- Email: [email protected]
Malignant schwannoma associated with xeroderma pigmentosum in a patient belonging to complementation group D
Cutaneous multi/obated T-cell lymphoma
6. 7.
8. 9.
retrospective study of 6 cases in Europe. Dermatologica 1988;177:82-97. van der Putte SCJ, Toonstra J, De Weger RA, et al. Cutaneous T-cell lymphoma, multilobated type. Histopathology 1982;6:35-54. Azar HA, Jaffe ES, Berard CW, et al. Diffuse large-cell lymphomas (reticulum cell sarcomas, histiocytic lymphomas): correlation of morphologic features with functional markers. Cancer 1980;46: 1428-41. Fattorossi A, Moretti S, Palermo A, et al. Cell surface marker studies in a patient with cutaneous multilobated Tcell lymphoma. Br J DermatoI1985;113:587-96. Wood GS, Burke IS, Horning S, et al. The immunologic and clinicopathologic heterogeneity of cutaneous lymphomas other than mycosis fungoides. Blood 1983;62:464-72.
10. Nasu K, Said J, Vonderheid E, et al. Immunopathology of cutaneous T-cell lymphoma. Am J Pathol 1985;119:43647. 11. van der Valk P, Willemze R, Meijer CJLM. Peripheral Tcell lymphomas: a clinicopathological and immunological study of 10 cases. Histopathol 1986;10:235-49. 12. van der PutteSCJ, Schuurman HJ, Toonstra J. Cutaneous T-cell lymphoma, multilobulated type, expressing membrane-differentiation antigens of precursor T-Iymphocytes. Br J Dermatol 1982;107:293-300. 13. Beljaards RC, Meijer CJLM, Scheffer E, et al. Prognostic significance of CD30 (Ki-l /Ber-H2) expression in primary cutaneous large-cell lymphomas of T-cell origin. Am J PathoI1989;135:1169-78.
Malignant schwannoma associated with xeroderma pigmentosum in a patient belonging to complementation group D Takehiko Nakamura, MD,a Tomomichi Ono, MD,a Koji Yoshimura, MD,a Tatsuyoshi Arao, MD,a Seiji Kondo, MD,b Masamitsu Ichihashi, MD,d Akira Matsumoto, MD,c and Yoshisada Fujiwara, MD, PhDc Kumamoto, Tokyo, and Kobe, Japan A 43-year-old man with xeroderma pigmentosum, XP97TO, was allocated to complementation group D. He had had moderate photosensitivity at age 1 year and freckles by age 6 but no neurologic abnormalities. Nevertheless, his fibroblasts in culture had the XP-D phenotype. They showed a sevenfold hypersensitivity to killing by 254 nm ultraviolet radiation and a diminished level (29%) of unscheduled DNA synthesis. Phototesting revealed delayed maximum erythema at 72 hours after UVB exposure and a lowered minimal erythema dose. Lentigo maligna developed on the patient's face, and a rapidly growing malignant schwannoma was found on the left trigeminal nerve. This may be the first case of a peripheral nervous tissue neoplasm in xeroderma pigmentosum. (J AM ACAD DERMATOL 1991:25;349-53.) Xeroderma pigmentosum (XP) consists of eight excision-defective complementation groups (A through H), and an XP variant group capable From the Department of Dermatology, Kumamoto University Medical School, Kumamoto;" the Department of Dermatology, School of Medicine, Tokyo Medical and Dental University, Tokyob; and the Departments of Radiation Biophysics and Dermato]ogy,d Kobe University School of Medicine, Kobe. Supported in part by agrant-in-aid for cancer research from the Ministry of Education, Science and Culture, Japan. Reprint requests: Dr. T. Nakamura, Department of Dermatology, Kumamoto University Medical School, 1-1-1 Banjo, Kumamoto 860, Japan. C
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of normally excising cyc10butane pyrimidine dimers. 1-3 Patients in certain XP groups (A, B, D, G, and H) often have cerebral and spinocerebellar abnormalities. In the major XP groups, they are found in most XP-A patients by 7 years of age. 4 - 6 Most XP-D patients show neurologic abnormalities between 7 and 20 years of age,4, 5 whereas some do not appear to have them beyond the second decade. 2, 7-9 The published reviews of Kraemer et aL 10,1 I on 830 XP patients disclosed a disproportionate increase in nervous tissue neoplasms-that is, astrocytoma, medulloblastoma, sarcoma (two cases)IO, II and glioblastoma,3, 12 in the brain and an astrocy349
Journal of the American Academy of Dermatology
350 Nakamura et al.
Fig. 1. Patient, 43 years of age, with xeroderma pigmentosum and tissue specimens from skin and internal cancers. A, Face shows moderate freckling, pigmentation, darkly pigmented macules (right cheek), and a slight swelling of the left cheek at site of subcutaneous tumor growth. B, Histologic features of pigmented macule stain reveal lentigo maligna. C, Low-power magnification D, High-power magnification views of subcutaneous trigeminal nerve tumor tissue. E, Peroxidase-antiperoxidase staining for positive 8-100 protein in trigeminal nerve tumor cells. (B, C, and D, Hematoxylin-eosin stain; B, X40; C, X20, D, X200; E, X400.)
toma in the spinal cord. i3 No malignant schwannoma has been described, however. We describe a case of malignant schwannoma of the trigeminal nerve in a 43-year-old XP-D patient who also had lentigo maligna of the face but no other skin cancers.
CASE REPORT
A 43-year-old Japanese man had mild cutaneous XP symptoms, lentigo maligna on the right cheek, and a tumor in the deep subcutaneous tissue of the left cheek (Fig. 1, A). His parents were second cousins, and two
Volume 25 Number 2, Part 2 August 1991
Malignant schwanoma associated with xeroderma pigmentosum 351
Fig. 2. Computed tomographic scanning of the brain. Arrows indicate tumor on left trigeminal nerve.
elder brothers had died of unknown causes soon after birth. A skin phototest was performed by exposing the patient's back to graded doses of broad UV-B radiation (280 to 370 nm, peak emission at 305 nm) from a Dermaray model M-DRM-l irradiation unit (Eisai, Tokyo) with five Torex FL-20SE-30 sun lamps (Toshiba Medical Supplies, Tokyo) at an average incident intensity of 0.7 mW Icm 2, as measured by a calibrated UVB radiometer, model UVR-305/365 D II (Eisai). The patient showed a delayed response of maximum erythema at 72
hours and a lowered minimal erythema dose of 42 millijoules/cm 2, compared with a range of 84 to 126 millijoulesjcm2 at 24 hours in normal subjects. The patient had experienced no mental or neurologic abnormalities until 42 years of age when paresthesia of the upper left part of the lip occurred after a tooth extraction. Four months later, we found a tender cordlike subcutaneous tumor ofthe left cheek (Fig. 1) and neuralgia along the second branch of the left trigeminal nerve. Except for the tumor-derived neuralgia, systemic neurologic examination revealed no abnormal findings in inte!-
352
Nakamura et al.
Journal of the American Academy of Dermatology
Fig. 3. Electron microscopy of tumor on trigeminal nerve. A, Axon; T, tumor cell with abundant mitochondria, dense bodies, vacuoles, and discontinuous basal lamina (XlI,OOO)
ligence, speech, motor and sensory activity, deep tendon reflexes, hearing by audiogram, and electroencephalogram. Computed tomography (CT) of the brain revealed a long thick cord indicative of a trigeminal nerve tumor arising from the left sella turcica, running through the foramen rotundum and the infraorbital canal, and protruding extracranially into the left cheek pouch (Fig. 2). The tumor was surgically excised.
MATERIAL AND METHODS Dermal fibroblasts culture (XP97TO) was established from a skin biopsy specimen. A complementation test to allocate XP97TO to one of the known XP complementation groups was carried out by the method of Fujiwara et a1. 3, 14 Clonogenic 254 nm UV survival curves and the characteristics of UV sensitivity in terms of extrapolation number (n) and mean lethal UV dose (Do) were determined by a method described elsewhere. 14 To elucidate the nerve origin of the tumor, we stained thin sections immunohistochemically by the peroxidaseantiperoxidase (PAP) method,15 using a rabbit IgG antibody raised against human 8-100 protein (Dakopatts, 1:320 dilution). The intensity of 8-100 protein staining in the tumor cells was compared with that in the reference peripheral nerve. RESULTS
Complementation-group assignment and unscheduled DNA synthesis. UV (10 joulesjm 2)-induced UDS in terms of mean grains per nucleus of dikary-
ons was assayed in heterodikaryons between XP97TO and each reference cell strain, XP97TO (test cell) homodikaryons, and reference-cell homodikaryons identified by differential labeling with small and large latex beads. 3, 14 Only the XP97TO j XP43KO (D) heterodikaryons exhibited 29% ofthe UDS found in the NHSF6 jNHSF6 normal homodikaryons. This figure was as low as the figures for the homodikaryons of XP43KO(D)j XP43KO(D) and XP97TOjXP97TO. All of the other heterodikaryon sets between XP97TO and the other XP groups (except the unavailable group B) restored almost the normal level (93% to 101%) of UDS. Thus XP97TO was assigned to complementation group D, and the mean UDS was 29% from the eight homodikaryon sets. aonogenic 254 nm UV survival. Post-UV survival curves show that on the basis of mean lethal UV dose (Do) comparison, the XP97TO fibroblasts were seven times as sensitive to the lethal effect of 254 nm UV (n = 1.0, Do = 0.70 jou1esjm2 ) as NHSF6 normal cells (n = 1.5, Do = 5.0 joulesjm2). This UV hypersensitivity of XP97TO cells was the same as that of the previously assigned reference XP-D strains ofXP43KO,9 XP59TO,9, 16 andXP6BE.9, 16 Histology and immunostaining of the trigeminal nerve tumor. Light microscopy indicated that the subcutaneous nerve tumor was certainly necrotic
Volume 25 Number 2, Part 2 August 1991
Malignant schwanoma associated with xeroderma pigmentosum 353
and demarcated distinctly from neighboring tissues by a fibrous capsule (Fig. 1, C). Fusiform and pleomorphic tumor cells were aligned in fine fascicles along the long axis (Fig. 1, D). Basophilic and chromatin-rich nuclei were atypical in both size and form, and mitotic figures were abundant (Fig. 1, D). The immunohistochemical method resulted in positive staining for 8-100 protein in tumor cells (Fig. 1, E). Electron microscopy showed that tumor cells had an ovoid and spindlelike cytoplasm with abundant mitochondria, dense bodies and vacuoles (Fig. 3), and irregularly indented spindle-shaped nuclei. Cell membranes were surrounded by thin and discontinuous basal lamina (Fig. 3). Axons were present in a few cells (Fig. 3), indicative of a Schwann cell origin. DISCUSSION
Our patient was the ninth Japanese in the XP-D group, which is still rare in Japan, although XP-D constitutes a major group, together with XP-A, XPC, and the XP variant group in the United States, Europe, and Egypt. I He had no detectable neurologic abnormalities except for recent neuralgia secondary to his trigeminal nerve neoplasm. In the other six Japanese XP-D patients between the second and seventh decades of age, one had sensorineural deafness, two had borderline charge in electroencephalography, and none had mental deterioration. Kraemer et a1. IO, II reviewed the cases of 830 XP patients in the world literature published between 1874 and 1982 and noted 17 internal neoplasms (four brain tumors, three oral-cavity neoplasms, two cases of leukemia, two of bronchogenic carcinoma, and one each of testicular sarcoma, choroidal melanoma, breast carcinoma, gastric cancer, and pancreatic carcinoma). Independently, Fujiwara et aP and Satoh and Nishigori l2 reported seven internal cancers: brain glioblastoma (XP-A), bile-duct carcinoma ()CP-F), gastric cancer (variant), bladder carcinoma (variant), pharyngeal carcinoma (variant), choroidal melanoma, and uterine carcinoma in 218 XP patients from Japan. In both instances, internal tumors occurred in 2% to 3% of the total XP patients, which is far less than the rate of occurrence for cutaneous neoplasms (45%) in XP patients. The
present malignant schwannoma is the first case to add to the six previously documented cases of nervous-tissue neoplasm. REFERENCES l. Kraemer KH, Slor H. Xeroderma pigmentosum. Clin Dermatol 1985;3:33-69. 2. Fujiwara Y. Xeroderma pigmentosum: DNA repair deficiency and the current status of cellular and molecular approaches. Gann Monogr Cancer Res 1988;35:99-112. 3. Fujiwara Y, Matsumoto A, Ichihashi M, et al. Heritable disorders of DNA repair: xeroderma pigmentosum and Fanconi's anemia. In: Goode-Dahl T Jr, Wueper KD, eds. Current problems in dermatology; vol 16. New York: S Karger AG, 1986:182-98. 4. Andrews AD, Barrett SF, Robbins JR. Xeroderma pigmentosum neurological abnormalities correlate with colony-forming ability after ultraviolet irradiation. Proc Nat! Acad Sci USA 1978;75:1984-8. 5. Robbins JR. Hypersensitivity to DNA damaging agents in primary degenerations ofexcitable tissue. In: Friedberg EC, Bridges BA, eds. Cellular responses to DNA damage. New York: Alan R Liss, 1983:671-700. 6. Mimaki T, Itoh N, Abe J, et at. Neurological manifestations in xeroderma pigmentosum. Ann Neurol 1986;20: 70-5. 7. Pawsey SA, Magnus lA, Ramssay CA, et al. Clinical, genetic and DNA repair studies on a consecutive series of patients with xeroderma pigmentosum. Q J Med 1979;48: 179-210. 8. Fischer E, Thielman HW, N eundorfer B, et al. Xeroderma pigmentosum patients from Germany: clinical symptoms and DNA repair characteristics. Arch Dermatol Res 1982;274:229-49. 9. Tchihashi M, Yamamura K, Hiramoto T, et at. No apparent neurologic defect in a patient with xeroderma pigmentosum complementation group D. Arch Dermatol 1988; 124:256-60. 10. Kraemer KH, Lee MM, Scotto J. DNA repair protects against cutaneous and internal neoplasia: evidence from xeroderma pigmentosum. Carcinogenesis 1984;5:511-14. 11. Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum: cutaneous, ocular and neurological abnormalities in 830 published cases. Arch DermatolI987;123:241-50. 12. Satoh Y, Nishigori C. xeroderma pigmentosum: clinical aspects. Gann Monogr Cancer Res 1988;35:113-26. 13. Kraemer KH, DiGiovanna J1, Moshell AN, et at. Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med 1988;318:1633-7. 14. Fujiwara Y, Uehara YM, Ichihashi M, et al. Assignment of 2 patients with xeroderma pigmentosum to complementation group E. Mutat Res 1985;145:55-61. 15. Nakajima T, Kameya T, Watanabe S, et al. S-100 protein distribution in normal and neoplastic tissues. In: Delellis RA, ed. Advances in immunohistochemistry. Masson, 141-58. 16. Fujiwara Y, Satoh Y. Assignment of two Japanese xeroderma pigmentosum patients to complementation group D and their characteristics. Jpn J Cancer Res (Gann) 1985; 76:162-6.
6. 7.
8. 9.
retrospective study of 6 cases in Europe. Dermatologica 1988;177:82-97. van der Putte SCJ, Toonstra J, De Weger RA, et al. Cutaneous T-cell lymphoma, multilobated type. Histopathology 1982;6:35-54. Azar HA, Jaffe ES, Berard CW, et al. Diffuse large-cell lymphomas (reticulum cell sarcomas, histiocytic lymphomas): correlation of morphologic features with functional markers. Cancer 1980;46: 1428-41. Fattorossi A, Moretti S, Palermo A, et al. Cell surface marker studies in a patient with cutaneous multilobated Tcell lymphoma. Br J DermatoI1985;113:587-96. Wood GS, Burke IS, Horning S, et al. The immunologic and clinicopathologic heterogeneity of cutaneous lymphomas other than mycosis fungoides. Blood 1983;62:464-72.
10. Nasu K, Said J, Vonderheid E, et al. Immunopathology of cutaneous T-cell lymphoma. Am J Pathol 1985;119:43647. 11. van der Valk P, Willemze R, Meijer CJLM. Peripheral Tcell lymphomas: a clinicopathological and immunological study of 10 cases. Histopathol 1986;10:235-49. 12. van der PutteSCJ, Schuurman HJ, Toonstra J. Cutaneous T-cell lymphoma, multilobulated type, expressing membrane-differentiation antigens of precursor T-Iymphocytes. Br J Dermatol 1982;107:293-300. 13. Beljaards RC, Meijer CJLM, Scheffer E, et al. Prognostic significance of CD30 (Ki-l /Ber-H2) expression in primary cutaneous large-cell lymphomas of T-cell origin. Am J PathoI1989;135:1169-78.
Malignant schwannoma associated with xeroderma pigmentosum in a patient belonging to complementation group D Takehiko Nakamura, MD,a Tomomichi Ono, MD,a Koji Yoshimura, MD,a Tatsuyoshi Arao, MD,a Seiji Kondo, MD,b Masamitsu Ichihashi, MD,d Akira Matsumoto, MD,c and Yoshisada Fujiwara, MD, PhDc Kumamoto, Tokyo, and Kobe, Japan A 43-year-old man with xeroderma pigmentosum, XP97TO, was allocated to complementation group D. He had had moderate photosensitivity at age 1 year and freckles by age 6 but no neurologic abnormalities. Nevertheless, his fibroblasts in culture had the XP-D phenotype. They showed a sevenfold hypersensitivity to killing by 254 nm ultraviolet radiation and a diminished level (29%) of unscheduled DNA synthesis. Phototesting revealed delayed maximum erythema at 72 hours after UVB exposure and a lowered minimal erythema dose. Lentigo maligna developed on the patient's face, and a rapidly growing malignant schwannoma was found on the left trigeminal nerve. This may be the first case of a peripheral nervous tissue neoplasm in xeroderma pigmentosum. (J AM ACAD DERMATOL 1991:25;349-53.) Xeroderma pigmentosum (XP) consists of eight excision-defective complementation groups (A through H), and an XP variant group capable From the Department of Dermatology, Kumamoto University Medical School, Kumamoto;" the Department of Dermatology, School of Medicine, Tokyo Medical and Dental University, Tokyob; and the Departments of Radiation Biophysics and Dermato]ogy,d Kobe University School of Medicine, Kobe. Supported in part by agrant-in-aid for cancer research from the Ministry of Education, Science and Culture, Japan. Reprint requests: Dr. T. Nakamura, Department of Dermatology, Kumamoto University Medical School, 1-1-1 Banjo, Kumamoto 860, Japan. C
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of normally excising cyc10butane pyrimidine dimers. 1-3 Patients in certain XP groups (A, B, D, G, and H) often have cerebral and spinocerebellar abnormalities. In the major XP groups, they are found in most XP-A patients by 7 years of age. 4 - 6 Most XP-D patients show neurologic abnormalities between 7 and 20 years of age,4, 5 whereas some do not appear to have them beyond the second decade. 2, 7-9 The published reviews of Kraemer et aL 10,1 I on 830 XP patients disclosed a disproportionate increase in nervous tissue neoplasms-that is, astrocytoma, medulloblastoma, sarcoma (two cases)IO, II and glioblastoma,3, 12 in the brain and an astrocy349
Journal of the American Academy of Dermatology
350 Nakamura et al.
Fig. 1. Patient, 43 years of age, with xeroderma pigmentosum and tissue specimens from skin and internal cancers. A, Face shows moderate freckling, pigmentation, darkly pigmented macules (right cheek), and a slight swelling of the left cheek at site of subcutaneous tumor growth. B, Histologic features of pigmented macule stain reveal lentigo maligna. C, Low-power magnification D, High-power magnification views of subcutaneous trigeminal nerve tumor tissue. E, Peroxidase-antiperoxidase staining for positive 8-100 protein in trigeminal nerve tumor cells. (B, C, and D, Hematoxylin-eosin stain; B, X40; C, X20, D, X200; E, X400.)
toma in the spinal cord. i3 No malignant schwannoma has been described, however. We describe a case of malignant schwannoma of the trigeminal nerve in a 43-year-old XP-D patient who also had lentigo maligna of the face but no other skin cancers.
CASE REPORT
A 43-year-old Japanese man had mild cutaneous XP symptoms, lentigo maligna on the right cheek, and a tumor in the deep subcutaneous tissue of the left cheek (Fig. 1, A). His parents were second cousins, and two
Volume 25 Number 2, Part 2 August 1991
Malignant schwanoma associated with xeroderma pigmentosum 351
Fig. 2. Computed tomographic scanning of the brain. Arrows indicate tumor on left trigeminal nerve.
elder brothers had died of unknown causes soon after birth. A skin phototest was performed by exposing the patient's back to graded doses of broad UV-B radiation (280 to 370 nm, peak emission at 305 nm) from a Dermaray model M-DRM-l irradiation unit (Eisai, Tokyo) with five Torex FL-20SE-30 sun lamps (Toshiba Medical Supplies, Tokyo) at an average incident intensity of 0.7 mW Icm 2, as measured by a calibrated UVB radiometer, model UVR-305/365 D II (Eisai). The patient showed a delayed response of maximum erythema at 72
hours and a lowered minimal erythema dose of 42 millijoules/cm 2, compared with a range of 84 to 126 millijoulesjcm2 at 24 hours in normal subjects. The patient had experienced no mental or neurologic abnormalities until 42 years of age when paresthesia of the upper left part of the lip occurred after a tooth extraction. Four months later, we found a tender cordlike subcutaneous tumor ofthe left cheek (Fig. 1) and neuralgia along the second branch of the left trigeminal nerve. Except for the tumor-derived neuralgia, systemic neurologic examination revealed no abnormal findings in inte!-
352
Nakamura et al.
Journal of the American Academy of Dermatology
Fig. 3. Electron microscopy of tumor on trigeminal nerve. A, Axon; T, tumor cell with abundant mitochondria, dense bodies, vacuoles, and discontinuous basal lamina (XlI,OOO)
ligence, speech, motor and sensory activity, deep tendon reflexes, hearing by audiogram, and electroencephalogram. Computed tomography (CT) of the brain revealed a long thick cord indicative of a trigeminal nerve tumor arising from the left sella turcica, running through the foramen rotundum and the infraorbital canal, and protruding extracranially into the left cheek pouch (Fig. 2). The tumor was surgically excised.
MATERIAL AND METHODS Dermal fibroblasts culture (XP97TO) was established from a skin biopsy specimen. A complementation test to allocate XP97TO to one of the known XP complementation groups was carried out by the method of Fujiwara et a1. 3, 14 Clonogenic 254 nm UV survival curves and the characteristics of UV sensitivity in terms of extrapolation number (n) and mean lethal UV dose (Do) were determined by a method described elsewhere. 14 To elucidate the nerve origin of the tumor, we stained thin sections immunohistochemically by the peroxidaseantiperoxidase (PAP) method,15 using a rabbit IgG antibody raised against human 8-100 protein (Dakopatts, 1:320 dilution). The intensity of 8-100 protein staining in the tumor cells was compared with that in the reference peripheral nerve. RESULTS
Complementation-group assignment and unscheduled DNA synthesis. UV (10 joulesjm 2)-induced UDS in terms of mean grains per nucleus of dikary-
ons was assayed in heterodikaryons between XP97TO and each reference cell strain, XP97TO (test cell) homodikaryons, and reference-cell homodikaryons identified by differential labeling with small and large latex beads. 3, 14 Only the XP97TO j XP43KO (D) heterodikaryons exhibited 29% ofthe UDS found in the NHSF6 jNHSF6 normal homodikaryons. This figure was as low as the figures for the homodikaryons of XP43KO(D)j XP43KO(D) and XP97TOjXP97TO. All of the other heterodikaryon sets between XP97TO and the other XP groups (except the unavailable group B) restored almost the normal level (93% to 101%) of UDS. Thus XP97TO was assigned to complementation group D, and the mean UDS was 29% from the eight homodikaryon sets. aonogenic 254 nm UV survival. Post-UV survival curves show that on the basis of mean lethal UV dose (Do) comparison, the XP97TO fibroblasts were seven times as sensitive to the lethal effect of 254 nm UV (n = 1.0, Do = 0.70 jou1esjm2 ) as NHSF6 normal cells (n = 1.5, Do = 5.0 joulesjm2). This UV hypersensitivity of XP97TO cells was the same as that of the previously assigned reference XP-D strains ofXP43KO,9 XP59TO,9, 16 andXP6BE.9, 16 Histology and immunostaining of the trigeminal nerve tumor. Light microscopy indicated that the subcutaneous nerve tumor was certainly necrotic
Volume 25 Number 2, Part 2 August 1991
Malignant schwanoma associated with xeroderma pigmentosum 353
and demarcated distinctly from neighboring tissues by a fibrous capsule (Fig. 1, C). Fusiform and pleomorphic tumor cells were aligned in fine fascicles along the long axis (Fig. 1, D). Basophilic and chromatin-rich nuclei were atypical in both size and form, and mitotic figures were abundant (Fig. 1, D). The immunohistochemical method resulted in positive staining for 8-100 protein in tumor cells (Fig. 1, E). Electron microscopy showed that tumor cells had an ovoid and spindlelike cytoplasm with abundant mitochondria, dense bodies and vacuoles (Fig. 3), and irregularly indented spindle-shaped nuclei. Cell membranes were surrounded by thin and discontinuous basal lamina (Fig. 3). Axons were present in a few cells (Fig. 3), indicative of a Schwann cell origin. DISCUSSION
Our patient was the ninth Japanese in the XP-D group, which is still rare in Japan, although XP-D constitutes a major group, together with XP-A, XPC, and the XP variant group in the United States, Europe, and Egypt. I He had no detectable neurologic abnormalities except for recent neuralgia secondary to his trigeminal nerve neoplasm. In the other six Japanese XP-D patients between the second and seventh decades of age, one had sensorineural deafness, two had borderline charge in electroencephalography, and none had mental deterioration. Kraemer et a1. IO, II reviewed the cases of 830 XP patients in the world literature published between 1874 and 1982 and noted 17 internal neoplasms (four brain tumors, three oral-cavity neoplasms, two cases of leukemia, two of bronchogenic carcinoma, and one each of testicular sarcoma, choroidal melanoma, breast carcinoma, gastric cancer, and pancreatic carcinoma). Independently, Fujiwara et aP and Satoh and Nishigori l2 reported seven internal cancers: brain glioblastoma (XP-A), bile-duct carcinoma ()CP-F), gastric cancer (variant), bladder carcinoma (variant), pharyngeal carcinoma (variant), choroidal melanoma, and uterine carcinoma in 218 XP patients from Japan. In both instances, internal tumors occurred in 2% to 3% of the total XP patients, which is far less than the rate of occurrence for cutaneous neoplasms (45%) in XP patients. The
present malignant schwannoma is the first case to add to the six previously documented cases of nervous-tissue neoplasm. REFERENCES l. Kraemer KH, Slor H. Xeroderma pigmentosum. Clin Dermatol 1985;3:33-69. 2. Fujiwara Y. Xeroderma pigmentosum: DNA repair deficiency and the current status of cellular and molecular approaches. Gann Monogr Cancer Res 1988;35:99-112. 3. Fujiwara Y, Matsumoto A, Ichihashi M, et al. Heritable disorders of DNA repair: xeroderma pigmentosum and Fanconi's anemia. In: Goode-Dahl T Jr, Wueper KD, eds. Current problems in dermatology; vol 16. New York: S Karger AG, 1986:182-98. 4. Andrews AD, Barrett SF, Robbins JR. Xeroderma pigmentosum neurological abnormalities correlate with colony-forming ability after ultraviolet irradiation. Proc Nat! Acad Sci USA 1978;75:1984-8. 5. Robbins JR. Hypersensitivity to DNA damaging agents in primary degenerations ofexcitable tissue. In: Friedberg EC, Bridges BA, eds. Cellular responses to DNA damage. New York: Alan R Liss, 1983:671-700. 6. Mimaki T, Itoh N, Abe J, et at. Neurological manifestations in xeroderma pigmentosum. Ann Neurol 1986;20: 70-5. 7. Pawsey SA, Magnus lA, Ramssay CA, et al. Clinical, genetic and DNA repair studies on a consecutive series of patients with xeroderma pigmentosum. Q J Med 1979;48: 179-210. 8. Fischer E, Thielman HW, N eundorfer B, et al. Xeroderma pigmentosum patients from Germany: clinical symptoms and DNA repair characteristics. Arch Dermatol Res 1982;274:229-49. 9. Tchihashi M, Yamamura K, Hiramoto T, et at. No apparent neurologic defect in a patient with xeroderma pigmentosum complementation group D. Arch Dermatol 1988; 124:256-60. 10. Kraemer KH, Lee MM, Scotto J. DNA repair protects against cutaneous and internal neoplasia: evidence from xeroderma pigmentosum. Carcinogenesis 1984;5:511-14. 11. Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum: cutaneous, ocular and neurological abnormalities in 830 published cases. Arch DermatolI987;123:241-50. 12. Satoh Y, Nishigori C. xeroderma pigmentosum: clinical aspects. Gann Monogr Cancer Res 1988;35:113-26. 13. Kraemer KH, DiGiovanna J1, Moshell AN, et at. Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med 1988;318:1633-7. 14. Fujiwara Y, Uehara YM, Ichihashi M, et al. Assignment of 2 patients with xeroderma pigmentosum to complementation group E. Mutat Res 1985;145:55-61. 15. Nakajima T, Kameya T, Watanabe S, et al. S-100 protein distribution in normal and neoplastic tissues. In: Delellis RA, ed. Advances in immunohistochemistry. Masson, 141-58. 16. Fujiwara Y, Satoh Y. Assignment of two Japanese xeroderma pigmentosum patients to complementation group D and their characteristics. Jpn J Cancer Res (Gann) 1985; 76:162-6.