Alveolar soft part sarcoma of the thyroid gland in a child☆

1. Introduction 

Sarcomas are malignant tumors that arise predominantly from the embryonic mesoderm and can be categorized as arising primarily from the bone or from the soft tissues. The World Health Organization has defined nearly 50 soft tissue sarcoma histologic subtypes [4]. Soft tissue sarcomas are relatively rare in children with less than 1000 new cases diagnosed per year in the United States. These include rhabdomyosarcomas (RMS) and non-RMS soft tissue sarcomas (NRSTS). RMS is the most common soft tissue sarcoma in children 14 years old or younger, and NRSTS is more common in adolescents and young adults. Infants may also get NRSTS, but their tumors constitute a distinctive set of histologies not seen in adolescents. Radiation may play a role in the local therapy of some pediatric soft tissue sarcomas, and chemotherapy is reserved for the subset of NRSTS that are high grade or unresectable. Surgery is the mainstay of treatment for NRSTS and its goal is to completely remove the mass with a margin of surrounding normal tissue.

Alveolar soft part sarcoma (ASPS) is a form of NRSTS and occurs with an incidence of 1 per 10 million for patients less than 20 years old. In a series of 7765 patients evaluated at The University of Texas M.D. Anderson Cancer Center between 1990 and 2003, less than 1% of cases of soft tissue sarcomas were of the ASPS histologic type [4]. ASPS accounts for less than 0.1% of sarcomas of the head and neck [5]. ASPS has a characteristic chromosomal alteration involving a translocation, t(X;17), especially at chromosome band 17q25 [1], [2]. The fusion gene seen in these tumors is ASPL-TFE3. The National Cancer Institute has created a histopathologic grading system of soft tissue tumors which places ASPS into the highest grade (III). Histologic grading remains the foundation of clinical decision making for most sarcomas. ASPS principally affects adolescents and young adults with a slight female predominance. Usually this tumor presents as a slow-growing, painless mass which may be apparent for months to years before the patient seeks medical attention. Unfortunately, metastatic disease to the lung or brain sometimes indicates the presence of an occult sarcoma [2].

Microscopically, ASPS shows a distinctive nested or organoid arrangement of large, polygonal cells with eosinophilic cytoplasm. The nests of cells are separated by thin-walled vascular channels. The tumor cells have distinct cell borders with eccentrically placed nuclei and prominent nucleoli. Periodic acid-Schiff stain highlights intracytoplasmic glycogen and emphasizes elongated and rhomboid-shaped crystalline structures within the cytoplasm, which are attributed to the ASPL-TFE fusion [2].

2. Case report 

The patient is an African-American male who was born at full gestation with an uneventful perinatal period. The patient was diagnosed with laryngomalacia and laryngeal webs by an outside ENT at the age of 6 months, for which he underwent true vocal cord web lysis. He had been lost to follow up. At age 2 years and 11 months, he was at his usual activity level until one evening he coughed up a small amount of phlegm and went to bathroom to spit it out. He then reported the inability to breathe and collapsed. The patient was transported to the nearest children's hospital. His mother reported that he had experienced an exacerbation of reactive airway disease 2–3 days before this episode. The mother had administered nebulization treatments and oral steroids at home during that time. The infant did not have any fevers. He was started on Solumedrol, albuterol, Pulmicort, and Singulair. He required increased supplemental vaporized oxygen.

Given his history of laryngomalacia and laryngeal webs, imaging was ordered that included airway fluoroscopy, barium swallow, and CT of the chest and neck. Neck CT showed a 3cm×3cm mass arising in the right lobe of the thyroid gland and extending cephalically 4.5cm along the right lateral border of the trachea (Fig. 1). The trachea was effaced and displaced anteriorly and to the left. The mass was positioned adjacent to the esophagus and extended superiorly almost to the pyriform sinus. There were multiple small (<1cm) lymph nodes in bilateral posterior cervical triangles. CT chest showed multiple bilateral pulmonary nodules in all lobes of the lung (Fig. 2).

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Fig. 1. CT of the neck showing right thyroid mass.

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Fig. 2. CT of the chest showing multiple pulmonary nodules.

He underwent direct laryngoscopy and bronchoscopy, which showed compression of the right lateral and anterior tracheal walls by a large paratracheal mass approximately 1cm below the true vocal cords. Tracheostomy was performed at that time, and the right thyroid mass showed a cobblestone appearance. The right thyroid mass was biopsied and showed alveolar soft part sarcoma. Two days later, the patient underwent right thyroid lobectomy, isthmusectomy, and excision of paralaryngeal and paratracheal tissue. The right recurrent laryngeal nerve was sacrificed, given its intimate involvement with the tumor. A vein traveling from the posterior aspect of the gland posteriorly to the prevertebral muscles had palpable material within its lumen which was felt to most likely be tumor embolus. The tumor at time of excision measured 5.5cm×4.0cm×2.5cm. Pathology returned showing soft part alveolar sarcoma in the right middle thyroid vein and the right thyroid lobe with positive margins and extensive lymphovascular permeation seen. Immunohistochemistry showed positivity for CD 99, Desmin, and HMB 45 (Table 1). The positivity for HMB45 was felt to be artifactual and related to EDTA in the immunostaining process and not true positivity. Chromosome analysis showed 46 X,Y karyotype. Twenty metaphases were counted and all but one were normal. The metaphase that contained 45 chromosomes was interpreted to be derived from the normal clone through random loss.

Table 1. Immunohistochemistry supporting ASPS.

	CD 99 (013)	Strong, diffuse, membranous
	Desmin	Strong, focal, cytoplasmic
	HMB 45	Faint, focal, cytoplasmic
	Cytokeratin AE1/AE3	Negative
	CD34	Negative
	Muscle specific actin	Negative
	Alpha fetoprotein	Negative
	Synaptophysin	Negative
	S-100	Negative
	Vimentin	Negative
	Myogenin	Negative
	MyoD1	Negative

Treatment options including palliative chemotherapy, phase I trial, or no therapy were discussed with the family. They elected no treatment and the patient was placed on hospice care. G tube was placed, but the patient did well with oral feeds and never required his G tube. He presented to the ENT clinic for monthly tracheostomy tube changes, as the tumor was wrapping around the tracheostomy tube and this was not felt safe for changing at home. The patient showed remarkable level of activity and even entered preschool. Repeat CT of the neck 5 months later showed the tumor occluding the suprastomal trachea and extending inferiorly to the tracheostomy tube. The mass invaded the tissues posterior to the trachea, abutted the left thyroid lobe, and extended posterior to the right common carotid and jugular vein. Nine and one half months postoperatively, CT scan showed effacement of the pyriform sinuses and hypopharynx. The number and size of involved level II–IV nodes had increased. One year post diagnosis, chest imaging showed marked increase in overall size, number, and extent of metastatic pulmonary nodules. The patient continued to do well clinically until 2 years after diagnosis, at which time he passed away at home with his family. He died 4 days prior to his fifth birthday.

3. Discussion 

In previously reported cases, ASPS was shown to arise primarily in the deep soft tissues of the lower extremity (44%), particularly the anterior thigh and the buttock, followed by the chest and abdominal wall [2], [5]. In children, ASPS has a tendency for the head and neck region (27%), with 41% of those cases involving the orbit and 25% occurring in the tongue. The tongue is the most common site of involvement in infants and children [7], [8], [10]. Cases of ASPS of the larynx, buccal space, and paravertebral space have also been described [6]. This is the first case of primary ASPS of the thyroid gland.

ASPS has a poor long-term survival, with a better prognosis in children than adults. Lieberman reported data from over 60 years showing median survival time of 3 years if metastatic disease was present at the time of diagnosis and 11 years if there was no metastatic disease at presentation. He reported a 5-year survival rate of 60%, a 10-year survival rate of 38%, and a 20-year survival rate of only 15% for patients presenting without metastatic disease [3]. These patients usually died of metastases to vital organs, with the lungs being the most common site [2]. Lorigan reported that lung metastases were present in 42–65% of patients at presentation [9]. Metastases were also noted to the brain and bone [3]. Lymphatic metastases were present in only 10% of reported cases [9]. Our patient had metastatic disease present at the time of diagnosis, survived 2 years after diagnosis, and died with metastases to the lungs.

4. Conclusion 

After reviewing English language literature, this is the first reported case of primary ASPS of the thyroid gland. ASPS should be included in the differential diagnosis of thyroid tumors in which a large mass is seen to involve the thyroid and compress the trachea in a child.