Original Article

Primary Lymphoma of Thyroid

Seema Khanna¹, Ram Niwas Meena¹, Mohan Kumar², Rahul Khanna¹

• ¹Department of Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, India
• ²Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, India

• Submitted: December 19, 2011;
• Accepted December 26, 2011
• Published: January 2, 2012

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction:

Primary lymphoma of the thyroid accounts for 5% of all thyroid malignancies [1]. It differs greatly from other thyroid neoplasms with regards to the diagnostic and therapeutic approach.

Patients and Methods:

We treated 12 patients with thyroid lymphoma over a 10 years period. The commonest presentation was thyroid mass with associated cervical lymph nodes or subcutaneous nodules. More than half the patients had hypothyroidism which was subclinical and detected on hormonal assay. The commonest histological variant was non Hodgkin’s lymphoma of B-cell origin followed by Mucosa Associated Lymphoid Tissue (MALT) cell lymphoma. The main stay of treatment was surgery with adjuvant chemotherapy. At 3 years follow-up 9 patients (75%) were recurrence free.

Discussion:

Lymphoma of the thyroid develops in a background of Hashimoto’s disease or chronic lymphocytic thyroiditis. Most patients have associated subclinical hypothyroidism. Fine Needle Aspiration Cytology (FNAC) is of limited help in diagnosis as it may not distinguish thyroid lymphoma from chronic lymphocytic thyroiditis or a follicular neoplasm. Histologically it is usually non Hodgkin’s lymphoma of B cell variety although 10% cases may be of MALT cell origin. Chemotherapy is the sheet anchor of treatment with surgery and/or radiotherapy playing an adjuvant role. Prognosis is usually excellent and 100% survival at 5 years have been reported.

Introduction

Primary lymphoma of the thyroid accounts for 5% of all thyroid malignancies [1]. The presentation is usually insidious and there might be preexisting thyroid disease which might confound the diagnosis. Unlike in other thyroid neoplasm where FNAC is the sheet anchor of diagnosis, the cytological features in thyroid lymphoma are confusing. Treatment is multimodality and depends on the facilities and infrastructure available to the treating physician. We review our experience of treating 12 patients with lymphoma of the thyroid. Primary thyroid lymphoma differs from other site non Hodgkin’s lymphomas by clinical presentation, radiological evaluation and histopathological confirmation. Only isolated involvement of thyroid is hallmark of diagnosing primary thyroid lymphoma and differentiating it from other site non Hodgkin’s lymphomas with thyroid secondary. Radiological evaluation might be useful to establish the diagnosis. Hence, clinical examination for any other swellings and ultrasound as well as computed tomography (CT) scan of any other mass settle the diagnosis of primary thyroid lymphoma. Histopathology is final tool for diagnosis and ruling out other conditions that mimic nonHodgkin's lymphomas and Hashimoto thyroiditis.

Material & Methods

The present study was carried out over a 10 years period from 1995 to 2005 at the Department of Surgery, Banaras Hindu University. Retrospective analysis of the records of all patients with thyroid lymphoma treated during this period was undertaken. The records were studied with respect to the clinical presentation, diagnostic approach and the therapeutic decisions taken. A median follow-up of 36 months was available for these patients.

Observations

Over a 10 years period from 1995 to 2005, 12 cases of the lymphoma of the thyroid were identified in the department of Surgery (Table 1). During the same period, 204 patients with thyroid cancer were treated. OF which, papillary carcinoma comprised 142 cases (70%), follicular carcinoma in 31 cases (15%), anaplastic carcinoma in 8 cases( 4%) and metastatic carcinoma in 11 cases(5%). Thyroid lymphomas constituted 6% of all malignant thyroid neoplasms. The mean age of patients was 52 years and the male: female ratio was 1:5. The clinical presentation of these patients was variable. Isolated thyroid mass was seen in 3 patients, thyroid mass with cervical lymphadenopathy was found in 6 patients and 3 patients had thyroid mass with multiple subcutaneous nodules (Table 2). The lesion in the thyroid was confined to one lobe in 8 patients while 4 patients had diffuse involvement of the thyroid gland. Clinically only 1 patient was hypothyroid but on thyroid hormone assay 7 patients were found to have sub clinical evidence of hypothyroidism (increased TSH and normal T3 and T4).

Table 1: Patient profile of thyroid lymphoma cases

Parameters	No of cases
Total thyroid cancer	204
Thyroid lymphoma	12
M: F ratio	1:5
Mean age	52 years
Period of study	1995 to 2005

Table 2: Spectrum of clinical presentation of thyroid lymphoma. (n=12)

Presentation	No of cases (%)
Isolated thyroid mass	3 (25%)
Thyroid mass with cervical lymphadenopathy	6(50%)
Thyroid mass with multiple subcutaneous nodules	3(25%)
Confined to 1 lobe	8(66%)
Diffuse involvement of thyroid	4(33%)
Clinically hypothyroid	1(8%)
Biochemically hypothyroid	7(58%)

On FNAC from the thyroidal mass, 3 patients were diagnosed as thyroid lymphoma, 5 had the diagnosis of chronic lymphocytic thyroiditis (raised thyroglobulin in 3 cases and raised thyroperoxidase in 2 cases) and 4 were diagnosed as follicular neoplasm (Table 3).

Total thyroidectomy was performed in 7 patients. These were the patients who had either diffuse involvement of the thyroid gland or had a diagnosis of a follicular neoplasm on FNAC. The remaining 5 patients underwent hemithyroidectomy. Modified neck dissection removing levels II, III and IV of cervical lymph nodes was done in 6 patients in whom they were involved.

On histological examination, 10 patients had a diagnosis of non Hodgkin’s lymphoma of B cell variety (7 patients with diffuse large B cell lymphoma and 3 patients with follicular lymphoma). The remaining 2 patients were diagnosed as extranodal marginal zone lymphoma (MALT cell origin).

After surgery and final histological diagnosis all patients received 6 cycles of chemotherapy consisting of cyclophosphamide, adriamycin, vincristine and prednisolone (CHOP). Postoperative radiotherapy was given in 3 patients who were found to have extra thyroidal spread in the form adjoining soft tissues or skin involvement at the time of surgery. One of these patients developed tracheal stenosis and needed a tracheostomy four months after radiotherapy.

Table 3: FNAC findings in patients with thyroid lymphoma.

Findings	No of cases(%)
Thyroid lymphoma:	3 (25%)
Chronic lymphocytic thyroiditis	5 (42%)
Follicular neoplasm:	4 (33%)

The subcutaneous nodules disappeared in all the 3 patients following the first cycle of chemotherapy.

At 36 months follow-up, 9 patients were recurrence free, 2 had developed recurrence in the liver and 1 had died. Among the two patients with recurrence, one had chronic liver disease due to hepatitis B infection and died subsequently but other did not have any liver pathology.

Discussion

Lymphoma of the thyroid is one of the differential diagnoses of a thyroid mass. It is an uncommon but not a rare lesion and authors have reviewed as many as 60 cases treated over a 20 years period from a specialist referral center in Saudi Arabia [2]. Females are more commonly afflicted and the median age is 52 years presenting as a rapidly growing nodular goiter with or without cervical lymphadenopathy. A previous history of Hashimoto’s thyroiditis may be observed in some patients [3]. Belal et al., found 31% of their 60 patients to have disease confined to the thyroid gland while 69% had associated disease in cervical lymph nodes and/or mediastinum [2]. In our own experience the commonest presentation was a thyroid mass with associated cervical lymphadenopathy which was seen in 50% of our patients.

Fine needle aspiration cytology is the sheet anchor for diagnosis of thyroid masses. However difficulties are encountered when using this technique to distinguish Hashimoto’s thyroiditis from thyroid lymphoma [4]. Lymphoma developing in a background of chronic lymphocytic thyroiditis may also be missed on FNAC. We found that in the 12 patients under review only 25% were correctly diagnosed as thyroid lymphoma on FNAC. The remaining 75% were diagnosed as chronic lymphocytic thyroiditis or follicular neoplasm. Ancillary techniques like light chain restriction, flow cytometry and immunohistochemical staining may enable the pathologist to make a more accurate diagnosis by FNA [5]. Authors have also reported upon the use of mean nuclear area as a criterion for distinguishing between Hashimoto’s thyroiditis, lymphoma and anaplastic thyroid carcinoma [6].

Thyroid lymphomas are always of non Hodgkin’s variety and are mainly B-cell derived and occasionally of T cell origin [7]. Evidence of tumor origin from MALT (mucosa associated lymphoid tissue) within the thyroid has also been reported and these tumors had a lower relapse rate compared to those tumors without MALT origin [8]. The causal role of Epstein Barr virus in the development of B-cell lymphoma has been suggested but it is not very common [9]. Lymphomas which develop in a background of Hashimoto’s thyroiditis or chronic lymphocytic thyroiditis show evidence of hypothyroidism and a high serum level of antithyroid antibodies [3]. Among the 12 patients reviewed by us 10 had non Hodgkin’s lymphoma of B cell origin and 2 had extranodal marginal zone (MALT cell) lymphoma. Although only 1 patient was clinically hypothyroid, another 7 had subclinical hypothyroidism diagnosed by thyroid hormone assay. This suggests that a significant proportion of our patients developed lymphoma in a setting of lymphocytic thyoiditis which is well known to produce hypothyroidism.

The mainstay of treatment is by systemic chemotherapy with radiotherapy and/or surgery playing an adjunctive role [4]. The surgical procedures performed vary form incision biopsy to limited tumor debulking with tracheostomy to thyroidectomy [10]. Because these tumors are exquisitely sensitive to both chemotherapy and radiation, the treatment of choice is combination chemotherapy with consolidated irradiation. The prognosis of patients receiving multimodality treatment is excellent and 5 years survival rate of nearly 100% have been reported regardless of histological type [11]. All our patients were subjected to surgical excision of the lesion because of the presence of a palpable lesion. Postoperative chemotherapy (CHOP regime) was given to all and only 3 received adjuvant radiotherapy because they had extrathyroidal spread at the time of surgery. At 3 years follow-up, 9 patients (75%) were recurrence free and 1(8%) had succumbed to her disease.

Conclusion

Primary thyroid lymphoma is an extremely rare condition difficult to diagnose only with FNAC. But diagnosis is established in all cases after surgery and prognosis is excellent after use of chemotherapy.

Authors' Contributions

SK: Prepared the draft manuscript & did literature search
RNM: Did the literature search and prepared draft
MK: Carried out the pathological work and contributed to the pathological part of the manuscript.
RK: Conceived and designed the study, recruited patients and helped in draft preparation.

Acknowledgements

None

Funding

None

Conflict of Interest

The authors declare that there are no conflict of interests.

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