Kutanöz Adneksiyal Tümörler
Özet
Kutanöz adneksiyal tümörler (KAT), normal derideki saç kökleri, yağ, apokrin ve ekrin bezler gibi adneksiyal bileşenlerin morfolojik farklılaşmasıyla ortaya çıkan, geniş bir benign ve malign neoplazm grubunu temsil eder. Genellikle dördüncü ve altıncı dekatlar arasında sporadik olarak gözlenen bu tümörler; Brooke-Spiegler, Birt-Hogg-Dubé ve Muir-Torre gibi nadir genetik sendromlarla da ilişkili olabilmektedir. Klinik görünümlerinin benzerliği ve girift yapıları sebebiyle yüzeyel biyopsiler hatalı sonuçlar verebildiğinden, kesin tanı için eksizyonel veya punch biyopsi yöntemi tercih edilmektedir. İyi huylu adneksiyal tümörlerde basit cerrahi eksizyon küratif ve yeterli olurken; oldukça nadir görülen, lokal agresif seyirli ve nüks oranı yüksek olan malign KAT'lerin tedavisinde negatif cerrahi sınırlarla geniş lokal eksizyon yapılması esastır. Metastatik veya ileri evre hastalıklarda ise radyoterapi ve kemoterapinin yanı sıra MAP kinaz ile PIK3CA/AKT1 gibi yolakları hedefleyen kişiselleştirilmiş hedefe yönelik tedaviler umut vadetmektedir.
Cutaneous adnexal tumors (CAT) constitute a broad category of benign and malignant neoplasms showing morphological differentiation toward normal skin adnexal structures, including hair follicles, sebaceous, apocrine, and eccrine glands. Mostly emerging sporadically between the fourth and sixth decades of life, these tumors can also manifest as components of rare genetic syndromes such as Brooke-Spiegler, Birt-Hogg-Dubé, and Muir-Torre. Due to significant clinical overlap among different subtypes, deep punch or excisional biopsies are essential over superficial ones to ensure accurate histopathological evaluation. While simple surgical excision provides an excellent prognosis for benign tumors, malignant CATs are extremely rare, locally aggressive, and carry a high recurrence risk. Wide local excision with negative margins is the primary treatment standard, whereas advanced or metastatic diseases require tailored therapeutic approaches, leveraging conventional chemotherapy, radiotherapy, or emerging targeted therapies that address specific molecular alterations like MAP kinase or PIK3CA/AKT1 pathways.
Referanslar
Alsaad, KO, Obaidat, NA, Ghazarian, D. Skin adnexal neoplasms-an approach to tumours of the pilosebaceous unit. Journal of clinical pathology, part 1, 2007;60(2), 129–144.
Rudolph P. Benigne Tumoren der Hautanhangsgebilde [Benign adnexal skin tumors]. Der Pathologe, 2002;23(1), 71–78.
Rodríguez-Díaz, E, Armijo, M. Mixed tumors with follicular differentiation: complex neoplasms of the primary epithelial germ. International journal of dermatology, 1995;34(11), 782–785.
Sato K, Kang WH, Saga K, et al. Biology of sweat glands and their disorders. I. Normal sweat gland function. J Am Acad Dermatol. 1989;20(4):537-63.
Winkelmann RK, Wolff K. Solid-cystic hidradenoma of the skin. Clinical and histopathologic study. Archives of dermatology, 1968;97(6), 651–661.
Martinez SR, Barr KL, Canter RJ. Rare tumors through the looking glass: an examination of malignant cutaneous adnexal tumors. Archives of dermatology, 2011;147(9), 1058–1062.
Williams K, Shinkai K. Evaluation and management of the patient with multiple syringomas: A systematic review of the literature. J Am Acad Dermatol. 2016;74(6):1234-1240.e9.
Polat M, Pelitli A, Oztaş P, et al. Eruptive syringoma associated with hyperthyroidism. Skinmed. 2010;8(2):124-5.
Wilkinson RD, Schopflocher P, Rozenfeld M. Hidrotic ectodermal dysplasia with diffuse eccrine poromatosis. Arch Dermatol. 1977;113(4):472-6.
Battistella M, Langbein L, Peltre B, et al. From hidroacanthoma simplex to poroid hidradenoma: clinicopathologic and immunohistochemic study of poroid neoplasms and reappraisal of their histogenesis. Am J Dermatopathol. 2010;32(5):459-68.
Fehr A, Kovács A, Löning T, et al. The MYB-NFIB gene fusion-a novel genetic link between adenoid cystic carcinoma and dermal cylindroma. J Pathol. 2011;224(3):322-7.
Kazakov DV, Kacerovska D, Hantschke M, et al. Cutaneous mixed tumor, eccrine variant: a clinicopathologic and immunohistochemical study of 50 cases, with emphasis on unusual histopathologic features. Am J Dermatopathol. 2011;33(6):557-68.
Panagopoulos I, Gorunova L, Lund-Iversen M, et al. Fusion of the Genes PHF1 and TFE3 in Malignant Chondroid Syringoma. Cancer Genomics Proteomics. 2019;16(5):345-351.
Guerin M, Droney T, Keohane C, et al. Eccrine syringofibroadenoma of the eyelid in association with eye prosthesis. Eye (Lond). 2011;25(8):1102-3.
Poonawalla T, Xia L, Patten S, et al. Clouston syndrome and eccrine syringofibroadenomas. Am J Dermatopathol. 2009;31(2):157-61.
Helwıg EB, Hackney VC. Syringadenoma papilliferum; lesions with and without naevus sebaceous and basal cell carcinoma. AMA Arch Derm. 1955;71(3):361-72.
Shen AS, Peterhof E, Kind P, et al. Activating mutations in the RAS/mitogen-activated protein kinase signaling pathway in sporadic trichoblastoma and syringocystadenoma papilliferum. Hum Pathol. 2015;46(2):272-6.
Baker GM, Selim MA, Hoang MP. Vulvar adnexal lesions: a 32-year, single-institution review from Massachusetts General Hospital. Arch Pathol Lab Med. 2013;137(9):1237-46.
Pfarr N, Sinn HP, Klauschen F, et al. Mutations in genes encoding PI3K-AKT and MAPK signaling define anogenital papillary hidradenoma. Genes Chromosomes Cancer. 2016;55(2):113-9.
Behboudi A, Winnes M, Gorunova L, et al. Clear cell hidradenoma of the skin-a third tumor type with a t(11;19)--associated TORC1-MAML2 gene fusion. Genes Chromosomes Cancer. 2005;43(2):202-5.
Kazakov DV, Spagnolo DV, Kacerovska D, et al. Cutaneous type adnexal tumors outside the skin. Am J Dermatopathol. 2011;33(3):303-15.
Liau JY, Tsai JH, Huang WC, et al. BRAF and KRAS mutations in tubular apocrine adenoma and papillary eccrine adenoma of the skin. Hum Pathol. 2018;73:59-65
Nazemi A, Higgins S, Swift R, et al. Eccrine Porocarcinoma: New Insights and a Systematic Review of the Literature. Dermatol Surg. 2018;44(10):1247-1261.
Harms PW, Hovelson DH, Cani AK, et al. Porocarcinomas harbor recurrent HRAS-activating mutations and tumor suppressor inactivating mutations. Hum Pathol. 2016;51:25-31.
Dores GM, Huycke MM, Devesa SS, et al. Primary cutaneous adenoid cystic carcinoma in the United States: incidence, survival, and associated cancers, 1976 to 2005. J Am Acad Dermatol. 2010;63(1):71-8.
Kamalpour L, Brindise RT, Nodzenski M, et al. Primary cutaneous mucinous carcinoma: a systematic review and meta-analysis of outcomes after surgery. JAMA Dermatol. 2014;150(4):380-4.
Zembowicz A, Garcia CF, Tannous ZS, et al. Endocrine mucin-producing sweat gland carcinoma: twelve new cases suggest that it is a precursor of some invasive mucinous carcinomas. Am J Surg Pathol. 2005;29(10):1330-9.
Mathew JG, Bowman AS, Saab J, et al. Next-generation sequencing analysis suggests varied multistep mutational pathogenesis for endocrine mucin-producing sweat gland carcinoma with comments on INSM1 and MUC2 suggesting a conjunctival origin. J Am Acad Dermatol. 2022;86(5):1072-1079.
Behbahani S, Yeh CJ, Pinto JO, et al. Microcystic adnexal carcinoma of the head and neck: Characteristics, treatment, and survival statistics. Dermatol Ther. 2021;34(1):e14559.
Chan MP, Plouffe KR, Liu Cj, et al. Next-generation sequencing implicates oncogenic roles for p53 and JAK/STAT signaling in microcystic adnexal carcinomas. Mod Pathol. 2020;33(6):1092-1103.
Duke WH, Sherrod TT, Lupton GP. Aggressive digital papillary adenocarcinoma (aggressive digital papillary adenoma and adenocarcinoma revisited). Am J Surg Pathol. 2000;24(6):775-84.
Bell D, Aung P, Prieto VG, et al. Next-generation sequencing reveals rare genomic alterations in aggressive digital papillary adenocarcinoma. Ann Diagn Pathol. 2015;19(6):381-4.
Suchak R, Wang WL, Prieto VG, et al. Cutaneous digital papillary adenocarcinoma: a clinicopathologic study of 31 cases of a rare neoplasm with new observations. Am J Surg Pathol. 2012;36(12):1883-91.
Konstantinova AM, Vanecek T, Martinek P, et al. Molecular alterations in lesions of anogenital mammary-like glands and their mammary counterparts including hidradenoma papilliferum, intraductal papilloma, fibroadenoma and phyllodes tumor. Ann Diagn Pathol. 2017;28:12-18
Barth P, Dulaimi Al-Saleem E, Edwards KW, et al. Metastatic Extramammary Paget's Disease of Scrotum Responds Completely to Single Agent Trastuzumab in a Hemodialysis Patient: Case Report, Molecular Profiling and Brief Review of the Literature. Case Rep Oncol Med. 2015;2015:895151.
Ha JH, Lee C, Lee KS, et al. The molecular pathogenesis of Trichilemmal carcinoma. BMC Cancer. 2020;3;20(1):516.
North JP, Golovato J, Vaske CJ, et al. Cell of origin and mutation pattern define three clinically distinct classes of sebaceous carcinoma. Nat Commun. 2018;14;9(1):1894.
Ota S, Sakamoto T, Ochiai R, et al. Successful Treatment with Taxane-Based Chemotherapy in Advanced Sebaceous Carcinoma: A Case Report and Literature Review. Case Rep Oncol. 2019 Jan 11;12(1):47-52
Avraham JB, Villines D, Maker VK, et al. Survival after resection of cutaneous adnexal carcinomas with eccrine differentiation: risk factors and trends in outcomes. J Surg Oncol. 2013;108(1):57-62.
Barnes M, Hestley A, Murray DR, et al. The risk of lymph node involvement in malignant cutaneous adnexal tumors. Am Surg. 2014;80(3):270-4.
De Iuliis F, Amoroso L, Taglieri L, et al. Chemotherapy of rare skin adnexal tumors: a review of literature. Anticancer Res. 2014;34(10):5263-8. PMID: 25275018.
Gutermuth J, Audring H, Voit C, et al. Antitumour activity of paclitaxel and interferon-alpha in a case of metastatic eccrine porocarcinoma. J Eur Acad Dermatol Venereol. 2004;18(4):477-9.
Mezger J, Remberger K, Schalhorn A, et al. Treatment of metastatic sweat gland carcinoma by a four drug combination chemotherapy: response in two cases. Med Oncol Tumor Pharmacother.1986;3(1):29-34.
