Metastatic spread to the lungs and/or to locoregional lymph nodes represents a very unusual event in D-TCGT [
7]. Such occurrence in principle should prompt reconsideration of the original diagnosis [
1,
5]. The clinical differential diagnosis between D-TCGT and its malignant variant is very difficult, due to overlapping radiologic features [
7,
10]. The designation malignant D-TGCT is used for lesions in which a typical-appearing benign D-TGCT coexists with overtly malignant areas, or when the typical benign D-TGCT recurs as a morphologically malignant mesenchymal lesions [
7]. The criteria of malignancy for D-TCGT were defined by Bertoni et al. [
5] who reported the presence of larger mononuclear cells, featuring round or round to oval hyperchromatic nuclei sometimes showing prominent nucleoli, and presence of atypical mitotic figures. Xanthomatous cells as well as giant cells decreased in number and sometimes absent. A nodular pattern of growth was most often seen. In some cases a gradient of differentiation (zoning phenomenon) between the periphery and the central part of the nodules was observed [
5]. To our knowledge, 32 cases of malignant D-TCGT are reported in literature: 17 cases were primary malignant D-TGCT and 15 arose from a prior histologically benign lesion [
1‐
6,
9]. Seven out of these 32 cases metastasized to regional lymph node: four patients died of disease with a rapid progression (mean 22 months, range 12–41 months), two were alive with disease 17, and 36 months after the first surgical treatment, respectively and only one patient was well without disease 10 months after the first surgical treatment. None of the above described morphologic features were observed in our case. However, despite absence of histologic features of malignancy lymph node metastases developed 28 years since first surgical procedure. The only two other cases reported in the literature describe a 50-year-old man with D-TGCT in the popliteal fossa of the knee that gave rise, after two local recurrences, to inguinal lymph node metastases 56 months after the first surgical treatment [
9], and a 44-year-old male with D-TGCT in the knee joint that developed, after multiple local recurrences, lymph nodes and lung metastases 9 years after the first surgical treatment [
4]. The morphologic features of our case are similar to those previously reported by Somerhausen and Fletcher [
9] and Asano et al. [
4].
The mechanism responsible for distant metastases in D-TGCT has not been established yet [
1,
4,
7]. It has been speculated that lymph node metastases might result from passive rather than active vascular involvement by the tumor, possibly prompted by repeated surgical manipulation [
4]. A similar process has been postulated to explain lung spread in other locally aggressive neoplasm such as giant cell tumor of the bone and chondroblastoma [
11].
Regional lymph node metastases of other benign soft tissue neoplasms have also been reported [
12]. Uterine leiomyoma is an example in which the term benign metastasizing smooth muscle tumor is used to describe cytologically bland, mitotically inactive smooth muscle neoplasms occurring in the lymph nodes or lungs of patients with benign-looking uterine smooth muscle tumors [
12].
We herein report a case of conventional D-GCT of the knee that, despite lacking any morphologic features of malignancy developed bilateral loco-regional lymph-node metastasis.
Even if this represents an extremely rare occurrence, long term follow-up is strongly advised, particularly for those patients experiencing multiple local recurrences.