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Immunohistology and Molecular Studies of Follicular Tumors

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Applied Immunohistochemistry in the Evaluation of Skin Neoplasms

Abstract

Follicular neoplasms are epithelial tumors with differentiation toward the hair follicle. These tumors include hamartomas, benign and malignant neoplasms, and hyperplasias. Making the specific diagnosis is of importance clinically as some of the lesions are cutaneous signs of underlying hereditary tumor syndromes (Birt–Hogg–Dube syndrome, Cowden’s disease). In this chapter, we focus on the utility of immunohistochemistry sorting out the challenging differential diagnosis often encountered in dermatopathology.

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References

  1. Abbas O, Mahalingam M. Tumor of the follicular infundibulum: an epidermal reaction pattern? Am J Dermatopathol. 2009;31:626–33.

    Article  PubMed  Google Scholar 

  2. Ackerman AB, Viragh PA, Chongchitnant N. Neoplasms with follicular differentiation. Philadelphia. Lea Febiger. 1993;553.

    Google Scholar 

  3. Mehregan AH, Butler JD. A tumor of follicular infundibulum. report of a case. Arch Dermatol. 1961;83:924–7.

    Article  CAS  PubMed  Google Scholar 

  4. Alomari A, Subtil A, Owen CE, McNiff JM. Solitary and multiple tumors of follicular infundibulum: a review of 168 cases with emphasis on staining patterns and clinical variants. J Cutan Pathol. 2013;40:532–7.

    Article  PubMed  Google Scholar 

  5. Kubba A, Batrani M, Taneja A, Jain V. Tumor of follicular infundibulum: an unsuspected cause of macular hypopigmentation. Indian J Dermatol Venereol Leprol. 2014;80(2):141–4.

    Article  PubMed  Google Scholar 

  6. Cribier B, Grosshans E. Tumor of the follicular infundibulum: a clinicopathologic study. J Am Acad Dermatol. 1995;33:979–84.

    Article  CAS  PubMed  Google Scholar 

  7. Schnitzler L, Civatte J, Robin F, Demay C. Multiple tumors of the follicular infundibulum with basocellular degeneration. Apropos of a case. Ann Dermatol Venereol. 1987;114:551–6.

    CAS  PubMed  Google Scholar 

  8. Kolivras A, Moulonguet I, Ruben BS, Sass U, Cappelletti L, André J. Eruptive tumors of the follicular infundibulum presenting as hypopigmented macules on the buttocks of two Black African males. J Cutan Pathol. 2012;39:444–8.

    Article  PubMed  Google Scholar 

  9. Kushner JA, Thomas RS, Young RJ. An unusual location of a pilar sheath acanthoma. Int J Trichol. 2014;6(4):185–6.

    Article  Google Scholar 

  10. Mehregan AH, Brownstein MH. Pilar sheath acanthoma. Arch Dermatol. 1978;114(10):1495–7.

    Article  CAS  PubMed  Google Scholar 

  11. Misago N, Kimura T, Toda S, Mori T, Narisawa Y. A revaluation of trichofolliculoma: the histopathological and immunohistochemical features. Am J Dermatopathol. 2010;32(1):35–43.

    Article  PubMed  Google Scholar 

  12. Gokalp H, Gurer MA, Alan S. Trichofolliculoma: a rare variant of hair follicle hamartoma. Dermatol Online J. 2013;19(8):19264.

    PubMed  Google Scholar 

  13. Abdou AG, Asaad NY. Sebaceous trichofolliculoma of the cheek in a 65-year-old man. Pol J Pathol. 2014;65(3):253–4.

    Article  PubMed  Google Scholar 

  14. Merklen-Djafri C, Batard ML, Guillaume JC, Kleinclauss I, Cribier B. Folliculosebaceous cystic hamartoma: anatomo-clinical study. Ann Dermatol Venereol. 2012;139(1):23–30.

    Article  CAS  PubMed  Google Scholar 

  15. Hartschuh W, Schulz T. Immunohistochemical investigation of the different developmental stages of trichofolliculoma with special reference to the Merkel cell. Am J Dermatopathol. 1999;21(1):8–15.

    Article  CAS  PubMed  Google Scholar 

  16. Sengul D, Sengul I, Astarci MH, Ustun H, Mocan G. CD10 for the distinct differential diagnosis of basal cell carcinoma and benign tumours of cutaneous appendages originating from hair follicle. Pol J Pathol. 2010;61(3):140–6.

    PubMed  Google Scholar 

  17. Gumaste P, Ortiz AE, Patel A, Baron J, Harris R, Barr R. Generalized basaloid follicular hamartoma syndrome: a case report and review of the literature. Am J Dermatopathol. 2015;37(3):e37–40.

    Article  PubMed  Google Scholar 

  18. Huang SH, Hsiao TF, Lee CC. Basaloid follicular hamartoma: a case report and review of the literature. Kaohsiung J Med Sci. 2012;28(1):57–60.

    Article  PubMed  Google Scholar 

  19. Mills O, Thomas LB. Basaloid follicular hamartoma. Arch Pathol Lab Med. 2010;134(8):1215–9.

    PubMed  Google Scholar 

  20. Patel AB, Harting MS, Smith-Zagone MJ, Hsu S. Familial basaloid follicular hamartoma: a report of one family. Dermatol Online J. 2008;14(4):14.

    Google Scholar 

  21. Brownstein MH. Basaloid follicular hamartoma: solitary and multiple types. J Am Acad Dermatol. 1992;27(2 Pt 1):237–40.

    Article  CAS  PubMed  Google Scholar 

  22. Morton S, Stevens A, Powell RJ. Basaloid follicular hamartoma, total body hair loss and SLE. Lupus. 1998;7(3):207–9.

    Article  CAS  PubMed  Google Scholar 

  23. Ramos-Ceballos FI, Pashaei S, Kincannon JM, Morgan MB, Smoller BR. Bcl-2, CD34 and CD10 expression in basaloid follicular hamartoma, vellus hair hamartoma and neurofollicular hamartoma demonstrate full follicular differentiation. J Cutan Pathol. 2008;35(5):477–83.

    Article  PubMed  Google Scholar 

  24. Honarpisheh H, Glusac EJ, Ko CJ. Cytokeratin 20 expression in basaloid follicular hamartoma and infundibulocystic basal cell carcinoma. J Cutan Pathol. 2014;41(12):916–21.

    Article  PubMed  Google Scholar 

  25. Bayer-Garner IB, Givens V, Smoller B. Immunohistochemical staining for androgen receptors:a sensitive marker of sebaceous differentiation. Am J Dermatopathol. 1999;21:426–31.

    Article  CAS  PubMed  Google Scholar 

  26. Izikson L, Bhan A, Zembowicz A. Androgen receptor expression helps to differentiate basal cell carcinoma from benign trichoblastic tumors. Am J Dermatopathol. 2005;27:91–5.

    Article  PubMed  Google Scholar 

  27. Katona TM, Ravis SM, Perkins SM, et al. Expression of androgen receptor by fibroepithelioma of Pinkus: evidence supporting classification as a basal cell carcinoma variant? Am J Dermatopathol. 2007;29:7–12.

    Article  PubMed  Google Scholar 

  28. Arits AH, Van Marion AM, Lohman BG, Thissen MR, Steijlen PM, Nelemans PJ, Kelleners-Smeets NW. Differentiation between basal cell carcinoma and trichoepithelioma by immunohistochemical staining of the androgen receptor: an overview. Eur J Dermatol. 2011;21(6):870–3.

    PubMed  Google Scholar 

  29. Poniecka AW, Alexis JB. An immunohistochemical study of basal cell carcinoma and trichoepithelioma. Am J Dermatopathol. 1999;21:332–6.

    Article  CAS  PubMed  Google Scholar 

  30. Abdelsayed RA, Guijarro-Rojas M, Ibrahim NA, et al. Immunohistochemical evaluation of basal cell carcinoma and trichoepithelioma using Bcl-2, Ki67, PCNA and P53. J Cutan Pathol. 2000;27:169–75.

    Article  CAS  PubMed  Google Scholar 

  31. Abesamis-Cubillan E, El-Shabrawi-Caelen L, LeBoit PE. Merkel cells and sclerosing epithelial neoplasms. Am J Dermatopathol. 2000;22:311–5.

    Article  CAS  PubMed  Google Scholar 

  32. Heidarpour M, Rajabi P, Sajadi F. CD10 expression helps to differentiate basal cell carcinoma from trichoepithelioma. J Res Med Sci. 2011;16(7):938–44.

    PubMed  PubMed Central  Google Scholar 

  33. Pham TT, Selim MA, Burchette Jr JL, Madden J, Turner J, Herman C. CD10 expression in trichoepithelioma and basal cell carcinoma. J Cutan Pathol. 2006;33:123–8.

    Article  PubMed  Google Scholar 

  34. Tebcherani AJ, de Andrade Jr HF, Sotto MN. Diagnostic utility of immunohistochemistry in distinguishing trichoepithelioma and basal cell carcinoma: evaluation using tissue microarray samples. Mod Pathol. 2012;25(10):1345–53.

    Article  CAS  PubMed  Google Scholar 

  35. Illueca C, Monteagudo C, Revert A, et al. Diagnostic value of CD34 immunostaining in desmoplastic trichilemmoma. J Cutan Pathol. 1998;25:435–9.

    Article  CAS  PubMed  Google Scholar 

  36. Kirchmann TT, Prieto VG, Smoller BR. CD34 staining pattern distinguishes basal cell carcinoma from trichoepithelioma. Arch Dermatol. 1994;130:589–92.

    Article  CAS  PubMed  Google Scholar 

  37. Basarab T, Orchard G, Russell-Jones R. The use of immunostaining for Bcl-2 and CD34 and the lectin peanut agglutinin in differentiating between basal cell carcinomas and trichoepitheliomas. Am J Dermatopathol. 1998;20:448–52.

    Article  CAS  PubMed  Google Scholar 

  38. Smoller BR, Van de Rijn M, Lebrun D, et al. Bcl-2 expression reliably distinguishes trichoepitheliomas from basal cell carcinomas. Br J Dermatol. 1994;131:28–31.

    Article  CAS  PubMed  Google Scholar 

  39. Choi CW, Park HS, Kim YK, Lee SH, Cho KH. Elastic fiber staining and cytokeratin 15 expression pattern in trichoepithelioma and basal cell carcinoma. J Dermatol. 2008;35(8):499–502.

    Article  PubMed  Google Scholar 

  40. Sellheyer K, Krahl D. PHLDA1 (TDAG51) is a follicular stem cell marker and differentiates between morphoeic basal cell carcinoma and desmoplastic trichoepithelioma. Br J Dermatol. 2011;164(1):141–7.

    Article  CAS  PubMed  Google Scholar 

  41. Battistella M, Carlson JA, Osio A, Langbein L, Cribier B. Skin tumors with matrical differentiation: lessons from hair keratins, beta-catenin and PHLDA-1 expression. J Cutan Pathol. 2014;41(5):427–36.

    Article  PubMed  Google Scholar 

  42. Sellheyer K, Nelson P. Follicular stem cell marker PHLDA1 (TDAG51) is superior to cytokeratin-20 in differentiating between trichoepithelioma and basal cell carcinoma in small biopsy specimens. J Cutan Pathol. 2011;38(7):542–50.

    Article  PubMed  Google Scholar 

  43. Sellheyer K, Nelson P, Kutzner H, Patel RM. The immunohistochemical differential diagnosis of microcystic adnexal carcinoma, desmoplastic trichoepithelioma and morpheaform basal cell carcinoma using BerEP4 and stem cell markers. J Cutan Pathol. 2013;40(4):363–70.

    Article  PubMed  Google Scholar 

  44. Tse JY, Nguyen AT, Le LP, Hoang MP. Microcystic adnexal carcinoma versus desmoplastic trichoepithelioma: a comparative study. Am J Dermatopathol. 2013;35(1):50–5.

    Article  PubMed  Google Scholar 

  45. Krahl D, Sellheyer K. Monoclonal antibody Ber-EP4 reliably discriminates between microcystic adnexal carcinoma and basal cell carcinoma. J Cutan Pathol. 2007;34:782–7.

    Article  PubMed  Google Scholar 

  46. Hoang MP, Dresser KA, Kapur P, et al. Microcystic adnexal carcinoma: an immunohistochemical reappraisal. Mod Pathol. 2008;21:178–85.

    CAS  PubMed  Google Scholar 

  47. Yeh I, McCalmont TH, LeBoit PE. Differential expression of PHLDA1 (TDAG51) in basal cell carcinoma and trichoepithelioma. Br J Dermatol. 2012;167(5):1106–10.

    Article  CAS  PubMed  Google Scholar 

  48. Costache M, Bresch M, Böer A. Desmoplastic trichoepithelioma versus morphoeic basal cell carcinoma: a critical reappraisal of histomorphological and immunohistochemical criteria for differentiation. Histopathology. 2008;52(7):865–76.

    Article  CAS  PubMed  Google Scholar 

  49. Katona TM, Perkins SM, Billings SD. Does the panel of cytokeratin 20 and androgen receptor antibodies differentiate desmoplastic trichoepithelioma from morpheaform/infiltrative basal cell carcinoma? J Cutan Pathol. 2008;35(2):174–9.

    PubMed  Google Scholar 

  50. Misago N, Satoh T, Miura Y, Nagase K, Narisawa Y. Merkel cell-poor trichoblastoma with basal cell carcinoma-like foci. Am J Dermatopathol. 2007;29(3):249–55.

    Article  PubMed  Google Scholar 

  51. Kurzen H, Esposito L, Langbein L, Hartschuh W. Cytokeratins as markers of follicular differentiation: an immunohistochemical study of trichoblastoma and basal cell carcinoma. Am J Dermatopathol. 2001;23(6):501–9.

    Article  CAS  PubMed  Google Scholar 

  52. Córdoba A, Guerrero D, Larrinaga B, Iglesias ME, Arrechea MA, Yanguas JI. Bcl-2 and CD10 expression in the differential diagnosis of trichoblastoma, basal cell carcinoma, and basal cell carcinoma with follicular differentiation. Int J Dermatol. 2009;48(7):713–7.

    Article  PubMed  Google Scholar 

  53. Vega Memije ME, Luna EM, de Almeida OP, Taylor AM, Cuevas González JC. Immunohistochemistry panel for differential diagnosis of Basal cell carcinoma and trichoblastoma. Int J Trichol. 2014;6(2):40–53.

    Article  Google Scholar 

  54. Battistella M, Peltre B, Cribier B. PHLDA1, a follicular stem cell marker, differentiates clear-cell/granular-cell trichoblastoma and clear-cell/granular cell basal cell carcinoma: a case-control study, with first description of granular-cell trichoblastoma. Am J Dermatopathol. 2014;36(8):643–50.

    Article  PubMed  Google Scholar 

  55. Kurokawa I, Mizutani H, Nishijima S, Kato N, Yasui K, Tsubura A. Trichoadenoma: cytokeratin expression suggesting differentiation towards the follicular infundibulum and follicular bulge regions. Br J Dermatol. 2005;153(5):1084–6.

    Article  CAS  PubMed  Google Scholar 

  56. Shimanovich I, Krahl D, Rose C. Trichoadenoma of Nikolowski is a distinct neoplasm within the spectrum of follicular tumors. J Am Acad Dermatol. 2010;62(2):277–83.

    Article  PubMed  Google Scholar 

  57. Blumenthal GM, Dennis PA. PTEN hamartoma tumor syndromes. Eur J Hum Genet. 2008;16:1289–300.

    Article  CAS  PubMed  Google Scholar 

  58. Brownstein MH, Mehregan AH, Bikowski JP. Trichilemmomas in Cowden’s disease. JAMA. 1977;238:267.

    Google Scholar 

  59. Brownstein MH, Mehregan AH, Bikowski JBB, Lupulescu A, Patterson JC. The dermatopathology of Cowden’s syndrome. Br J Dermatol. 1979;100:667–73.

    Article  CAS  PubMed  Google Scholar 

  60. Tsai JH, Huang WC, Jhuang JY, Jeng YM, Cheng ML, Chiu HY, Kuo KT, Liau JY. Frequent activating HRAS mutations in trichilemmoma. Am J Dermatopathol. 2013;35(6):637–40.

    Article  Google Scholar 

  61. Kanoh M, Amoh Y, Sato Y, Katsuoka K. Expression of the hair stem cell-specific marker nestin in epidermal and follicular tumors. Eur J Dermatol. 2008;18(5):518–23.

    CAS  PubMed  Google Scholar 

  62. Alsaad KO, Obaidat NA, Ghazarian D. Skin adnexal neoplasms—part 1: An approach to tumours of the pilosebaceous unit. J Clin Pathol. 2007;60:129–44.

    Article  CAS  PubMed  Google Scholar 

  63. Jin M, Hampel H, Pilarski R, Zhou X, Peters S, Frankel WL. Phosphatase and tensin homolog immunohistochemical staining and clinical criteria for Cowden syndrome in patients with trichilemmoma or associated lesions. Am J Dermatopathol. 2013;35(6):637–40.

    Article  PubMed  Google Scholar 

  64. Al-Zaid T, Ditelberg JS, Prieto VG, Lev D, Luthra R, Davies MA, Diwan AH, Wang WL, Lazar AJ. Trichilemmomas show loss of PTEN in Cowden syndrome but only rarely in sporadic tumors. J Cutan Pathol. 2012;39(5):493–9.

    Article  PubMed  Google Scholar 

  65. Hunt SJ, Kilzer B, Santa Cruz DJ. Desmoplastic trichilemmoma: histologic variant resembling invasive carcinoma. J Cutan Pathol. 1990;17(1):45–52.

    Article  CAS  PubMed  Google Scholar 

  66. Illueca C, Monteagudo C, Revert A, Llombart-Bosch A. Diagnostic value of CD34 immunostaining in desmoplastic trichilemmoma. J Cutan Pathol. 1998;25(8):435–9.

    Article  CAS  PubMed  Google Scholar 

  67. Kurokawa I, Senba Y, Nishimura K, Habe K, Hakamada A, Isoda K, Yamanaka K, Mizutani H, Tsubura A. Cytokeratin expression in trichilemmal carcinoma suggests differentiation towards follicular infundibulum. In Vivo. 2006;20(5):583–5.

    CAS  PubMed  Google Scholar 

  68. Wong TY, Suster S. Tricholemmal carcinoma: a clinicopathologic study of 13 cases. Am J Dermatopathol. 1994;16:463–73.

    Article  CAS  PubMed  Google Scholar 

  69. Poblet E, Jiménez F. CD34 in human hair follicle. J Invest Dermatol. 2003;121:1220–1.

    Article  CAS  PubMed  Google Scholar 

  70. Sajin M, Luchian MC, Hodorogea Prisăcaru A, Dumitru A, Pătraşcu OM, Costache D, Dumitrescu D, Oproiu AM, Simionescu O, Costache M. Trichilemmal carcinoma - a rare cutaneous malignancy: report of two cases. Rom J Morphol Embryol. 2014;55(2 Suppl):687–91.

    PubMed  Google Scholar 

  71. Chaichamnan K, Satayasoontorn K, Puttanupaab S, Attainsee A. Malignant proliferating trichilemmal tumors with CD34 expression. J Med Assoc Thai. 2010;93 Suppl 6:S28–34.

    PubMed  Google Scholar 

  72. Fernández-Figueras MT, Casalots A, Puig L, Llatjós R, Ferrándiz C, Ariza A. Proliferating trichilemmal tumor: p53 immunoreactivity in association with p27 Kip1 over-expression indicates a low-grade carcinoma profile. Histopathology. 2001;38:454–7.

    Article  PubMed  Google Scholar 

  73. Rangel-Gamboa L, Reyes-Castro M, Dominguez-Cherit J, Vega-Memije E. Proliferating trichilemmal cyst: the value of ki67 immunostaining. Int J Trichol. 2013;5(3):115–7.

    Article  Google Scholar 

  74. Alici O, Keles MK, Kurt A. A rare cutaneous adnexal tumor: malignant proliferating trichilemmal tumor. Case Rep Med. 2015;2015:742920.

    PubMed  PubMed Central  Google Scholar 

  75. Malhotra KP, Shukla S, Singhal A, Husain N. Proliferating trichilemmal cyst with nodal enlargement mimicking metastatic squamous cell carcinoma. Indian J Dermatol Venereol Leprol. 2015;81:418–20.

    Article  PubMed  Google Scholar 

  76. González-Guerra E, Requena L, Kutzner H. Immunohistochemical study of calretinin in normal hair follicles and tumors with follicular differentiation. Actas Dermosifiliogr. 2008;99(6):456–63.

    Article  PubMed  Google Scholar 

  77. Hassanein AM, Glanz SM. Beta-catenin expression in benign and malignant pilomatrix neoplasms. Br J Dermatol. 2004;150(3):511–6.

    Article  CAS  PubMed  Google Scholar 

  78. Czerniawska E, Pogrzebielski A, Romanowska-Dixon B. Malherbe’s calcifying epithelioma (pilomatrixoma). Klin Oczna. 2011;113(7-9):274–6.

    PubMed  Google Scholar 

  79. Nishioka M, Tanemura A, Yamanaka T, Tani M, Miura H, Asakura M, Tamai N, Katayama I. Pilomatrix carcinoma arising from pilomatricoma after 10-year senescent period: Immunohistochemical analysis. J Dermatol. 2010;37(8):735–9.

    Article  PubMed  Google Scholar 

  80. Haskell HD, Haynes HA, McKee PH, Redston M, Granter SR, Lazar AJ. Basal cell carcinoma with matrical differentiation: a case study with analysis of beta-catenin. J Cutan Pathol. 2005;32(3):245–50.

    Article  PubMed  Google Scholar 

  81. Sorin T, Eluecque H, Gauchotte G, De Runz A, Chassagne JF, Mansuy L, Gisquet H, Simon E. Pilomatrix Carcinoma of the scalp. A case report and review of the literature. Ann Chir Plast Esthet. 2015;60(3):242–6.

    Article  CAS  PubMed  Google Scholar 

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Sokumbi, O., Plaza, J.A. (2016). Immunohistology and Molecular Studies of Follicular Tumors. In: Plaza, J., Prieto, V. (eds) Applied Immunohistochemistry in the Evaluation of Skin Neoplasms. Springer, Cham. https://doi.org/10.1007/978-3-319-30590-5_3

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