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Metastatic paraganglionoma presenting as a scalp nodule
Metastatic paraganglionoma presenting as a scalp nodule Jami L. Miller, MD,a and Alan S. Boyd, MDa,b Nashville, Tennessee Malignant neoplasms with neural differentiation uncommonly present as cutaneous masses. However, a rapidly growing skin lesion in patients with a past history of retroperitoneal soft tissue tumors suggests that dissemination of that lesion may be taking place. (J Am Acad Dermatol 2001;44:321-3.)
P
araganglionomas are tumors that arise within the sympathetic nervous system.1 They are composed of hormonally active cells that frequently secrete catecholamines and often arise within the adrenal glands. These lesions may also originate in extra-adrenal sites. They are considered benign tumors and are best treated with surgical excision. About 10% of paraganglionomas previously diagnosed as benign eventually spread to distant sites, usually bones, liver, lung, and central nervous system.1 There has not been a reported case of cutaneous involvement by this tumor, and here we describe a patient with a metastatic paraganglionoma presenting as a soft nodule on the scalp.
CASE REPORT A 19-year-old white woman presented to our clinic with a 2- to 3-month history of a right frontoparietal scalp lesion. It was initially asymptomatic but had recently enlarged and become tender. She denied any systemic symptoms. The tumor was 2.5 cm in diameter and a soft, almost fluctuant, nodule, which was freely mobile within the skin. There was no evidence of hemorrhage, pulsatile activity, or bone erosion. During a pregnancy 4 years earlier, a retroperitoneal extra-adrenal mass was discovered, and during a cesarean section, it was removed. The tumor was diagnosed as a paraganglionoma with clear surgical margins, and the patient was believed
This supplement is made possible through an educational grant from Ortho Dermatological to the American Academy of Dermatology. Departments of Medicine (Dermatology)a and Pathology,b Vanderbilt University. Reprint requests: Alan S. Boyd, MD, 3900 The Vanderbilt Clinic, Nashville, TN 37232. E-mail: [email protected]. Copyright © 2001 by the American Academy of Dermatology, Inc. 0190-9622/2001/$35.00 + 0 16/4/103035 doi:10.1067/mjd.2001.103035
to have been cured. She had recently experienced low back pain after a work injury and was being treated with nonsteroidal anti-inflammatory drugs. Grossly, the mass was a highly vascular soft tumor. Histologically, the tissue showed aggregates of small slightly polygonal cells with faintly granular cytoplasm. Intracytoplasmic eosinophilic globules were rare. Spindle cells and mitotic figures were not seen, and minimal atypia was noted. The cells stained positive for S-100, neuron-specific enolase, periodic acid–Schiff (PAS), and chromogranin (Fig 1, A and B). A cranial magnetic resonance imaging (MRI) scan showed a mass protruding from the extradural space to the skin of the right frontoparietal scalp (Fig 2). Masses were also noted in the left cerebral hemisphere and midbrain area. An MRI of the spine revealed a destructive lesion at L-5/S-1. The patient was referred to neurosurgery, and the intracranial masses were excised. The histologic features of the lesions were similar to that from her scalp. The cells demonstrated focal areas of necrosis, slight spindling, and an absence of intracytoplasmic eosinophilic globules. The patient has subsequently died.
DISCUSSION Tumors of paraganglionic tissue often arise within the adrenal glands (pheochromocytoma) and extraadrenal retroperitoneum but may originate anywhere from the neck to the pelvis in locations paralleling the sympathetic ganglion chain. They are also associated with the multiple endocrine neoplasia type 2 syndrome (medullary carcinoma of the thyroid, mucosal neuromas, marfanoid body habitus, and pheochromocytoma). Malignant potential has been difficult to determine histologically and is defined after a metastatic lesion or direct invasion is found in a site with no residual embryonic paraganglionic tissue.1 Malignant degeneration occurs in about 10% of paraganglionomas arising within the adrenal gland. 321
322 Miller and Boyd
A
J AM ACAD DERMATOL FEBRUARY 2001
B Fig 1. A, PAS stain of paraganglioma demonstrates small nests of slightly polygonal cells. B, Tumor cells stain briskly with chromogranin stain.
Fig 2. MRI scan of the cranium showing large mass in right frontoparietal area that extends from brain parenchyma, through cranial vault, and involves overlying skin.
This increases to greater than 24% for those of extraadrenal origin2 although this has been disputed.3 Paraganglionomas both of adrenal and extra-adrenal origin are often active secretors of catecholamines, which cause symptoms such as labile hypertension, palpitations, headache, and sweating. Most patients are male,2 although in 1 series 70% were female.1 Lesions are most common in the fifth and sixth decades.1,4 Histologically, paraganglionomas are solid and often encapsulated. They have large cells with eosinophilic cytoplasm in a trabecular or honeycomb pattern, dense fibrous septa, and prominent vascularization. Intratumoral hemorrhage is common. Intracellular eosinophilic granules are present
and may become as large as the nucleus.5 Mitotic activity is rare in benign and malignant tumors and both may have large, bizarre-shaped cells. Cells typically stain for S-100, chromogranin, and neuron-specific enolase proteins. It is difficult to distinguish tumors prone to metastasize from benign lesions. Because the cells of a parganglionoma tend to be aggregated, small, and polygonal, the differential diagnosis includes Merkel cell carcinoma, clear cell sarcoma, glomus cell tumor, intradermal nevus with intratumoral hemorrhage, and neuroblastoma. The presence of intracytoplasmic eosinophilic globules and characteristic staining as a tumor of neuroectodermal derivation will assist in arriving at the appropriate diagnosis. Malignant lesions demonstrate uptake of 131I, increased staining with chromogranin A and neurospecific enolase, and a few sustentacular cells.6,7 Tumors with tetraploid and aneuploid DNA are associated with more aggressive behavior.8 Linnoila and coworkers2 found that malignant lesions more commonly demonstrate necrosis and possess fewer eosinophilic granules. The treatment of choice is surgical excision for the primary tumor and for metastatic lesions.1,4 Metastases grow slowly and respond poorly to radiation and/or chemotherapy. REFERENCES 1. Montresor E, Iacono C, Nifosi F, Zanza A, Modena A, Zamboni G et al. Retroperitoneal paraganglionomas: role of immunohistochemistry in the diagnosis of malignancy and in assessment of prognosis. Eur J Surg 1994;160:547-52. 2. Linnoila R, Keiser H, Steinberg S, Lack E. Histopathology of benign versus malignant sympathoadrenal paragangliomas: clinicopathologic study of 120 cases including unusual histologic features. Hum Pathol 1990;21:1168-80.
J AM ACAD DERMATOL VOLUME 44, NUMBER 2
3. Pommier RF, Vetto JT, Billingsly K, Woltering EA, Brenna MF. Comparison of adrenal and extraadrenal pheochromocytomas. Surgery 1993;114:1160-6. 4. Kryger-Baggesen N, Kjaegard J, Sehested M. Nonchromaffin paragangliomas of the retroperitoneum. J Urol 1985;134:536-8. 5. Enzinger FM, Weiss SM. Soft tissue tumors. New York: Mosby; 1995. 6. McCarthy EF, Bonfiglio M, Lawton W. A solitary functioning osseous metastasis from a malignant pheochromocytoma of the organ of zuckerandl. Cancer 1977;40:1987-2004.
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7. Hall G, Morris D, Mason RG. Nonfunctioning retroperitoneal paragangliomas. Am J Surg 1980;139:257-61. 8. Pang L, Tsao K. Flow cytometric DNA analysis for the determination of malignant potential in adrenal and extra-adrenal pheochromocytomas or paragangliomas. Arch Pathol Lab Med 1993;117:1142-7.
P
araganglionomas are tumors that arise within the sympathetic nervous system.1 They are composed of hormonally active cells that frequently secrete catecholamines and often arise within the adrenal glands. These lesions may also originate in extra-adrenal sites. They are considered benign tumors and are best treated with surgical excision. About 10% of paraganglionomas previously diagnosed as benign eventually spread to distant sites, usually bones, liver, lung, and central nervous system.1 There has not been a reported case of cutaneous involvement by this tumor, and here we describe a patient with a metastatic paraganglionoma presenting as a soft nodule on the scalp.
CASE REPORT A 19-year-old white woman presented to our clinic with a 2- to 3-month history of a right frontoparietal scalp lesion. It was initially asymptomatic but had recently enlarged and become tender. She denied any systemic symptoms. The tumor was 2.5 cm in diameter and a soft, almost fluctuant, nodule, which was freely mobile within the skin. There was no evidence of hemorrhage, pulsatile activity, or bone erosion. During a pregnancy 4 years earlier, a retroperitoneal extra-adrenal mass was discovered, and during a cesarean section, it was removed. The tumor was diagnosed as a paraganglionoma with clear surgical margins, and the patient was believed
This supplement is made possible through an educational grant from Ortho Dermatological to the American Academy of Dermatology. Departments of Medicine (Dermatology)a and Pathology,b Vanderbilt University. Reprint requests: Alan S. Boyd, MD, 3900 The Vanderbilt Clinic, Nashville, TN 37232. E-mail: [email protected]. Copyright © 2001 by the American Academy of Dermatology, Inc. 0190-9622/2001/$35.00 + 0 16/4/103035 doi:10.1067/mjd.2001.103035
to have been cured. She had recently experienced low back pain after a work injury and was being treated with nonsteroidal anti-inflammatory drugs. Grossly, the mass was a highly vascular soft tumor. Histologically, the tissue showed aggregates of small slightly polygonal cells with faintly granular cytoplasm. Intracytoplasmic eosinophilic globules were rare. Spindle cells and mitotic figures were not seen, and minimal atypia was noted. The cells stained positive for S-100, neuron-specific enolase, periodic acid–Schiff (PAS), and chromogranin (Fig 1, A and B). A cranial magnetic resonance imaging (MRI) scan showed a mass protruding from the extradural space to the skin of the right frontoparietal scalp (Fig 2). Masses were also noted in the left cerebral hemisphere and midbrain area. An MRI of the spine revealed a destructive lesion at L-5/S-1. The patient was referred to neurosurgery, and the intracranial masses were excised. The histologic features of the lesions were similar to that from her scalp. The cells demonstrated focal areas of necrosis, slight spindling, and an absence of intracytoplasmic eosinophilic globules. The patient has subsequently died.
DISCUSSION Tumors of paraganglionic tissue often arise within the adrenal glands (pheochromocytoma) and extraadrenal retroperitoneum but may originate anywhere from the neck to the pelvis in locations paralleling the sympathetic ganglion chain. They are also associated with the multiple endocrine neoplasia type 2 syndrome (medullary carcinoma of the thyroid, mucosal neuromas, marfanoid body habitus, and pheochromocytoma). Malignant potential has been difficult to determine histologically and is defined after a metastatic lesion or direct invasion is found in a site with no residual embryonic paraganglionic tissue.1 Malignant degeneration occurs in about 10% of paraganglionomas arising within the adrenal gland. 321
322 Miller and Boyd
A
J AM ACAD DERMATOL FEBRUARY 2001
B Fig 1. A, PAS stain of paraganglioma demonstrates small nests of slightly polygonal cells. B, Tumor cells stain briskly with chromogranin stain.
Fig 2. MRI scan of the cranium showing large mass in right frontoparietal area that extends from brain parenchyma, through cranial vault, and involves overlying skin.
This increases to greater than 24% for those of extraadrenal origin2 although this has been disputed.3 Paraganglionomas both of adrenal and extra-adrenal origin are often active secretors of catecholamines, which cause symptoms such as labile hypertension, palpitations, headache, and sweating. Most patients are male,2 although in 1 series 70% were female.1 Lesions are most common in the fifth and sixth decades.1,4 Histologically, paraganglionomas are solid and often encapsulated. They have large cells with eosinophilic cytoplasm in a trabecular or honeycomb pattern, dense fibrous septa, and prominent vascularization. Intratumoral hemorrhage is common. Intracellular eosinophilic granules are present
and may become as large as the nucleus.5 Mitotic activity is rare in benign and malignant tumors and both may have large, bizarre-shaped cells. Cells typically stain for S-100, chromogranin, and neuron-specific enolase proteins. It is difficult to distinguish tumors prone to metastasize from benign lesions. Because the cells of a parganglionoma tend to be aggregated, small, and polygonal, the differential diagnosis includes Merkel cell carcinoma, clear cell sarcoma, glomus cell tumor, intradermal nevus with intratumoral hemorrhage, and neuroblastoma. The presence of intracytoplasmic eosinophilic globules and characteristic staining as a tumor of neuroectodermal derivation will assist in arriving at the appropriate diagnosis. Malignant lesions demonstrate uptake of 131I, increased staining with chromogranin A and neurospecific enolase, and a few sustentacular cells.6,7 Tumors with tetraploid and aneuploid DNA are associated with more aggressive behavior.8 Linnoila and coworkers2 found that malignant lesions more commonly demonstrate necrosis and possess fewer eosinophilic granules. The treatment of choice is surgical excision for the primary tumor and for metastatic lesions.1,4 Metastases grow slowly and respond poorly to radiation and/or chemotherapy. REFERENCES 1. Montresor E, Iacono C, Nifosi F, Zanza A, Modena A, Zamboni G et al. Retroperitoneal paraganglionomas: role of immunohistochemistry in the diagnosis of malignancy and in assessment of prognosis. Eur J Surg 1994;160:547-52. 2. Linnoila R, Keiser H, Steinberg S, Lack E. Histopathology of benign versus malignant sympathoadrenal paragangliomas: clinicopathologic study of 120 cases including unusual histologic features. Hum Pathol 1990;21:1168-80.
J AM ACAD DERMATOL VOLUME 44, NUMBER 2
3. Pommier RF, Vetto JT, Billingsly K, Woltering EA, Brenna MF. Comparison of adrenal and extraadrenal pheochromocytomas. Surgery 1993;114:1160-6. 4. Kryger-Baggesen N, Kjaegard J, Sehested M. Nonchromaffin paragangliomas of the retroperitoneum. J Urol 1985;134:536-8. 5. Enzinger FM, Weiss SM. Soft tissue tumors. New York: Mosby; 1995. 6. McCarthy EF, Bonfiglio M, Lawton W. A solitary functioning osseous metastasis from a malignant pheochromocytoma of the organ of zuckerandl. Cancer 1977;40:1987-2004.
Miller and Boyd 323
7. Hall G, Morris D, Mason RG. Nonfunctioning retroperitoneal paragangliomas. Am J Surg 1980;139:257-61. 8. Pang L, Tsao K. Flow cytometric DNA analysis for the determination of malignant potential in adrenal and extra-adrenal pheochromocytomas or paragangliomas. Arch Pathol Lab Med 1993;117:1142-7.