The Journal of Laryngology and Otology August 1992, Vol. 106, pp. 748-750
Malignant parotid salivary gland peripheral nerve sheath tumour in a twelve-year-old girl ANNA C. ATHOW, F.R.C.S.,* NIGEL KIRKHAM, M.R.C.PATH.t (Brighton)
Abstract A case of a malignant parotid salivary gland nerve sheath tumour is reported in a 12-year-old girl who developed a right parotid mass. Initial incisional biopsy showed a tumour with a mesenchymal spindle cell appearance. Immunohistochemical studies showed positive staining of tumour cells for vimentin and focally for S-100 protein. These features together with ultrastructural evidence of basal lamina material suggested that the tumour was of nerve sheath origin. After subtotal parotidectomy the tumour metastasised to cervical lymph node and lung. There was evidence of a partial response to chemotherapy. A detailed illustrated histopathological description of the tumour is given.
lobe. There was no evidence of local recurrence in the parotid region, or other signs or symptoms of disease, in March 1992.
Introduction Primary malignant parotid tumours are rare in childhood. We describe such a case in which the tumour showed the appearances of a malignant peripheral nerve sheath tumour and illustrate the histopathological features of the tumour.
Pathological findings The initial biopsy showed a mesenchymal neoplasm composed of spindle to oval cells with single nucleoli. The tumour had a uniform pattern apart from slight variation in nuclear shape. Small blood vessels were present in moderate numbers, with tumour cells arranged around them (Fig. la). Occasional incomplete septa were also present. Mitoses were present at a count of 47 per mm2. These appearances were interpreted as malignant. The precise classification of the tumour was difficult, as it did not appear to correspond to any particular recognized form of primary parotid tumour. In view of the cytological and architectural features a diagnosis of malignant myoepithelioma or glomus tumour was suggested. The parotidectomy contained a well circumscribed tumour, 35 x 25 x 25 mm, at the lower pole of the gland, with a thin pseudocapsule (Fig. lb), but with tumour extending beyond the capsule and to the excision margins. Immunohistochemistry showed strong reactivity for vimentin and diffuse reactivity of some tumour cells for S-100. Staining for cytokeratin, epithelial membrane antigen, glial fibrillary acidic protein, chromogranin, PGP 9.5, neuron specific enolase, muscle specific actin, desmin, and Leu 7 was negative. Electron microscopy showed tumour cells with a complex pattern of interdigitating cells processes and patchy basal lamina. Microvilli were present in occasional intercellular spaces. A few pinocytotic vesicles and intercellular junctions were found, a small amount of rough endoplasmic reticulum and a few drops of mucin were seen. There was no evidence of smooth muscle or myoepithelial differentiation. The positive findings of S-100 staining and the ultrastructural identification of interdigitating cell processes and patchy basal lamina material were all in keeping with a pathological diagnosis of a peripheral nerve sheath tumour. The biopsy from the left side showed essentially similar tumour, but with more noticeable nuclear pleomorphism. Mitoses were present at a count of 14 per mm2. This tumour was interpreted as a metastasis from the primary tumour in the right parotid gland (Figs, le & f).
Case history A 12-year-old girl was admitted in February 1990 for elective excision of a compound pigmented naevus of the scalp. She had been previously healthy apart from mild asthma. An enlarged firm slightly tender right preauricular mass, 20 mm in diameter, interpreted as a lymph node, was found, the lesion had appeared in the previous three weeks. By April 1990, the mass had enlarged to 40 x 30 mm in diameter to form a firm, tender, craggy mass. Through a vertical preauricular incision, the contents of what appeared to be a large lymph node in the superficial parotid gland were expressed and the defect packed with Surgicel, before closing the capsule to staunch brisk bleeding. The expressed material was sent for bacterial culture and for histopathological examination. This showed an epithelioid tumour, possibly a primary salivary tumour with features suggestive of myoepithelial or glomus tumour differentiation. No evidence of infection was found. Her management continued in collaboration with a tertiary paediatric referral centre. A postoperative CT scan showed a discrete residual nodule in the parotid gland. The CT scan of the chest was normal. In July 1990, a subtotal parotidectomy was performed. The excised tumour showed similar appearances to the initial biopsy, details of which are given below. In view of the clinical behaviour of the tumour, with rapid growth and recurrence, and the pathological features of malignancy, a course of external beam radiotherapy was given to the area. In February 1991, an enlarged lymph node was excised from behind the left ear. Within one month, three pulmonary metastases and a malignant pleural effusion had developed. Bone marrow trephine and aspiration was clear and a CT scan of the head showed no further disease. Chemotherapy was commenced. In August 1991, after two courses of IVAD-3 (ifosfamide, vincristine and adriamycin), the lung metastases had become smaller. They were excised in December, but a post-operative CT scan showed a further subpleural nodule in the right middle
Discussion Primary tumours in the parotid gland are rare in children.
From Departments of *Paediatric Surgery, Royal Alexandra Hospital, and tHistopathology, Royal Sussex County Hospital, Brighton. Accepted for publication: 15 April 1992. 748
CLINICAL RECORDS
749
FIG. 1 (a) Initial biopsy showing perivascular growth of spindle to oval tumour cells, (b) Parotidectomy. The tumour has a well formed peripheral pseudocapsule. (c) Imprint cytology. The tumour cells have oval nuclei with single nucleoli and inconspicuous cytoplasm (d) Parotidectomy Tumour cells appear regular with small nucleoli and occasional atypical mitosis, (e) Metastasis. The tumour shows similar differentiation but with more frequent mitoses, (f) Metastasis. Nuclei are more pleomorphic than the primary tumour.
750 When they do occur diagnosis can be difficult. The potential diagnoses include malignant fibrous histiocytoma, neurosarcoma, rhabdomyosarcoma, fibrosarcoma and osteosarcoma (Luna et al., 1991). In the present case the initial clinical impression suggested a reactive lymph node. The histopathological differential diagnosis of the case included malignant peripheral nerve sheath tumour (Hasan and Kazi, 1986; Coffin and Dehner, 1990) and malignant myoepithelioma (Barnes et al., 1985; Dardick, 1985). Embryonal rhabdomyosarcoma is the commonest tumour of the head and neck in childhood, but this tumour showed no features of striated muscle differentiation. The features in favour of a diagnosis of malignant nerve sheath tumour are the histopathological pattern of growth, the positive immunoreactivity for vimentin and S-100 protein, the negative staining for markers of epithelial, neuroendocrine or muscular differentiation, and the ultrastructural findings including the presence of basal lamina and the absence of epithelial or myoepithelial features. The designation 'malignant peripheral nerve sheath tumour' represents a step back from previous attempts to make precise distinctions between malignant schwannomas and closely related tumours with features of fibroblastic or perineural fibroblast differentiation. In practice tumours may show features of all three of these cell types, making precise differential diagnosis difficult. Such tumours share an aggressive clinical behaviour and so the generic diagnosis is useful, because it is more easily applied by pathologists and describes a group of tumours with a similarly aggressive behaviour (Ducatman et al., 1986). The presence of high cellularity and frequent mitoses in the absence of anaplasia suggested that the tumour might be of low grade malignancy, prone to local recurrence if surgical excision was incomplete. The early spread to the other side of the neck, together with an increase in nuclear pleomorphism indicated a progression to more aggressive growth, which was confirmed by the early development of pulmonary metastases. Remission of metastatic malignant nerve sheath tumour has been reported after combination chemotherapy (Goldman et al., 1977). There was some evidence of a response in this case. Complete surgical excision remains the form of primary treatment most likely to be effective, as salivary gland sarcomas behave in
Key words: Parotid gland; Nervous system, neoplasms
A. C. ATHOW, N. KIRKHAM
the same way as soft tissue sarcomas at other sites (Luna et al., 1991). Acknowledgements We thank Mr Adrian J. Allaway for permission to report this case, Prof Louis P. Dehner for his opinion on the tumour, Dr T. Palmer for details of the resection specimen and Dr C. Fisher details of the tumour ultrastructure.
References Barnes, L., Appel, B. N., Perez, H., El-Attar, A. M. (1985) Myoepitheiomas of the head and neck: case report and review. Journal of Surgical Oncology, 28: 21-28. Coffin, C. M., Dehner, L. P. (1990) Cellular peripheral neural tumours (neurofibromas) in children and adolescents: a clinicopathological and immunohistochemical study. Pediatric Pathology, 10: 351-361. Dardick, I. (1985) Malignant myoepithelioma of parotid salivary gland. Ultrastructural Pathology, 9: 163-168. Ducatman, B. S., Scheithauer, B. W., Piepgras, D. G., Reiman, H. M., Ilstrup, D. M. (1986) Malignant peripheral nerve sheath tumours. A clinicopathologic study of 120 cases. Cancer, 57: 2006-2021. Goldman, R. L., Jones, S. E., Heusinkveld, R. S. (1977) Combination chemotherapy of metastatic malignant schwannoma with vincristine, adriamycin, cyclophosphamide and imidazole carboxamide. Cancer, 39: 1955-1958. Hasan, N. U., Kazi, T. (1986) Malignant schwannoma of facial nerve. Journal of Pediatric Surgery, 2 1 : 926-928. Luna, M. A., Tortoledo, M. E., Ordonez, N. G., Frankenthaler, R. A., Batsakis, J. G. (1991) Primary sarcomas of the major salivary glands. Archives of Otolaryngology—Head and Neck Surgery, 117: 302-306. Address for correspondence: Dr N. Kirkham, Dept of Histopathology, Royal Sussex County Hospital, Brighton BN2 5BE, UK. Fax 0273 600182
Malignant parotid salivary gland peripheral nerve sheath tumour in a twelve-year-old girl ANNA C. ATHOW, F.R.C.S.,* NIGEL KIRKHAM, M.R.C.PATH.t (Brighton)
Abstract A case of a malignant parotid salivary gland nerve sheath tumour is reported in a 12-year-old girl who developed a right parotid mass. Initial incisional biopsy showed a tumour with a mesenchymal spindle cell appearance. Immunohistochemical studies showed positive staining of tumour cells for vimentin and focally for S-100 protein. These features together with ultrastructural evidence of basal lamina material suggested that the tumour was of nerve sheath origin. After subtotal parotidectomy the tumour metastasised to cervical lymph node and lung. There was evidence of a partial response to chemotherapy. A detailed illustrated histopathological description of the tumour is given.
lobe. There was no evidence of local recurrence in the parotid region, or other signs or symptoms of disease, in March 1992.
Introduction Primary malignant parotid tumours are rare in childhood. We describe such a case in which the tumour showed the appearances of a malignant peripheral nerve sheath tumour and illustrate the histopathological features of the tumour.
Pathological findings The initial biopsy showed a mesenchymal neoplasm composed of spindle to oval cells with single nucleoli. The tumour had a uniform pattern apart from slight variation in nuclear shape. Small blood vessels were present in moderate numbers, with tumour cells arranged around them (Fig. la). Occasional incomplete septa were also present. Mitoses were present at a count of 47 per mm2. These appearances were interpreted as malignant. The precise classification of the tumour was difficult, as it did not appear to correspond to any particular recognized form of primary parotid tumour. In view of the cytological and architectural features a diagnosis of malignant myoepithelioma or glomus tumour was suggested. The parotidectomy contained a well circumscribed tumour, 35 x 25 x 25 mm, at the lower pole of the gland, with a thin pseudocapsule (Fig. lb), but with tumour extending beyond the capsule and to the excision margins. Immunohistochemistry showed strong reactivity for vimentin and diffuse reactivity of some tumour cells for S-100. Staining for cytokeratin, epithelial membrane antigen, glial fibrillary acidic protein, chromogranin, PGP 9.5, neuron specific enolase, muscle specific actin, desmin, and Leu 7 was negative. Electron microscopy showed tumour cells with a complex pattern of interdigitating cells processes and patchy basal lamina. Microvilli were present in occasional intercellular spaces. A few pinocytotic vesicles and intercellular junctions were found, a small amount of rough endoplasmic reticulum and a few drops of mucin were seen. There was no evidence of smooth muscle or myoepithelial differentiation. The positive findings of S-100 staining and the ultrastructural identification of interdigitating cell processes and patchy basal lamina material were all in keeping with a pathological diagnosis of a peripheral nerve sheath tumour. The biopsy from the left side showed essentially similar tumour, but with more noticeable nuclear pleomorphism. Mitoses were present at a count of 14 per mm2. This tumour was interpreted as a metastasis from the primary tumour in the right parotid gland (Figs, le & f).
Case history A 12-year-old girl was admitted in February 1990 for elective excision of a compound pigmented naevus of the scalp. She had been previously healthy apart from mild asthma. An enlarged firm slightly tender right preauricular mass, 20 mm in diameter, interpreted as a lymph node, was found, the lesion had appeared in the previous three weeks. By April 1990, the mass had enlarged to 40 x 30 mm in diameter to form a firm, tender, craggy mass. Through a vertical preauricular incision, the contents of what appeared to be a large lymph node in the superficial parotid gland were expressed and the defect packed with Surgicel, before closing the capsule to staunch brisk bleeding. The expressed material was sent for bacterial culture and for histopathological examination. This showed an epithelioid tumour, possibly a primary salivary tumour with features suggestive of myoepithelial or glomus tumour differentiation. No evidence of infection was found. Her management continued in collaboration with a tertiary paediatric referral centre. A postoperative CT scan showed a discrete residual nodule in the parotid gland. The CT scan of the chest was normal. In July 1990, a subtotal parotidectomy was performed. The excised tumour showed similar appearances to the initial biopsy, details of which are given below. In view of the clinical behaviour of the tumour, with rapid growth and recurrence, and the pathological features of malignancy, a course of external beam radiotherapy was given to the area. In February 1991, an enlarged lymph node was excised from behind the left ear. Within one month, three pulmonary metastases and a malignant pleural effusion had developed. Bone marrow trephine and aspiration was clear and a CT scan of the head showed no further disease. Chemotherapy was commenced. In August 1991, after two courses of IVAD-3 (ifosfamide, vincristine and adriamycin), the lung metastases had become smaller. They were excised in December, but a post-operative CT scan showed a further subpleural nodule in the right middle
Discussion Primary tumours in the parotid gland are rare in children.
From Departments of *Paediatric Surgery, Royal Alexandra Hospital, and tHistopathology, Royal Sussex County Hospital, Brighton. Accepted for publication: 15 April 1992. 748
CLINICAL RECORDS
749
FIG. 1 (a) Initial biopsy showing perivascular growth of spindle to oval tumour cells, (b) Parotidectomy. The tumour has a well formed peripheral pseudocapsule. (c) Imprint cytology. The tumour cells have oval nuclei with single nucleoli and inconspicuous cytoplasm (d) Parotidectomy Tumour cells appear regular with small nucleoli and occasional atypical mitosis, (e) Metastasis. The tumour shows similar differentiation but with more frequent mitoses, (f) Metastasis. Nuclei are more pleomorphic than the primary tumour.
750 When they do occur diagnosis can be difficult. The potential diagnoses include malignant fibrous histiocytoma, neurosarcoma, rhabdomyosarcoma, fibrosarcoma and osteosarcoma (Luna et al., 1991). In the present case the initial clinical impression suggested a reactive lymph node. The histopathological differential diagnosis of the case included malignant peripheral nerve sheath tumour (Hasan and Kazi, 1986; Coffin and Dehner, 1990) and malignant myoepithelioma (Barnes et al., 1985; Dardick, 1985). Embryonal rhabdomyosarcoma is the commonest tumour of the head and neck in childhood, but this tumour showed no features of striated muscle differentiation. The features in favour of a diagnosis of malignant nerve sheath tumour are the histopathological pattern of growth, the positive immunoreactivity for vimentin and S-100 protein, the negative staining for markers of epithelial, neuroendocrine or muscular differentiation, and the ultrastructural findings including the presence of basal lamina and the absence of epithelial or myoepithelial features. The designation 'malignant peripheral nerve sheath tumour' represents a step back from previous attempts to make precise distinctions between malignant schwannomas and closely related tumours with features of fibroblastic or perineural fibroblast differentiation. In practice tumours may show features of all three of these cell types, making precise differential diagnosis difficult. Such tumours share an aggressive clinical behaviour and so the generic diagnosis is useful, because it is more easily applied by pathologists and describes a group of tumours with a similarly aggressive behaviour (Ducatman et al., 1986). The presence of high cellularity and frequent mitoses in the absence of anaplasia suggested that the tumour might be of low grade malignancy, prone to local recurrence if surgical excision was incomplete. The early spread to the other side of the neck, together with an increase in nuclear pleomorphism indicated a progression to more aggressive growth, which was confirmed by the early development of pulmonary metastases. Remission of metastatic malignant nerve sheath tumour has been reported after combination chemotherapy (Goldman et al., 1977). There was some evidence of a response in this case. Complete surgical excision remains the form of primary treatment most likely to be effective, as salivary gland sarcomas behave in
Key words: Parotid gland; Nervous system, neoplasms
A. C. ATHOW, N. KIRKHAM
the same way as soft tissue sarcomas at other sites (Luna et al., 1991). Acknowledgements We thank Mr Adrian J. Allaway for permission to report this case, Prof Louis P. Dehner for his opinion on the tumour, Dr T. Palmer for details of the resection specimen and Dr C. Fisher details of the tumour ultrastructure.
References Barnes, L., Appel, B. N., Perez, H., El-Attar, A. M. (1985) Myoepitheiomas of the head and neck: case report and review. Journal of Surgical Oncology, 28: 21-28. Coffin, C. M., Dehner, L. P. (1990) Cellular peripheral neural tumours (neurofibromas) in children and adolescents: a clinicopathological and immunohistochemical study. Pediatric Pathology, 10: 351-361. Dardick, I. (1985) Malignant myoepithelioma of parotid salivary gland. Ultrastructural Pathology, 9: 163-168. Ducatman, B. S., Scheithauer, B. W., Piepgras, D. G., Reiman, H. M., Ilstrup, D. M. (1986) Malignant peripheral nerve sheath tumours. A clinicopathologic study of 120 cases. Cancer, 57: 2006-2021. Goldman, R. L., Jones, S. E., Heusinkveld, R. S. (1977) Combination chemotherapy of metastatic malignant schwannoma with vincristine, adriamycin, cyclophosphamide and imidazole carboxamide. Cancer, 39: 1955-1958. Hasan, N. U., Kazi, T. (1986) Malignant schwannoma of facial nerve. Journal of Pediatric Surgery, 2 1 : 926-928. Luna, M. A., Tortoledo, M. E., Ordonez, N. G., Frankenthaler, R. A., Batsakis, J. G. (1991) Primary sarcomas of the major salivary glands. Archives of Otolaryngology—Head and Neck Surgery, 117: 302-306. Address for correspondence: Dr N. Kirkham, Dept of Histopathology, Royal Sussex County Hospital, Brighton BN2 5BE, UK. Fax 0273 600182
