Hypopharyngeal Epithelioid Malignant Schwannoma Following Treatment of Hodgkin ’ s Lymphoma

The objective of this study is to present a patient with hypopharyngeal epithelioid malignant schwannoma as a secondary malignant neoplasm following treatment with MOPP and radiotherapy. The patient, presently a 43 year-old man, was diagnosed at clinical stage III Hodgkin’s lymphoma (HL) with mixed cellularity histopathology at the age of thirteen. He had received 40 Gy radiotherapy to the neck region and MOPP + maintenance MOPP (a total 10 cycles), while malignant schwannoma developed 30 years after the treatment. Although the patient further received four cycles of ifosfamide + adriamycin combination chemotherapy, he died with progression of his malignant schwannoma six months after diagnosis.


Introduction
Developments in chemotherapy and radiotherapy have enabled most patients with HL to be cured.However, the longterm effects of anticancer treatment include an increased risk of second malignant neoplasms (SMNs).The incidence of SMNs has been extensively investigated in the treated cases of HL.A wide variety of SMNs have been reported, including leukemias, NHL and solid tumors, especially breast and thyroid cancers.
Breast cancer was the most common solid tumor with an estimated actuarial incidence in women that approached 35%

Abstract
The objective of this study is to present a patient with hypopharyngeal epithelioid malignant schwannoma as a secondary malignant neoplasm following treatment with MOPP and radiotherapy.The patient, presently a 43 year-old man, was diagnosed at clinical stage III Hodgkin's lymphoma (HL) with mixed cellularity histopathology at the age of thirteen.He had received 40 Gy radiotherapy to the neck region and MOPP + maintenance MOPP (a total 10 cycles), while malignant schwannoma developed 30 years after the treatment.Although the patient further received four cycles of ifosfamide + adriamycin combination chemotherapy, he died with progression of his malignant schwannoma six months after diagnosis.(Bhatia, et al., 1996).These SMNs occurred from 3 months to 21 years after the diagnosis of HL with leukemias, having a median latent period of 5.5 years and solid tumors 9.5 years from the time of diagnosis.The majority of SMNs developed in tissues exposed to radiotherapy (Meadows, et al., 1985).A few cases with malignant schwannoma after radiotherapy for HL were reported in the literature (Adamson, et al., 2004).

Keywords
Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue neoplasms, including 5-10% of all soft tissue sarcomas, about one-fourth to one-half occurring with neurofibromatosis 1 (NF1) (Weiss and Goldblum, 2001;Layfield, 2002).The tumor originates usually from a preexisting nerve sheath tumor (i.e.neurofibroma) or a major nerve trunk.The epithelioid variant is an unusual form of MPNSTs with a poor prognosis and represents approximately 5% of MPNSTs (Reis et al, 2002).The tumor is composed of predominantly or exclusively Schwann cells with a polygonal epithelioid appearance (Layfield, 2002).An unusual case with hypopharyngeal epithelioid-malignant schwannoma (EMPNST) following treatment for HL is presented in the following.

Case Report
A 43-year old man presented with more than two-months-history of progressive dysphagia, dyspnea and weight loss.His medical history revealed that, he was diagnosed as clinical stage III HL with mixed cellular histopathology at the age of 13 and had received 40 Gy radiotherapy to the neck region and MOPP (mustargen + oncovin + procarbazine + prednisone) + maintenance MOPP (total 10 cycles).A swan-like neck was observed 12 years later after the treatment (Figure 1).Immunohistochemically, the tumor cells were strongly positive for vimentin, S-100 protein (Figure 5), CD57 (Leu-1), and GFAP (Figure 6).On the other hand, in addition to chemoradiotherapy, genetic predisposing factors such as Li-Fraumeni syndrome, neurofibromatosis, genetic retinoblastoma have a potential for developing secondary neoplasms.It is also important to note that, genetic susceptibility may also play a role (Boice, 1996).Genomic analysis revealed alterations in cell cycle, repair, while detoxification and stress response pathways are suggested to be involved in the development of HL and in the occurrence of second neoplasias in these patients (Lorenzo et al., 2009).M'Kacher et al. ( 2007) investigated the relationship between telomere shortening in peripheral blood lymphocytes, increased chromosome abnormalities, radiation sensitivity and secondary cancers.Prior to treatment, patients with HL showed ageindependent shorter telomeres, increased spontaneous chromosomal abnormalities and increased in-vitro radiation sensitivity.After treatment, telomere shortening was associated with cytogenetic profiles characterized by the persistence of complex chromosomal rearrangement and clonal aberrations.Patients with second cancers were characterized by markedly short telomeres, the presence of complex chromosome rearrangements and increased in vitro radiation sensitivity.An intimate relationship between pretreatment telomere shortening, chromosomal instability, radiation sensitivity and occurrence of second cancers was determined in the cases (M' Kacher et al., 2007).
The age at treatment has a major effect on risk of second malignancy after therapy for HL.A cohort of 5,519 patients with HL treated during 1963-1993 was evaluated and followed-up for second malignancy.Three hundred twenty-two second malignancy occurred.Relative risks of cancers and of leukemia increased significantly with younger age at first treatment.However, absolute excess risks and cumulative risks of cancers and leukemia were greater at older ages.Although absolute excess risks are greater for older patients, relative risks of several important malignancies are much greater for patients who were treated when young (Swerdlow et al., 2000).

Conclusion
The clinicians should be aware of and alert for SMNs, especially in the patients treated with radiotherapy.Monitoring for the detection of SMNs in the survivors of childhood cancer necessitates a good collaboration between pediatric and adult oncology departments.

Figure 1 :
Figure 1: Appearance of swan-like neck

Figure 2 :
Figure 2: Axial CT image demonstrates a hypodense mass originating from the posterior hypopharyngeal wall infiltrating the esophagus, thyroid gland and trachea.Thorax CT displayed enlarged paratracheal and subcarinal lymph-nodes and multiple small metastatic lung nodules.Cervical ultrasound imaging revealed a hypervascular and heterogeneous hypoechoic soft tissue mass invading the posterior thyroid gland.Tracheal rings and upper (cervical) esophageal invasion were also visualized, especially on the left side.Under ultrasound guidance, a percutaneous fine-needle aspiration biopsy was performed from the hypopharyngeal mass.Cytopathologic examination smears revealed a hypercellular structure