Recurrent Aggressive Fibromatosis Coexisting With Papillary Carcinoma Thyroid – Case Report

Introduction

Aggressive fibromatosis (AF) also called desmoid-type fibromatosis (DTF) is a benign mesenchymal tumor characterized by the proliferation of fibroblasts and myofibroblasts with increased production of intercellular collagen. Though benign, it has an infiltrative growth pattern and tends to recur locally after surgery. The peak age for this tumor is 25–40 years of age ¹ and is more common in females. Few case reports reported an association between aggressive fibromatosis and malignancies. Apart from thyroid cancer, other malignancies reported in association with AF include breast cancer, gastric cancer, lung cancer, and cholangiocarcinoma. ² In most of these cases AF occurred at the site of surgery that was done as part of treatment for a malignant tumor except in one case where a desmoid tumor occurred concurrently in the neck with gastric scirrhous carcinoma.

Association between AF and thyroid cancer is rare. In the literature, thyroid cancer has been described to be associated with a desmoid tumor in 2 ways – Firstly and more commonly papillary thyroid cancer (PTC) with desmoid-like stroma also called PTC with nodular fasciitis, ³ and secondly, as 2 distinct tumors happening concurrently. ² Here we report a case of desmoid-type fibromatosis that occurred concurrently with papillary thyroid carcinoma.

Case discussion

A 49-year-old female with no prior co-morbidities presented to our hospital with complaints of insidious onset of painless swelling involving the front and right side of the neck in May 2019. On examination, she had 2 separate nodules palpable in the right lateral aspect of the trachea. She underwent ultrasound and magnetic resonance imaging of the neck. The findings of the ultrasound neck were as described in Table 1. There were 2 nodules in the right lobe of the thyroid gland measuring 2 × 2 × 0.4 cm and 2.1 × 1.5 × 1.5 cm, respectively. The left lobe of the thyroid gland had a single lesion measuring 1.8 × 0.5 × 0.5 cm.

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Table 1.

Findings from the ultrasound of the neck.

Feature	Right lobe posteroinferior lesion	Right lobe anteroinferior and posterosuperior	Left lobe super-anterior
Morphology	Predominantly hyperechoic with cystic component and peripheral lucent halo	A completely anechoic cystic lesion in the posterosuperior shows peripheral calcification	Predominantly iso-hyperechoic with peripheral lucent halo
Size	1.9 × 1.6 × 1.5 cm	0.4 × 0.4 × 0.3 cm and 0.4 × 0.3 × 0.2 cm	1.4 × 1.0 × 0.8 cm
Hetero-echoic solid component	No	No	No
Micro lobulations	No	No	No
Microcalcifications	No	No	No
Taller than wider	No	No	No
Intralesional vascularity	No	No	No
TIRADS category	2	2 (Colloid type-II)	2

Apart from the thyroid nodules, the patient had a separate swelling in the posterior cervical space of the right side of the neck measuring 4 × 3 × 2.7 cm MRI neck characteristics of this swelling are shown in Figure 1. This was an ill-defined heterogeneous T2 hyperintense and T1 isointense mass with intense enhancement and minimal restriction. Fat planes were lost with prevertebral muscles with no intervertebral foraminal extension.OPEN IN VIEWER

FNAC was done from the posteroinferior nodule in the right lobe of the thyroid gland and it was suggestive of thyroid neoplasm. A biopsy of the swelling in the posterior cervical space was suggestive of aggressive fibromatosis. We did a CTNNB1 mutation testing in the tumor sample and was negative.

She underwent a total thyroidectomy and excision of the lesion in August 2019. Post-operative histopathology findings from the left thyroid nodule were suggestive of papillary thyroid carcinoma. One in the right thyroid lobe was suggestive of a follicular variant of papillary thyroid carcinoma. A swelling separate from the thyroid gland was excised and was suggestive of desmoid-type fibromatosis. According to the ATA classification, the patient had a low-risk disease. Following surgery, she received radio-Iodine therapy with 50 mCi 131I and started on thyroid supplementation. Post-treatment serum thyroglobulin level was <0.2 ng/mL. The serum thyroglobulin level was within the recommended levels. The fibromatosis lesion was completely excised during the same surgery.

Because there was no residual disease, we planned to keep the patient under close observation and follow up with serial thyroglobulin levels monitoring. Post 1 year following surgery she developed recurrent neck swelling along with restricted movements of the neck and pain in the swelling. MRI imaging of the neck showed a 3 × 5 cm mass in the posterior cervical space. There was no residual disease in the thyroid bed. The serum thyroglobulin level was not raised. We did a biopsy of the lesion and it was suggestive of fibromatosis. We started her on tablet sorafenib 200 mg OD. The patient had significant symptomatic improvement after 3 months of starting sorafenib. Serial images done at the interval of 3 months showed stable disease. (Figure 2) The patient is currently on sorafenib for more than 12 months and clinically doing well without any disease-related symptoms or sorafenib toxicity.OPEN IN VIEWER

Discussion

This is the second case reported in the literature that described the concurrent occurrence of the desmoid tumor with malignancy. Here, we like to mention that the more common association between desmoid tumor and thyroid carcinoma is called thyroid carcinoma with desmoid type fibromatosis where conventional papillary thyroid carcinoma is admixed with prominent mesenchymal proliferation. The desmoid tumor is not distinct from papillary thyroid carcinoma in these cases. This tumor is also called by name papillary thyroid carcinoma with nodular fasciitis. Both these terms namely, papillary thyroid carcinoma (PTC) with nodular fasciitis-like stroma or PTC with fibromatosis-like stroma are used interchangeably. According to the World Health Organization (WHO) classification of Tumors of Endocrine Organs, these two histological subtypes of papillary thyroid carcinoma are synonyms. The mesenchymal component in this tumor will have typical aberrant nuclear and cytoplasmic immunoreactivity for β-catenin and harbors a heterozygous somatic activating mutation in the corresponding CTNNB1 gene. ³

Our case is different from the more common type of papillary thyroid carcinoma with desmoid type fibromatosis in that patient had a distinct tumor separate from thyroid cancer. The only other case reported in the literature is by Yao Li et al., who reported a case of a 52-years female who had concurrent papillary thyroid carcinoma and concurrent desmoid tumor in the neck. Our case had similar clinical features like age at diagnosis which is 49 years and desmoid tumor location.

Aggressive fibromatosis (AF) usually occurs sporadically. A β-catenin mutation is seen in 65%–85% of sporadic desmoid tumor cases. Mutation inhibits phosphorylation of β-catenin, which protects β-catenin from degradation by the APC complex, resulting in nuclear accumulation of β-catenin, where it binds to TCF/LEF family of transcription factors and turns on the number of target genes. ⁴ β-catenin mutation is also detected in the case of papillary thyroid carcinoma with desmoid-type fibromatosis. However, the β-catenin mutation was not detected in our case. In a similar case of distinct desmid tumor and papillary thyroid carcinoma mentioned earlier, β-catenin was positive by IHC and they did not do β-catenin mutation testing in the tumor.

Also, unlike the only previous case reported, our patient had recurrent desmoid tumor following initial resection. In the case reported by Yao Li et al. ² the desmoid tumor was managed with resection. In our case also patient had tumor resection done with thyroidectomy. Our patient had a recurrence after 1 year of surgery. Due to the locally invasive nature of desmoid tumors, surgery involves extensive local resection along with skin grafting. Even after extensive surgery recurrence rate is higher following surgery. The risk of recurrence is independent of the surgical margin. ⁵ Current treatment strategy involves observation and medical management at progression unless a life-threatening condition exists.

Medical management has recently become the standard treatment for recurrent fibromatosis. In symptomatic disease, tyrosine kinase inhibitors and chemotherapy have become the most often used regimens. In a trial by Mirnal M et al. ⁶ sorafenib showed an overall objective response rate of 33% in the sorafenib group compared to 20% in the placebo group. The 2-year progression-free rate was 81% in the sorafenib group as compared to 36% in the placebo. We used sorafenib in the management of recurrent desmoid tumors in our patients. There was an adequate clinical response. The patient had complete relief in pain and radiologically there was a decrease in hyperintensity in T2 images of the tumor. The patient is tolerating sorafenib well for more than 1 year at the time of reporting this case.

Conclusion

We report a rare case of desmoid-type fibromatosis co-existent with papillary thyroid carcinoma as a distinct separate tumor. We could treat the recurrent desmoid tumor with a lower dose of sorafenib than recommended with good tolerability and disease control.