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Solitary solid stromal gastrointestinal tumors in von recklinghausen's disease with minimal smooth muscle differentiation
Solitary Solid Stromal Gastrointestinal Tumors in von Recklinghausen's Disease with Minimal Smooth Muscle Differentiation JOHN D. SCHALDENBRAND, MD, AND HENRY D. APPELMAN, MD Neurofibromatosis (von Recldinghausen's disease) is occasionally associated with large, solid stromal tumors of the gastrointestinal tract. The authors examined by electron microscopy two such cases o f cellular spindle cell neoplasms of the small bowel histologically that resembled leiomyomas, in an attempt to clarify the cell of origin of these lesions. Ultrastructurally, the tumor cells predominantly contained moderate to large numbers o f intracellular filaments, small cell processes, discontinuous adherent dense basement-membrane-like material, and abundant intercellular collagen. Definite fusiform dense bodies or structures highly suggestive of them and pinocytotic vesicles were seen in rare cells of each lesion after viewing multiple blocks. While patients with neurofibromatosis are certainly at risk of developing gastrointestinal Schwann cell neoplasms, these two cases suggest that they are also at risk for developing poorly differenitated stromal tumors, resembling leiomyomas by light microscopy, which may show only characteristic cytoplasmic differentiation o f smooth muscle cells after ultrastructural examination o f many sections. HUM PATnOL 15:229--232, 1984.
G a s t r o i n t e s t i n a l i n v o l v e m e n t in y o n R e c k l i n g h a u s e n ' s disease has b e e n e s t i m a t e d to o c c u r in I 1 to 25 p e r c e n t o f cases, 1-3 with t u m o r s in all levels o f b o w e l r e p o r t e d . H i s t o l o g i c e x a m i n a t i o n s o f t h e lesions h a v e r e v e a l e d d i v e r s e f e a t u r e s , a n d d i a g n o s e s of neurofibroma, neurilemoma, neurofibrosarcoma, 4 l e i o m y o m a , 5 a n d g a n g l i o n e u r o f i b r o m a 6 h a v e all b e e n r e p o r t e d . Few cases h a v e b e e n s t u d i e d u l t r a s t r u c t u r ally, h o w e v e r . W e r e p o r t two a d d i t i o n a l cases, w h i c h w e r e a n a l y z e d b o t h by light a n d e l e c t r o n m i c r o s c o p y in a n a t t e m p t to f u r t h e r clarify t h e cell o f o r i g i n o f at least o n e g r o u p o f these t u m o r s , those w h i c h a r e l a r g e a n d solid.
REPORT OF TWO CASES Case 1. A-52-year-old white man had a long history of "ulcer disease," with prior vagotomy and antrectomy. He was hospitalized for the evahmtion of nausea, vomiting, and intermittent epigastric pain o f four weeks' duration. T h e cutaneous stigmata o f neurofibromatosis were present, and the patient had a family history o f this disorder. Computerized tomographic examination o f the abdomen revealed a right posterior hepatic nmss and an enlarged left adrenal gland. An exploratory laparotomy revealed an adrenal pheochromocytoma and numerous small abscesses within
Received June 29, 1982, from the Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan. Accepted for publication March 8, 1983. Address correspondence and reprint requests to Dr. Schaldenbrand: Department of Pathology, University of Michigan, M4231 Medical Science l, Ann Arbor, MI 48109.
the liver. An intramural mass observed within the wall of the jejunum was resected. T h e jejunal lesion was gray-tan and lobulated and 3.5 x 3 x 2 cm in size. On light microscopy, the lesion was observed to be confined entirely within the muscularis propria o f tile jejunum. T h e tumor consisted of muhiple interweaving bundles of spindled cells with indistinct cell borders (figs. 1 and 2). T h e nuclei were, for the most part, oval with blunted ends, and one or two small, round nucleoli could be seen in many cells. In other areas, the nuclei were more pleomorphic, becoming larger and more rectangular, but no mitotic figures were seen. In some areas, imperfect palisades o f nuclei were observed. T h e cytoplasm was eosinophilic. N u m e r o u s tifin-walled vascular spaces were present tlaroughout the lesion, some of which showed prominent "hyalinization" o f their walls. A single small focus of necrosis was observed. Large globules and strands of smooth eosinophilic material were present between cells (fig. 3). In the trichrome-stained sections, tiffs intercellular material was blue and fibrillar. Reticulin stains revealed abundant dark, interlacing, branching fibers surrounding fascicles o f cells arranged parallel to their long axes, but the eosinophilic intercellular material did not stain with silver. Case 2. A 45-year-old white woman who had known neurofibromatosis since childhood complained o f intermittent nausea and vomiting o f five )'ears' duration. Fluoroscopy of the upper gastrointestinal tract revealed an intramural 3 • 2-cm mass in the fourth part of the duodennm, which was resected. This tumor was a tan, somewhat firm, Iobulated 5.0cm nodule that was slightly cystic on cut section and appeared to infiltrate the overlying bowel mucosa. Hematoxylin-eosin-stained sections revealed a non-encapsulated ulcerated celhdar neoplasm in the muscularis propria and subnmcosa, consisting o f fascicles of spindled cells (figs. 1 and 2). T h e spindled cells were moderately large with somewlmt distinct borders. Globules and strands o f smoothstaining eosinophilic material were seen between cells, as in case I (fig. 3). Cell nuclei were, for the most part, oval or cigar-shaped with blunted ends, fine reticular chromatin, and one or occasionally two nucleoli. M o d e r a t e pleomorphism of nuclear size and shape was observed, and in one area a few cells with very large nuclei and dark chromatin were seen. Careful examination of many fields revealed no mitotic figures. T h e cytoplasm o f the t u m o r cells was homogenous and eosinophilic. Numerous large, thinwalled, congested and slit-like vascular spaces were located at the periphery of the lesion, but no hyalinization of vascular walls was noted. Several small necrotic foci were seen. Trichrome-stained sections revealed moderate amounts o f blue fibrillar intercelhdar material throughout the tumor. The hyaline globules also stained blue. Reticulin stains revealed abundant interlacing, branched, dark-staining fibers parallel to the long axes o f the tumor cells, but, as in case 1, the globular material did not take the silver stain.
229
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FIGURE 1 (top left). Characteristic spindled cells with fibrillar cytoplasm and small nucleoli in a representative section from the lesion in case 1. [[Hematoxylin-eosin stain, x 328.] FIGURE 2. (top right]. Looser, more disorganized cells were observed in both lesions. (Hematoxyiin-eosin stain, x 328]. FIGURE 3 (left). Hyalin globules belween the spindled cells were observed in both lesions. [Hematoxylin-eosin stain. x 328.)
ULTRASTRUCTURAL EXAMINATION Freshly sampled, glutaraldeh);de-fixed material from both lesions was cut into 1 mm cubes, post-fixed in osmium tetroxide, sectioned, stained with lead citrate and uranyl acetate, and examined in an electron microscope. Muhiple grids from at least three blocks of each tumor were viewed. Ultrastructurally, both neoplasms consisted o f small spindled cells surrounded by abtmdant collagen fibers (fig. 4). Nuclear outlines of the cells in both cases were irregular, in 230
the second case to such a degree that apparent segmentation of nuclear material was observed. T h e nuclear chromatin of both lesions was fine, with denser material peripherally. Nucleoli were small and round. The cytosol of both lesions contained many small, oval mitochondria, ahhough fewer were observed in the first lesion than in tile second. Small amounts of smooth and rough endoplasmic reticulum were seen in both lesions. Intracytoplasmic microfilaments were present in both lesions, bnt they were much more p r o m i n e n t in the second (figs. 5 and 6). In each
GASTROINTESTINAL TUMORS IN VON RECKLINGHAUSEN'S DISEASE [Schaldenbrand & Appelman)
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FIGURE 4 (top left). Irregularly outlined nuclei, small circular nucleoli, and thin, short cytoplasmic processes from case 1. The abundant intercellular collagen fibrils are a g g r e g a t e d into nodules, corresponding to the hyaline globules observed light microscopically. ( x 3,500.] FIGURE 5 (top right]. Cytoplasm containing abundant filaments, from case 1. In this field, as in most fields, there are no dense bodies. A small intermediate junction is present [arrow]. At the bottom is a whorled nodule of collagen. ( x 15,200.] FIGURE 6 [bottom left). Cells from case 2 with fewer cytoplasmic filaments than in case 1. Focally, small amounts of basement-membranelike material adhere to the cell m e m b r a n e [arrows]. Notice the short cytoplasmic processes. ( x 15,200.) FIGURE 7 [bottom right]. Fusiform dense bodies from case 2, like those observed in case 1. Rows of pinocytotic vesicles can b e seen in the upper middle portion of the field. (x19,000.)
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t u m o r t h e r e were o n e o r two cells with structures closely resembling f n s i f o r m dense bodies, f o r m e d apparently f r o m linear aggregates o f the microfilaments (fig. 7). No vascular h t m e n s were adjacent to these cells, and the cells lacked b a s e m e n t m e m b r a n e . T h e s e cells also c o n t a i n e d occasional pinocytotic vesicles, which w e r e a b s e n t in t h e o t h e r t u m o r cells. Cell b o u n d a r i e s o f both lesions that b o r d e r e d o n intercellular matrix revealed a few thin, interlacing cytoplasmic processes w i t h o u t organelles, which w e r e partially covered by small "flecks" o f dense basementm e m b r a n e - l i k e material (fig. 6). No material similar to this was seen between adjacent t u m o r cells. Occasional intermediate-type j u n c t i o n s were present between t u m o r cells (fig. 5). T h e intercellular free space o f both lesions contained a b u n d a n t discrete strands and whorled aggregates o f collagen fibrillae with 64n m periodicity, c o r r e s p o n d i n g to the eosinophilic globules (figs. 4 to 6).
DISCUSSION Histologically, these two lesions most closely res e m b l e d fairly typical small intestinal l e i o m y o m a s . Despite the history o f n e u r o f i b r o m a t o s i s , these lesions lacked the histologic features of n e u r o f i b r o m a , were not encapsulated, a n d did not show the Antoni A and B areas characteristic o f neurilemomas. 7 Hyalinized blood vessels identical to those described in n e u r i l e m o m a were observed in the first case, but the a p p e a r a n c e o f that lesion was not otherwise consistent with that diagnosis. U h r a s t r u c t u r a l l y , the lesions a p p e a r e d similar. Rare intercellular j u n c t i o n s were present. In that the nuclei w e r e oval, i r r e g u l a r in outline, a n d , in the second case, segmented, with central r o u n d nucleoli, t h e y most closely r e s e m b l e d the nuclei o f s m o o t h muscle. While t h e r e were a b u n d a n t microfilaments in the cytoplasm o f both lesions, muhiple blocks were r e q u i r e d to f i n d an o c c a s i o n a l cell with f u s i f o r m dense bodies a n d / o r pinocytotic vesicles. Short interdigitating cytoplasmic processes with discontinuous b a s e m e n t - m e m b r a n e - l i k e material were observed in both cases, but they lacked the characteristic a p p e a r ance described in neurilemoma and neurofibroma, s-l~ P r o c e s s e s similar to t h e s e h a v e b e e n d e s c r i b e d in s m o o t h muscle neoplasms. In short, these two lesions u h r a s t r u c t u r a l l y had the n u c l e a r characteristics o f s m o o t h muscle a n d r a r e cytoplasmic f e a t u r e s suggesting s m o o t h muscle, but most o f the cells by far failed to show cytoplasmic characteristics o f any particular mesenchymal cell. We view these t u m o r s as being p r e d o m i n a n t l y u n d i f f e r e n t i a t e d mesenchymal neoplasms with focal differentiation toward s m o o t h muscle. O t h e r s might r e g a r d them as poorly differentiated leiomyomas, but the overwhelming majority o f the t u m o r cells did not have the cytoplasmic characteristics o f smooth muscle. T h e f n d i n g o f a few fusiform dense bodies does not constitute conchtsive e v i d e n c e that t h e e n t i r e n e o p l a s m was o f s m o o t h muscle type. F u r t h e r m o r e , the tumors o c c u r r e d in patients with von Recklinghausen's disease, which is
characterized by the f o r m a t i o n o f m a n y n e r v e sheath tumors. Weiss and MacKay, 11 in their study o f malignant smooth muscle gastrointestinal tumors, e m p h a sized that m a n y t u m o r s that seem to be o f smooth muscle type on light microscopy lack the ultrastructural cytoplasmic f e a t u r e s characteristic o f s m o o t h muscle. T h e y consider the uhrastructural characteristics o f t u m o r s that, on light microscopy, a p p e a r as leiomyosarcomas, to r e p r e s e n t "a spectrum f r o m unc o m m i t t e d m e s e n c h y m a l cells . . . to cells d e m o n strating u n e q u i v o c a l f e a t u r e s o f s m o o t h muscle. TM Welsh a n d M e y e r 12 r e p o r t e d this same f i n d i n g in their study o f gastric leiomyomas ten years earlier. T h e two t u m o r s d e s c r i b e d h e r e a r e c o m p o s e d o f t h e s e r e l a t i v e l y t m c o m m i t t e d m e s e n c h y m a l cells, which, only rarely d e m o n s t r a t e some cytoplasmic differentiation. N e o p l a s m s r e s e m b l i n g l e i o m y o m a s in the gastrointestinal tract o f patients with neurofibromatosis were first r e p o r t e d by Lukash. 5 T h e ultrastructural f e a t u r e s o f s u c h lesions h a v e not b e e n r e p o r t e d . While some might a r g u e that such cases r e p r e s e n t the c o i n c i d e n t a l o c c u r r e n c e o f l e i o m y o m a s in the gastrointestinal tract o f patients with neurofibromatosis, the relative rarity o f both gastrointestinal leiomyomas and neurofibromatosis, plus the presence o f gastrointestinal i n v o h ' e m e n t in as m a n y as one f o u r t h o f patients with neurofibromatosis, would a r g u e against this. F r o m o u r r e p o r t , it appears that patients with neurofibromatosis, while at risk for d e v e l o p i n g typical p e r i p h e r a l n e r v e s h e a t h n e o p l a s m s within the gastrointestinal tract, may also develop poorly differentiated stromal t u m o r s that resemble leiomyomas on light microscopy. Like previously r e p o r t e d "smooth muscle" t u m o r s o f the gut, these tumors uhrastructurally have few cytoplasmic features characteristic o f any specific cell line.
REFERENCES 1. Reeder MM, Celford GJ, Robb PL: Case of tile month from the AFIP. Radiology 90:1023, 1968 2. Sivak MV Jr, Sullivan BH Jr, Farmer RG: Neurogenic tumors of the small intestine. Gastroenterology 68:374:1975 3. Davis GB, Berk RN: Intestinal neurofibromas in von Recklinghausen's disease. Am J Gastroenterol 45:410, 1966 4. Russell JY: Neurofibromatosis: a bizarre disease. Br J Surg 52:251, 1965 5. Lukash WM, Jolmson BB: Gastrointestinal neoplasms in von Recklinghausen's disease. South Med J 62:1237, 1969 6. Donnelly WH, Sieber WK, Yunis EJ: Polypoid ganglioneurofibromatosis of the large bowel. Arch Pathol 87:537, 1969 7. Abell MR, Hart WR, Oslon JR: Tumors of the peripheral nervous s)'stem. Itu.xl PATIIOL1:503, 1970 8. Waggener JD: Uhrastructure of benign peripheral nerve sheath tumors. Cancer 19:699, 1966 9. Razzuk MA, Urshel HC, MartinJA, et al: Electron microscopical observations on mediastinal neurilemmoma, neurofibroma, and ganglioneuroma. Ann Thorac Surg 15:73, 1973 10. Erlandson RA, WoodruffJM: Peripheral nerve sheath tumors: an electron microscopic stud)" of 43 cases. Cancer 49:273, 1982 11. Weiss RA, MacKay B: Malignant smooth muscle tumors of the gastrointestinal tract: a light and electron microscopic stt,dy of twenty cases. Uhrastruct Pathol 2:231, 1981 12. Welsh RA, Meyer A: Uhrastructure of gastric leiomyoma. Arch Pathol 87:71, 1969
232
G a s t r o i n t e s t i n a l i n v o l v e m e n t in y o n R e c k l i n g h a u s e n ' s disease has b e e n e s t i m a t e d to o c c u r in I 1 to 25 p e r c e n t o f cases, 1-3 with t u m o r s in all levels o f b o w e l r e p o r t e d . H i s t o l o g i c e x a m i n a t i o n s o f t h e lesions h a v e r e v e a l e d d i v e r s e f e a t u r e s , a n d d i a g n o s e s of neurofibroma, neurilemoma, neurofibrosarcoma, 4 l e i o m y o m a , 5 a n d g a n g l i o n e u r o f i b r o m a 6 h a v e all b e e n r e p o r t e d . Few cases h a v e b e e n s t u d i e d u l t r a s t r u c t u r ally, h o w e v e r . W e r e p o r t two a d d i t i o n a l cases, w h i c h w e r e a n a l y z e d b o t h by light a n d e l e c t r o n m i c r o s c o p y in a n a t t e m p t to f u r t h e r clarify t h e cell o f o r i g i n o f at least o n e g r o u p o f these t u m o r s , those w h i c h a r e l a r g e a n d solid.
REPORT OF TWO CASES Case 1. A-52-year-old white man had a long history of "ulcer disease," with prior vagotomy and antrectomy. He was hospitalized for the evahmtion of nausea, vomiting, and intermittent epigastric pain o f four weeks' duration. T h e cutaneous stigmata o f neurofibromatosis were present, and the patient had a family history o f this disorder. Computerized tomographic examination o f the abdomen revealed a right posterior hepatic nmss and an enlarged left adrenal gland. An exploratory laparotomy revealed an adrenal pheochromocytoma and numerous small abscesses within
Received June 29, 1982, from the Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan. Accepted for publication March 8, 1983. Address correspondence and reprint requests to Dr. Schaldenbrand: Department of Pathology, University of Michigan, M4231 Medical Science l, Ann Arbor, MI 48109.
the liver. An intramural mass observed within the wall of the jejunum was resected. T h e jejunal lesion was gray-tan and lobulated and 3.5 x 3 x 2 cm in size. On light microscopy, the lesion was observed to be confined entirely within the muscularis propria o f tile jejunum. T h e tumor consisted of muhiple interweaving bundles of spindled cells with indistinct cell borders (figs. 1 and 2). T h e nuclei were, for the most part, oval with blunted ends, and one or two small, round nucleoli could be seen in many cells. In other areas, the nuclei were more pleomorphic, becoming larger and more rectangular, but no mitotic figures were seen. In some areas, imperfect palisades o f nuclei were observed. T h e cytoplasm was eosinophilic. N u m e r o u s tifin-walled vascular spaces were present tlaroughout the lesion, some of which showed prominent "hyalinization" o f their walls. A single small focus of necrosis was observed. Large globules and strands of smooth eosinophilic material were present between cells (fig. 3). In the trichrome-stained sections, tiffs intercellular material was blue and fibrillar. Reticulin stains revealed abundant dark, interlacing, branching fibers surrounding fascicles o f cells arranged parallel to their long axes, but the eosinophilic intercellular material did not stain with silver. Case 2. A 45-year-old white woman who had known neurofibromatosis since childhood complained o f intermittent nausea and vomiting o f five )'ears' duration. Fluoroscopy of the upper gastrointestinal tract revealed an intramural 3 • 2-cm mass in the fourth part of the duodennm, which was resected. This tumor was a tan, somewhat firm, Iobulated 5.0cm nodule that was slightly cystic on cut section and appeared to infiltrate the overlying bowel mucosa. Hematoxylin-eosin-stained sections revealed a non-encapsulated ulcerated celhdar neoplasm in the muscularis propria and subnmcosa, consisting o f fascicles of spindled cells (figs. 1 and 2). T h e spindled cells were moderately large with somewlmt distinct borders. Globules and strands o f smoothstaining eosinophilic material were seen between cells, as in case I (fig. 3). Cell nuclei were, for the most part, oval or cigar-shaped with blunted ends, fine reticular chromatin, and one or occasionally two nucleoli. M o d e r a t e pleomorphism of nuclear size and shape was observed, and in one area a few cells with very large nuclei and dark chromatin were seen. Careful examination of many fields revealed no mitotic figures. T h e cytoplasm o f the t u m o r cells was homogenous and eosinophilic. Numerous large, thinwalled, congested and slit-like vascular spaces were located at the periphery of the lesion, but no hyalinization of vascular walls was noted. Several small necrotic foci were seen. Trichrome-stained sections revealed moderate amounts o f blue fibrillar intercelhdar material throughout the tumor. The hyaline globules also stained blue. Reticulin stains revealed abundant interlacing, branched, dark-staining fibers parallel to the long axes o f the tumor cells, but, as in case 1, the globular material did not take the silver stain.
229
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FIGURE 1 (top left). Characteristic spindled cells with fibrillar cytoplasm and small nucleoli in a representative section from the lesion in case 1. [[Hematoxylin-eosin stain, x 328.] FIGURE 2. (top right]. Looser, more disorganized cells were observed in both lesions. (Hematoxyiin-eosin stain, x 328]. FIGURE 3 (left). Hyalin globules belween the spindled cells were observed in both lesions. [Hematoxylin-eosin stain. x 328.)
ULTRASTRUCTURAL EXAMINATION Freshly sampled, glutaraldeh);de-fixed material from both lesions was cut into 1 mm cubes, post-fixed in osmium tetroxide, sectioned, stained with lead citrate and uranyl acetate, and examined in an electron microscope. Muhiple grids from at least three blocks of each tumor were viewed. Ultrastructurally, both neoplasms consisted o f small spindled cells surrounded by abtmdant collagen fibers (fig. 4). Nuclear outlines of the cells in both cases were irregular, in 230
the second case to such a degree that apparent segmentation of nuclear material was observed. T h e nuclear chromatin of both lesions was fine, with denser material peripherally. Nucleoli were small and round. The cytosol of both lesions contained many small, oval mitochondria, ahhough fewer were observed in the first lesion than in tile second. Small amounts of smooth and rough endoplasmic reticulum were seen in both lesions. Intracytoplasmic microfilaments were present in both lesions, bnt they were much more p r o m i n e n t in the second (figs. 5 and 6). In each
GASTROINTESTINAL TUMORS IN VON RECKLINGHAUSEN'S DISEASE [Schaldenbrand & Appelman)
.] .
2--
I" ".~
[,. i~:
y,, ~/i' r o
FIGURE 4 (top left). Irregularly outlined nuclei, small circular nucleoli, and thin, short cytoplasmic processes from case 1. The abundant intercellular collagen fibrils are a g g r e g a t e d into nodules, corresponding to the hyaline globules observed light microscopically. ( x 3,500.] FIGURE 5 (top right]. Cytoplasm containing abundant filaments, from case 1. In this field, as in most fields, there are no dense bodies. A small intermediate junction is present [arrow]. At the bottom is a whorled nodule of collagen. ( x 15,200.] FIGURE 6 [bottom left). Cells from case 2 with fewer cytoplasmic filaments than in case 1. Focally, small amounts of basement-membranelike material adhere to the cell m e m b r a n e [arrows]. Notice the short cytoplasmic processes. ( x 15,200.) FIGURE 7 [bottom right]. Fusiform dense bodies from case 2, like those observed in case 1. Rows of pinocytotic vesicles can b e seen in the upper middle portion of the field. (x19,000.)
231
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t u m o r t h e r e were o n e o r two cells with structures closely resembling f n s i f o r m dense bodies, f o r m e d apparently f r o m linear aggregates o f the microfilaments (fig. 7). No vascular h t m e n s were adjacent to these cells, and the cells lacked b a s e m e n t m e m b r a n e . T h e s e cells also c o n t a i n e d occasional pinocytotic vesicles, which w e r e a b s e n t in t h e o t h e r t u m o r cells. Cell b o u n d a r i e s o f both lesions that b o r d e r e d o n intercellular matrix revealed a few thin, interlacing cytoplasmic processes w i t h o u t organelles, which w e r e partially covered by small "flecks" o f dense basementm e m b r a n e - l i k e material (fig. 6). No material similar to this was seen between adjacent t u m o r cells. Occasional intermediate-type j u n c t i o n s were present between t u m o r cells (fig. 5). T h e intercellular free space o f both lesions contained a b u n d a n t discrete strands and whorled aggregates o f collagen fibrillae with 64n m periodicity, c o r r e s p o n d i n g to the eosinophilic globules (figs. 4 to 6).
DISCUSSION Histologically, these two lesions most closely res e m b l e d fairly typical small intestinal l e i o m y o m a s . Despite the history o f n e u r o f i b r o m a t o s i s , these lesions lacked the histologic features of n e u r o f i b r o m a , were not encapsulated, a n d did not show the Antoni A and B areas characteristic o f neurilemomas. 7 Hyalinized blood vessels identical to those described in n e u r i l e m o m a were observed in the first case, but the a p p e a r a n c e o f that lesion was not otherwise consistent with that diagnosis. U h r a s t r u c t u r a l l y , the lesions a p p e a r e d similar. Rare intercellular j u n c t i o n s were present. In that the nuclei w e r e oval, i r r e g u l a r in outline, a n d , in the second case, segmented, with central r o u n d nucleoli, t h e y most closely r e s e m b l e d the nuclei o f s m o o t h muscle. While t h e r e were a b u n d a n t microfilaments in the cytoplasm o f both lesions, muhiple blocks were r e q u i r e d to f i n d an o c c a s i o n a l cell with f u s i f o r m dense bodies a n d / o r pinocytotic vesicles. Short interdigitating cytoplasmic processes with discontinuous b a s e m e n t - m e m b r a n e - l i k e material were observed in both cases, but they lacked the characteristic a p p e a r ance described in neurilemoma and neurofibroma, s-l~ P r o c e s s e s similar to t h e s e h a v e b e e n d e s c r i b e d in s m o o t h muscle neoplasms. In short, these two lesions u h r a s t r u c t u r a l l y had the n u c l e a r characteristics o f s m o o t h muscle a n d r a r e cytoplasmic f e a t u r e s suggesting s m o o t h muscle, but most o f the cells by far failed to show cytoplasmic characteristics o f any particular mesenchymal cell. We view these t u m o r s as being p r e d o m i n a n t l y u n d i f f e r e n t i a t e d mesenchymal neoplasms with focal differentiation toward s m o o t h muscle. O t h e r s might r e g a r d them as poorly differentiated leiomyomas, but the overwhelming majority o f the t u m o r cells did not have the cytoplasmic characteristics o f smooth muscle. T h e f n d i n g o f a few fusiform dense bodies does not constitute conchtsive e v i d e n c e that t h e e n t i r e n e o p l a s m was o f s m o o t h muscle type. F u r t h e r m o r e , the tumors o c c u r r e d in patients with von Recklinghausen's disease, which is
characterized by the f o r m a t i o n o f m a n y n e r v e sheath tumors. Weiss and MacKay, 11 in their study o f malignant smooth muscle gastrointestinal tumors, e m p h a sized that m a n y t u m o r s that seem to be o f smooth muscle type on light microscopy lack the ultrastructural cytoplasmic f e a t u r e s characteristic o f s m o o t h muscle. T h e y consider the uhrastructural characteristics o f t u m o r s that, on light microscopy, a p p e a r as leiomyosarcomas, to r e p r e s e n t "a spectrum f r o m unc o m m i t t e d m e s e n c h y m a l cells . . . to cells d e m o n strating u n e q u i v o c a l f e a t u r e s o f s m o o t h muscle. TM Welsh a n d M e y e r 12 r e p o r t e d this same f i n d i n g in their study o f gastric leiomyomas ten years earlier. T h e two t u m o r s d e s c r i b e d h e r e a r e c o m p o s e d o f t h e s e r e l a t i v e l y t m c o m m i t t e d m e s e n c h y m a l cells, which, only rarely d e m o n s t r a t e some cytoplasmic differentiation. N e o p l a s m s r e s e m b l i n g l e i o m y o m a s in the gastrointestinal tract o f patients with neurofibromatosis were first r e p o r t e d by Lukash. 5 T h e ultrastructural f e a t u r e s o f s u c h lesions h a v e not b e e n r e p o r t e d . While some might a r g u e that such cases r e p r e s e n t the c o i n c i d e n t a l o c c u r r e n c e o f l e i o m y o m a s in the gastrointestinal tract o f patients with neurofibromatosis, the relative rarity o f both gastrointestinal leiomyomas and neurofibromatosis, plus the presence o f gastrointestinal i n v o h ' e m e n t in as m a n y as one f o u r t h o f patients with neurofibromatosis, would a r g u e against this. F r o m o u r r e p o r t , it appears that patients with neurofibromatosis, while at risk for d e v e l o p i n g typical p e r i p h e r a l n e r v e s h e a t h n e o p l a s m s within the gastrointestinal tract, may also develop poorly differentiated stromal t u m o r s that resemble leiomyomas on light microscopy. Like previously r e p o r t e d "smooth muscle" t u m o r s o f the gut, these tumors uhrastructurally have few cytoplasmic features characteristic o f any specific cell line.
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