Malignant peripheral nerve sheath tumour of thyroid: a diagnostic dilemma

Abstract

Malignant peripheral nerve sheath tumours of thyroid are rare entities that can present a diagnostic dilemma. We present the case of a patient who presented with neck mass with a history of multiple neck surgeries and airway compression. The patient’s previous histopathology was mistaken for Riedel’s thyroiditis in an outside hospital, which delayed appropriate treatment leading to suffering on part of the patient and frustration on part of the physician. We emphasise that rare malignancies should be considered in rapidly growing neck masses that are causing airway compression, and histopathology of such tumours should be reported by expert pathologists.

Background

Thyroid spindle cell lesions (T-SCLs) are rare entities. These can be primary or secondary to a metastatic disease. The primary T-SCLs include post-fine-needle aspiration spindle cell nodules of the thyroid, Riedel thyroiditis (RT), peripheral nerve sheath tumours (PNSTs), the spindle cell variants of papillary, medullary, anaplastic and squamous cell carcinoma.¹ PNSTs of the thyroid gland are divided into benign and malignant types.² Malignant peripheral nerve sheath tumour (MPNST) is a rare entity. Most common sites are proximal upper and lower extremities and the trunk.³ But it can occur in any area of the body ranging from orbit-temporal region to the very rarely parapharyngeal space.⁴ Apart from primary MPNST of thyroid, MPNSTs of other areas can present with metastatic MPNST of thyroid.⁵ We report a MPNST of the thyroid gland so that the surgeons dealing with neck masses be reminded of the possibility of this rare entity.

Case presentation

A 34-year-old woman with the history of right thyroid lobectomy for a cold nodule in right thyroid lobe at 15 years of age that was diagnosed on final histopathology as a case of RT. She underwent right thyroidectomy again at 26 years of age. After her second surgery, she had compromised airway for which emergency tracheostomy was done. The patient had multiple incidents of reinsertion and removal of tracheostomy since then, complete records were not available.

Now she presented to us with tracheostomy in place and with complaint of right neck swelling for the last 8 months that was associated with severe pain in neck referred to right arm, associated with dysphagia, dyspnoea and palpitations. The patient’s main concern was the tracheostomy tube, and she wanted it to be removed.

The neck swelling was about 7×7×7 cm on right side of neck crossing the midline to the left side; extending superiorly from the larynx to inferiorly just above the clavicle. Overlying skin was erythematous and warm. Swelling was tender to touch. On flexible laryngoscopy, right vocal cord was paralysed. She was advised further workup.

Investigations

For radiological examination, we advised a CT scan head and neck with intravenous contrast.

The CT scan showed a large heterogeneously enhancing mass was identified in the right neck region involving the glottic and infraglottic location and also partially extending to the supraglottic region. This lesion measured 75×69×63 mm in anteroposterior, transverse and craniocaudal dimensions. (figure 1A, B) It was crossing the midline and extending towards the contralateral side posteriorly. It was closely abutting the prevertebral fascia and compressing the oesophagus posteriorly; however, the intervening fat planes were intact representing no definite infiltration. Laterally, it was invading the carotid space and encasing the right common and internal carotid and abutting the right internal jugular vein as well but no definite vascular infiltration was identified. This mass was resulting in complete obstruction of the airway.

Figure 1.

(A) and (B) CT scan neck coronal view.

The CT scan findings suggested the possibility of a tumour of laryngeal origin, which was therefore considered a strong differential diagnosis.

To confirm the final diagnosis and to relieve compressive symptoms, the patient was taken to the operating room (OR) and debulking surgery was done and specimen for histopathology was obtained.

The histopathological examination revealed fragments of a cellular neoplastic lesion involving deeper soft tissue of skin-covered piece. The lesion was arranged in form of short haphazard fascicles and abundant collagen in between. The lesional cells were epithelioid and variably spindly (figure 2A, B) and showed increased mitosis (up to 12/10 HPF). Scattered lymphocytic aggregate was also noted within the lesion. No residual thyroid follicles were seen and tumour was seen replacing all normal tissue. Immunohistochemical stains S100 and CD34 (figure 3A, B) were positive, while CKAE1/AE3, TTF1, SOX10, H3K27me, anti-smooth muscle actin, desmin, HMB45 and Melan A were negative. The negative stains ruled out the possibility of anaplastic thyroid carcinoma, leiomyosarcoma, rhabdomyosarcoma and melanoma. The final diagnosis was MPNST, French Federation of Cancer Centers Sarcoma Group (FNCLCC) grade 2.

Figure 2.

(A). A cellular tumour arranged in short fascicles (H&E, 200× magnification). (B) The tumour cells are epithelioid to spindle exhibiting prominent nucleoli and increased mitoses (H&E, 400× magnification).

Figure 3.

Tumour cells showed positivity for S100 protein (A) and CD34 (B) immunohistochemical stains (400× magnification).

Differential diagnosis

The histopathology from the thyroid surgery done in 1998 showed extensive fibroblastic proliferation along with fibrous replacement of normal architecture. There was scattered focal inflammatory infiltrate composed of lymphocytes and plasma cells. These findings were consistent with RT. But the findings on the CT scan along with a history of symptoms of airway obstruction suggested the possibility of a laryngeal malignancy with possible invasion into thyroid tissue.

The clinical course of the disease can be explained with this differential diagnosis of anaplastic carcinoma that could not be ruled out on the basis of morphology alone.

The microscopic features of our tissue specimen suggested spindle cell lesion. Immunohistochemistry was used to rule out leiomyosarcoma, rhabdomyosarcoma, melanoma and anaplastic carcinoma, and therefore, the final diagnosis was MPNST.

Treatment

The findings on CT scan showed invasion of the right carotid space and encasement of the right common and internal carotids by the disease. The family was counselled that the disease cannot be resected completely and only debulking surgery can be done to improve compressive symptoms and that we might be able to reach a definite tissue diagnosis after the procedure to plan further treatment, and that the tracheostomy needs to remain in place for now. The patient was finally taken to the OR with the intension of debulking and obtaining tissue for histopathology.

Outcome and follow-up

Postoperatively, the patient’s compressive symptoms improved.

The patient did not follow up in our clinic after she was discharged from the hospital. She returned to her home town and followed the doctors there. She was last contacted on phone in February 2019, she was alive and doing well. She was started on chemotherapy by an oncologist in her city and was responding well to the treatment. The long clinical course suggests malignant transformation in a benign neurofibroma, however, residual neurofibroma areas were not seen in the slides examined.

Discussion

MPNSTs of thyroid are rare tumours. Number of cases reported in the literature is less than 30 as per our knowledge.² MPNSTs have also been recognised in the literature as neurogenic sarcomas or malignant schwannomas in the past.

MPNSTs of the thyroid can present as firm neck swelling progressively increasing in size. The symptoms can range from being asymptomatic to compressive symptoms of dyspnoea and dysphagia.^{2 6}

These tumours are usually diagnosed only after the thyroid gland has been removed and subjected to histopathology as Fine Needle Aspiration Cytology (FNAC) is usually inconclusive in these cases.⁷ And even on final histopathology, differentiating MPNSTs of thyroid from conditions like RT and anaplastic carcinoma can be very difficult.⁸

RT was the initial diagnosis on histopathology when the patient underwent thyroidectomy at 15 years of age. RT can present in a very similar manner to our patient’s presentation. It presents with a woody hard thyroid with compressive symptoms and sometimes extension into extra-thyroid tissues mimicking malignancy. FNAC is usually non-diagnostic.¹ RT has been reported to present as a massive mass encasing the great vessels of the neck and involving the recurrent laryngeal nerve leading to vocal cord palsy.⁹ Surgery is indicated in RT to relieve oesophageal and tracheal compression and should be limited to resection only for decompression.⁹ The primary treatment of RT is medical, that is with systemic corticosteroids, whereas for MNPST of thyroid the primary treatment is surgical excision.⁹ Recurrence after surgery is known.¹⁰

Sometimes MPNSTs of neck are also confused with thyroid malignancies with the diagnosis of neck malignancy becoming clear only on the operating table.¹¹

The diagnosis of MPNST is difficult to obtain even after final histopathology. As in our case, it was misdiagnosed as RT, which resulted in inadequate treatment and subsequent recurrence. This rare entity remains a diagnostic dilemma, and even after the correct diagnosis, the patients have a very poor prognosis with all possible treatment options.

Aggressive surgical resection in combination with or without radiation therapy is considered the standard for MPNSTs.^{12 13} Because of the high incidence of local recurrence, many physicians recommend adjuvant treatment in the form of radiation therapy and chemotherapy. Radiation therapy is known to improve local recurrence rates but has not shown to reduce the rate of distant metastasis.¹³ Sixty-seven per cent of the deaths are associated with distant metastasis and only 9% with local recurrence.¹³ In cases of extensive disease where complete excision is not possible due to encasement of great vessels and involvement of structures of the neck, surgical debulking is done to relieve compression of airway and great vessels similar to our case.¹⁴

Learning points.

• Malignant peripheral nerve sheath tumours (MPNSTs) of thyroid should be considered in rapidly growing thyroid masses.

• Differentiating MPNSTs from Riedell’s thyroiditis is very difficult and these specimens should be reported by expert histopathologists so that appropriate treatment should be started timely.

• Whenever the clinical course of the disease is not correlating with previous histopathology, alternative diagnosis should be considered.