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Introduction

Primary thyroid lymphoma (PTL) is a rare tumor accounting only about 1% to 5% of thyroid malignant tumors [1,2] or 2 cases per million [3]. PTL is more frequent in women than men, with the ratio of occurrence ranging from 2:1 to 8:1 [4,5] and is strongly associated with Hashimoto’s thyroiditis [6].

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and its incidence has been increasing in the last few decades, with a large prevalence of small tumors [7].

PTC in patients affected by Hashimoto’s thyroiditis (HT) is a well-known event reported by literature [8]. PTC occurs mainly in women, accounts approximately 70% to 80% of all thyroid carcinomas and has an excellent prognosis [9].

The co-existence of PTC and PTL in the same patient is rare, and the present case report aims to describe the co-existence of PTC with B-Cell Lymphoma in a background of Hashimoto’s thyroiditis. Treatment and follow-up issues are also addressed.

Case Report

Here, we describe the case of a 75-year-old woman, with no family history of thyroid cancer, she referred recent painless enlargement in the left anterior side of the neck, complaining of mild and intermittent dysphagia to solid foods, she denied any voice change or dyspnea, while physical examination demonstrated an enlarged thyroid gland with a palpable, firm nodular lesion in the left lobe, moving with deglutition. She did not complain before, for thyroid disease.

Thyroid ultrasonography (US) demonstrated the growth of a hypoechogene nodule in the left lobe, measuring 38x33 mm.

Her serological tests at the admission were as following (Table 1):

US-guided fine needle aspiration (FNA) of the left -sided nodule and cytological examination revealed atypical epithelial cells concluding for indeterminate lesion (Bethesda System Category IV /THYR4).The patient underwent total thyroidectomy. Macroscopic examination revealed right thyroid lobe 11x6x5 cm, with multinodular nodules. Left thyroid lobe: 10 x5x3 cm, with a whitish nodule 33 mm.

Histology revealed thyroid follicles surrounded by aggregates of lymphoid infiltrates with germinal centers consistent with Hashimoto`s thyroiditis, diffuse monotonous lymphoid infiltrates with irregular nuclei, condensed chromatin and small nucleoli suggestive for Non Hodgkin Lymphoma. Immunohistochemistry showed immunoreactivity for CD 45, CD 20, CD79a,Bcl-6,PAX-5,of these cells, Ki-67-60%. Moreover, papillary carcinoma, folicular variant was discovered (Figure 1).

HPF-High Power Field

Hematological parameters were within the normal limits, hence, the final diagnosis of HT coexisting with papillary carcinoma and primary NHL (B-cell lineage) was made.

The patient was then treated with chemotherapy for the PTL, after she undergo radioactive iodine treatment for the PTC according to the guidelines [10].

In our knowledge, this is the first case of an Albanian patient diagnosed with the co-existing PTC and PTL in Hashimoto`s Thyroiditis.

The patient 5 weeks after surgery, TSH and Anti TG resulted respectively 69 mlU/L and 78mlU/L. In the scintigraphy there was minimal fixation in thyroid lodge. Iodine radioactive 100 mci and suppressive therapy with Levothyroxine 150 mcg/day was done in our case.

There is no need for calcium exogene. The chemotherapy consisted in six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone).

Discussion

Multiple primary cancers diagnosis is based on the international standards developed by Warren and Gates in 1932 [11].

Most of the HT patients, where thyroid architecture is usually altered by the chronic inflammation, can develop PTC which could be explained with the progressive rise in TSH levels caused by long-standing thyroiditis. TSH is a known growth factor for thyroid nodules [12,13].

On the other hand, several other papers report a better prognosis for PTC if it co-occurs with HT, which somehow could play a protective role against the aggressiveness of neoplasia: thyroid peroxidase antibodies (TPOAb) could probably drive a cytotoxic response against the inflammation [14,15]. Most of these lesions are detected incidentally suggesting the requirement of a routine follow-up in HT patients [16]. According to some studies, FNA has a sensitivity of > 90% in detecting these lesions [16,17]. FNA is the procedure of choice for evaluating thyroid nodules and selecting candidates for surgery [18]. In our case FNA showed an epithelial neoplasia.

HT, is also a risk factor for PTL, due to chronic antigenic stimulation of the lymphocytes in the setting of autoimmune thyroiditis predisposes the normal cells to lymphomatous transformation and further to a lymphoid malignancy and some alterations of some oncogenes like RET/PTC, which might regulate the early stages of tumor development; however many steps of oncogenic transformation are probably unknown [19].

Usually, the onset of PTL happens many years after the diagnosis of HT, but Watanabe et al. reported some cases of PTL discovered on average 18 months after the diagnosis of HT [20].

Approximately two-thirds of patients with co-existing PTL and PTC with HT were Non-Hodgkin B-cell lymphomas followed by MALT-Lymphoma and Small Lymphocytic Lymphoma [21].

The main treatment for PTC is surgery, but a comprehensive treatment strategy is needed for coexisting PTL and PTC. Some studies suggest that surgical resection, radiotherapy, and combined chemotherapy may be important factors in improving the prognosis of these patients [22]. Our patient after surgery and radioactive iodine therapy underwent chemotherapy.

Conclusion

Our case highlights the importance of regular follow-up in order to reach an early diagnosis: in particular, a sudden thyroid enlargement in elder patients with HT should lead physicians to consider PTC/PTL in the differential diagnosis.

Declaration of Conflicting Interest

The authors declare that there is no conflict of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.