Mediastinal Mature Teratoma With Malignant Transformation to Colorectal-Type Adenocarcinoma

Abstract

Mature teratomas represent 5% to 10% of all mediastinal tumors, and malignant transformation is exceedingly rare. A 51-year-old man with newly diagnosed prostate cancer was incidentally found to have an anterior mediastinal mass suggestive of a teratoma on staging workup. Robotic thymectomy was performed, revealing a mature teratoma with malignant transformation to colorectal-type adenocarcinoma. Circulating tumor DNA was negative for measurable residual disease. The patient was managed with surveillance, including serial imaging and tumor markers.

Mature teratomas are benign, primary germ cell neoplasms composed of well-differentiated tissue derived from all 3 embryonic germ layers: ectoderm, mesoderm, and endoderm. Although they most commonly arise in the gonads, mature teratomas occurring in extragonadal sites, including the cranial cavity, retroperitoneum, and mediastinum, have been described.¹ Within the mediastinum, teratomas are the most frequent germ cell tumor (GCT) subtype, accounting for ∼80% of surgically resected mediastinal GCTs.²

Despite their generally benign behavior, mature teratomas can rarely harbor malignant features in the form of an immature teratoma, incorporation of other GCT components, or transformation into a somatic-type malignancy.^1,3 Teratoma with malignant transformation is exceedingly rare and is defined by the emergence of a non–germ cell malignancy within a preexisting teratoma.⁴ These malignant transformations are postulated to be either therapy-induced, occurring in patients previously treated with chemotherapy or radiotherapy, or spontaneously occurring in unexposed patients.⁵

Moran and Suster¹ have proposed a classification system for teratomas with malignant transformation, subcategorizing them into 4 groups based on the malignant elements present: (I) with another germ cell tumor, (II) with a non–germ cell epithelial component, (III) with a malignant mesenchymal component, and (IV) with mixed malignant histology. Carcinomatous transformation within mediastinal teratomas is particularly unusual, with colorectal-type adenocarcinoma described only in isolated case reports. We present a patient with an incidentally found anterior mediastinal mass ultimately diagnosed as a mature teratoma with transformation to colorectal-type adenocarcinoma and review relevant diagnostic, therapeutic, and prognostic considerations.

A 51-year-old healthy man with newly diagnosed prostate cancer, but no prior history of colorectal adenocarcinoma, was referred for evaluation of an anterior mediastinal mass incidentally discovered on staging prostate-specific membrane antigen positron emission tomography. Chest computed tomography (CT) revealed a 6.2- × 5.2- × 6.0-cm encapsulated anterior mediastinal lesion containing peripheral calcifications, without invasion of adjacent structures (Figure 1). Results of further laboratory evaluations, including acetylcholine receptor antibodies, α-fetoprotein, β-human chorionic gonadotropin, complete blood count, and thyroid studies, were unremarkable. A core biopsy specimen showed respiratory epithelium associated with squamous metaplasia, suggestive of, but not diagnostic for, teratoma.

Figure 1.

(A) Chest computed tomography demonstrates a 6.2- × 5.2- × 6.0-cm anterior mediastinal mass with areas of central heterogenous low attenuation and peripheral calcification. (B) The mass abuts the pericardium and exerts a mild mass effect on the main pulmonary artery.

The patient underwent radical prostatectomy, with pathology confirming organ-confined prostate adenocarcinoma without nodal involvement, and no adjuvant therapy was recommended.

After recovery, left-sided robotic thymectomy was performed using the da Vinci Xi surgical system (Intuitive Surgical). Intraoperatively, the mass was found to be encapsulated, abutting, but not invading the left phrenic nerve. There was no gross extension into mediastinal fat, pericardium, or other adjacent structures (Figure 2). His postoperative course was uncomplicated, and the patient was discharged the following day.

Figure 2.

Intraoperative images demonstrate a (A) firm, encapsulated mediastinal mass (B) abutting the left phrenic nerve without gross invasion (black arrow). (C) Resection bed shows preserved tissue margins surrounding the pericardium, brachiocephalic vein, and phrenic nerve (white arrows).

Gross pathologic examination revealed a well-encapsulated, partially cystic mass, measuring 6.1 cm in maximum diameter. Microscopically, the lesion consisted predominantly of mature teratomatous elements, including bronchial-type respiratory epithelium, cartilage, smooth muscle, nerve tissue, and submucosal glands.

Importantly, a distinct component of malignant adenocarcinoma was identified. This malignant population consisted of complex glandular structures with marked cytologic atypia, nuclear pleomorphism, and mitotic activity (Figures 3A, 3B). Immunohistochemistry was strongly positive for caudal type homeobox 2 (CDX2) and negative for thyroid transcription factor-1 (TTF-1) and homeobox protein Nkx-3.1 (NKX3.1) in the malignant component, consistent with colorectal-type adenocarcinoma. In contrast, the benign respiratory epithelium was weakly positive for TTF-1 and negative for CDX2 and NKX3.1 (Figures 3C, 3D). The surrounding thymic tissue appeared unremarkable. There was no evidence of immature teratomatous elements, additional GCT subtypes, or metastatic prostate carcinoma. All margins were negative for neoplasm.

Figure 3.

(A) Benign, mature, disorganized bronchial tissues comprising respiratory, pseudostratified, ciliated, columnar epithelium with admixed goblet cells overlying mature hyaline cartilage. (Hematoxylin & eosin [H&E]; original magnification ×400.) (B) Malignant, gland-forming, adenocarcinoma. (H&E; original magnification ×400.) (C) Transition from benign respiratory epithelium (right) to malignant epithelium (left). (H&E; original magnification ×200.) (D) Benign epithelium is negative for caudal type homeobox 2 (CDX2) by immunohistochemistry, and the malignant epithelium is positive for CDX2. (3,3′-Diaminobenzidine chromogen with hematoxylin counterstain; original magnification ×200.)

The final diagnosis was mature teratoma with associated somatic-type malignancy resembling colorectal-type adenocarcinoma (stage I: Moran and Suster proposed clinical staging for mediastinal GCT).¹ Circulating tumor DNA (ctDNA) using a measurable residual disease assay was undetectable. Given negative surgical margins, the absence of metastatic disease, and undetectable ctDNA, the patient was managed with surveillance, including serial imaging (CT chest/abdomen/pelvis) and tumor markers (α-fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase).

Comment

Mature teratomas represent 5% to 10% of all mediastinal tumors,² and malignant transformation is exceedingly rare.^2,3 According to the World Health Organization, teratoma with somatic-type malignancy is defined by a non–germ cell malignant component arising within a teratoma itself.⁴ Although sarcomas are the most frequently reported malignancies in these tumors, carcinomas, particularly adenocarcinomas, are rarely described.²

Somatic-type malignancies arising in teratomas are thought to occur by malignant transformation of preexisting mature tissue elements or through malignant differentiation of totipotent germ cells.⁶ The process is poorly understood, but several risk factors have been proposed, including older age, long-standing teratomas, and tumor size >10 cm.^2,3 Transformation has also been described in patients who received chemotherapy, suggesting potential treatment-related mechanisms.⁵

Radiologically, cystic teratomas typically appear as encapsulated, heterogenous masses. Focal wall thickening may raise suspicion for malignant transformation.^7,8 Surgery remains the cornerstone of treatment. Prognosis is generally poor in unresectable or metastatic disease, with median survival rates of <1 year.³ Radical resection without rupture offers the best outcomes, whereas incomplete excision is associated with recurrence.² Conventional chemotherapy is usually ineffective, although histology-directed regimens, such as fluoropyrimidines for adenocarcinoma, have shown oncologic benefit in select cases.⁶

This case highlights the importance of meticulous surgical technique and comprehensive histopathologic assessment of mediastinal teratomas, even when malignancy is not initially suspected. The case reported here incorporated ctDNA assessment to inform both adjuvant treatment decisions and postoperative surveillance and provides preliminary, real-world insight into a potentially valuable adjunct for risk stratification and follow-up in these uncommon cases.