MALIGNANT TRANSFORMATION OF A BENIGN ENCAPSULATED NEURILEMOMA
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1 TUB AMERICAN JOURNAL OF CLINICAL PATHOLOGY Copyright 19C9 by The Williams & Wilkins Co. Vol. 51, No. 1 Printed in U.S.A. MALIGNANT TRANSFORMATION OF A BENIGN ENCAPSULATED NEURILEMOMA PER HENRIK BECKER CARSTENS, M.D., AND GEORGE RANDOLPH SCHRODT, M.D. Department of Pathology, University of Louisville School of Medicine, Louisville, Kentucky Malignant transformation in a benign tumor is a most difficult event to document. Previous reports of such changes in neurilemomas have been rejected by authors subsequently reviewing the problem. Recently we had the opportunity to study an example of indisputable histologically malignant changes occurring in an encapsulated neurilemoma. BEPOKT OF CASE The patient was a 93-year-old Caucasian female who consulted her physician because of a painful enlarging tumor on the palmar aspect of the base of the right thumb. The tumor had been present for many years but had recently enlarged and become tender. No other skin nodules were present. The excised tumor was solid, encapsulated, and measured 2.5 by 2 by 2 cm. The cut surface was glistening, gray, and uniformly granular. There was one subcapsular and one central area of hemorrhage (Fig. 1). Microscopic Findings The tumor was completely encapsulated. The paracapsular tissue contained large nerve fibers (Fig. 2). The predominant pattern of the tumor was that of a benign neurilemoma with a mixture of Antoni types A and B patterns. The Antoni type A portions showed the usual compact pattern, with elongated spindle cells and fibers forming interlacing bands and parallel rows. Several structures resembling Wagner-Meissner tactile corpuscles (Verocay bodies) were present (Fig. 3). The Antoni type B areas consisted of loose edematous tissue containing a few haphazardly arranged spindle cells. In some areas cystic degenerative changes and hemorrhage were noted. Blood vessels were irregularly distributed throughout the tumor. The thick hyaline collar characteristic of neurilemomas was present. Received September 27, Small pieces of the tissue obtained for electron microscopic examination unfortunately contained only benign tumor. Characteristic features of benign neurilemoma, as described by Luse, 10 were noted. These included spindle-shaped cross-band fibrils (Fig. 4). The malignant portion was situated near the area of subcapsular hemorrhage. The maximal diameter of the malignant area was 9 mm. It consisted of irregular clusters of small cells without any particular pattern. The cells were uniform in size but variable in shape. Each cell had a large nucleus containing from one to three nucleoli. The chromatin network was sharply defined. The scanty eosinophilic cytoplasm was surrounded by an indistinct cell membrane. In the very delicate supporting stroma many capillaries were noted. There were over 20 mitoses per high power microscopic field (Fig. 5). A few pseudo-rosettes were noted. The malignant area was sharply demarcated from the capsule but intermingled on all other sides with both Antoni tjrpes A and B tissue (Fig. 6). Reticulum stains revealed delicate wirelike fibrils. The patient died in uremia, with arteriosclerotic cardiovascular disease. No other skin nodules had appeared. Permission for autopsy was not obtained. DISCUSSION The criteria required for acceptance of malignant change in a benign neurilemoma have recently been defined by Evans. 5 He included features such as pleomorphism, increased cellular density, many mitoses, deficient encapsulation, progressive neoplastic infiltration of the epineurium, invasion of the perineurium, perhaps extension along the nerve fascicles, together with evidence of unequivocal benign neurilemoma. By using most of the above-mentioned
2 Jan NEURILEMOMA 145 X & } \ (flil jlllllllll METRIC ll CM 2 liiirnit 3 iinii FIG. 1. External surface (left) and cut surface (right) of the tumor. The dark areas represent fresh hemorrhage. The arrow indicates the area of malignant change. criteria, which obviously refer to the ideal documentation, the authors have not been able to find such a case in the literature. Stout, 12 in his report on 144 neurilemomas arising from the peripheral, sympathetic, and cranial nerves, found none which became malignant and only one which recurred locally following incomplete removal. Earlier reports of malignant transformation in neurilemomas by Bertrand and Bernard, 1 Brandes, 2 Denecke, 4 Fittipaldi, 6 Hume, 7 and Guleke, 8 were all rejected by Stout, 11 on the grounds that it was not stated whether the benign tumor was a neurilemoma or a neurifibroma. The latter are known to become malignant. The few reported malignant neurilemomas appear to have been malignant from the start, rather than to have evolved from a benign neurilemoma. Vieta and Pack 13 re? viewed 20 cases of malignant neurilemoma without stigmata of von Recklinghausen's disease. No malignant neurilemoma originating in an encapsulated benign neurilemoma was observed. Kragh and associates 9 at the Mayo Clinic reported four patients, during the period through 1957, who had malignant neurilemomas arising in the head and neck. The authors stated that all four tumors exhibited microscopic evidence of malignancy, as required by Evans, in addition to the recognizable patterns of benign neurilemomas. Three tumors did not have a capsule. Two of the tumors were considered to be of low grade malignancy, whereas the other two caused the death of the patients 1 and 3 years after the initial attempt to remove them. None was associated with the stigmata of von Recklinghausen's disease. Two years later D'Agostino and colleagues, 3 also at the Mayo Clinic, studied 24 cases of primary malignant tumors of nerves, including the two cases previously reported by Kragh in which the tumor caused the death of the patient. They were unable to detect a relationship between benign encapsulated neurilemoma and malignant neurilemoma. None of the 24 tumors revealed any trace of a cellular pattern resembling benign neurilemoma. SUMMARY Malignant transformation of a benign, encapsulated neurilemoma of the thumb in a 93-year-old woman is reported. There was no evidence of von Recklinghausen's disease. The benign portions of the neurilemoma were composed of both Antoni types A and B tissue. The malignant areas appeared to be neuroblastomatous transformation. A review of the literature revealed no previously reported similar case.
3 il'v'?)r/'mi,tv^^»t/?^vf n.yvv' I -v: (VO ft 11 i; ; } ' «yv / i u -m'lr L' ac t. " - 1";, :.1':1J: 3 /iff / ^ s v, v,-;^^ ;i> H..-,...-, v,. %'. La V -1,_,. -\- ^ Lite.? ;» ' %!..' > % «" v "=4I, ^. «V A ^ ^,. V-% I.».. ' J PIG. 2 (upper). Field of the benign tumor and its capsule. Note the nerve fibers at the left, outside the capsule. Hematoxylin and eosin. X 150. Pic. 3 (lower). Close-up of several Verocay bodies. Hematoxylin and eosin. X
4 Jan NEURILEMOMA F I G. 4. Electron microscopic photomicrograph of the benign portion of the tumor iv, nucleus; CBF, cross-banded fibrils; arrow, basal membrane. Gluteraldehydeosmium fixation. Maraglas embedding, lead stain. X
5 F I G. 5 (upper). Field of t h e malignant portion of t h e tumor. N o t e the numerous mitoses. H e m a toxylin and eosin. X 600. F I G. 6 (lower). Field of an admixture of t h e benign and malignant portion of t h e tumor. N o t e the gradual transformation from benign to malignant tumor. T h e benign portion is represented by Antoni t y p e A. Hematoxylin and eosin. X
6 Jan NEURILEMOMA 149.REFERENCES 1. Bertrand, I., and Bernard, R.: Ddgdndrescence maligne d'une tumeur Schwannique du nerf radial dans un cas de maladie de Recklinghausen. Rev. neurol., 2: 66-70, Brandes, W. W.: A malignant neurinoma (Schwannoma) with epithelial elements. Arch. Path., 16: , D'Agostino, A. N., Soule, E. H., and Miller, R. H.: Primary malignant neoplasms of nerves (malignant neurilemomas) in patients without manifestations of multiple neurofibromatosis (von Recklinghausen's disease). Cancer, 16: , Denecke, K.: tlber zwei Fiille von metastasierenden Neurinomen des Magendarmkanals. Beitr. path. Anafc., 89: , Evans, R. W.: Neurilemoma. In Histological Appearances of Tumours, Ed. 2. Edinburgh: E. and S. Livingstone Ltd., 1966, Fittipaldi, C: Contribute) alio studio dei neurinomi. Riv. pat. nerv., 39: S, Hume, G. H.: Cases of tumour of nerve trunks. Lancet, 2: , 1S91. 8 Guleke, N.: ZurKlinik des Neurinoms. Arch. klin. Chir., H2: 47S-49S, Kragh, L. V., Soule, E. H., and Masson, J. Iv.: Benign and malignant neurilemmomas of the head and neck. Surg. Gynec. & Obst., Ill: , Luse, S. A.: Electron microscopic studies of brain tumors. Neurology, 10: 8S1-905, Stout, A. P.: The peripheral manifestations of the specific nerve sheath tumor (neurilemoma). Am. J. Cancer, 24-' , Stout, A. P.: Neurofibroma and neurilemoma. Clin. Proc, 5: 1-12, Vieta, J. O., and Pack, G. T.: Malignant neurilemomas of peripheral nerves. Am. J. Surg., 82: , 1951.
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