Malignant epithelial neoplasia with hair follicle differentiation in dogs

J. COMP. PATH. 1976.Vo~.86.

121

MALIGNANT EPITHELIAL NEOPLASIA FOLLICLE DIFFERENTIATION MALIGNANT

IN

WITH DOGS

HAIR

PILOMATRIXOMA BY

D. M. Department

SELLS

andJ.

D. CONROY

of Veterinary Pathology and Hygiene, College of Veterinary University of Illinois, Urbana, Illinois 61801, U.S.A.

Medicine,

INTRODUCTIOK

Pilomatrixoma (calcifying epithelioma) and trichoepithelioma (epithelioma adenoides cysticum) have been classified by Lever (1967) as benign epidermal appendage tumours with hair follicle differentiation. Basosquamous tumours have been reported in man (Montgomery, 1928; Borel, 1973) and animals, mainly in cats and dogs (Cotchin, 1961; Jubb and Kennedy, 1970; Weiss and Frese, 1974). However, the clinical features of animal basosquamous tumours have not been adequately characterized. The purpose of this paper is to describe epithelial neoplasia in two dogs, one with a solitary and one with multiple and recurrent lesions. The lesions in both casespresented difficulties in diagnosis and prognosis because they had many features usually associated with benign hair follicle neoplasms, but were malignant in behaviour. MATERIALS

AND

METHODS

Clinical information on the cases reported here was obtained from the records of the Small Animal Clinic and the Laboratory of Veterinary Diagnostic Medicine at the University of Illinois, Urbana, Illinois. The tissues were fixed in 10 per cent. neutral buffered formalin. Tissue sections were stained with HE. Bony tissues were decalcified prior to histological processing. RESULTS

Case1 An 1l-year-old male Siberian Husky was presented to the Small Animal Clinic in 1971 with multiple tumours of approximately 6 months duration involving the skin of the ventral cervical area. Three skin lesions and a portion of the right thyroid were excised and submitted for histopathological examination. The dog died in post-surgical shock and a necropsy was performed. Neoplastic tissue was found in the right thyroid, oropharynx, mandible and a cervical lymph node. Other neoplasms had been removed elsewhere from the skin and subcutis of the shoulder and cervical area in 1968 and 1970 and were diagnosed as epithelial tumours of hair follicle origin. Histological sections of the lesions excised in 1968 were obtained and examined. Histologically the neoplasm was characterized by the proliferation of basaloid cells with a scant pale eosinophilic cytoplasm, ovoid nuclei and finely condensed

122

D. M.

SELLS

AND

J. D. CONROY

chromatin. These cells were arranged in irregular islands, bands and sheets, but peripheral palisading was not commonly observed. Occasionally a few islands of cells were connected by tracts of basaloid cells. The neoplasm appeared to be continuous with the overlying epidermis in a few places. There was central necrosis of some of the islands and sheets of basaloid cells. Clusters of squamoid

Fig.

1. Focus of squamoid keratin surrounded

Fig. 2. Keratin

cyst formed

cells (arrow), some containing trichohyalin, by basaloid cells. Skin. HE. x 330.

by abrupt

keratinization

within

an island

with

of basaloid

a centre

of laminated

cells. Skin. HE.

x

330.

MALIGNANT

PILOMATRiXOMA

Fig. 3. Neoplasm composed chiefly of basaloid cells forming large masses of shadow cells. Skin. HE. x 130.

Fig. 4. Invasion

of the subcutis

by neoplastic

IN

concentric

epithelial

123

DOGS

keratinized

cells. Skin.

structures

HE.

x

130.

(K)

and

124

D. M. SELLS

AND

J. D. CONROY

cells with an abundant eosinophilic cytoplasm were located within or at the periphery of the islands of basaloid cells. Several layers of these squamous-like cells were sometimes interposed between basaloid cells and areas of keratinization or shadow cell* formation. In other locations, the squamoid cells were

Fig. 5. Neoplastic

focus with

associated

stromal

reaction

in the thyroid

gland.

HE.

x 130.

flattened and arranged in whorls with or without keratin centres (Fig. 1). Dark red granules resembling trichohyalin and, less often, dark blue granules resembling keratohyalin were present in the cytoplasm of these cells. Keratin cysts formed of concentrically arranged keratin lined by basaloid or parakeratotic cells were common (Fig. 2). Bands of basaloid cells partially lined large deposits of keratin and shadow cells (Fig. 3) which occasionally contained cholesterol-like clefts or focal calcification. (The calcification occurred primarily among shadow cells.) Keratinization was either abrupt or more gradual with squamoid cells between the basaloid cells and areas of keratinization. There was proliferation of fibrous connective tissue, which on occasion was hyalinized, around the islands and sheets of basaloid cells. Lymphocytes, plasma cells, macrophages and a few multinucleated giant cells were found in the stroma. In the skin, the neoplasm showed moderate numbers of mitoses and evidence of stromal invasion (Fig. 4). Neoplastic tissue identical to that described in the skin was observed in thyroid (Fig. 5), mandible (Fig. 6) and cervical lymph node, and provided evidence of invasive behaviour. A sebaceous adenoma of the skin and an interstitial cell tumour of the testicle were the only other significant lesions found at necropsy. Case 2 An adult male crossbred dog of unknown age was submitted from the Small Animal Clinic for necropsy. A greyish-white, roughened, slightly elevated, * Shadow

cell (ghost

cell)-pale

eosinophilic

cells with

an outline

of the nucleus.

MALIGNANT

PILOMATRIXOMA

IN

125

DOGS

hairless tumour about 8 cm. in diameter was present on the skin of the right thoracic area caudal to the scapula. The histological features of the neoplasm were virtually identical to those described for case 1. The predominant cell type, the basaloid cell (Fig. 7) was arranged in small islands and sheets which joined the overlying epidermis in a

Fig. 6. Invasion trabecula

of the mandible by multiple (arrow). HE. x 150.

Fig. 7. Basaloid cells with abrupt cells can be seen (arrow).

keratinization Skin. HE.

neoplastic

and shadow x 330.

foci with

shadow

cell formation.

cell formation

A small

whorl

and

bony

of squamoid

126

D. M.

SELLS

Fig. 8. Metastatic neoplastic focus consisting keratin formation. Lung. HE. x 130.

AND

J. D. CONROY

of basaloid

TABLE

Basaloid cells Shadow cells Hyalinized shadow cells Whorls of squamoid cells with trichohyalin and/or keratohyalin Squamous (epithelial or horn) pearls Necrosis (amorphous debris) Calcification Foreign body reaction Cleft formation Polarizing keratinization of shadow cells Keratin (horn) cysts Sheets of keratin Peripheral palisading of basaloid cells Continuity with epidermis Abortive hair shafts and papillae Invasiveness Metastasis

i- = Usually found. * Slight birefringence

+ = Occasionally in keratin cysts.

squamoid

cells with

shadow

TRICHOEPITHELIOMA, DIFFERENTIATION

Trichoepithdioma

PILOMATRIXOMA, (CASES 1 AND 2)

Pilomatrixoma

Case 1

i-

+ + it

: *

+ + f

-t + +

i: + i -I-

+ + i

+ Lk or present

to a slight

degree.

-

Case 2

t rl: + : -i +

T+ +

found

cell and

1

HISTOLOGICAL FEATURES OF BASOSQUAMOUS CARCINOMA, AND MALIGNANT NEoPLASIA WITH HAIR FOLLICLE

Basosquamous carcinoma

and

= Absent.

:I -t I-t + +

MALIGNANT

PILOMATRIXOMA

IN

DOGS

127

few places. Squamoid cells with eosinophilic cytoplasm were slightly more prominent although present in the same pattern as described above. Trichohyalin and keratohyalin granules were present in the cytoplasm of some of these cells. Keratin cysts and other cyst-like structures, partially lined by basaloid cells and containing keratin, shadow cells and occasional areas of calcification also were prominent. The inflammatory cell response and connective tissue proliferation around islands of neoplastic cells were similar to that seen in case 1. Numerous metastatic foci were present in the lung (Fig. 8). Basaloid and squamoid cells were arranged in small aggregates and bands which partially lined large masses of keratin and collections of shadow cells. Pulmonary and cutaneous lesions had identical features, but there was no direct communication of the two processes through the thoracic wall thus ruling out extension of the neoplasm through the body wall. The histological features of the neoplasm are summarized and compared with basosquamous carcinoma, trichoepithelioma and pilomatrixoma in Table 1. DISCUSSION

The differential diagnosis in both cases included pilomatrixoma, trichoepithelioma, keratinizing basal cell carcinoma and basosquamous carcinoma. The neoplasms described had histological features which most closely resembled pilomatrixoma. Shadow cells are a constant feature of pilomatrixoma, although not pathognomonic, having been found in epidermal cysts, inflamed hair follicles and chronic dermatoses with hyperkeratosis (Forbis and Helwig, 196 1; Bingul, Graham and Helwig, 1962). Basaloid cells are usually present in pilomatrixoma and squamoid cells with trichohyalin or keratohyalin granules, and cholesterol-like cleft formations are additional features of pilomatrixoma (Forbis and Helwig, 1961; Bingul et al., 1962) which were also present in our cases. However, the biological behaviour of the tumours described in our cases differs significantly from that of pilomatrixoma which is non-invasive and does not metastasize (Neilsen and Cole, 1960 ; Forbis and Helwig, 1961; Bingul et al., 1962; Weiss and Frese, 1974), with the possible exception of those invasive variants of pilomatrixoma described below (Reed and Lamar, 1966). Trichoepithelioma is formed of basophilic cells arranged in a lace-like network and solid islands containing keratin cysts (Gray and Helwig, 1963 ; Lever, 1967). Shadow cells are not a feature of the human tumour, but have been described in small numbers in animals (Neilsen and Cole, 1960). The prominence of shadow cells and the necrosis of neoplastic cells in the tumours studied distinguish them from trichoepithelioma. Keratotic basal cell carcinoma is formed of basaloid cells with differentiation toward parakeratotic cells which line keratin cysts (Lever, 1967). The keratinization is abrupt without a transitional layer of granular cells and the keratin cysts are thought by some authors to represent attempts at hair shaft formation (Foot, 1947; Lever, 1967). The absence in keratotic basal cell carcinoma of shadow cells, foreign body reaction, calcification, necrosis and squamoid cells with trichohyahn and keratohyalin serve to differentiate it from the tumours in this study.

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J. D. CONROY

Basosquamous carcinoma has been described in man as an infiltrating lesion characterized by the proliferation of basaloid cells with peripheral palisading. Squamous cells, sometimes having intracellular bridges and arranged in whorls, usually without keratinized centres, are reported to occur within the clusters of basaloid cells (Montgomery, 1928; Borel, 1973). The biological behaviour of basosquamous tumours is considered by some to be equivalent to squamous cell carcinoma (Montgomery, 1928; Borel, 1973) and by others to be similar to basal cell carcinoma (Allen, 1966). Some authors do not recognize basosquamous tumours as distinct entities, but rather as variants of basal cell carcinomas (Lennox and Wells, 1951; Lever, 1967 ; Pinkus and Mehregan, 1969). The absence in basosquamous carcinoma of shadow cells, necrosis, calcification, keratin cysts and foreign body reaction plus the arrangement and quantity of squamoid cells provide a basis of its differentiation from the tumours in this study. Several uncommon tumours have been described in man which occur mainly in the female, almost exclusively in the scalp, under the names of trichochlamydocarcinoma (Holmes, 1968)) invasive hair matrix tumours (Reed and Lamar, 1966)) proliferating epidermoid cysts (Jones, 1966)) and subepidermal acanthoma (Lund, 1957). Although McGavran (1971) has suggested that these atypical histological types should be considered as a relatively homogeneous group, we believe that our cases most closely resemble the invasive hair matrix tumour for which Reed and Lamar (1966) suggested the name invasive pilomatrixoma. Our conclusion was based on a number of histological features shared by this invasive pilomatrixoma and our neoplasm, namely the presence of shadow cells, abrupt keratinization, calcification of keratinized material, necrosis and foreign body reaction. The other tumours grouped by McGavran differed from ours in that they did not have a prominent basaloid component, lacked the prominent necrosis, mummification and shadow cell calcification, but did have clear cells and a greater proportion of squamoid cells. Of the human neoplasms mentioned above, metastasis has been observed in only 1 of 7 cases in trichochlamydocarcinoma. Intracutaneous cornifying epithelioma (“keratoacanthoma”) is a benign tumour which bears superficial resemblance to the tumours described. It is composed of single or multiple cavities lined by stratified cornifying squamous epithelium. The cavities are filled with lamellated, concentrically arranged or homogeneous horny material, and an epithelial pore is often found providing a connection with the epidermal surface (Weiss and Frese, 1974). The predominance of squamous cells and lack of shadow cells are sufficient characteristics to differentiate intracutaneous cornifying epithelioma from the tumours described in this study. Hair follicle tumours in animals, and in man with a few exceptions, are considered to be benign. This notion seems inconsistent with the behaviour of glandular skin appendage neoplasms, since malignant forms of these tumours are not rare in dogs. Malignant neoplasia of the hair follicle may not be as uncommon as the literature indicates. We propose that the neoplasms described represent malignant variants of pilomatrixoma. Hence, we are exercising even greater care in assessing the clinical implications ofcanine hair follicle neoplasms.

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PILOMATRIXOMA

IN

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SUMMARY

Epithelial neoplasia with hair follicle differentiation and malignant behaviour is described in two dogs. The neoplasia (solitary and multiple forms) were characterized by the proliferation of basaloid cells with central necrosis and the formation of shadow cells, keratin cysts, nests and whorls of squamoid cells containing keratohyalin or trichohyalin, and occasionally focal calcification. The tumours are compared with pilomatrixoma, trichoepithelioma, keratotic basal cell carcinoma and basosquamous carcinoma and are considered to be a malignant variant of the first of these. REFERENCES

Allen,

A. C. (1966). The Skin, 2nd edit., pp. 873-875. Grune and Stratton Inc., New York. Bingul, O., Graham, J. H., and Helwig, E. B. (1962). Pilomatrixoma (calcifying epithelioma) in children. Pediatrics, 99, 2333240. Borel, D. M. (1973). Cutaneous basosquamous carcinoma. Archives of Pathology, 95, 293-297. Cotchin, E. (1961). Skin turnouts of cats. Research in Veterinary Science, 2, 353-361. Foot, N. C. (1947). Adnexal carcinoma of the skin. American Journal of Pathology, 23, l-27. Forbis, R., Jr., and Helwig, E. B. (1961). Pilomatrixoma (calcifying epithelioma). Archives of DermatoloQ, 83, 606-6 18. Gray, H. R., and Helwig, E. B. (1963). Epithelioma adenoides cysticum and solitary trichoepithelioma. Archives of Dermatology, 87, 102-l 14. Holmes, E. J. (1968). Tumors of lower hair sheath. Cancer, 21, 234-248. Jones, E. W. (1966). Proliferating epidermoid cysts. Archives of Dermatology, 94,11-19. Jubb, K. V. F., and Kennedy, P. C. (1970). Pathology of Domestic Animals, 2nd edit., 2, 646. Academic Press, New York and London. Lennox, B., and Wells, A. L. (1951). Differentiation in the rodent ulcer group of tumors. British Journal of Cancer, 5, 195-212. Lever, W. F. (1967). Histojathology of the Skin, 4th edit., pp. 534-606. J. B. Lippincott Co., Philadelphia and Toronto. Lund, H. Z. (1957). Tumors of the skin. In Atlas of Tumor Pathology, sec. 1, pt. 2, p. 246. Armed Forces Institute of Pathology, Washington, D.C. McGavran, M. H. (197 1). The pathologic anatomy of the human pilosebaceous unit. In The Skin. Helwig, E. B., and Mostofi, F. K., Eds., pp. 72-73. The Williams and Wilkins Co., Baltimore. Montgomery, H. (1928). Basal squamous cell epithelioma. Archives of Dermatology and Syjhilology, 18, 50-73. Nielsen, S. W., and Cole, C. R. (1960). Cutaneous epithelial neoplasms of the dog-a report of 153 cases. American Journal of Veterinary Research, 21, 931-948. Pinkus, H., and Mehregan, A. H. (1969). A Guide to Dermatohistopathology, pp. 454-478. Appleton-Century-Crofts, Meredith Corporation, New York. Reed, R. J., and Lamar, L. M. (1966). I nvasive hair matrix tumors of the scalp. Invasive pilomatrixoma. Archives of Dermatology, 94, 310-316. Weiss, E., and Frese, K. (1974). Tumors of the skin. In International Histological Classijication of Tumors of Domestic Animals. Beveridge, W. I. B., and Sobin, L. H., Eds. Bulletin of World Health Organization, 50, no. 1-2, 79-100. [Received for publication,

324~ 15th, 19751