Background
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.
Pathophysiology
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]
Etiology
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.
Epidemiology
Frequency
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.
Race
The fibroepithelioma of Pinkus, like other basal cell carcinomas, is more common in lighter skin types and relatively rare in dark skin types.
Sex
Available reports indicate that this tumor has an equal sexual distribution.
Age
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]
Prognosis
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.
Patient Education
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.
History
The tumor can present alone or in association with seborrheic keratoses and/or other basal cell carcinomas.
Its frequency is higher in areas of prior radiation-damaged epidermis.[9]
Reports have described two women who had an associated malignancy. One was found to have intraductal breast carcinoma underlying the fibroepithelioma of Pinkus,[11] and the other was found to have a perianal fibroepithelioma harboring Paget cells.[12]
Physical Examination
The fibroepithelioma of Pinkus usually presents as a slowly enlarging, fleshy, raised or pedunculated papilloma or sessile fibroma with a broad base, most commonly on the trunk or the extremities.
The color is usually pink or reddish, but, in some instances, a tinge of brown may be present.
It may be single or multiple and shows a strong predilection for the lumbosacral area. However, numerous cases have occurred elsewhere, including the head, the abdomen, the anus, the penis,[13] the breasts, and the scrotum.
This tumor can clinically resemble seborrheic keratosis, pedunculated fibroma, nevus sebaceus of Jadassohn, papillomatous melanocytic nevus, amelanotic melanoma, and neurofibroma.
Dermoscopy shows fine arborizing vessels alone or associated with dotted vessels and white streaks. Gray-brown areas of pigmentation and variable gray-blue dots may be observed.[14] A white reticulated network has also been described, but this may also be seen in nevi, dermatofibroma, and melanoma.[15]
Complications
Fibroepithelioma of Pinkus can be classified as malignant with a low metastatic potential.
Procedures
The diagnosis can be easily confirmed by performing a skin biopsy.
Histologic Findings
The classic fibroepithelioma of Pinkus typically shows long, thin, branching and anastomosing strands of basal cell carcinoma embedded in a loose fibrovascular stroma. Many strands show a connection with the epidermis. The basaloid strands show 2 distinct-appearing cells. A lighter staining cell comprises the bulk of the strand. Scattered, small groups of darker cells are seen tapering off the main trunk in a palisading arrangement like buds on a branch.
Nuclear pleomorphism may be present, and staining with proliferation markers such as Ki-67 shows an increased proliferative index.[16] Coexpression of androgen receptor, diffuse expression of Bcl-2, and the scattered presence of Merkel cells as marked by cytokeratin 20 may aid in the diagnosis of fibroepithelioma of Pinkus.[17] The tumor is superficial and well demarcated at its lower border. It bears strong histologic resemblance to reticulated seborrheic keratosis but lacks a typical horn and pseudohorn pearls. Hyperkeratosis is rarely present.
See the image below.
View Image | Basal cell fibroepithelioma (Pinkus tumor). Courtesy of L Wozniak & KW Zielinski (own work), via Wikimedia Commons. |
Medical Care
Treatment is primarily surgical. In rare instances, intralesional or topical chemotherapy may be useful.
Vismodegib, a selective Hedgehog pathway inhibitor that binds to and inhibits smoothened (SMO), is the first US Food and Drug Administration (FDA)–approved treatment for patients with locally advanced, unresectable, or metastatic basal cell carcinomas.[18]
Surgical Care
Options for treatment are similar to those for other forms of basal cell carcinoma, and the clinician's choice will likely be case dependent. Recommended treatment options include complete surgical excision or electrodesiccation followed by curettage. Cryosurgery, Mohs micrographic surgery, or radiation therapy may also be used.
Prevention
Encourage all patients to use sunscreens with a sun protective factor of at least 15. Avoidance of sun exposure during the peak intensity hours of the day, from 10 am to 3 pm, is also recommended.
Long-Term Monitoring
The development of one nonmelanoma skin cancer predisposes the patient to a higher risk for developing a second cancer. Therefore, close follow-up care is recommended to monitor for the development of similar tumors at the site of treatment and at alternate locations. Current recommendations suggest yearly skin examinations by a dermatologist.
Author
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
Disclosure: Nothing to disclose.
Coauthor(s)
Rahil M Dharia, Wayne State University School of Medicine
Disclosure: Nothing to disclose.
Specialty Editors
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
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
Disclosure: Received royalty from Lippincott Williams Wilkins for textbook editor.
Chief Editor
Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
Jennifer Michelle Heyl, MD, Resident Physician, Department of Dermatology, Wayne State University School of Medicine
Disclosure: Nothing to disclose.
Maureen B Poh-Fitzpatrick, MD, Professor Emerita of Dermatology and Special Lecturer, Columbia University College of Physicians and Surgeons
Disclosure: Nothing to disclose.
Acknowledgements
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.
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