Gynecological lesions in hereditary cancer predisposition syndromes

Czech version

Authors: Pavel Dundr ¹; David Cibula ²; Lenka Foretová ³; Milan Macek jr. ⁴; Kateřina Kopečková ⁵; Luboš Petruželka ⁶; Kristýna Němejcová ¹; Michaela Bártů ¹; Jan Hojný ¹; Nikola Hájková ¹; Radek Jakša ¹; Pavol Janega ^7,8; Ivana Stružinská ¹
Authors‘ workplace: Ústav patologie 1. LF UK a VFN v Praze ¹; Onkogynekologické centrum, Gynekologicko-porodnická klinika 1. LF UK a VFN v Praze ²; Oddělení epidemiologie a genetiky nádorů, Masarykův onkologický ústav, Brno ³; Ústav biologie a lékařské genetiky 2. LF UK a FN Motol ⁴; Onkologická klinika 2. LF UK a FN Motol ⁵; Onkologická klinika 1. LF UK a VFN v Praze ⁶; Ústav patologickejanatómie, Lekárská fakulta, Univerzita Komenského v Bratislave ⁷; Medirex Group Academy, Trnava, n. o. ⁸
Published in: Čes.-slov. Patol., 57, 2021, No. 2, p. 96-104
Category: Reviews Article

Overview

Hereditary tumor syndromes with a possible manifestation in the female internal genital tract represent a heterogeneous group of diseases. The two most common entities are the hereditary breast and ovarian cancer syndrome, and the Lynch syndrome. The less common syndromes include the rhabdoid tumor predisposition syndrome, Cowden syndrome, tuberous sclerosis complex, DICER1 syndrome, nevoid basal cell carcinoma syndrome, Peutz-Jeghers syndrome, von Hippel-Lindau disease, and hereditary leiomyomatosis and renal cell cancer syndrome. The goal of this manuscript is to provide a comprehensive overview of those hereditary tumor syndromes which can manifest in the area of the female genital system, with an emphasis on their summary, the characteristics of the tumors which can develop in association with these syndromes, and the approach to the processing of prophylactically removed tissues and organs. The issue of Lynch syndrome screening is also discussed.

Keywords:

mesenchymal uterine tumors – smooth muscle tumors – endometrial stromal tumors – undifferentiated uterine sarcoma – immunohistochemistry – molecular classification – hereditary cancer predisposition syndromes – female genital tract – Lynch syndrome – hereditary breast and ovarian cancer syndrome – Peutz-Jeghers syndrome

Sources

Garber JE, Offit K. Hereditary cancer predisposition syndromes. J Clin Oncol 2005; 23(2): 276-292.
Foretova L. Hereditary cancer syndromes, their testing and prevention. Cas Lek Cesk 2019; 158(1): 15-21.
Foretova L, Petrakova K, Palacova M, et al. Genetic testing and prevention of hereditary cancer at the MMCI - over 10 years of experience. Klin Onkol 2010; 23(6): 388-400.
Pal T, Permuth-Wey J, Betts JA, et al. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer 2005; 104(12): 2807-2816.
Risch HA, Mclaughlin JR, Cole DE, et al. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: A kin-cohort study in ontario, canada. J Natl Cancer Inst 2006; 98(23): 1694-1706.
Helder-Woolderink JM, Blok EA, Vasen HF, et al. Ovarian cancer in lynch syndrome; a systematic review. Eur J Cancer 2016; 55: 65-73.
Garg K, Karnezis AN, Rabban JT. Uncommon hereditary gynaecological tumour syndromes: Pathological features in tumours that may predict risk for a germline mutation. Pathology 2018; 50(2): 238-256.
Struewing JP, Hartge P, Wacholder S, et al. The risk of cancer associated with specific mutations of brca1 and brca2 among ashkenazi jews. N Engl J Med 1997; 336(20): 1401-1408.
Petrakova K, Palacova M, Schneiderova M, Standara M. [hereditary breast and ovarian cancer syndrome]. Klin Onkol 2016; 29 Suppl 1: S14-21.
Plevova P, Novotny J, Petrakova K, et al. Hereditary breast and ovarian cancer syndrome. Klin Onkol 2009; 22 Suppl: S8-11.
Antoniou A, Pharoah PD, Narod S, et al. Average risks of breast and ovarian cancer associated with brca1 or brca2 mutations detected in case series unselected for family history: A combined analysis of 22 studies. Am J Hum Genet 2003; 72(5): 1117-1130.
King MC, Marks JH, Mandell JB, New York Breast Cancer Study G. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 2003; 302(5645): 643-646.
Mavaddat N, Peock S, Frost D, et al. Cancer risks for BRCA1 and BRCA2 mutation carriers: Results from prospective analysis of embrace. J Natl Cancer Inst 2013; 105(11): 812-822.
Hanley GE, Mcalpine JN, Miller D, et al. A population-based analysis of germline BRCA1 and BRCA2 testing among ovarian cancer patients in an era of histotype-specific approaches to ovarian cancer prevention. BMC Cancer 2018; 18(1): 254.
Mersch J, Jackson MA, Park M, et al. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer 2015; 121(2): 269-275.
Ibrahim M, Yadav S, Ogunleye F, Zakalik D. Male BRCA mutation carriers: Clinical characteristics and cancer spectrum. BMC Cancer 2018; 18(1): 179.
Soslow RA, Han G, Park KJ, et al. Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma. Mod Pathol 2012; 25(4): 625-636.
Reyes MC, Arnold AG, Kauff ND, Levine DA, Soslow RA. Invasion patterns of metastatic high-grade serous carcinoma of ovary or fallopian tube associated with brca deficiency. Mod Pathol 2014; 27(10): 1405-1411.
Garg K, Levine DA, Olvera N, et al. BRCA1 immunohistochemistry in a molecularly characterized cohort of ovarian high-grade serous carcinomas. Am J Surg Pathol 2013; 37(1): 138-146.
Foretova L, Machackova E, Palacova M, et al. Recommended extension of indication criteria for genetic testing of BRCA1 and BRCA2 mutations in hereditary breast and ovarian cancer syndrome. Klin Onkol 2016; 29 Suppl 1: S9-13.
Zikan M, Kalabova R. Recommendation for prophylactic surgery for decreasing the risk of gynaecological cancer in women with hereditary risk. Klin Onkol 2009; 22 Suppl: S58-59.
Lee Y, Medeiros F, Kindelberger D, et al. Advances in the recognition of tubal intraepithelial carcinoma: Applications to cancer screening and the pathogenesis of ovarian cancer. Adv Anat Pathol 2006; 13(1): 1-7.
Cancer Genome Atlas Research N. Integrated genomic analyses of ovarian carcinoma. Nature 2011; 474(7353): 609-615.
Da Cunha Colombo Bonadio RR, Fogace RN, Miranda VC, Diz M. Homologous recombination deficiency in ovarian cancer: A review of its epidemiology and management. Clinics (Sao Paulo) 2018; 73(suppl 1): e450s.
Hampel H, De La Chapelle A. How do we approach the goal of identifying everybody with Lynch syndrome? Fam Cancer 2013; 12(2): 313-317.
Bonadona V, Bonaiti B, Olschwang S, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA 2011; 305(22): 2304-2310.
Dunlop MG, Farrington SM, Carothers AD, et al. Cancer risk associated with germline DNA mismatch repair gene mutations. Hum Mol Genet 1997; 6(1): 105-110.
Grindedal EM, Renkonen-Sinisalo L, Vasen H, et al. Survival in women with MMR mutations and ovarian cancer: A multicentre study in Lynch syndrome kindreds. J Med Genet 2010; 47(2): 99-102.
Downes MR, Allo G, Mccluggage WG, et al. Review of findings in prophylactic gynaecological specimens in Lynch syndrome with literature review and recommendations for grossing. Histopathology 2014; 65(2): 228-239.
Chui MH, Gilks CB, Cooper K, Clarke BA. Identifying Lynch syndrome in patients with ovarian carcinoma: The significance of tumor subtype. Adv Anat Pathol 2013; 20(6): 378-386.
Sjursen W, Haukanes BI, Grindedal EM, et al. Current clinical criteria for Lynch syndrome are not sensitive enough to identify msh6 mutation carriers. J Med Genet 2010; 47(9): 579-585.
Lancaster JM, Powell CB, Chen LM, Richardson DL, Committee SGOCP. Society of gynecologic oncology statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol 2015; 136(1): 3-7.
Evaluation of Genomic Applications In P, Prevention Working G. Recommendations from the egapp working group: Genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Genet Med 2009; 11(1): 35-41.
Dillon JL, Gonzalez JL, Demars L, Bloch KJ, Tafe LJ. Universal screening for Lynch syndrome in endometrial cancers: Frequency of germline mutations and identification of patients with Lynch-like syndrome. Hum Pathol 2017; 70(121-128.
Cho KR, Cooper K, Croce S, et al. International society of gynecological pathologists (ISGYP) endometrial cancer project: Guidelines from the special techniques and ancillary studies group. Int J Gynecol Pathol 2019; 38 Suppl 1: S114-S122.
Mills AM, Longacre TA. Lynch syndrome screening in the gynecologic tract: Current state of the art. Am J Surg Pathol 2016; 40(4): e35-44.
Mcconechy MK, Talhouk A, Li-Chang HH, et al. Detection of DNA mismatch repair (MMR) deficiencies by immunohistochemistry can effectively diagnose the microsatellite instability (MSI) phenotype in endometrial carcinomas. Gynecol Oncol 2015; 137(2): 306-310.
Sarode VR, Robinson L. Screening for Lynch syndrome by immunohistochemistry of mismatch repair proteins: Significance of indeterminate result and correlation with mutational studies. Arch Pathol Lab Med 2019; 143(10): 1225-1233.
Goodfellow PJ, Billingsley CC, Lankes HA, et al. Combined microsatellite instability, MLH1 methylation analysis, and immunohistochemistry for lynch syndrome screening in endometrial cancers from GOG210: An NRG oncology and gynecologic oncology group study. J Clin Oncol 2015; 33(36): 4301-4308.
Lu FI, Gilks CB, Mulligan AM, et al. Prevalence of loss of expression of DNA mismatch repair proteins in primary epithelial ovarian tumors. Int J Gynecol Pathol 2012; 31(6): 524-531.
Schmeler KM, Lynch HT, Chen LM, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med 2006; 354(3): 261-269.
Gammon A, Jasperson K, Champine M. Genetic basis of Cowden syndrome and its implications for clinical practice and risk management. Appl Clin Genet 2016; 9(83-92.
Mahdi H, Mester JL, Nizialek EA, et al. Germline PTEN, SDHB-d, and KLLN alterations in endometrial cancer patients with Cowden and Cowden-like syndromes: An international, multicenter, prospective study. Cancer 2015; 121(5): 688-696.
Baker WD, Soisson AP, Dodson MK. Endometrial cancer in a 14-year-old girl with Cowden syndrome: A case report. J Obstet Gynaecol Res 2013; 39(4): 876-878.
Djordjevic B, Hennessy BT, Li J, et al. Clinical assessment of PTEN loss in endometrial carcinoma: Immunohistochemistry outperforms gene sequencing. Mod Pathol 2012; 25(5): 699-708.
Nemes K, Bens S, Bourdeaut F, et al. Rhabdoid tumor predisposition syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K and Amemiya A, eds. Genereviews((r)) ed). Seattle (WA): 1993:
Kupryjanczyk J, Dansonka-Mieszkowska A, Moes-Sosnowska J, et al. Ovarian small cell carcinoma of hypercalcemic type - evidence of germline origin and SMARCA4 gene inactivation. A pilot study. Pol J Pathol 2013; 64(4): 238-246.
Hruska L, Sirak I, Laco J, et al. Rare hereditary burden associated with a hypercalcemic small-cell carcinoma of cervix in a young female patient. Klin Onkol 2019; 32(6): 456-462.
Witkowski L, Goudie C, Foulkes WD, Mccluggage WG. Small-cell carcinoma of the ovary of hypercalcemic type (malignant rhabdoid tumor of the ovary): A review with recent developments on pathogenesis. Surg Pathol Clin 2016; 9(2): 215-226.
Conlon N, Silva A, Guerra E, et al. Loss of SMARCA4 expression is both sensitive and specific for the diagnosis of small cell carcinoma of ovary, hypercalcemic type. Am J Surg Pathol 2016; 40(3): 395-403.
Menko FH, Maher ER, Schmidt LS, et al. Hereditary leiomyomatosis and renal cell cancer (HLRCC): Renal cancer risk, surveillance and treatment. Fam Cancer 2014; 13(4): 637-644.
Plevova P, Hladikova A, Tesarova M. Hereditary leiomyomatosis and renal cell cancer - hlrcc/multiple cutaneous and uterine leimomyomatosis - MCUL. Klin Onkol 2012; 25 Suppl(S55-58.
Reyes C, Karamurzin Y, Frizzell N, et al. Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: Detailed morphologic analysis and correlation with s-(2-succino)-cysteine immunohistochemistry. Mod Pathol 2014; 27(7): 1020-1027.
Gregova M, Hojny J, Nemejcova K, et al. Leiomyoma with bizarre nuclei: A study of 108 cases focusing on clinicopathological features, morphology, and fumarate hydratase alterations. Pathol Oncol Res 2019; 26(3): 1527-1537.
Ubago JM, Zhang Q, Kim JJ, Kong B, Wei JJ. Two subtypes of atypical leiomyoma: Clinical, histologic, and molecular analysis. Am J Surg Pathol 2016; 40(7): 923-933.
Van Lier MG, Wagner A, Mathus-Vliegen EM, et al. High cancer risk in Peutz-jeghers syndrome: A systematic review and surveillance recommendations. Am J Gastroenterol 2010; 105(6): 1258-1264; author reply 1265.
Hearle N, Lucassen A, Wang R, et al. Mapping of a translocation breakpoint in a Peutz-jeghers hamartoma to the putative PJS locus at 19q13.4 and mutation analysis of candidate genes in polyp and stk11-negative pjs cases. Genes Chromosomes Cancer 2004; 41(2): 163-169.
Chen HY, Jin XW, Li BR, et al. Cancer risk in patients with Peutz-jeghers syndrome: A retrospective cohort study of 336 cases. Tumour Biol 2017; 39(6): 1010428317705131.
Jones MA, Young RH, Scully RE. Diffuse laminar endocervical glandular hyperplasia. A benign lesion often confused with adenoma malignum (minimal deviation adenocarcinoma). Am J Surg Pathol 1991; 15(12): 1123-1129.
Stewart DR, Best AF, Williams GM, et al. Neoplasm risk among individuals with a pathogenic germline variant in DICER1. J Clin Oncol 2019; 37(8): 668-676.
Cowan M, Suntum T, Olivas AD, et al. Second primary rhabdomyosarcoma of the uterine cervix presenting with synchronous ovarian sertoli-leydig cell tumor: An illustrative case of DICER1 syndrome. Gynecol Oncol Rep 2018; 25: 94-97.
Kim J, Schultz KaP, Hill DA, Stewart DR. The prevalence of germline DICER1 pathogenic variation in cancer populations. Mol Genet Genomic Med 2019; 7(3): e555.
De Kock L, Terzic T, Mccluggage WG, et al. DICER1 mutations are consistently present in moderately and poorly differentiated sertoli-leydig cell tumors. Am J Surg Pathol 2017; 41(9): 1178-1187.
Melendez-Zajgla J, Mercado-Celis GE, Gaytan-Cervantes J, et al. Genomics of a pediatric ovarian fibrosarcoma. Association with the dicer1 syndrome. Sci Rep 2018; 8(1): 3252.
Hasbani DM, Crino PB. Tuberous sclerosis complex. Handb Clin Neurol 2018; 148(813-822.
Caban C, Khan N, Hasbani DM, Crino PB. Genetics of tuberous sclerosis complex: Implications for clinical practice. Appl Clin Genet 2017; 10: 1-8.
Hayashi T, Kumasaka T, Mitani K, et al. Prevalence of uterine and adnexal involvement in pulmonary lymphangioleiomyomatosis: A clinicopathologic study of 10 patients. Am J Surg Pathol 2011; 35(12): 1776-1785.
Conlon N, Soslow RA, Murali R. Perivascular epithelioid tumours (PECOMas) of the gynaecological tract. J Clin Pathol 2015; 68(6): 418-426.
Bennett JA, Braga AC, Pinto A, et al. Uterine pecomas: A morphologic, immunohistochemical, and molecular analysis of 32 tumors. Am J Surg Pathol 2018; 42(10): 1370-1383.
Evans DG, Farndon PA. Nevoid basal cell carcinoma syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K and Amemiya A, eds. Genereviews((r)) ed). Seattle (WA): 1993.
Kimonis VE, Goldstein AM, Pastakia B, et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 1997; 69(3): 299-308.
Van Leeuwaarde RS, Ahmad S, Links TP, Giles RH. Von hippel-lindau syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K and Amemiya A, eds. Genereviews((r)) ed). Seattle (WA): 1993.
Van Der Horst-Schrivers ANA, Sluiter WJ, Kruizinga RC, et al. The incidence of consecutive manifestations in von hippel-lindau disease. Fam Cancer 2019; 18(3): 369-376.
Cox R, Vang R, Epstein JI. Papillary cystadenoma of the epididymis and broad ligament: Morphologic and immunohistochemical overlap with clear cell papillary renal cell carcinoma. Am J Surg Pathol 2014; 38(5): 713-718.
Brady A, Nayar A, Cross P, et al. A detailed immunohistochemical analysis of 2 cases of papillary cystadenoma of the broad ligament: An extremely rare neoplasm characteristic of patients with von Hippel-Lindau disease. Int J Gynecol Pathol 2012; 31(2): 133-140.