Proliferating Pilar Tumor
Updated: Jan 27, 2020
Author: Marjon Vatanchi, MD; Chief Editor: William D James, MD
Overview
Background
A proliferating pilar tumor (PPT) is a rare neoplasm arising from the isthmus region of the outer root sheath of the hair follicle. It is also commonly called a proliferating trichilemmal cyst or, less commonly, proliferating follicular-cystic neoplasm. It was first described by Wilson-Jones[1] as a proliferating epidermoid cyst in 1966. PPT was then distinguished from proliferating epidermoid cysts in 1995.[2] It occurs most commonly on the scalp in women older than 50 years.[3] Most tumors arise within a preexisting pilar cyst. Even though they usually are benign in nature, malignant transformation with local invasion and metastasis has been described.[4, 5, 6, 7, 8] A tentative stratification of PPTs into groups as benign, low-grade malignancy, and high-grade malignancy has been introduced. They may be inherited in an autosomal-dominant mode, linked to chromosome 3. See Pilar Cyst for more information.
Pathophysiology
A proliferating pilar tumor (PPT) usually arises in the setting of single or multiple pilar cysts. An asymptomatic nodule is often present for months to years before a rapid increase occurs in the size of the lesion. This is thought to signal neoplastic transformation of the cyst, with progression into a PPT. The underlying stimulus for this transformation is not known, but it has been hypothesized to be secondary to trauma, irritation, or chronic inflammation. In a review of 76 cases of PPTs seen in consultation from 1989-2000, Ye et al proposed a distinction between benign and malignant variants. The authors also proposed histologic criteria that could predict behavior.[9]
It is believed to be analogous to proliferating onycholemmal cyst, an entity that is even rarer in the literature as it pertains to the nail bed.[10]
Etiology
A spectrum of transformation is hypothesized, which begins with a benign pilar cyst, proceeding to a proliferating pilar tumor (PPT), and then to a malignant PPT. The stimulus for changes in these lesions is currently unknown, although trauma, inflammation, and irritation may play roles.
Epidemiology
Frequency
Proliferating pilar tumor (PPT) are rare.
Sex
These tumors occur more commonly in females than in males.
Age
PPTs are most common in older individuals aged 50-75 years, although they have been reported in individuals aged 20-30 years.
Prognosis
The prognosis is excellent with complete excision. Local recurrence and metastasis are extremely rare in benign cases. However, in proven malignant cases, metastasis has been suggested to occur in 30% of cases.
Patient Education
For patient education resources, visit the Skin Conditions and Beauty Center. Also, see the patient education article Skin Cancer.
Presentation
History
Patients usually report a slowly or rapidly enlarging nodule. Patients may give a history of recent trauma to the site. The nodule may have been present for months to years without symptoms.
Physical Examination
Lesions usually are single, firm-to-soft, painless nodules. However, there is a case report of multiple benign proliferating pilar tumors occurring in a single patient over a period of 20 years in several anatomic regions, including the gluteal region, groin, perineum, bilateral axillae, face, and neck.[11]
The size may range from 1-10 cm, although lesions as large as 25 cm have been reported.
Inflammation, ulceration, bleeding, and/or yellowish discharge may occur.
The most common (90%) location is the scalp. Other reported sites include back, chest, axilla, groin, gluteal region,[12] thigh, vulva,[13] , face, and eyelid.[14]
Complications
The lesions are usually painless. Exophytic growth with ulceration and foul-smelling discharge may occur. Some lesions may grow very large and cause pressure necrosis on underlying tissues, especially on the scalp. Local recurrence following excision and/or metastasis has been reported in rare instances in which malignancy has occurred. While proliferating pilar tumors (PPTs) may have varying levels of cellular atypia on histologic examination, there have been cases of squamous cell carcinomas diagnosed within PPTs, with one reported case of squamous cell carcinoma progressing to distant nodal metastasis and death.[15]
Case reports have described PPTs that displayed intracranial extension and cases of metastases to the pancreas or lungs.[16, 17] While rare, patients can also have multiple lesions or have secondary changes such as ulceration.[18]
DDx
Differential Diagnoses
Workup
Imaging Studies
Imaging studies are not usually indicated, but they may show a lobulated cystic mass, coarse calcification, or ringlike mineralization.
Because some subcutaneous tumors located in the midline of the body may have connections to the central nervous system (eg, scalp cavernous angioma, which may be part of the symptom complex known as sinus pericranii), imaging tumors in this location with CT or MRI prior to removal should be considered.
The best modality to determine bony invasion or erosion is CT scanning, and proliferating pilar tumors (PPTs) are frequently found as incidental subcutaneous nodules on brain CT scans.[19] They most frequently display isointensity on T1-weighted images and heterogeneous signal on T2-weighted images.[20] However, for deeper tissue invasion, MRI is best.
Additional imaging may be necessary on a case-by-case basis. A 62-year-old with a PTT on the shoulder had a positron emission tomography scan that displayed a high uptake of 18F-FDG (fluorodeoxyglucose).[21] In a different case, an endoscopic ultrasound with fine-needle aspiration was used to discover PPT metastasis to the pancreas in a 65-year-old man.[22]
Procedures
Performing an excisional biopsy is recommended. Send as much of the lesion as possible for pathologic evaluation. Ideally, the entire lesion should be excised and submitted at the time of the biopsy.
Histologic Findings
Proliferating pilar tumors (PPTs) are well circumscribed, with islands of squamous epithelium undergoing trichilemmal keratinization. Brightly eosinophilic keratinocytes are present in the outer portion of the tumor and cornify into compact cystic spaces filled with keratin. Horn pearls or squamous eddies may be present, as may foci of calcification and glycogen-rich clear cells.
The epithelial cells lining the cyst lack intercellular bridges. The peripheral layers palisade, while the deeper layer cells are swollen.
Anticytokeratin 5/6 may also stain strongly positive in this neoplasm. This is a monoclonal antibody that recognizes high molecular weight keratin intermediate filaments.
An increase in staining of nucleolar organizer regions, an indicator of proliferation, has also been proposed as an adjunct to differentiate benign and malignant proliferating trichilemmal tumors.[23]
Calretinin is a calcium-binding protein member of the EF-hand family and is reported to be focally positive. Calretinin may be helpful to identify the innermost cell layer of the outer root sheath in an anagen hair follicle, with the cutaneous adnexal proliferations showing differentiation toward this structure. Calretinin immunoreactivity supports eccrine differentiation in some sweat gland neoplasms, and it is also useful in identifying neoplasms with ductal sebaceous differentiation.[24]
Immunohistochemical staining with Ki-67, P53, and CD34 has been using to classify malignant PTT from PTT.[25]
A series of histological slides follows:
Proliferating trichilemmal cystic neoplasm. Well-circumscribed neoplasm with central cornified cells (2X). Courtesy of Steve A. McClain, MD.
Proliferating trichilemmal cystic neoplasm (20X). Courtesy of Steve A. McClain, MD.
Proliferating trichilemmal cystic neoplasm (400X). Note the pleomorphism of keratinocytes and mitotic figures. Courtesy of Steve A. McClain, MD.
Ye et al proposed a stratification of PPTs into the following three groups[9] :
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Group 1 - Circumscribed silhouettes with "pushing" margins; modest nuclear atypia; and an absence of pathologic mitoses, necrosis, and invasion of nerves or vessels
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Group 2 - Similar to group 1 but manifest as irregular, locally invasive silhouettes with involvement of the deep dermis and subcutis
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Group 3 - Invasive growth patterns, marked nuclear atypia, pathologic mitotic forms, and geographic necrosis, with or without involvement of nerves or vascular structures.
Group 1 may be regarded as benign, group 2 as having the potential for locally aggressive growth, and group 3 as also having metastatic potential. The latter 2 categories might be equated with low and high grades of malignancy among PPTs of the skin. Occasionally, PPTs have been misdiagnosed at squamous cell carcinomas.[26]
Therefore, determining the malignant potential of a proliferating pilar tumor may be challenging and additional parameters are often needed. For instance, malignant proliferating pilar tumors are more likely to stain positive with p53 and Ki-67 relative to benign proliferating pilar tumors and trichilemmal cysts, and CD34 immunoreactivity may distinguish a malignant proliferating pilar tumor from a squamous cell carcinoma.[26]
The cyst cavity contains amorphous eosinophilic keratin. The content is commonly calcified.
The cyst may also have dedifferentiated parts, further emphasizing the need for careful analysis.[27]
Treatment
Approach Considerations
Complete excision with a margin of normal tissue is recommended. No consensus has been reached regarding the margin size of normal tissue.
In a case study of malignant proliferating pilar tumor (PPT) with multinodal metastasis, wide local excision with 1-cm margins was performed, followed by adjuvant chemotherapy and radiation to prevent recurrence.[28]
Of note, in 2017 a case report described successful treatment of a malignant proliferating trichilemmal tumor with radical radiotherapy in a patient who was not a good candidate for surgery (aged 93 years, with multiple comorbidities).[29]
Long-Term Monitoring
Monitor the patient for local recurrence and periodically examine the lymph nodes to rule out metastasis. No recommendations exist for the interval or length of follow-up.
Screening for proliferating pilar tumor (PPT) is suggested in patients with keratitis-ichthyosis-deafness (KID) syndrome.[30]