Journal of Cytology
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CASE REPORT  
Year : 2014  |  Volume : 31  |  Issue : 4  |  Page : 218-220
Primary thyroid lymphoma: A rare disease


Department of Pathology, Lady Hardinge Medical College and Shrimati Sucheta Kriplani Hospital, New Delhi, India

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Date of Web Publication10-Feb-2015
 

   Abstract 

Primary thyroid lymphomas are rare neoplasms comprising of 1-5% of thyroid malignancies. These are predominantly B-cell in origin. Here, we report a case of 60 years lady, a known case of lymphocytic thyroiditis, diagnosed as thyroid lymphoma (diffuse large B-cell) on fine needle aspiration and confirmed histopathogically and immunohistochemically. She presented with a sudden increase in thyroid swelling. Fine needle aspiration performed showed highly cellular smears comprising predominantly of the monomorphic population of medium to large sized lymphoid cells with high nuclear/cytoplasmic ratio and scant cytoplasm. A possibility of thyroid lymphoma possibly diffuse large B-cell lymphoma was suggested which was later confirmed on biopsy. Fine needle aspiration provides an easy mode for diagnosing large cell lymphoma like diffuse large B-cell. Hence, an early diagnosis is possible for a timely intervention. Also, cases of lymphocytic thyroiditis should be regularly followed for the development of lymphoma.

Keywords: Lymphoma; primary; thyroid; thyroiditis; fine needle aspiration cytology

How to cite this article:
Verma D, Puri V, Agarwal S, Bhaskar A. Primary thyroid lymphoma: A rare disease. J Cytol 2014;31:218-20

How to cite this URL:
Verma D, Puri V, Agarwal S, Bhaskar A. Primary thyroid lymphoma: A rare disease. J Cytol [serial online] 2014 [cited 2019 Sep 23];31:218-20. Available from: http://www.jcytol.org/text.asp?2014/31/4/218/151139



   Introduction Top


Primary thyroid lymphoma is a rare neoplasm comprising 1-5% of all thyroid malignancies and 1-7% of all extra nodal lymphomas. [1] They typically occur in the middle to old aged individuals with a predilection for females. [2] Most thyroid lymphomas are of B-cell origin. [3] Early recognition of this disease is important as it is curable if treated timely.

In this case report, we discuss this rare case of primary thyroid lymphoma recognized on fine needle aspiration and confirmed on histology and immunohistochemistry.


   Case Report Top


A 60-year-old female a known case of lymphocytic thyroiditis for 2 years presented to surgery outpatient department with the complaints of a sudden increase in size of thyroid swelling since last 1-month. There was no history of pain, change in voice, difficulty in deglutition/breathing, cold or heat intolerance, change in appetite and palpitations.

On examination, a diffuse nontender thyroid swelling measuring 4 cm × 2 cm moving with deglutition was noted involving the entire thyroid gland. No lymphadenopathy was found clinically. Thyroid hormone levels were normal. The anti-thyroglobulin and thyroid peroxidase antibodies were negative in blood.

Ultrasonography neck showed diffuse enlargement of the thyroid with increased vascularity. Multiple enlarged cervical lymph nodes were noted on both sides (size <0.5 cm). No hepatosplenomegaly was noted.

Fine needle aspiration smears from the thyroid [Figure 1] were highly cellular comprising predominantly of monomorphic population of medium to large sized lymphoid cells with high nuclear/cytoplasmic (N/C) ratio and scant cytoplasm. Nuclei were round to oval with fine chromatin, few of them showing irregular nuclear membrane, 0-2 eccentrically located nucleoli. Few centrocytes, small mature lymphocytes, occasional tingible body macrophages, plasma cells and mast cells along with lymphoglandular bodies were seen in the background. Occasional cluster of thyroid follicular cells was seen. No Hόrthle cell change/granulomas/giant cells were noticed. Possibility of thyroid lymphoma possibly diffuse large B-cell lymphoma was suggested.
Figure 1: Highly cellular fine needle aspiration smear comprising predominantly of the monomorphic population of medium to large sized lymphoid cells with high nuclear/cytoplasmic ratio and scant cytoplasm (Giemsa, ×400)

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Trucut biopsy from the thyroid gland was also performed, which predominantly showed monomorphic medium to large sized lymphoid population with increased N/C ratio and scant cytoplasm, round to oval nuclei with irregular nuclear membrane, open chromatin, 0-2 nucleoli [Figure 2]. Few thyroid follicles were seen entrapped in between this lymphoid infiltrate. However, no lymphoepithelial lesions, follicular destruction, Hόrthle cell change, granuloma or giant cells were appreciated.
Figure 2: Monomorphic population of medium to large sized cells with high
nuclear/cytoplasmic ratio and scant cytoplasm, open chromatin and 0-2
nucleoli (H and E, ×400). Left and right inset (×400) show strong CD20 and
lambda positivity in tumor cells respectively


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Immunohistochemical markers were put up on biopsy tissue showing a strong positivity for CD20 in these cells [Figure 2]. However, CD3, CD5, CD10, cyclin D1, cytokeratin (CK) and epithelial membrane antigen (EMA) were negative. Monoclonality was proven by the selective expression of lambda light chains in the neoplastic lymphoid cells [Figure 2]. Ki-67 index was 50%. Based on these findings, a diagnosis of non-Hodgkin's lymphoma possibly centroblastic variant of diffuse large B-cell lymphoma was given.

Contrast-enhanced computed tomography (CECT ) of neck and abdomen was done to differentiate between primary and secondary thyroid lymphoma which showed enlarged and homogenously enhancing left and right thyroid lobe with multiple enlarged homogenously enhancing lymph nodes in bilateral level 2-4 and posterior triangle of neck, bilateral supraclavicular, pre/para tracheal, trachea-esophageal region (size <0.5 cm), possibility of thyroid lymphoma was considered. No organomegaly or abdominal lymphadenopathy was noticed.

Bone marrow aspirate and biopsy did not show any evidence of lymphoma. Serum lactate dehydrogenase was also within normal limits.


   Discussion Top


Primary thyroid lymphoma is a rare disease. Most thyroid lymphomas are of B-cell origin. [3] Main concern in our case was to distinguish it from secondary thyroid lymphoma. The primary thyroid lymphoma occurs in older age group (median age: 60 years), limited to thyroid and usually originates in setting of autoimmune thyroiditis. On the contrary, in secondary thyroid lymphoma (i.e., the thyroid being secondarily affected by lymphoma), the middle-aged population (median age: 42 years) is affected more, usually patient presents with disseminated disease and has no complaints of thyroiditis.

There appears to be two distinct clinical and prognostic groups of thyroid lymphoma. More common subtype comprising up to 70% of cases is a diffuse large B-cell lymphoma. [3] This subtype has more aggressive clinical course with almost 60% diagnosed with disseminated disease. Another subtype includes mucosa associated lymphoid tissue (MALT) lymphoma forming 6-27% of thyroid lymphomas. [3] These have relatively indolent course and male to female ratio of 2-4:1. Majority of these have underlying Hashimoto's thyroiditis that increases the risk of thyroid lymphoma by 50 times. [3]

Two subtypes of diffuse large B-cell lymphomas (DLBCL) can be distinguished histologically. [4]

  1. MALT lymphoma secondarily transformed into an aggressive DLBCL at the time of diagnosis.
  2. DLBCL without associated marginal zone lymphoma (MZL) lesions.
Patients with DLBCL and MALT lymphomas generally have a previous history of thyroid disease. However, clinical course of DLBCL evolving from MALT and DLBCL without associated MZL lesions seem to be similar. [5]

Our case does not show any features of MALT lymphoma and appears to be DLBCL originating in the background of lymphocytic thyroiditis. Fine needle aspiration can be a very important diagnostic tool in picking thyroid lymphoma.

Nearly half of the thyroid non-Hodgkin's lymphomas have a clinical history of chronic lymphocytic thyroiditis and up to two thirds of cases show pathological clues consistent with chronic lymphocytic thyroiditis. [2] It is thought that lymphomas originating in this wide variety of primary sites represent a malignant transformation of acquired lymphocytic tissue during the course of a chronic inflammatory or an autoimmune process. [6]

Diffuse large B-cell lymphomas in cytology [1],[7] show a population of noncohesive atypical cells. These are large cells with irregular nuclear membrane, vesicular nuclei, and prominent nucleoli. There is scant to absent thyroid follicular cells with scattered small cytoplasmic fragments of lymphocytes in background (lymphoglandular bodies) as seen in our case.

Another important differential diagnosis of DLBCL thyroid [7] is anaplastic carcinoma that shows pleomorphic, round, oval or spindle-shaped cells either isolated or in tissue fragments. Lack of cohesion and absence of lymphoglandular bodies with CK and EMA negativity pointed strongly against anaplastic carcinoma.

Hypothyroidism at the time of diagnosis is found in 30-40% of patients due to replacement of thyroid parenchyma by the lymphomatous process due to underlying Hashimoto's thyroiditis. [3] Our patient however was euthyroid.

The choice of treatment in thyroid lymphoma depends on histological subtype and stage of the disease. For aggressive DLBCL treatment is based on chemotherapy (CHOP) with anthracycline containing multidrug regimen (CHOP/CHOP like). Combination of CHOP and radiotherapy is the standard treatment of localized aggressive lymphoma but in some patients under 60 years and without any adverse prognostic factors CHOP alone may be proposed. [4]

Our patient was in stage 2a till now and had received three cycles of R-CHOP following which the CT was performed which showed regression of size of the thyroid and disappearance of cervical lymph nodes.

To conclude, large cell lymphoma like DLBCL can easily be diagnosed on fine needle aspiration so that a timely intervention can be undertaken. Patients of lymphocytic thyroiditis should be regularly followed for the development of lymphoma. Any rapid or short history of thyroid enlargement as present in our case should alarm the clinician for an urgent fine needle aspiration to rule out development of lymphoma in the background of thyroiditis.

 
   References Top

1.
Paras CA, Salpin AP, Veloso JD. Primary thyroid lymphoma. Philipp J Otolaryngol Head Neck Surg 2012;27:38-40.  Back to cited text no. 1
    
2.
Foppiani L, Secondo V, Arlandini A, Quilici P, Cabria M, Del Monte P. Thyroid lymphoma: A rare tumor requiring combined management. Hormones (Athens) 2009;8:214-8.  Back to cited text no. 2
    
3.
Gupta N, Nijhawan R, Srinivasan R, Rajwanshi A, Dutta P, Bhansaliy A, et al. Fine needle aspiration cytology of primary thyroid lymphoma: A report of ten cases. Cytojournal 2005;2:21.  Back to cited text no. 3
    
4.
Thieblemont C, Mayer A, Dumontet C, Barbier Y, Callet-Bauchu E, Felman P, et al. Primary thyroid lymphoma is a heterogeneous disease. J Clin Endocrinol Metab 2002;87:105-11.  Back to cited text no. 4
    
5.
Derringer GA, Thompson LD, Frommelt RA, Bijwaard KE, Heffess CS, Abbondanzo SL. Malignant lymphoma of the thyroid gland: A clinicopathologic study of 108 cases. Am J Surg Pathol 2000;24:623-39.  Back to cited text no. 5
    
6.
Thieblemont C, Bastion Y, Berger F, Rieux C, Salles G, Dumontet C, et al. Mucosa-associated lymphoid tissue gastrointestinal and nongastrointestinal lymphoma behavior: Analysis of 108 patients. J Clin Oncol 1997;15:1624-30.  Back to cited text no. 6
    
7.
Daneshbod Y, Omidvari S, Daneshbod K, Negahban S, Dehghani M. Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: A case report. Cytojournal 2006;3:23.  Back to cited text no. 7
    

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Correspondence Address:
Deepti Verma
Department of Pathology, Lady Hardinge Medical College and Shrimati Sucheta Kriplani Hospital, Shaheed Bhagat Singh Marg, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9371.151139

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