. The risk of overlooking an early tumor diagnosis is emphasized. Patients with a known nephropathy with papillary necrosis should be followed continuously, and even the finding of a discrete microscopic hematuria should prompt reinvestigation with radiologic examination of the kidneys. The diagnosis of a uroepithelial tumor of the renal pelvis should always lead to an analysis of the analgesic consumption, besides looking for occupational factors. On the basis of present knowledge of urinary tract carcinogens and phenacetin metabolites it is assumed that phenacetin is the crucial factor for the development of uroepithelial tumors in this study.

Histochemical characterization of mucosubstances in bone and soft tissue tumors

The present investigation endeavors to characterize the mucosubstance content of 170 myxoid and chondromatous tumors and chordomas by histochemical methods. The results obtained using the critical electrolyte concentration (CEC) method as introduced by Scott and co‐workers23,24 were compared with those obtained by staining with alcian blue and toluidine blue at different pHs with and without pretreatment with bovine testicular hyaluronidase. Tissues known biochemically to contain different heteroglycans were used as controls: synovial fluid and cocks comb (hyaluronic acid) stained with alcian blue up to a MgCl2 concentration of 0.1 M; fetal cartilage (chondroitin 4‐ and 6‐sulphate) up to 0.55 M; mast cells (heparin) up to 0.75 M; and adult cartilage and nucleus pulposus with notochordal remnants (keratan sulphate) up to 1.0 M. The staining reaction of intramuscular myxoma and myxoid liposarcoma corresponded to that of synovial fluid and cocks comb (containing hyaluronic acid). Benign chondromatous tumors (osteochondroma, enchondroma, extraskeletal chondroma, chondromatosis in bursae, synovia, and tendon) as well as well‐differentiated chondrosarcomas had a similar staining reaction to that of adult cartilage (containing keratan sulphate). However, the intensity of the reaction was lower in these tumors than in the adult cartilage, indicating that the keratan sulphate content of the tumors is lower. Most of the moderately well‐differentiated chondrosarcomas, the poorly differentiated chondrosarcomas, and pulmonary metastases of chondrosarcoma, as well as mesenchymal chondrosarcoma and extra‐skeletal chondrosarcoma possessed the same staining properties as fetal cartilage, known to contain chondroitin 4‐ and 6‐sulphate but not keratan sulphate. A few of the moderately well‐differentiated chondrosarcomas stained up to a MgCl2 concentration of 1.0 M. Three cases of poorly differentiated chondrosarcomas stained with alcian blue up to 0.35–0.45 M in the lowest differentiated areas, indicating the presence of sulphated heteroglycans, as chondroitin 4‐ and 6‐sulphate. Most chordomas possessed the same staining properties as fetal cartilage; however, a few chordomas stained in the same way as notochordal remnants of nucleus pulposus (containing keratan sulphate), which are thought to be the origin of these tumors. The results of staining of the tumors in the present series with the Scott technique corresponds well with toluidine blue and alcian blue at different pHs with and without pretreatment of the sections with testicular hyaluronidase. Since bone and soft tissue tumors may contain varying mucosubstances depending on the tissue of origin and on differentiation, histochemical investigation of the heteroglycan content of these tumors may be a valuable diagnostic aid.

Leiomyosarcomas of venous origin in the extremities. A correlated clinical, roentgenologic, and morphologic study with diagnostic and surgical implications

This article presents a correlated clinical, roentgenologic, and morphologic study of six cases of leiomyosarcoma of large veins in the extremities. Growth of the tumor within the lumen of the affected vein was demonstrated by phlebography in one case and by angiography and computed tomography in one case. In all six cases, such growth was demonstrated by dissection of the surgical specimen. In four cases, arteriography showed both neovascularity at the site of the lesion and compression of the artery accompanying the affected vein. The compression apparently was caused by entrapment of the artery within the same preformed fibrous sheath (conjunctiva vasorum) that enclosed the tumor and the vein from which it had arisen. The histologic diagnosis was based on the light microscopic appearance in all cases and was supported by electron microscopic findings in three cases by the demonstration of ultrastrucctural features of leiomyoblasts. All six tumors were light microscopically of high‐grade malignancy. Five of the patients died of metastatic tumor disease and one is alive with lung metastases. The information obtained by a careful physical examination combined with phlebography, arteriography, and computed tomography may be helpful in the clinical diagnosis and the planning of adequate surgical treatment.

Cellular schwannoma : a clinicopathologic study of 29 cases

A series of 29 cellular schwannomas is described in terms of their clinical presentation and course, light and electron-microscopic appearance, immunohistochemical properties and cytogenetics. The study indicates that cellular schwannoma can be defined as a subtype of classical schwannoma, characterized by spindle cells forming a compact fascicular, sometimes fibrosarcoma-like growth pattern, a low mitotic activity, a generally moderate nuclear and cellular polymorphism and a high degree of Schwann cell differentiation as seen by electron microscopy and immunohistochemistry. The tumour is characteristically located close to the vertebral column, in the mediastinum or retroperitoneum and has a benign course. Occasionally bone destruction and neurological symptoms develop. The clinical appearance together with the high cellularity, fascicular pattern and mitotic activity had led to the erroneous diagnosis of a soft tissue sarcoma in a few cases, and cellular schwannoma may thus be considered to be a pseudosarcoma. Immunohistochemically, cellular schwannomas appear to deviate from classical schwannomas and malignant peripheral nerve sheath tumours by their expression of glial fibrillary acidic protein. The chromosome analysis revealed a normal diploid stemline karyotype, with a variety of abnormal clones, including one with monosomy 22.

Dermal nerve sheath myxoma: A light and electron microscopic, histochemical and immunohistochemical study

Two cases of dermal nerve sheath myxoma have been examined by light and electron microscopy, and by immunohistochemical and histochemical methods. The nomenclature of this tumor has been debated, and the histogenesis unsettled. Light microscopically, the lobulated myxoid tumors were generally composed of spindle‐shaped and stellate tumor cells in an abundant matrix of mucosubstances. Ultrastructural features indicated an origin from the peripheral nerve sheath; among the pertinent findings were a single or duplicated external lamina investing the cells, desmosome‐like junctions, cytoplasmic microfilaments and myelin figures, and interdigitating cytoplasmic processes. S‐100 protein was demonstrated by means of the immunoperoxidase technique within both tumors, further supporting this origin. The histochemical analysis of the mucosubstance showed the presence of sulphated glucosaminoglycans. The name dermal nerve sheath myxoma, suggested by Harkin and Reed, is recommended.

Epithelioid malignant schwannoma

We report a light and electron microscopic, immunohistochemical, clinical and prognostic study of 14 patients with epithelioid malignant schwannoma. In 8 patients the tumour involved a major nerve. The tumours were rather small in most instances, the largest diameter being less than 5 cm in 7 cases. Light microscopically, they showed highly cellular areas of epithelioid, polygonal or rounded cells characteristically forming cords and rows and arranged in nodules of varying size. Spindle cell sarcoma areas as in classical malignant schwannoma were seen in 9 cases, and neurofibromatous areas in one case. Four cases were entirely epithelioid in appearance. Electron microscopically the epithelioid tumour cells showed nuclei with mostly even contours containing one or two trabecular or reticular nucleoli, cytoplasmic projections, intra-cytoplasmic myelin-like figures, intercellular junctions and discontinuous, sometimes multilayered external lamina material. The ultrastructural findings indicate that epithelioid malignant schwannoma is a tumour of neural crest derivation having features of Schwann cell differentiation. Immunohistochemically, S-100 protein was demonstrated in 7 tumours and neuron specific enolase in 3. There was a female predominance, 9/14, and a median age of 38.5 years (range 17-74). The extremities, including the hip and shoulder regions, were the most common sites, 12/14. The tumour proved highly malignant; 9 of 14 patients were dead at the time of follow-up and a high incidence of metastasis (7 of 14) was observed.

Hemangiopericytoma. A clinicopathologic, angiographic and microangiographic study

A clinicopathologic study of 11 hemangiopericytomas is reported, and the results of clinical angiography in 4 patients and a correlated microangiographic‐histologic study of 1 tumor are presented. Six of the tumors were collected and accepted as hemangiopericytomas in a review of 42 tumors registered as hemangiopericytoma in the Swedish Cancer Registry during the period 1958‐1968. The other 5 tumors occurred in patients treated by us. The histologic examination and the follow‐up information showed that it can be difficult to predict the prognosis on morphologic grounds, that borderline tumors exist and that a recurrence as well as a metastasis may dedifferentiate. The tumors studied by clinical angiography all proved to be highly vascular. Irregular vessels of varying caliber were filled with contrast medium and, in addition, a prominent diffuse opacification took place. Early filling of veins was not noted despite the high vascularity. The correlated microangiographic‐histologic study suggests that the irregular vessels seen on clinical angiograms corresponded to wide, angulated, thin‐walled vessels without muscle coat or elastic tissue, while the diffuse opacification was caused by a dense network of delicate, branching, slit‐like capillary spaces. Cancer 42:2412–2427, 1978.