CASO CLÍNICO REVISTA PORTUGUESA DE CIÊNCIAS VETERINÁRIAS

Metastatic malignant pilomatricoma with bone and lung metastasis in a Portuguese Water Dog

Pilomatricoma maligno metastizante com metastização óssea e pulmonar num Cão de Água Português

Rute M. Noiva1*, Fabíola B. Costa2, Rafael Pratas3, Maria C. Peleteiro1

1Interdisciplinary Centre of Research in Animal Health (CIISA), Faculty of Veterinary Medicine, Technical University of Lisbon, 1300-477 Lisboa, Portugal 2Universidade Federal Fluminense, Rua Vital Brasil, 64, Santa Rosa, Niterói, Rio de Janeiro – RJ 24320-340 – Brasil 3Centro de Cirurgia Veterinária de Loures, Rua José Manuel Cerqueira Afonso dos Santos, 35B 2685-402 Prior Velho, Portugal

Summary: Pilomatricomas consist of neoplastic proliferations the hair follicle in three distinctive areas (infundibu- of germinative cells of the follicular matrix or hair bulb. lum, isthmus and hair bulb) facilitates characterization Malignant pilomatricomas are considered rare, with only a of the various tumor types, in which malignant behavior small number of cases reported in dogs. Here we present a case of malignant pilomatricoma in a Portuguese Water Dog with a is seldom reported. 3-year clinical history of recurrent pilomatricomas with evi- A pilomatricoma (pilomatrixoma or calcifying dence of cellular atypia from the first diagnosis. The malignant epithelioma of Malherbe) consists of a neoplastic pro- behavior of the tumour in this animal included bone and lung liferation of germinative cells of the follicular matrix, metastasis. The bone invasion in the C1 vertebra resulted in or hair bulb (Gross et al., 2005; Lopansri and Mihm, severe pain and discomfort that finally led to euthanasia after a severe crisis of respiratory distress. 1980). Pilomatricomas occur most commonly in rela- tively young animals on the proximal legs and dorsal Keywords: malignant pilomatricoma, Portuguese Water Dog, trunk, particularly over the rump and shoulders, and bone and lung metastasis usually present as solitary, well circumscribed, firm to hard dermal and/or subcutaneous masses (Gold- Resumo: Pilomatricomas são neoplasias com origem nas et al células germinativas da matriz dos folículos pilosos. Os schmidt and Shofer, 1992; Neto ., 2009). Some pilomatricomas malignos são considerados neoplasias raras, tumors have a gritty or bony consistency and lesions com apenas um reduzido número de casos relatados em may be chalky when sectioned (Goldschmidt and canídeos. No presente trabalho regista-se um caso de piloma- Shofer, 1992; Gross et al., 2005; Massone et al., tricoma em Cão de Água Português, que evoluiu ao longo de 3 2005). The overlying epidermis is often atrophic and anos, com recidivas nas quais se registou sinais de atipia celular et al et al desde o primeiro diagnóstico. O comportamento maligno deste alopecic (Gross ., 2005; Massone ., 2005). tumor, que conduziu ao desfecho final, caracterizou-se por Histologically, pilomatricomas are composed of metastização no tecido ósseo e pulmonar. A invasão óssea na multiple cystic structures of varying size, lined pre- vértebra C1 resultou em dor severa e desconforto que levaram à dominantly by small, basaloid keratinocytes which decisão de eutanásia, após uma grave crise de insuficiência resemble the matrix cells of the anagenic hair bulb. respiratória. Mitotic activity is fairly high but nuclear or mitotic Palavras-chave: pilomatricoma maligno, Cão de Água Portu- atypia is not present (Goldschmidt and Shofer, 1992; guês, metástases ósseas e pulmonares Gross et al., 2005). The neoplastic cells undergo matrical-type keratinization characterized by abrupt transition to large masses of keratinized ‘ghost’ or Introduction ‘shadow’ cells that fill the cysts’ lumen (Goldschmidt and Shofer, 1992; Gross et al., 2005; Neto et al., Follicular tumors are a relatively common event in 2009). Ghost cells have a nucleus that does not stain small animal dermatology, more frequently reported with Hematoxylin&Eosin appearing as acidophilic in dogs and rarely in cats (Goldschmidt and Shofer cells with an apparent central void. They often become 1992; Scott et al., 2001). Separating the structure of mineralized, and osseous metaplasia may occur, particularly in later stages, so that some tumors of chronic duration exhibit a predominance of ghost cells *Correspondência: [email protected] and bone with little residual epithelium (Gross et al., Tel: +351 3652838; Fax: +351 213652895 2005).

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A survey of follicular neoplasias diagnosed in the Laboratory of Pathological Anatomy of the Faculty of Veterinary Medicine of the Technical University of Lisbon, between 2005 and 2010, identified 182 cases (Table 1). Pilomatricomas accounted for 31 of these tumors, with a single case of malignant behavior; the one reported here. Malignant pilomatricomas are considered rare, with only a small number of cases reported in dogs, some of which describing metastatization to the lymph nodes, lungs and bone (Maxie et al. 2007). The aim of the present work is to add a new case to these rare reports of malignant pilomatricoma in dogs (Carroll et al., 2010; Jackson et al., 2009; Johnson et al., 1983; Rodriguez et al., 1995; Sells and Conroy, 1976), this Figure 1 - Dorsal pilomatricoma. The tumor exhibits several lobules time in a Portuguese breed. separated by moderate fibrous stroma. Above and on the left, foci of abrupt keratinization, some of which calcified, can be seen. Clefts corresponding to cholesterol crystals are shown in the center of the image. The insert shows ghost cells in close contact with tumour cells Case Report with vacuolated nuclei showing moderate anysokariosis. A few mitosis can be seen (arrows) (H&E, 100x, insert x400) In August 2008, Black, a three-year-old Portuguese Water Dog underwent surgery to remove a 3 cm dorsal nodule which was then sent to the Laboratory of Pathological Anatomy of the Faculty of Veterinary Medicine (Lisbon) for analysis. Histopathology reported this nodule to be a pilomatricoma, a prolife- ration of basaloid cells forming lobules with cystic central abrupt matrical keratinization and numerous ghost cells. Although the mitotic index was low, with less than one dividing cell per ten high power fields, there was some evidence of cellular atypia. Several lobules showed foci of bone formation and necrosis with cholesterol crystal clefts (Figure 1). In some areas, ruptured cysts had triggered inflammation and desmoplasia. Eighteen months later, Black was again submitted to Figure 2 - Pilomatricoma over the left eye. The tumor is composed of undifferentiated cells similar to the atypical ones of the first tumor. surgery to remove three small nodules. These new These cells can be seen infiltrating the stromal interstitial tissue towards masses were located (i) in the head over the left eye the left. An area of abrupt matrical keratinization is patent above on the (2 cm), (ii) in the left pectoral region (0.5 cm) and (iii) right (H&E, 100x) in the lumbar left area (1 cm). Upon histopathological analysis all three tumors showed characteristics were frequent, accounting for a mean of two dividing already described for the tumor previously removed, cells per high power field. No calcification or bone although with clearer signs of malignant behavior, formation were present in any of these nodules. especially in the facial and pectoral nodules, such as Six weeks after the last surgery, Black was presented indistinct limits and dermal infiltration (Figure 2). The for orthopedic evaluation due to severe right thoracic neoplastic cells had a less basaloid appearance, and limb lameness without evidence of joint pathology were larger, with paler nucleus and distinct nucleoli. distally to the shoulder. Clinical examination revealed Single cell necrosis was common and mitotic figures a severe cervical pain on manipulation of the neck.

Table 1 - Retrospective survey of the archives of the Laboratory of Pathologic Anatomy of the Faculty of Veterinary Medicine (2005-2010). Follicular neoplasm type, species and sex distribution Type of Neoplasm Cats Dogs Other Animals Female Male Female Male Guinea Pig Gerbil Rabbit Trichoepithelioma 3 4 29 33 0 0 Trichoblastoma 6 7 28 39 0 0 1*+1± Pilomatricoma 0 0 17 11 1* 1* Malignant pilomatricoma 0 0 0 1 0 0 *Male; ± Female

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Radiographic studies were performed, showing bone proliferation over the left wing of C1 (Figure 3). In the following weeks, Black’s condition worsened. The owners opted for euthanasia after a severe crisis of respiratory distress and pleural effusion. Upon necropsy, the only mass present in the skin was a nodule, 1.5 cm in diameter, located over the right eye. The left wing of the atlas (C1) was markedly enlarged, its dimensions being 5.5 x 3.5 x 3 cm, slightly pro- jecting into the spinal canal and lightly compressing the spinal cord (Figure 4A). A negligible number of small blood clots were present in the epidural space. The pleural cavity contained around 100 ml of hemor- rhagic fluid and both lungs exhibited various nodules, ranging from 0.5 to 4 cm in diameter (Figure 4B). Figure 3 - Radiographic image of the cervical area, ventrodorsal view. Sectioning the nodules revealed a white, rough and Note how the left wing of the atlas (bottom side of the image) appears deformed by a mottled, irregularly radiopaque mass pasty cut surface with the consistency of calcified tissue. The surrounding pulmonary parenchyma was severely congestive. Various tissue samples were collected from the necropsy and fixed in 10% buffered formalin. They were submitted for routine histopathological proces- sing, except for the bone tissue, which was previously submitted for 24h to a commercial decalcifying solu- tion (OSTEOMOLL®, MERCK). Sections obtained Figure 4 - Necropsy images. A) Atlas exhibiting marked thickening of from the processed tissue samples were all stained the left wing. B) Dorsal surface of the lungs. A large nodule can be seen in the right lung (thin arrow) as well as other, smaller nodules. The left with Hematoxylin&Eosin (H&E). Giemsa stain was lung also exhibits small metastatic nodules (thick arrow) additionally applied to the decalcified bone sections. Histopathological analysis of the nodule over the eye confirmed it was a pilomatricoma. However, although the cells still formed cystic lobules, they were now clearly smaller and more loosely arranged than in the other lesions. Analysis of the pulmonary nodules revealed them to be similar to this nodule, with wide cystic cavities containing matrical keratin and ghost cells, occasion- Figure 5 - Photomicrographs of necropsy material showing metastases ally surrounded by a thin rim of neoplastic cells. of the pilomatricoma. A) Pulmonary metastasis showing nodules of Although calcification was frequent, no bone forma- loosely arranged epithelial cells within a dense fibrous stroma or organi- tion was detected (Figure 5A). Lesions of purulent zed around islets of ghost cells that were extensive and frequent (H&E, 100x). B) Bone tissue from the left wing of C1. The compact bone is pneumonia were visible throughout the remainder of infiltrated by trabecullae of keratinized ghost cells staining pale blue (*) the pulmonary tissue. (Giemsa, 100x) Histopathology of the C1 mass revealed infiltration of bone trabecullae by neoplastic tissue that stands out the matrical cells of an anagenic hair follicle. Reports due to the pale blue colour of keratinized cells in con- of malignant pilomatricomas are rare and restricted to trast with the bone tissue staining purple (Figura 5B). dogs, in which metastatization to the lymph nodes, In fact, staining with Giemsa contributed to enhance lungs and bone has been previously described (Maxie the perception of the keratinized cells also improving et al., 2007). the visualization of cellular details that were not so Histologically, malignant pilomatricomas can be clear in the decalcified tissue stained with H&E. distinguished from benign processes due to charac- teristics such as a low cellular differentiation, fast or erratic growth, high mitotic index, infiltration of Discussion neighbouring tissue and, finally, metastatization. In fact, malignant pilomatricomas generally assume a Pilomatricomas are most commonly benign tumors similar clinical presentation to benign pilomatricomas that originate from the germinative cells of the in the skin itself. In certain cases, the iatrotropic follicular matrix, taking the form of dermal and/or stimulus (the motive for owners to seek medical subdermal masses composed of multiple cystic struc- support) may be related not to the primary tumor but tures lined by small basaloid keratinocytes, similar to to some degree of dysfunction associated with distant

103 Noiva RM et al. RPCV (2012) 111 (581-582) 101-104 metastasis (e.g., lameness) (Carroll et al., 2010). Bibliography Here we present the case of a Portuguese Water Dog with a clinical history of recurrent neoplastic lesions Carroll EE, Fossey SL, Mangus LM, Carsillo ME, Rush LJ, diagnosed as pilomatricomas, which became progres- McLeod CG and Johnson TO (2010). Malignant piloma- sively more frequent and numerous and eventually tricoma in 3 dogs. Vet Pathol, 47, 937-943. invaded both bone and lung, severely compromising Goldschmidt MH and Shofer FS (1992). Skin tumors of the the animal’s quality of life. The multiple neoplastic dog and cat, 1st edn. Pergamon Press, Oxford [England]; New York. pp xi, 316. lesions observed upon necropsy and histopathological Gross TL (2005). Skin diseases of the dog and cat: clinical analysis were attributed to metastasis of one of the and histopathologic diagnosis. 2nd Ed. Blackwell previously removed pilomatricomas, namely the one Science, Ames, Iowa. pp xi, 932. located over the right eye. Black’s severe right thoracic Jackson K, Boger L, Goldschmidt M and Walton RM limb lameness was attributed to medullary compression. (2009). Malignant pilomatricoma in a soft-coated To the best of our knowledge, Black’s case is the Wheaten Terrier. Vet Clin Pathol, 39, 236-240. first case of a malignant pilomatricoma ever to be Johnson RP, Johnson JA, Groom SC and Burgess L (1983). reported in this particular breed. Although most cases Malignant pilomatrixoma in an old english sheepdog. Can of pilomatricoma described in the literature are related Vet J, 24, 392-394. to the benign variant of this neoplasia, there is now a Lopansri S and Mihm MC Jr (1980). Pilomatrix carcinoma growing suspicion that malignant pilomatricoma may or calcifying epitheliocarcinoma of Malherbe: a case report and review of literature. Cancer, 45, 2368-2373. actually be a more common, aggressive and potentially et al Massone AR, Quiroga MA, Diessler ME, Machuca MA, del fatal entity than previously assumed (Carroll ., Amo AN and Idiart JR (2005). Neoplasias del folículo 2010; Meuten, 2002). piloso del canino: estudio retrospectivo (1981- 2003). As reports of aggressiveness become more frequent, Analecta Veterinaria, 25, 29-32. awareness to the presentation and behavior of these Maxie MG, Jubb KVF, Kennedy PC and Palmer N (2007). tumors becomes increasingly important to both Jubb, Kennedy, and Palmer's pathology of domestic pathologists and clinicians (Carroll et al., 2010), as a animals, 5th edn. Elsevier Saunders, Edinburgh, 761-763. precocious diagnosis and an adequate treatment are Meuten DJ (2002). Tumors in domestic animals, 4th edn. essential in improving the patient's quality of life and Iowa State Press, Ames, Iowa. pp xii, 788. extending life expectancy. Neto NMA, Monteiro BS, Carlo RJ, Parzanini G and Carlo EC (2009). Pilomatricoma em um cão: relato de caso. Veterinária e Zootecnia, 16, 309-315. Rodriguez F, Herraez P, Rodriguez E, Gomez-Villamandos Acknowledgements JC and Espinosa de los Monteros A (1995). Metastatic pilomatrixoma associated with neurological signs in a The authors wish to thank the laboratory technicians dog. Vet Rec, 137, 247-248. Sandra Carvalho and Maria do Rosário Luís for their Scott DW, Miller WH and Griffin CE (2001). Muller and excellent technical assistance. Kirk's Small Animal Dermatology, 6th edn. W.B. Saunder Co., Philadelphia. pp x, 1213. Sells DM and Conroy JD (1976). Malignant epithelial neoplasia with hair follicle differentiation in dogs: Malignant pilomatrixoma. J Comp Pathol, 86, 121-129.

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