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TUMORS OF THE SOFT TISSUES Arthur Purdy Stout, M. D. ARMED FORCES INSTITUTE OF PATHOLOGY

ATLAS OF TUMOR PATHOLOGY Section II—Fascicle 5 TUMORS OF THE SOFT TISSUES by Arthur Purely Stout, M. D. Professor of Pathology Columbia University, College of Physicians and Surgeons New York City Published by the ARMED FORCES INSTITUTE OF PATHOLOGY Under the Auspices of the SUBCOMMITTEE ON ONCOLOGY of the COMMITTEE ON PATHOLOGY of the NATIONAL RESEARCH COUNCIL Washington, D. C. 1953 For sale by the American Registry of Pathology Armed Forces Institute oi Pathology Washington, 25, D. C.-Price $2.00

f ATLAS OF TUMOR PATHOLOGY Sponsored and Supported by AMERICAN CANCER SOCIETY ANNA FULLER FUND ARMED FORCES INSTITUTE OF PATHOLOGY JANE COFFIN CHILDS MEMORIAL FUND FOR MEDICAL RESEARCH NATIONAL CANCER INSTITUTE, U.S. PUBLIC HEALTH SERVICE UNITED STATES VETERANS ADMINISTRATION

Tumors of the Soft Tissues ACKNOWLEDGMENTS The author acknowledges with gratitude the helpful suggestions oi his iriend, Dr. Pierre Masson, Professor of Pathology of the University of Montreal, who kindly consented to ad as special critic of this fascicle. The photomicrographic illustrations in this fascicle have been made by Mr. Walter I. O'Neill, Photographer of the Department of Surgery, Columbia University, with the exception of plate II-A, which was taken by Dr. Raffaele Lattes, Professor of Surgery, Columbia University. The tissue cultures were all prepared and interpreted by Dr. Margaret R. Murray, Assistant Professor of Surgery and Director of the Tissue Culture Division of the Laboratory of Surgical Pathology, Columbia University. Dr. E. B. Powell and Dr. A. J. Cracovaner have kindly given permission for the use of illustrations which were used in previous publications. Figure 70 was obtained through the courtesy of Dr. A. H. Davis, Peterson General Hospital, Paterson, N. J. Permission to use copyrighted illustrations has been granted by: Francis Carter Wood, M. D., Editor: Am. J. Cancer, 24:255-272, 1935. For our figures 32, 33, 34. 29:435-469, 1937. For our figure 17. American Association of Pathologists and Bacteriologists: Am. J. Path., 18:183-203, 1942. For our figure 31. 19:751-763, 1943. For our figures 53-B, 54. J. B. Lippincott Co.: Ann. Surg., 118:445-464, 1943. For our figures 27, 61, 62. 119:86-107,1944. For our figures 49,50, 51,52, 53-A. 120:826-842,1944. For our figures 71. 72,73. 120:843-851, 1944. For our figure 74. 121:361-372, 1945. For our figure 60. 123:447-472, 1946. For our figures 56, 58. 124:218-227, 1946. For our figure 22. 127:278-290, 1948. For our figure 75. American Medical Association: Arch. Path., 34:951-964, 1942. For our figure 77. 42:517-524, 1946. For our figure 20, Paul B. Hoeber, Ine.: Cancer, 2:1027-1054, 1949. For our figure 63.

Tumors of fhe Soff Tissues Missouri State Medical Association: J. Missouri M. A., 44:329-334,1947. For our figures 51-8.67,78. 44:674-682, 1947. For our figure 76. 46:275-277, 1949. For our figure 68. The Laryngoscope: Laryngoscope, 45:891-893, 1935. For our figure 23. Franklin H. Martin Memorial Foundation: Surg., Gynee. and Obst., 76:315-318,1943. For our figure 21. State Medical Association of Texas: Texas State J. Med., 41:582-583, 1946. For our figure 55. All illustrations are the author's own unless otherwise acknowledged. The A. F. I. P. accession numbers are for identification of negatives at the Armed Forces Institute of Pathology. • Arthur Purdy Stout

Tumors of the Soft Tissues TUMORS OF THE SOFT TISSUES TABLE OF CONTENTS Page No. INTRODUCTION 9 Table I 12 Table II 13 BENIGN TUMORS AND TUMOR-LIKE PROLIFERATIONS 15 Fibromatoses 15 Fibroma Durum 15 Figs. 1, 2 Fibroma Molle 15 Nonmetastasizing Fibrosarcomas 15 Desmoid Tumor 15 Plate I-A Keloid 18 Plate I-D Cicatricial Fibromatosis •. . . . 18 Palmar Fibromatosis (fibroma or pseudotumor of Dupuytren's contracture) 18 Plantar Fibromatosis 18 Fig. 3, Plate I-E Penile Fibromatosis (Peyronie's disease) 18 Fibromatosis Colli (congenital wry neck) 18 Fig. 4 Progressive Myositis Fibrosa (hereditary polyfibromatosis) . . 18 Irradiation Fibromatosis 19 Myxomatoses 19 Ganglion 19 Plate I-F Localized Myxedema 23 Figs. 5, 6 Xanthomatoses 23 Xanthoma Diabeticorum 23 Multiple Xanthomatous Giant Cell Tumors 23 Fig. 7 Xanthelasma 23 Fibrous Xanthoma 23 Fig. 8, Plate I-B, C Sclerosing hemangioma 28 Figs. 9, 10 F5-5

Tumors of fhe Soff Tissues BENIGN TUMORS AND TUMOR-LIKE PROLIFERATIONS—Continued Xanthomatoses—Continued Page No. Xanthogranuloma 28 Fig. 11 Giant Cell Tumor. 28 Figs. 12, 13, Plate II-B Eosinophilic granuloma 29 Histiocytoma 29 Fat Necrosis 29 Lipomatoses 29 Lipoma 29 Fig. 15 Multiple Lipomas 29 Multiple Symmetrical Lipomatosis 29 Fig. 14 Lipoma Dolorosa 29 Lipoma Arborescens 35 Fig. 16 Myelolipoma 35 Myxolipoma, lipomyxoma, myxotibrolipoma, etc. 35 Hibemoma 35 Plate II-A Benign Tumors of Muscle 38 Leiomyoma . . . 38 Superficial Leiomyomas 38 Vascular Leiomyomas 38 Figs. 17-19 Rhabdomyoma 39 Granular Cell Myoblastoma 39 Figs. 20, 22, 23, Plate II-C, D Benign Angiomatoses 46 Hemangiomatoses 46 Capillary Hemangioma 47 Fig. 24 Cavernous Hemangioma 47 Capillary Hemangioma, Granuloma Type (granuloma pyo- genicum) 47 Fig. 25 Venous Hemangioma 47 Fig. 26, Plate II-E, F Benign Hemangioendothelioma (or infantile hemangioendo- thelioma) 47 Fig. 27

Tumors of the Soft Tissues ' ' BENIGN TUMORS AND TUMOR-LIKE PROLIFERATIONS Continued Benign Angiomatoses—Continued Hemangiomatoses— Continued Page No. Benign Hemangiopericytoma 47 Fig. 28 Glomus Tumor -4? Figs. 29-34 Cirsoid Aneurysm 56 Venous Racemose Aneurysm 56 Diffuse Angiomatosis 56 Lymphangioma , 56 Lymphatic Cysts 57 Cystic hygroma (hygroma cysticum colli) 57 Figs. 35, 36 Other Benign Tumors 57 Benign Tumors Composed of Cartilage or Bone 57 Osteoma, Osteochondroma, Chondroma 57 Solitary Myositis Ossificans 57 Fig. 37 Progressive Myositis Ossificans 60 Benign Synovioma 60 Fig. 38 Mixed Tumor 60 Fig. 39 Benign Mesenchymoma 61 Benign Mesothelioma 61 Benign Mesothelioma of the Genital Tract 61 Fig. 40 Benign Solitary Fibrous Mesothelioma 64 Benign Diffuse Fibrous Mesothelioma 64 Blue Nevus 64 MALIGNANT TUMORS OF THE SOFT TISSUES 69 Fibrosarcoma 69 Figs. 44-47, Plate III-A Dermatofibrosarcoma Protuberans of Hoffmann 78 Figs. 41-43 Progressive and Recurring Dermatofibroma of Darier .... 78 Myxoma 78 Fig. 48, Plate III-B, C Liposarcoma 79 Differentiated Liposarcoma 81 Fig. 49 F5-7

Tumors of the Soft Tissues MALIGNANT TUMORS OF THE SOFT TISSUES—Continued Liposarcoma—Continued Page No. Undifferentiated Liposarcoma 81 Figs. 50-54, Plate IV-A, B Malignant Tumors of Muscle 88 Leiornyosarcorna 88 Fig. 55 Rhabdomyosarcoma.' 89 Figs. 56-59, Plate V-A Malignant Granular Cell Mybblastoma 98 Figs. 60, 21 Angiosarcomatoses 99 Malignant Hemangioendothelioma 99 Figs. 61, 62 Malignant Hemangiopericytoma 101 Fig. 63 Kaposi,s Sarcoma 106 Figs. 64, 65 Lymphangiosarcoma 106 Malignant Lymphoid and Reticuloendothelial Tumors 107 Lymphosarcoma 107 Giant Follicle Lymphosarcoma 107 Lymphocytic Cell Lymphosarcoma 107 Reticulum Cell Lymphosarcoma 107 Reticulum Cell Sarcoma 107 Figs. 66, 67 Mycosis Fungoides . . f 110 Plasma Cell Tumor 110 Fig. 68 Other Malignant Tumors 110 Osteogenic Sarcoma and Chondrosarcoma 110 Figs. 69, 70 Synovial Sarcoma Ill Figs. 71-74, Plate V-B Malignant Mesenchymoma 118 Fig. 75, Plate VI-A, B Malignant Mesothelioma 119 Figs. 76, 77 Melanosarcoma (?) 121 Fig. 78 DIAGNOSIS AND TREATMENT 126 REFERENCES. 128 F5-8

Tumors of the Soft Tissues TUMORS OF THE SOFT TISSUES • INTRODUCTION In order that one may understand the tumors that arise in the soft tissues of the body, it is necessary to take cognizance of certain facts. !f the tumors of the epidermis and the ectodermal structures of the skin and those of the lymph nodes are excluded, all of the neoplasms develop from two primitive sources: the mesoderm and the neurectodermal tissues of the peripheral nervous system. From the primitive mesenchyme come the supportive and reticulo- endothelial tissues and their corresponaing tumors, and from the neurectoderm come the schwannian sheath, possibly the endoneurium, and conceivably the perineurium, which in turn form the prototypes of most of the tumors of the peripheral nerves. If the various tumors developing from these tissues repro- duced their prototypic tissues in pure form, albeit in various stages of differen- tiation, recognition would be relatively simple. Unfortunately this is not always the case, and it is these aberrations which result in the formation of the meta- typical conglomerations that are so difficult to recognize. It is well known that the repair which follows injury takes place by the proliferation of fibroblastic cells primarily, accompanied by endothelial proliferations forming capillaries. No other tissues with the exception of Schwann cells reproduce themselves with the same facility. It need not surprise us, therefore, to find that many tumors, especially the malignant ones, show a tendency in greater or less degree to produce fibroblastic elements. This may be carried to such an extent that these transformed areas are histologically indistinguishable from fibrosarcomas; or the metaplasia may be incomplete so that, for example. lipoblasts, leiomyoblasts, or rhabdomyoblasts may retain their distinguishing characteristics while at the same time acting as fibroblasts and producing connective tissue fibers. Indeed in one tumor, the synovial sarcoma, this is invariably the case. It is always made up of two elements inextricably intermingled. This tendency to form multiple tissues is sometimes carried much further, so that one tumor may be compounded of several more or less differentiated tissues without the predominance of any one type. In this fashion is produced the mixed mesodermal tumor or mesenchymoma, which is seen in both benign and malignant examples. The best known benign form consists of an admix- ture of adult fat, blood vessels, and smooth muscle in varying quantities. Malignant mesenchymomas may have an admixture of as many as five F5-9

Tumors of the Soft Tissues different cellular types in the same tumor. The combinations formed are almost endless and no two of these strange tumors are ever exactly alike. Inevitably one is reminded of mixed tumprs and teratomas in which are found admixtures of both epithelium and tissues resembling the derivatives of the mesenchyme. These latter develop in certain definite situations such as the salivary glands, the male and female genitourinary systems, and the breast; and in regions where congenital malformations of development are apt to occur, such as the sacral region. The mesenchymomas may be found in these areas, but they also develop in other situations such as the thigh, where teratomas are unknown. One might expect that tumors of certain types would arise in areas where corresponding varieties of tissue are normally found, but this is by no means necessarily the rule. It seems to hold for tumors of schwannian and other neurectodermal cells; and of course since connective tissue, fat, and vascular elements including smooth muscle are almost universal, there need be no surprise if tumors composed of their cells are encountered almost anywhere. On the other hand, striated muscle, bone, and cartilage are restricted in their distribution; yet malignant tumors composed of rhabdomyoblasts, osteoblasts, and chondroblasts in pure or compound form can develop in situations where normally such tissues are never found. While the ordinary hematoxylin and eosin stain properly carried out after good fixation will suffice to permit recognition of many of these tumors if one is thoroughly familiar with their vagaries of growth, it will not do for all and must be supplemented in some cases by differential fiber stains, adequate silver reticulin impregnations, and stains for special substances like lipoid, mucoid or hyaluronic acid, hemosiderin, melanin, elastic tissue, amyloid, and nerve fibers. If in addition one can call upon the aid of tissue culture, obscure tumors can sometimes be elucidated, because in most instances, no matter how anaplastic, explanted tumor cells will grow in vitro with sufficient resem- blance to their normal prototypes to permit recognition. At the present time this aid is not available in most laboratories, and there are very few individuals capable of the proper interpretation of differential tissue growth. Even with all our knowledge about tumor cells and their growth in vivo and in vitro, there are still a few tumors which can be recognized and named, the exact nature of which remains obscure. Prominent among these is the tumor originally called myoblastic myoma but now better known as the granu- lar cell myoblastoma or myoma. This was originally believed to be a myoblastic tumor. Considerable doubt arose as to the truth of this assumption, because embryonal myoblasts do not have granules in them, and because the tumor sometimes grows in places where striated muscle is never found. It has been suggested that these are tumors of histiocytes (Martin), of granular cell fibroblasts (Pearse), that they are tumors induced by parasites (Gullino), that they are tumors of Schwann cells (Fust and Custer), that some of them are paragangliomas F5-10

Tumors of the Soft Tissues (Smetana and Scott), and that they are forms of granular myolysis of muscle and not tumors at all (Roffo). Tissue culture has shown that the cellular outgrowth in vitro most nearly resembles striated muscle but does not account for the intracellular granules, so that the tumor's exact nature remains a mystery. The failure properly to label the soft tissue tumors, especially the malignant ones, has led to a great deal of confusion regarding the distribution, relative • frequency, and relative malignancy of many of them. This has been largely responsible for the fact that mesenchymal tumors of the soft tissues of the extremities, especially the malignant ones, are the least understood and probably the most inadequately treated of all tumors. While the rumors of bone, bone marrow, and peripheral nerves will not be dealt with in detail in this fascicle because there are separate fascicles devoted to them, it should be remembered that the nerve tumors grow in the soft tissues, and certain tumors of bone, notably the fibrosarcoma of the periosteum and Swing's sarcoma, secondarily invade and may form larger tumor masses in the soft tissues than in their tissue of origin. If one is quite familiar with the usual distribution, relative frequency, and gross growth characteristics of the soft tissue tumors, it is sometimes possible to make a more or less accurate diagnosis on physical examination alone: The surface hemangiomas are familiar to all and the deep hemangiomas or benign vascular mesenchymomas involving muscle often contain phleboliths, which give a characteristic roentgenogram; lipomas of the skin forming pedun- culated growths, and lipomas of the subcutaneous tissues forming soft, diffuse, and sometimes multiple masses are generally identifiable; the slow-growing multinodular so-called dermatofibrosarcoma protuberans has an appearance not often assumed by other tumors; if a tumor is deep, bulky, and nodular, often it proves to be a liposarcoma; if it starts deeply and grows into the skin producing a projecting, dark red, fungating mass, it may be a rhabdomyosarcoma; if it produces a fusiform swelling, movable from side to side but not in the long axis of the extremity, it is apt to be a nerve sheath tumor, whether or not there is any interference with function or sensation; and if it is a subungual lesion producing attacks of paroxysmal pain, it will almost surely prove to be a glomus tumor. But these examples and a few others that can be added to them cover a relatively small proportion of the soft tissue tumors; and even the examples given in most instances may be imitated by something else, so that in a vast majority of instances, indeed it would be safer to say in all cases, accurate diagnosis depends upon histologic examination. In order to give a comprehensive picture of the neoplasms of the soft tissues, it will be necessary to enumerate not only the malignant and benign neoplasms but also the tumor-like lesions about which there is some uncertainty as to whether or not they are neoplasms. In each instance a succinct note will describe the important facts concerning each lesion. It is difficult to know F5-11

Tumors of the Soft Tissues Table I 7,337 BENIGN MESENCHYMAL TUMORS* Surgical Pathology Laboratory, Columbia University Feb. 1, 1906—Sept. 1, 1951 Tumors Number of tumors in subgroupings Total number of tumors Fibromatoses 1,596 Fibromas 1 144 Keloids 390 Desmoids 19 Cases of Peyronie's Disease Cases of Palmar and Plantar Fibro- matoses . . 0 31 Cases of Fibromatosis Colli Cases of Progressive Myositis Fibrosa . Benign Myxomatoses 5 7 646 Ganglions ... 643 Cases of Localized Myxedema .... 3 Xanthomatoses 783 Xanthomas and Xanthelasmas .... Multiple Xanthomatoses Fibrous Xanthomas** 189 9 187 Xanthogranulomas . ... ... 17 Histiocytomas . . 9 Giant Cell Tumors 322 Fat Necrosis Tumors*** 50 Lipomatoses ****2,411 Benign Myomatoses ... 338 Leiomyomas ..... 217 Rhabdomyomas . . 1 Granular Cell Myoblastomas .... Benign Angiomatoses 120 1,236 Hemangiomas 885 Hemangiomatoses 34 Cirsoid Aneurysms -. . . . 6 Venous Racemose Aneurysms .... Benign Hemangioendotheliomas . . . Benign Hemangiopericytomas .... Glomus Tumors 9 41 74 83 Lymphangiomas . ... 104 Benign Tumors of Bone and Cartilage . . Osteomas 76 123 Osteochondromas Chondromas 9 6 Cases of Myositis Ossincans Cases of Myositis Ossificans Progres- sive 23 9 *A11 skeletal tumors, all benign lymphomas, and leiomyoma of uterus are omitted. "Includes sclerosing hemangiomas. '"So-called traumatic fat necrosis. ""Includes 6 cases of hibernoma. F5-12

Tumors of the Soft Tissues 7,337 BENIGN MESENCHYMAL TUMORS—Continued Tumors Number of tumors in subgroupi ngs Total number of tumors Benign Synoviomas 2 Mixed Tumors of Skin 21 Benign Mesenchymomas 48 Benign Mesotheliomas 58 Blue Nevi 75 Total ' 7,337 Table II 1,349 MALIGNANT MESENCHYMAL TUMORS* Surgical Pathology Laboratory.Columbia University Feb. 1, 1906 Sept. 1, 1951 Tumors Number of tumors Fibrosarcoma 403 Myxoma 99 Liposarcoma 262 Leiomyosarcoma 117 Rhabdomyosarcoma . .... 112 Malignant Granular Cell Myoblastoma . 4 Malignant Organoid Granular Cell Myoblastoma .... Malignant Hemangioendothelioma • . . . . Malignant Hemangiopericytoma 12 34 32 Kaposi,s Sarcoma 43 Lymphangiosarcoma 7 Osteogenic and Chondrosarcoma (extraskeletal) Synovial Sarcoma . . 13 38 Malignant Mesenchymoma . . . 78 Malignant Mesothelioma 40 Reticulum Cell Sarcoma 27 Plasmocytoma 28 Total 1,349 ,All skeletal tumors, lymphosarcomas, and neurogenous tumors are omitted. F5-13

Tumors of fhe Safi Tissues where to draw the line in such an enumeration, since there are a good many infections—for example, tuberculosis, sarcoid, syphilis, rheumatic nodules, ete.— which can produce gross lesions closely resembling neoplasms but which can be identified on microscopic examination. These have been omitted. It is also difficult to know what to exclude from the term "soft tissues." Broadly interpreted it could mean everything except the bones. It is customary, however, to exclude all the organs, epithelial-lined tubes, the epithelial structures of the skin, the bone marrow, and the lymph nodes. This leaves the remaining tissues covering the bones of the head, neck, trunk, and extremities, as well as the internal soft tissues. Most of the latter will be dealt with in other fascicles, but for the sake of completeness the distribution of some of these soft tissue tumors in the abdominal and thoracic cavities and in the orbit will be touched upon. The benign and malignant tumors will be considered separately. Although the writer has dealt with all of the benign and malignant tumors of mesenchymal derivation with which he is familiar both personally and by repute, the reader need not expect to find here recorded all of the tumor forms that can grow. There are many cases of undiagnosed tumors in the files of every laboratory of pathology awaiting future study and recognition. This is true particularly of many puzzling varieties which develop in infancy and childhood. Tissue culture and meticulous cytologic and histochemical techniques no doubt will eventually lead to the clarification of these mysteries. In order that the reader may have some conception of the relative numbers of the different varieties of growths to be discussed in this fascicle it may be stated that there have been recorded in the Laboratory of Surgical Pathology of Columbia University during the 45 Vz years from February 1, 1906, to Sep- tember 1, 1951, 8,686 tumors and tumor-like lesions of the soft tissues of which 7,337 were benign (table I) and 1,349 malignant (table II). It must be empha- sized that almost all of the diagnoses have been made on surgical material and that doubtless the mah'gnant tumors are heavily overweighted because many of them come from other institutions and there is a much greater tendency to request consultations on malignant than on benign tumors. It is useful, how- ever, to know something about the relative frequency of the different tumor types in a sequence such as this. F5-14

Tumors of the Soft Tissues BENIGN TUMORS AND TUMOR-LIKE PROLIFERATIONS FIBROMATOSES It is exceedingly difficult to decide whether or not there is a true benign neoplasm composed of fibroblasts. It has been customary to use this term for the small fibrous proliferations making hard thickenings in the skin, fibroma durum. These resemble proliferating cicatrices but apparently develop spon- taneously. The term fibroma is also applied to the pedunculated epidermal- covered growth, the core of which is made up of the normal-appearing, fibrous elements of the corium, and which almost certainly is a congenital malformation, fibroma molle. These latter may grow to a relatively large size and have an admixture of fat. If there is an appreciable amount of this, they are generally classified as lipomas or fibrolipomas. The pedunculated fibroma is soft and has no known relationship to malignant tumors. The small, locally infiltrating fibrous growth is hardly ever found anywhere in the soft tissues, except in the skin. If these librous growths attain a size of 2 or 3 cm. or less and then stop gi owing, it is customary to speak of them as fibromas. If excised they do not recur even if the line of excision passes close to or through their environs (figs. 1, 2). If, however, they display progressive infiltrative growth and attain a larger size, they have been called recurring dermatofibroma of Darier when a single boss is formed, or dermatofibrosarcoma protuberans (Hoffmann) when multinodular (see p. 78); they are then classified as fibrosarcomas, because they will recur following incomplete excision. Cases with metastases have been reported, although the writer personally has never observed this. The term fibroma is applied frequently to the fibrous, well differentiated tumors of the mesentery that usually impinge upon the small intestine and produce distortion and obstruction. These are well differentiated fibrous growths that demonstrate progressive infiltration and will recur if not completely excised. For this reason this writer prefers to classify them as nonmetastasizing fibrosarcomas. They are very much like the fibrous growths of the periosteum, most of which are well differentiated and very few of which metastasize. Strangely enough benign fibromas and fibro- sarcomas are hardly ever recorded in the retroperitoneum, mediastinum, and other deeper soft tissues, with the exception above recorded. Occasionally a fibrous tumor develops in the abdominal muscles of women, most of whom have had pregnancies, and in this situation it is called a desmoid tumor. This is a mass of proliferated, scarlike tissue and may be nothing more than a hypertrophied scar. Rarely it is found elsewhere in other muscles. The desmoid reaches a size rarely exceeding a diameter of 12 cm. and, in spite of F5-15

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