Cytology of mixed germ cell tumor with mediastinal metastasis.

Nonseminomatous germ cell tumors of the testis are common and are very aggressive malignant tumors. Most of the cases have metastases at the time of diagnosis, and involvement of the posterior mediastinum in particular is well known. A 33 year-old male patient presented with complaints of a swelling on the right side of the neck that had been growing for the last month, as well as shortness of breath and cough. His thoracic computed tomography (CT) showed a 1.5 cm lymph node on the anterior mediastinum and a mass of about 11 × 10 × 8 cm extending from the right lung apex to the right hilus, with regular contours and without contrast enhancement. The patient, who was given the preliminary diagnosis of a mixture metastatic bronchial tumor plus lymphoma, was subjected to transthoracic fine needle aspiration cytology (FNAC). His abdominal CT revealed a hypodense, heterogeneous and cystic necrotic mass of about 10 × 7 × 5 cm that was para-aortic at the infrarenal level (initially predicted as a lymphoma). The patient, who could not be typed in his cytopathological examination, was diagnosed with malignant epithelial tumor and was recommended to undergo a genitourinary system examination. Upon finding a high alpha fetoprotein (AFP) value, a scrotal ultra sonography was performed which showed a mass filling the right testis. Histopathological examination of the orchiectomy material resulted in the diagnosis of mixed germ cell tumor (60% mature teratoma and 40% yolk sac tumor). Even though metastatic lesions are mostly seen in the posterior mediastinum, our findings reveal that specimens obtained with FNAC from the anterior mediastinum bear discohesive, pleomorphic, small nuclei in epithelial cells with microvacoules in the cytoplasm. These cytopathological alterations in specimens from the anterior mediastinum might promote germ cell and yolk sac tumors.

Introduction

Primary tumors of the mediastinum are generally seen in the anterior mediastinum, whereas metastatic tumors usually occur in the posterior mediastinum.[1] Particularly in young males, this is due to the fact that retroperitoneal lymphatic drainage of the testis occurs along the descending thoracic aorta towards the posterior mediastinum.[2] The role of clinical and radiological findings in the differential diagnosis of tumors located in the mediastinum is highly limited and fine needle aspiration cytology (FNAC) is accepted as the standard diagnostic procedure.[34] However, the proximity of this area to the heart and major vessels decreases the usefulness of FNAC and leads to a failure to adequately describe cytomorphological characteristics of the tumors.[3]

Case Report

Our case, a 33 year-old male patient presented with the complaints of swelling on the right side of the neck that had been gradually growing for one month, as well as shortness of breath and cough. His thoracic computed tomography (CT) showed a 1.5 cm lymph node on the anterior mediastinum and a mass of about 11 × 10 × 8 cm, extending from the right lung apex to the right hilus, with regular contours and without contrast enhancement. His abdominal CT revealed a hypodense, heterogeneous, and cystic necrotic mass of about 10 × 7 × 5 cm that was para-aortic at the infrarenal level. The patient was given a preliminary diagnosis of a central bronchus tumor and the lymphoma was then subjected to transthoracic FNAC. Cytopathological examination demonstrated pleomorphic epithelial cells, either individually or in groups, having cytoplasm with vacuoles. It was noted that these cells had eccentric located nuclei containing one or more nucleoli. In light of these findings, the patient was diagnosed with a nontypeable, malignant, epithelial tumor and was directed to undergo a genitourinary examination [Figure 1]. Upon finding a high alpha fetoprotein (AFP) value (5724 IU/mL), scrotal ultra sonography (USG) was performed and showed a mass filling the whole testis on the right side. The patient was diagnosed with a mixed germ cell tumor (60% mature teratoma and 40% yolk sac tumor) by histopathological examination of the orchiectomy material.

Figure 1a and b

Microscopic appearance of pleomorphic epithelial cells from testis with yolk sac tumor characterised with microvacuolar cytoplasm (MGG, ×1000)

Discussion

Most (almost 70%) of the nonseminomatous germ cell tumors contain two or more germ cell components and are thus classified as mixed germ cell tumors.[5] Although pure germ cell tumors are extremely rare in adulthood, mixed tumors comprise about 33% of all germ cell tumors. Yolk sac tumor and teratoma are the most common components of the mixed type.[6]

More recently, Wang et al.,[7] described nonseminomatous germ cell tumors as well known, aggressive, malignant tumors of the testis. Many of the patients show metastatic disease at presentation. The usual mode of presentation in a testicular mixed germ cell tumor is testicular enlargement which is usually associated with pain. This may change depending on the tumor components, with a greater propensity for distant metastases in tumors with high-risk histology (e.g., choriocarcinoma). Pulmonary metastasis is associated with secondary hemoptysis, retroperitoneal metastasis associated with back pain, gastrointestinal system metastasis with gastrointestinal bleeding, and brain metastasis with neurological symptoms.[7] Our case presented with complaints of dyspnoea and cough associated with mediastinal metastasis. As lung and oesophageal tumors metastasise more commonly to the mediastinum, germ cell tumors of the testis are generally not considered in the differential diagnosis of mediastinal masses. A central metastatic bronchial tumor and lymphoma were initially considered in our case as well.

Depending on the sampling, it may not be possible to see all components of the mixed germ cell tumors with fine needle aspiration biopsy.[4] In a study by Shabb et al.,[3] although cystic, necrotic, and fibrotic characteristics were seen in most of the mediastinal lesions by FNAC, specimen adequacy was found to be 83% to diagnosis and diagnostic accuracy was 86%. It was reported in another study that cytological examination along with immunohistochemical analysis is quite reliable in the diagnosis of germ cell tumors.[4]

The cytological picture of yolk sac tumors shows pleomorphic epithelial cells with vacuolar cytoplasm, individually or in groups.[4] Intracytoplasmic or extracellular hyaline globules may be seen. Extracellular globules are PAS-, D-PAS- and AFP-positive. However, the presence of these globules is seen in many different neoplasms, and is therefore not diagnostic.[8] Metachromatic basal membrane material with extracellular accumulation may help the diagnosis of yolk sac tumor.[4] Papillary structures may be encountered and necrosis is common. Schiller-Duval bodies which are a characteristic finding in histological investigations are rarely found in cytological examinations.[7] Cytological diagnoses is difficult due to detection of a few number of cells by aspirations of mature teratoma; however, cytologically diagnosed few cases have been reported, previously. As cyst f luid is generally not diagnostic, repeated aspiration after evacuation may show epithelial structures, fibroblasts, or pieces of cartilage. However, signs indicating a germ cell tumor, which is the dominant component, are seen in FNAC taken from the teratoma, which is usually co-existent with other germ cell tumors of the testis. That is because germ cell tumors are highly cellular with low cohesiveness.[9]

Chemotherapy brings about an 80% cure in cases in which nonseminomatous germ cell tumors of the testis metastasise. It has been argued that removal of residual masses after chemotherapy will increase the efficacy of treatment as well as life expectancy.[10] FNAC was taken from our cases after the administration of six cures of bleomycin, etoposide, and cisplatin. A mature teratoma was diagnosed upon seeing an abundance of flat epithelial cells, some of which had lost their nuclei, on a floor of inflammatory cells in the cytopathological examination [Figure 2]. Histopathological examination of the mass removed thereafter, showed alterations associated with a mature teratoma and chemotherapy. A cytological picture of a teratoma, as in our case, might be helpful to guide surgery. Recurrence or metastasis was not found in the follow-up of our case to date (one year follow-up).

Figure 2

Multiple of flat epithelial cells belonging to teratoma component of the mixed germ cell tumor taken from the mass after chemotherapy (a - MGG, ×200, b - Pap, ×200)

In conclusion, even though metastatic lesions are mostly seen in the posterior mediastinum, our findings reveal that specimens obtained with FNAB from the anterior mediastinum bear discohesive, pleomorphic, small nuclei in epithelial cells with microvacoules in the cytoplasm. These cytopathological changes in specimens from the anterior mediastinum may be responsible in promoting germ cell and yolk sac tumors.