THE DOUBLE EDGE SWORD STEROID FACILITATED DIAGNOSIS OF PRIMARY THYROID LYMPHOMA

Mudassir Ali (1), Phillip Mounter (2), Vivek Shanker (3), Shafie Kamaruddin (1)

1 Endocrinology, County Durham & Darlington Foundation Trust, DL3 6HX

2 Haematology, County Durham & Darlington Foundation Trust, DL3 6HX

3 ENT Surgery, County Durham & Darlington Foundation Trust, DL3 6HX

Introduction

Primary thyroid lymphoma (PTL) is a rare cause of malignancy, accounting for < 5% of thyroid malignancies and < 2% of extra-nodal lymphomas. Women are more commonly affected than men and typically present in the sixth or seventh decade of life. Most thyroid lymphomas are non-Hodgkin’s lymphomas of B-cell origin. Patients with Hashimoto’s thyroiditis are at greater risk for developing PTL. Early diagnosis is important as treatment and prognosis of PTL depend upon the histology and stage of the tumour at diagnosis. (1)(2)

Unlike other thyroid cancers this is not associated with radiation exposure. (1)

We report a rare case of primary thyroid lymphoma in a patient presenting with a rapidly enlarging thyroid goitre highly suspicious of anaplastic thyroid carcinoma posing as a diagnostic histological challenge due to underlying Hashimoto’s thyroiditis which was unmasked after a short course of oral steroids.

Case description

A 51 years old female was referred by GP with increasing painless swelling over the right side of neck over a period of 3 weeks (Nov 2018). She did not have any difficulty in swallowing or breathing. There was no history of any weight loss or night sweats. Her TSH was 9.57 mIU/L with a normal free T3, T4 and positive thyroid peroxidase antibody suggestive of subclinical hypothyroidism secondary to Hashimoto’s thyroiditis. The scan showed a large mass on the right side of the thyroid gland measuring 4.8 x 4.6 x 3.7 cm, encasing the common carotid artery with complete compression and thrombosis of the internal jugular vein. There were multiple lymph nodes on the right side of neck.

Initial imaging was highly suspicious of anaplastic thyroid cancer which carries a poor prognosis. She was referred to our thyroid surgeon and had a core biopsy which unexpectedly only showed inflammatory/reactive picture with no clear signs of malignancy. She was given oral steroids for 4 days, which decreased the size of the neck swelling followed by a core biopsy (Dec 2018), which was inconclusive. She later had another biopsy in Jan 2019 and the resultant histology showed clearance of the inflammatory picture whilst unravelling histological features of a high grade lymphoma. A diagnosis of B cell lymphoma was confirmed by the Haematologist. From a haematological perspective, giving steroids prior to diagnostic biopsy for suspected lymphoma is strongly discouraged as steroids can partially treat high-grade lymphomas, induce necrosis and render the biopsy uninterpretable.

She later had PET CT which showed bulky thyroid and bilateral cervical and right supra-clavicular lymphadenopathy. Case was discussed in the MDT and outcome was to start her on R-CHOP regimen. She had recently completed x 6 cycles of chemotherapy and a repeat PET-CT scan 3 weeks post chemotherapy (17/6/19), which reported thyroid to be of normal size but with residual FDG uptake. She then had consolidation radiotherapy based on MDT

decision, which was completed on 16th August 2019. She had a repeat PET CT 12 weeks post radiotherapy (13/11/19), which reported as Lymphoma in complete metabolic remission, diffuse symmetrical bilateral FDG uptake, felt to be more suggestive of thyroiditis. Clinically she remains asymptomatic, tolerated the chemotherapy and radiotherapy well and is being followed up in Haematology clinic every 3 months. There are no cases reported so far, where steroid helped in unmasking the actual diagnosis. A case reported in Journal of Thyroid disorders and Therapy (3) where a symptomatic patient received a course of steroid after open surgical biopsy, and had dramatic resolution with an eventual diagnosis of PTL.

Conclusion

This case highlights the unexpected paradoxical role of steroids in unmasking the histopathological diagnostic dilemma of PTL which carries a more favourable prognosis compared to anaplastic thyroid carcinoma whilst shrinking the mass. This earlier diagnosis will have an impact on overall prognosis of the disease. The British Thyroid Association guidelines for thyroid cancer highlights the need for high index of suspicion for PTL where a core or open biopsy is required to make a diagnosis at an early stage (2). However, this case highlights without the use of steroids it could have been difficult to interpret the histological findings to make a correct diagnosis.

Key points:

– In a rapidly enlarging neck mass, always think about PTL versus anaplastic cancer

– Use of steroid is controversial, but it could help in making diagnosis of PTL earlier, which ultimately changes management plan.

– Research and evidence is required regarding use of steroids in challenging cases of thyroid cancer, where diagnosis is in dilemma.

References:

1. Stein SA, Wartofsky L. Primary Thyroid Lymphoma: A Clinical Review. J Clin Endocrinol Metab [Internet]. 2013 Aug;98(8):3131–8. Available from:https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2013-1428

2. Perros P, Boelaert K, Colley S, Evans C, Evans RM, Gerrard BA G, et al. Guidelines for the management of thyroid cancer. Clin Endocrinol (Oxf) [Internet]. 2014 Jul;81:1–122. Available from: http://doi.wiley.com/10.1111/cen.12515

3. Hafez MT, Nason RW. Proper Management of Rapidly Growing Large B-Cell Primary Thyroid Lymphoma, Case Report and Review of Literature. J Thyroid Disord Ther 2017;06. doi:10.4172/2167-7948.1000210.

Thyroid. Jun 2016, 26(6): 765-769

BACKGROUND:

There is little information regarding the natural history of subclinical hyperthyroidism (SH) due to Graves’ disease (GD).

METHODS:

A prospective analysis was conducted of patients with SH due to GD between 2007 and 2013 with at least 12 months of follow-up. SH was diagnosed if serum thyrotropin (TSH) was below the laboratory reference range (0.4-4.0 mIU/L) and when thyroid hormones were normal. GD was confirmed by either a raised TSH receptor antibody (TRAb) level or uniform uptake on Technetium scan.

RESULTS:

Forty-four patients (89% female, 16% current smokers, and 5% with active Graves’ orbitopathy) were diagnosed with SH due to GD. Over the follow-up period (median 32 months), approximately one third (34%) of the cohort progressed to overt hyperthyroidism, one third (34%) normalized their thyroid function, slightly less than one third (30%) remained in the SH state, while one person became hypothyroid. Multivariate regression analysis showed that older age and positive antithyroid peroxidase (TPO) antibody status had a positive association with risk of progression to overt hyperthyroidism, with hazard ratios of 1.06 ([confidence interval (CI) 1.02-1.10], p < 0.01) per year and 10.15 ([CI 1.83-56.23], p < 0.01), respectively, independent of other risk factors including, smoking, TRAb levels at diagnosis, and sex.

CONCLUSIONS:

A third each of patients with SH due to GD progress, normalize, or remain in the SH state. Older people and those with positive anti-TPO antibodies have a higher risk of progression of the disease. These novel data need to be verified and confirmed in larger cohorts and over longer periods of follow-up.