Chordoma cutis

ARTICLE

Auteur(s) : Vinicio BONESCHI¹, Athanasia TOURLAKI¹, Antonina PARAFIORITI², Emilio BERTI³ Marinella BRAMBATI¹, Lucia BRAMBILLA¹

¹ Institute of Dermatology, University of Milan, IRCCS Ospedale Maggiore, via Pace 9, 20122 Milan, Italy
² Pathology Service, Istituto Ortopedico Gaetano Pini, Milan, Italy
³ Department of Clinical Medicine, Prevention and Sanitary Biotechnology, University of Milan–Bicocca, Milan, Italy

Article accepted on 8/09/2003

Chordomas are rare malignant tumours originating from remnants of the notochord [from the Greek noton (back) and chorde (cord)], an embryonic rod-shaped structure that defines the primitive axis of the body [1]. Chordomas develop mainly in the sacrococcygeal (50%) and spheno-occipital region (35%) [2], probably because the anatomy of the rostral and caudal ends of the notochord is complex, and cell rests could be left behind when the notochord regresses elsewhere [3]. These tumours usually have a slow rate of growth and are locally aggressive. Metastases generally appear late in the course of the disease and mainly affect the lungs, lymph nodes, liver, bones, skin and skeletal muscles. Occasionally, cutaneous metastases can occur even before the primary tumour has been diagnosed [4]. Skin involvement can also occur by direct extension or by local recurrence after surgical excision. We describe a case of chordoma with cutaneous involvement by direct infiltration as the first manifestation of the tumour.

Case report

An 85-year-old man was admitted to our institute because of a diffuse form of psoriasis. He was in a bad state of health due to a chronic heart disease, and reported a 1-month history of minor weight loss and changes in bowel habits. The patient also complained of a large, asymptomatic subcutaneous tumour in the sacrococcygeal region that had grown slowly in size during the previous 3 years.
On physical examination, the mass was approximately 10 cm wide and flesh-coloured (Fig. 1). On palpation it appeared firm, smooth, and lobulated. Haematological and biochemical laboratory tests revealed a mild iron-deficiency anaemia, and an erythrocyte sedimentation rate of 45 mm/h. Computed tomography (CT) scan of the pelvis demonstrated “a voluminous, soft-tissue neoformation, involving the last coccygeal vertebrae, and showing retro-coccygeal extension to the skin and pre-coccygeal extension to the rectum” (Fig. 2). Digital rectal examination and sigmoidoscopy confirmed the invasion of the posterior rectal wall.
A cutaneous incisional biopsy of the tumour was performed, and a subcutaneous neoplasia with a grey-white, glistening, friable surface was appreciable on cut section. Histologically, the deep dermis was infiltrated by cords and nests of pleomorphic cells embedded in an abundant mucinous stroma; many cells were round-shaped, with a clear eosinophilic cytoplasm, with or without vacuoles. Large multivacuolated cells (physaliphorous cells), occasional signet-ring cells and large atypical cells were also observed (Fig. 3a). Immunohistochemically, the tumour cells were positive for cytokeratins (CAM 5.2, AE1/AE3) (Fig. 3b), vimentin, S100 protein, and epithelial membrane antigen (EMA) (Fig. 3c), but negative for carcinoembryonic antigen (CEA). These histological and immunohistochemical studies confirmed the diagnosis of classic chordoma. Ultrastructurally, the tumour cells presented intracytoplasmic, single-membrane vacuoles, sometimes empty and electron-lucent, sometimes glycogen-filled. Considering the extension of the tumour, and the patient's bad state of health, surgical excision of the chordoma was not possible, and so he underwent palliative care only.

Discussion

Chordomas are malignant neoplasms arising from remnants of the notochord, the embryonic precursor of the axial skeleton. The notochord forms from ectodermal cells during the third week of human embryonal development, and is believed to act as an organizer of chondrification and vertebral body segmentation [5]. As segmentation proceeds, the notochordal tissue differentiates and becomes part of the nucleus pulposus of the future intervertebral discs while regressing elsewhere [6]. The persistence of aberrant chordal tissue can be demonstrated in 0.5-2.0% of autopsies [1], mainly in the sacrococcygeal region and at the base of the skull. Most, if not all, chordomas originate from these notochordal vestiges in the bone substance rather than the nucleus pulposus [7]. From 1 to 4% of biopsy-analysed primary bone tumours are chordomas. The majority of sacrococcygeal chordomas affect men (M:F = 2:1), occur during the fifth and the sixth decade [8], have a slow rate of growth, and extensively infiltrate adjacent structures with symptoms attributable to many different diseases [9].
CT scanning and MRI are valuable in the demonstration of the neoplasm and especially of its extension. On the other hand, performing a biopsy is essential for the diagnosis of chordoma. Macroscopically, chordoma is a lobulated, usually blue-grey gelatinous tumour, and it may contain areas of cystic degeneration and haemorrhage [7]. Histologically, conventional chordomas consist of eosinophilic pleomorphic cells embedded in a mucinous matrix, and arranged in cords or nests. A key feature is the demonstration of the so-called physaliphorous (Greek, bubbly) cells which possess voluminous, vacuolated, clear cytoplasm, and nucleus displaced to the periphery, reflecting the notochordal cells in their late stage. Chondroid chordoma is a subtype presenting foci of cartilage-like tissue within areas of conventional chordoma. Dedifferentiated (sarcomatoid) chordoma is an aggressive variant showing areas of classical chordoma associated to sarcomatous areas resembling malignant fibrous histiocytoma, fibrosarcoma, or osteosarcoma [10]. Ultrastructurally, the physaliphorous cells are full of large, intracytoplasmic, glycogen-containing vacuoles. Other vacuoles that contain a granular, amorphous substance are formed by intracytoplasmic inclusions of the intercellular mucinous matrix. Endoplasmic reticulum-mitochondria complexes are typical, but not pathognomonic of chordoma, as identical structures have been described in clear cell chondrosarcoma [11]. Chordoma is considered to present features of both epithelial and mesenchymal differentiation. The immunohistochemical studies show positivity for cytokeratins (CKs), vimentin, S100 protein, and occasionally for EMA and CEA. Positivity for neuron-specific enolase (NSA) has also been reported [12]. In particular, the immunoreactivity includes a broad spectrum of CKs such as 8, 18, 19 (using monoclonal antibody CAM 5.2), 1-8, 10, 14-16 and 19 (monoclonal antibodies AE1/AE3), also in areas of chondroid or sarcomatous appearance. It is noteworthy that notochord is constantly positive for CKs 8 and 19: the tumour retains the expression of such CKs, while the expression of other CKs is added. No other mesenchymal tumours histologically similar to chordoma, in particular chondrosarcoma, myxoid liposarcoma and parachordoma, show similar wide CK positivity, and this condition is particularly useful when examining small biopsy specimens not suitable for morphological observation [12].
Chordoma metastasises late in its course to the lungs, bones, soft tissues, and liver in 20-40% of patients. It may involve the skin by direct extension, local recurrence, or metastases. From 70 to 80% of patients with chordoma are dead within 5 to 10 years, mostly from involvement of local structures rather than metastases [5]. Wide surgical resection of primary chordomas followed by irradiation is the treatment of choice, but local recurrences, sometimes multiple, occur in 25-64% of cases [13]. n

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