Continuing Education Activity

In 1953, Dr. Herman Pinkus first described the fibroepithelial tumor of Pinkus (FEP) as a pre-malignant epithelial tumor. Although there has been some dispute over the classification of FEP, its histologic appearance is unique and distinguishes it from other fibroepithelial tumors. Several important distinctions can be made between FEP and basal cell carcinoma (BCC.) Most notable is the presence of Merkel cells in FEP and the absence of those cells in BCC. FEP also occurs more frequently in females and has no association with sun exposure. It typically occurs on the lower trunk; whereas, BCC is more common in sun-exposed areas of the body. From a prognostic standpoint, FEP does not have an aggressive course and has not been reported to invade or metastasize. Basal cell carcinoma, on the other hand, can invade and metastasize if left untreated. This activity reviews the evaluation of premalignant fibroepithelial tumors and identifies the role of the interprofessional team in managing this condition.

Objectives:

• Review the etiology of fibroepithelial tumor of Pinkus.
• Describe the presentation of fibroepithelial tumor of Pinkus.
• Summarize the treatment of fibroepithelial tumor of Pinkus.
• Outline the evaluation of premalignant fibroepithelial tumors and identifies the role of the interprofessional team in managing this condition.

Introduction

In 1953, Dr. Herman Pinkus first described the fibroepithelial tumor of Pinkus (FEP) as a pre-malignant epithelial tumor. Although there has been some dispute over the classification of FEP, its histologic appearance is unique and distinguishes it from other fibroepithelial tumors. Several important distinctions can be made between FEP and basal cell carcinoma (BCC.) Most notable is the presence of Merkel cells in FEP and the absence of those cells in BCC. FEP also occurs more frequently in females and has no association with sun exposure. It typically occurs on the lower trunk; whereas, BCC is more common in sun-exposed areas of the body. [1] From a prognostic standpoint, FEP does not have an aggressive course and has not been reported to invade or metastasize. [2] Basal cell carcinoma, on the other hand, can invade and metastasize if left untreated. 

Etiology

The origin of FEP is enigmatic. Some have suggested that it develops in seborrheic keratosis. [3] Others have suggested that it represents the eccrine spread of basal cell carcinoma. This theory is based upon the histopathologic observation of small CEA-positive gland-like structures in the fine anastomosing network of cells that surround the basaloid nubbins of FEP as well as the observed resemblance of the fine anastomosing strands to some reactive eccrine sweat gland changes. [4] [5] This concept has been refuted by other authors who reject the idea of basal cell carcinoma spreading along eccrine ducts, noting that eccrine ducts grow vertically and rarely anastomose with each other, making lateral spread challenging. [6] Other work suggests that that the microscopically-fine anastomosing strands of FEP are PHLDA1 positive and represent a “tumor-specific type of epidermal hyperplasia” within which the basaloid nubbins are nestled, giving FEP its characteristic fenestrated appearance. The fine anastomosing strands also exhibit a high content of Merkel cells. The basaloid nubbins, which are both low in Merkel cells and PHLDA1 negative, are postulated to potentially give rise to nodular BCC, which is not uncommonly seen adjacent to or in continuity with FEP. In addition, the basaloid nubbins stain positive for nestin, which is a marker that is positive in the stroma of BCC. [7]

Epidemiology

It is considered a rare tumor, though some authors suggest that FEP may not be as rare as it seems, and its rarity may be a product of misdiagnosis. [8] FEP typically presents in males between age 40 and 60 but can be found at any age. It has been reported in children. [2]

Pathophysiology

FEP is not related to sun exposure. Development of FEP may be related to activation of the Hedgehog pathway by mutation of PTCH (patched transmembrane molecule), which decreases the negative regulation of the Hedgehog pathway. This is known to occur in some basal cell carcinomas and may also play a role in the development of FEP. Ionizing radiation has also been implicated. [1]

Histopathology

FEP exhibits a “fenestrated pattern” consisting of islands of the tumor, often referred to as nests, holes or nubbins surrounded by thin anastomosing strands of basaloid or squamous cells. [9] FEP occurs in the dermis, proliferating, and pushing the epidermis upward, forming the clinical appearance of a papillary or polypoid growth. In its isolated form, that is, without an accompanying nodular basal cell carcinoma, FEP does not invade the subcutis. [1]

History and Physical

FEP typically presents as a single or multiple papillary or polypoid growths on the skin. The tumor may be pink, tan, brown, or skin-colored. It can be sub-divided into pigmented and non-pigmented types based upon gross coloration. There may also be some superficial excoriation or erosion, but typically not deep ulceration. [8] FEP usually occurs on the trunk and is not associated with ultraviolet (UV) light exposure. [1]

Evaluation

Some authors advocate for dermoscopy and reflectance confocal microscopy (RCM) to aid in the diagnosis of these lesions. On dermoscopy, one can see finely branching short vessels as well as punctate vessels around the periphery. If a polarized light source is used, short, white streaks called crystalline, or chrysalis structures can be seen. In pigmented lesions, dermoscopy can reveal gray-brown areas and/or gray-blue dots, which suggests FEP. [8] In a case series evaluating dermoscopy, one author reported an accurate diagnosis of FEP in nine out of ten patients. [10] Reflectance confocal microscopy of FEP can reveal the classic “fenestrated pattern” at the dermo-epidermal junction showing “holes” of fibrous stroma surrounded by fine cords of palisading cells. This correlates well to the histologic appearance of these tumors. [9] A histopathologic analysis makes diagnosis following excision. [1]

Treatment / Management

Treatment involves recognition of the lesion followed by complete excision. Because of its potentially benign gross appearance, a fibroepithelial tumor of Pinkus may be an under-recognized and under-reported condition. Electrodesiccation and curettage of the lesion may be effective, but since this is a rare and likely under-recognized tumor, evidence for the efficacy of these treatments is not available. Mohs surgery has been performed for this type of tumor and is indicated if the anatomic location on the body limits clear margins. There is no role for chemotherapy or radiation. FEP has not been reported to result in patient death. [1]

Differential Diagnosis

The differential diagnosis of a skin lesion which is FEP can include many other pathologies, both benign and malignant. When FEP is mistaken for a benign lesion, such as acrochordon, seborrheic keratosis, dermal nevus, pedunculated fibroma, lipomatous nevus or neurofibroma, this delays biopsy. Since many benign skin lesions are treated without submitting tissue for biopsy, the diagnosis of FEP may never be made. [1]

Prognosis

It generally runs an indolent course. Prognosis is generally excellent and excision is considered curative. [1]

Complications

The controversy about whether FEP is a subtype of basal cell carcinoma or a trichoblastoma is ongoing, though the most recent literature supports FEP as a subtype of basal cell carcinoma. The presence of Merkel cells and weak expression of the p53 oncogene in both FEP and trichoblastoma leads to the association of the two entities and separates them from BCC. [1] On the other hand, androgen receptor presence in FEP is similar to BCC, unlike trichoepitheliomas and trichoblastomas, which do not express androgen receptors, suggesting that FEP is a variant of BCC. [11] More recent work using the stem cell marker PHLDA1 offers an embryologic explanation for the presence of Merkel cells in FEP and provides this as evidence that FEP is truly a subtype of basal cell carcinoma. [7] Whether or not one considers FEP a subtype of BCC or a trichoblastoma has a direct bearing on whether or not one considers FEP malignant or benign, which is also controversial. Its clinical behavior suggests benignity unless FEP happens to be found in association with a nodular basal cell carcinoma, which has been reported. [2]

Deterrence and Patient Education

Although the development of fibroepithelioma of Pinkus is not related to sun exposure, it is vital to properly educate all patients with basal cell carcinoma about the proper use of sunscreens, the avoidance of excessive sun exposure and the dangers of tanning.

Enhancing Healthcare Team Outcomes

Identification and treatment of fibroepithelial tumors of Pinkus are best done by an interprofessional team consisting of primary care, dermatology, pathologist, and specialty trained nurses. Dermatology nurses provide patient education, arrange follow up, and supply updates to the team. Evidence related to diagnosis and management of fibroepithelial tumors of Pinkus is limited to class 3, 4, and 5 evidence, due to the rarity of the condition.