SARCOMA ASSOCIATED WITH METASTASES FROM BREAST CARCINOMA

Transcription

1 SARCOMA ASSOCIATED WITH METASTASES FROM BREAST CARCINOMA CHARLES W. LESTER, M.D. The association of two malignant tumors of an entirely different type in the same individual is sufficiently uncommon to warrant more than passing interest. I am indebted to Dr. William Crawford White for the privilege of reporting this unique case. Mrs. J. C. was admitted to the Roosevelt Hospital as a private patient of Dr. William Crawford White, July 8, Four weeks previously she had noticed a lump in her right breast. Her past history was essentially negative. She was married and had had four children, the youngest being then thirty years old. She had nursed from both breasts, but more from the left than from the right. Physical examination showed an obese woman, fifty-eight years of age. Both breasts were large. In the right breast there was a large,hard, centrally situated tumor. It was adherent to the overlying structures so as to cause retraction of the nipple and a pig-skin appearance of the integument. In the axilla at the outer border of the pectoral muscles a group of nodes could be felt. There were none above the clavicle. The remainder of the physical examination was essentially negative. Operation was performed July 9, 1927, by Dr. White. A radical mastectomy was done after the technic of Handley. Through a wide incision the breast, rectus fascia, sternal portion of the pectoralis major, and the pectoralis minor were removed. The axillary and subclavian nodes were carefully dissected out. Gross Pathological Examination: The specimen consists of a mammary gland covered by skin, pectoralis major, pectoralis minor, and axillary contents. A separate piece of tissue marked by a black thread is reported as having been removed from the neighborhood of the axillary vein below the clavicle. A third piece of tissue measuring 12 x 4 em. consists of skin and subcutaneous fat. The largest portion of the specimen weighs 1800 gm, and comprises breast, muscles, and axillary contents. It is covered by an ellipse of skin measuring 20 x 18 em. The nipple is markedly retracted and there is a slight dimpling of the skin just above and medial to the nipple, but no ulceration. Adherent to the skin at this place is a large, hard mass which can be grasped in the fingers. It extends below the nipple for 2 to 3 em. and above the nipple for 4 to 5 em. It overlies the muscles but is not adherent to them. On section the knife cuts the tissue with a grating sound 850

2 SARCOMA ASSOCIATED WITH METASTASES FROM CARCINOMA 851 and discloses a pale yellowish, granular tumor, 7 x 5 x 372 em. There is no capsule, but the tumor extends finger-like processes in all directions. Section of the remainder of the breast reveals no separate nodules nor anything else of note. Section of the muscles does not reveal any nodules or any extension of the tumor to these structures. In the large amount of axillary fat four or five discrete nodes measuring 0.75 to 1.5 em. in diameter and numerous smaller nodes are found. The FIG. 1. BREAST TuMOR nodes are hard and on section show a cut surface similar in character to that of the breast tumor. In the subclavian tissue marked by the black thread two small discrete nodes are found which are similar to the axillary nodes on section. The separate piece of skin and underlying fat seems normal. Microscopic Examination: Sections show the tumor to be composed of poorly differentiated epithelial cells growing in a dense fibrous tissue stroma. For the most part the cells are growing diffusely and without apparent restraint. Occasionally they show a tendency to glandular arrangement, and occasionally they seem to be growing in cords (Fig. I).

3 852 CHARLES W. LESTER The individual cells vary somewhat among themselves in size, and staining capacity, but the usual cell is of medium size and oval in shape. The nucleus which occupies most of the cell body is large and hyperchromatic. Nucleoli are seen and mitotic figures are readily found. There is no evidence of any secretory activity on the part of any of the cells. The fibrous tissue stroma is dense and in parts almost acellular. It has the appearance of scar tissue and shows no evidence of malignant characteristics. The axillary nodes all show almost total replacement of the lymphoid tissue with tumor growth. The metastatic growth has all the character- Subcutaneous,/ :'.. : I V t l' ~III~ e, (,.:.~~ A.. ; ~. j'.-...j.. :~ J).,. I..:::::. 1:7 j7 I ~ ~l FIG. 2. LOCATION OF NODULES WHICH ApPEARED ONE YEAR AFTER RADICAL MASTECTOMY istics of the primary tumor in the breast. Likewise the subclavian nodes show similar invasion. Sections of the muscle under the tumor show no evidence of any extension of the tumor to this tissue. Sections of the breast adjacent to the tumor show invasion of the growth. There are a few normal glands, but other glands are cystic and lined with large cuboidal cells characteristic of chronic cystic mastitis. Diagnosis: Carcinoma of the right breast-grade 2 (Greenough) with metastases to the axillary and subclavian nodes. Chronic cystic mastitis. Later Course: The patient was discharged from the hospital July 19, 1927, with the wound well healed after an uneventful convalescence. In October 1927 she received a course of three high-voltage x-ray treatments

4 SARCOMA ASSOCIATED WITH METASTASES FROM CARCINOMA 853 under the direction of Dr. J. M. Steiner. She was seen by Dr. White in May 1928, at which time there was no evidence of recurrence. The patient was seen again Oct. 5, 1928, by Dr. White, at which time nodules were noted in the vicinity of the scar as indicated in the accompanying diagram (Fig. 2). No supraclavicular nodes could be felt. X-ray examination of the chest showed it to be free from metastases, and the patient was given a course of three more high-voltage x-ray treatments by Dr. Steiner. She was readmitted to the hospital Nov. 26, Operation was done by Dr. White Nov. 27,1928. Through an irregular skin incision the skin and cutaneous nodules were excised, together with the nodules in the axilla and the subclavian nodules with the underlying muscle. So much skin was removed that the wound edges were approximated with difficulty and under considerable tension. Pathological Examination: The various nodules may be located by reference to the accompanying diagram (Fig. 2). A is a small subcutaneous nodule about 1 em. in diameter. On section it is found to consist of adipose tissue with white fibrous tissue around the periphery. B is composed of four separate nodules involving the remaining portion of the pectoralis major. One of these nodules is covered by an elliptical piece of skin measuring 4 x 2.75 em. Two others are surrounded and embedded in adipose tissue. Section of the one covered by skin shows a fused nodular area projecting up into the cutaneous layer. The other two show a somewhat similar picture. The fourth measures 6 x 4 x 3 cm. and is covered by an elliptical piece of skin measuring 4 x 3 em. in length. In the depth of this mass is muscle tissue. Within the mass is a single nodule. C consists of two separate nodules intimately associated with the overlying skin. This specimen is entirely covered by a long strip of skin measuring 13 em. in length. In this strip were two definite thickened and elevated areas of skin with no gross changes in the subcutaneous fatty tissues. These areas were approximately 1.5 em. in diameter. D consists of one subcutaneous nodule removed with an elliptical piece of skin measuring 5 x 2 cm., in which there was a slight thickening of the skin but no change in the subcutaneous tissue. Microscopic Examination: Two sections were made of the nodule A. One section shows an indefinitely circumscribed area in which there has been an invasion of the subcutaneous adipose tissue by large epithelial cells. The cells are poorly differentiated, irregularly polygonal or oval in shape, and contain large, hyperchromatic nuclei. Surrounding this area is a definite zone of chronic inflammatory cells. The other section shows the inflammatory infiltration with only a few of the epithelial cells. Six sections were cut from the B tissue. All these sections show striated muscle. In the muscle are numerous circumscribed areas of densely packed epithelial cells similar to those described above. Other sections show an entirely different type of tissue in the muscle. This tissue is composed of densely packed spindle cells with nuclei which occupy most of the cell body. The nuclei are hyperchromatic and contain occasional mitotic figures. The epithelial cells are not found in these

5 854 CHARLES W. LESTER nodules, which seem to be sarcomatous rather than carcinomatous (Fig. 3). Seven sections were cut from the C nodules. Five were taken serially between the outer portions of the nodules. Two were taken from the center of the nodules. Of those taken between the outer portions of the nodules, two sections show small collections of tumor cells in the reticular FIG. 3. NEUROGENIC SARCOMA. B NODULES. X 200 portion of the derma. The intervening slides show a mild degree of chronic inflammatory reaction but no tumor cells. Of the two slides taken from the center of the nodules, both show large collections of the epithelial tumor cells. The cells are situated in the reticular portion of the derma and diffuse up towards the papillary layer and laterally. The lateral diffusions thin out and at the outer edges of the section there is nothing but a mild chronic inflammatory reaction. Quite prominent in one of the slides is the involvement of the subcutaneous fat in the tumor recurrence (Fig. 4).

6 SARCOMA ASSOCIATED WITH METASTASES FROM CARCINOMA 855 Two sections were made of the D nodule. Both show the presence of the epithelial tumor diffusing through the reticular layer of the derma. Comparison of the epithelial tumor nodules of the second operation with the original breast tumor show them to be similar. Diagnosis: Postoperative recurrence of carcinoma of right breast in skin and clavicular portion of pectoralis major. Neurogenic sarcoma of right chest wall. FIG. 4. TUMOR RECURRENCE IN FAT. C NODULES. X 200 Study of the sections of the recurrence brings up several interesting points. As regards the recurrence of the carcinoma, it is to be noted that there were prominent areas of the tumor in the clavicular portion of the pectoralis major. It has often been considered that this portion of the muscle is practically immune from involvement in carcinoma of the breast, and surgeons frequently feel that it can safely be left in situ. These sections would seem to disprove this contention.

7 856 CHARLES W. LESTER There is a theory that skin recurrences in carcinoma of the breast extend along the cutaneous lymphatics and do not come to the skin from a focus in the deeper structures. The study of the C sections seems to indicate that the tumor nodules in the skin came from a deep focus, as there was no apparent connection between the nodules by way of growth along the skin lymphatics. The intervening sections showed no tumor tissue at all, but the deeper portions of the section showed the greatest amount of the epithelial cells. This finding corroborates the theory of Handley, who contends that skin nodules come from involved subcutaneous lymphatics. The examination of tissue from one case cannot be said to prove or disprove the theory. However, the weight of evidence in this case would seem to indicate a deep origin of the skin nodules rather than an extension via the cutaneous lymphatics. Perhaps the most interesting feature of the tissue in this case is the presence of neurogenic sarcoma in the same group of nodules in which metastatic carcinoma was found. Histologically these were distinct and separate tumors and can not be classed with the so-called adenosarcomas of the breast, which are mixed tumors. Dr. Francis Carter Wood, who has made an exhaustive study of mixed tumors, has been good enough to examine these slides and agrees that the tumors are separate. As the tumors appeared in the metastases and as we have no definite evidence that they were both primary in the breast, it is not possible to state with certainty that the sarcoma did not arise elsewhere. Unfortunately the gross specimen was not saved and further sections can not be made. Careful review of the slides taken from the original specimen does not disclose anything which can be interpreted as sarcoma. There is no reason to believe that sarcoma and carcinoma may not be associated in the same breast, but to judge from the reported cases such an association is a rarity. Furthermore, a study of the descriptions in the reported cases indicates that many have to deal with single mixed tumors containing both sarcomatous and carcinomatous elements, rather than with distinct sarcoma and carcinoma. The cases reported by Coenen, Kerbirion and Danel, Secousse, Wehner, Pfeiffer, Dorsch, Helwig, and Lecene undoubtedly fall in this class. They are mentioned in detail because they are often referred to in the literature as separate tumors. On the other hand, Gould, Kettle, Kennedy and Case, and

8 SARCOMA ASSOCIATED WITH METASTASES FROM CARCINOMA 857 Schlagenhaufer report cases in which the two tumors are separate and distinct. Cornil mentions another but gives no description of the tumors. Schlagenhaufer suggests a sarcomatous metaplasia in his case, but the tumors were distinct both in the gross and microscopic appearances, except in one area where they were adjacent. The appearance of sarcomatous metaplasia in transplanted mouse tumors is noted by Russell, by Haaland and by Ehrlich and Apolant. Ewing, in discussing a sarcomatous appearance in human breast carcinoma, is inclined to believe that the spindle cells are modified epithelium. However, Dr. Ewing has been good enough to look at the slides from the case described in this paper and considers that the two tumors are distinct. Schwarz has reported a case in which the metastases were so similar to those in the present case that it will bear summarizing here. In June 1909 a tumor was removed from the left breast of a married woman of fifty-eight and reported as chronic mastitis. In November 1909 the tumor had recurred and a radical mastectomy was done. The tumor proved to be carcinoma, and metastases were found in the axillary nodes. In July 1910 hysterectomy was done for a tumor which the pathologist called a degenerated myoma. In December 1912 a radical mastectomy was performed on the right breast for a breast tumor and an enlarged subclavian node. Examination showed the breast tumor to be carcinoma, but the subclavian node was sarcoma composed of spindle and giant cells. In June 1913 nodules were removed from the right shoulder and from the abdominal wall near the umbilicus, which proved to be spindle-cell sarcoma. At the same time a nodule was removed from the right axilla, which proved to be carcinoma. Schwarz believes that the carcinoma in the left breast had metastasized to the left axilla, the right breast, and the right axilla; and that the uterine tumor was a sarcoma which had metastasized to the other locations. Perhaps there was a similar condition in our case. The patient died some months later of malignancy, but there was no evidence of sarcomatous growth elsewhere, as far as could be learned, although no autopsy was obtainable. If the sarcomatous nodules were metastatic, the parent growth would probably, although not necessarily, have been in evidence. The likely origin of the sarcoma, then, is either the breast, where it was so small that it was overlooked, or the nodule where it was found in close association

9 858 CHARLES W. LESTER with carcinomatous metastases. uncommon to be noteworthy. Either instance is sufficiently BIBLIOGRAPHY COENEN, R.: Beitr. z. klin. Chir. 68: 605,1910. CORNIL, V.: Les tumeurs du sein, Bailliere et Cie, Paris, 1908, p DEAVER, J. B., AND McFARLAND, J.: The Breast: Its Anomalies, Its Diseases and Their Treatment, P. Blakiston's Son & Co., Philadelphia, 1917, pp DORSCH, M.: tiber Carcinom und Sarcom derselben Mamma, Wiirzburg EHRLICH, P., AND ApOLANT, H.: Berl. klin. Wchnschr. 2: 871,1905; 1: 37, EWING, J.: Neoplastic Diseases, W. B. Saunders Co., Philadelphia, 1928, Ed. 3, p GOULD, P.: Carcinoma and Sarcoma of the Same Breast, Middlesex Hosp. Rep. 1901, London, 81, HAALAND: Third Scientific Report, Imperial Cancer Research Fund, London, 1908, p HANDLEY, W. S.: Cancer of the Breast, Paul Roeber, New York, 1922, Ed. 2, pp HELWIG, F. C.: Arch. Path. & Lab. Med. 4: 102, KENNEDY, J. W., AND CASE, E. A.: Proc. Path. Soc. Phila. 18: 40, KERBIRION AND DANEL: Jour. d. soc. med. d. Lille 1: 175, KETTLE, E. H.: Lancet 2: 750, LECENE, P.: Bull. d. 1. Soc. anat. d. Paris 79: 698, PFEIFFER: Proc. Path. Soc. PhiIa. 13: 267, RUSSELL, B. R. G.: J. Path. & Bacteriol. 14: 344, SCHLAGENHAUFER: Centralbl. f. allgem, Path. u. path. Anat. 17: 385,1906. SCHWARZ, E.: Am. J. Obst. & Gynec. 68: 752,1913. SECOUSSE: J. d. med, de Bordeaux 42: 791, WEHNER, E.: Frankfurt. Ztschr. f. Path. 16: 167, 1914.