Malignant Transformation of a Teratoma Presenting with Metastasis to the Hip

Case Report

Malignant Transformation of a Teratoma Presenting with Metastasis to the Hip

McCready Mariah^* and Jozef Malysz
Department of Pathology, Penn State Milton S Hershey Medical Center, USA

^*Corresponding author: McCready Mariah, Department of Pathology, Penn State Milton S Hershey Medical Center, 500 University Drive, Hershey, Pa 17033, USA

Published: 23 Nov, 2016
Cite this article as: McCready Mariah, Malysz J. Malignant Transformation of a Teratoma Presenting with Metastasis to the Hip. Ann Clin Case Rep. 2016; 1: 1184.

Abstract

Teratomas are germ cell tumors composed of cells recapitulating the three germ cell layers. Malignant transformation of a teratoma (TMT) is defined as a non-germ cell malignant tumor arising in a preexisting mature teratoma, and it is a rare occurrence. Metastases associated with malignant transformation are even more infrequent, mostly having been reported arising from gonadal teratomas. This report describes a case of a 41 year old female presenting with metastatic adenocarcinoma to the hip as the initial clinical manifestation of malignant transformation of a mediastinal teratoma, along with a review of relevant literature.

Introduction

Teratomas are germ cell tumors composed of cells recapitulating the three germ cell layers. They are most common in the gonads; however they can occur any where along the midline axis due to migration of germ cells during embryogenesis. Teratomas are the most common germ cell tumor of the mediastinum [1]. Malignant transformation of a teratoma (TMT) is defined as a non-germ cell malignant tumor arising in a preexisting mature teratoma, and it is a rare occurrence. The nongerm cell component can be a carcinoma or sarcoma. This is to be differentiated from malignant teratoma, which includes TMT, as well as teratoma with a malignant germ cell component, and a combination of germ cell and non-germ cell components [2].
Metastases associated with malignant transformation are even more infrequent, mostly having been reported arising from gonadal teratomas. This report describes a case of metastatic adenocarcinoma to the hip as the presenting manifestation of malignant transformation of a mediastinal teratoma.

Case Presentation

A 41-year old female presented with several months of right hip pain following a fall. There was no improvement with medications and physical therapy, and so the patient was evaluated by orthopedics. She was found to have an expansile lesion in the right femur, with impending fracture, as well as multiple other areas suspicious for metastatic disease. She under went an orthopedic pinning procedure, and a biopsy taken at the time of surgery demonstrated a metastatic adenocarcinoma of nonspecific phenotype (Figure 1). Immunohistochemical stains revealed the tumor to highlight with chromogen against pankeratin, polyclonal CEA, and CK 20. The neoplastic cells werenegative for CK7, as well as TTF-1, CDX2, GCDFP, ER, PR, CA19.9, CA125, and p63. These results were considered non-specific with respect to a possible primary site.
Subsequent imaging demonstrated an anterior mediastinal mass. The resection of the mass was a 4.5x2.5x2 cm unilocular cyst containing hair and sebaceous material. The cyst wall ranged in thickness from 0.1 to 1.0 cm, and areas of the lesion were completely solid, consisting of tan-white soft tissue. Microscopic examination revealed the presence of bone, smooth muscle, hair, respiratory epithelium, and intestinal epithelium, consistent with a teratoma. Within the intestinal epithelium, there were dysplastic changes, which ranged from low grade, as in a tubular adenoma, to high grade, with loss of nuclear polarity and increased nuclear pleomorphism. This latter area was associated with invasive glands present in the wall of the tumor, consistent with invasive adenocarcinoma (Figure 2). The majority of the adenocarcinoma was poorly differentiated, growing in cords, sheets, and single cell pattern. Immunohistochemical stains on the mediastinal mass revealed the tumor was positive for CK20 and CDX2 and negative for CK7 and TTF-1. Given the presence of an insitu component to the tumor, as well as the immunohistochemical staining pattern, the tumor was diagnosed as an invasive adenocarcinoma of intestinal type, arising in a mature teratoma.
The patient received chemotherapy and radiation for her metastatic disease. The last report available had her doing well at a 2 month post-operatively. The patient was subsequently lost to followup.

Figure 1

Figure 1
Poorly differentiated adenocarcinoma in right femur curettings.

Figure 2

Figure 2
Mediastinal mass with mesenchymal tissue, adenomatous tissue, and infiltrative carcinoma.

Discussion

TMT is a rare occurrence; present in 1-2% of ovarian mature teratomas [3]. The incidence in mediastinal teratomas has not been widely studied, however one large study of 322 cases of primary mediastinal germ cell tumors found it to occur in 4% of teratomatous lesions in this site [2]. The majority of cases of TMT have been reported in men [4,5]. A study of 17 male patients found that TMT localized to the testis had a better prognosis than those with disease outside the testis, including the mediastinum [5]. Several studies have found that the most common malignant non-germ cell differentiation in men with TMT was sarcomatous, followed by carcinomatous; the usual types of sarcoma included rhabdomyosarcoma, undifferentiated sarcoma, primitive neuroectodermal tumor, chondrosarcoma, and malignant peripheral nerve sheath tumor [5-8]. In contrast, the majority of females with ovarian TMT show an epithelial malignancy, with squamous cell carcinoma being the most common diagnosis [3].
Four cases of metastatic disease arising from a mediastinal TMT have been reported previously. As opposed to the current case, the metastasis in these cases were found after the primary tumor had been diagnosed or in conjunction with the primary tumor. The metastatic tumor in these cases was sarcoma in two cases and adenocarcinoma in the other half [9-12]. One paper describes that half of the patients with malignant teratomas have metastasis outside of the mediastinum, however it does not distinguish between the different types of malignant teratoma, and so the true incidence of metastatic disease in mediastinal TMT is still not known [13,14].
To the best of our knowledge, this is the first reported case of a metastasis as the presenting manifestation of a TMT arising in the mediastinum. In addition, this case is in a female, which is not widely reported in the literature. This case illustrates the need to keep a wide differential when faced with a metastatic carcinoma with an unknown primary. Had the metastatic carcinoma showed the same immunohistochemical profile as the primary tumor (CK 20 and CDX2 positive, CK7 negative), the likely interpretation would have been that of a gastrointestinal, probably colonic, primary malignancy.
This could have led down the wrong diagnostic pathway, and demonstrates a possible pitfall of depending on immunohistochemical stains to determine the primary site of a metastatic carcinoma. It is well known that the decalcification process can lead to false results with immunohistochemical staining. We submit the proposal that after the diagnosis of metastatic tumor, especially adenocarcinoma, is made, a thorough work-up, by imaging and blood work, may be the best way to discover the primary site. While immunohistochemical stains can be instrumental in narrowing down the possible primary sites of a metastatic tumor, care should be taken to not exclude other possibilities based on their results.

Case Report