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Weichteiltumoren bei hereditären Tumorsyndromen

Soft tissue tumors in hereditary tumor syndromes

  • Schwerpunkt: Hereditäre Tumorerkrankungen
  • Published:
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Zusammenfassung

Benigne und maligne Weichteiltumoren treten in der Regel de novo auf, ohne identifizierbare Risikofaktoren oder prädisponierende Konditionen. Jedoch wurden in den letzten Jahrzehnten zunehmend genetische Hintergründe bei diversen Weichteiltumoren identifiziert. Dies ist den modernen Untersuchungsmethoden wie Next Generation Sequencing (NGS) und ganzgenomischen Verfahren zu verdanken. Diverse hereditär bedingte Weichteiltumoren zeigen häufig klinisch-pathologische Besonderheiten, welche deren Identifizierung im diagnostischen Alltag ermöglichen. Da es nicht selten der Fall ist, dass der Pathologe den ersten Hinweis auf eine potenziell zugrunde liegende erbliche Erkrankung feststellen und weitergeben kann, kommt einer umfassenden Kenntnis der klinisch-pathologischen Eigenschaften und Besonderheiten der syndromassoziierten Weichteiltumoren eine besondere Bedeutung zu. Im Folgenden werden die wichtigsten Syndrome mit assoziierten Weichteiltumoren erläutert und deren diagnostische Besonderheiten besprochen.

Abstract

Benign and malignant soft tissue tumors usually develop de novo without identifiable risk factors or predisposing conditions. However, in recent decades, soft tissue tumors have been increasingly recognized to be associated with diverse hereditary tumor syndromes as a consequence of germline mutations involving mainly tumor suppressor genes, but rarely also affecting proto-oncogenes. This is mainly the consequence of increasing application of modern genetic analysis tools, such as next-generation sequencing (NGS) and whole genome analyses. Syndrome-associated soft tissue tumors frequently show distinctive clinicopathological features and peculiarities that facilitate and potentially enhance their recognition and identification during routine surgical pathology practice. As it is not uncommon that pathologists are the first medical specialists to recognize a potential hereditary etiology of neoplastic diseases on the basis of specific pathological features, it is mandatory that pathologists be familiar with the main features that characterize those soft tissue tumors with inherited etiology, at least the most common and important of them. This review summarizes the main syndromes and their associated soft tissue tumors and discusses their characteristic pathological features that help in the recognition of hereditary syndromes.

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Literatur

  1. Hartmann A (2017) Pathologie familiärer Tumorsyndrome. Pathologe. doi:10.1007/s00292-017-0299-4

  2. Bisgaard ML, Bülow S (2006) Familial adenomatous polyposis (FAP): genotype correlation to FAP phenotype with osteomas and sebaceous cysts. Am J Med Genet A 140:200–204

    Article  PubMed  Google Scholar 

  3. Enomoto M, Konishi M, Iwama T, Utsunomiya J, Sugihara KI, Miyaki M (2000) The relationship between frequencies of extracolonic manifestations and the position of APC germline mutation in patients with familial adenomatous polyposis. Jpn J Clin Oncol 30:82–88

    Article  CAS  PubMed  Google Scholar 

  4. Fisher C, Thway K (2014) Aggressive fibromatosis. Pathology 46:135–140

    Article  CAS  PubMed  Google Scholar 

  5. Coffin CM, Hornick JL, Zhou H, Fletcher CD (2007) Gardner fibroma: a clinicopathologic and immunohistochemical analysis of 45 patients with 57 fibromas. Am J Surg Pathol 31:410–416

    Article  PubMed  Google Scholar 

  6. Ferner RE (2007) Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective. Lancet Neurol 6:340–351

    Article  PubMed  Google Scholar 

  7. Gottfried ON, Viskochil DH, Couldwell WT (2010) Neurofibromatosis Type 1 and tumorigenesis: molecular mechanisms and therapeutic implications. Neurosurg Focus 28:E8

    Article  PubMed  Google Scholar 

  8. Thway K, Fisher C (2014) Malignant peripheral nerve sheath tumor: pathology and genetics. Ann Diagn Pathol 18(2):109–116

    Article  PubMed  Google Scholar 

  9. Schaefer IM, Fletcher CD (2015) Malignant peripheral nerve sheath tumor (MPNST) arising in diffuse-type neurofibroma: clinicopathologic characterization in a series of 9 cases. Am J Surg Pathol 39:1234–1241

    Article  PubMed  Google Scholar 

  10. Miettinen M, Fetsch JF, Sobin LH et al (2006) Gastrointestinal stromal tumors in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases. Am J Surg Pathol 30:90–96

    Article  PubMed  Google Scholar 

  11. Agaimy A, Vassos N, Croner RS (2012) Gastrointestinal manifestations of neurofibromatosis type 1 (Recklinghausen’s disease): clinicopathological spectrum with pathogenetic considerations. Int J Clin Exp Pathol 5(9):852–862

    PubMed  PubMed Central  Google Scholar 

  12. Schaefer IM, Ströbel P, Thiha A, Sohns JM, Mühlfeld C, Küffer S, Felmerer G, Stepniewski A, Pauli S, Agaimy A (2013) Soft tissue perineurioma and other unusual tumors in a patient with neurofibromatosis type 1. Int J Clin Exp Pathol 6(12):3003–3008

    PubMed  PubMed Central  Google Scholar 

  13. Agaimy A, Schaefer IM, Kotzina L, Knolle J, Baumann I, Ströbel P, Vieth M (2014) Juvenile-like (inflammatory/hyperplastic) mucosal polyps of the gastrointestinal tract in neurofibromatosis type 1. Histopathology 64:777–786

    Article  PubMed  Google Scholar 

  14. Varley JM, McGown G, Thorncroft M, Santibanez-Koref MF, Kelsey AM, Tricker KJ, Evans DG, Birch JM (1997) Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. Cancer Res 57:3245–3252

    CAS  PubMed  Google Scholar 

  15. Ruijs MW, Broeks A, Menko FH, Ausems MG, Wagner A, Oldenburg R, Meijers-Heijboer H, van’t Veer LJ, Verhoef S (2009) The contribution of CHEK2 to the TP53-negative Li-Fraumeni phenotype. Hered Cancer Clin Pract 7(1):4

    Article  PubMed  PubMed Central  Google Scholar 

  16. Blanquet V, Turleau C, Gross-Morand MS, Sénamaud-Beaufort C, Doz F, Besmond C (1995) Spectrum of germline mutations in the RB1 gene: a study of 232 patients with hereditary and non hereditary retinoblastoma. Hum Mol Genet 4:383–388

    Article  CAS  PubMed  Google Scholar 

  17. Fletcher O, Easton D, Anderson K, Gilham C, Jay M, Peto J (2004) Lifetime risks of common cancers among retinoblastoma survivors. J Natl Cancer Inst 96:357–363

    Article  PubMed  Google Scholar 

  18. Pinto CI, Carvalho PJ, Correia MM (2017) Madelung’s disease: revision of 59 surgical cases. Aesthetic Plast Surg 41:359–368

    Article  PubMed  Google Scholar 

  19. Fanburg-Smith JC, Devaney KO, Miettinen M, Weiss SW (1998) Multiple spindle cell lipomas: a report of 7 familial and 11 nonfamilial cases. Am J Surg Pathol 22:40–48

    Article  CAS  PubMed  Google Scholar 

  20. Li FP, Abramson DH, Tarone RE, Kleinerman RA, Fraumeni JF Jr, Boice JD Jr (1997) Hereditary retinoblastoma, lipoma, and second primary cancers. J Natl Cancer Inst 89:83–84

    Article  CAS  PubMed  Google Scholar 

  21. Genuardi M, Klutz M, Devriendt K, Caruso D, Stirpe M, Lohmann DR (2001) Multiple lipomas linked to an RB1 gene mutation in a large pedigree with low penetrance retinoblastoma. Eur J Hum Genet 9:690–694

    Article  CAS  PubMed  Google Scholar 

  22. Evans HL (2016) Anisometric cell Lipoma: a predominantly subcutaneous fatty tumor with notable variation in fat cell size but not more than slight nuclear enlargement and atypia. AJSP Rev Rep 21:195–199

    Google Scholar 

  23. Agaimy A (2017) Anisometric cell lipoma: Insight from a case series and review of the literature on adipocytic neoplasms in survivors of retinoblastoma suggest a role for RB1 loss and possible relationship to fat-predominant (“fat-only”) spindle cell lipoma. Ann Diagn Pathol. (in Press)

  24. Lagos JC, Gomez MR (1967) Tuberous sclerosis: reappraisal of a clinical entity. Mayo Clin Proc 42:26–49

    CAS  PubMed  Google Scholar 

  25. von Ranke FM, Zanetti G, e Silva JL, Araujo Neto CA, Godoy MC, Souza CA, Mançano AD, Souza AS Jr, Escuissato DL, Hochhegger B, Marchiori E (2015) Tuberous sclerosis complex: state-of-the-art review with a focus on pulmonary involvement. Lung 193:619–627

    Article  Google Scholar 

  26. Agaimy A, Hartmann A (2010) Hereditäre und nicht-hereditäre syndromale gastointestinale Stromatumore. Pathologe 31:430–437

    Article  CAS  PubMed  Google Scholar 

  27. Agaimy A, Märkl B, Arnholdt H, Wünsch PH, Terracciano LM, Dirnhofer S, Hartmann A, Tornillo L, Bihl MP (2009) Multiple sporadic gastrointestinal stromal tumours arising at different gastrointestinal sites: pattern of involvement of the muscularis propria as a clue to independent primary GISTs. Virchows Arch 455:101–108

    Article  CAS  PubMed  Google Scholar 

  28. Agaimy A, Märkl B, Arnholdt H, Hartmann A, Schneider-Stock R, Chetty R (2010) Sporadic segmental interstitial cell of cajal hyperplasia (microscopic GIST) with unusual diffuse longitudinal growth replacing the muscularis propria: differential diagnosis to hereditary GIST syndromes. Int J Clin Exp Pathol 3(5):549–556

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Stratakis CA, Carney JA (2009) The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney-Stratakis syndrome): molecular genetics and clinical implications. J Intern Med 266:43–52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Haller F, Moskalev EA, Faucz FR, Barthelmeß S, Wiemann S, Bieg M, Assie G, Bertherat J, Schaefer IM, Otto C, Rattenberry E, Maher ER, Ströbel P, Werner M, Carney JA, Hartmann A, Stratakis CA, Agaimy A (2014) Aberrant DNA hypermethylation of SDHC: a novel mechanism of tumor development in Carney triad. Endocr Relat Cancer 21:567–577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Salpea P, Stratakis CA (2014) Carney complex and McCune Albright syndrome: an overview of clinical manifestations and human molecular genetics. Mol Cell Endocrinol 386:85–91

    Article  CAS  PubMed  Google Scholar 

  32. Fu S, Tian Z, Zhang C, He Y (2015) Monosotic fibrous dysplasia and solitary intramuscular myxoma of the head and neck: a unique presentation of Mazabraud’s syndrome and a literature review. Oncol Lett 10:3087–3094

    PubMed  PubMed Central  Google Scholar 

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  1. Institut für Pathologie, Universitätsklinikum Erlangen, Krankenhausstraße 12, 91054, Erlangen, Deutschland

    A. Agaimy

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A. Hartmann, Erlangen

S. Lax, Graz

A. Agaimy, Erlangen

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Agaimy, A. Weichteiltumoren bei hereditären Tumorsyndromen. Pathologe 38, 170–178 (2017). https://doi.org/10.1007/s00292-017-0296-7

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