Case 3-1 -

Proliferating Follicular-cystic Neoplasm (Proliferating Pilar Tumor) Philip E. LeBoit, M.D. Depts. of Pathology and Dermatology University of California, San Francisco

Clinical history: A 47 year old woman had a nodule on the side of her head. Case 3-1 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Diagnosis: Proliferating follicular-cystic neoplasm (proliferating pilar tumor). Histopathologic features of this case: Large lobulated dermal or dermal and subcutaneous proliferation Smooth outer border Compressed rim of fibrous tissue at periphery Interconnecting columns of squamous keratinocytes, surrounding… Many small central cystic areas of compact hyperkeratosis with focal calcification Protrusions of columns of squamous keratinocytes into cystic areas Confluence of solid aggregations Small cells in basal layer Progressively larger keratinocytes toward the interface with cornified cells Abrupt cornification with pale cells that bulge into cornified material Variable features that you can see in other examples: Marked cytologic atypia Many mitototic figures, including atypical mitotic figures Areas in which cystic architecture is lost, with sheets of large keratinocytes with atypical nuclei First called to wide attention among pathologists as "proliferating trichilemmal cyst" in a paper by Brownstein and Arluk in 1981, the exact nosology of this unusual lesion is debatable. It had long been recognized that there were a variety of lesions on the scalp that had features that overlapped with those of hair follicles- giant hair matrix tumor, proliferating epidermoid cyst, subepidermal cystic acanthoma and trichochlamydoacanthoma are just a few of the terms that pathologists used for entity a half century ago. The recognition of this entity lagged as it took some time for pilar or trichilemmal cysts to be recognized as distinct lesions that had wall resembling that of the upper part of the outer root sheath (near the isthmus), or the follicle in catagen. The outer root sheath, or trichilemma has a lower portion with small cuboidal cells that comprise its peripheral layer and larger clear cells toward its center. As the outer root sheath ascends toward the isthmus of the follicle, its cells acquire pinker cytoplasm and cornify abruptly, without the interposition of a granular layer. Large, pale eosinophilic keratinocytes abut compact cornified material. This type of wall, and type of cornification is characteristic of proliferating pilar tumors. The condition occurs mainly on the scalp, most often in middle aged or older patients, usually as a solitary mass. More women than men are affected. Most lesions are several cm. in diameter, but giant lesions of upto 25 cm. can occur. Until recently, the entity has been regarded as benign, and cases in which there were keratinocytes that had crowded, large atypical nuclei had been thought of as pseudomalignancies. A few reports detail metastatic spread from lesions initially regarded as proliferating pilar cysts or tumors, often with areas recognizable as conventional or as spindled cell squamous cell carcinoma. Ackerman and colleagues proposed that this condition is a form of squamous cell carcinoma, rather than capable of de-differentiating into one. He terms it "proliferating tricholemmal cystic squamous cell carcinoma". They hold that there is a rare, benign analogue that should be called "proliferating tricholemmal cystic acanthoma". It features a rounder, less complex border, a simpler lining (without marked protrusion of keratinocytes into the cornified center) and an absence of crowding of nuclei and increased mitoses. The case that I submitted for your viewing has some features of a pilar (trichilemmal, isthmus-catagen) cyst, just as "proliferating tricholemmal cystic acanthoma" does. It also has areas in which there are crowded aggregates that form a nearly solid mass, just as in "proliferating tricholemmal cystic squamous cell carcinoma." I believe that these two entities represent a spectrum, rather than being dichotomous. Ye and co-workers recently proposed three classes of lesions (benign, low-grade malignant, and high-grade malignant) based on histopathologic findings, and found that this assessment correlated with outcome, with no recurrences in the first group, local recurrences in 15% of the second group, and local recurrence or metastasis in 50% of the third group (although only 2/8 patients in this group had metastases). The differential diagnosis includes: Pilar (trichilemmal or isthmus-catagen) cyst Verrucous squamous cell carcinoma (if incompletely biopsied) Keratoacanthoma (if incompletely biopsied) Cystic, but otherwise conventional squamous cell carcinoma References: Ye J, Nappi O, Swanson PE, Patterson JW, Wick MR. Proliferating pilar tumors: a clinicopathologic study of 76 cases with a proposal for definition of benign and malignant variants. Am J Clin Pathol. 2004 Oct;122(4):566-74. Folpe AL, Reisenauer AK, Mentzel T, Rutten A, Solomon AR. Proliferating trichilemmal tumors: clinicopathologic evaluation is a guide to biologic behavior. J Cutan Pathol. 2003 Sep;30(8):492-8. Mathis ED, Honningford JB, Rodriguez HE, Wind KP, Connolly MM, Podbielski FJ. Malignant proliferating trichilemmal tumor. Am J Clin Oncol. 2001 Aug;24(4):351-3. Rutty GN, Richman PI, Laing JH. Malignant change in trichilemmal cysts: a study of cell proliferation and DNA content. Histopathology. 1992 Nov;21(5):465-8. Mehregan AH, Lee KC. Malignant proliferating trichilemmal tumors--report of three cases. J Dermatol Surg Oncol. 1987 Dec;13(12):1339-42. Ackerman AB, Reddy VB, Soyer HP. Proliferating tricholemmal cystic squamous cell carcinoma. In Neoplasms with follicular differentiation. Ardor Scribendi, New York, 2001, p. 1037-1076