Clustering of sebaceous gland carcinoma, papillary thyroid carcinoma and breast cancer in a woman as a new cancer susceptibility disorder: a case report

Clustering of sebaceous gland carcinoma, papillary thyroid carcinoma and breast cancer in a woman as a new cancer susceptibility disorder: a case report

Bigler Steven A, Koch Christian A, Newman Brian D, Subauste Jose S, Uwaifo Gabriel I
Journal of Medical Case Reports 2009, 3:6905
Published: August 2009
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Introduction: Multiple distinct tumors arising in a single individual or within members of a family raise the suspicion of a genetic susceptibility disorder.

Case presentation: We present the case of a 52-year-old Caucasian woman diagnosed with sebaceous gland carcinoma of the eyelid, followed several years later with subsequent diagnoses of breast cancer and papillary carcinoma of the thyroid. Although the patient was also exposed to radiation from a pipe used in the oil field industry, the constellation of neoplasms in this patient suggests the manifestation of a known hereditary susceptibility cancer syndrome. However, testing for the most likely candidates such as Muir-Torre and Cowden syndrome proved negative.

Conclusion: We propose that our patient’s clustering of neoplasms either represents a novel cancer susceptibility disorder, of which sebaceous gland carcinoma is a characteristic feature, or is a variant of the Muir-Torre syndrome.

Introduction
Multiple distinct tumors arising in a single individual or within members of a family raise the suspicion of a genetic susceptibility disorder 1,2. Tumor suppressor genes, such as PTEN in Cowden syndrome and BRCA1/2 in breast cancer, function by eliciting apoptosis and G1 cycle arrest. However, expression and tissue-specific splicing may lead to the differential expression of splice variants (SVs) with subsequent downstream signaling consequences. SVs resulting from alterations in the splicing of cancer-related genes could represent novel cases of familiar syndromes that do not reveal classic mutations. The diagnosis of sebaceous gland carcinoma can represent a marker of an associated heritable disorder, and some authors recommend patients be evaluated for other visceral malignancies 3. Additionally, prompt diagnosis enables routine surveillance of occult cancers, identification of low-grade tumors that would be more responsive to treatment, and identification of family members at risk for developing cancer.

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References:
  1. Georgitsi M, Heliovaara E, Paschke R et al: Large genomic deletions in AIP in pituitary adenoma predisposition. J Clin Endocrinol Metab 2008, 93:4146-4151.
  2. Koch CA: Molecular pathogenesis of MEN2-associated tumors. Fam Cancer 2005, 4:3-7.
  3. Demirci H, Nelson CC, Shields CL, Eagle RC Jr, Shields JA: Eyelid sebaceous carcinoma associated with Muir-Torre syndrome in two cases. Ophthal Plast Reconstr Surg 2007, 23:77-79.
  4. Shields JA, Demirci H, Marr BP, Eagle RC Jr, Shields CL: Sebaceous Carcinoma of the Eyelids: Personal Experience with 60 Cases. Ophthalmology 2004, 111:2151-2157.
  5. Kass LG, Hornblass A: Sebaceous carcinoma of the ocular adnexa. Surv Ophthalmol 1989, 33:477-490.
  6. Chao AN, Shields Cl, Krema H, Shields JA: Outcome with periocular sebaceous gland carcinoma with and without conjunctival intraepithelial invasion. Ophthalmology 2001, 108:1877-1883.
  7. Finan MC, Connolly SM: Sebaceous gland tumors and systemic disease: a clinicopathologic analysis. Medicine 1984, 63:63-70.
  8. Hay ID: Papillary thyroid carcinoma. Endocrinol Metab Clin North Am 1990, 19:545-576.
  9. Hay ID, Hutchinson ME, Gonzales-Losada T, McIver B, Reinalda ME, Grant CS, Thompson GB, Sebo TJ, Goellner JR: Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery 2008, 144:980-987.
  10. Hay ID, Thompson GB, Grant CS, Bergstralh EJ, Dvorak CE, Gorman GA, Maurer MS, McIver B, Mullan BP, Oberg AL, Powell CC, van Heerden JA, Goellner JR: Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients. World J Surg 2002, 26:879-885.
  11. Nikiforov YE: Thyroid carcinoma: molecular pathways and therapeutic targets. Mod Pathol 2008, 21:S37-S43.
  12. Koch CA, Sarlis NJ: The spectrum of thyroid diseases in childhood and its evolution during transition to adulthood: natural history, diagnosis, differential diagnosis and management. J Endocrinol Invest 2001, 24:659-675.
  13. Weber F, Eng C: Update on the Molecular Diagnosis of Endocrine Tumors: Toward –omics-Based Personalized Healthcare? J Clin Endocrinol Metab 2008, 93:1097-1104.
  14. Rippberger T, Gadzicki D, Meindl A, Schlegelberger B: Breast cancer susceptibility: current knowledge and implications for genetic counseling. Eur J Hum Genet 2008, 17:722-731.
  15. Celebi JT, Wanner M, Ping Xl et al: Association of splicing defects in PTEN leading to exon skipping or partial intron RETention in Cowden syndrome. Hum Genet 2000, 107:234-238.
  16. Propeck PA, Warner T, Scanlan KA: Sebaceous carcinoma of the breast in a patient with Muir-Torre syndrome. AJR 2000, 174:541-542.
  17. Chen J, Lindblom A: Germline mutation screening of the STK11/LKB1 gene in familial breast cancer with LOH on 19p. Clin Genet 2000, 57:394-397.
  18. Entius MM, Keller JJ, Drillenburg P et al: Microsatellite instability and expression of hMLH-1 and hMSH-2 in sebaceous gland carcinomas as markers for Muir-Torre Syndrome. Colon Cancer Res 2000, 6:1784-1789.
  19. Honchel R, Halling KC, Schaid DJ: Microsatellite instability in Muir-Torre syndrome. Cancer Res 1994, 54:1159-1163.
  20. Weinstein A, Nouri K, Bassiri-Tehrani S, Jimenez G: Muir-Torre syndrome: a case of this uncommon entity. Int J Dermatol 2006, 45:311-313.
  21. Ponti G, Ponz de Leon M, Pedroni M et al: Attenuated familial adenomatous polyposis and Muir-Torre syndrome linked to compound biallelic constitutional MYH gene mutations. Clin Genet 2005, 68:442-447.
  22. Phoung M, Korde L, Kramer J et al: A possible new syndrome with growth-hormone secRETing pituitary adenoma, colonic polyposis, lipomatosis, lentigines and renal carcinoma in association with familiar testicular germ cell malignancy: A case report. J Med Case Rep 2007, 1:9.
  23. Chibon F, Primois C, Bressieux JM, Lacombe D, Lok C, Mauriac L, Taieb A, Longy M: Contribution of PTEN large rearrangements in Cowden disease: a MAPH screening approach. J Med Genet 2008, 45:657-65.
  24. Zbuk KM, Patocs A, Shealy A, Sylvester H, Miesfeldt S, Eng C: Germline mutations in PTEN and SDHC in a woman with epithelial thyroid cancer and carotid paraganglioma. Nat Clin Pract Oncol 2007, 4:608-612.
  25. Ni, Zbuk KM, Sadler T, Patocs A, Lobo G, Edelman E, Platzer P, Orloff MS, Waite KA, Eng C: Germline mutations and variants in the succinate dehydrogenase genes in Cowden and Cowdenlike syndromes. Am J Hum Genet 2008, 83:261-268.
  26. Plon SE, Pirics ML, Nuchtern J, Hicks J, Russel H, Agrawal S, Zbuk K, Eng C, Hegde M, Chin EPH: Multiple tumors in a child with germline mutations in TP53 and PTEN. N Engl J Med 2008, 359:537-539.
  27. Frew IJ, Minola A, Georgiev S, Hitz M, Moch H, Richard S, Vortmeyer AO, Krek W: Combined VHLH and PTEN mutation causes genital tract cystadenoma and squamous metaplasia. Mol Cell Biol 2008, 28:4536-4548.
  28. Donnellan KA, Bigler SA, Wein RO: Papillary thyroid carcinoma and familial adenommatous polyposis of the colon. Am J Otolaryngol 2009, 30:58-60.
  29. Ahmad S, Aaltonen LA, Georgitsi M, Parent A, Fratkin J, Gomez- Sanchez EP, Koch CA: Do single nucleotide polymorphisms in the AIP gene and MEN 1 gene predispose individuals to the development of familial isolated pituitary tumors? Exp Clin Endocrinol Diabetes 2007, 115:S35-S36.
  30. Koch CA, Friedrich CA, Majumdar S, Fraktin JD, Moll GW: Novel splice donor region DNA sequence variant in the succinate dehydrogenase subunit B gene in a boy with malignant paraganglioma in a family with non-classical congenital adrenal hyperplasia. Exp Clin Endocrinol Diabetes 2007, 115:S39.
  31. Koch CA, Brouwers FM, Vortmeyer AO, Tannapfel A, Libutti SK, Zhuang Z, Pacak K, Neumann HPH, Paschke R: Somatic VHL gene alterations in MEN 2-associated medullary thyroid carcinoma. BMC Cancer 2006, 6:131.
  32. Koch CA, Huang SC, Zhuang Z, Stolle C, Azumi N, Chrousos GP, Vortmeyer AO, Pacak K: Somatic VHL gene deletion and point mutation in MEN 2A-related pheochromocytoma. Oncogene 2002, 21:479-482.
  33. Orban TI, Olah E: Expression profiles of BRCA1 splice variants in asynchronous and in G1/S synchronized tumor cell lines. Biochem Biophys Res Commun 2001, 280:32-38.
  34. Sato N, Hori O, Yamaguchi I, Lambert JC et al: A novel presenilin-2 splice varian in human Alzheimer's disease brain tissue. J Neurochem 1999, 72:2498-2505.
  35. Vijayakrishnan L, Slavik JM, Illes Z et al: An autoimmune diseaseassociated CTLA-4 splice variant lacking the B7 binding domain signals negatively in T cells. Immunity 2004, 20:563-575.
  36. Weng MW, Lai JC, Hsu CP et al: Alternative splicing of MDM2 mRNA in lung carcinomas and lung cell lines. Environ Mol Mutagen 2005, 46:1-11.
  37. Rohaly G, Chemnitz J, Dehde S et al: A novel human p53 isoform is an essential element of the ATR-intra-S phase checkpoint. Cell 2005, 122:21-32.
  38. Agrawal S, Eng C: Differential expression of novel naturally occurring splice variants of PTEN and their functional consequences in Cowden syndrome and sporadic breast cancer. Hum Mol Genet 2006, 15:777-787.

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