Fine-Needle Aspirationof a Chordoma and itsRecurrence 19 Years After

Dear Dr Bedrossian:

Chordoma is an uncommon malignant mesenchymal tu-

mor of fetal notochord origin that occurs exclusively

along the spinal axis, with a predilection for the sacrum,

base of the skull, and, occasionally, the mobile spine.1 It

usually occurs in the fifth to seventh decades and shows a

male predominance. Although it is a slow-growing neo-

plasm that recurs locally if incompletely excised, distant

metastasis may occur in late stages of the disease. Better

patient survival is achieved with complete surgical exci-

sion of the primary tumor, currently the only curative

form of treatment.2 The clinical features are related to the

location and spread of the neoplasm; usually, as a slow

growing-tumor, chordoma produces nonspecific symptoms

for months to years before the diagnosis is made. Charac-

teristically, the most frequent symptoms are pain referred

to the lower back and nerve dysfunctions such as anesthe-

sia and paresthesia as late manifestations.3 Patients tend

to live for a prolonged time but have significant morbidity

because of neurologic problems. The most common radio-

graphic appearance was a solitary, lytic destructive mid-

line mass, often with lobulations.4 Chordomas are divided

into three subtypes, based on microscopic morphology:

(1) conventional, (2) chondroid, and (3) dedifferentiated.

Chondroid and dedifferentiated chordomas account for

less than 5% of all chordomas.5 Macroscopically, they are

soft, tan, myxoid masses that frequently show areas of

hemorrhage. Patients with chondroid chordomas have a

longer survival than those with conventional chordoma,

whereas patients with dedifferentiated chordoma have a

very poor prognosis.5 The natural history of the dediffer-

entiated chordoma is unknown. Some researchers6 sug-

gested that the ‘‘dedifferentiated component’’ arose de

novo in conjunction with conventional chordoma and usu-

ally portends an accelerated clinical course, but other

researchers7 reported a dedifferentiated chordoma arising

in an irradiated sacral conventional chordoma, suggesting

the possible malignant transformation of chordoma.

In this article we describe the cytomorphological fea-

tures of a conventional chordoma and its local recurrence

as a dedifferentiated chordoma 19 yr after the diagnosis.

In both cases the diagnosis was made using fine-needle

aspiration biopsy, which was confirmed after excisional

biopsy.

At the first diagnosis in 1986, the patient (a 53-year-old

man) presented a sacrococcygeal mass with extension into

the adjacent soft tissue. X-ray studies showed an aggres-

sive mass with osteolytic areas. Initial fine-needle aspira-

tion (FNA) on this mass was reported as a conventional

chondroma, which was confirmed after excision biopsy.

Multiple Diff-Quik-stained smears showed high cellular-

ity, with classic physaliphorous cells arranged in clusters

and single cells in a fibrillary, myxoid background. This

*Correspondence to: Ana Saiz, M.D., Departamento de AnatomıaPatologica, Hospital ‘‘Doce de Octubre,’’ Avenida de Codoba s/n, 28041Madrid, Spain. E-mail: vmpozuelo@hotmail.com

DOI 10.1002/dc.20472Published online in Wiley InterScience (www.interscience.wiley.com).

Fig. 1. Cytomorphology of a conventional chordoma: classic physalipho-rous cells arranged in clusters and single cells in a fibrillary, myxoid,metachromatic background (MGG, 340). [Color figure can be viewed inthe online issue, which is available at www.interscience.wiley.com.]

' 2006 WILEY-LISS, INC. Diagnostic Cytopathology, Vol 34, No 9 663

myxoid stroma showed the distinctive, but nonspecific,

metachromatic staining (Fig. 1). At the time of the origi-

nal histopathological diagnosis, there were no cellular

pleomorphisms, multinucleation, nuclear holes, or mito-

ses. These features have been described as markers of

atypical and aggressive tumors.8,9 Papanicolaou (Pap)-

stained smears showed the same features. Immunocyto-

chemical studies were performed on one Pap smear. The

tumor cells were positive for cytokeratin CAM 5.2 imu-

nostaining. The patient was free of disease for 19 yr,

when it recurred in the same location. New FNA was

made, with the diagnosis of dedifferentiated chordoma. In

this case the Diff-Quik-stained smears showed high cellu-

larity with intense pleomorphism, cells with nucleoli and

intranuclear cytoplasmic inclusions resulting in nuclear

holes. Typical phisaliphorous cells were uncommon, and

when present, usually appeared as single cells. Abundant

fibrillary, mixoid, metachromatic background was present

in all smears. Pap-stained smears showed the same fea-

tures (Fig. 2).

According to the current English literature, the most

important cytomorphologic diagnostic feature of chor-

doma is the presence of occasional large physalipherous

cells.4,5–9 Other cytomorphological features are the pres-

ence of a rich myxofibrillary background within cuboidal

cells arranged in cohesive clusters or scattered individu-

ally.4,5–9 The common cytological differential diagnoses

of chordoma include myxochondrosarcoma, myxoliposar-

coma, myxopapillary ependimoma, alveolar soft-tissue

sarcoma, and metastatic clear-cell malignancies from

other primary sites.5,9 At this point immunocytochemistry

would help us: cytokeratin (AE-1/AE-4; CAM 5.2) would

be positive in chordoma and metastatic mucinous adeno-

carcinoma and negative in the other differential diagnoses,

and on the other hand S-100 would be positive in all

except metastatic mucinous adenocarcinoma.5

To the best of our knowledge, this is the first case in

the literature of a conventional chordoma with a recur-

rence 19 years after with pleomorphic cytology, resulting

in the diagnosis of a dedifferentiated chordoma.

Ana Saiz, M.D.*

Department of Pathology

Hospital ‘‘Doce de Octubre’’

Madrid, Spain

Pedro de Agustın, Ph.D., F.I.A.C.

Andres Perez Barrios, M.D.

Nuria Alberti, M.D.

Division of Cytopathology

Department of Pathology

Hospital ‘‘Doce de Octubre’’

Madrid, Spain

References1. Dorfman HD, Czerniak B. Chordoma and related lesions. In: Bone

tumors. St. Louis, MO: Mosby; 1998. P 974–1007.

2. Mirra JM, Nelson SD, Della Rocca C, Mertens F. Chordoma. In:Fletcher C, Unni K, Mertens F, editors. World Health Organizationclassification of tumours: Tumours of soft tissue and bone. Lyon,Paris: IARC Press; 2002. p 316–317.

3. Kay PA, Nascimento AG, Krishnan Unni K, Salomao DR. Chor-doma. Cytomorphologic findings in 14 cases diagnosed by fine nee-dle aspiration. Acta Cytol 2003;47:202–208.

4. Crapanzano JP, Ali SZ, Ginsberg MS, Zakowski MF. Chordoma. Acytologic study with histologic and radiologic correlation. Cancer(cancer cytopathol) 2001;93:40–51.

5. Kfoury H, Haleem A, Burgess A. Fine-needle aspiration biopsy ofmetastatic chordoma: Case report and review of the literature. DiagnCytopathol 2000;22:104–106.

6. Meiss JM, Raymond AK, Evans HL, Charles RE, Giraldo AA.Dedifferentiated chordoma. A clinicopathologic and immunohisto-chemical study of three cases. Am J Surg Pathol 1987;11(7):516–525.

7. Ikeda H, Honjo J, Sakurai H, Mitsuhashi N, Fukuda T, Niibe H.Dedifferentiated chordoma arising in irradiated sacral chordoma.Radiat Med 1997;15(2):109–111.

8. Waalas L, Kindblom LG. Fine-needle aspiration biopsy in the preop-erative diagnosis of chordoma: A study of 17 cases with applicationof electron microscopic, histochemical, and immunocytochemical ex-amination. Human Pathol 1991;22:22–28.

9. Plaza JA, Ballestin C, Perez-Barrios A, Martinez MA, de Agustin P.Cytologic, cytochemical, immunocytochemical and ultrastructuraldiagnosis of a sacrococcygeal chordoma in a fine-needle aspirationbiopsy specimen. Acta Cytol 1998;33(1):89–92.

Fig. 2. Cytomorphology of a dedifferentiated chordoma: high cellularitywith intense pleomorphism, cells with nucleoli and intranuclear cytoplas-mic inclusions resulting in nuclear holes. Scattered phisaliphorous cells(Papanicolaou, 340). [Color figure can be viewed in the online issue,which is available at www.interscience.wiley.com.]

SAIZ ET AL.

664 Diagnostic Cytopathology, Vol 34, No 9

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