Metastatic pilomatrixoma presenting as paraplegia in a dog

CASE REPORT

INTRODUCTION

Metastatic pilomatrixoma presenting as I!araplegia in a m

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L. Van Ham, H. van Bree, T. Maenhout*, M. Tshamala, D. Broekaertt, J. Hoorens* and D. Mattheeuws Department of Small Animal Medicine, *Department of Veterinary Pathology and +Department of Physiological Chemistry, State University of Ghent, Casinoplein 24, B-9000 Ghent and t K . L. Ledeganckstraat 35, B-9000 Ghent, Belgium fournai of Small Animal Practice (1990) 32,27-30

ABSTRACT A three-year-old giant poodle with a subacute paraplegia had a metastasic pilomatrixoma in vertebrae T1, L 1 and L4, ulna, humerus, tibia and lymph nodes. Pilomatrixoma is generally considered as a benign tumour of the skin. This is the first report on pilomatrixoma metastasing to bone and causing neurological signs.

Pilomatrixoma is an uncommon skin tumour, thought to arise from the hair matrix, and is characterised by a variable proliferation of basophilic cells (which resemble hair matrix cells) and shadow cells or ghost cells (fully keratinised, faintly eosinophilic cells with a central, unstained nucleus). There is abrupt keratinisation (no stratum granulosum), and the keratin is homogeneous, relatively amorphous, and non-fibrillar (tricholemnal keratin). A frequent but not constant feature of pilomatrixoma is calcification within the areas of shadow cells (Muller and others 1989).It occurs almost exclusively in man and dogs (Stannard and Pulley 1978, Johnson and others 1983, Theilen and Madewell 1987). It is rarely invasive or metastatic (Nielsen and Cole 1960, Forbis and Helwig 1961, Bingul and others 1962, Weiss and Frese 1974, Stannard and Pulley 1978, Muller and others 1989). In dogs there have been several reports on benign pilomatrixoma (Head 1953, von Sandersleben 1958, Nielsen and Cole 1960, Smith and others 1972), and there are reports on two malignant epithelial tumours with hair follicle differentiation (Sells and Conroy 1976) and one malignant pilomatrixoma with both aggressive local growth and metastasis to the lung (Johnson and others 1983). This report describes a dog with neurological signs caused by metastatic pilomatrixoma in vertebrae.

CASE REPORT ~-

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A three-year-old male giant poodle was referred to the clinic with paraplegia of a few days duration. According to the referring veterinarian the dog had nephritis three weeks before presentation and had been treated with amoxycillin. The week before presentation it had difficulty in walking and it was finally presented in a paraplegic state. General physical examination revealed an increased temperature (40°C) and painful swelling of the right radius and ulna. On neurological examination, conscious proprioception, hopping and tactile placing reflexes were absent in both hindlegs. There was also increased tone on passive manipulation. Pain perception was present. There was spinal hyperaegthesia in the lumbar area. Based on the history, the physical and the neurological examination the lesion was localised to the thoracolumbar spinal cord and a differential diagnosis of myelitis, discospondylitis, neoplasia, or disc disease was considered. Radiographs revealed involvement of the vertebral bodies of T1, L1 and L4, and the diaphyses of the right tibia, humerus and ulna. The lesions 27

L. VAN HAM AND OTHERS

FIG 1. Metastatic pilomatrixoma in the vertebral column: the lesions within L1 and L4 have a destructive pattern with a moth-eaten aspect surrounded by an osteosclerotic rim (large arrows). Irregular periosteal new bone is in the ventral area of L1 (small arrow)

within L1 and L4 had a destructive pattern with mottled lysis surrounded by an osteosclerotic rim. Irregular periostal new bone was present in the ventral area of T1 and L1 (Fig 1).The lesions within the proximal part of the ulna were quite extensive and lytic combined with an irregular periosteal response. A small radiolucent osteolytic area with a small periosteal reaction was visible within the medial condyle of the right humerus (Fig 2). The lesion within the right tibia was predominantly characterised by a rather smooth periosteal reaction creating an osteosclerotic shadow upon the bone cavity (Fig 3). Survey radiographs of the thorax and abdomen revealed no abnormalities. The radiographic differential diagnosis was neoplasia or osteomyelitis. However, the multicentric origin of the bony lesions was suggestive of bone metastases. Complete blood count, serum biochemical analysis and urinalysis revealed no significant abnormalities. A biopsy of the ulna was taken surgically with a trephine. Microbiological and mycotic culture of this was negative. Histopathological examination revealed well differentiated bone tissue with some neutrophilic infiltration, but no definitive diagnosis could be made. However, based on negative culture results, a diagnosis of neoplasia was likely. Because the dogs general condition deteriorated progressively it was finally killed humanely. Necropsy revealed a very thin dog with decubital ulcers on the extremities. The muscles of the hindlegs were atrophic. Tumours were found in the right tibia, ulna and the first and the fourth lumbar vertebrae. The mediastinal, bronchial, iliacal, axillary and prescapular lymph node were enlarged. On the cut surface of the kidney radial striations were present. The right epididymis was swollen. No skin or other tumours were detected. Histological examination revealed metastatic pilomatrixoma in the bone (Fig 4) and lymph nodes (Fig 5). The epididymis showed a purulent inflammation, but no neoplasia. Tumour metastases contained two cell types, ie, sheets or groups of basaloid cells and typical shadow cells. Some cells had a hyperchromatic nucleus, with or without a prominent nucleolus, while others had a swollen and pale nucleus. Few mitoses were present. Focally squamous metaplasia of 28

the basaloid cells was observed in the immediate vicinity of shadow cells. In one lymph node necrotic foci and calcification were present. An immunohistochemical study was performed on the tumour of the ulna. Monoclonal antibodies for human vimentin, desmin, and different cytokeratins (CKs) were used in the indirect immunoperoxidase technique on frozen sections (Broekaert and others 1988). The cytokeratins tested were CK 4, 5, 7, 8, 10, 13, 14, 18 and 19 (Moll and others 1982). Tumour staining was FIG 2. Metastatic pilomatrixoma in ulna: the lesions within the proximal part of the ulna are quite extensive and have a moth-eaten aspect combined with an irregular periosteal response (large arrow). A small radiolucent osteolytic area with a small periosteal reaction is visible within the medial condyle of the right humerus (small arrow)

FIG 3. Metastatic pilomatrixoma in the right tibia: the lesion is predominantly characterised by a rather smooth periosteal reaction creating an osteosclerotic shadow upon the bone cavity (arrow)

Metastic pilomatrixorno

FIG 4. Metastatic pilomatrixoma in bone. There are two cell types: basaloid cells (1)and shadow cells (2). Haematoxylin andeosin. X 250

restricted to clone 80 and RCK 103 (both broad spectrum probes) and to RCK 102 (recognising CK 5 and CK 8) and LE 41 (recognising CK 8). Clone 80, RCK 102 and RCK 103 variably stained basaloid cells, as well as typical ghost cells and squamoid depositions, leaving, however, numerous sites unstained. CK 8 was shown variably in basaloid and maturing cells, but was never observed in ghost cell areas. Vimentin staining was prominent in the tumourous stroma. In addition it was locally observed in ghost cell regions, suggesting coexpression of CK’s and vimentin. The final diagnosis was metastatic pilomatrixoma in vertebrae, limb bones and lymph nodes. The owner revealed that the dog had a skin tumour removed from the back in the previous year. No histopathological examination was performed at that time.

DISCUSSION Pilomatrixomas account for 1 (Theilen and Madewell 1987) to 3 per cent (Nielsen and Cole 1960) of canine skin tumours. They appear especially in Kerry blue terriers and poodles, with an average age of six years, and also in bedlington terriers, schnauzers and some other breeds. There is no sex predilection. These tumours are usually solitary and have a predilection for the shoulder, back, flanks and legs. They are firm, well-circumscribed, freely moveable masses. The overlying skin is usually thin, hairless, and frequently ulcerated (Nielsen and Cole 1960, Stannard and Pulley 1978, Theilen and Madewell 1987, Muller and others 1989). The animal presented here was a poodle, three years of age, and according to the owner, the suspected primary tumour had appeared one year before, at the age of two years. Radiography revealed aggressive lesions in both vertebrae and appendicular bones. Aggressive bone lesions are likely to produce a mixture of osteolytic and osteoproliferative changes. Cortical erosion and irregular, active bone produc-

tion are characteristic findings in aggressive bone lesions, and there may be an associated soft tissue component. Both infections and malignant neoplasms tend to cause changes in bone structure described as aggressive (Oliver and others 1987). A surgical biopsy was not diagnostic. Bacterial and fungal infection were excluded on the basis of negative culture results. This allowed us to make a presumptive diagnosis of neoplasia. Secondary bone tumours occur infrequently in dogs (Goedegebuure 1979, Morgan and others 1980). Humerus, femur and vertebrae seem to be the sites of predilection for metastatic bone lesions (Goedegebuure 1979). Secondary vertebral tumours often involve multiple vertebrae (Kornegay 1986), Embolic tumour cells may pass directly to the lumbar vertebrae through the vertebral veins (Morgan and others 1980). According to Stannard and Pulley (1978) pilomatrixoma is characterised by variably-shaped masses of epithelial cells. Two distinct cell types are present, basophilic cells and shadow cells. The basophilic cells closely resemble the hair matrix cells found in the hair bulbs of actively growing hairs, are small and stain deeply with only scant amounts of cytoplasm. The cellular borders are distinct, and it appears as if the nuclei are embedded in a symplasic mass. The fully keratinised shadow cells are faintly eosinophilic with haematoxylin and eosin and have a distinct border with a central unstained area at the site of the nucleus. A frequent but not constant feature of pilomatrixomas is calcification within the areas of shadow cells; ossification occurs rarely. Usually, at least a portion of the tumour stroma contains a foreign-body giant cell reaction (Stannard and Pulley 1978). Most of these features were present in the metastatic tumours in this case. Pilomatrixoma must be differentiated from trichoepithelioma, keratinising basal cell carcinoma, and basosquamous carcinoma (Forbis and Helwig 1961, Sells and Conroy 1976). Shadow cells are a constant feature of pilomatrixoma, but

FIG 5. Metastatic pilomatrixoma in lymph node, showing basaloid cells (1)and necrosis ( 2 ) . Haematoxylin and eosin. x 100

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L. VAN HAM AND OTHERS

are not pathognomonic. They are also present in epidermoid cysts, inflamed hair follicles and chronic hyperkeratotic dermatoses. A frequent but not constant feature of pilomatrixomas is calcification within the areas of shadow cells (Muller and others 1989). 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 and others 1962). Pilomatrixoma is normally benign in man and dogs, being slow growing and rarely invasive or metastic (Nielsen and Cole 1960, Forbis and Helwig 1961, Bingul and others 1962, Theilen and Madewell 1987, Muller and others 1989). However, in dogs, after reports on two malignant epithelial tumours with hair follicle differentiation [Sells and Conroy 1976) and one malignant pilomatrixoma with both aggressive local growth and metastasis to the lung (Johnson and others 1983), this report on pilomatrixoma with metastasis to bones and lymph nodes further indicates the possible malignant character of pilomatrixoma in this species. This malignant character is difficult to predict histologically [Johnson and others 1983). Locally aggressive pilomatrixomas are also described in man (Forbis and Helwig 1961, Reed and Lamar 1966, Lopranski and Mihm 1980), and there are two cases of metastatic basal cell tumours with the characteristic ghost cells (Farmer and Helwig 1980). These tumours probably represent the malignant form of pilomatrixoma in man (Johnson and others 1983). Clinical management of pilomatrixomas may include surgical excision, cryotherapy, or observation without treatment (Muller and others 1989). However, the reports by Sells and Conroy (1976), by Johnson and others (1983), and this case, indicate that surgical excision is the treatment of choice.

ACKNOWLEDGEMENTS We are indebted to H. Eto, E. B. Lane, I. M. Leigh, F. C. S. Ramaekers and G. N. P. Van Muijen for the gift of monoclonal antibodies and the Belgian F. G. W. 0. for the research contract number 3.0012.87. Thanks are due to C. Puttvils for photography of histological sections, and to J. P. Logge for technical assistance.

REFERENCES BINGUI., O., GRAHAM,J. H. & HELWIG, E. B. (1962) Piloma-

trixoma (calcifying epithelioma) in children. Pediatrics 30, 233-240

BROEKAERT, D., CORNILLE, A., ETO,H., LEIGH,I., RAMAEKERS, F., VANMUIJEN, G., COUCKE, P., DE BERSAQUES,J., KLUYSKENS, P. & GILLIS,E. (1988) A comparative immunohistochemical study of cytokeratin and vimentin expression in middle ear cholesteatoma, and in epidermis. Virchows Archives A Pathological Anatomy 413, 39-51 FARMER, E. R. & HELWIG, E. B. (1980) Metastatic basal cell carcinoma: a clinic0 pathologic study of seventeen cases. Cancer 46, 748-757 FORBIS, R. JR. & HELWIG, E. B. (1961) Pilomatrixoma (calcifying epithelioma). Archives of Dermatology 83,606-618 GOEDEGEBUURE, S . A. (1979) Secondary bone tumours in the dog. Veterinary Pathology 16, 520-529 HEAD,K. W. (1953) Skin diseases, Neoplastic diseases. Veterinary Record 65,926-929 JOHNSON, R. P., JOHNSON, J. A., GROOM,S. C. & BURGESS,L. (1983) Malignant Pilomatrixoma in an Old English Sheepdog. Canadian VeterinaryJournal 24, 392-394 KORNEGAY, J. N. (1986) Vertebral diseases of large breed dogs, Vertebral neoplasia, in Contemporary issues in small animal practice, volume 5, Neurologic disorders. Churchill Livingstone. New York. pp 211-215 LOPRANKSI, S . & MIHM,M. C. JR. (1980) Pilomatrix carcinoma or calcifying epitheliocarcinoma of Malherbe. Cancer 4 5 , 2368-2373

MORGAN, J. P., ACKERMAN, N., BAILEY,C. S. & POOL,R. P. (1980) Vertebral tumours in the dog: a clinical, radiologic, and pathologic study of 61 primary and secondary lesions. Veterinary Radiology 21,197-212 MOLL,R., FRANKE, W. W., SCHILLER, D. L., GEIGER, B. & KROPLER, R. (1982) The catalog of human cytokeratins: patterns of expression in normal epithelia, tumours and cultured cells. Cell 3 1 , l l - 2 4 MULLER, G. H., KIRK, R. W. & SCOTT,D. W. (1989) Neoplastic Diseases, Pilomatrixoma, in Small Animal Dermatology, 4th edn. W. B. Saunders. Philadelphia. pp 863-866 NIELSEN, S. W. & COLE,C. R. (1960) Cutaneous epithelial neoplasms of the dog - a report of 153 cases. American Journal of Veterinary Research 21,931-948 OLIVER, J. E. JR., HOERLEIN, B. F. & MAYHEW, I. G. (1987) Neuroradiography, Ventral column and spinal cord. In: Veterinary Neurology. W. B Saunders. Philadelphia. pp 78-90 REED,R. J. & LAMAR, L. M. (1966) Invasive hair matrix tumours of the scalp. (Invasive pilomatrixoma). Archives of DermatOlOgy94, 310-316 SELLS,D.M. & CONROY, D. J. (1976) Malignant epithelial neoplasia with hair follicle differentiation in dogs. Malignant pilomatrixoma. Journal of Comparative Pathology 86, 121129

SMITH,H. A., JONES, T. C. & HUNT, R. D. (1972) Neoplasia, Hair matrix tumour, Benign calcifying epithelioma (of Malherbe), in Veterinary Pathology. 4th edn. Lea and Febriger. Philadelphia. p 230 STANNARD, A. A. & PULLEY, L. T. (1978) Tumours of the skin and soft tissue, Pilomatricoma, in Tumours in domestic animals. 2nd edn. J. E. Moulton. University of California Press. Berkely - Los Angeles - London. pp 51-53 THEILEN, G. H. & MADEWELL, B. R. (1987) Tumours of the skin and subcutaneous tissues, Hair matrix tumour In Veterinary Cancer Medicine 2nd edn. Lea & Febiger. Philadelphia. p 257 VON SANDERSLEBEN, J. (1958) Uber epitheliale Neubildungen in der Haut des Hundes. Berliner und Miinchener tierarztlicher Wochenschrif? 71, 287-290 WEISS,E. & FRESE,K. (1974) Tumours of the skin, Tumours of hair follicle, Necrotizing and calcifying epithelioma (Malherbe), in Bulletin WHO, 50, 1-2, International histological classification of tumours of domestic animals. p 97