Trichofolliculoma of the Guinea Pig 1,2 Raymond D. Ediger, Garrett S. Dill, Jr., and Robert M. Kovatch, Aerobiology and Evaluation Laboratories and Medical Sciences Laboratories, Fort Detrick, Frederick, Maryland 21701 SUMMARY-Trichofolliculoma, a spontaneously occurring skin tumor, was found in 21 Hartley strain guinea pigs. Except for 2, these benign neoplasms were located in the hypodermis and were collected during 7,670 necropsy examinations performed on guinea pigs over a 41!2-year period. They were characterized by: formation of either medullary or cortical hair components (or both), well-differentiated follicular structures, the presence of sebaceous glands, 1 large cyst accompanied by smaller cysts, and loose connective tissue stroma.-j Nat Cancer Inst 46: 517-523,1971. ONLY 5 spontaneous skin tumors have been reported in the guinea pig. One was described and called an epithelioma adenoides cysticum by Haranghy et al. (1). One sebaceous adenoma each has been reported by Murray (2) and Mosinger (3), and two sebaceous adenomas have been reported by Lombard (4). This report concerns a series of 21 cutaneous tumors classified as trichofolliculoma, which were found during 7,670 necropsy examinations performed on guinea pigs in the Fort Detrick colony from January 1965 to July 1969. These necropsies included a large number of discarded breeders and surplus animals, all animals that died spontaneously, and all animals with grossly visible lesions. This guinea pig colony was derived from a group of Dunkin-Hartley strain breeders imported from England in 1952. No other stock has been added since that time, and the colony has been randombred. HISTORY AND GROSS FINDINGS AT NECROPSY The data compiled on these 21 neoplasms revealed that all the tumors clinically appeared as solitary nodules elevating the skin. The largest lesion was 4.5 cm in diameter and the smallest, 1 X 1 X 0.5 cm. Seventeen of these skin tumors were in the dorsal lumbar region; three were in the lateral femoral area, and the other was at the cranial aspect of the shoulder. The tumors were observed in animals 6 weeks to 32 months of age (mean age, 17.6 months). Nine of the tumors were found in male and twelve in female animals. 1 Received August 10, 1970; accepted November 6, 1970. 2 In conducting the research reported herein, we adhered to the Guide for Laboratory Animal Facilities and Care established by a special committee appointed by the Institute of Laboratory Animal Resources, National Academy of Sciences, National Research Council. 412-946-71-9 517
518 EDIGER, DILL, AND KOVATCH On cut section, the tumors were found to be nonencapsulated and consisted of a central cyst surrounded by smaller cysts divided by an apparent stromal network (fig. 1). These cysts were filled with a caseous, white-to-yellow material, sometimes containing hair. All but 2 were located entirely in the hypodermis. These 2 neoplasms penetrated the epidermis; one was a papillary projection and the other had a central pore connecting the cyst to the skin surface. HISTOPATHOLOGY The tumors were usually multiloculated, cystic, and epithelial (fig. 2). The walls of the cysts were composed of stratified squamous epithelium, abortive hair follicles, and sebaceous glands scattered throughout a stroma of loose connective tissue. The smaller cysts were generally filled with keratinous debris, and some had birefringent hair shafts. Several tumors were more cellular and contained fewer smaller cysts. The hair follicle and keratin production varied morphologically. One type of hair follicle, morphologically similar to a normal follicle although arranged haphazardly, produced birefringent hair shafts (fig. 3). Another type was made up of stratified squamous epithelium, in crescentic, semicircular, and circular shapes (figs. 4 and 5). The stratum granulosum of this epithelium had prominent trichohyalin granules (fig. 6) and formed keratin, which was contained in a small cyst or streamed away in ribbons into larger cysts. The tumors with follicles producing birefringent hair structures (5 of the 21) also contained many follicles of the other type. The sebaceous glands generally were scattered haphazardly throughout the stroma, but occasionally they were in the usual histological position when associated with normally structured follicles (fig. 7). In all cases, the sebaceous glands appeared mature and frequently seemed to be contributing to the cyst content. Two neoplasms, in addition to the components described, contained masses and cords of compactly arranged basal cells with small compact nuclei and scant cytoplasm. These cells did not appear to be related to the follicular structures. In all tumors, mitotic figures were infrequent, and no nuclear abnormalities were seen. None of the neoplasms appeared locally invasive, and an inflammatory reaction was not a morphologic feature. DISCUSSION The trichofolliculoma in man was described by Gray and Helwig (5) as a harmartoma showing a definite differentiation toward hair structures. Histologically, the epithelial proliferation of these guinea pig tumors showed all stages of pilar formation. Leblond (6) discussed soft keratin, which makes up the medulla and inner root sheath, and hard keratin, which composes the cortex and cuticle of hair. Normal guinea pig hair has both a cortex and medulla. The brightly birefringent hair structures seen in some of the follicles in these tumors had only a cortex. The soft keratin, formed from the epithelium with trichohyalin granules, was the medullary portion or inner root sheath of the hair. In this tumor, both of the principal hair components were being formed separately, but complete hair was not being formed. When it is present, the birefringent cortex makes differentiation from the trichoepithelioma obvious. We believe the soft keratin component, when recognized as such, is equally distinctive. There are, however, minor differences between the tumor in the guinea pig and the tumor described in man. In the latter, an umbilicated area opening to the surface is often present, but a pore connecting the cyst to the surface was seen in only one of our tumors. The tumor in man occasionally extends from the corium into the hypodermis (5); however, in the guinea pig all but two of the tumors were confined to the hypodermis. In addition, the human tumor is encapsulated, but the trichofolliculoma in guinea pigs was not. Although sebaceous glands were described by Gray and Helwig (5) in 16% of 32 human cases, they were found in all trichofolliculomas of the guinea pig. JOURNAL OF THE NATIONAL CANCER INSTITUTE
TRICHOFOLLICULOMA OF THE GUINEA PIG 519 Gray and Helwig (5) adequately described the differential diagnosis of trichofolliculoma from multiple or solitary trichoepithelioma, basal cell carcinoma, and the dilated pore of Winer. In the tumors reported here, the maturity of the abortive hair follicle, the central cyst, the consistent preduction of hair components, and the general absence of islands of basal cells classify this group as trichofolliculomas. Other authors reported that spontaneous tumgrs rarely occur in guinea pigs that do not survive to senility (7); however, these supposedly rare tumors occurred in Hartley strain guinea pigs as early as six weeks of age. This suggests that either these tumors are more common in this colony or have been encountered elsewhere but not reported. REFERENCES (1) HARANGHY L, GYERGYAY F, ANTALFFY A, et al: Meerschweinchentumoren. Acta Morphol 4:301-307, 1954 (2) MURRAY JA: A transplantable sarcoma of the guinea pig. J Path Bact 20:260-268,1916 (3) MOSINGER M: On the carcinoresistance of the guinea pig. I. Spontaneous guinea-pig tumors. Bull Assoc Franc Cancer 48 :217-235, 1961 (4) LOMBARD C: La cancero-resistance du cobaye. Bull Assoc Franc Cancer 47:167-171,1960 (5) GRAY HR, HELWIG EB: Trichofolliculoma. Arch Derm (Cbicago) 86 :619-625, 1962 (6) LEBLOND CP: Histological structure of hair, with a brief comparison to other epithelial appendages and epidermis itself. Ann NY Acad Sci 53 :464-475, 1951 (7) ROGER JB, BLUMENTHAL HT: Studies of guinea pig tumors. I. Report of fourteen spontaneous guinea pig tumors, with a review of the literature. Cancer Res 20:191-197, 1960 VOL. 46, NO.3, MARCH 1971
FIGURE I.-Two small cut sections (left.) and one larger section (right) represent neoplasms from 2 animals and show the central cyst surrounded by smaller cysts. FIGURE 2.-Neoplasm in the hypodermis, showing the multiloculated, cystic, and epithelial features. Hematoxylin and eosin. X 13 520 EDIGER, DILL, AND KOVATCH
FIGURE 3.-Abortive hair follicles producing the cortical component of hair. Hematoxylin and eosin. X 40 FIGURE 4.-Abortive hair follicles producing the soft keratin component of hair. Hematoxylin and eosin. X 40 EDIGER, DILL, AND KOVATCH 521
FIGURE 5.-Abortive hair follicles producing the soft keratin component of hair. Hematoxylin and eosin. X 125 FIGURE 5.-Numerous trichohyalin granules which stain brightly eosinophilic in soft keratin structures. Hematoxylin and eosin. X 1000 522 EDIGER, DILL, AND KOVATCH
FIGURE 7.-Sebaceous glands scattered haphazardly throughout the stroma. Hematoxylin and eosin. X 125 EDIGER, DILL, AND KOVATCH 523