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Cutaneous lichen amyloidosis in a family with familial medullary thyroid cancer
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Cutaneous lichen amyloidosis in a family with familial medullary thyroid cancer Fizan Abdullah, MD, PhD, and Robert Udelsman, MD, MBA, New Haven, Conn
From the Department of Surgery, Yale University School of Medicine, New Haven, Conn
A 39-YEAR-OLD WOMAN of Indian descent was referred to our department after her primary medical doctor palpated bilateral thyroid nodules (1.7 cm right, 2 cm left) and noted an interscapular hyperpigmented cutaneous lesion. Medullary thyroid carcinoma (MTC) was diagnosed after bilateral fine-needle aspirations were performed; the specimen tested positive for calcitonin staining. A biopsy of the skin lesion revealed hyperkeratosis and deposits of amorphous amyloid-like material immediately beneath and in contiguity with the dermoepidermal junction. The amyloid-like material tested positive for cytokeratin 903. Her serum calcitonin was elevated at 1845 pg/mL (reference range <4). A 24-hour urinary catecholamine screen was negative, as was a preoperative computed tomography scan of the neck, chest, and abdomen. The patient was tested for the RET proto-oncogene, which was positive for a mutation at codon 634. Specifically, 2 nucleotide changes were detected at the first and second nucleotide positions. A diagnosis of familial MTC was also confirmed by family history (Fig 1). The patient’s mother, at approximately 40 years of age, under-
Accepted for publication November 14, 2002. Reprint requests: Robert Udelsman, MD, MBA, Chairman, Department of Surgery, Yale University School of Medicine, 333 Cedar Street, FMB 102, New Haven, CT 06520-8047. Surgery 2004;135:563-4. 0039-6060/$ - see front matter Ó 2004, Elsevier Inc. All rights reserved. doi:10.1016/S0039-6060(02)21685-2
went a thyroidectomy for nodules. Furthermore, she reported an aunt who died during surgery for thyroid cancer. She also had other family members afflicted with thyroid cancer. Of note, the patient reported similar interscapular, hyperpigmented lesions consistent with cutaneous lichen amyloidosis in her mother (Fig 2) and her niece. The patient underwent a total thyroidectomy with bilateral central and modified radical neck dissections, at which time MTC was confined to the thyroid gland, and 1 of 80 lymph nodes tested positive for metastatic carcinoma. Her postoperative course was uneventful, and her serum calcitonin decreased below detectable limits. The patient’s niece (age 14 years) also tested positive for RET proto-oncogene and subsequently underwent prophylactic thyroidectomy.
DISCUSSION Familial or hereditary MTC can occur alone or as part of the multiple endocrine neoplasia (MEN) syndromes (type IIA or B). Ninety-eight percent of all mutations in the RET oncogene (a tyrosinekinase receptor) responsible for familial MTC have been identified, which makes genetic testing a powerful marker for guiding surgical therapy. This underscores the importance of ensuring the complete screening of families suspected to have familial MTC or MEN syndromes. Cutaneous lichen amyloidosis is characterized by amyloid deposits in the papillary dermis, typically occurring in the interscapular region. The association of this lesion with MEN type IIA was first SURGERY 563
564 Abdullah and Udelsman
Surgery May 2004
Fig 1. Pedigree of family. Propositus (arrow). Symbols as shown represent thyroid disease and skin changes.
family members with skin lesions.3 Thus, as in the family described here, the presence of the interscapular lesion serves as a phenotypic marker for members of the family and is therefore useful for guiding clinical recommendations.
REFERENCES
Fig 2. Cutaneous lichen amyloidosis in propositus (left) and her mother (right).
described more than a decade ago.1,2 In a study of 5 families with known MEN IIA syndrome, the presence of MEN IIA was documented in 97% of
1. Nunziata V, Giannattasio R, Di Giovanni G, D’Armiento MR, Mancini M. Hereditary localized pruritus in affected members of a kindred with multiple endocrine neoplasia type 2A (Sipple’s syndrome). Clin Endocrinol 1989;30:57-63. 2. Gagel RF, Levy ML, Donovan DT, Alford BR, Wheeler T, Tschen JA. Multiple endocrine neoplasia type 2a associated with cutaneous lichen amyloidosis. Ann Intern Med 1989;111:802-6. 3. Robinson MF, Furst EJ, Nunziata V, Brandi ML, Ferrer JP, Martins Bugalho MJG, et al. Characterization of the clinical features of 5 families with hereditary primary cutaneous lichen amyloidosis and multiple endocrine neoplasia type 2. Henry Ford Hosp Med J 1992;40:249-52.
Cutaneous lichen amyloidosis in a family with familial medullary thyroid cancer Fizan Abdullah, MD, PhD, and Robert Udelsman, MD, MBA, New Haven, Conn
From the Department of Surgery, Yale University School of Medicine, New Haven, Conn
A 39-YEAR-OLD WOMAN of Indian descent was referred to our department after her primary medical doctor palpated bilateral thyroid nodules (1.7 cm right, 2 cm left) and noted an interscapular hyperpigmented cutaneous lesion. Medullary thyroid carcinoma (MTC) was diagnosed after bilateral fine-needle aspirations were performed; the specimen tested positive for calcitonin staining. A biopsy of the skin lesion revealed hyperkeratosis and deposits of amorphous amyloid-like material immediately beneath and in contiguity with the dermoepidermal junction. The amyloid-like material tested positive for cytokeratin 903. Her serum calcitonin was elevated at 1845 pg/mL (reference range <4). A 24-hour urinary catecholamine screen was negative, as was a preoperative computed tomography scan of the neck, chest, and abdomen. The patient was tested for the RET proto-oncogene, which was positive for a mutation at codon 634. Specifically, 2 nucleotide changes were detected at the first and second nucleotide positions. A diagnosis of familial MTC was also confirmed by family history (Fig 1). The patient’s mother, at approximately 40 years of age, under-
Accepted for publication November 14, 2002. Reprint requests: Robert Udelsman, MD, MBA, Chairman, Department of Surgery, Yale University School of Medicine, 333 Cedar Street, FMB 102, New Haven, CT 06520-8047. Surgery 2004;135:563-4. 0039-6060/$ - see front matter Ó 2004, Elsevier Inc. All rights reserved. doi:10.1016/S0039-6060(02)21685-2
went a thyroidectomy for nodules. Furthermore, she reported an aunt who died during surgery for thyroid cancer. She also had other family members afflicted with thyroid cancer. Of note, the patient reported similar interscapular, hyperpigmented lesions consistent with cutaneous lichen amyloidosis in her mother (Fig 2) and her niece. The patient underwent a total thyroidectomy with bilateral central and modified radical neck dissections, at which time MTC was confined to the thyroid gland, and 1 of 80 lymph nodes tested positive for metastatic carcinoma. Her postoperative course was uneventful, and her serum calcitonin decreased below detectable limits. The patient’s niece (age 14 years) also tested positive for RET proto-oncogene and subsequently underwent prophylactic thyroidectomy.
DISCUSSION Familial or hereditary MTC can occur alone or as part of the multiple endocrine neoplasia (MEN) syndromes (type IIA or B). Ninety-eight percent of all mutations in the RET oncogene (a tyrosinekinase receptor) responsible for familial MTC have been identified, which makes genetic testing a powerful marker for guiding surgical therapy. This underscores the importance of ensuring the complete screening of families suspected to have familial MTC or MEN syndromes. Cutaneous lichen amyloidosis is characterized by amyloid deposits in the papillary dermis, typically occurring in the interscapular region. The association of this lesion with MEN type IIA was first SURGERY 563
564 Abdullah and Udelsman
Surgery May 2004
Fig 1. Pedigree of family. Propositus (arrow). Symbols as shown represent thyroid disease and skin changes.
family members with skin lesions.3 Thus, as in the family described here, the presence of the interscapular lesion serves as a phenotypic marker for members of the family and is therefore useful for guiding clinical recommendations.
REFERENCES
Fig 2. Cutaneous lichen amyloidosis in propositus (left) and her mother (right).
described more than a decade ago.1,2 In a study of 5 families with known MEN IIA syndrome, the presence of MEN IIA was documented in 97% of
1. Nunziata V, Giannattasio R, Di Giovanni G, D’Armiento MR, Mancini M. Hereditary localized pruritus in affected members of a kindred with multiple endocrine neoplasia type 2A (Sipple’s syndrome). Clin Endocrinol 1989;30:57-63. 2. Gagel RF, Levy ML, Donovan DT, Alford BR, Wheeler T, Tschen JA. Multiple endocrine neoplasia type 2a associated with cutaneous lichen amyloidosis. Ann Intern Med 1989;111:802-6. 3. Robinson MF, Furst EJ, Nunziata V, Brandi ML, Ferrer JP, Martins Bugalho MJG, et al. Characterization of the clinical features of 5 families with hereditary primary cutaneous lichen amyloidosis and multiple endocrine neoplasia type 2. Henry Ford Hosp Med J 1992;40:249-52.