Premalignant Fibroepithelial Tumor (Pinkus Tumor)

Premalignant Fibroepithelial Tumor (Pinkus Tumor)

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The fibroepithelioma of Pinkus is an unusual neoplasm that was first described by Hermann Pinkus in 1953 as a premalignant fibroepithelial tumor. [1] Clinically, the lesion is a benign-appearing, pedunculated, pink tumor that may resemble an acrochordon. However, Pinkus noted 4 such lesions to have a peculiar histologic appearance that resembled both a reticulated seborrheic keratosis and a basal cell carcinoma. Pinkus considered the tumor to be a variant of basal cell carcinoma, which illustrated the interaction and interdependence of stromal and epithelial components of basal cell carcinoma.

Current advances in molecular biology are allowing new insights into the pathogenesis of skin cancer. The TP53 gene codes for a protein product that is a strong negative regulator of normal human cell growth and is thought to act as a tumor suppressor. [2] Deletion or mutation of this gene results in decreased control of cellular proliferation and can contribute to the formation of an immortalized cell. It is now believed that this gene is intricately involved in the development of nonmelanoma skin cancer, including the fibroepithelioma of Pinkus. Further study of this pathway is currently underway.

Evidence implicates another genetic pathway that may be involved in the transformation of cells in skin cancer. Studies of both nevoid basal cell carcinoma syndrome and sporadic basal cell carcinomas have shown mutations in the PATCHED gene. [3] Mutation of this gene eliminates a crucial inhibitory signal for a cellular regulation pathway known as the Hedgehog pathway, which is named after a similar pathway found in Drosophila. Loss of this inhibition results in increased expression of the GLI family of transcription factors, promoting cell growth. Constitutive activation of this pathway in human keratinocytes has been shown to produce a neoplasm identical to basal cell carcinoma. Further study of this pathway is also underway and will likely have considerable relevance to the pathogenesis of basal cell carcinoma and the fibroepithelioma of Pinkus.

Although the fibroepithelioma of Pinkus has been accepted as a variant of basal cell carcinoma, the reason for its distinct histologic pattern remains a mystery. [4, 5, 6] Several authors have proposed that the initial change is the invasion of an eccrine duct by a basal cell carcinoma. [7] Eventual obliteration of the ductal lumen would then impart the characteristic histologic pattern. Other authors have considered this to be a possible variant of trichoblastoma. However, definite follicular origin has not been established. [8]

Basal cell carcinomas are most commonly associated with chronic ultraviolet light exposure, previous radiation damage, [9] or prior ingestion of arsenic. Whether any of these predisposing factors is a relevant cause of fibroepithelioma of Pinkus is unproven.

The true frequency of the fibroepithelioma of Pinkus is unknown. Its epidemiology is thought to mirror that of basal cell skin cancer. Unlike other histologic types of basal cell carcinoma, lesions are more common on the trunk and extremities than the face.

The fibroepithelioma of Pinkus, like other basal cell carcinomas, is more common in lighter skin types and relatively rare in dark skin types.

Available reports indicate that this tumor has an equal sexual distribution.

Available reports indicate that this tumor usually develops in persons aged 40-60 years, similar to other forms of basal cell carcinoma. However, a few cases have been reported in children. [10]

The fibroepithelioma of Pinkus generally runs an indolent course. It can, however, ulcerate and invade into underlying tissue. To date, none has resulted in death.

The treatments discussed in Surgical Care yield 5-year disease-free intervals in 80-90% of patients with basal cell skin cancer. With procedures, such as Mohs surgery, 5-year disease-free intervals can be expected in 98% of patients. Because the fibroepithelioma of Pinkus is a variant of basal cell skin cancer, expected disease-free intervals should closely match those of other forms of basal cell carcinoma.

Educate all patients with basal cell carcinoma in the proper use of sunscreens, the dangers of tanning, and the avoidance of sun during the peak hours of midday.

Pinkus H. Premalignant fibroepithelial tumors of skin. AMA Arch Derm Syphilol. 1953 Jun. 67(6):598-615. [Medline].

Matsumura Y, Nishigori C, Yagi T, Imamura S, Takebe H. Characterization of p53 gene mutations in basal-cell carcinomas: comparison between sun-exposed and less-exposed skin areas. Int J Cancer. 1996 Mar 15. 65(6):778-80. [Medline].

Aszterbaum M, Rothman A, Johnson RL, Fisher M, Xie J, Bonifas JM, et al. Identification of mutations in the human PATCHED gene in sporadic basal cell carcinomas and in patients with the basal cell nevus syndrome. J Invest Dermatol. 1998 Jun. 110(6):885-8. [Medline].

Sellheyer K, Nelson P, Kutzner H. Fibroepithelioma of Pinkus is a true basal cell carcinoma developing in association with a newly identified tumour-specific type of epidermal hyperplasia. Br J Dermatol. 2012 Jan. 166(1):88-97. [Medline].

Tarallo M, Cigna E, Fino P, Lo Torto F, Corrias F, Scuderi N. Fibroepithelioma of Pinkus: variant of basal cell carcinoma or trichoblastoma? Case report. G Chir. 2011 Jun-Jul. 32(6-7):326-8. [Medline].

Ioannidis O, Papaemmanuil S, Kakoutis E, Papadopoulos G, Chatzopoulos S, Kotronis A, et al. Fibroepithelioma of pinkus in continuity with nodular basal cell carcinoma: supporting evidence of the malignant nature of the disease. Pathol Oncol Res. 2011 Mar. 17(1):155-7. [Medline].

Stern JB, Haupt HM, Smith RR. Fibroepithelioma of Pinkus. Eccrine duct spread of basal cell carcinoma. Am J Dermatopathol. 1994 Dec. 16(6):585-7. [Medline].

Haddock ES, Cohen PR. Fibroepithelioma of Pinkus Revisited. Dermatol Ther (Heidelb). 2016 Sep. 6 (3):347-62. [Medline].

Hartschuh W, Schulz T. Merkel cell hyperplasia in chronic radiation-damaged skin: its possible relationship to fibroepithelioma of Pinkus. J Cutan Pathol. 1997 Sep. 24(8):477-83. [Medline].

Pan Z, Huynh N, Sarma DP. Fibroepithelioma of pinkus in a 9-year-old boy: a case report. Cases J. 2008. 1(1):21. [Medline].

Bryant J. Fibroepithelioma of Pinkus overlying breast cancer. Arch Dermatol. 1985 Mar. 121(3):310. [Medline].

Warner TF, Burgess H, Mohs FE. Extramammary Paget’s disease in fibroepithelioma of Pinkus. J Cutan Pathol. 1982 Oct. 9(5):340-4. [Medline].

Heymann WR, Soifer I, Burk PG. Penile premalignant fibroepithelioma of Pinkus. Cutis. 1983 May. 31(5):519-21. [Medline].

Zalaudek I, Leinweber B, Ferrara G, Soyer HP, Ruocco E, Argenziano G. Dermoscopy of fibroepithelioma of pinkus. J Am Acad Dermatol. 2005 Jan. 52(1):168-9. [Medline].

Kornreich DA, Lee JB. White network in fibroepithelioma of Pinkus. JAAD Case Rep. 2016 Sep. 2 (5):400-402. [Medline].

Naeyaert JM, Pauwels C, Geerts ML, Verplancke P. CD-34 and Ki-67 staining patterns of basaloid follicular hamartoma are different from those in fibroepithelioma of Pinkus and other variants of basal cell carcinoma. J Cutan Pathol. 2001 Nov. 28(10):538-41. [Medline].

Katona TM, Ravis SM, Perkins SM, Moores WB, Billings SD. Expression of androgen receptor by fibroepithelioma of Pinkus: evidence supporting classification as a basal cell carcinoma variant?. Am J Dermatopathol. 2007 Feb. 29(1):7-12. [Medline].

Fecher LA, Sharfman WH. Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors. Biologics. 2015. 9:129-40. [Medline].

Mehregan AH. Proliferation of sweat ducts in certain diseases of the skin. Am J Dermatopathol. 1981. 3(1):27-31. [Medline].

Darius Mehregan, MD Associate Professor, Hermann Pinkus Chairman of Dermatology, Department of Dermatology, Wayne State University School of Medicine; Clinical Associate Professor of Pathology, University of Toledo College of Medicine; Dermatopathologist, Pinkus Dermatopathology Laboratory; Consulting Staff, Department of Dermatology, J Dingell Veterans Affairs Medical Center

Darius Mehregan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society of Dermatopathology, International Society of Dermatology, International Society of Dermatopathology, Phi Beta Kappa, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Rahil M Dharia Wayne State University School of Medicine

Rahil M Dharia is a member of the following medical societies: American Association of Physicians of Indian Origin, American Medical Association, American Medical Student Association/Foundation, Association of Students for Hinduism Awareness, Michigan Association of Physicians of Indian Heritage

Disclosure: Nothing to disclose.

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Rosalie Elenitsas, MD Herman Beerman Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System

Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society of Dermatopathology, Pennsylvania Academy of Dermatology

Disclosure: Received royalty from Lippincott Williams Wilkins for textbook editor.

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Maureen B Poh-Fitzpatrick, MD Professor Emerita of Dermatology and Special Lecturer, Columbia University College of Physicians and Surgeons

Maureen B Poh-Fitzpatrick, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, New York Dermatological Society

Disclosure: Nothing to disclose.

Jennifer Michelle Heyl, MD Resident Physician, Department of Dermatology, Wayne State University School of Medicine

Disclosure: Nothing to disclose.

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, David Pegouske MD, to the development and writing of this article.

Premalignant Fibroepithelial Tumor (Pinkus Tumor)

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