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2. Bures C, Barnes L. Benign mesenchymomas of the head and neck. Arch Pathol Lab Med 1978;102:237-241. 3. Chaitin BA, Goldman RL, Linker DC Angiomyolipoma of the penis. Urology 1984;23:305-306. 4. Chen KTK, Bauer V. Extrarenal angiomyolipoma. J Surg Oncol 1984;25:89-91. 5. Combes B, Ledoux A, Provendier B. Volumineux fibrome du ligament rond a developpement abdominal mais extraperitoneal. J Gynecol Obstet Biol Reprod 1988;17:347-349. 6. Demopoulous RI, Denarvaez F, Kaji V. Benign mixed mesodermal tumors of the uterus: A histogenetic study. Am J Clin Pathol 1973;60:377-383. 7. Enzinger FM, Weiss SW. Benign lipomatous tumors. In: Enzinger FM, Weiss SW, eds. Soft tissue tumors. St Louis: C.V. Mosby Company 1983:199-247. 8. Fernandez FA, Val-Bernal F, Garijo-Ayensa F. Mixed lipomas of the uterus and the broad ligament. Appl Pathol 1989;7:70-71.
A.J.C.P. • March 1990
9. Goodman ZD, Ishak KG. Angiomyolipomas of the liver. Am J Surg Pathol 1984;8:745-750. 10. Islam M. Benign mesenchymoma of seminal vesicles. Urology 1979;13:203-205. 11. Lattes R. Tumors of the soft tissues. Fascicle 1 in the Series: Atlas of Tumor Pathology. Washington DC: Armed Forces Institute of Pathology 1982; 101-104. 12. Le Ber MS, Stout AP. Benign mesenchymomas in children. Cancer 1962;15:598-605. 13. Mezzetti M. On tumors of the round ligament of the uterus (translated). Arch Ital Chir 1969;95:868-872. 14. Peh SC, Sivanesaratnam V. Angiomyolipoma of the vagina: An uncommon tumour. Case report. Br J Obstet Gynaecol 1988;95: 820-823. 15. Randazzo RF, Neustein P, Koyle MA. Spontaneous perinephric hemorrhage from extrarenal angiomyolipoma. Urology 1987;29: 428-431. 16. Stout AP. Mesenchymoma, the mixed tumor of mesenchymal derivatives. Ann Surg 1948;127:278-290.
Clinicopathologic, Immunohistochemical, and Ultrastructural Features of a Rare Primary Bone Tumor JEFFREY L. MYERS, M.D., WANDA BERNREUTER, M.D., AND WILLIAM DUNHAM, M.D.
The authors report a 35-year-old woman who presented with a lytic and blastic tumor of the ilium with soft tissue extension. The resected tumor showed light microscopic and ultrastructural features characteristic of a melanotic schwannoma. An unusual histologic finding was the presence of laminated concretions resembling psammoma bodies. Immunohistochemical stains for S-100, HMB-45, and vimentin were strongly positive. The patient is free of disease 18 months after complete surgical excision. (Key words: Melanotic schwannoma; Nerve sheath tumors; Bone neoplasms; Soft tissue neoplasms; Psammoma bodies) Am J Clin Pathol 1990;93:424-429 INTRAOSSEOUS SCHWANNOMAS are rare, representing less than 1% of the primary benign bone tumors reported by Dahlin and Unni. 3 Such tumors can occur at virtually any age and affect both sexes with nearly equal frequency.3,4'7 The most commonly involved site is the mandible.3-4'7 Radiographically they appear as well circumscribed lytic lesions and often are associated with a sclerotic border. Like their soft tissue counterparts, intraosseous schwannomas usually are solitary and behave
Received April 17, 1989; accepted for publication July 17, 1989. Dr. Dunham's current address is Medical Center East, Birmingham, Alabama. Address reprint requests to Dr. Myers: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905.
Division of Surgical Pathology, Department of Radiology, and Division of Orthopedic Oncology, University of Alabama at Birmingham, Birmingham, Alabama
in a benign fashion. Histologically they have features typical of schwannomas elsewhere and are composed of alternating Antoni A and B areas. Cellular Antoni A areas predominate in some cases.4 Melanotic schwannomas, also referred to as melanocyte schwannomas, represent uncommon variants of nerve sheath tumors that differ from typical schwannomas in that they show light microscopic and ultrastructural evidence of melanocyte differentiation. They affect males and females equally and generally occur in young adults, with a peak incidence in the third and fourth decades.5 They have been reported in a variety of visceral and soft tissue sites but arise most commonly within spinal nerve roots or sympathetic ganglia.5'1' Complete resection is curative in most patients. Metastases and death are rare and have occurred only in patients with tumors of the sympathetic ganglia.5 The authors report a melanotic schwannoma arising in bone that clinically and radiologically mimicked a malignant tumor.
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Melanotic Schwannoma of Bone
SINGLE CASE REPORTS
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expansion and remodeling of the medullary space by tumor with an associated soft tissue component that appeared to project from a bony A 35-year-old black woman presented with a 5-year history of pain pedicle (Fig. 1). Nuclear magnetic resonance imaging confirmed the CT in her right lateral thigh. The pain recently had worsened. Five weeks findings and showed low signal on Tl weighted images and high signal before admission, she complained of increasing discomfort in her right on T2 weighted images consistent with a nonlipomatous neoplasm. The groin, lateral thigh, and posterior hip. The pain limited her ability to radiographic differential diagnosis included chondrosarcoma, either priambulate. Her family history and review of systems were unremarkable. mary or arising in an osteochondroma, and osteosarcoma. A staging Physical examination revealed tenderness in her posterolateral right hip workup including CT and MRI scanning of the thorax and a bone scan were negative for metastases. associated with a palpable mass that measured approximately 13 cm in She underwent open incisional biopsy followed by wide resection, greatest dimension. There was diminished perception of pin-prick in the distribution of S1, S2, and S3. The remainder of her physical examination which required a right internal hemipelvectomy. Her reconstruction was was unremarkable. All laboratory data were within normal limits. accomplished using her own autoclaved bony hemipelvis and a bipolar Plain AP and frog lateral views of the right hip and pelvis showed a arthroplasty. Briefly, the soft tissue component of the tumor was dissected destructive lesion of the ilium and ischium associated with soft tissue from the surface of the excised bone and the intraosseous component was curetted from the specimen. The bone graft was then autoclaved for extension (Fig. 1). The bone lesion contained mixed areas of lucency and sclerosis and had an incomplete sclerotic rim. The soft tissue mass 5 minutes and reimplanted into the patient as described by Harrington had matrix calcifications. A computed tomographic (CT) scan showed and colleagues.6 Her postoperative course was complicated by persistent
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FIG 1. A (left). A plain roentgenogram of therighthip shows a destructive lesion of the ilium and ischium. The lesion shows mixed areas of lucency and sclerosis bounded by an incomplete sclerotic rim. The tumor extends into the soft tissues and is associated with matrix calcifications. B (right). A CT scan of the pelvis shows expansion and remodeling of the ilium by tumor, which extends into the adjacent soft tissues. The soft tissue component projects from the bone on a broad based pedicle.
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wound infection, which failed to respond to multiple drainage procedures and parenteral antibiotic therapy, and she underwent removal of the autograft 4.5 months after her initial surgery. She is free of recurrent disease 18 months after her initial surgery.
Materials and Methods
Results The specimen from herfirstsurgery consisted of an 8.5 X 5.5 X 2.0 cm lightly pigmented tan brown tumor with
expansile pushing borders and was bounded by a connective tissue pseudocapsule (Fig. 2). The cut surface had a lobular configuration, and the tumor lobules were separated by incomplete fibrous septa. Histologically the tumor was composed of plump spindle cells with centrally located nuclei and variably abundant granular eosinophilic cytoplasm (Fig. 3). The spindle cells interdigitated with mature adipocytes and were, for the most part, distributed in a haphazard growth pattern. Elsewhere the cells were arranged in compact interlacing fascicles with vague nuclear palisading. Mitotic figures were not seen, and there was no necrosis. Numerous tumor cells contained abundant cytoplasmic pigment that had afinelygranular dusty brown appearance. FontanaMasson stains were positive in these areas. Occasional cells also contained coarse refractile golden-brown pigment that stained positively for iron. An unusual feature was the presence of laminated concretions throughout the neoplasm (Fig. 4). The calcified concretions were round and resembled psammoma bodies except that they varied widely in size. In some areas the laminated concretions coalesced into large irregularly shaped islands. The autograft excised 4.5 months after the patient's initial surgery consisted of most of the ilium, including a portion of the sacroiliac joint. The bone was largely ne-
FlG. 2. The cut surface of the tumor is pigmented and has a lobulated appearance. The tumor lobules are separated by delicatefibroussepta.
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The tissue was fixed primarily in formalin for routine light microscopy. Fontana-Masson and Prussian blue iron stains were done on selected blocks. A portion of the initially excised tumor was fixed in 95% (weight/volume) ethanol for immunohistochemical staining. The tumor was examined for S-100 protein, HMB-45, Leu 7, myelin basic protein, glialfibrillaryacidic protein, vimentin, desmin, and keratin (48-60 kD) using the peroxidase-antiperoxidase technique. Tissue from the first specimen was minced into 1 mm cubes for electron microscopy, fixed in 4% (w/v) formaldehyde, 1% (w/v) glutaraldehyde and processed in the usual manner. Thin sections were stained with uranyl acetate-lead citrate and examined in a Philips 201 transmission electron microscope.
A.J.C.P. • March 1990
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FIG. 3 (upper, left). Photomicrograph of the tumor showing spindle cells arranged in loosely organized fascicles. The fascicles interdigitate between adipocytes. Widely scattered tumor cells containfinelygranular pigment (arrow) (X275). FIG. 4 (upper, right). Low magnification photomicrograph showing lamellated calcific concretions randomly distributed within the tumor. Vague nuclear palisading is seen in the lower portion of thefield,and there are occasional pigmented cells (arrows) (XI10). FIG. 5 (lower, left). Electron micrograph showing pigmented and nonpigmented tumor cells. The cytoplasm contains varying proportions of mitochondria and melanosomes. Individual cells are invested by basal lamina, which is also arranged in redundant coils between the cells (X4,170). FIG. 6 (lower, right). Higher magnification electron micrograph showing a tumor cell containing numerous pigmented melanosomes. Abundant basal lamina is also present (X9,500).
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Discussion The authors are aware of only a single previous report of intraosseous melanotic schwannoma.9 In that patient, however, melanotic schwannoma was combined with an adamantinoma in a complex cystic neoplasm of the mandible. This report is the first example of an intraosseous melanotic schwannoma arising within an extragnathic bone. Multiple radiographic studies confirmed the intraosseous origin of the tumor and showed a destructive lytic lesion with soft tissue extension. These findings are highly suggestive of a malignant bone tumor and contrast with the banal radiographic appearance characteristic of typical (nonpigmented) intraosseous schwannomas.3,4,7 Melanotic schwannomas have been described as a component of a complex familial syndrome characterized by the presence of myxomatous masses, pigmented skin lesions, and endocrine disorders.' 10 Specific lesions associated with this syndrome include solitary or multiple cardiac myxomas, cutaneous myxomas, epithelial cysts, lentigines and blue nevi, myxoid fibroadenomas of the breast, primary pigmented nodular adrenocortical disease, testicular stromal tumors, and growth hormone-producing pituitary adenomas. Cardiac myxomas are the most common manifestation of this syndrome and were seen in 29 of 40 (72.5%) patients initially described by Carney and
colleagues.1 Melanotic schwannomas were present in only two patients from that same series; both were soft tissue masses arising within the retroperitoneum and around the knee. Interestingly, both of those tumors also contained laminated concretions resembling psammoma bodies. Although the clinical history and physical examination failed to reveal other features of this syndrome in the authors' patient, detailed cardiac and endocrine evaluations were not performed. The histologic features of this case resemble previous descriptions of melanotic schwannomas. 1,5 " 6 "" 13 The main findings were pigmented spindle cells with vague nuclear palisading and stromal calcifications. Most of the pigment was melanin, but hemosiderin also was present. The laminated calcific concretions undoubtedly accounted for the radiographically detectable matrix calcifications. Identical calcifications have been observed in other cases and are considered characteristic of this lesion by some authors.5 Immunohistochemical studies showed a staining pattern typical of other nerve sheath tumors. Staining for S100 and vimentin has been observed by others in similar soft tissue tumors. 13 Leu 7, myelin basic protein, and glial fibrillary acidic protein are expressed less commonly and were not present in this case. Positive staining with HMB45, a monoclonal antibody that recognizes a cytoplasmic and cell membrane determinant in melanocytic cells, was an interesting and unexpected finding. This antibody is relatively specific for malignant melanomas, although positive staining has been reported in other neoplasms of neural crest origin, including nonpigmented schwannomas.2,14 HMB-45 expression in this case further substantiates the closely related histogenesis of schwannoma and malignant melanoma. Electron microscopy showed features of Schwann cell differentiation as well as melanogenesis within the neoplastic cells. These findings support the observations of others and are consistent with the contention that neoplastic Schwann cells are capable of melanin synthesis. An unusual finding that has not been emphasized in previous reports was the accumulation of structurally abnormal mitochondria in some tumor cells. This finding correlated with the "oxyphilic" appearance of many of the tumor cells by light microscopy and likely represents a nonspecific degenerative change. The light microscopic features of melanotic schwannoma are distinctive and unlikely to be confused with other primary bone tumors. Spindle cell tumors that might enter the differential diagnosis include nonossifying fibroma, desmoplastic fibroma, and certain sarcomas. Nonossifying fibromas differ from melanotic schwannoma in that the spindle cells frequently are arranged in a storiform pattern without nuclear palisading, multinucleated giant cells usually are present, and they lack melanin pig-
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erotic and showed extensive osteomyelitis. Although no grossly visible tumor was seen, microscopic examination revealed numerous foci of residual viable tumor. The residual tumor was confined to the intraosseous compartment without soft tissue extension. Immunohistochemical stains for S-100, HMB-45, and vimentin were strongly positive. The spindle cells showed diffuse cytoplasmic positivity throughout the tumor. Faint cytoplasmic staining for keratin was seen in a minority of tumor cells. Immunohistochemical stains for Leu 7, myelin basic protein, glial fibrillary acidic protein, and desmin were negative. Ultrastructural examination showed bipolar spindle cells with slender interdigitating cytoplasmic processes (Fig. 5). The cell bodies and cytoplasmic processes were invested by basal laminae, which often were redundant. The nuclei were irregularly shaped with finely dispersed delicate euchromatin. Nucleoli were absent or poorly developed. The cytoplasm of numerous cells contained variable numbers of pigmented stage III and IV melanosomes (Fig. 6). Immature stage II melanosomes (premelanosomes) were present in some cells. Melanosomes occasionally were fused to form irregularly shaped masses that displaced the nucleus. Many cells contained abundant mitochondria that frequently had abnormal configurations. Mitochondria were present to the exclusion of melanosomes in some cells, while both were present in others.
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3.
4.
5. 6.
7.
8.
9.
10.
11. 12.
References 13. 1. Carney J, Gordon H, Carpenter P, et al. The complex of myxomas, spotty pigmentation, and endocrine overeactivity. Medicine 1985;64:270-283. 2. Colombari R, Bonetti F, Zamboni G, et al. Distribution of melanoma specific antibody (HMB-45) in benign and malignant melanocyte
14.
tumours. An immunohistochemical study on paraffin sections. Virchow Archiv A Pathol Anat 1988;413:17-24. Dahlin D, Unni K. Bone Tumors General Aspects and Data on 8,542 Cases. 4th ed. Springfield: Charles C. Thomas, 1986,186192. De La Monte S, Dorfman H, Chandra R, Malawer M. Intraosseous schwannoma: Histologic features, ultrastructure, and review of the literature. Hum Pathol 1984;15:551-558. Enzinger F, Weiss S. Soft Tissue Tumors. St. Louis, MO: The C. V. Mosby Company, 1988,832-833. Font R, Truong L. Melanotic schwannoma of soft tissues. Electronmicroscopic observations and review of literature. Am J Surg Pathol 1984;8:129-138. Gordon E. Solitary intraosseous neurilemmoma of the tibia. Review of intraosseous neurilemmoma and neurofibroma. Clin Orthop 1976;117:271-282. Harrington K, Johnston J, Kaufer H, et al. Limb salvage and prosthetic joint reconstruction for low-grade and selected high-grade sarcomas of bone after wide resection and replacement by autoclaved autogeneic grafts. Clin Orthop 1986;211:180-214. Hodson J. An intra-osseous tumour combination of biological importance: Invasion of a melanotic schwannoma by an adamantinoma. J Pathol Bacteriol 1961;82:257-266. Leedman P, Cohen A, Matz L. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Clin Endocrinol 1986;25:527-534. McGavran W III, Sypert G, Ballinger W. Melanotic schwannoma. Neurosurgery 1978;2:47-51. Mennemeyer R, Hammar S, Tytus J, et al. Melanotic schwannoma. Clinical and ultrastructural studies of three cases with evidence of intracellular melanin synthesis. Am J Surg Pathol 1979;3:310. Miettinen M. Melanotic schwannoma coexpression of vimentin and glial fibrillary acidic protein. Ultrastruct Pathol 1987;! 1:39-46. Wick M, Stanley S, Swanson P. Immunohistochemical diagnosis of sinonasal melanoma, carcinoma, and neuroblastoma with monoclonal antibodies HMB-45 and anti-synaptophysin. Arch Pathol Lab Med 1988;! 12:616-620.
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ment and laminated concretions. Desmoplastic fibromas are characterized by the presence of spindled fibroblasts that are arranged in broad fascicles with a prominent collagenous matrix. The absence of nuclear palisading, pigment, and laminated calcifications, coupled with the presence of collagen fibrosis serve to distinguish this tumor from melanotic schwannoma. A number of malignant bone tumors also may have a predominantly spindled appearance, including some osteosarcomas, fibrosarcomas, and malignant fibrous histiocytomas. The presence of nuclear hyperchromasia and pleomorphism, a high mitotic rate, and tumor necrosis help to separate these malignant neoplasms from melanotic schwannoma. The natural history of melanotic schwannomas is difficult to predict on the basis of histologic features alone. Most are cured with adequate excision, but there is no experience with primary intraosseous tumors to compare with this patient. Although she has suffered no local recurrence or distant metastases to date, long-term followup and observation of additional cases is required before a more definitive statement can be made concerning prognosis of this rare entity.
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2. Bures C, Barnes L. Benign mesenchymomas of the head and neck. Arch Pathol Lab Med 1978;102:237-241. 3. Chaitin BA, Goldman RL, Linker DC Angiomyolipoma of the penis. Urology 1984;23:305-306. 4. Chen KTK, Bauer V. Extrarenal angiomyolipoma. J Surg Oncol 1984;25:89-91. 5. Combes B, Ledoux A, Provendier B. Volumineux fibrome du ligament rond a developpement abdominal mais extraperitoneal. J Gynecol Obstet Biol Reprod 1988;17:347-349. 6. Demopoulous RI, Denarvaez F, Kaji V. Benign mixed mesodermal tumors of the uterus: A histogenetic study. Am J Clin Pathol 1973;60:377-383. 7. Enzinger FM, Weiss SW. Benign lipomatous tumors. In: Enzinger FM, Weiss SW, eds. Soft tissue tumors. St Louis: C.V. Mosby Company 1983:199-247. 8. Fernandez FA, Val-Bernal F, Garijo-Ayensa F. Mixed lipomas of the uterus and the broad ligament. Appl Pathol 1989;7:70-71.
A.J.C.P. • March 1990
9. Goodman ZD, Ishak KG. Angiomyolipomas of the liver. Am J Surg Pathol 1984;8:745-750. 10. Islam M. Benign mesenchymoma of seminal vesicles. Urology 1979;13:203-205. 11. Lattes R. Tumors of the soft tissues. Fascicle 1 in the Series: Atlas of Tumor Pathology. Washington DC: Armed Forces Institute of Pathology 1982; 101-104. 12. Le Ber MS, Stout AP. Benign mesenchymomas in children. Cancer 1962;15:598-605. 13. Mezzetti M. On tumors of the round ligament of the uterus (translated). Arch Ital Chir 1969;95:868-872. 14. Peh SC, Sivanesaratnam V. Angiomyolipoma of the vagina: An uncommon tumour. Case report. Br J Obstet Gynaecol 1988;95: 820-823. 15. Randazzo RF, Neustein P, Koyle MA. Spontaneous perinephric hemorrhage from extrarenal angiomyolipoma. Urology 1987;29: 428-431. 16. Stout AP. Mesenchymoma, the mixed tumor of mesenchymal derivatives. Ann Surg 1948;127:278-290.
Clinicopathologic, Immunohistochemical, and Ultrastructural Features of a Rare Primary Bone Tumor JEFFREY L. MYERS, M.D., WANDA BERNREUTER, M.D., AND WILLIAM DUNHAM, M.D.
The authors report a 35-year-old woman who presented with a lytic and blastic tumor of the ilium with soft tissue extension. The resected tumor showed light microscopic and ultrastructural features characteristic of a melanotic schwannoma. An unusual histologic finding was the presence of laminated concretions resembling psammoma bodies. Immunohistochemical stains for S-100, HMB-45, and vimentin were strongly positive. The patient is free of disease 18 months after complete surgical excision. (Key words: Melanotic schwannoma; Nerve sheath tumors; Bone neoplasms; Soft tissue neoplasms; Psammoma bodies) Am J Clin Pathol 1990;93:424-429 INTRAOSSEOUS SCHWANNOMAS are rare, representing less than 1% of the primary benign bone tumors reported by Dahlin and Unni. 3 Such tumors can occur at virtually any age and affect both sexes with nearly equal frequency.3,4'7 The most commonly involved site is the mandible.3-4'7 Radiographically they appear as well circumscribed lytic lesions and often are associated with a sclerotic border. Like their soft tissue counterparts, intraosseous schwannomas usually are solitary and behave
Received April 17, 1989; accepted for publication July 17, 1989. Dr. Dunham's current address is Medical Center East, Birmingham, Alabama. Address reprint requests to Dr. Myers: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905.
Division of Surgical Pathology, Department of Radiology, and Division of Orthopedic Oncology, University of Alabama at Birmingham, Birmingham, Alabama
in a benign fashion. Histologically they have features typical of schwannomas elsewhere and are composed of alternating Antoni A and B areas. Cellular Antoni A areas predominate in some cases.4 Melanotic schwannomas, also referred to as melanocyte schwannomas, represent uncommon variants of nerve sheath tumors that differ from typical schwannomas in that they show light microscopic and ultrastructural evidence of melanocyte differentiation. They affect males and females equally and generally occur in young adults, with a peak incidence in the third and fourth decades.5 They have been reported in a variety of visceral and soft tissue sites but arise most commonly within spinal nerve roots or sympathetic ganglia.5'1' Complete resection is curative in most patients. Metastases and death are rare and have occurred only in patients with tumors of the sympathetic ganglia.5 The authors report a melanotic schwannoma arising in bone that clinically and radiologically mimicked a malignant tumor.
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Melanotic Schwannoma of Bone
SINGLE CASE REPORTS
Vol. 93 • No. 3
425
Case Report
expansion and remodeling of the medullary space by tumor with an associated soft tissue component that appeared to project from a bony A 35-year-old black woman presented with a 5-year history of pain pedicle (Fig. 1). Nuclear magnetic resonance imaging confirmed the CT in her right lateral thigh. The pain recently had worsened. Five weeks findings and showed low signal on Tl weighted images and high signal before admission, she complained of increasing discomfort in her right on T2 weighted images consistent with a nonlipomatous neoplasm. The groin, lateral thigh, and posterior hip. The pain limited her ability to radiographic differential diagnosis included chondrosarcoma, either priambulate. Her family history and review of systems were unremarkable. mary or arising in an osteochondroma, and osteosarcoma. A staging Physical examination revealed tenderness in her posterolateral right hip workup including CT and MRI scanning of the thorax and a bone scan were negative for metastases. associated with a palpable mass that measured approximately 13 cm in She underwent open incisional biopsy followed by wide resection, greatest dimension. There was diminished perception of pin-prick in the distribution of S1, S2, and S3. The remainder of her physical examination which required a right internal hemipelvectomy. Her reconstruction was was unremarkable. All laboratory data were within normal limits. accomplished using her own autoclaved bony hemipelvis and a bipolar Plain AP and frog lateral views of the right hip and pelvis showed a arthroplasty. Briefly, the soft tissue component of the tumor was dissected destructive lesion of the ilium and ischium associated with soft tissue from the surface of the excised bone and the intraosseous component was curetted from the specimen. The bone graft was then autoclaved for extension (Fig. 1). The bone lesion contained mixed areas of lucency and sclerosis and had an incomplete sclerotic rim. The soft tissue mass 5 minutes and reimplanted into the patient as described by Harrington had matrix calcifications. A computed tomographic (CT) scan showed and colleagues.6 Her postoperative course was complicated by persistent
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
FIG 1. A (left). A plain roentgenogram of therighthip shows a destructive lesion of the ilium and ischium. The lesion shows mixed areas of lucency and sclerosis bounded by an incomplete sclerotic rim. The tumor extends into the soft tissues and is associated with matrix calcifications. B (right). A CT scan of the pelvis shows expansion and remodeling of the ilium by tumor, which extends into the adjacent soft tissues. The soft tissue component projects from the bone on a broad based pedicle.
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wound infection, which failed to respond to multiple drainage procedures and parenteral antibiotic therapy, and she underwent removal of the autograft 4.5 months after her initial surgery. She is free of recurrent disease 18 months after her initial surgery.
Materials and Methods
Results The specimen from herfirstsurgery consisted of an 8.5 X 5.5 X 2.0 cm lightly pigmented tan brown tumor with
expansile pushing borders and was bounded by a connective tissue pseudocapsule (Fig. 2). The cut surface had a lobular configuration, and the tumor lobules were separated by incomplete fibrous septa. Histologically the tumor was composed of plump spindle cells with centrally located nuclei and variably abundant granular eosinophilic cytoplasm (Fig. 3). The spindle cells interdigitated with mature adipocytes and were, for the most part, distributed in a haphazard growth pattern. Elsewhere the cells were arranged in compact interlacing fascicles with vague nuclear palisading. Mitotic figures were not seen, and there was no necrosis. Numerous tumor cells contained abundant cytoplasmic pigment that had afinelygranular dusty brown appearance. FontanaMasson stains were positive in these areas. Occasional cells also contained coarse refractile golden-brown pigment that stained positively for iron. An unusual feature was the presence of laminated concretions throughout the neoplasm (Fig. 4). The calcified concretions were round and resembled psammoma bodies except that they varied widely in size. In some areas the laminated concretions coalesced into large irregularly shaped islands. The autograft excised 4.5 months after the patient's initial surgery consisted of most of the ilium, including a portion of the sacroiliac joint. The bone was largely ne-
FlG. 2. The cut surface of the tumor is pigmented and has a lobulated appearance. The tumor lobules are separated by delicatefibroussepta.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
The tissue was fixed primarily in formalin for routine light microscopy. Fontana-Masson and Prussian blue iron stains were done on selected blocks. A portion of the initially excised tumor was fixed in 95% (weight/volume) ethanol for immunohistochemical staining. The tumor was examined for S-100 protein, HMB-45, Leu 7, myelin basic protein, glialfibrillaryacidic protein, vimentin, desmin, and keratin (48-60 kD) using the peroxidase-antiperoxidase technique. Tissue from the first specimen was minced into 1 mm cubes for electron microscopy, fixed in 4% (w/v) formaldehyde, 1% (w/v) glutaraldehyde and processed in the usual manner. Thin sections were stained with uranyl acetate-lead citrate and examined in a Philips 201 transmission electron microscope.
A.J.C.P. • March 1990
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FIG. 3 (upper, left). Photomicrograph of the tumor showing spindle cells arranged in loosely organized fascicles. The fascicles interdigitate between adipocytes. Widely scattered tumor cells containfinelygranular pigment (arrow) (X275). FIG. 4 (upper, right). Low magnification photomicrograph showing lamellated calcific concretions randomly distributed within the tumor. Vague nuclear palisading is seen in the lower portion of thefield,and there are occasional pigmented cells (arrows) (XI10). FIG. 5 (lower, left). Electron micrograph showing pigmented and nonpigmented tumor cells. The cytoplasm contains varying proportions of mitochondria and melanosomes. Individual cells are invested by basal lamina, which is also arranged in redundant coils between the cells (X4,170). FIG. 6 (lower, right). Higher magnification electron micrograph showing a tumor cell containing numerous pigmented melanosomes. Abundant basal lamina is also present (X9,500).
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Discussion The authors are aware of only a single previous report of intraosseous melanotic schwannoma.9 In that patient, however, melanotic schwannoma was combined with an adamantinoma in a complex cystic neoplasm of the mandible. This report is the first example of an intraosseous melanotic schwannoma arising within an extragnathic bone. Multiple radiographic studies confirmed the intraosseous origin of the tumor and showed a destructive lytic lesion with soft tissue extension. These findings are highly suggestive of a malignant bone tumor and contrast with the banal radiographic appearance characteristic of typical (nonpigmented) intraosseous schwannomas.3,4,7 Melanotic schwannomas have been described as a component of a complex familial syndrome characterized by the presence of myxomatous masses, pigmented skin lesions, and endocrine disorders.' 10 Specific lesions associated with this syndrome include solitary or multiple cardiac myxomas, cutaneous myxomas, epithelial cysts, lentigines and blue nevi, myxoid fibroadenomas of the breast, primary pigmented nodular adrenocortical disease, testicular stromal tumors, and growth hormone-producing pituitary adenomas. Cardiac myxomas are the most common manifestation of this syndrome and were seen in 29 of 40 (72.5%) patients initially described by Carney and
colleagues.1 Melanotic schwannomas were present in only two patients from that same series; both were soft tissue masses arising within the retroperitoneum and around the knee. Interestingly, both of those tumors also contained laminated concretions resembling psammoma bodies. Although the clinical history and physical examination failed to reveal other features of this syndrome in the authors' patient, detailed cardiac and endocrine evaluations were not performed. The histologic features of this case resemble previous descriptions of melanotic schwannomas. 1,5 " 6 "" 13 The main findings were pigmented spindle cells with vague nuclear palisading and stromal calcifications. Most of the pigment was melanin, but hemosiderin also was present. The laminated calcific concretions undoubtedly accounted for the radiographically detectable matrix calcifications. Identical calcifications have been observed in other cases and are considered characteristic of this lesion by some authors.5 Immunohistochemical studies showed a staining pattern typical of other nerve sheath tumors. Staining for S100 and vimentin has been observed by others in similar soft tissue tumors. 13 Leu 7, myelin basic protein, and glial fibrillary acidic protein are expressed less commonly and were not present in this case. Positive staining with HMB45, a monoclonal antibody that recognizes a cytoplasmic and cell membrane determinant in melanocytic cells, was an interesting and unexpected finding. This antibody is relatively specific for malignant melanomas, although positive staining has been reported in other neoplasms of neural crest origin, including nonpigmented schwannomas.2,14 HMB-45 expression in this case further substantiates the closely related histogenesis of schwannoma and malignant melanoma. Electron microscopy showed features of Schwann cell differentiation as well as melanogenesis within the neoplastic cells. These findings support the observations of others and are consistent with the contention that neoplastic Schwann cells are capable of melanin synthesis. An unusual finding that has not been emphasized in previous reports was the accumulation of structurally abnormal mitochondria in some tumor cells. This finding correlated with the "oxyphilic" appearance of many of the tumor cells by light microscopy and likely represents a nonspecific degenerative change. The light microscopic features of melanotic schwannoma are distinctive and unlikely to be confused with other primary bone tumors. Spindle cell tumors that might enter the differential diagnosis include nonossifying fibroma, desmoplastic fibroma, and certain sarcomas. Nonossifying fibromas differ from melanotic schwannoma in that the spindle cells frequently are arranged in a storiform pattern without nuclear palisading, multinucleated giant cells usually are present, and they lack melanin pig-
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erotic and showed extensive osteomyelitis. Although no grossly visible tumor was seen, microscopic examination revealed numerous foci of residual viable tumor. The residual tumor was confined to the intraosseous compartment without soft tissue extension. Immunohistochemical stains for S-100, HMB-45, and vimentin were strongly positive. The spindle cells showed diffuse cytoplasmic positivity throughout the tumor. Faint cytoplasmic staining for keratin was seen in a minority of tumor cells. Immunohistochemical stains for Leu 7, myelin basic protein, glial fibrillary acidic protein, and desmin were negative. Ultrastructural examination showed bipolar spindle cells with slender interdigitating cytoplasmic processes (Fig. 5). The cell bodies and cytoplasmic processes were invested by basal laminae, which often were redundant. The nuclei were irregularly shaped with finely dispersed delicate euchromatin. Nucleoli were absent or poorly developed. The cytoplasm of numerous cells contained variable numbers of pigmented stage III and IV melanosomes (Fig. 6). Immature stage II melanosomes (premelanosomes) were present in some cells. Melanosomes occasionally were fused to form irregularly shaped masses that displaced the nucleus. Many cells contained abundant mitochondria that frequently had abnormal configurations. Mitochondria were present to the exclusion of melanosomes in some cells, while both were present in others.
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References 13. 1. Carney J, Gordon H, Carpenter P, et al. The complex of myxomas, spotty pigmentation, and endocrine overeactivity. Medicine 1985;64:270-283. 2. Colombari R, Bonetti F, Zamboni G, et al. Distribution of melanoma specific antibody (HMB-45) in benign and malignant melanocyte
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tumours. An immunohistochemical study on paraffin sections. Virchow Archiv A Pathol Anat 1988;413:17-24. Dahlin D, Unni K. Bone Tumors General Aspects and Data on 8,542 Cases. 4th ed. Springfield: Charles C. Thomas, 1986,186192. De La Monte S, Dorfman H, Chandra R, Malawer M. Intraosseous schwannoma: Histologic features, ultrastructure, and review of the literature. Hum Pathol 1984;15:551-558. Enzinger F, Weiss S. Soft Tissue Tumors. St. Louis, MO: The C. V. Mosby Company, 1988,832-833. Font R, Truong L. Melanotic schwannoma of soft tissues. Electronmicroscopic observations and review of literature. Am J Surg Pathol 1984;8:129-138. Gordon E. Solitary intraosseous neurilemmoma of the tibia. Review of intraosseous neurilemmoma and neurofibroma. Clin Orthop 1976;117:271-282. Harrington K, Johnston J, Kaufer H, et al. Limb salvage and prosthetic joint reconstruction for low-grade and selected high-grade sarcomas of bone after wide resection and replacement by autoclaved autogeneic grafts. Clin Orthop 1986;211:180-214. Hodson J. An intra-osseous tumour combination of biological importance: Invasion of a melanotic schwannoma by an adamantinoma. J Pathol Bacteriol 1961;82:257-266. Leedman P, Cohen A, Matz L. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Clin Endocrinol 1986;25:527-534. McGavran W III, Sypert G, Ballinger W. Melanotic schwannoma. Neurosurgery 1978;2:47-51. Mennemeyer R, Hammar S, Tytus J, et al. Melanotic schwannoma. Clinical and ultrastructural studies of three cases with evidence of intracellular melanin synthesis. Am J Surg Pathol 1979;3:310. Miettinen M. Melanotic schwannoma coexpression of vimentin and glial fibrillary acidic protein. Ultrastruct Pathol 1987;! 1:39-46. Wick M, Stanley S, Swanson P. Immunohistochemical diagnosis of sinonasal melanoma, carcinoma, and neuroblastoma with monoclonal antibodies HMB-45 and anti-synaptophysin. Arch Pathol Lab Med 1988;! 12:616-620.
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ment and laminated concretions. Desmoplastic fibromas are characterized by the presence of spindled fibroblasts that are arranged in broad fascicles with a prominent collagenous matrix. The absence of nuclear palisading, pigment, and laminated calcifications, coupled with the presence of collagen fibrosis serve to distinguish this tumor from melanotic schwannoma. A number of malignant bone tumors also may have a predominantly spindled appearance, including some osteosarcomas, fibrosarcomas, and malignant fibrous histiocytomas. The presence of nuclear hyperchromasia and pleomorphism, a high mitotic rate, and tumor necrosis help to separate these malignant neoplasms from melanotic schwannoma. The natural history of melanotic schwannomas is difficult to predict on the basis of histologic features alone. Most are cured with adequate excision, but there is no experience with primary intraosseous tumors to compare with this patient. Although she has suffered no local recurrence or distant metastases to date, long-term followup and observation of additional cases is required before a more definitive statement can be made concerning prognosis of this rare entity.
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